@article{LiebscherTessmarGroll2020, author = {Liebscher, Julia and Teßmar, Joerg Karl and Groll, J{\"u}rgen}, title = {In Situ Polymer Analogue Generation of Azlactone Functions at Poly(oxazoline)s for Peptide Conjugation}, series = {Macromolecular Chemistry and Physics}, volume = {221}, journal = {Macromolecular Chemistry and Physics}, number = {1}, doi = {10.1002/macp.201900500}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208147}, pages = {1900500}, year = {2020}, abstract = {The physical and chemical stability of peptides for biomedical applications can be greatly enhanced through the conjugation of polymers. A well-known but rather underemployed selective coupling functionality is the azlactone group, which readily reacts with a number of different nucleophiles without the need for activation and the formation of any by-products. For example, azlactone functional polymers are used to react with peptides and proteins, rich in amino and thiol groups, to form polymeric beads for affinity-based column chromatography. So far, side chain functional azlactone polymers have been mainly synthesized by radical polymerization using 2-vinyl-4,4-dimethyl azlactone together with different acrylate monomers. Here, a new azlactone precursor equipped with a functional thiol is presented, which can be attached to any vinyl functional polymer by thiol-ene chemistry. Subsequently, the formation of the reactive azlactone ring can be performed in situ at high conversion rate without the need for illumination. This approach is tested on an azlactone side functional poly(2-oxazoline) by coupling amine containing molecules including a model peptide and is proven via \(^1\)H NMR spectroscopy, IR spectroscopy, as well as HPLC measurements.}, language = {en} } @article{WeissenbergerHeinzRueckletal.2020, author = {Weissenberger, Manuel and Heinz, Tizian and Rueckl, Kilian and Rudert, Maximilian and Klug, Alexander and Hoffmann, Reinhard and Schmidt-Horloh{\´e}, Kay}, title = {No functional differences in anatomic reconstruction with one vs. two suture anchors after non-simultaneous bilateral distal biceps brachii tendon rupture: a case report and review of the literature}, series = {BMC Musculoskeletal Disorders}, volume = {21}, journal = {BMC Musculoskeletal Disorders}, doi = {10.1186/s12891-020-03304-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229266}, year = {2020}, abstract = {Background Surgical reattachment of the tendon is still the gold standard for ruptures of the distal biceps brachii tendon. Several fixation techniques have been described in the literature, with suture anchors being one of the most common fixation techniques. Currently, there is no data available on how many anchors are required for a safe and stable refixation. In this case report clinical data of a patient with non-simultaneous bilateral distal biceps tendon ruptures treated with a different number of suture anchors for each side (one vs. two) are demonstrated. Case presentation A 47-year-old factory worker suffered a rupture of the distal biceps tendon on both arms following two different occasions. The left side was fixed using a single suture anchor, while refixation on the right side was performed with two anchors. The patient was prospectively followed for one year. Functional outcome was assessed using the Andrews Carson Score (ACS), the Oxford Elbow Score (OES), and the Disabilities of Arm, Shoulder and Hand (DASH) Score after six, twelve, 24 and 48 weeks. Furthermore, an isokinetic strength measurement for flexion strength was performed after 24 and 48 weeks. After 48 weeks the patient presented with excellent functional outcome scores and no follow-up complications. During the follow-up period, no differences in the functional scores nor in the isokinetic flexion strength measurement could be detected. Furthermore, no radiological complications (like heterotopic ossifications) could be detected in the postoperative radiographs after one year. Conclusions Anatomic reattachment of the distal biceps tendon is a successful operative treatment option for distal biceps tendon ruptures. Suture anchor fixation remains one of the most common techniques, as it allows fast surgery and provides good results with respect to range of motion (ROM) and functional scoring according to the current literature. However, the number of anchors required for a stable fixation remains unclear. As indicated by our presented case, we hypothesize, that there are no significant differences between a one-point or a two-point fixation. In the presented case report, no intraindividual differences between the usage of one versus two suture anchors were evident in the short-term follow-up.}, language = {en} } @article{BerveWestMartinietal.2020, author = {Berve, Kristina and West, Brian L. and Martini, Rudolf and Groh, Janos}, title = {Sex- and region-biased depletion of microglia/macrophages attenuates CLN1 disease in mice}, series = {Journal of Neuroinflammation}, volume = {17}, journal = {Journal of Neuroinflammation}, doi = {10.1186/s12974-020-01996-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230234}, year = {2020}, abstract = {Background The neuronal ceroid lipofuscinoses (CLN diseases) are fatal lysosomal storage diseases causing neurodegeneration in the CNS. We have previously shown that neuroinflammation comprising innate and adaptive immune reactions drives axonal damage and neuron loss in the CNS of palmitoyl protein thioesterase 1-deficient (Ppt1\(^{-/-}\)) mice, a model of the infantile form of the diseases (CLN1). Therefore, we here explore whether pharmacological targeting of innate immune cells modifies disease outcome in CLN1 mice. Methods We applied treatment with PLX3397 (150 ppm in the chow), a potent inhibitor of the colony stimulating factor-1 receptor (CSF-1R) to target innate immune cells in CLN1 mice. Experimental long-term treatment was non-invasively monitored by longitudinal optical coherence tomography and rotarod analysis, as well as analysis of visual acuity, myoclonic jerks, and survival. Treatment effects regarding neuroinflammation, neural damage, and neurodegeneration were subsequently analyzed by histology and immunohistochemistry. Results We show that PLX3397 treatment attenuates neuroinflammation in CLN1 mice by depleting pro-inflammatory microglia/macrophages. This leads to a reduction of T lymphocyte recruitment, an amelioration of axon damage and neuron loss in the retinotectal system, as well as reduced thinning of the inner retina and total brain atrophy. Accordingly, long-term treatment with the inhibitor also ameliorates clinical outcomes in CLN1 mice, such as impaired motor coordination, visual acuity, and myoclonic jerks. However, we detected a sex- and region-biased efficacy of CSF-1R inhibition, with male microglia/macrophages showing higher responsiveness toward depletion, especially in the gray matter of the CNS. This results in a better treatment outcome in male Ppt1\(^{-/-}\) mice regarding some histopathological and clinical readouts and reflects heterogeneity of innate immune reactions in the diseased CNS. Conclusions Our results demonstrate a detrimental impact of innate immune reactions in the CNS of CLN1 mice. These findings provide insights into CLN pathogenesis and may guide in the design of immunomodulatory treatment strategies.}, language = {en} } @article{NaseemOthmanFathyetal.2020, author = {Naseem, Muhammad and Othman, Eman M. and Fathy, Moustafa and Iqbal, Jibran and Howari, Fares M. and AlRemeithi, Fatima A. and Kodandaraman, Geema and Stopper, Helga and Bencurova, Elena and Vlachakis, Dimitrios and Dandekar, Thomas}, title = {Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-70253-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231317}, year = {2020}, abstract = {Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.}, language = {en} } @article{Bobineau2020, author = {Bobineau, Julien}, title = {Belgiens gespaltene Erinnerung: Aufarbeitung und Verdr{\"a}ngung von kolonialer Geschichte in Flandern und Wallonien}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244224}, pages = {23-42}, year = {2020}, abstract = {This article examines so-called colonial discourses in Belgium on the former Sub-Saharan colony owned by the Belgian King, Leopold II., which today is known as the Democratic Republic of Congo (DR Congo) or the Congo-Kinshasa. After having introduced the colonial history of the DR Congo from the 15th century until 1910, an empirical analysis of the colonial discourses in Belgium from the 1890s until today will be illustrated in conjunction with Belgium's linguistic-cultural division and the age-related divergence. Belgian colonial discourse is characterized by a historical misrepresentation by the political authorities while especially social forces have pled for a critical examination of their own colonial history in Belgium since the year 2000.}, language = {de} } @article{HirschPachnerFischeretal.2020, author = {Hirsch, Florian and Pachner, Kai and Fischer, Ingo and Issler, Kevin and Petersen, Jens and Mitric, Roland and Bakels, Sjors and Rijs, Anouk M.}, title = {Do Xylylenes Isomerize in Pyrolysis?}, series = {ChemPhysChem}, volume = {21}, journal = {ChemPhysChem}, number = {14}, doi = {10.1002/cphc.202000317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218316}, pages = {1515 -- 1518}, year = {2020}, abstract = {We report infrared spectra of xylylene isomers in the gas phase, using free electron laser (FEL) radiation. All xylylenes were generated by flash pyrolysis. The IR spectra were obtained by monitoring the ion dip signal, using a IR/UV double resonance scheme. A gas phase IR spectrum of para-xylylene  was recorded, whereas ortho- and meta-xylylene were found to partially rearrange to benzocyclobutene and styrene. Computations of the UV oscillator strength  for all molecules were carried out and provde an explanation for the observation of the isomerization products.}, language = {en} } @article{AngermannAssmusAnkeretal.2020, author = {Angermann, Christiane E. and Assmus, Birgit and Anker, Stefan D. and Asselbergs, Folkert W. and Brachmann, Johannes and Brett, Marie-Elena and Brugts, Jasper J. and Ertl, Georg and Ginn, Greg and Hilker, Lutz and Koehler, Friedrich and Rosenkranz, Stephan and Zhou, Qian and Adamson, Philip B. and B{\"o}hm, Michael}, title = {Pulmonary artery pressure-guided therapy in ambulatory patients with symptomatic heart failure: the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF)}, series = {European Journal of Heart Failure}, volume = {22}, journal = {European Journal of Heart Failure}, number = {10}, doi = {10.1002/ejhf.1943}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218061}, pages = {1891 -- 1901}, year = {2020}, abstract = {Aims Heart failure (HF) leads to repeat hospitalisations and reduces the duration and quality of life. Pulmonary artery pressure (PAP)-guided HF management using the CardioMEMS™ HF system was shown to be safe and reduce HF hospitalisation (HFH) rates in New York Heart Association (NYHA) class III patients. However, these findings have not been replicated in health systems outside the United States. Therefore, the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF) evaluated the safety, feasibility, and performance of this device in Germany, The Netherlands, and Ireland. Methods and results A total of 234 NYHA class III patients (68 ± 11 years, 22\% female, ≥1 HFH in the preceding year) from 31 centres were implanted with a CardioMEMS sensor and underwent PAP-guided HF management. One-year rates of freedom from device- or system-related complications and from sensor failure (co-primary outcomes) were 98.3\% [95\% confidence interval (CI) 95.8-100.0] and 99.6\% (95\% CI 97.6-100.0), respectively. Survival rate was 86.2\%. For the 12 months post- vs. pre-implant, HFHs decreased by 62\% (0.60 vs. 1.55 events/patient-year; hazard ratio 0.38, 95\% CI 0.31-0.48; P < 0.0001). After 12 months, mean PAP decreased by 5.1 ± 7.4 mmHg, Kansas City Cardiomyopathy Questionnaire (KCCQ) overall/clinical summary scores increased from 47.0 ± 24.0/51.2 ± 24.8 to 60.5 ± 24.3/62.4 ± 24.1 (P < 0.0001), and the 9-item Patient Health Questionnaire sum score improved from 8.7 ± 5.9 to 6.3 ± 5.1 (P < 0.0001). Conclusion Haemodynamic-guided HF management proved feasible and safe in the health systems of Germany, The Netherlands, and Ireland. Physician-directed treatment modifications based on remotely obtained PAP values were associated with fewer HFH, sustainable PAP decreases, marked KCCQ improvements, and remission of depressive symptoms.}, language = {en} } @article{RickertWagenhaeuserNordbecketal.2020, author = {Rickert, V. and Wagenh{\"a}user, L. and Nordbeck, P. and Wanner, C. and Sommer, C. and Rost, S. and {\"U}{\c{c}}eyler, N.}, title = {Stratification of Fabry mutations in clinical practice: a closer look at α-galactosidase A-3D structure}, series = {Journal of Internal Medicine}, volume = {288}, journal = {Journal of Internal Medicine}, number = {5}, doi = {10.1111/joim.13125}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218125}, pages = {593 -- 604}, year = {2020}, abstract = {Background Fabry disease (FD) is an X-linked lysosomal storage and multi-system disorder due to mutations in the α-galactosidase A (α-GalA) gene. We investigated the impact of individual amino acid exchanges in the α-GalA 3D-structure on the clinical phenotype of FD patients. Patients and methods We enrolled 80 adult FD patients with α-GalA missense mutations and stratified them into three groups based on the amino acid exchange location in the α-GalA 3D-structure: patients with active site mutations, buried mutations and other mutations. Patient subgroups were deep phenotyped for clinical and laboratory parameters and FD-specific treatment. Results Patients with active site or buried mutations showed a severe phenotype with multi-organ involvement and early disease manifestation. Patients with other mutations had a milder phenotype with less organ impairment and later disease onset. α-GalA activity was lower in patients with active site or buried mutations than in those with other mutations (P < 0.01 in men; P < 0.05 in women) whilst lyso-Gb3 levels were higher (P < 0.01 in men; <0.05 in women). Conclusions The type of amino acid exchange location in the α-GalA 3D-structure determines disease severity and temporal course of symptom onset. Patient stratification using this parameter may become a useful tool in the management of FD patients.}, language = {en} } @article{RichterWechWengetal.2020, author = {Richter, Julian A. J. and Wech, Tobias and Weng, Andreas M. and Stich, Manuel and Weick, Stefan and Breuer, Kathrin and Bley, Thorsten A. and K{\"o}stler, Herbert}, title = {Free-breathing self-gated 4D lung MRI using wave-CAIPI}, series = {Magnetic Resonance in Medicine}, volume = {84}, journal = {Magnetic Resonance in Medicine}, number = {6}, doi = {10.1002/mrm.28383}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218075}, pages = {3223 -- 3233}, year = {2020}, abstract = {Purpose The aim of this study was to compare the wave-CAIPI (controlled aliasing in parallel imaging) trajectory to the Cartesian sampling for accelerated free-breathing 4D lung MRI. Methods The wave-CAIPI k-space trajectory was implemented in a respiratory self-gated 3D spoiled gradient echo pulse sequence. Trajectory correction applying the gradient system transfer function was used, and images were reconstructed using an iterative conjugate gradient SENSE (CG SENSE) algorithm. Five healthy volunteers and one patient with squamous cell carcinoma in the lung were examined on a clinical 3T scanner, using both sampling schemes. For quantitative comparison of wave-CAIPI and standard Cartesian imaging, the normalized mutual information and the RMS error between retrospectively accelerated acquisitions and their respective references were calculated. The SNR ratios were investigated in a phantom study. Results The obtained normalized mutual information values indicate a lower information loss due to acceleration for the wave-CAIPI approach. Average normalized mutual information values of the wave-CAIPI acquisitions were 10\% higher, compared with Cartesian sampling. Furthermore, the RMS error of the wave-CAIPI technique was lower by 19\% and the SNR was higher by 14\%. Especially for short acquisition times (down to 1 minute), the undersampled Cartesian images showed an increased artifact level, compared with wave-CAIPI. Conclusion The application of the wave-CAIPI technique to 4D lung MRI reduces undersampling artifacts, in comparison to a Cartesian acquisition of the same scan time. The benefit of wave-CAIPI sampling can therefore be traded for shorter examinations, or enhancing image quality of undersampled 4D lung acquisitions, keeping the scan time constant.}, language = {en} } @article{UllmannNillSchiestletal.2020, author = {Ullmann, Tobias and Nill, Leon and Schiestl, Robert and Trappe, Julian and Lange-Athinodorou, Eva and Baumhauer, Roland and Meister, Julia}, title = {Mapping buried paleogeographical features of the Nile Delta (Egypt) using the Landsat archive}, series = {E\&G Quartnerny Science Journal}, volume = {69}, journal = {E\&G Quartnerny Science Journal}, number = {2}, doi = {10.5194/egqsj-69-225-2020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230349}, pages = {225-245}, year = {2020}, abstract = {The contribution highlights the use of Landsat spectral-temporal metrics (STMs) for the detection of surface anomalies that are potentially related to buried near-surface paleogeomorphological deposits in the Nile Delta (Egypt), in particular for a buried river branch close to Buto. The processing was completed in the Google Earth Engine (GEE) for the entire Nile Delta and for selected seasons of the year (summer/winter) using Landsat data from 1985 to 2019. We derived the STMs of the tasseled cap transformation (TC), the Normalized Difference Wetness Index (NDWI), and the Normalized Difference Vegetation Index (NDVI). These features were compared to historical topographic maps of the Survey of Egypt, CORONA imagery, the digital elevation model of the TanDEM-X mission, and modern high-resolution satellite imagery. The results suggest that the extent of channels is best revealed when differencing the median NDWI between summer (July/August) and winter (January/February) seasons (ΔNDWI). The observed difference is likely due to lower soil/plant moisture during summer, which is potentially caused by coarser-grained deposits and the morphology of the former levee. Similar anomalies were found in the immediate surroundings of several Pleistocene sand hills ("geziras") and settlement mounds ("tells") of the eastern delta, which allowed some mapping of the potential near-surface continuation. Such anomalies were not observed for the surroundings of tells of the western Nile Delta. Additional linear and meandering ΔNDWI anomalies were found in the eastern Nile Delta in the immediate surroundings of the ancient site of Bubastis (Tell Basta), as well as several kilometers north of Zagazig. These anomalies might indicate former courses of Nile river branches. However, the ΔNDWI does not provide an unambiguous delineation.}, language = {en} } @article{GeorgievChaoCastroetal.2020, author = {Georgiev, Kostadin B. and Chao, Anne and Castro, Jorge and Chen, Yan-Han and Choi, Chang-Yong and Fontaine, Joseph B. and Hutto, Richard L. and Lee, Eun-Jae and M{\"u}ller, J{\"o}rg and Rost, Josep and Żmihorski, Michal and Thorn, Simon}, title = {Salvage logging changes the taxonomic, phylogenetic and functional successional trajectories of forest bird communities}, series = {Journal of Applied Ecology}, volume = {57}, journal = {Journal of Applied Ecology}, number = {6}, doi = {10.1111/1365-2664.13599}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214887}, pages = {1103 -- 1112}, year = {2020}, abstract = {Salvage logging following natural disturbances may alter the natural successional trajectories of biological communities by affecting the occurrences of species, functional groups and evolutionary lineages. However, few studies have examined whether dissimilarities between bird communities of salvaged and unsalvaged forests are more pronounced for rare species, functional groups and evolutionary lineages than for their more common counterparts. We compiled data on breeding bird assemblages from nine study areas in North America, Europe and Asia, covering a 17-year period following wildfire or windstorm disturbances and subsequent salvage logging. We tested whether dissimilarities based on non-shared species, functional groups and evolutionary lineages (a) decreased or increased over time and (b) the responses of rare, common and dominant species varied, by using a unified statistical framework based on Hill numbers and null models. We found that dissimilarities between bird communities caused by salvage logging persisted over time for rare, common and dominant species, evolutionary lineages and for rare functional groups. Dissimilarities of common and dominant functional groups increased 14 years post disturbance. Salvage logging led to significantly larger dissimilarities than expected by chance. Functional dissimilarities between salvaged and unsalvaged sites were lower compared to taxonomic and phylogenetic dissimilarities. In general, dissimilarities were highest for rare, followed by common and dominant species. Synthesis and applications. Our research demonstrates that salvage logging did not decrease dissimilarities of bird communities over time and taxonomic, functional and phylogenetic dissimilarities persisted for over a decade. We recommend resource managers and decision makers to reserve portions of disturbed forest to enable unmanaged post-disturbance succession of bird communities, particularly to conserve rare species found in unsalvaged disturbed forests.}, language = {en} } @article{FeldheimKesslerSchmittetal.2020, author = {Feldheim, Jonas and Kessler, Almuth F. and Schmitt, Dominik and Salvador, Ellaine and Monoranu, Camelia M. and Feldheim, Julia J. and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten}, title = {Ribosomal Protein S27/Metallopanstimulin-1 (RPS27) in Glioma — A New Disease Biomarker?