@unpublished{HennigPrustyKauferetal.2021, author = {Hennig, Thomas and Prusty, Archana B. and Kaufer, Benedikt and Whisnant, Adam W. and Lodha, Manivel and Enders, Antje and Thomas, Julius and Kasimir, Francesca and Grothey, Arnhild and Herb, Stefanie and J{\"u}rges, Christopher and Meister, Gunter and Erhard, Florian and D{\"o}lken, Lars and Prusty, Bhupesh K.}, title = {Selective inhibition of microRNA processing by a herpesvirus-encoded microRNA triggers virus reactivation from latency}, edition = {submitted version}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267858}, year = {2021}, abstract = {Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation thereof 1,2. A long appreciated, yet elusively defined relationship exists between the lytic-latent switch and viral non-coding RNAs 3,4. Here, we identify miRNA-mediated inhibition of miRNA processing as a novel cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defense and drive the latent-lytic switch. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective pri-miRNA hairpin loops. Subsequent loss of miR-30 and activation of miR-30/p53/Drp1 axis triggers a profound disruption of mitochondrial architecture, which impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 was sufficient to trigger virus reactivation from latency thereby identifying it as a readily drugable master regulator of the herpesvirus latent-lytic switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 provides exciting therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders like myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and Long-COVID.}, language = {en} } @phdthesis{Qureischi2021, author = {Qureischi, Musga}, title = {Selective modulation of alloreactive T cells in preclinical models of acute Graft-versus-Host Disease}, doi = {10.25972/OPUS-23603}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236031}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Hematopoietic cell transplantation (HCT) is a curative therapy for the treatment of malignant and non-malignant bone marrow diseases. The major complication of this treatment is a highly inflammatory reaction called Graft-versus-Host Disease (GvHD). Here, transplanted donor T cells cause massive tissue destruction and inflammation in the main target organs liver, skin and the intestine. Currently, this inflammatory reaction can be treated successfully using strong immunosuppressive agents. One efficient group of immunosuppressants are calcineurin inhibitors such as Cyclosporin A (CsA) and Tacrolimus (FK506). These treatment strategies target all T lymphocytes subsets equally and do not separate GvH from the desirable Graft-versus-Leukemia (GvL) effect. Therefore, we aimed to find immunological targets on alloreactive T cells in order to develop novel treatment strategies, which selectively modulates alloreactive T cells without impairing the GvL effect or hematopoietic immune reconstitution. The aim of this thesis was to develop a predictive marker panel to track alloreactive T cells in the peripheral blood (PB) of murine allo-HCT recipients. In clinically relevant model of aGvHD we demonstrated that alloreactive T cells have a distinct surface marker expression profile and can be detected in the PB before aGvHD manifestation. Based on our data, we propose a combinatory panel consisting of 4 surface markers (a4b7 integrin, CD162E, CD162P und CD62L) on circulating CD8+ T cells to identify the risk of aGvHD after allo-HCT. Since tumor necrosis factor receptor superfamily (TNFR SF) members are involved in several immunological processes, we did extensive surface marker expression analysis of several TNFR superfamily members and other immunomodulatory molecules on conventional and regulatory T cells (Tcons vs. Tregs) on different time points during aGvHD progression. The aim of this study was to find subset-specific immunomodulatory molecules on recently activated Tcons and Tregs. We found that GITR, 4-1BB and CD27 were highly expressed on alloreactive and na{\"i}ve Tregs. In contrast, PD1 expression was highly upregulated on recently activated alloreactive Tcons. The data of this study serves as basis for future approaches, which aim to develop T cell subset specific therapeutic antibody fusion proteins. a4b7 integrin and CD162P (P-Selectin ligand) are highly upregulated on alloreactive T cells and mediate the infiltration of these cells into GvHD target organs. We developed recombinant (antibody) fusion proteins to target these two homing molecules and could show that antibody-based fusion proteins are superior to ligand-based fusion proteins regarding production efficiency and binding affinity. Therefore, we propose for future studies to focus on the described antibody-based fusion proteins for the selective targeting of T cells. Since the widely used calcineurin inhibitors are impairing the desirable GvL effect, we investigated if selective NFATc1 inhibition might be a novel strategy to prevent or reduce alloreactivity, while hopefully maintaining the GvL effect. In particular, we addressed the role of the isoform NFATc1 and inhibited its posttranslational modification by SUMO (Small Ubiquitin-related Modifier). Indeed, inhibition of NFATc1 SUMOylation resulted in reduced inflammation and increased Treg frequencies in a murine MHC major mismatch aGvHD model. Conclusively, we showed that alloreactive T cells can be identified by their surface profile in the PB of allo-HCT recipients before aGvHD symptoms appeared. Furthermore, we introduced a approach to selectively target alloreactive T cells by antibody fusion proteins, which might serve as a novel strategy to separate GvH from GvL. Additionally, we demonstrated that averted posttranslational modification of NFATc1 by SUMOylation serves as potential target to reduce alloreactivity of T cells.