}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {5}, issn = {2072-6694}, doi = {10.3390/cancers12051085}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203648}, year = {2020}, abstract = {Despite its significant overexpression in several malignant neoplasms, the expression of RPS27 in the central nervous system (CNS) is widely unknown. We identified the cell types expressing RPS27 in the CNS under normal and disease conditions. We acquired specimens of healthy brain (NB), adult pilocytic astrocytoma (PA) World Health Organization (WHO) grade I, anaplastic PA WHO grade III, gliomas WHO grade II/III with or without isocitrate dehydrogenase (IDH) mutation, and glioblastoma multiforme (GBM). RPS27 protein expression was examined by immunohistochemistry and double-fluorescence staining and its mRNA expression quantified by RT-PCR. Patients' clinical and tumor characteristics were collected retrospectively. RPS27 protein was specifically expressed in tumor cells and neurons, but not in healthy astrocytes. In tumor tissue, most macrophages were positive, while this was rarely the case in inflamed tissue. Compared to NB, RPS27 mRNA was in mean 6.2- and 8.8-fold enhanced in gliomas WHO grade II/III with (p < 0.01) and without IDH mutation (p = 0.01), respectively. GBM displayed a 4.6-fold increased mean expression (p = 0.02). Although RPS27 expression levels did not affect the patients' survival, their association with tumor cells and tumor-associated macrophages provides a rationale for a future investigation of a potential function during gliomagenesis and tumor immune response.}, language = {en} } @article{Luetzelberger2020, author = {L{\"u}tzelberger, Florian}, title = {Federico Garc{\´i}a Lorcas Trilog{\´i}a dram{\´a}tica de la tierra espa{\~n}ola als Knotenpunkt von Kontinuit{\"a}t und Wandel von der Antike bis zu Netflix: Tradition, Adaption, Innovation, Inspiration}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244280}, pages = {131-153}, year = {2020}, abstract = {To this day, Lorca's most popular plays, the Trilog{\´i}a dram{\´a}tica de la tierra espa{\~n}ola, are considered to be among the most widely read texts of twentieth century Spanish literature. By combining elements from Antiquity with classic and modern features of Spanish theatre and placing them in new functional contexts, the author succeeds in creating an innovative theatre of sociocritical nature in times of political repression. This article analyses several of these innovations and aims to demonstrate the influence Lorca's Tragedias rurales still have on today's literature and culture. Simon Stone's play Yerma (2017) and the Netflix series Las Chicas del Cable (2017-2020) are approached here with this purpose.}, language = {de} } @article{Koehler2020, author = {K{\"o}hler, Britta}, title = {A Room of One's Own : Weiblichkeit, Schreiben und kollektive Erfahrung in Elena Ferrantes Tetralogie L'amica geniale (2011-2014) und Annie Ernaux' Les Ann{\´e}es (2008)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244246}, pages = {87-104}, year = {2020}, abstract = {With her famous suggestion to «give her [the woman] a room of her own and five hundred a year, let her speak her mind» from 1929, Virginia Woolf verbalized a core issue of female writing by hinting at the socioeconomic circumstances and domestic obligations of most women - valid at her times, but still today. Both Elena Ferrante and Annie Ernaux discuss, in their respective novels, the topics of being women in the particular sociocultural landscape (in Italy and, respectively, in France) after World War II and up to these days, the themes of marriage and motherhood, employment and especially (female) authorship. This article aims to show in a close reading of both Ferrante and Ernaux that the two writers play with the literary form of the (auto-)biography on a diegetic, but also extradiegetic level, while formulating at the same time a collective work that embraces the experience of womanhood but circumvents the hazard of a merely subjective and sensitive writing, as female writing has sometimes been claimed to be.}, language = {de} } @article{KochFroehlich2020, author = {Koch-Fr{\"o}hlich, Melanie}, title = {S'inventer {\`a} partir de l'autre : Les Origines d'Amin Maalouf}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244268}, pages = {69-84}, year = {2020}, abstract = {The present article examines the narrative modes in which Lebanese author Amin Maalouf investigates his roots in Origines a hybrid work which stands in contrast with his previous essays and fictions as to its (auto)biographical dimension. Resembling what Dominique Viart and Bruno Vercier in their analysis of predominant themes and narrative strategies in contemporary French literature name «r{\´e}cit de filiation», Maalouf's quest for his familial past explores the concept of intergenerational transmission of memory. However, despite this individual postmemorial approach, Maalouf's intimate writing is intrinsically linked with the complex history of the Ottoman Empire and therefore with collective narratives of war, diasporic identities, and migration relating to the present time or the recent past.}, language = {fr} } @article{Hesselbach2020, author = {Hesselbach, Robert}, title = {<> - A Corpus-based Approach of Official French, Italian, and Spanish Social Media Discourse in the Light of the Coronavirus Crisis}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244251}, pages = {45-66}, year = {2020}, abstract = {France, Italy, and Spain are three Romance-speaking countries which - at least in Europe - have been affected to a very high degree by the consequences of the Corona pandemic. This paper examines discursive strategies on social media (Twitter and Facebook) by the three heads of government/state of the aforementioned countries - namely Emmanuel Macron (France), Giuseppe Conte (Italy), and Pedro S{\´a}nchez (Spain)- from a corpuslinguistic point of view. For this purpose, a corpus was created which contains all Twitter and Facebook messages posted by these heads of government/state from the beginning of February until the end of April 2020. By applying corpus-linguistic methods we find that all three politicians consciously use social media to sensitize, inform, and - in view of a dramatic pandemic situation - unite their respective populations behind them.}, language = {en} } @article{BurekBurmesterSalvadoretal.2020, author = {Burek, Malgorzata and Burmester, Sandra and Salvador, Ellaine and M{\"o}ller-Ehrlich, Kerstin and Schneider, Reinhard and Roewer, Norbert and Nagai, Michiaki and F{\"o}rster, Carola Y.}, title = {Kidney Ischemia/Reperfusion Injury Induces Changes in the Drug Transporter Expression at the Blood-Brain Barrier in vivo and in vitro}, series = {Frontiers in Physiology}, volume = {11}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2020.569881}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216413}, year = {2020}, abstract = {Ischemia/reperfusion injury is a major cause of acute kidney injury (AKI). AKI is characterized by a sudden decrease in kidney function, systemic inflammation, oxidative stress, and dysregulation of the sodium, potassium, and water channels. While AKI leads to uremic encephalopathy, epidemiological studies have shown that AKI is associated with a subsequent risk for developing stroke and dementia. To get more insights into kidney-brain crosstalk, we have created an in vitro co-culture model based on human kidney cells of the proximal tubule (HK-2) and brain microvascular endothelial cells (BMEC). The HK-2 cell line was grown to confluence on 6-well plates and exposed to oxygen/glucose deprivation (OGD) for 4 h. Control HK-2 cells were grown under normal conditions. The BMEC cell line cerebED was grown to confluence on transwells with 0.4 μm pores. The transwell filters seeded and grown to confluence with cereEND were inserted into the plates with HK-2 cells with or without OGD treatment. In addition, cerebEND were left untreated or treated with uremic toxins, indole-3-acetic acid (IAA) and indoxyl sulfate (IS). The protein and mRNA expression of selected BBB-typical influx transporters, efflux transporters, cellular receptors, and tight junction proteins was measured in BMECs. To validate this in vitro model of kidney-brain interaction, we isolated brain capillaries from mice exposed to bilateral renal ischemia (30 min)/reperfusion injury (24 h) and measured mRNA and protein expression as described above. Both in vitro and in vivo systems showed similar changes in the expression of drug transporters, cellular receptors, and tight junction proteins. Efflux pumps, in particular Abcb1b, Abcc1, and Abcg2, have shown increased expression in our model. Thus, our in vitro co-culture system can be used to study the cellular mechanism of kidney and brain crosstalk in renal ischemia/reperfusion injury.}, language = {en} } @article{KablauBergRutschmannetal.2020, author = {Kablau, Arne and Berg, Stefan and Rutschmann, Benjamin and Scheiner, Ricarda}, title = {Short-term hyperthermia at larval age reduces sucrose responsiveness of adult honeybees and can increase life span}, series = {Apidologie}, volume = {51}, journal = {Apidologie}, issn = {0044-8435}, doi = {10.1007/s13592-020-00743-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232462}, pages = {570-582}, year = {2020}, abstract = {Honeybees are very sensitive to their breeding temperature. Even slightly lower temperatures during larval development can significantly affect adult behavior. Several devices which are employed for killing the honeybee ectoparasite Varroa destructor rely on short-term hyperthermia in the honeybee hive. The device used here applies 43.7 °C for 2 h, which is highly effective in killing the mites. We study how short-term hyperthermia affects worker brood and behavior of emerging adult bees. Sucrose responsiveness was strongly reduced after treatment of larvae early or late of larval development. Hyperthermia significantly enhanced life span, particularly in bees receiving treated early in larval development. To ask whether increased life span correlated with foraging performance, we used radio frequency identification (RFID). Onset and offset of foraging behavior as well as foraging trip duration and lifetime foraging effort were unaffected by hyperthermia treatment as prepupa.}, language = {en} } @article{PalmisanoBrandtVissanietal.2020, author = {Palmisano, Chiara and Brandt, Gregor and Vissani, Matteo and Pozzi, Nicol{\´o} G. and Canessa, Andrea and Brumberg, Joachim and Marotta, Giorgio and Volkmann, Jens and Mazzoni, Alberto and Pezzoli, Gianni and Frigo, Carlo A. and Isaias, Ioannis U.}, title = {Gait Initiation in Parkinson's Disease: Impact of Dopamine Depletion and Initial Stance Condition}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {8}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2020.00137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200801}, year = {2020}, abstract = {Postural instability, in particular at gait initiation (GI), and resulting falls are a major determinant of poor quality of life in subjects with Parkinson's disease (PD). Still, the contribution of the basal ganglia and dopamine on the feedforward postural control associated with this motor task is poorly known. In addition, the influence of anthropometric measures (AM) and initial stance condition on GI has never been consistently assessed. The biomechanical resultants of anticipatory postural adjustments contributing to GI [imbalance (IMB), unloading (UNL), and stepping phase) were studied in 26 unmedicated subjects with idiopathic PD and in 27 healthy subjects. A subset of 13 patients was analyzed under standardized medication conditions and the striatal dopaminergic innervation was studied in 22 patients using FP-CIT and SPECT. People with PD showed a significant reduction in center of pressure (CoP) displacement and velocity during the IMB phase, reduced first step length and velocity, and decreased velocity and acceleration of the center of mass (CoM) at toe off of the stance foot. All these measurements correlated with the dopaminergic innervation of the putamen and substantially improved with levodopa. These results were not influenced by anthropometric parameters or by the initial stance condition. In contrast, most of the measurements of the UNL phase were influenced by the foot placement and did not correlate with putaminal dopaminergic innervation. Our results suggest a significant role of dopamine and the putamen particularly in the elaboration of the IMB phase of anticipatory postural adjustments and in the execution of the first step. The basal ganglia circuitry may contribute to defining the optimal referent body configuration for a proper initiation of gait and possibly gait adaptation to the environment.}, language = {en} } @article{MayrRamirezZavalaKruegeretal.2020, author = {Mayr, Eva-Maria and Ram{\´i}rez-Zavala, Bernardo and Kr{\"u}ger, Ines and Morschh{\"a}user, Joachim}, title = {A Zinc Cluster Transcription Factor Contributes to the Intrinsic Fluconazole Resistance of Candida auris}, series = {mSphere}, volume = {5}, journal = {mSphere}, number = {2}, doi = {10.1128/mSphere.00279-20}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229937}, year = {2020}, abstract = {ABSTRACT The recently emerged pathogenic yeast Candida auris is a major concern for human health, because it is easily transmissible, difficult to eradicate from hospitals, and highly drug resistant. Most C. auris isolates are resistant to the widely used antifungal drug fluconazole due to mutations in the target enzyme Erg11 and high activity of efflux pumps, such as Cdr1. In the well-studied, distantly related yeast Candida albicans, overexpression of drug efflux pumps also is a major mechanism of acquired fluconazole resistance and caused by gain-of-function mutations in the zinc cluster transcription factors Mrr1 and Tac1. In this study, we investigated a possible involvement of related transcription factors in efflux pump expression and fluconazole resistance of C. auris. The C. auris genome contains three genes encoding Mrr1 homologs and two genes encoding Tac1 homologs, and we generated deletion mutants lacking these genes in two fluconazole-resistant strains from clade III and clade IV. Deletion of TAC1b decreased the resistance to fluconazole and voriconazole in both strain backgrounds, demonstrating that the encoded transcription factor contributes to azole resistance in C. auris strains from different clades. CDR1 expression was not or only minimally affected in the mutants, indicating that Tac1b can confer increased azole resistance by a CDR1-independent mechanism. IMPORTANCE Candida auris is a recently emerged pathogenic yeast that within a few years after its initial description has spread all over the globe. C. auris is a major concern for human health, because it can cause life-threatening systemic infections, is easily transmissible, and is difficult to eradicate from hospital environments. Furthermore, C. auris is highly drug resistant, especially against the widely used antifungal drug fluconazole. Mutations in the drug target and high activity of efflux pumps are associated with azole resistance, but it is not known how drug resistance genes are regulated in C. auris. We have investigated the potential role of several candidate transcriptional regulators in the intrinsic fluconazole resistance of C. auris and identified a transcription factor that contributes to the high resistance to fluconazole and voriconazole of two C. auris strains from different genetic clades, thereby providing insight into the molecular basis of drug resistance of this medically important yeast."}, language = {en} } @article{SodemannDaehlingKlopfleischetal.2020, author = {Sodemann, Elisa B. and D{\"a}hling, Sabrina and Klopfleisch, Robert and Boiarina, Ekaterina and Cataldo, Didier and Alhasan, Moumen M. and Yildirim, Ali {\"O}. and Witzenrath, Martin and Tabeling, Christoph and Conrad, Melanie L.}, title = {Maternal asthma is associated with persistent changes in allergic offspring antibody glycosylation}, series = {Clinical \& Experimental Allergy}, volume = {50}, journal = {Clinical \& Experimental Allergy}, number = {4}, doi = {10.1111/cea.13559}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214071}, pages = {520 -- 531}, year = {2020}, abstract = {Background Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status. Objective Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. Methods Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn-297 IgG glycosylation was analysed in maternal and offspring serum. Results When mothers and offspring were sensitized to the same allergen (OVA-OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS-OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro-inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn-297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. Conclusions and Clinical Relevance We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro-inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies.}, language = {en} } @article{GeigerAcharyaReutteretal.2020, author = {Geiger, Michael and Acharya, Rachana and Reutter, Eric and Ferschke, Thomas and Zschieschang, Ute and Weis, J{\"u}rgen and Pflaum, Jens and Klauk, Hagen and Weitz, Ralf Thomas}, title = {Effect of the Degree of the Gate-Dielectric Surface Roughness on the Performance of Bottom-Gate Organic Thin-Film Transistors}, series = {Advanced Materials Interfaces}, volume = {7}, journal = {Advanced Materials Interfaces}, number = {10}, doi = {10.1002/admi.201902145}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214830}, year = {2020}, abstract = {In organic thin-film transistors (TFTs) fabricated in the inverted (bottom-gate) device structure, the surface roughness of the gate dielectric onto which the organic-semiconductor layer is deposited is expected to have a significant effect on the TFT characteristics. To quantitatively evaluate this effect, a method to tune the surface roughness of a gate dielectric consisting of a thin layer of aluminum oxide and an alkylphosphonic acid self-assembled monolayer over a wide range by controlling a single process parameter, namely the substrate temperature during the deposition of the aluminum gate electrodes, is developed. All other process parameters remain constant in the experiments, so that any differences observed in the TFT performance can be confidently ascribed to effects related to the difference in the gate-dielectric surface roughness. It is found that an increase in surface roughness leads to a significant decrease in the effective charge-carrier mobility and an increase in the subthreshold swing. It is shown that a larger gate-dielectric surface roughness leads to a larger density of grain boundaries in the semiconductor layer, which in turn produces a larger density of localized trap states in the semiconductor.}, language = {en} } @article{Schwalb‐WillmannRemelgadoSafietal.2020, author = {Schwalb-Willmann, Jakob and Remelgado, Ruben and Safi, Kamran and Wegmann, Martin}, title = {moveVis: Animating movement trajectories in synchronicity with static or temporally dynamic environmental data in R}, series = {Methods in Ecology and Evolution}, volume = {11}, journal = {Methods in Ecology and Evolution}, number = {5}, doi = {10.1111/2041-210X.13374}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214856}, pages = {664 -- 669}, year = {2020}, abstract = {Visualizing movement data is challenging: While traditional spatial data can be sufficiently displayed as two-dimensional plots or maps, movement trajectories require the representation of time in a third dimension. To address this, we present moveVis, an R package, which provides tools to animate movement trajectories, overlaying simultaneous uni- or multi-temporal raster imagery or vector data. moveVis automates the processing of movement and environmental data to turn such into an animation. This includes (a) the regularization of movement trajectories enforcing uniform time instances and intervals across all trajectories, (b) the frame-wise mapping of movement trajectories onto temporally static or dynamic environmental layers, (c) the addition of customizations, for example, map elements or colour scales and (d) the rendering of frames into an animation encoded as GIF or video file. moveVis is designed to display interactions and concurrencies of animal movement and environmental data. We present examples and use cases, ranging from data exploration to visualizing scientific findings. Static spatial plots of movement data disregard the temporal dimension that distinguishes movement from other spatial data. In contrast, animations allow to display relocation in both time and space. We deem animations a powerful way to visually explore movement data, frame analytical findings and display potential interactions with spatially continuous and temporally dynamic environmental covariates.}, language = {en} } @article{MayrPetersEardleyetal.2020, author = {Mayr, Antonia V. and Peters, Marcell K. and Eardley, Connal D. and Renner, Marion E. and R{\"o}der, Juliane and Steffan-Dewenter, Ingolf}, title = {Climate and food resources shape species richness and trophic interactions of cavity-nesting Hymenoptera}, series = {Journal of Biogeography}, volume = {47}, journal = {Journal of Biogeography}, number = {4}, doi = {10.1111/jbi.13753}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208101}, pages = {854-865}, year = {2020}, abstract = {Aim: Temperature, food resources and top-down regulation by antagonists are considered as major drivers of insect diversity, but their relative importance is poorly understood. Here, we used cavity-nesting communities of bees, wasps and their antagonists to reveal the role of temperature, food resources, parasitism rate and land use as drivers of species richness at different trophic levels along a broad elevational gradient. Location: Mt. Kilimanjaro, Tanzania. Taxon: Cavity-nesting Hymenoptera (Hymenoptera: Apidae, Colletidae, Megachilidae, Crabronidae, Sphecidae, Pompilidae, Vespidae). Methods: We established trap nests on 25 study sites that were distributed over similar large distances in terms of elevation along an elevational gradient from 866 to 1788 m a.s.l., including both natural and disturbed habitats. We quantified species richness and abundance of bees, wasps and antagonists, parasitism rates and flower or arthropod food resources. Data were analysed with generalized linear models within a multi-model inference framework. Results: Elevational species richness patterns changed with trophic level from monotonically declining richness of bees to increasingly humped-shaped patterns for caterpillar-hunting wasps, spider-hunting wasps and antagonists. Parasitism rates generally declined with elevation but were higher for wasps than for bees. Temperature was the most important predictor of both bee and wasp host richness patterns. Antagonist richness patterns were also well predicted by temperature, but in contrast to host richness patterns, additionally by resource abundance and diversity. The conversion of natural habitats through anthropogenic land use, which included biomass removal, agricultural inputs, vegetation structure and percentage of surrounding agricultural habitats, had no significant effects on bee and wasp communities. Main conclusions: Our study underpins the importance of temperature as a main driver of diversity gradients in ectothermic organisms and reveals the increasingly important role of food resources at higher trophic levels. Higher parasitism rates at higher trophic levels and at higher temperatures indicated that the relative importance of bottom-up and top-down drivers of species richness change across trophic levels and may respond differently to future climate change.