}, language = {en} } @unpublished{HeidenreichGassenmaierAnkenbrandetal.2021, author = {Heidenreich, Julius F. and Gassenmaier, Tobias and Ankenbrand, Markus J. and Bley, Thorsten A. and Wech, Tobias}, title = {Self-configuring nnU-net pipeline enables fully automatic infarct segmentation in late enhancement MRI after myocardial infarction}, edition = {accepted version}, doi = {10.1016/j.ejrad.2021.109817}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323418}, year = {2021}, abstract = {Purpose To fully automatically derive quantitative parameters from late gadolinium enhancement (LGE) cardiac MR (CMR) in patients with myocardial infarction and to investigate if phase sensitive or magnitude reconstructions or a combination of both results in best segmentation accuracy. Methods In this retrospective single center study, a convolutional neural network with a U-Net architecture with a self-configuring framework ("nnU-net") was trained for segmentation of left ventricular myocardium and infarct zone in LGE-CMR. A database of 170 examinations from 78 patients with history of myocardial infarction was assembled. Separate fitting of the model was performed, using phase sensitive inversion recovery, the magnitude reconstruction or both contrasts as input channels. Manual labelling served as ground truth. In a subset of 10 patients, the performance of the trained models was evaluated and quantitatively compared by determination of the S{\o}rensen-Dice similarity coefficient (DSC) and volumes of the infarct zone compared with the manual ground truth using Pearson's r correlation and Bland-Altman analysis. Results The model achieved high similarity coefficients for myocardium and scar tissue. No significant difference was observed between using PSIR, magnitude reconstruction or both contrasts as input (PSIR and MAG; mean DSC: 0.83 ± 0.03 for myocardium and 0.72 ± 0.08 for scars). A strong correlation for volumes of infarct zone was observed between manual and model-based approach (r = 0.96), with a significant underestimation of the volumes obtained from the neural network. Conclusion The self-configuring nnU-net achieves predictions with strong agreement compared to manual segmentation, proving the potential as a promising tool to provide fully automatic quantitative evaluation of LGE-CMR.}, language = {en} } @article{KrishnaRodriguesMitschkeetal.2021, author = {Krishna, Anand and Rodrigues, Johannes and Mitschke, Vanessa and Eder, Andreas B.}, title = {Self-reported mask-related worrying reduces relative avoidance bias toward unmasked faces in individuals with low Covid19 anxiety syndrome}, series = {Cognitive Research: Principles and Implications}, volume = {6}, journal = {Cognitive Research: Principles and Implications}, doi = {10.1186/s41235-021-00344-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265720}, year = {2021}, abstract = {Facial masks have become and may remain ubiquitous. Though important for preventing infection, they may also serve as a reminder of the risks of disease. Thus, they may either act as cues for threat, priming avoidance-related behavior, or as cues for a safe interaction, priming social approach. To distinguish between these possibilities, we assessed implicit and explicit evaluations of masked individuals as well as avoidance bias toward relatively unsafe interactions with unmasked individuals in an approach-avoidance task in an online study. We further assessed Covid19 anxiety and specific attitudes toward mask-wearing, including mask effectiveness and desirability, hindrance of communication from masks, aesthetic appeal of masks, and mask-related worrying. Across one sample of younger (18-35 years, N = 147) and one of older adults (60+ years, N = 150), we found neither an average approach nor avoidance bias toward mask-wearing compared to unmasked individuals in the indirect behavior measurement task. However, across the combined sample, self-reported mask-related worrying correlated with reduced avoidance tendencies toward unmasked individuals when Covid19 anxiety was low, but not when it was high. This relationship was specific to avoidance tendencies and was not observed in respect to explicit or implicit preference for mask-wearing individuals. We conclude that unsafe interaction styles may be reduced by targeting mask-related worrying with public interventions, in particular for populations that otherwise have low generalized Covid19 anxiety.}, language = {en} } @article{YuanBorrmannHouetal.2021, author = {Yuan, Yijun and Borrmann, Dorit and Hou, Jiawei and Ma, Yuexin and N{\"u}chter, Andreas and Schwertfeger, S{\"o}ren}, title = {Self-Supervised point set local descriptors for Point Cloud Registration}, series = {Sensors}, volume = {21}, journal = {Sensors}, number = {2}, issn = {1424-8220}, doi = {10.3390/s21020486}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223000}, year = {2021}, abstract = {Descriptors play an important role in point cloud registration. The current state-of-the-art resorts to the high regression capability of deep learning. However, recent deep learning-based descriptors require different levels of annotation and selection of patches, which make the model hard to migrate to new scenarios. In this work, we learn local registration descriptors for point clouds in a self-supervised manner. In each iteration of the training, the input of the network is merely one unlabeled point cloud. Thus, the whole training requires no manual annotation and manual selection of patches. In addition, we propose to involve keypoint sampling into the pipeline, which further improves the performance of our model. Our experiments demonstrate the capability of our self-supervised local descriptor to achieve even better performance than the supervised model, while being easier to train and requiring no data labeling.}, language = {en} } @article{SchembriKimLiessetal.2021, author = {Schembri, Tim and Kim, Jin Hong and Liess, Andreas and Stepanenko, Vladimir and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Semitransparent Layers of Social Self-Sorting Merocyanine Dyes for Ultranarrow Bandwidth Organic Photodiodes}, series = {Advanced Optical Materials}, volume = {9}, journal = {Advanced Optical Materials}, number = {15}, doi = {10.1002/adom.202100213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244762}, year = {2021}, abstract = {Two dipolar merocyanines consisting of the same π-conjugated chromophore but different alkyl substituents adopt very different packing arrangements in their respective solid state with either H- or J-type exciton coupling, leading to ultranarrow absorption bands at 477 and 750 nm, respectively, due to exchange narrowing. The social self-sorting behavior of these push-pull chromophores in their mixed thin films is evaluated and the impact on morphology as well as opto-electronical properties is determined. The implementation of this well-tuned two-component material with tailored optical features allows to optimize planar heterojunction organic photodiodes with fullerene ​(C\(_{60}\)) with either dual or single wavelength selectivity in the blue and NIR spectral range with ultranarrow bandwidths of only 11 nm (200 cm\(^{-1}\)) and an external quantum efficiency of up to 18\% at 754 nm under 0 V bias. The application of these photodiodes as low-power consuming heart rate monitors is demonstrated by a reflectance-mode photoplethysmography (PPG) sensor.}, language = {en} } @article{SalvadorBurekLoehretal.2021, author = {Salvador, Ellaine and Burek, Malgorzata and L{\"o}hr, Mario and Nagai, Michiaki and Hagemann, Carsten and F{\"o}rster, Carola Y.}, title = {Senescence and associated blood-brain barrier alterations in vitro}, series = {Histochemistry and Cell Biology}, volume = {156}, journal = {Histochemistry and Cell Biology}, number = {3}, issn = {1432-119X}, doi = {10.1007/s00418-021-01992-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267435}, pages = {283-292}, year = {2021}, abstract = {Progressive deterioration of the central nervous system (CNS) is commonly associated with aging. An important component of the neurovasculature is the blood-brain barrier (BBB), majorly made up of endothelial cells joined together by intercellular junctions. The relationship between senescence and changes in the BBB has not yet been thoroughly explored. Moreover, the lack of in vitro models for the study of the mechanisms involved in those changes impede further and more in-depth investigations in the field. For this reason, we herein present an in vitro model of the senescent BBB and an initial attempt to identify senescence-associated alterations within.}, language = {en} } @article{AnkenbrandShainbergHocketal.2021, author = {Ankenbrand, Markus J. and Shainberg, Liliia and Hock, Michael and Lohr, David and Schreiber, Laura M.}, title = {Sensitivity analysis for interpretation of machine learning based segmentation models in cardiac MRI}, series = {BMC Medical Imaging}, volume = {21}, journal = {BMC Medical Imaging}, number = {1}, doi = {10.1186/s12880-021-00551-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259169}, pages = {27}, year = {2021}, abstract = {Background Image segmentation is a common task in medical imaging e.g., for volumetry analysis in cardiac MRI. Artificial neural networks are used to automate this task with performance similar to manual operators. However, this performance is only achieved in the narrow tasks networks are trained on. Performance drops dramatically when data characteristics differ from the training set properties. Moreover, neural networks are commonly considered black boxes, because it is hard to understand how they make decisions and why they fail. Therefore, it is also hard to predict whether they will generalize and work well with new data. Here we present a generic method for segmentation model interpretation. Sensitivity analysis is an approach where model input is modified in a controlled manner and the effect of these modifications on the model output is evaluated. This method yields insights into the sensitivity of the model to these alterations and therefore to the importance of certain features on segmentation performance. Results We present an open-source Python library (misas), that facilitates the use of sensitivity analysis with arbitrary data and models. We show that this method is a suitable approach to answer practical questions regarding use and functionality of segmentation models. We demonstrate this in two case studies on cardiac magnetic resonance imaging. The first case study explores the suitability of a published network for use on a public dataset the network has not been trained on. The second case study demonstrates how sensitivity analysis can be used to evaluate the robustness of a newly trained model. Conclusions Sensitivity analysis is a useful tool for deep learning developers as well as users such as clinicians. It extends their toolbox, enabling and improving interpretability of segmentation models. Enhancing our understanding of neural networks through sensitivity analysis also assists in decision making. Although demonstrated only on cardiac magnetic resonance images this approach and software are much more broadly applicable.}, language = {en} } @article{WidowskiReynaertOpheldersetal.2021, author = {Widowski, Helene and Reynaert, Niki L. and Ophelders, Daan R. M. G. and H{\"u}tten, Matthias C. and Nikkels, Peter G. J. and Severens-Rijvers, Carmen A. H. and Cleutjens, Jack P. M. and Kemp, Matthew W. and Newnham, John P. and Saito, Masatoshi and Usuda, Haruo and Payne, Matthew S. and Jobe, Alan H. and Kramer, Boris W. and Delhaas, Tammo and Wolfs, Tim G. A. M.}, title = {Sequential Exposure to Antenatal Microbial Triggers Attenuates Alveolar Growth and Pulmonary Vascular Development and Impacts Pulmonary Epithelial Stem/Progenitor Cells}, series = {Frontiers in Medicine}, volume = {8}, journal = {Frontiers in Medicine}, issn = {2296-858X}, doi = {10.3389/fmed.2021.614239}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229695}, year = {2021}, abstract = {Perinatal inflammatory stress is strongly associated with adverse pulmonary outcomes after preterm birth. Antenatal infections are an essential perinatal stress factor and contribute to preterm delivery, induction of lung inflammation and injury, pre-disposing preterm infants to bronchopulmonary dysplasia. Considering the polymicrobial nature of antenatal infection, which was reported to result in diverse effects and outcomes in preterm lungs, the aim was to examine the consequences of sequential inflammatory stimuli on endogenous epithelial stem/progenitor cells and vascular maturation, which are crucial drivers of lung development. Therefore, a translational ovine model of antenatal infection/inflammation with consecutive exposures to chronic and acute stimuli was used. Ovine fetuses were exposed intra-amniotically to Ureaplasma parvum 42 days (chronic stimulus) and/or to lipopolysaccharide 2 or 7 days (acute stimulus) prior to preterm delivery at 125 days of gestation. Pulmonary inflammation, endogenous epithelial stem cell populations, vascular modulators and morphology were investigated in preterm lungs. Pre-exposure to UP attenuated neutrophil infiltration in 7d LPS-exposed lungs and prevented reduction of SOX-9 expression and increased SP-B expression, which could indicate protective responses induced by re-exposure. Sequential exposures did not markedly impact stem/progenitors of the proximal airways (P63+ basal cells) compared to single exposure to LPS. In contrast, the alveolar size was increased solely in the UP+7d LPS group. In line, the most pronounced reduction of AEC2 and proliferating cells (Ki67+) was detected in these sequentially UP + 7d LPS-exposed lambs. A similar sensitization effect of UP pre-exposure was reflected by the vessel density and expression of vascular markers VEGFR-2 and Ang-1 that were significantly reduced after UP exposure prior to 2d LPS, when compared to UP and LPS exposure alone. Strikingly, while morphological changes of alveoli and vessels were seen after sequential microbial exposure, improved lung function was observed in UP, 7d LPS, and UP+7d LPS-exposed lambs. In conclusion, although sequential exposures did not markedly further impact epithelial stem/progenitor cell populations, re-exposure to an inflammatory stimulus resulted in disturbed alveolarization and abnormal pulmonary vascular development. Whether these negative effects on lung development can be rescued by the potentially protective responses observed, should be examined at later time points.