}, language = {en} } @article{KaussnerKuraszkiewiczSchochetal.2020, author = {Kaussner, Y. and Kuraszkiewicz, A. M. and Schoch, S. and Markel, Petra and Hoffmann, S. and Baur-Streubel, R. and Kenntner-Mabiala, R. and Pauli, P.}, title = {Treating patients with driving phobia by virtual reality exposure therapy - a pilot study}, series = {PLoS ONE}, volume = {15}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0226937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201051}, pages = {e0226937}, year = {2020}, abstract = {Objectives Virtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with fear of driving as measured by a post-treatment driving test in real traffic. Methods The therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients' anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed. Results The treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71\% showed an adequate driving behavior as assessed by the driving instructor, and 93\% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale-Self Report: p < .05). Conclusions VRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.}, language = {en} } @article{SchoenBerkingBiedermannetal.2020, author = {Sch{\"o}n, Michael P. and Berking, Carola and Biedermann, Tilo and Buhl, Timo and Erpenbeck, Luise and Eyerich, Kilian and Eyerich, Stefanie and Ghoreschi, Kamran and Goebeler, Matthias and Ludwig, Ralf J. and Sch{\"a}kel, Knut and Schilling, Bastian and Schlapbach, Christoph and Stary, Georg and von Stebut, Esther and Steinbrink, Kerstin}, title = {COVID-19 and immunological regulations - from basic and translational aspects to clinical implications}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14169}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218205}, pages = {795 -- 807}, year = {2020}, abstract = {The COVID-19 pandemic caused by SARS-CoV-2 has far-reaching direct and indirect medical consequences. These include both the course and treatment of diseases. It is becoming increasingly clear that infections with SARS-CoV-2 can cause considerable immunological alterations, which particularly also affect pathogenetically and/or therapeutically relevant factors. Against this background we summarize here the current state of knowledge on the interaction of SARS-CoV-2/COVID-19 with mediators of the acute phase of inflammation (TNF, IL-1, IL-6), type 1 and type 17 immune responses (IL-12, IL-23, IL-17, IL-36), type 2 immune reactions (IL-4, IL-13, IL-5, IL-31, IgE), B-cell immunity, checkpoint regulators (PD-1, PD-L1, CTLA4), and orally druggable signaling pathways (JAK, PDE4, calcineurin). In addition, we discuss in this context non-specific immune modulation by glucocorticosteroids, methotrexate, antimalarial drugs, azathioprine, dapsone, mycophenolate mofetil and fumaric acid esters, as well as neutrophil granulocyte-mediated innate immune mechanisms. From these recent findings we derive possible implications for the therapeutic modulation of said immunological mechanisms in connection with SARS-CoV-2/COVID-19. Although, of course, the greatest care should be taken with patients with immunologically mediated diseases or immunomodulating therapies, it appears that many treatments can also be carried out during the COVID-19 pandemic; some even appear to alleviate COVID-19.}, language = {en} } @article{Ingerslev2020, author = {Ingerslev, Line Ryberg}, title = {Inhibited Intentionality: On Possible Self-Understanding in Cases of Weak Agency}, series = {Frontiers in Psychology}, volume = {11}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2020.558709}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212950}, year = {2020}, abstract = {The paper addresses the question of how to approach consciousness in unreflective actions. Unreflective actions differ from reflective, conscious actions in that the intentional description under which the agent knows what she is doing is not available or present to the agent at the moment of acting. Yet, unreflective actions belong to the field in which an agent experiences herself as capable of acting. Some unreflective actions, however, narrow this field and can be characterized by intentionality being inhibited. By studying inhibited intentionality in unreflective actions, the aim of the paper is to show how weaker forms of action urge us to expand our overall understanding of action. If we expand the field of actions such that it encompasses also some of the involuntary aspects of action, we are able to understand how unreflective actions can remain actions and do not fall under the scope of automatic behavior. With the notion of weak agency, the paper thus addresses one aspect of unreflective action, namely, "inhibited intentionality" in which an agent feels a diminished sense of authorship in relation to her possibility for self-understanding. The notion of weak agency clarifies how agency itself remains intact but can involve a process of appropriation of one's actions as one's own. With a diachronic account of consciousness in unreflective action, the paper accounts for possible self-understanding in cases where none seems available at the moment of action.}, language = {en} } @article{PetersClassenMuelleretal.2020, author = {Peters, Marcell K. and Classen, Alice and M{\"u}ller, J{\"o}rg and Steffan‑Dewenter, Ingolf}, title = {Increasing the phylogenetic coverage for understanding broad-scale diversity gradients}, series = {Oecologia}, volume = {192}, journal = {Oecologia}, issn = {0029-8549}, doi = {10.1007/s00442-020-04615-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232519}, pages = {629-639}, year = {2020}, abstract = {Despite decades of scientific effort, there is still no consensus on the determinants of broad-scale gradients of animal diver-sity. We argue that general drivers of diversity are unlikely to be found among the narrowly defined taxa which are typically analyzed in studies of broad-scale diversity gradients because ecological niches evolve largely conservatively. This causes constraints in the use of available niche space leading to systematic differences in diversity gradients among taxa. We instead advocate studies of phylogenetically diverse animal communities along broad environmental gradients. Such multi-taxa communities are less constrained in resource use and diversification and may be better targets for testing major classical hypotheses on diversity gradients. Besides increasing the spatial scale in analyses, expanding the phylogenetic coverage may be a second way to achieve higher levels of generality in studies of broad-scale diversity gradients}, language = {en} } @article{AppeltshauserBrunderHeiniusetal.2020, author = {Appeltshauser, Luise and Brunder, Anna-Michelle and Heinius, Annika and K{\"o}rtv{\´e}lyessy, Peter and Wandinger, Klaus-Peter and Junker, Ralf and Villmann, Carmen and Sommer, Claudia and Leypoldt, Frank and Doppler, Kathrin}, title = {Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy}, series = {Neurology: Neuroimmunology \& Neuroinflammation}, volume = {7}, journal = {Neurology: Neuroimmunology \& Neuroinflammation}, number = {5}, doi = {10.1212/NXI.0000000000000817}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230079}, year = {2020}, abstract = {Objective To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples. Methods We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively. Results We detected antiparanodal autoantibodies with a prevalence of 4.3\% (7/161), more often in A-CIDP (4/23, 17.4\%) compared with GBS (3/114, 2.6\%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4. Conclusion Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.}, language = {en} } @article{GernertTonySchwanecketal.2020, author = {Gernert, Michael and Tony, Hans-Peter and Schwaneck, Eva Christina and Fr{\"o}hlich, Matthias and Schmalzing, Marc}, title = {Low B cell counts as risk factor for infectious complications in systemic sclerosis after autologous hematopoietic stem cell transplantation}, series = {Arthritis Research \& Therapy}, volume = {22}, journal = {Arthritis Research \& Therapy}, doi = {10.1186/s13075-020-02255-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229962}, year = {2020}, abstract = {Background Autologous hematopoietic stem cell transplantation (aHSCT) is a treatment option for a selected group of systemic sclerosis (SSc) patients with good available evidence but can be associated with considerable morbidity and mortality. The aim of this study was to describe infectious complications and distinct immune reconstitution patterns after aHSCT and to detect risk factors in lymphocyte subsets, which are associated with an elevated rate of infections after aHSCT. Methods Seventeen patients with SSc were included in this single-center retrospective cohort study. Clinical and laboratory data was collected before and for 12 months after aHSCT, including immunophenotyping of peripheral whole blood by fluorescence-activated cell sorting. Results Cytomegalovirus (CMV) reactivations were common in CMV-IgG-positive patients (50\%) and needed treatment. Mycotic infections occurred in 17.6\%. One patient died (resulting in a mortality of 5.9\%) due to pneumonia with consecutive sepsis. All patients showed decreased T helper cells (CD3\(^+\)/CD4\(^+\)) and within the B cell compartment decreased post-switched memory B cells (CD19\(^+\)/CD27\(^+\)/IgD\(^-\)) and elevated naive B cells (CD19\(^+\)/CD27\(^-\)/IgD\(^+\)) until 12 months after aHSCT. Patients who developed infections had significantly lower B cells before aHSCT than patients who did not develop infections. Conclusion After aHSCT, monitoring for infectious complications, especially for CMV reactivations, is crucial as the reconstitution of the immune system takes longer than 12 months. Low peripheral B cells might be a risk factor for an elevated infection rate.}, language = {en} } @article{ThornSeiboldLeverkusetal.2020, author = {Thorn, Simon and Seibold, Sebastian and Leverkus, Alexandro B and Michler, Thomas and M{\"u}ller, J{\"o}rg and Noss, Reed F and Stork, Nigel and Vogel, Sebastian and Lindenmayer, David B}, title = {The living dead: acknowledging life after tree death to stop forest degradation}, series = {Frontiers in Ecology and the Environment}, volume = {18}, journal = {Frontiers in Ecology and the Environment}, number = {9}, doi = {10.1002/fee.2252}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218575}, pages = {505 -- 512}, year = {2020}, abstract = {Global sustainability agendas focus primarily on halting deforestation, yet the biodiversity crisis resulting from the degradation of remaining forests is going largely unnoticed. Forest degradation occurs through the loss of key ecological structures, such as dying trees and deadwood, even in the absence of deforestation. One of the main drivers of forest degradation is limited awareness by policy makers and the public on the importance of these structures for supporting forest biodiversity and ecosystem function. Here, we outline management strategies to protect forest health and biodiversity by maintaining and promoting deadwood, and propose environmental education initiatives to improve the general awareness of the importance of deadwood. Finally, we call for major reforms to forest management to maintain and restore deadwood; large, old trees; and other key ecological structures.}, language = {en} } @article{Prieto‐GarciaHartmannReisslandetal.2020, author = {Prieto-Garcia, Cristian and Hartmann, Oliver and Reissland, Michaela and Braun, Fabian and Fischer, Thomas and Walz, Susanne and Sch{\"u}lein-V{\"o}lk, Christina and Eilers, Ursula and Ade, Carsten P. and Calzado, Marco A. and Orian, Amir and Maric, Hans M. and M{\"u}nch, Christian and Rosenfeldt, Mathias and Eilers, Martin and Diefenbacher, Markus E.}, title = {Maintaining protein stability of ∆Np63 via USP28 is required by squamous cancer cells}, series = {EMBO Molecular Medicine}, volume = {12}, journal = {EMBO Molecular Medicine}, number = {4}, doi = {10.15252/emmm.201911101}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218303}, year = {2020}, abstract = {The transcription factor ∆Np63 is a master regulator of epithelial cell identity and essential for the survival of squamous cell carcinoma (SCC) of lung, head and neck, oesophagus, cervix and skin. Here, we report that the deubiquitylase USP28 stabilizes ∆Np63 and maintains elevated ∆NP63 levels in SCC by counteracting its proteasome-mediated degradation. Impaired USP28 activity, either genetically or pharmacologically, abrogates the transcriptional identity and suppresses growth and survival of human SCC cells. CRISPR/Cas9-engineered in vivo mouse models establish that endogenous USP28 is strictly required for both induction and maintenance of lung SCC. Our data strongly suggest that targeting ∆Np63 abundance via inhibition of USP28 is a promising strategy for the treatment of SCC tumours.}, language = {en} } @article{HessMengSchulteetal.2020, author = {Heß, Verena and Meng, Karin and Schulte, Thomas and Neuderth, Silke and Bengel, J{\"u}rgen and Faller, Hermann and Schuler, Michael}, title = {Prevalence and predictors of cancer patients' unexpressed needs in the admission interview of inpatient rehabilitation}, series = {Psycho-Oncology}, volume = {29}, journal = {Psycho-Oncology}, number = {10}, doi = {10.1002/pon.5450}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228369}, pages = {1549 -- 1556}, year = {2020}, abstract = {Objective The admission interview in oncological inpatient rehabilitation might be a good opportunity to identify cancer patients' needs present after acute treatment. However, a relevant number of patients may not express their needs. In this study, we examined (a) the proportion of cancer patients with unexpressed needs, (b) topics of unexpressed needs and reasons for not expressing needs, (c) correlations of not expressing needs with several patient characteristics, and (d) predictors of not expressing needs. Methods We enrolled 449 patients with breast, prostate, and colon cancer at beginning and end of inpatient rehabilitation. We obtained self-reports about unexpressed needs and health-related variables (quality of life, depression, anxiety, adjustment disorder, and health literacy). We estimated frequencies and conducted correlation and ordinal logistic regression analyses. Results A quarter of patients stated they had "rather not" or "not at all" expressed all relevant needs. Patients mostly omitted fear of cancer recurrence. Most frequent reasons for not expressing needs were being focused on physical consequences of cancer, concerns emerging only later, and not knowing about the possibility of talking about distress. Not expressing needs was associated with several health-related outcomes, for example, emotional functioning, adjustment disorder, fear of progression, and health literacy. Depression measured at the beginning of rehabilitation showed only small correlations and is therefore not sufficient to identify patients with unexpressed needs. Conclusions A relevant proportion of cancer patients reported unexpressed needs in the admission interview. This was associated with decreased mental health. Therefore, it seems necessary to support patients in expressing needs.}, language = {en} } @article{ElHossaryAbdelHalimIbrahimetal.2020, author = {El-Hossary, Ebaa M. and Abdel-Halim, Mohammad and Ibrahim, Eslam S. and Pimentel-Elardo, Sheila Marie and Nodwell, Justin R. and Handoussa, Heba and Abdelwahab, Miada F. and Holzgrabe, Ulrike and Abdelmohsen, Usama Ramadan}, title = {Natural Products Repertoire of the Red Sea}, series = {Marine Drugs}, volume = {18}, journal = {Marine Drugs}, number = {9}, issn = {1660-3397}, doi = {10.3390/md18090457}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213110}, year = {2020}, abstract = {Marine natural products have achieved great success as an important source of new lead compounds for drug discovery. The Red Sea provides enormous diversity on the biological scale in all domains of life including micro- and macro-organisms. In this review, which covers the literature to the end of 2019, we summarize the diversity of bioactive secondary metabolites derived from Red Sea micro- and macro-organisms, and discuss their biological potential whenever applicable. Moreover, the diversity of the Red Sea organisms is highlighted as well as their genomic potential. This review is a comprehensive study that compares the natural products recovered from the Red Sea in terms of ecological role and pharmacological activities.}, language = {en} } @article{SteinhardtZhouKrummenastetal.2020, author = {Steinhardt, Maximilian Johannes and Zhou, Xiang and Krummenast, Franziska and Meckel, Katharina and Nickel, Katharina and B{\"o}ckle, David and Messerschmidt, Janin and Knorz, Sebastian and Dierks, Alexander and Heidemeier, Anke and Lapa, Constantin and Einsele, Hermann and Rasche, Leo and Kort{\"u}m, Klaus Martin}, title = {Sequential CD38 monoclonal antibody retreatment leads to deep remission in a patient with relapsed/refractory multiple myeloma}, series = {International Journal of Immunopathology and Pharmacology}, volume = {34}, journal = {International Journal of Immunopathology and Pharmacology}, doi = {10.1177/2058738420980258}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236235}, pages = {1-5}, year = {2020}, abstract = {We report on a currently 76-year-old female patient with relapsed/refractory (RR) multiple myeloma (MM) treated at our institution. This patient had received six lines of therapy including tandem autologous stem cell transplant, proteasome inhibitor, immunomodulatory drugs and CD38 antibody MOR202. At the last relapse, she progressed during treatment with pomalidomide and MOR202. In an individualized therapy concept, we started a multi-agent salvage therapy with pomalidomide, bortezomib, doxorubicin, dexamethasone, and CD38 antibody daratumumab ("Pom-PAD-Dara"), which resulted in a stringent complete remission with minimal residual disease (MRD) negativity after nine cycles. So far, our patient shows a progression free survival of more than 12 months. Our case demonstrates the feasibility of successful CD38 antibody retreatment in a patient with heavily pretreated CD38 antibody resistant MM.}, language = {en} } @article{SchumannScherthanFranketal.2020, author = {Schumann, Sarah and Scherthan, Harry and Frank, Torsten and Lapa, Constantin and M{\"u}ller, Jessica and Seifert, Simone and Lassmann, Michael and Eberlein, Uta}, title = {DNA Damage in Blood Leukocytes of Prostate Cancer Patients Undergoing PET/CT Examinations with [\(^{68}\)Ga]Ga-PSMA I\&T}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {2}, issn = {2072-6694}, doi = {10.3390/cancers12020388}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200585}, pages = {388}, year = {2020}, abstract = {The aim was to investigate the induction and repair of radiation-induced DNA double-strand breaks (DSBs) as a function of the absorbed dose to the blood of patients undergoing PET/CT examinations with [68Ga]Ga-PSMA. Blood samples were collected from 15 patients before and at four time points after [68Ga]Ga-PSMA administration, both before and after the PET/CT scan. Absorbed doses to the blood were calculated. In addition, blood samples with/without contrast agent from five volunteers were irradiated ex vivo by CT while measuring the absorbed dose. Leukocytes were isolated, fixed, and stained for co-localizing γ-H2AX+53BP1 DSB foci that were enumerated manually. In vivo, a significant increase in γ-H2AX+53BP1 foci compared to baseline was observed at all time points after administration, although the absorbed dose to the blood by 68Ga was below 4 mGy. Ex vivo, the increase in radiation-induced foci depended on the absorbed dose and the presence of contrast agent, which could have caused a dose enhancement. The CT-dose contribution for the patients was estimated at about 12 mGy using the ex vivo calibration. The additional number of DSB foci induced by CT, however, was comparable to the one induced by 68Ga. The significantly increased foci numbers after [68Ga]Ga-PSMA administration may suggest a possible low-dose hypersensitivity.}, language = {en} } @article{AssfalgSeligTolksdorfetal.2020, author = {Assfalg, Volker and Selig, Katharina and Tolksdorf, Johanna and van Meel, Marieke and de Vries, Erwin and Ramsoebhag, Anne-Marie and Rahmel, Axel and Renders, Lutz and Novotny, Alexander and Matevossian, Edouard and Schneeberger, Stefan and Rosenkranz, Alexander R. and Berlakovich, Gabriela and Ysebaert, Dirk and Knops, No{\"e}l and Kuypers, Dirk and Weekers, Laurent and Muehlfeld, Anja and Rump, Lars-Christian and Hauser, Ingeborg and Pisarski, Przemyslaw and Weimer, Rolf and Fornara, Paolo and Fischer, Lutz and Kliem, Volker and Sester, Urban and Stippel, Dirk and Arns, Wolfgang and Hau, Hans-Michael and Nitschke, Martin and Hoyer, Joachim and Thorban, Stefan and Weinmann-Menke, Julia and Heller, Katharina and Banas, Bernhard and Schwenger, Vedat and Nadalin, Silvio and Lopau, Kai and H{\"u}ser, Norbert and Heemann, Uwe}, title = {Repeated kidney re-transplantation—the Eurotransplant experience: a retrospective multicenter outcome analysis}, series = {Transplant International}, volume = {33}, journal = {Transplant International}, number = {6}, doi = {10.1111/tri.13569}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214161}, pages = {617 -- 631}, year = {2020}, abstract = {In Eurotransplant kidney allocation system (ETKAS), candidates can be considered unlimitedly for repeated re-transplantation. Data on outcome and benefit are indeterminate. We performed a retrospective 15-year patient and graft outcome data analysis from 1464 recipients of a third or fourth or higher sequential deceased donor renal transplantation (DDRT) from 42 transplant centers. Repeated re-DDRT recipients were younger (mean 43.0 vs. 50.2 years) compared to first DDRT recipients. They received grafts with more favorable HLA matches (89.0\% vs. 84.5\%) but thereby no statistically significant improvement of patient and graft outcome was found as comparatively demonstrated in 1st DDRT. In the multivariate modeling accounting for confounding factors, mortality and graft loss after 3rd and ≥4th DDRT (P < 0.001 each) and death with functioning graft (DwFG) after 3rd DDRT (P = 0.001) were higher as compared to 1st DDRT. The incidence of primary nonfunction (PNF) was also significantly higher in re-DDRT (12.7\%) than in 1st DDRT (7.1\%; P < 0.001). Facing organ shortage, increasing waiting time, and considerable mortality on dialysis, we question the current policy of repeated re-DDRT. The data from this survey propose better HLA matching in first DDRT and second DDRT and careful selection of candidates, especially for ≥4th DDRT.}, language = {en} } @article{DuekingZinnerReedetal.2020, author = {D{\"u}king, Peter and Zinner, Christoph and Reed, Jennifer L. and Holmberg, Hans-Christer and Sperlich, Billy}, title = {Predefined vs data-guided training prescription based on autonomic nervous system variation: A systematic review}, series = {Scandinavian Journal of Medicine \& Science in Sports}, volume = {30}, journal = {Scandinavian Journal of Medicine \& Science in Sports}, number = {12}, doi = {10.1111/sms.13802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217893}, pages = {2291 -- 2304}, year = {2020}, abstract = {Monitoring variations in the functioning of the autonomic nervous system may help personalize training of runners and provide more pronounced physiological adaptations and performance improvements. We systematically reviewed the scientific literature comparing physiological adaptations and/or improvements in performance following training based on responses of the autonomic nervous system (ie, changes in heart rate variability) and predefined training. PubMed, SPORTDiscus, and Web of Science were searched systematically in July 2019. Keywords related to endurance, running, autonomic nervous system, and training. Studies were included if they (a) involved interventions consisting predominantly of running training; (b) lasted at least 3 weeks; (c) reported pre- and post-intervention assessment of running performance and/or physiological parameters; (d) included an experimental group performing training adjusted continuously on the basis of alterations in HRV and a control group; and (e) involved healthy runners. Five studies involving six interventions and 166 participants fulfilled our inclusion criteria. Four HRV-based interventions reduced the amount of moderate- and/or high-intensity training significantly. In five interventions, improvements in performance parameters (3000 m, 5000 m, Loadmax, Tlim) were more pronounced following HRV-based training. Peak oxygen uptake (VO\(_{2peak}\)) and submaximal running parameters (eg, LT1, LT2) improved following both HRV-based and predefined training, with no clear difference in the extent of improvement in VO\(_{2peak}\). Submaximal running parameters tended to improve more following HRV-based training. Research findings to date have been limited and inconsistent. Both HRV-based and predefined training improve running performance and certain submaximal physiological adaptations, with effects of the former training tending to be greater.}, language = {en} } @article{GronwaldHoos2020, author = {Gronwald, Thomas and Hoos, Olaf}, title = {Correlation properties of heart rate variability during endurance exercise: A systematic review}, series = {Annals of Noninvasive Electrocardiology}, volume = {25}, journal = {Annals of Noninvasive Electrocardiology}, number = {1}, doi = {10.1111/anec.12697}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213548}, year = {2020}, abstract = {Background Non-linear measures of heart rate variability (HRV) may provide new opportunities to monitor cardiac autonomic regulation during exercise. In healthy individuals, the HRV signal is mainly composed of quasi-periodic oscillations, but it also possesses random fluctuations and so-called fractal structures. One widely applied approach to investigate fractal correlation properties of heart rate (HR) time series is the detrended fluctuation analysis (DFA). DFA is a non-linear method to quantify the fractal scale and the degree of correlation of a time series. Regarding the HRV analysis, it should be noted that the short-term scaling exponent alpha1 of DFA has been used not only to assess cardiovascular risk but also to assess prognosis and predict mortality in clinical settings. It has also been proven to be useful for application in exercise settings including higher exercise intensities, non-stationary data segments, and relatively short recording times. Method Therefore, the purpose of this systematic review was to analyze studies that investigated the effects of acute dynamic endurance exercise on DFA-alpha1 as a proxy of correlation properties in the HR time series. Results The initial search identified 442 articles (351 in PubMed, 91 in Scopus), of which 11 met all inclusion criteria. Conclusions The included studies show that DFA-alpha1 of HRV is suitable for distinguishing between different organismic demands during endurance exercise and may prove helpful to monitor responses to different exercise intensities, movement frequencies, and exercise durations. Additionally, non-linear DFA of HRV is a suitable analytical approach, providing a differentiated and qualitative view of exercise physiology.}, language = {en} } @article{Richter2020, author = {Richter, Verena}, title = {Das Mittelmeer als pluraler Erinnerungsraum im franz{\"o}sischen Essayfilm: zu Jean-Daniel Pollets M{\´e}diterran{\´e}e (1963)}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244292}, pages = {155-175}, year = {2020}, abstract = {The present article aims to examine images of the Mediterranean Sea in Jean-Daniel Pollet's essay film M{\´e}diterran{\´e}e (1963), with a particular focus on its representation as a multifaceted space of cultural memory. After some preliminary observations on the relation between the essay film as a genre and images of the Mediterranean, I shall, on the one hand, have a look at the semantic processes through which the film builds up a recognizable image of the Great Sea. On the other hand, however, I will argue that, at the same time, M{\´e}diterran{\´e}e calls this signifying process into question by representing the sea as a space of cultural memory understood as a space of becoming and of deferral of meaning.}, language = {de} } @article{vonRoeder2020, author = {von Roeder, Alena}, title = {Salvador als Opfer seiner eigenen Triebe im Film Los girasoles ciegos. Die filmische Darstellung der Fokalisierung unter psychoanalytischer Betrachtung}, series = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, volume = {6}, journal = {promptus - W{\"u}rzburger Beitr{\"a}ge zur Romanistik}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244303}, pages = {177-196}, year = {2020}, abstract = {This paper analyzes the mental development of the main character Salvador in the Spanish movie Los girasoles ciegos (2008) by Jos{\´e} Luis Cuerda, based on the camera perspective and focalization, as well as the three-instance model according to Sigmund Freud. For this purpose, screen captures from the movie are examined to see how Salvador's loss of control is pictured. This is applied to Freud's three-instance model to prove the takeover of the Id. Throughout the whole movie, the inner conflict between his Ego and Id, i.e. his life as a deacon versus his life as a soldier, is present. The whole process of the breakdown of his mental state is revealed through the camera perspective and visual focalization.}, language = {de} } @article{SturmGeisselMartinetal.2020, author = {Sturm, Laura and Geißel, Bernadette and Martin, Ronny and Wagener, Johannes}, title = {Differentially Regulated Transcription Factors and ABC Transporters in a Mitochondrial Dynamics Mutant Can Alter Azole Susceptibility of Aspergillus fumigatus}, series = {Frontiers in Microbiology}, volume = {11}, journal = {Frontiers in Microbiology}, issn = {1664-302X}, doi = {10.3389/fmicb.2020.01017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204874}, year = {2020}, abstract = {Azole resistance of the fungal pathogen Aspergillus fumigatus is an emerging problem. To identify novel mechanisms that could mediate azole resistance in A. fumigatus, we analyzed the transcriptome of a mitochondrial fission/fusion mutant that exhibits increased azole tolerance. Approximately 12\% of the annotated genes are differentially regulated in this strain. This comprises upregulation of Cyp51A, the azole target structure, upregulation of ATP-binding cassette (ABC) superfamily and major facilitator superfamily (MFS) transporters and differential regulation of transcription factors. To study their impact on azole tolerance, conditional mutants were constructed of seven ABC transporters and 17 transcription factors. Under repressed conditions, growth rates and azole susceptibility of the mutants were similar to wild type. Under induced conditions, several transcription factor mutants showed growth phenotypes. In addition, four ABC transporter mutants and seven transcription factor mutants exhibited altered azole susceptibility. However, deletion of individual identified ABC transporters and transcription factors did not affect the increased azole tolerance of the fission/fusion mutant. Our results revealed the ability of multiple ABC transporters and transcription factors to modulate the azole susceptibility of A. fumigatus and support a model where mitochondrial dysfunctions trigger a drug resistance network that mediates azole tolerance of this mold.}, language = {en} } @article{GrohRoessler2020, author = {Groh, Claudia and R{\"o}ssler, Wolfgang}, title = {Analysis of Synaptic Microcircuits in the Mushroom Bodies of the Honeybee}, series = {Insects}, volume = {11}, journal = {Insects}, number = {1}, issn = {2075-4450}, doi = {10.3390/insects11010043}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200774}, year = {2020}, abstract = {Mushroom bodies (MBs) are multisensory integration centers in the insect brain involved in learning and memory formation. In the honeybee, the main sensory input region (calyx) of MBs is comparatively large and receives input from mainly olfactory and visual senses, but also from gustatory/tactile modalities. Behavioral plasticity following differential brood care, changes in sensory exposure or the formation of associative long-term memory (LTM) was shown to be associated with structural plasticity in synaptic microcircuits (microglomeruli) within olfactory and visual compartments of the MB calyx. In the same line, physiological studies have demonstrated that MB-calyx microcircuits change response properties after associative learning. The aim of this review is to provide an update and synthesis of recent research on the plasticity of microcircuits in the MB calyx of the honeybee, specifically looking at the synaptic connectivity between sensory projection neurons (PNs) and MB intrinsic neurons (Kenyon cells). We focus on the honeybee as a favorable experimental insect for studying neuronal mechanisms underlying complex social behavior, but also compare it with other insect species for certain aspects. This review concludes by highlighting open questions and promising routes for future research aimed at understanding the causal relationships between neuronal and behavioral plasticity in this charismatic social insect.}, language = {en} } @article{FleischmannGrobRoessler2020, author = {Fleischmann, Pauline N. and Grob, Robin and R{\"o}ssler, Wolfgang}, title = {Kompass im Kopf : wie W{\"u}stenameisen lernen heimzukehren}, series = {Biologie in unserer Zeit}, volume = {50}, journal = {Biologie in unserer Zeit}, number = {2}, issn = {1521-415X}, doi = {10.1002/biuz.202010699}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219260}, pages = {100-109}, year = {2020}, abstract = {Erfolgreiche r{\"a}umliche Orientierung ist f{\"u}r viele Tiere eine allt{\"a}gliche Herausforderung. Cataglyphis-W{\"u}stenameisen sind bekannt f{\"u}r ihre Navigationsf{\"a}higkeiten, mit deren Hilfe sie nach langen Futtersuchl{\"a}ufen problemlos zum Nest zur{\"u}ckfinden. Wie aber nehmen naive Ameisen ihre Navigationssysteme in Betrieb? Nach mehrw{\"o}chigem Innendienst im dunklen Nest werden sie zu Sammlerinnen bei hellem Sonnenschein. Dieser Wechsel erfordert einen drastischen Wandel im Verhalten sowie neuronale Ver{\"a}nderungen im Gehirn. Erfahrene Ameisen orientieren sich vor allem visuell, sie nutzen einen Himmelskompass und Landmarkenpanoramen. Daher absolvieren naive Ameisen stereotype Lernl{\"a}ufe, um ihren Kompass zu kalibrieren und die Nestumgebung kennenzulernen. W{\"a}hrend der Lernl{\"a}ufe blicken sie wiederholt zum Nesteingang zur{\"u}ck und pr{\"a}gen sich so ihren Heimweg ein. Zur Ausrichtung ihrer Blicke nutzen sie das Erdmagnetfeld als Kompassreferenz. Cataglyphis-Ameisen besitzen hierf{\"u}r einen Magnetkompass, der bislang unbekannt war.}, language = {de} } @article{HirschJahnZwick2020, author = {Hirsch, Boris and Jahn, Elke J. and Zwick, Thomas}, title = {Birds, Birds, Birds: Co-Worker Similarity, Workplace Diversity and Job Switches}, series = {British Journal of Industrial Relations}, volume = {58}, journal = {British Journal of Industrial Relations}, number = {3}, doi = {10.1111/bjir.12509}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208666}, pages = {690-718}, year = {2020}, abstract = {We investigate how the demographic composition of the workforce along the sex, nationality, education, age and tenure dimensions affects job switches. Fitting duration models for workers' job-to-job turnover rate that control for workplace fixed effects in a representative sample of large manufacturing plants in Germany during 1975-2016, we find that larger co-worker similarity in all five dimensions substantially depresses job-to-job moves, whereas workplace diversity is of limited importance. In line with conventional wisdom, which has that birds of a feather flock together, our interpretation of the results is that workers prefer having co-workers of their kind and place less value on diverse workplaces.}, language = {en} } @article{LiedertNemitzHaffnerLuntzeretal.2020, author = {Liedert, Astrid and Nemitz, Claudia and Haffner-Luntzer, Melanie and Schick, Fabian and Jakob, Franz and Ignatius, Anita}, title = {Effects of estrogen receptor and Wnt signaling activation on mechanically induced bone formation in a mouse model of postmenopausal bone loss}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {21}, issn = {1422-0067}, doi = {10.3390/ijms21218301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285487}, year = {2020}, abstract = {In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. We demonstrated that both pathways interact in the regulation of bone mass adaption in response to mechanical loading and that the activation of Wnt/β-catenin signaling considerably increased mechanically induced bone formation, whereas the effects of estrogen treatment strictly depended on the estrogen status in the mice.}, language = {en} } @article{GeyerPaisWotte2020, author = {Geyer, Gerd and Pais, Miguel Caldeira and Wotte, Thomas}, title = {Unexpectedly curved spines in a Cambrian trilobite: considerations on the spinosity in Kingaspidoides spinirecurvatus sp. nov. from the Anti-Atlas, Morocco, and related Cambrian ellipsocephaloids}, series = {PalZ}, volume = {94}, journal = {PalZ}, issn = {0031-0220}, doi = {10.1007/s12542-020-00514-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231873}, pages = {645-660}, year = {2020}, abstract = {The new ellipsocephaloid trilobite species Kingaspidoides spinirecurvatus has a spectacular morphology because of a unique set of two long and anteriorly recurved spines on the occipital ring and the axial ring of thoracic segment 8. Together with the long genal spines this whimsical dorsally directed spine arrangement is thought to act as a non-standard protective device against predators. This is illustrated by the body posture during different stages of enrolment, contrasting with the more sophisticated spinosities seen in later trilobites, which are discussed in brief. Kingaspidoides spinirecurvatus from the lower-middle Cambrian boundary interval of the eastern Anti-Atlas in Morocco has been known for about two decades, with specimens handled as precious objects on the fossil market. Similar, but far less spectacular, spine arrangements on the thoracic axial rings are known from other ellipsocephaloid trilobites from the Anti-Atlas of Morocco and the Franconian Forest region of Germany. This suggests that an experimental phase of spine development took place within the Kingaspi-doides clade during the early-middle Cambrian boundary interval.}, language = {en} } @article{RasouliKianiPouyaLietal.2020, author = {Rasouli, Fatemeh and Kiani-Pouya, Ali and Li, Leiting and Zhang, Heng and Chen, Zhonghua and Hedrich, Rainer and Wilson, Richard and Shabala, Sergey}, title = {Sugar beet (Beta vulgaris) guard cells responses to salinity stress: a proteomic analysis}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {7}, issn = {1422-0067}, doi = {10.3390/ijms21072331}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285765}, year = {2020}, abstract = {Soil salinity is a major environmental constraint affecting crop growth and threatening global food security. Plants adapt to salinity by optimizing the performance of stomata. Stomata are formed by two guard cells (GCs) that are morphologically and functionally distinct from the other leaf cells. These microscopic sphincters inserted into the wax-covered epidermis of the shoot balance CO\(_2\) intake for photosynthetic carbon gain and concomitant water loss. In order to better understand the molecular mechanisms underlying stomatal function under saline conditions, we used proteomics approach to study isolated GCs from the salt-tolerant sugar beet species. Of the 2088 proteins identified in sugar beet GCs, 82 were differentially regulated by salt treatment. According to bioinformatics analysis (GO enrichment analysis and protein classification), these proteins were involved in lipid metabolism, cell wall modification, ATP biosynthesis, and signaling. Among the significant differentially abundant proteins, several proteins classified as "stress proteins" were upregulated, including non-specific lipid transfer protein, chaperone proteins, heat shock proteins, inorganic pyrophosphatase 2, responsible for energized vacuole membrane for ion transportation. Moreover, several antioxidant enzymes (peroxide, superoxidase dismutase) were highly upregulated. Furthermore, cell wall proteins detected in GCs provided some evidence that GC walls were more flexible in response to salt stress. Proteins such as L-ascorbate oxidase that were constitutively high under both control and high salinity conditions may contribute to the ability of sugar beet GCs to adapt to salinity by mitigating salinity-induced oxidative stress.}, language = {en} } @article{BiscottiCarducciBaruccaetal.2020, author = {Biscotti, Maria Assunta and Carducci, Federica and Barucca, Marco and Gerdol, Marco and Pallavicini, Alberto and Schartl, Manfred and Canapa, Adriana and Contar Adolfi, Mateus}, title = {The transcriptome of the newt Cynops orientalis provides new insights into evolution and function of sexual gene networks in sarcopterygians}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-62408-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227326}, year = {2020}, abstract = {Amphibians evolved in the Devonian period about 400 Mya and represent a transition step in tetrapod evolution. Among amphibians, high-throughput sequencing data are very limited for Caudata, due to their largest genome sizes among terrestrial vertebrates. In this paper we present the transcriptome from the fire bellied newt Cynops orientalis. Data here presented display a high level of completeness, comparable to the fully sequenced genomes available from other amphibians. Moreover, this work focused on genes involved in gametogenesis and sexual development. Surprisingly, the gsdf gene was identified for the first time in a tetrapod species, so far known only from bony fish and basal sarcopterygians. Our analysis failed to isolate fgf24 and foxl3, supporting the possible loss of both genes in the common ancestor of Rhipidistians. In Cynops, the expression analysis of genes described to be sex-related in vertebrates singled out an expected functional role for some genes, while others displayed an unforeseen behavior, confirming the high variability of the sex-related pathway in vertebrates.}, language = {en} } @article{RuedenauerRaubenheimerKessnerBeierleinetal.2020, author = {Ruedenauer, Fabian A. and Raubenheimer, David and Kessner-Beierlein, Daniela and Grund-Mueller, Nils and Noack, Lisa and Spaethe, Johannes and Leonhardt, Sara D.}, title = {Best be(e) on low fat: linking nutrient perception, regulation and fitness}, series = {Ecology Letters}, volume = {23}, journal = {Ecology Letters}, number = {3}, doi = {10.1111/ele.13454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208709}, pages = {545-554}, year = {2020}, abstract = {Preventing malnutrition through consuming nutritionally appropriate resources represents a challenge for foraging animals. This is due to often high variation in the nutritional quality of available resources. Foragers consequently need to evaluate different food sources. However, even the same food source can provide a plethora of nutritional and non-nutritional cues, which could serve for quality assessment. We show that bumblebees, Bombus terrestris , overcome this challenge by relying on lipids as nutritional cue when selecting pollen. The bees 'prioritised' lipid perception in learning experiments and avoided lipid consumption in feeding experiments, which supported survival and reproduction. In contrast, survival and reproduction were severely reduced by increased lipid contents. Our study highlights the importance of fat regulation for pollen foraging bumblebees. It also reveals that nutrient perception, nutrient regulation and reproductive fitness can be linked, which represents an effective strategy enabling quick foraging decisions that prevent malnutrition and maximise fitness.