}, language = {en} } @article{KanzowRaharjaSchwartz2021, author = {Kanzow, Christian and Raharja, Andreas B. and Schwartz, Alexandra}, title = {Sequential optimality conditions for cardinality-constrained optimization problems with applications}, series = {Computational Optimization and Applications}, volume = {80}, journal = {Computational Optimization and Applications}, number = {1}, issn = {1573-2894}, doi = {10.1007/s10589-021-00298-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269052}, pages = {185-211}, year = {2021}, abstract = {Recently, a new approach to tackle cardinality-constrained optimization problems based on a continuous reformulation of the problem was proposed. Following this approach, we derive a problem-tailored sequential optimality condition, which is satisfied at every local minimizer without requiring any constraint qualification. We relate this condition to an existing M-type stationary concept by introducing a weak sequential constraint qualification based on a cone-continuity property. Finally, we present two algorithmic applications: We improve existing results for a known regularization method by proving that it generates limit points satisfying the aforementioned optimality conditions even if the subproblems are only solved inexactly. And we show that, under a suitable Kurdyka-Łojasiewicz-type assumption, any limit point of a standard (safeguarded) multiplier penalty method applied directly to the reformulated problem also satisfies the optimality condition. These results are stronger than corresponding ones known for the related class of mathematical programs with complementarity constraints.}, language = {en} } @article{AboagyeWeberMerdianetal.2021, author = {Aboagye, B. and Weber, T. and Merdian, H. L. and Bartsch, D. and Lesch, K. P. and Waider, J.}, title = {Serotonin deficiency induced after brain maturation rescues consequences of early life adversity}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, issn = {2045-2322}, doi = {10.1038/s41598-021-83592-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258626}, year = {2021}, abstract = {Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.}, language = {en} } @article{SteinMarufMuelleretal.2021, author = {Stein, Kiera and Maruf, Abdullah Al and M{\"u}ller, Daniel J. and Bishop, Jeffrey R. and Bousman, Chad A.}, title = {Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis}, series = {Journal of Personalized Medicine}, volume = {11}, journal = {Journal of Personalized Medicine}, number = {12}, issn = {2075-4426}, doi = {10.3390/jpm11121334}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252294}, year = {2021}, abstract = {Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.}, language = {en} } @article{JanschZieglerForeroetal.2021, author = {Jansch, Charline and Ziegler, Georg C. and Forero, Andrea and Gredy, Sina and W{\"a}ldchen, Sina and Vitale, Maria Rosaria and Svirin, Evgeniy and Z{\"o}ller, Johanna E. M. and Waider, Jonas and G{\"u}nther, Katharina and Edenhofer, Frank and Sauer, Markus and Wischmeyer, Erhard and Lesch, Klaus-Peter}, title = {Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly}, series = {Journal of Neural Transmission}, volume = {128}, journal = {Journal of Neural Transmission}, number = {2}, issn = {1435-1463}, doi = {10.1007/s00702-021-02303-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268519}, pages = {225-241}, year = {2021}, abstract = {Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42\%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders.}, language = {en} } @article{JanzenSlavikZeheetal.2021, author = {Janzen, Dieter and Slavik, Benedikt and Zehe, Markus and Sotriffer, Christoph and Loos, Helene M. and Buettner, Andrea and Villmann, Carmen}, title = {Sesquiterpenes and sesquiterpenoids harbor modulatory allosteric potential and affect inhibitory GABA\(_{A}\) receptor function in vitro}, series = {Journal of Neurochemistry}, volume = {159}, journal = {Journal of Neurochemistry}, number = {1}, doi = {10.1111/jnc.15469}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259546}, pages = {101-115}, year = {2021}, abstract = {Naturally occurring compounds such as sesquiterpenes and sesquiterpenoids (SQTs) have been shown to modulate GABA\(_{A}\) receptors (GABA\(_{A}\)Rs). In this study, the modulatory potential of 11 SQTs at GABA\(_{A}\)Rs was analyzed to characterize their potential neurotropic activity. Transfected HEK293 cells and primary hippocampal neurons were functionally investigated using electrophysiological whole-cell recordings. Significantly different effects of β-caryophyllene and α-humulene, as well as their respective derivatives β-caryolanol and humulol, were observed in the HEK293 cell system. In neurons, the concomitant presence of phasic and tonic GABA\(_{A}\)R configurations accounts for differences in receptor modulation by SQTs. The in vivo presence of the γ\(_{2}\) and δ subunits is important for SQT modulation. While phasic GABA\(_{A}\) receptors in hippocampal neurons exhibited significantly altered GABA-evoked current amplitudes in the presence of humulol and guaiol, negative allosteric potential at recombinantly expressed α\(_{1}\)β\(_{2}\)γ\(_{2}\) receptors was only verified for humolol. Modeling and docking studies provided support for the binding of SQTs to the neurosteroid-binding site of the GABA\(_{A}\)R localized between transmembrane segments 1 and 3 at the (\(^{+}\)α)-(\(^{-}\)α) interface. In sum, differences in the modulation of GABA\(_{A}\)R isoforms between SQTs were identified. Another finding is that our results provide an indication that nutritional digestion affects the neurotropic potential of natural compounds.}, language = {en} } @article{NotzLotzHerrmannetal.2021, author = {Notz, Quirin and Lotz, Christopher and Herrmann, Johannes and Vogt, Marius and Schlesinger, Tobias and Kredel, Markus and Muellges, Wolfgang and Weismann, Dirk and Westermaier, Thomas and Meybohm, Patrick and Kranke, Peter}, title = {Severe neurological complications in critically ill COVID‑19 patients}, series = {Journal of Neurology}, journal = {Journal of Neurology}, issn = {0340-5354}, doi = {10.1007/s00415-020-10152-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232429}, pages = {1576-1579}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{StrekalovaVeniaminovaSvirinetal.2021, author = {Strekalova, Tatyana and Veniaminova, Ekaterina and Svirin, Evgeniy and Kopeikina, Ekaterina and Veremeyko, Tatyana and Yung, Amanda W. Y. and Proshin, Andrey and Tan, Shawn Zheng Kai and Khairuddin, Sharafuddin and Lim, Lee Wei and Lesch, Klaus-Peter and Walitza, Susanne and Anthony, Daniel C. and Ponomarev, Eugene D.