}, language = {en} } @article{WoelfelSaetteleZechmeisteretal.2020, author = {W{\"o}lfel, Angela and S{\"a}ttele, Mathias and Zechmeister, Christina and Nikolaev, Viacheslov O. and Lohse, Martin J. and Boege, Fritz and Jahns, Roland and Boivin-Jahns, Val{\´e}rie}, title = {Unmasking features of the auto-epitope essential for β\(_1\)-adrenoceptor activation by autoantibodies in chronic heart failure}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {4}, doi = {10.1002/ehf2.12747}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235974}, pages = {1830-1841}, year = {2020}, abstract = {Aims Chronic heart failure (CHF) can be caused by autoantibodies stimulating the heart via binding to first and/or second extracellular loops of cardiac β1-adrenoceptors. Allosteric receptor activation depends on conformational features of the autoantibody binding site. Elucidating these features will pave the way for the development of specific diagnostics and therapeutics. Our aim was (i) to fine-map the conformational epitope within the second extracellular loop of the human β\(_1\)-adrenoceptor (β1ECII) that is targeted by stimulating β\(_1\)-receptor (auto)antibodies and (ii) to generate competitive cyclopeptide inhibitors of allosteric receptor activation, which faithfully conserve the conformational auto-epitope. Methods and results Non-conserved amino acids within the β\(_1\)EC\(_{II}\) loop (compared with the amino acids constituting the ECII loop of the β\(_2\)-adrenoceptor) were one by one replaced with alanine; potential intra-loop disulfide bridges were probed by cysteine-serine exchanges. Effects on antibody binding and allosteric receptor activation were assessed (i) by (auto)antibody neutralization using cyclopeptides mimicking β1ECII ± the above replacements, and (ii) by (auto)antibody stimulation of human β\(_1\)-adrenoceptors bearing corresponding point mutations. With the use of stimulating β\(_1\)-receptor (auto)antibodies raised in mice, rats, or rabbits and isolated from exemplary dilated cardiomyopathy patients, our series of experiments unmasked two features of the β\(_1\)EC\(_{II}\) loop essential for (auto)antibody binding and allosteric receptor activation: (i) the NDPK\(^{211-214}\) motif and (ii) the intra-loop disulfide bond C\(^{209}\)↔C\(^{215}\). Of note, aberrant intra-loop disulfide bond C\(^{209}\)↔C\(^{216}\) almost fully disrupted the functional auto-epitope in cyclopeptides. Conclusions The conformational auto-epitope targeted by cardio-pathogenic β\(_1\)-receptor autoantibodies is faithfully conserved in cyclopeptide homologues of the β\(_1\)EC\(_{II}\) loop bearing the NDPK\(^{211-214}\) motif and the C\(^{209}\)↔C\(^{215}\) bridge while lacking cysteine C216. Such molecules provide promising tools for novel diagnostic and therapeutic approaches in β\(_1\)-autoantibodypositive CHF.}, language = {en} } @article{PoetzschGermanakosHuestegge2020, author = {Poetzsch, Tristan and Germanakos, Panagiotis and Huestegge, Lynn}, title = {Toward a Taxonomy for Adaptive Data Visualization in Analytics Applications}, series = {Frontiers in Artificial Intelligence}, volume = {3}, journal = {Frontiers in Artificial Intelligence}, issn = {2624-8212}, doi = {10.3389/frai.2020.00009}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202074}, year = {2020}, abstract = {Data analytics as a field is currently at a crucial point in its development, as a commoditization takes place in the context of increasing amounts of data, more user diversity, and automated analysis solutions, the latter potentially eliminating the need for expert analysts. A central hypothesis of the present paper is that data visualizations should be adapted to both the user and the context. This idea was initially addressed in Study 1, which demonstrated substantial interindividual variability among a group of experts when freely choosing an option to visualize data sets. To lay the theoretical groundwork for a systematic, taxonomic approach, a user model combining user traits, states, strategies, and actions was proposed and further evaluated empirically in Studies 2 and 3. The results implied that for adapting to user traits, statistical expertise is a relevant dimension that should be considered. Additionally, for adapting to user states different user intentions such as monitoring and analysis should be accounted for. These results were used to develop a taxonomy which adapts visualization recommendations to these (and other) factors. A preliminary attempt to validate the taxonomy in Study 4 tested its visualization recommendations with a group of experts. While the corresponding results were somewhat ambiguous overall, some aspects nevertheless supported the claim that a user-adaptive data visualization approach based on the principles outlined in the taxonomy can indeed be useful. While the present approach to user adaptivity is still in its infancy and should be extended (e.g., by testing more participants), the general approach appears to be very promising.}, language = {en} } @article{PagelTwisselmannRauschetal.2020, author = {Pagel, Julia and Twisselmann, Nele and Rausch, Tanja K. and Waschina, Silvio and Hartz, Annika and Steinbeis, Magdalena and Olbertz, Jonathan and Nagel, Kathrin and Steinmetz, Alena and Faust, Kirstin and Demmert, Martin and G{\"o}pel, Wolfgang and Herting, Egbert and Rupp, Jan and H{\"a}rtel, Christoph}, title = {Increased Regulatory T Cells Precede the Development of Bronchopulmonary Dysplasia in Preterm Infants}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.565257}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212409}, year = {2020}, abstract = {Regulatory T cells (Tregs) are important for the ontogenetic control of immune activation and tissue damage in preterm infants. However, the role of Tregs for the development of bronchopulmonary dysplasia (BPD) is yet unclear. The aim of our study was to characterize CD4+ CD25+ forkhead box protein 3 (FoxP3)+ Tregs in peripheral blood of well-phenotyped preterm infants (n = 382; 23 + 0 - 36 + 6 weeks of gestational age) with a focus on the first 28 days of life and the clinical endpoint BPD (supplemental oxygen for longer than 28 days of age). In a subgroup of preterm infants, we characterized the immunological phenotype of Tregs (n = 23). The suppressive function of Tregs on CD4+CD25- T cells was compared in preterm, term and adult blood. We observed that extreme prematurity was associated with increased Treg frequencies which peaked in the second week of life. Independent of gestational age, increased Treg frequencies were noted to precede the development of BPD. The phenotype of preterm infant Tregs largely differed from adult Tregs and displayed an overall na{\"i}ve Treg population (CD45RA+/HLA-DR-/Helios+), especially in the first days of life. On day 7 of life, a more activated Treg phenotype pattern (CCR6+, HLA-DR+, and Ki-67+) was observed. Tregs of preterm neonates had a higher immunosuppressive capacity against CD4+CD25- T cells compared to the Treg compartment of term neonates and adults. In conclusion, our data suggest increased frequencies and functions of Tregs in preterm neonates which display a distinct phenotype with dynamic changes in the first weeks of life. Hence, the continued abundance of Tregs may contribute to sustained inflammation preceding the development of BPD. Functional analyses are needed in order to elucidate whether Tregs have potential as future target for diagnostics and therapeutics.}, language = {en} } @article{MahmoodSchmalzingDoerneretal.2020, author = {Mahmood, Zafar and Schmalzing, Marc and D{\"o}rner, Thomas and Tony, Hans-Peter and Muhammad, Khalid}, title = {Therapeutic Cytokine Inhibition Modulates Activation and Homing Receptors of Peripheral Memory B Cell Subsets in Rheumatoid Arthritis Patients}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.572475}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212380}, year = {2020}, abstract = {Memory B cells have known to play an important role in the pathogenesis of rheumatoid arthritis (RA). With the emergence of B cell-targeted therapies, the modulation of memory B cells appears to be a key therapeutic target. Human peripheral memory B cells can be distinguished based on the phenotypic expression of CD27 and IgD, characterizing the three major B cell subpopulations: CD27+IgD+ pre-switch, CD27+IgD- post-switch, and CD27-IgD- double-negative memory B cells. We evaluated different memory cell populations for activation markers (CD95 and Ki-67) and chemokine receptors (CXCR3 and 4) expressing B cells in active RA, as well as under IL6-R blockade by tocilizumab (TCZ) and TNF-α blockade by adalimumab (ADA). Memory B cells were phenotypically analyzed from RA patients at baseline, week 12, and week 24 under TCZ or ADA treatment, respectively. Using flow cytometry, surface expression of CD95, intracellular Ki-67, and surface expressions of CXCR3 and CXCR4 were determined. Compared with healthy donors (n = 40), the phenotypic analysis of RA patients (n = 80) demonstrated that all three types of memory B cells were activated in RA patients. Surface and intracellular staining of B cells showed a significantly higher percentage of CD95+ (p < 0.0001) and Ki-67+ (p < 0.0001) cells, with numerically altered CXCR3+ and CXCR4+ cells in RA. CD95 and Ki-67 expressions were highest in post-switch memory B cells, whereas CD19+CXCR3+ and CD19+CXCR4+ expressing cells were substantially higher in the pre-switch compartment. In all subsets of the memory B cells, in vivo IL-6R, and TNF-α blockade significantly reduced the enhanced expressions of CD95 and Ki-67. Based on our findings, we conclude that the three major peripheral memory B cell populations, pre-, post-switch, and double-negative B cells, are activated in RA, demonstrating enhanced CD95 and Ki-67 expressions, and varied expression of CXCR3 and CXCR4 chemokine receptors when compared with healthy individuals. This activation can be efficaciously modulated under cytokine inhibition in vivo.}, language = {en} } @article{YousefStrzalkowskaHillenkampetal.2020, author = {Yousef, Yousef Al and Strzalkowska, Alicja and Hillenkamp, Jost and Rosentreter, Andr{\´e} and Loewen, Nils A.}, title = {Comparison of a second-generation trabecular bypass (iStent inject) to ab interno trabeculectomy (Trabectome) by exact matching}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {258}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-04933-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232613}, pages = {2775-2780}, year = {2020}, abstract = {Purpose To achieve a highly balanced comparison of trabecular bypass stenting (IS2, iStent inject) with ab interno trabeculectomy (T, Trabectome) by exact matching. Methods Fifty-three IS2 eyes were matched to 3446 T eyes. Patients were matched using exact matching by baseline intraocular pressure (IOP), the number of glaucoma medications, and glaucoma type, and using nearest neighbor matching by age. Individuals without a close match were excluded. All surgeries were combined with phacoemulsification. Results A total of 78 eyes (39 in each group) could be matched as exact pairs with a baseline IOP of 18.3 ± 5.1 mmHg and glaucoma medications of 2.7 ± 1.2 in each. IOP in IS2 was reduced to 14.6 ± 4.2 mmHg at 3 months and in T to a minimum of 13.1 ± 3.2 mmHg at 1 month. In IS2, IOP began to rise again at 6 months, eventually exceeding baseline. At 24 months, IOP in IS2 was 18.8 ± 9.0 mmHg and in T 14.2 ± 3.5 mmHg. IS2 had a higher average IOP than T at all postoperative visits (p < 0.05 at 1, 12, 18 months). Glaucoma medications decreased to 2.0 ± 1.5 in IS2 and to 1.5 ± 1.4 in T. Conclusion T resulted in a larger and sustained IOP reduction compared with IS2 where a rebound occurred after 6 months to slightly above preoperative values.}, language = {en} } @article{GenslerLeikeimMoellmannetal.2020, author = {Gensler, Marius and Leikeim, Anna and M{\"o}llmann, Marc and Komma, Miriam and Heid, Susanne and M{\"u}ller, Claudia and Boccaccini, Aldo R. and Salehi, Sahar and Groeber-Becker, Florian and Hansmann, Jan}, title = {3D printing of bioreactors in tissue engineering: A generalised approach}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242615}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231368}, year = {2020}, abstract = {3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.}, language = {en} } @article{LandwehrAltieriSchreineretal.2020, author = {Landwehr, Laura-Sophie and Altieri, Barbara and Schreiner, Jochen and Sbiera, Iuliu and Weigand, Isabel and Kroiss, Matthias and Fassnacht, Martin and Sbiera, Silviu}, title = {Interplay between glucocorticoids and tumor-infiltrating lymphocytes on the prognosis of adrenocortical carcinoma}, series = {Journal for ImmunoTherapy of Cancer}, volume = {8}, journal = {Journal for ImmunoTherapy of Cancer}, doi = {10.1136/jitc-2019-000469}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229893}, year = {2020}, abstract = {Background Adrenocortical carcinoma (ACC) is a rare endocrine malignancy. Tumor-related glucocorticoid excess is present in similar to 60\% of patients and associated with particularly poor prognosis. Results of first clinical trials using immune checkpoint inhibitors were heterogeneous. Here we characterize tumor-infiltrating T lymphocytes (TILs) in ACC in association with glucocorticoids as potential explanation for resistance to immunotherapy. Methods We performed immunofluorescence analysis to visualize tumor-infiltrating T cells (CD3\(^+\)), T helper cells (CD3\(^+\)CD4\(^+\)), cytotoxic T cells (CD3\(^+\)CD8\(^+\)) and regulatory T cells (Tregs; CD3\(^+\)CD4\(^+\)FoxP3\(^+\)) in 146 ACC tissue specimens (107 primary tumors, 16 local recurrences, 23 metastases). Quantitative data of immune cell infiltration were correlated with clinical data (including glucocorticoid excess). Results 86.3\% of ACC specimens showed tumor infiltrating T cells (7.7 cells/high power field (HPF)), including T helper (74.0\%, 6.7 cells/HPF), cytotoxic T cells (84.3\%, 5.7 cells/HPF) and Tregs (49.3\%, 0.8 cells/HPF). The number of TILs was associated with better overall survival (HR for death: 0.47, 95\% CI 0.25 to 0.87), which was true for CD4\(^+\)- and CD8\(^+\) subpopulations as well. In localized, non-metastatic ACC, the favorable impact of TILs on overall and recurrence-free survival was manifested even independently of ENSAT (European Network for the Study of Adrenal Tumors) stage, resection status and Ki67 index. T helper cells were negatively correlated with glucocorticoid excess (Phi=-0.290, p=0.009). Patients with glucocorticoid excess and low TILs had a particularly poor overall survival (27 vs. 121 months in patients with TILs without glucocorticoid excess). Conclusion Glucocorticoid excess is associated with T cell depletion and unfavorable prognosis. To reactivate the immune system in ACC by checkpoint inhibitors, an inhibition of adrenal steroidogenesis might be pivotal and should be tested in prospective studies.}, language = {en} } @article{HerrmannKarunakaranFichtner2020, author = {Herrmann, Thomas and Karunakaran, Mohindar Murugesh and Fichtner, Alina Suzann}, title = {A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human γδ T-cells}, series = {Immunological Reviews}, volume = {298}, journal = {Immunological Reviews}, number = {1}, doi = {10.1111/imr.12919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218373}, pages = {218 -- 236}, year = {2020}, abstract = {Both, jawless and jawed vertebrates possess three lymphocyte lineages defined by highly diverse antigen receptors: Two T-cell- and one B-cell-like lineage. In both phylogenetic groups, the theoretically possible number of individual antigen receptor specificities can even outnumber that of lymphocytes of a whole organism. Despite fundamental differences in structure and genetics of these antigen receptors, convergent evolution led to functional similarities between the lineages. Jawed vertebrates possess αβ and γδ T-cells defined by eponymous αβ and γδ T-cell antigen receptors (TCRs). "Conventional" αβ T-cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non-conventional T-cells, which can be αβ or γδ T-cells, recognize a large variety of ligands and differ strongly in phenotype and function between species and within an organism. This review describes similarities and differences of non-conventional T-cells of various species and discusses ligands and functions of their TCRs. A special focus is laid on Vγ9Vδ2 T-cells whose TCRs act as sensors for phosphorylated isoprenoid metabolites, so-called phosphoantigens (PAg), associated with microbial infections or altered host metabolism in cancer or after drug treatment. We discuss the role of butyrophilin (BTN)3A and BTN2A1 in PAg-sensing and how species comparison can help in a better understanding of this human Vγ9Vδ2 T-cell subset.}, language = {en} } @article{PellegrinoDelBufaloDeAngelisetal.2020, author = {Pellegrino, Marsha and Del Bufalo, Francesca and De Angelis, Biagio and Quintarelli, Concetta and Caruana, Ignazio and de Billy, Emmanuel}, title = {Manipulating the metabolism to improve the efficacy of CAR T-cell immunotherapy}, series = {Cells}, volume = {10}, journal = {Cells}, number = {1}, issn = {2073-4409}, doi = {10.3390/cells10010014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220140}, year = {2020}, abstract = {The adoptive transfer of the chimeric antigen receptor (CAR) expressing T-cells has produced unprecedented successful results in the treatment of B-cell malignancies. However, the use of this technology in other malignancies remains less effective. In the setting of solid neoplasms, CAR T-cell metabolic fitness needs to be optimal to reach the tumor and execute their cytolytic function in an environment often hostile. It is now well established that both tumor and T cell metabolisms play critical roles in controlling the immune response by conditioning the tumor microenvironment and the fate and activity of the T cells. In this review, after a brief description of the tumoral and T cell metabolic reprogramming, we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and efficacy of CAR T-cell products.}, language = {en} } @article{DeaneBrunkCurranetal.2020, author = {Deane, Katrina E. and Brunk, Michael G. K. and Curran, Andrew W. and Zempeltzi, Marina M. and Ma, Jing and Lin, Xiao and Abela, Francesca and Aksit, S{\"u}meyra and Deliano, Matthias and Ohl, Frank W. and Happel, Max F. K.}, title = {Ketamine anaesthesia induces gain enhancement via recurrent excitation in granular input layers of the auditory cortex}, series = {The Journal of Physiology}, volume = {598}, journal = {The Journal of Physiology}, number = {13}, doi = {10.1113/JP279705}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216123}, pages = {2741 -- 2755}, year = {2020}, abstract = {Ketamine is commonly used as an anaesthetic agent and has more recently gained attention as an antidepressant. It has been linked to increased stimulus-locked excitability, inhibition of interneurons and modulation of intrinsic neuronal oscillations. However, the functional network mechanisms are still elusive. A better understanding of these anaesthetic network effects may improve upon previous interpretations of seminal studies conducted under anaesthesia and have widespread relevance for neuroscience with awake and anaesthetized subjects as well as in medicine. Here, we investigated the effects of anaesthetic doses of ketamine (15 mg kg\(^{-1}\) h\(^{-1}\)i.p.) on the network activity after pure-tone stimulation within the auditory cortex of male Mongolian gerbils (Meriones unguiculatus). We used laminar current source density (CSD) analysis and subsequent layer-specific continuous wavelet analysis to investigate spatiotemporal response dynamics on cortical columnar processing in awake and ketamine-anaesthetized animals. We found thalamocortical input processing within granular layers III/IV to be significantly increased under ketamine. This layer-dependent gain enhancement under ketamine was not due to changes in cross-trial phase coherence but was rather attributed to a broadband increase in magnitude reflecting an increase in recurrent excitation. A time-frequency analysis was indicative of a prolonged period of stimulus-induced excitation possibly due to a reduced coupling of excitation and inhibition in granular input circuits - in line with the common hypothesis of cortical disinhibition via suppression of GABAergic interneurons.}, language = {en} } @article{BuhlBeissertGaffaletal.2020, author = {Buhl, Timo and Beissert, Stefan and Gaffal, Evelyn and Goebeler, Matthias and Hertl, Michael and Mauch, Cornelia and Reich, Kristian and Schmidt, Enno and Sch{\"o}n, Michael P. and Sticherling, Michael and Sunderk{\"o}tter, Cord and Traidl-Hoffmann, Claudia and Werfel, Thomas and Wilsman-Theis, Dagmar and Worm, Margitta}, title = {COVID-19 and implications for dermatological and allergological diseases}, series = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, volume = {18}, journal = {JDDG: Journal der Deutschen Dermatologischen Gesellschaft}, number = {8}, doi = {10.1111/ddg.14195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217860}, pages = {815 -- 824}, year = {2020}, abstract = {COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.}, language = {en} } @article{LeverkusGustafssonLindenmayeretal.2020, author = {Leverkus, Alexandro B and Gustafsson, Lena and Lindenmayer, David B and Castro, Jorge and Rey Benayas, Jos{\´e} Mar{\´i}a and Ranius, Thomas and Thorn, Simon}, title = {Salvage logging effects on regulating ecosystem services and fuel loads}, series = {Frontiers in Ecology and the Environment}, volume = {18}, journal = {Frontiers in Ecology and the Environment}, number = {7}, doi = {10.1002/fee.2219}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216111}, pages = {391 -- 400}, year = {2020}, abstract = {Salvage logging, or logging after natural disturbances such as wildfires, insect outbreaks, and windstorms, is carried out to recover some of a forest's natural and/or economic capital. However, trade-offs between management objectives and a lack of consensus on the ecological consequences of salvage logging impair science-based decision making on the management of forests after natural disturbances. We conducted a global meta-analysis of the impacts of salvage logging on regulating ecosystem services and on fuel loads, as a frequent post-disturbance objective is preventing subsequent wildfires that could be fueled by the accumulation of dead trunks and branches. Salvage logging affected ecosystem services in a moderately negative way, regardless of disturbance type and severity, time elapsed since salvage logging, intensity of salvage logging, and the group of regulating ecosystem services being considered. However, prolonging the time between natural disturbance and salvage logging mitigated negative effects on regulating ecosystem services. Salvage logging had no overall effect on surface fuels; rather, different fuel types responded differently depending on the time elapsed since salvage logging. Delaying salvage logging by ~2-4 years may reduce negative ecological impacts without affecting surface fuel loads.}, language = {en} } @article{GoelSiegertKraussetal.2020, author = {Goel, Mahima and Siegert, Marie and Krauss, Gert and Mohanraj, John and Hochgesang, Adrian and Heinrich, David C. and Fried, Martina and Pflaum, Jens and Thelakkat, Mukundan}, title = {HOMO-HOMO Electron Transfer: An Elegant Strategy for p-Type Doping of Polymer Semiconductors toward Thermoelectric Applications}, series = {Advanced Materials}, volume = {32}, journal = {Advanced Materials}, number = {43}, doi = {10.1002/adma.202003596}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217850}, year = {2020}, abstract = {Unlike the conventional p-doping of organic semiconductors (OSCs) using acceptors, here, an efficient doping concept for diketopyrrolopyrrole-based polymer PDPP[T]\(_{2}\)-EDOT (OSC-1) is presented using an oxidized p-type semiconductor, Spiro-OMeTAD(TFSI)\(_{2}\) (OSC-2), exploiting electron transfer from HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\). A shift of work function toward the HOMO\(_{OSC-1}\) upon doping is confirmed by ultraviolet photoelectron spectroscopy (UPS). Detailed X-ray photoelectron spectroscopy (XPS) and UV-vis-NIR absorption studies confirm HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\) electron transfer. The reduction products of Spiro-OMeTAD(TFSI)\(_{2}\) to Spiro-OMeTAD(TFSI) and Spiro-OMeTAD is also confirmed and their relative amounts in doped samples is determined. Mott-Schottky analysis shows two orders of magnitude increase in free charge carrier density and one order of magnitude increase in the charge carrier mobility. The conductivity increases considerably by four orders of magnitude to a maximum of 10 S m\(^{-1}\) for a very low doping ratio of 8 mol\%. The doped polymer films exhibit high thermal and ambient stability resulting in a maximum power factor of 0.07 µW m\(^{-1}\) K\(^{-2}\) at a Seebeck coefficient of 140 µV K\(^{-1}\) for a very low doping ratio of 4 mol\%. Also, the concept of HOMO\(_{OSC-1}\) to HOMO\(_{OSC-2}\) electron transfer is a highly efficient, stable and generic way to p-dope other conjugated polymers.}, language = {en} } @article{ChenWaxmanWangetal.2020, author = {Chen, Si and Waxman, Susannah and Wang, Chao and Atta, Sarah and Loewen, Ralitsa and Loewen, Nils A.}, title = {Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract}, series = {Graefe's Archive for Clinical and Experimental Ophthalmology}, volume = {258}, journal = {Graefe's Archive for Clinical and Experimental Ophthalmology}, issn = {0721-832X}, doi = {10.1007/s00417-020-04691-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231893}, pages = {1211-1216}, year = {2020}, abstract = {Purpose To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). Wehypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT)that removes the TM. Methods Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n= 32) and without circumferential AIT (n= 32). Cultures were exposed to 0.1, 1, and 10μM netarsudil (N= 8 eyes per concentration). For each concentration,IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters wereassessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series). Results Netarsudil at 1μM reduced IOP both in eyes with TM (-0.60 ± 0.24 mmHg,p= 0.01) and in eyes without TM (-1.79 ±0.42 mmHg,p< 0.01). At this concentration, vessels of the distal outflow tract dilated by 72\%. However, at 0.1μMnetarsudilelevated IOP in eyes with TM (1.59 ± 0.36 mmHg,p< 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg,p<0.001). Vessels of the distal outflow tract constricted by 31\%. Similarly, netarsudil at a concentration of 10μM elevated IOP both in eyeswith TM (1.91 ± 0.193,p< 0.001) and in eyes without TM (3.65 ± 0.86 mmHg,p< 0.001). At this concentration, outflow tractvessels constricted by 27\%. Conclusion In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameterchanges of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal}, language = {en} } @article{LiesnerKirschPfisteretal.2020, author = {Liesner, Marvin and Kirsch, Wladimir and Pfister, Roland and Kunde, Wilfried}, title = {Spatial action-effect binding depends on type of action-effect transformation}, series = {Attention, Perception, \& Psychophysics}, volume = {82}, journal = {Attention, Perception, \& Psychophysics}, issn = {1943-3921}, doi = {10.3758/s13414-020-02013-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232781}, pages = {2531-2543}, year = {2020}, abstract = {Spatial action-effect binding denotes the mutual attraction between the perceived position of an effector (e.g., one's own hand) and a distal object that is controlled by this effector. Such spatial binding can be construed as an implicit measure of object ownership, thus the belonging of a controlled object to the own body. The current study investigated how different transformations of hand movements (body-internal action component) into movements of a visual object (body-external action component) affect spatial action-effect binding, and thus implicit object ownership. In brief, participants had to bring a cursor on the computer screen into a predefined target position by moving their occluded hand on a tablet and had to estimate their final hand position. In Experiment 1, we found a significantly lower drift of the proprioceptive position of the hand towards the visual object when hand movements were transformed into laterally inverted cursor movements, rather than cursor movements in the same direction. Experiment 2 showed that this reduction reflected an elimination of spatial action-effect binding in the inverted condition. The results are discussed with respect to the prerequisites for an experience of ownership over artificial, noncorporeal objects. Our results show that predictability of an object movement alone is not a sufficient condition for ownership because, depending on the type of transformation, integration of the effector and a distal object can be fully abolished even under conditions of full controllability.}, language = {en} } @article{SchicklerReichertGeigeretal.2020, author = {Schickler, Marc and Reichert, Manfred and Geiger, Philip and Winkler, Jens and Funk, Thomas and Weilbach, Micha and Pryss, R{\"u}diger}, title = {Flexible development of location-based mobile augmented reality applications with AREA}, series = {Journal of Ambient Intelligence and Humanized Computing}, volume = {11}, journal = {Journal of Ambient Intelligence and Humanized Computing}, issn = {1868-5137}, doi = {10.1007/s12652-020-02094-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232773}, pages = {5809-5824}, year = {2020}, abstract = {Mobile applications have garnered a lot of attention in the last years. The computational capabilities of mobile devices are the mainstay to develop completely new application types. The provision of augmented reality experiences on mobile devices paves one alley in this field. For example, in the automotive domain, augmented reality applications are used to experience, inter alia, the interior of a car by moving a mobile device around. The device's camera then detects interior parts and shows additional information to the customer within the camera view. Another application type that is increasingly utilized is related to the combination of serious games with mobile augmented reality functions. Although the latter combination is promising for many scenarios, technically, it is a complex endeavor. In the AREA (Augmented Reality Engine Application) project, a kernel was implemented that enables location-based mobile augmented reality applications. Importantly, this kernel provides a flexible architecture that fosters the development of individual location-based mobile augmented reality applications. The work at hand shows the flexibility of AREA based on a developed serious game. Furthermore, the algorithm framework and major features of it are presented. As the conclusion of this paper, it is shown that mobile augmented reality applications require high development efforts. Therefore, flexible frameworks like AREA are crucial to develop respective applications in a reasonable time.}, language = {en} } @article{YangHeydarianKozjakPavlovicetal.2020, author = {Yang, Tao and Heydarian, Motaharehsadat and Kozjak-Pavlovic, Vera and Urban, Manuela and Harbottle, Richard P. and Rudel, Thomas}, title = {Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {10}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {422}, issn = {2235-2988}, doi = {10.3389/fcimb.2020.00422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211372}, year = {2020}, abstract = {Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.}, language = {en} } @article{HorasvanHerckMaieretal.2020, author = {Horas, Konstantin and van Herck, Ulrike and Maier, Gerrit S. and Maus, Uwe and Harrasser, Norbert and Jakob, Franz and Weissenberger, Manuel and Arnholdt, J{\"o}rg and Holzapfel, Boris M. and Rudert, Maximilian}, title = {Does vitamin D deficiency predict tumour malignancy in patients with bone tumours? Data from a multi-center cohort analysis}, series = {Journal of Bone Oncology}, volume = {25}, journal = {Journal of Bone Oncology}, doi = {10.1016/j.jbo.2020.100329}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230314}, year = {2020}, abstract = {Vitamin D deficiency is a global health concern that is estimated to afflict over one billion people globally. The major role of vitamin D is that of a regulator of calcium and phosphate metabolism, thus, being essential for proper bone mineralisation. Concomitantly, vitamin D is known to exert numerous extra-skeletal actions. For example, it has become evident that vitamin D has direct anti-proliferative, pro-differentiation and pro-apoptotic actions on cancer cells. Hence, vitamin D deficiency has been associated with increased cancer risk and worse prognosis in several malignancies. We have recently demonstrated that vitamin D deficiency promotes secondary cancer growth in bone. These findings were partly attributable to an increase in bone remodelling but also through direct effects of vitamin D on cancer cells. To date, very little is known about vitamin D status of patients with bone tumours in general. Thus, the objective of this study was to assess vitamin D status of patients with diverse bone tumours. Moreover, the aim was to elucidate whether or not there is an association between pre-diagnostic vitamin D status and tumour malignancy in patients with bone tumours. In a multi-center analysis, 25(OH)D, PTH and calcium levels of 225 patients that presented with various bone tumours between 2017 and 2018 were assessed. Collectively, 76\% of all patients had insufficient vitamin D levels with a total mean 25(OH)D level of 21.43 ng/ml (53.58 nmol/L). In particular, 52\% (117/225) of patients were identified as vitamin D deficient and further 24\% of patients (55/225) were vitamin D insufficient. Notably, patients diagnosed with malignant bone tumours had significantly lower 25(OH)D levels than patients diagnosed with benign bone tumours [19.3 vs. 22.75 ng/ml (48.25 vs. 56.86 nmol/L); p = 0.04). In conclusion, we found a widespread and distressing rate of vitamin D deficiency and insufficiency in patients with bone tumours. However, especially for patients with bone tumours sufficient vitamin D levels seem to be of great importance. Thus, we believe that 25(OH)D status should routinely be monitored in these patients. Collectively, there should be an increased awareness for physicians to assess and if necessary correct vitamin D status of patients with bone tumours in general or of those at great risk of developing bone tumours.}, language = {en} } @article{AuerHuegelschaefferFischeretal.2020, author = {Auer, Daniela and H{\"u}gelsch{\"a}ffer, Sophie D. and Fischer, Annette B. and Rudel, Thomas}, title = {The chlamydial deubiquitinase Cdu1 supports recruitment of Golgi vesicles to the inclusion}, series = {Cellular Microbiology}, volume = {22}, journal = {Cellular Microbiology}, number = {5}, doi = {10.1111/cmi.13136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208675}, pages = {e13136}, year = {2020}, abstract = {Chlamydia trachomatis is the main cause of sexually transmitted diseases worldwide. As obligate intracellular bacteria Chlamydia replicate in a membrane bound vacuole called inclusion and acquire nutrients for growth and replication from their host cells. However, like all intracellular bacteria, Chlamydia have to prevent eradication by the host's cell autonomous system. The chlamydial deubiquitinase Cdu1 is secreted into the inclusion membrane, facing the host cell cytosol where it deubiquitinates cellular proteins. Here we show that inactivation of Cdu1 causes a growth defect of C. trachomatis in primary cells. Moreover, ubiquitin and several autophagy receptors are recruited to the inclusion membrane of Cdu1-deficient Chlamydia . Interestingly, the growth defect of cdu1 mutants is not rescued when autophagy is prevented. We find reduced recruitment of Golgi vesicles to the inclusion of Cdu1 mutants indicating that vesicular trafficking is altered in bacteria without active deubiquitinase (DUB). Our work elucidates an important role of Cdu1 in the functional preservation of the chlamydial inclusion surface.}, language = {en} } @article{MaternKochPetersmannetal.2020, author = {Matern, Johannes and Koch, Raphael and Petersmann, Astrid and Kocher, Thomas and Eickholz, Peter and Lorenz, Katrin and Kim, Ti-Sun and Meyle, J{\"o}rg and Kaner, Doğan and Schlagenhauf, Ulrich and Gravemeier, Martina and Harks, Inga and Ehmke, Benjamin}, title = {Effect of periodontal therapy on adipokine biomarkers in overweight}, series = {Journal of Clinical Periodontology}, volume = {47}, journal = {Journal of Clinical Periodontology}, number = {7}, doi = {10.1111/jcpe.13288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215546}, pages = {842 -- 850}, year = {2020}, abstract = {Aim The aim of this study was to evaluate the effect of non-surgical periodontal therapy on circulating levels of the systemic inflammation-associated biomarkers orosomucoid (ORM), high-sensitivity C-reactive protein (hsCRP), chemerin, and retinol-binding protein 4 (RBP4) in overweight or normal-weight patients with periodontitis at 27.5 months after therapy. Materials and methods This exploratory subanalysis includes patients from the ABPARO-trial (ClinicalTrials.gov NCT00707369). The per-protocol collective provided untreated periodontitis patients with high (≥28 kg/m\(^{2}\)) or moderate (21-24 kg/m\(^{2}\)) BMI. Out of the per-protocol collective, 80 patients were randomly selected and stratified for BMI group, sex, and treatment group (antibiotics/placebo), resulting in 40 overweight and normal-weight patients. Patients received non-surgical periodontal therapy and maintenance at 3-month intervals. Plasma samples from baseline and 27.5 months following initial treatment were used to measure the concentrations of ORM, hsCRP, chemerin, and RBP4. Results At the 27.5-month examination, ORM and hsCRP decreased noticeably in the overweight group (ORM: p = .001, hsCRP: p = .004) and normal-weight patients (ORM: p = .007, hsCRP: p < .001). Chemerin decreased in the overweight group (p = .048), and RBP4 concentrations remained stable. Conclusion Non-surgical periodontal therapy reduced systemically elevated inflammation-associated biomarkers in periodontitis patients. These improvements were more pronounced in overweight patients than in normal-weight patients.}, language = {en} } @article{HutmacherKuhbandner2020, author = {Hutmacher, Fabian and Kuhbandner, Christof}, title = {Does the Attentional Boost Effect Depend on the Intentionality of Encoding? Investigating the Mechanisms Underlying Memory for Visual Objects Presented at Behaviorally Relevant Moments in Time}, series = {Frontiers in Psychology}, volume = {11}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2020.584187}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215902}, year = {2020}, abstract = {Pictures in a rapid serial visual presentation (RSVP) stream are better remembered when they are simultaneously presented with targets of an unrelated detection task than when they are presented with distractors. However, it is unclear whether this so-called "attentional boost effect" depends on the intentionality of encoding. While there are studies suggesting that the attentional boost effect even occurs when encoding is incidental, there are several methodological issues with these studies, which may have undermined the incidental encoding instructions. The present study (N = 141) investigated the role of the intentionality of encoding with an improved experimental design. Specifically, to prevent a spill-over of intentional resources to the pictures in the RSVP stream, the speed of the stream was increased (to four pictures per second) and each picture was presented only once during the course of the experiment. An attentional boost effect was only found when encoding was intentional but not when encoding was incidental. Interestingly, memory performance for incidentally encoded pictures was nevertheless substantially above chance, independently of whether images were presented with search-relevant targets or distractors. These results suggest that the attentional boost effect is a memory advantage that occurs only under intentional encoding conditions, and that perceptual long-term memory representations are formed as a natural product of perception, independently of the presence of behaviorally relevant events.}, language = {en} } @article{GlutschAmaralGarbeetal.2020, author = {Glutsch, Valerie and Amaral, Teresa and Garbe, Claus and Thoms, Kai-Martin and Mohr, Peter and Hauschild, Axel and Schilling, Bastian}, title = {Indirect Comparison of Combined BRAF and MEK Inhibition in Melanoma Patients with Elevated Baseline Lactate Dehydrogenase}, series = {Acta Dermato-Venereologica}, volume = {100}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-3526}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230190}, year = {2020}, abstract = {The approval of BRAF and MEK inhibitors has signifi-cantly improved treatment outcomes for patients with BRAF-mutated metastatic melanoma. The 3 first-line targeted therapy trials have provided similar results, and thus the identification of predictive biomarkers may generate a more precise basis for clinical deci-sion-making. Elevated baseline lactate dehydrogenase (LDH) has already been determined as a strong prog-nostic factor. Therefore, this indirect analysis compa-red subgroups with elevated baseline LDH across the pivotal targeted therapy trials co-BRIM, COMBI-v and COLUMBUS part 1. The Bucher method was used to compare progression-free survival, objective response rate and overall survival indirectly. The results show a non-significant risk reduction for progression in the subgroup with elevated baseline LDH receiving vemu-rafenib plus cobimetinib compared with dabrafenib plus trametinib and encorafenib plus binimetinib. Al-though an indirect comparison, these data might pro-vide some guidance for treatment recommendations in melanoma patients with elevated LDH.}, language = {en} } @article{WhisnantJuergesHennigetal.2020, author = {Whisnant, Adam W. and J{\"u}rges, Christopher S. and Hennig, Thomas and Wyler, Emanuel and Prusty, Bhupesh and Rutkowski, Andrzej J. and L'hernault, Anne and Djakovic, Lara and G{\"o}bel, Margarete and D{\"o}ring, Kristina and Menegatti, Jennifer and Antrobus, Robin and Matheson, Nicholas J. and K{\"u}nzig, Florian W. H. and Mastrobuoni, Guido and Bielow, Chris and Kempa, Stefan and Liang, Chunguang and Dandekar, Thomas and Zimmer, Ralf and Landthaler, Markus and Gr{\"a}sser, Friedrich and Lehner, Paul J. and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars}, title = {Integrative functional genomics decodes herpes simplex virus 1}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-15992-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229884}, year = {2020}, abstract = {The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.}, language = {en} } @article{JobsVontheinKoenigetal.2020, author = {Jobs, Alexander and Vonthein, Reinhard and K{\"o}nig, Inke R. and Sch{\"a}fer, Jane and Nauck, Matthias and Haag, Svenja and Fichera, Carlo Federico and Stiermaier, Thomas and Ledwoch, Jakob and Schneider, Alisa and Valentova, Miroslava and von Haehling, Stephan and St{\"o}rk, Stefan and Westermann, Dirk and Lenz, Tobias and Arnold, Natalie and Edelmann, Frank and Seppelt, Philipp and Felix, Stephan and Lutz, Matthias and Hedwig, Felix and Borggrefe, Martin and Scherer, Clemens and Desch, Steffen and Thiele, Holger}, title = {Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA-ADHF-DZHK10 trial}, series = {ESC Heart Failure}, volume = {7}, journal = {ESC Heart Failure}, number = {3}, doi = {10.1002/ehf2.12598}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212692}, pages = {973 -- 983}, year = {2020}, abstract = {Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right-sided haemodynamic congestion. The CAVA-ADHF-DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA-ADHF-DZHK10 is a randomized, controlled, patient-blinded, multicentre, parallel-group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion-related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50\% in the intervention group. The primary endpoint is change in N-terminal pro-brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA-ADHF-DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF.}, language = {en} } @article{JanzenBakirciWielandetal.2020, author = {Janzen, Dieter and Bakirci, Ezgi and Wieland, Annalena and Martin, Corinna and Dalton, Paul D. and Villmann, Carmen}, title = {Cortical Neurons form a Functional Neuronal Network in a 3D Printed Reinforced Matrix}, series = {Advanced Healthcare Materials}, volume = {9}, journal = {Advanced Healthcare Materials}, number = {9}, doi = {10.1002/adhm.201901630}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215400}, year = {2020}, abstract = {Impairments in neuronal circuits underly multiple neurodevelopmental and neurodegenerative disorders. 3D cell culture models enhance the complexity of in vitro systems and provide a microenvironment closer to the native situation than with 2D cultures. Such novel model systems will allow the assessment of neuronal network formation and their dysfunction under disease conditions. Here, mouse cortical neurons are cultured from embryonic day E17 within in a fiber-reinforced matrix. A soft Matrigel with a shear modulus of 31 ± 5.6 Pa is reinforced with scaffolds created by melt electrowriting, improving its mechanical properties and facilitating the handling. Cortical neurons display enhance cell viability and the neuronal network maturation in 3D, estimated by staining of dendrites and synapses over 21 days in vitro, is faster in 3D compared to 2D cultures. Using functional readouts with electrophysiological recordings, different firing patterns of action potentials are observed, which are absent in the presence of the sodium channel blocker, tetrodotoxin. Voltage-gated sodium currents display a current-voltage relationship with a maximum peak current at -25 mV. With its high customizability in terms of scaffold reinforcement and soft matrix formulation, this approach represents a new tool to study neuronal networks in 3D under normal and, potentially, disease conditions.