}, title = {Sex-specific ADHD-like behaviour, altered metabolic functions, and altered EEG activity in sialyltransferase ST3GAL5-deficient mice}, series = {Biomolecules}, volume = {11}, journal = {Biomolecules}, number = {12}, issn = {2218-273X}, doi = {10.3390/biom11121759}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250071}, year = {2021}, abstract = {A deficiency in GM3-derived gangliosides, resulting from a lack of lactosylceramide-alpha-2,3-sialyltransferase (ST3GAL5), leads to severe neuropathology, including epilepsy and metabolic abnormalities. Disruption of ganglioside production by this enzyme may also have a role in the development of neuropsychiatric disorders. ST3Gal5 knock-out (St3gal5\(^{-/-}\)) mice lack a-, b-, and c-series gangliosides, but exhibit no overt neuropathology, possibly owing to the production of compensatory 0-series glycosphingolipids. Here, we sought to investigate the possibility that St3gal5\(^{-/-}\) mice might exhibit attention-deficit/hyperactivity disorder (ADHD)-like behaviours. In addition, we evaluated potential metabolic and electroencephalogram (EEG) abnormalities. St3gal5\(^{-/-}\) mice were subjected to behavioural testing, glucose tolerance tests, and the levels of expression of brain and peripheral A and B isoforms of the insulin receptor (IR) were measured. We found that St3gal5\(^{-/-}\) mice exhibit locomotor hyperactivity, impulsivity, neophobia, and anxiety-like behavior. The genotype also altered blood glucose levels and glucose tolerance. A sex bias was consistently found in relation to body mass and peripheral IR expression. Analysis of the EEG revealed an increase in amplitude in St3gal5\(^{-/-}\) mice. Together, St3gal5\(^{-/-}\) mice exhibit ADHD-like behaviours, altered metabolic and EEG measures providing a useful platform for better understanding of the contribution of brain gangliosides to ADHD and associated comorbidities.}, language = {en} } @article{GrobHeinigGruebeletal.2021, author = {Grob, Robin and Heinig, Niklas and Gr{\"u}bel, Kornelia and R{\"o}ssler, Wolfgang and Fleischmann, Pauline N.}, title = {Sex-specific and caste-specific brain adaptations related to spatial orientation in Cataglyphis ants}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, number = {18}, doi = {10.1002/cne.25221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257299}, pages = {3882-3892}, year = {2021}, abstract = {Cataglyphis desert ants are charismatic central place foragers. After long-ranging foraging trips, individual workers navigate back to their nest relying mostly on visual cues. The reproductive caste faces other orientation challenges, i.e. mate finding and colony foundation. Here we compare brain structures involved in spatial orientation of Cataglyphis nodus males, gynes, and foragers by quantifying relative neuropil volumes associated with two visual pathways, and numbers and volumes of antennal lobe (AL) olfactory glomeruli. Furthermore, we determined absolute numbers of synaptic complexes in visual and olfactory regions of the mushroom bodies (MB) and a major relay station of the sky-compass pathway to the central complex (CX). Both female castes possess enlarged brain centers for sensory integration, learning, and memory, reflected in voluminous MBs containing about twice the numbers of synaptic complexes compared with males. Overall, male brains are smaller compared with both female castes, but the relative volumes of the optic lobes and CX are enlarged indicating the importance of visual guidance during innate behaviors. Male ALs contain greatly enlarged glomeruli, presumably involved in sex-pheromone detection. Adaptations at both the neuropil and synaptic levels clearly reflect differences in sex-specific and caste-specific demands for sensory processing and behavioral plasticity underlying spatial orientation.}, language = {en} } @article{Freitag‐WolfMunzJungeetal.2021, author = {Freitag-Wolf, Sandra and Munz, Matthias and Junge, Olaf and Graetz, Christian and Jockel-Schneider, Yvonne and Staufenbiel, Ingmar and Bruckmann, Corinna and Lieb, Wolfgang and Franke, Andre and Loos, Bruno G. and Jepsen, S{\o}ren and Dommisch, Henrik and Schaefer, Arne S.}, title = {Sex-specific genetic factors affect the risk of early-onset periodontitis in Europeans}, series = {Journal of Clinical Periodontology}, volume = {48}, journal = {Journal of Clinical Periodontology}, number = {11}, doi = {10.1111/jcpe.13538}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262445}, pages = {1404 -- 1413}, year = {2021}, abstract = {Aims Various studies have reported that young European women are more likely to develop early-onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype-by-sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods Using the case-only design, we tested for differences in genetic effects between men and women in 896 North-West European early-onset cases, using imputed genotypes from the OmniExpress genotyping array. Population-representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S-associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome-wide-associated with heel bone mineral density (CPEB4, MECOM), waist-to-hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter-sex phenotypic variation in early-onset periodontitis.}, language = {en} } @phdthesis{Heller2021, author = {Heller, Aline}, title = {Sicherheit und Effektivit{\"a}t von Amisulprid zur Therapie von {\"U}belkeit und Erbrechen nach Narkosen}, doi = {10.25972/OPUS-24176}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241762}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {PONV stellt mit einer Inzidenz von circa 30 \% ein relevantes Problem in der postoperativen Phase dar. Amisulprid ist ein atypisches Neuroleptikum, das zur Behandlung der Schizophrenie verwendet wird und geh{\"o}rt zur Gruppe der D2-Rezeptor-Antagonisten. Hier{\"u}ber wirkt Amisulprid antiemetisch. Ziel der Studie war, die Sicherheit und Effektivit{\"a}t einer intraven{\"o}sen Einmalgabe von Amisulprid in den Dosierungen 5 mg und 10 mg zur Therapie von PONV, nach Versagen einer PONV-Prophylaxe, untereinander und gegen{\"u}ber einem Placebo zu vergleichen. Es handelte sich hierbei um eine multizentrische, randomisierte, doppelblinde Phase-III-Studie. Amisulprid zeigte ein benignes Nebenwirkungsprofil. Amisulprid zeigte in der Dosierung 10 mg eine statistisch signifikante {\"U}berlegenheit gegen{\"u}ber Placebo sowohl zur Therapie von PONV, als auch im Auftreten signifikanter {\"U}belkeit und im Gebrauch einer Rescue-Medikation. Eine weitere interessante Fragestellung w{\"a}re der Vergleich der Sicherheit und Effektivit{\"a}t von Amisulprid mit einem weiteren Antiemetikum.