}, language = {en} } @article{KollmannPretzschKunzetal.2020, author = {Kollmann, Cath{\´e}rine T. and Pretzsch, Elise B. and Kunz, Andreas and Isbert, Christoph and Krajinovic, Katica and Reibetanz, Joachim and Kim, Mia}, title = {Anorectal angle at rest predicting successful sacral nerve stimulation in idiopathic fecal incontinence—a cohort analysis}, series = {International Journal of Colorectal Disease}, volume = {35}, journal = {International Journal of Colorectal Disease}, issn = {0179-1958}, doi = {10.1007/s00384-020-03720-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232379}, pages = {2293-2299}, year = {2020}, abstract = {Purpose Sacral nerve stimulation is an effective treatment for patients suffering from fecal incontinence. However, less is knownabout predictors of success before stimulation. The purpose of this study was to identify predictors of successful sacral nervestimulation in patients with idiopathic fecal incontinence. Methods Consecutive female patients, receiving peripheral nerve evaluation and sacral nerve stimulation between September2008 and October 2014, suffering from idiopathic fecal incontinence were included in this study. Preoperative patient'scharac-teristics, anal manometry, and defecography results were collected prospectively and investigated by retrospective analysis. Mainoutcome measures were independent predictors of treatment success after sacral nerve stimulation. Results From, all in all, 54 patients suffering from idiopathic fecal incontinence receiving peripheral nerve evaluation, favorableoutcome was achieved in 23 of 30 patients after sacral nerve stimulation (per protocol 76.7\%; intention to treat 42.6\%). From allanalyzed characteristics, wide anorectal angle at rest in preoperative defecography was the only independent predictor offavorable outcome in multivariate analysis (favorable 134.1 ± 13.9° versus unfavorable 118.6 ± 17.1°). Conclusions Anorectal angle at rest in preoperative defecography might present a predictor of outcome after sacral nervestimulation in patients with idiopathic fecal incontinence.}, language = {en} } @article{OhlebuschBorstFrankenbachetal.2020, author = {Ohlebusch, Barbara and Borst, Angela and Frankenbach, Tina and Klopocki, Eva and Jakob, Franz and Liedtke, Daniel and Graser, Stephanie}, title = {Investigation of alpl expression and Tnap-activity in zebrafish implies conserved functions during skeletal and neuronal development}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-70152-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230024}, year = {2020}, abstract = {Hypophosphatasia (HPP) is a rare genetic disease with diverse symptoms and a heterogeneous severity of onset with underlying mutations in the ALPL gene encoding the ectoenzyme Tissue-nonspecific alkaline phosphatase (TNAP). Considering the establishment of zebrafish (Danio rerio) as a new model organism for HPP, the aim of the study was the spatial and temporal analysis of alpl expression in embryos and adult brains. Additionally, we determined functional consequences of Tnap inhibition on neural and skeletal development in zebrafish. We show that expression of alpl is present during embryonic stages and in adult neuronal tissues. Analyses of enzyme function reveal zones of pronounced Tnap-activity within the telencephalon and the mesencephalon. Treatment of zebrafish embryos with chemical Tnap inhibitors followed by axonal and cartilage/mineralized tissue staining imply functional consequences of Tnap deficiency on neuronal and skeletal development. Based on the results from neuronal and skeletal tissue analyses, which demonstrate an evolutionary conserved role of this enzyme, we consider zebrafish as a promising species for modeling HPP in order to discover new potential therapy strategies in the long-term.}, language = {en} } @article{HabensteinAminiGruebeletal.2020, author = {Habenstein, Jens and Amini, Emad and Gr{\"u}bel, Kornelia and el Jundi, Basil and R{\"o}ssler, Wolfgang}, title = {The brain of Cataglyphis ants: Neuronal organization and visual projections}, series = {Journal of Comparative Neurology}, volume = {528}, journal = {Journal of Comparative Neurology}, number = {18}, doi = {10.1002/cne.24934}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218212}, pages = {3479 -- 3506}, year = {2020}, abstract = {Cataglyphis ants are known for their outstanding navigational abilities. They return to their inconspicuous nest after far-reaching foraging trips using path integration, and whenever available, learn and memorize visual features of panoramic sceneries. To achieve this, the ants combine directional visual information from celestial cues and panoramic scenes with distance information from an intrinsic odometer. The largely vision-based navigation in Cataglyphis requires sophisticated neuronal networks to process the broad repertoire of visual stimuli. Although Cataglyphis ants have been subjected to many neuroethological studies, little is known about the general neuronal organization of their central brain and the visual pathways beyond major circuits. Here, we provide a comprehensive, three-dimensional neuronal map of synapse-rich neuropils in the brain of Cataglyphis nodus including major connecting fiber systems. In addition, we examined neuronal tracts underlying the processing of visual information in more detail. This study revealed a total of 33 brain neuropils and 30 neuronal fiber tracts including six distinct tracts between the optic lobes and the cerebrum. We also discuss the importance of comparative studies on insect brain architecture for a profound understanding of neuronal networks and their function.}, language = {en} } @article{StolteHechtXieetal.2020, author = {Stolte, Matthias and Hecht, Reinhard and Xie, Zengqi and Liu, Linlin and Kaufmann, Christina and Kudzus, Astrid and Schmidt, David and W{\"u}rthner, Frank}, title = {Crystal Engineering of 1D Exciton Systems Composed of Single- and Double-Stranded Perylene Bisimide J-Aggregates}, series = {Advanced Optical Materials}, volume = {8}, journal = {Advanced Optical Materials}, number = {18}, doi = {10.1002/adom.202000926}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218221}, year = {2020}, abstract = {Single crystals of three at bay area tetraphenoxy-substituted perylene bisimide dyes are grown by vacuum sublimation. X-ray analysis reveals the self-assembly of these highly twisted perylene bisimides (PBIs) in the solid state via imide-imide hydrogen bonding into hydrogen-bonded PBI chains. The crystallographic insights disclose that the conformation and sterical congestion imparted by the phenoxy substituents can be controlled by ortho-substituents. Accordingly, whilst sterically less demanding methyl and isopropyl substituents afford double-stranded PBI chains of complementary P and M atropo-enantiomers, single hydrogen-bonded chains of homochiral PBIs are observed for the sterically more demanding ortho-phenyl substituents. Investigation of the absorption and fluorescence properties of microcrystals and thin films of these PBIs allow for an unambiguous interpretation of these exciton systems. Thus, the J-aggregates of the double-stranded crystals exhibit a much larger (negative) exciton coupling than the single-stranded one, which in contrast has the higher solid-state fluorescence quantum yield.}, language = {en} } @article{BoetzlSchueleKraussetal.2020, author = {Boetzl, Fabian A. and Schuele, Maren and Krauss, Jochen and Steffan-Dewenter, Ingolf}, title = {Pest control potential of adjacent agri-environment schemes varies with crop type and is shaped by landscape context and within-field position}, series = {Journal of Applied Ecology}, volume = {57}, journal = {Journal of Applied Ecology}, number = {8}, doi = {10.1111/1365-2664.13653}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218265}, pages = {1482 -- 1493}, year = {2020}, abstract = {Increasing natural pest control in agricultural fields is an important aim of ecological intensification. Combined effects of landscape context and local placement of agri-environmental schemes (AES) on natural pest control and within-field distance functions of natural pest control agents have rarely been addressed but might affect the distribution of biocontrol providers. Importantly, it is currently unknown whether ecosystem services provided by adjacent AES are consistent for different crop types during crop rotation. In this study, we assessed whether crop rotation from oilseed rape to cereals altered within-field distance functions of ground-dwelling predators from adjacent agri-environmental fields along a gradient in landscape context. Additionally, we recorded crop pests, predation rates, parasitoids as well as crop yields on a total of 30 study sites. Distance functions varied between trophic levels: Carabid richness decreased while densities of carabid beetles, staphylinid beetles as well as crop yields increased towards the field centres. Distance functions of parasitoids and pests were modulated by the amount of semi-natural habitat in the surrounding landscape, while the effects of adjacent AES were limited. Distance decay functions found for ground-dwelling predators in oilseed rape in the previous year were not always present in cereals. Increasing distance to the field edge also increased effects of crop rotation on carabid beetle assemblages, indicating a source habitat function of field edges. Synthesis and applications. Distance functions of natural pest control are not universal and the effects of agri-environmental schemes (AES) in different adjacent crops during crop rotation vary and depend on ecological contrasts. A network of semi-natural habitats and spatially optimized AES habitats can benefit pest control in agricultural landscapes, but constraints as a result of crop type need to be addressed by annually targeted, spatially shifting agri-environment schemes for different crops.}, language = {en} } @article{RabevanOorschotJentschke2020, author = {Rabe, A. and van Oorschot, B. and Jentschke, E.}, title = {Suizidalit{\"a}t bei Krebspatienten}, series = {Der Onkologe}, volume = {26}, journal = {Der Onkologe}, issn = {Suizidalit{\"a}t bei Krebspatienten}, doi = {10.1007/s00761-020-00712-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232401}, pages = {163-168}, year = {2020}, abstract = {Hintergrund Die Diagnose Krebs und ihre Behandlung kann eine große Belastung f{\"u}r die Betroffenen darstellen. Neben k{\"o}rperlichen Beschwerden kann auch die Psyche in Mitleidenschaft gezogen werden. Fehlt es an entsprechenden Bew{\"a}ltigungsstrategien, kann der selbstbestimmte Tod als einziger Ausweg erscheinen. Ziel und Fragestellung Die vorliegende {\"U}bersichtsarbeit zur Suizidalit{\"a}t bei Krebspatienten befasst sich mit einem Thema, das in der Forschung und Praxis in Deutschland nur wenig Aufmerksamkeit findet. Material und Methoden Eine themenbezogene Literaturrecherche stellt die Basis der Arbeit dar. Ergebnisse Todesw{\"u}nsche unter Krebspatienten sind nicht selten und k{\"o}nnen Suizidgedanken/-absichten beinhalten. Psychische Beschwerden, insbesondere Hoffnungslosigkeit und Depression, sind ernstzunehmende Risikofaktoren. Das Erkennen einer hohen psychischen Belastung/von Todesw{\"u}nschen ist ein wichtiger Aspekt f{\"u}r die Suizidpr{\"a}vention. F{\"u}r die Praxis empfiehlt sich zun{\"a}chst die Verwendung von Frageb{\"o}gen. Bei auff{\"a}lligen Werten muss die Suizidalit{\"a}t proaktiv in einem pers{\"o}nlichen Gespr{\"a}ch exploriert werden. Betroffene sind meist ambivalent bez{\"u}glich ihrer Entscheidung f{\"u}r oder gegen das Leben. Dies stellt eine große Chance f{\"u}r Interventionen dar. Schlussfolgerungen Suizidalit{\"a}t kann verhindert werden, wenn die hohe Belastung erkannt wird. Bereits das Gespr{\"a}ch zwischen Arzt und Patient {\"u}ber Todesw{\"u}nsche kann eine erste Entlastung darstellen.}, language = {de} } @article{FroehlichSchwaneckGernertetal.2020, author = {Froehlich, Matthias and Schwaneck, Eva C. and Gernert, Michael and Gadeholt, Ottar and Strunz, Patrick-Pascal and Morbach, Henner and Tony, Hans-Peter and Schmalzing, Marc}, title = {Autologous Stem Cell Transplantation in Common Variable Immunodeficiency: A Case of Successful Treatment of Severe Refractory Autoimmune Encephalitis}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, number = {1317}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.01317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206972}, year = {2020}, abstract = {Common variable immunodeficiency (CVID) is the most common primary immunodeficiency in adults. It is associated with hypogammaglobulinemia, recurring infections and autoimmune phenomena. Treatment includes immunoglobulin substitution and immunosuppressants. Autoimmune neurological manifestations of CVID are rare and occur predominantly as granulomatous disease. We report the case of a 35-year-old woman with CVID who developed autoimmune encephalitis as demonstrated by double cerebral biopsy. Infectious or malignant causes could be excluded. Despite intensive immunosuppressive therapy with common regimens no significant improvement could be achieved. Ultimately, an autologous hematopoietic stem cell transplantation (HSCT) was performed, resulting in lasting complete remission of the encephalitis. To our knowledge, this is the first report of refractory autoimmune phenomena in CVID treated by autologous HSCT.}, language = {en} } @article{MairBiskupKressetal.2020, author = {Mair, Dorothea and Biskup, Saskia and Kress, Wolfram and Abicht, Angela and Br{\"u}ck, Wolfgang and Zechel, Sabrina and Knop, Karl Christian and Koenig, Fatima Barbara and Tey, Shelisa and Nikolin, Stefan and Eggermann, Katja and Kurth, Ingo and Ferbert, Andreas and Weis, Joachim}, title = {Differential diagnosis of vacuolar myopathies in the NGS era}, series = {Brain Pathology}, volume = {30}, journal = {Brain Pathology}, number = {5}, doi = {10.1111/bpa.12864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216048}, pages = {877 -- 896}, year = {2020}, abstract = {Altered autophagy accompanied by abnormal autophagic (rimmed) vacuoles detectable by light and electron microscopy is a common denominator of many familial and sporadic non-inflammatory muscle diseases. Even in the era of next generation sequencing (NGS), late-onset vacuolar myopathies remain a diagnostic challenge. We identified 32 adult vacuolar myopathy patients from 30 unrelated families, studied their clinical, histopathological and ultrastructural characteristics and performed genetic testing in index patients and relatives using Sanger sequencing and NGS including whole exome sequencing (WES). We established a molecular genetic diagnosis in 17 patients. Pathogenic mutations were found in genes typically linked to vacuolar myopathy (GNE, LDB3/ZASP, MYOT, DES and GAA), but also in genes not regularly associated with severely altered autophagy (FKRP, DYSF, CAV3, COL6A2, GYG1 and TRIM32) and in the digenic facioscapulohumeral muscular dystrophy 2. Characteristic histopathological features including distinct patterns of myofibrillar disarray and evidence of exocytosis proved to be helpful to distinguish causes of vacuolar myopathies. Biopsy validated the pathogenicity of the novel mutations p.(Phe55*) and p.(Arg216*) in GYG1 and of the p.(Leu156Pro) TRIM32 mutation combined with compound heterozygous deletion of exon 2 of TRIM32 and expanded the phenotype of Ala93Thr-caveolinopathy and of limb-girdle muscular dystrophy 2i caused by FKRP mutation. In 15 patients no causal variants were detected by Sanger sequencing and NGS panel analysis. In 12 of these cases, WES was performed, but did not yield any definite mutation or likely candidate gene. In one of these patients with a family history of muscle weakness, the vacuolar myopathy was eventually linked to chloroquine therapy. Our study illustrates the wide phenotypic and genotypic heterogeneity of vacuolar myopathies and validates the role of histopathology in assessing the pathogenicity of novel mutations detected by NGS. In a sizable portion of vacuolar myopathy cases, it remains to be shown whether the cause is hereditary or degenerative.}, language = {en} } @article{KandelsPietschBisonetal.2020, author = {Kandels, Daniela and Pietsch, Torsten and Bison, Brigitte and Warmuth-Metz, Monika and Thomale, Ulrich-Wilhelm and Kortmann, Rolf-Dieter and Timmermann, Beate and Hern{\´a}iz Driever, Pablo and Witt, Olaf and Schmidt, Ren{\´e} and Gnekow, Astrid K.}, title = {Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low-grade glioma patients—Report from the German SIOP-LGG 2004 cohort}, series = {International Journal of Cancer}, volume = {147}, journal = {International Journal of Cancer}, number = {12}, doi = {10.1002/ijc.33170}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216130}, pages = {3471 -- 3489}, year = {2020}, abstract = {First-line treatment of pediatric low-grade glioma using surgery, radio- or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP-LGG 2004 study (2004-2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98\%/96\% at 5/10 years, 15\% neurofibromatosis type 1 [NF1]). During follow-up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment-lines, accompanied by up to 4 tumor-reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first-line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression-free survival rates declined with subsequent treatment-lines, yet remaining higher for patients with NF1. In non-NF1-associated tumors, vinblastine monotherapy vs platinum-based chemotherapy was noticeably less effective when used as second-line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long-term tumor biology.}, language = {en} } @article{HuangWangDewhurstetal.2020, author = {Huang, Zhenguo and Wang, Suning and Dewhurst, Rian D. and Ignat'ev, Nikolai V. and Finze, Maik and Braunschweig, Holger}, title = {Boron: Its Role in Energy-Related Processes and Applications}, series = {Angewandte Chemie International Edition}, volume = {59}, journal = {Angewandte Chemie International Edition}, number = {23}, doi = {10.1002/anie.201911108}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218514}, pages = {8800 -- 8816}, year = {2020}, abstract = {Boron's unique position in the Periodic Table, that is, at the apex of the line separating metals and nonmetals, makes it highly versatile in chemical reactions and applications. Contemporary demand for renewable and clean energy as well as energy-efficient products has seen boron playing key roles in energy-related research, such as 1) activating and synthesizing energy-rich small molecules, 2) storing chemical and electrical energy, and 3) converting electrical energy into light. These applications are fundamentally associated with boron's unique characteristics, such as its electron-deficiency and the availability of an unoccupied p orbital, which allow the formation of a myriad of compounds with a wide range of chemical and physical properties. For example, boron's ability to achieve a full octet of electrons with four covalent bonds and a negative charge has led to the synthesis of a wide variety of borate anions of high chemical and electrochemical stability—in particular, weakly coordinating anions. This Review summarizes recent advances in the study of boron compounds for energy-related processes and applications.}, language = {en} } @article{Lichtenberg2020, author = {Lichtenberg, Crispin}, title = {Main-Group Metal Complexes in Selective Bond Formations Through Radical Pathways}, series = {Chemistry - A European Journal}, volume = {26}, journal = {Chemistry - A European Journal}, number = {44}, doi = {10.1002/chem.202000194}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214758}, pages = {9674 -- 9687}, year = {2020}, abstract = {Recent years have witnessed remarkable advances in radical reactions involving main-group metal complexes. This includes the isolation and detailed characterization of main-group metal radical compounds, but also the generation of highly reactive persistent or transient radical species. A rich arsenal of methods has been established that allows control over and exploitation of their unusual reactivity patterns. Thus, main-group metal compounds have entered the field of selective bond formations in controlled radical reactions. Transformations that used to be the domain of late transition-metal compounds have been realized, and unusual selectivities, high activities, as well as remarkable functional-group tolerances have been reported. Recent findings demonstrate the potential of main-group metal compounds to become standard tools of synthetic chemistry, catalysis, and materials science, when operating through radical pathways.}, language = {en} } @article{GrabenhenrichTrendelenburgBellachetal.2020, author = {Grabenhenrich, Linus and Trendelenburg, Val{\´e}rie and Bellach, Johanna and Y{\"u}rek, Song{\"u}l and Reich, Andreas and Fiandor, Ana and Rivero, Daniela and Sigurdardottir, Sigurveig and Clausen, Michael and Papadopoulos, Nikolaos G. and Xepapadaki, Paraskevi and Sprikkelman, Aline B. and Dontje, Bianca and Roberts, Graham and Grimshaw, Kate and Kowalski, Marek L. and Kurowski, Marcin and Dubakiene, Ruta and Rudzeviciene, Odilija and Fern{\´a}ndez-Rivas, Montserrat and Couch, Philip and Versteeg, Serge A. and van Ree, Ronald and Mills, Clare and Keil, Thomas and Beyer, Kirsten}, title = {Frequency of food allergy in school-aged children in eight European countries—The EuroPrevall-iFAAM birth cohort}, series = {Allergy}, volume = {75}, journal = {Allergy}, number = {9}, doi = {10.1111/all.14290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214746}, pages = {2294 -- 2308}, year = {2020}, abstract = {Background The prevalence of food allergy (FA) among European school children is poorly defined. Estimates have commonly been based on parent-reported symptoms. We aimed to estimate the frequency of FA and sensitization against food allergens in primary school children in eight European countries. Methods A follow-up assessment at age 6-10 years of a multicentre European birth cohort based was undertaken using an online parental questionnaire, clinical visits including structured interviews and skin prick tests (SPT). Children with suspected FA were scheduled for double-blind, placebo-controlled oral food challenges (DBPCFC). Results A total of 6105 children participated in this school-age follow-up (57.8\% of 10 563 recruited at birth). For 982 of 6069 children (16.2\%), parents reported adverse reactions after food consumption in the online questionnaire. Of 2288 children with parental face-to-face interviews and/or skin prick testing, 238 (10.4\%) were eligible for a DBPCFC. Sixty-three foods were challenge-tested in 46 children. Twenty food challenges were positive in 17 children, including seven to hazelnut and three to peanut. Another seventy-one children were estimated to suffer FA among those who were eligible but refused DBPCFC. This yielded prevalence estimates for FA in school age between 1.4\% (88 related to all 6105 participants of this follow-up) and 3.8\% (88 related to 2289 with completed eligibility assessment). Interpretation In primary school children in eight European countries, the prevalence of FA was lower than expected even though parents of this cohort have become especially aware of allergic reactions to food. There was moderate variation between centres hampering valid regional comparisons.}, language = {en} } @article{ShuklaMannheim2020, author = {Shukla, A. and Mannheim, K.}, title = {Gamma-ray flares from relativistic magnetic reconnection in the jet of the quasar 3C 279}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-17912-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231328}, year = {2020}, abstract = {Spinning black holes in the centres of galaxies can release powerful magnetised jets. When the jets are observed at angles of less than a few degrees to the line-of-sight, they are called blazars, showing variable non-thermal emission across the electromagnetic spectrum from radio waves to gamma rays. It is commonly believed that shock waves are responsible for this dissipation of jet energy. Here we show that gamma-ray observations of the blazar 3C 279 with the space-borne telescope Fermi-LAT reveal a characteristic peak-in-peak variability pattern on time scales of minutes expected if the particle acceleration is instead due to relativistic magnetic reconnection. The absence of gamma-ray pair attenuation shows that particle acceleration takes place at a distance of ten thousand gravitational radii from the black hole where the fluid dynamical kink instability drives plasma turbulence.}, language = {en} } @article{MasotaVoggHelleretal.2020, author = {Masota, Nelson E. and Vogg, Gerd and Heller, Eberhard and Holzgrabe, Ulrike}, title = {Comparison of extraction efficiency and selectivity between low-temperature pressurized microwave-assisted extraction and prolonged maceration}, series = {Archiv der Pharmazie}, volume = {353}, journal = {Archiv der Pharmazie}, number = {10}, doi = {10.1002/ardp.202000147}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218529}, year = {2020}, abstract = {Extraction is a key step in studying compounds from plants and other natural sources. The common use of high temperatures in pressurized microwave-assisted extraction (PMAE) makes it unsuitable for the extraction of compounds with low or unknown thermal stability. This study aimed at determining the suitability of low-temperature, short-time PMAE in attaining yields comparable to those of prolonged maceration at room temperature. Additionally, we explored the phytochemical differences of the extracts from both techniques. Maceration at room temperature for 24 hr and PMAE at 40-45°C and 10 bar for 30 min were carried out on 18 samples from 14 plant species at a solvent-to-feeds ratio of 10. The PMAE yields of 16 out of 18 samples were within the proportions of 91-139.2\% as compared with the respective extracts from maceration. Varying numbers of nonmatching peaks were noted in MS chromatograms of five extract pairs, indicating selective extraction of some compounds. Low-temperature PMAE can attain reasonable extraction efficiency with the added value of sparing compounds of low thermal stability. The method can also enable the recovery of compounds distinct from those obtained by maceration.}, language = {en} } @inproceedings{OPUS4-21158, title = {Neue Materialien des Bayerischen Neolithikums 3. Tagung im Kloster Windberg vom 16. bis 18. November 2018}, editor = {Husty, Ludwig and Link, Thomas and Pechtl, Joachim}, edition = {1. Auflage}, publisher = {W{\"u}rzburg University Press}, address = {W{\"u}rzburg}, isbn = {978-3-95826-144-0}, issn = {2367-0681}, doi = {10.25972/WUP-978-3-95826-145-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211585}, pages = {257}, year = {2020}, abstract = {Vom 16. bis 18. November 2018 fand im Kloster Windberg bei Straubing zum dritten Mal nach 2014 eine Tagung unter dem Titel "Neue Materialien des Bayerischen Neolithikums" statt. Dabei wurden neue, bislang unpublizierte Fundkomplexe vorgestellt und diskutiert, die alle Phasen der Jungsteinzeit vom Altneolithikum bis zum Endneolithikum abdeckten und die aus verschiedenen Landesteilen des Freistaats Bayern stammen. Mit einer diachronen und Regionen {\"u}bergreifenden Betrachtung charakteristischer Inventare aus den verschiedenen Landschaftsr{\"a}umen und Zeitabschnitten wurde das Ziel verfolgt, neues Material zu erschließen und damit die arch{\"a}ologische Quellenbasis zu erweitern und der Neolithforschung in Bayern neue Impulse zu geben. Im vorliegenden Band werden sieben der Vortr{\"a}ge dieser Tagung sowie drei Beitr{\"a}ge der vorangegangenen Arbeitstreffen zusammengestellt.}, subject = {Bayern}, language = {de} } @article{ElhfnawyElsalamawyAbdelraoufetal.2020, author = {Elhfnawy, Ahmed Mohamed and Elsalamawy, Doaa and Abdelraouf, Mervat and Schliesser, Mira and Volkmann, Jens and Fluri, Felix}, title = {Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review}, series = {Acta Neurologica Belgica}, volume = {120}, journal = {Acta Neurologica Belgica}, number = {6}, issn = {0300-9009}, doi = {10.1007/s13760-020-01344-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315610}, pages = {1389-1398}, year = {2020}, abstract = {Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25\% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1\%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100\%), but only five (7.9\%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70\% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke.}, language = {en} } @article{McNeillZieglerRadtkeetal.2020, author = {McNeill, Rhiannon V. and Ziegler, Georg C. and Radtke, Franziska and Nieberler, Matthias and Lesch, Klaus‑Peter and Kittel‑Schneider, Sarah}, title = {Mental health dished up — the use of iPSC models in neuropsychiatric research}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02197-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235666}, pages = {1547-1568}, year = {2020}, abstract = {Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006-2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient's own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease.}, language = {en} } @article{EndlichRichterMarxetal.2020, author = {Endlich, Darius and Richter, Tobias and Marx, Peter and Lenhard, Wolfgang and Moll, Kristina and Witzel, Bj{\"o}rn and Schulte-K{\"o}rne, Gerd}, title = {Spelling Error Detection : A Valid and Economical Task for Assessing Spelling Skills in Elementary-School Children}, series = {Zeitschrift f{\"u}r Entwicklungspsychologie und P{\"a}dagogische Psychologie}, volume = {52}, journal = {Zeitschrift f{\"u}r Entwicklungspsychologie und P{\"a}dagogische Psychologie}, number = {1-2}, issn = {0049-8637}, doi = {10.1026/0049-8637/a000227}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244665}, pages = {25-40}, year = {2020}, abstract = {The ability to spell words correctly is a key competence for educational and professional achievement. Economical procedures are essential to identifying children with spelling problems as early as possible. Given the strong evidence showing that reading and spelling are based on the same orthographic knowledge, error-detection tasks (EDTs) could be considered such an economical procedure. Although EDTs are widely used in English-speaking countries, the few studies in German-speaking countries investigated only pupils in secondary school. The present study investigated N = 1,513 children in elementary school. We predicted spelling competencies (measured by dictation or gap-fill dictation) based on an EDT via linear regression. Error-detection abilities significantly predicted spelling competencies (R² between .509 and .679), indicating a strong connection. Predictive values in identifying children with poor spelling abilities with an EDT proved to be sufficient. Error detection for the assessment of spelling skills is therefore a valid instrument for transparent languages as well.}, language = {en} } @article{AndreskaLueningschroerSendtner2020, author = {Andreska, Thomas and L{\"u}ningschr{\"o}r, Patrick and Sendtner, Michael}, title = {Regulation of TrkB cell surface expression — a mechanism for modulation of neuronal responsiveness to brain-derived neurotrophic factor}, series = {Cell and Tissue Research}, volume = {382}, journal = {Cell and Tissue Research}, doi = {10.1007/s00441-020-03224-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235055}, pages = {5-14}, year = {2020}, abstract = {Neurotrophin signaling via receptor tyrosine kinases is essential for the development and function of the nervous system in vertebrates. TrkB activation and signaling show substantial differences to other receptor tyrosine kinases of the Trk family that mediate the responses to nerve growth factor and neurotrophin-3. Growing evidence suggests that TrkB cell surface expression is highly regulated and determines the sensitivity of neurons to brain-derived neurotrophic factor (BDNF). This translocation of TrkB depends on co-factors and modulators of cAMP levels, N-glycosylation, and receptor transactivation. This process can occur in very short time periods and the resulting rapid modulation of target cell sensitivity to BDNF could represent a mechanism for fine-tuning of synaptic plasticity and communication in complex neuronal networks. This review focuses on those modulatory mechanisms in neurons that regulate responsiveness to BDNF via control of TrkB surface expression.}, language = {en} } @article{StengelVulinovicMeieretal.2020, author = {Stengel, Felix and Vulinovic, Franca and Meier, Britta and Gr{\"u}tz, Karen and Klein, Christine and Capetian, Philipp}, title = {Impaired differentiation of human induced neural stem cells by TOR1A overexpression}, series = {Molecular Biology Reports}, volume = {47}, journal = {Molecular Biology Reports}, doi = {10.25972/OPUS-24117}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241177}, pages = {3993-4001}, year = {2020}, abstract = {DYT-TOR1A is the most common inherited dystonia caused by a three nucleotide (GAG) deletion (dE) in the TOR1A gene. Death early after birth and cortical anomalies of the full knockout in rodents underscore its developmental importance. We therefore explored the timed effects of TOR1A-wt and TOR1A-dE during differentiation in a human neural in vitro model. We used lentiviral tet-ON expression of TOR1A-wt and -dE in induced neural stem cells derived from healthy donors. Overexpression was induced during proliferation of neural precursors, during differentiation and after differentiation into mature neurons. Overexpression of both wildtype and mutated protein had no effect on the viability and cell number of neural precursors as well as mature neurons when initiated before or after differentiation. However, if induced during differentiation, overexpression of TOR1A-wt and -dE led to a pronounced reduction of mature neurons in a dose dependent manner. Our data underscores the importance of physiological expression levels of TOR1A as crucial for proper neuronal differentiation. We did not find evidence for a specific impact of the mutated TOR1A on neuronal maturation.}, language = {en} } @article{ReinersDrozdYamashita2020, author = {Reiners, Christoph and Drozd, Valentina and Yamashita, Shunichi}, title = {Hypothyroidism after radiation exposure: brief narrative review}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, issn = {0300-9564}, doi = {10.1007/s00702-020-02260-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235653}, pages = {1455-1466}, year = {2020}, abstract = {The thyroid gland is among the organs at the greatest risk of cancer from ionizing radiation. Epidemiological evidence from survivors of radiation therapy, atomic bombing, and the Chernobyl reactor accident, clearly shows that radiation exposure in childhood can cause thyroid cancer and benign thyroid nodules. Radiation exposure also may induce hypothyroidism and autoimmune reactions against the thyroid, but these effects are less well-documented. The literature includes only a few, methodologically weak animal studies regarding genetic/molecular mechanisms underlying hypothyroidism and thyroid autoimmunity after radiation exposure. Rather, evidence about radiation-induced hypothyroidism and thyroid autoimmunity derives mainly from follow-up studies in patients treated with external beam radiotherapy (EBRT) or iodine-131, and from epidemiological studies in the atomic bombing or nuclear accident survivors. Historically, hypothyroidism after external irradiation of the thyroid in adulthood was considered not to develop below a 10-20 Gy dose threshold. Newer data suggest a 10 Gy threshold after EBRT. By contrast, data from patients after iodine-131 "internal radiation therapy" of Graves´ disease indicate that hypothyroidism rarely occurs below thyroid doses of 50 Gy. Studies in children affected by the Chernobyl accident indicate that the dose threshold for hypothyroidism may be considerably lower, 3-5 Gy, aligning with observations in A-bomb survivors exposed as children. The reasons for these dose differences in radiosensitivity are not fully understood. Other important questions about the development of hypothyroidism after radiation exposure e.g., in utero, about the interaction between autoimmunity and hypofunction, and about the different effects of internal and external irradiation still must be answered.}, language = {en} } @article{CaoChenHaendel2020, author = {Cao, Liyu and Chen, Xinyu and Haendel, Barbara F.}, title = {Overground Walking Decreases Alpha Activity and Entrains Eye Movements in Humans}, series = {Frontiers in Human Neuroscience}, volume = {14}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2020.561755}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219872}, year = {2020}, abstract = {Experiments in animal models have shown that running increases neuronal activity in early visual areas in light as well as in darkness. This suggests that visual processing is influenced by locomotion independent of visual input. Combining mobile electroencephalography, motion- and eye-tracking, we investigated the influence of overground free walking on cortical alpha activity (~10 Hz) and eye movements in healthy humans. Alpha activity has been considered a valuable marker of inhibition of sensory processing and shown to negatively correlate with neuronal firing rates. We found that walking led to a decrease in alpha activity over occipital cortex compared to standing. This decrease was present during walking in darkness as well as during light. Importantly, eye movements could not explain the change in alpha activity. Nevertheless, we found that walking and eye related movements were linked. While the blink rate increased with increasing walking speed independent of light or darkness, saccade rate was only significantly linked to walking speed in the light. Pupil size, on the other hand, was larger during darkness than during light, but only showed a modulation by walking in darkness. Analyzing the effect of walking with respect to the stride cycle, we further found that blinks and saccades preferentially occurred during the double support phase of walking. Alpha power, as shown previously, was lower during the swing phase than during the double support phase. We however could exclude the possibility that the alpha modulation was introduced by a walking movement induced change in electrode impedance. Overall, our work indicates that the human visual system is influenced by the current locomotion state of the body. This influence affects eye movement pattern as well as neuronal activity in sensory areas and might form part of an implicit strategy to optimally extract sensory information during locomotion.}, language = {en} } @article{WertgenRichter2020, author = {Wertgen, Andreas G. and Richter, Tobias}, title = {Source credibility modulates the validation of implausible information}, series = {Memory \& Cognition}, volume = {48}, journal = {Memory \& Cognition}, issn = {0090-502X}, doi = {10.3758/s13421-020-01067-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234825}, pages = {1359-1375}, year = {2020}, abstract = {Validation of text information as a general mechanism for detecting inconsistent or false information is an integral part of text comprehension. This study examined how the credibility of the information source affects validation processes. Two experiments investigated combined effects of source credibility and plausibility of information during validation with explicit (ratings) and implicit (reading times) measurements. Participants read short stories with a high-credible versus low-credible person that stated a consistent or inconsistent assertion with general world knowledge. Ratings of plausibility and ratings of source credibility were lower when a credible source stated a world-knowledge inconsistent assertion compared with a low-credible source. Reading times on target sentences and on spillover sentences were slower when a credible source stated an assertion inconsistent with world knowledge compared with a low-credible source, suggesting that source information modulated the validation of implausible information. These results show that source credibility modulates validation and suggest a bidirectional relationship of perceived plausibility and source credibility in the reading process.}, language = {en} } @article{LapuenteArandjelovicKuehletal.2020, author = {Lapuente, Juan and Arandjelovic, Mimi and K{\"u}hl, Hjalmar and Dieguez, Paula and Boesch, Christophe and Linsenmair, K. Eduard}, title = {Sustainable Peeling of Kapok Tree (Ceiba pentandra) Bark by the Chimpanzees (Pan troglodytes verus) of Como{\´e} National Park, Ivory Coast}, series = {International Journal of Primatology}, volume = {41}, journal = {International Journal of Primatology}, issn = {0164-0291}, doi = {10.1007/s10764-020-00152-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232581}, pages = {962-988}, year = {2020}, abstract = {Primates often consume either bark or cambium (inner bark) as a fallback food tocomplete their diet during periods of food scarcity. Wild chimpanzees exhibit greatbehavioral diversity across Africa, as studies of new populations frequently reveal.Since 2014, we have been using a combination of camera traps and indirect signs tostudy the ecology and behavior of wild chimpanzees (Pan troglodytes verus) in Como{\´e}National Park, Ivory Coast, to document and understand the behavioral adaptations thathelp them to survive in a savanna-forest mosaic landscape. We found that Como{\´e}chimpanzees peel the bark of the buttresses of kapok tree (Ceiba pentandra) trees to eatthe cambium underneath. Individuals of all sex/age classes across at least six neigh-boring communities peeled the bark, but only during the late rainy season andbeginning of the dry season, when cambium may represent an important fallback food.Baboons (Papio anubis) also target the same trees but mainly eat the bark itself. Mostof the bark-peeling wounds onCeibatrees healed completely within 2 years, seeminglywithout any permanent damage. We recorded chimpanzees visiting trees in early stagesof wound recovery but leaving them unpeeled. Only 6\% of peeled trees (N= 53) werereexploited after a year, suggesting that chimpanzees waited for the rest of the trees toregrow the bark fully before peeling them again, thus using them sustainably. Manyhuman groups of hunter-gatherers and herders exploited cambium sustainably in thepast. The observation that similar sustainable bark-peeling behavior evolved in bothchimpanzees and humans suggests that it has an important adaptive value in harshenvironments when other food sources become seasonally scarce, by avoiding thedepletion of the resource and keeping it available for periods of scarcity.}, language = {en} } @article{GesellNiklasSchmiedeleretal.2020, author = {Gesell, Nathalie and Niklas, Frank and Schmiedeler, Sandra and Segerer, Robin}, title = {Mindfulness and romantic relationship outcomes: the mediating role of conflict resolution styles and closeness}, series = {Mindfulness}, volume = {11}, journal = {Mindfulness}, issn = {1868-8527}, doi = {10.1007/s12671-020-01449-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235080}, pages = {2314-2324}, year = {2020}, abstract = {Objectives The association of mindfulness and romantic relationship outcomes such as partnership quality and satisfaction is well-established; however, the mechanisms of action are not yet clear. The current study tested conflict resolution styles and closeness as possible mediating factors. We hypothesized that trait mindfulness would increase the use of constructive conflict resolution styles (positive problem solving), decrease the use of destructive styles (conflict engagement, withdrawal, and compliance), and promote feelings of closeness between partners, which in turn would predict positive relationship outcomes (namely partnership quality, partnership satisfaction, and sexual satisfaction). Methods A total of 209 individuals (86\% German, 76\% female, mean age = 32 years) living in a relationship (31\% married) participated in an online questionnaire. Results Mediation analyses revealed that positive problem solving mediated the association between mindfulness and partnership quality with b = .09 (95\% CI = .03-.17), mindfulness and partnership satisfaction with b = .07 (95\% CI = .02-.13), and mindfulness and sexual satisfaction with b = .04 (95\% CI = .00-.10). Furthermore, a mediating role of withdrawal and closeness was shown for individual relationship outcomes. Conclusions Findings suggest that more positive problem solving, less withdrawal, and more closeness are mechanisms by which mindfulness is associated with positive relationship outcomes. The results of our study thus broaden our understanding of the processes that underlie fulfilling romantic relationships and, in turn, underline the positive effects of mindfulness.}, language = {en} }