}, subject = {Amisulprid}, language = {de} } @phdthesis{Raban2021, author = {Raban, Rebecca Emmi Hildegard}, title = {Sicherheit und Wirksamkeit von intrathekalem Triamcinolon bei Patienten mit chronisch-progredienter Multipler Sklerose : eine retrospektive Longitudinalstudie}, doi = {10.25972/OPUS-22047}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220478}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Im Zeitraum von 2004 bis 2016 erhielten an der Neurologischen Universit{\"a}tsklinik W{\"u}rzburg Patienten mit einer chronisch progredienten Multiplen Sklerose insgesamt 595 Injektionen von intrathekalem Triamcinolonacetonid. Diese Arbeit befasst sich mit Sicherheit, Nebenwirkungen und Wirksamkeit der intrathekalen Therapieform.}, subject = {Intrathekale Applikation}, language = {de} } @article{MachataSreekantapuramHuennigeretal.2021, author = {Machata, Silke and Sreekantapuram, Sravya and H{\"u}nniger, Kerstin and Kurzai, Oliver and Dunker, Christine and Schubert, Katja and Kr{\"u}ger, Wibke and Schulze-Richter, Bianca and Speth, Cornelia and Rambach, G{\"u}nter and Jacobsen, Ilse D.}, title = {Significant Differences in Host-Pathogen Interactions Between Murine and Human Whole Blood}, series = {Frontiers in Immunology}, volume = {11}, journal = {Frontiers in Immunology}, issn = {1664-3224}, doi = {10.3389/fimmu.2020.565869}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222575}, year = {2021}, abstract = {Murine infection models are widely used to study systemic candidiasis caused by C. albicans. Whole-blood models can help to elucidate host-pathogens interactions and have been used for several Candida species in human blood. We adapted the human whole-blood model to murine blood. Unlike human blood, murine blood was unable to reduce fungal burden and more substantial filamentation of C. albicans was observed. This coincided with less fungal association with leukocytes, especially neutrophils. The lower neutrophil number in murine blood only partially explains insufficient infection and filamentation control, as spiking with murine neutrophils had only limited effects on fungal killing. Furthermore, increased fungal survival is not mediated by enhanced filamentation, as a filament-deficient mutant was likewise not eliminated. We also observed host-dependent differences for interaction of platelets with C. albicans, showing enhanced platelet aggregation, adhesion and activation in murine blood. For human blood, opsonization was shown to decrease platelet interaction suggesting that complement factors interfere with fungus-to-platelet binding. Our results reveal substantial differences between murine and human whole-blood models infected with C. albicans and thereby demonstrate limitations in the translatability of this ex vivo model between hosts.}, language = {en} } @phdthesis{Riensch2021, author = {Riensch, Nicolas Alexander}, title = {Silicon/Boron Exchange Routes to Novel Inorganic-Organic Hybrid Molecules, Oligomers, Polymers and Macrocycles}, doi = {10.25972/OPUS-23865}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238657}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Industrially used semiconducting materials, building blocks of modern electronics and computer industry, are mostly based on inorganic, crystalline solids, which have the drawback of relatively high production costs. As an alternative, organic pi-conjugated systems show enhanced flexibility and processability as well as the opportunity to obtain light-weight materials. They have emerged as attractive candidates, especially since elements beyond hydrogen and carbon can be used to create pi-conjugated frameworks. In recent years, pi-conjugated oligomers and polymers with tricoordinate boron centers incorporated into the main chain of such organic polymers have attracted considerable attention as the interaction of the vacant p orbital on boron with an adjacent pi system of the chain leads to extended conjugated materials. These materials show intriguing optical and electronic properties and potential applications in organic electronics and optoelectronics (OLEDs, OFETs, photovoltaics) or as sensory materials. In this thesis, a catalytic Si/B exchange reaction protocol is used as a facile and highly effective B-C bond formation method to synthesize organoboron molecules, oligomers, polymers and macrocycles. This reaction is applied to synthesize a series of thienyl- and furylborane based materials. Special focus is on furylborane based materials, which, in general, have been only scarcely explored so far. This is mainly due to synthetic challenges since furan decomposes readily in the presence of light and oxygen. Our mild and highly selective reaction protocol in combination with sufficient kinetic protection of the boron centers gives access to a series of extended organoboranes featuring furylborane units in the main chain. Furthermore, kinetically stabilized furylboranes are established as highly robust and versatile building blocks for pi conjugated materials. The obtained materials reveal remarkable luminescence properties. The scope of potential starting materials was investigated by a catalyst screening, demonstrating that the Si/B exchange reaction can also be performed for less reactive aryldichloroboranes. Furthermore, borazine-based hybrid cyclomatrix microspheres have been synthesized via a Si/B exchange condensation reaction under precipitation polymerization conditions. Finally, synthetic routes to tetrabora- and diboraporphyrinogens were attempted in a multi-step reaction procedure. In the case for tetraboraporphyrinogens, the final macrocyclization reaction under pseudo high-dilution conditions afforded a mixture of macrocycles with different ring sizes. UV-vis and fluorescence spectroscopic analysis indicated significant differences in comparison to their linear congeners.}, subject = {Bororganische Verbindungen}, language = {en} } @article{RokhafrouzLatifiAbkaretal.2021, author = {Rokhafrouz, Mohammad and Latifi, Hooman and Abkar, Ali A. and Wojciechowski, Tomasz and Czechlowski, Mirosław and Naieni, Ali Sadeghi and Maghsoudi, Yasser and Niedbała, Gniewko}, title = {Simplified and hybrid remote sensing-based delineation of management zones for nitrogen variable rate application in wheat}, series = {Agriculture}, volume = {11}, journal = {Agriculture}, number = {11}, issn = {2077-0472}, doi = {10.3390/agriculture11111104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250033}, year = {2021}, abstract = {Enhancing digital and precision agriculture is currently inevitable to overcome the economic and environmental challenges of the agriculture in the 21st century. The purpose of this study was to generate and compare management zones (MZ) based on the Sentinel-2 satellite data for variable rate application of mineral nitrogen in wheat production, calculated using different remote sensing (RS)-based models under varied soil, yield and crop data availability. Three models were applied, including (1) a modified "RS- and threshold-based clustering", (2) a "hybrid-based, unsupervised clustering", in which data from different sources were combined for MZ delineation, and (3) a "RS-based, unsupervised clustering". Various data processing methods including machine learning were used in the model development. Statistical tests such as the Paired Sample T-test, Kruskal-Wallis H-test and Wilcoxon signed-rank test were applied to evaluate the final delineated MZ maps. Additionally, a procedure for improving models based on information about phenological phases and the occurrence of agricultural drought was implemented. The results showed that information on agronomy and climate enables improving and optimizing MZ delineation. The integration of prior knowledge on new climate conditions (drought) in image selection was tested for effective use of the models. Lack of this information led to the infeasibility of obtaining optimal results. Models that solely rely on remote sensing information are comparatively less expensive than hybrid models. Additionally, remote sensing-based models enable delineating MZ for fertilizer recommendations that are temporally closer to fertilization times.}, language = {en} } @article{Graetz2021, author = {Graetz, Jonas}, title = {Simulation study towards quantitative X-ray and neutron tensor tomography regarding the validity of linear approximations of dark-field anisotropy}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, doi = {10.1038/s41598-021-97389-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261844}, year = {2021}, abstract = {Tensor tomography is fundamentally based on the assumption of a both anisotropic and linear contrast mechanism. While the X-ray or neutron dark-field contrast obtained with Talbot(-Lau) interferometers features the required anisotropy, a preceding detailed study of dark-field signal origination however found its specific orientation dependence to be a non-linear function of the underlying anisotropic mass distribution and its orientation, especially challenging the common assumption that dark-field signals are describable by a function over the unit sphere. Here, two approximative linear tensor models with reduced orientation dependence are investigated in a simulation study with regard to their applicability to grating based X-ray or neutron dark-field tensor tomography. By systematically simulating and reconstructing a large sample of isolated volume elements covering the full range of feasible anisotropies and orientations, direct correspondences are drawn between the respective tensors characterizing the physically based dark-field model used for signal synthesization and the mathematically motivated simplified models used for reconstruction. The anisotropy of freely rotating volume elements is thereby confirmed to be, for practical reconstruction purposes, approximable both as a function of the optical axis' orientation or as a function of the interferometer's grating orientation. The eigenvalues of the surrogate models' tensors are found to exhibit fuzzy, yet almost linear relations to those of the synthesization model. Dominant orientations are found to be recoverable with a margin of error on the order of magnitude of 1 degrees. Although the input data must adequately address the full orientation dependence of dark-field anisotropy, the present results clearly support the general feasibility of quantitative X-ray dark-field tensor tomography within an inherent yet acceptable statistical margin of uncertainty.}, language = {en} } @article{WinterAndelovicKampfetal.2021, author = {Winter, Patrick M. and Andelovic, Kristina and Kampf, Thomas and Hansmann, Jan and Jakob, Peter Michael and Bauer, Wolfgang Rudolf and Zernecke, Alma and Herold, Volker}, title = {Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {23}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {1}, doi = {10.1186/s12968-021-00725-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259152}, pages = {34}, year = {2021}, abstract = {Purpose Wall shear stress (WSS) and pulse wave velocity (PWV) are important parameters to characterize blood flow in the vessel wall. Their quantification with flow-sensitive phase-contrast (PC) cardiovascular magnetic resonance (CMR), however, is time-consuming. Furthermore, the measurement of WSS requires high spatial resolution, whereas high temporal resolution is necessary for PWV measurements. For these reasons, PWV and WSS are challenging to measure in one CMR session, making it difficult to directly compare these parameters. By using a retrospective approach with a flexible reconstruction framework, we here aimed to simultaneously assess both PWV and WSS in the murine aortic arch from the same 4D flow measurement. Methods Flow was measured in the aortic arch of 18-week-old wildtype (n = 5) and ApoE\(^{-/-}\) mice (n = 5) with a self-navigated radial 4D-PC-CMR sequence. Retrospective data analysis was used to reconstruct the same dataset either at low spatial and high temporal resolution (PWV analysis) or high spatial and low temporal resolution (WSS analysis). To assess WSS, the aortic lumen was labeled by semi-automatically segmenting the reconstruction with high spatial resolution. WSS was determined from the spatial velocity gradients at the lumen surface. For calculation of the PWV, segmentation data was interpolated along the temporal dimension. Subsequently, PWV was quantified from the through-plane flow data using the multiple-points transit-time method. Reconstructions with varying frame rates and spatial resolutions were performed to investigate the influence of spatiotemporal resolution on the PWV and WSS quantification. Results 4D flow measurements were conducted in an acquisition time of only 35 min. Increased peak flow and peak WSS values and lower errors in PWV estimation were observed in the reconstructions with high temporal resolution. Aortic PWV was significantly increased in ApoE\(^{-/-}\) mice compared to the control group (1.7 ± 0.2 versus 2.6 ± 0.2 m/s, p < 0.001). Mean WSS magnitude values averaged over the aortic arch were (1.17 ± 0.07) N/m\(^2\) in wildtype mice and (1.27 ± 0.10) N/m\(^2\) in ApoE\(^{-/-}\) mice. Conclusion The post processing algorithm using the flexible reconstruction framework developed in this study permitted quantification of global PWV and 3D-WSS in a single acquisition. The possibility to assess both parameters in only 35 min will markedly improve the analyses and information content of in vivo measurements.}, language = {en} } @article{TufarelliFriedrichGrossetal.2021, author = {Tufarelli, Tommaso and Friedrich, Daniel and Groß, Heiko and Hamm, Joachim and Hess, Ortwin and Hecht, Bert}, title = {Single quantum emitter Dicke enhancement}, series = {Physical Review Research}, volume = {3}, journal = {Physical Review Research}, doi = {10.1103/PhysRevResearch.3.033103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261459}, year = {2021}, abstract = {Coupling N identical emitters to the same field mode is a well-established method to enhance light-matter interaction. However, the resulting √N boost of the coupling strength comes at the cost of a "linearized" (effectively semiclassical) dynamics. Here, we instead demonstrate a new approach for enhancing the coupling constant of a single quantum emitter, while retaining the nonlinear character of the light-matter interaction. We consider a single quantum emitter with N nearly degenerate transitions that are collectively coupled to the same field mode. We show that in such conditions an effective Jaynes-Cummings model emerges with a boosted coupling constant of order √N. The validity and consequences of our general conclusions are analytically demonstrated for the instructive case N=2. We further observe that our system can closely match the spectral line shapes and photon autocorrelation functions typical of Jaynes-Cummings physics, proving that quantum optical nonlinearities are retained. Our findings match up very well with recent broadband plasmonic nanoresonator strong-coupling experiments and will, therefore, facilitate the control and detection of single-photon nonlinearities at ambient conditions.}, language = {en} } @article{KruegerMausKressetal.2021, author = {Kr{\"u}ger, Timothy and Maus, Katharina and Kreß, Verena and Meyer-Natus, Elisabeth and Engstler, Markus}, title = {Single-cell motile behaviour of Trypanosoma brucei in thin-layered fluid collectives}, series = {The European Physical Journal E}, volume = {44}, journal = {The European Physical Journal E}, number = {3}, issn = {1292-895X}, doi = {10.1140/epje/s10189-021-00052-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273022}, year = {2021}, abstract = {We describe a system for the analysis of an important unicellular eukaryotic flagellate in a confining and crowded environment. The parasite Trypanosoma brucei is arguably one of the most versatile microswimmers known. It has unique properties as a single microswimmer and shows remarkable adaptations (not only in motility, but prominently so), to its environment during a complex developmental cycle involving two different hosts. Specific life cycle stages show fascinating collective behaviour, as millions of cells can be forced to move together in extreme confinement. Our goal is to examine such motile behaviour directly in the context of the relevant environments. Therefore, for the first time, we analyse the motility behaviour of trypanosomes directly in a widely used assay, which aims to evaluate the parasites behaviour in collectives, in response to as yet unknown parameters. In a step towards understanding whether, or what type of, swarming behaviour of trypanosomes exists, we customised the assay for quantitative tracking analysis of motile behaviour on the single-cell level. We show that the migration speed of cell groups does not directly depend on single-cell velocity and that the system remains to be simplified further, before hypotheses about collective motility can be advanced.}, language = {en} } @article{KlemmtKoenig2021, author = {Klemmt, Chantal and K{\"o}nig, Sarah}, title = {Situational Judgement Test als Unterrichtsmethode f{\"u}r die kritische Diskussion zu wissenschaftlicher Praxis und Fehlverhalten}, series = {Wiener Medizinische Wochenschrift}, volume = {171}, journal = {Wiener Medizinische Wochenschrift}, issn = {0043-5341}, doi = {10.1007/s10354-020-00780-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235304}, pages = {174-181}, year = {2021}, abstract = {Wissenschaftskompetenz ist eine Schl{\"u}sselqualifikation f{\"u}r jede {\"a}rztliche T{\"a}tigkeit und sollte ebenso wie die Auseinandersetzung mit Entscheidungsprozessen von Beginn an ins Medizinstudium integriert werden. Ziel der Studie war, die Themen der guten wissenschaftlichen Praxis und des wissenschaftlichen Fehlverhaltens zu vermitteln. Ferner wurde durch die methodische Intervention „Gruppendiskussion" eine Reflexion im Kontext der wissenschaftlichen Angemessenheit herbeigef{\"u}hrt. Hierf{\"u}r wurde der Situational Judgement Test (SJT) von den Studierenden (N = 743) (individuell und in der Gruppe) bearbeitet, und dessen Resultate wurden mit den Antworten von Expert/innen/en (N = 23) verglichen. Nach der Gruppendiskussion n{\"a}herten sich die Ergebnisse in der Verteilung und Reihenfolge den Antwortm{\"o}glichkeiten der Expert/innen/en an. Jedoch tendierten die Studierenden signifikant h{\"a}ufiger zu jenen Antworten, die hilfesuchende, passive und verantwortungs{\"u}bertragende Optionen bedeuteten. Insgesamt hat sich der SJT als didaktische Intervention bew{\"a}hrt. Die Studierenden setzten sich aktiv mit den Themen auseinander, eine Diskussion konnte angeregt und das eigene Verhalten kritisch reflektiert werden.}, language = {de} } @article{HojsgaardSchartl2021, author = {Hojsgaard, Diego and Schartl, Manfred}, title = {Skipping sex: A nonrecombinant genomic assemblage of complementary reproductive modules}, series = {BioEssays}, volume = {43}, journal = {BioEssays}, number = {1}, doi = {10.1002/bies.202000111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225818}, year = {2021}, abstract = {The unusual occurrence and developmental diversity of asexual eukaryotes remain a puzzle. De novo formation of a functioning asexual genome requires a unique assembly of sets of genes or gene states to disrupt cellular mechanisms of meiosis and gametogenesis, and to affect discrete components of sexuality and produce clonal or hemiclonal offspring. We highlight two usually overlooked but essential conditions to understand the molecular nature of clonal organisms, that is, a nonrecombinant genomic assemblage retaining modifiers of the sexual program, and a complementation between altered reproductive components. These subtle conditions are the basis for physiologically viable and genetically balanced transitions between generations. Genomic and developmental evidence from asexual animals and plants indicates the lack of complementation of molecular changes in the sexual reproductive program is likely the main cause of asexuals' rarity, and can provide an explanatory frame for the developmental diversity and lability of developmental patterns in some asexuals as well as for the discordant time to extinction estimations.}, language = {en} } @phdthesis{Lang2021, author = {Lang, Konstantin}, title = {SLC6A2-regulierende microRNAs bei Angsterkrankungen: Genexpressions- und Assoziationsuntersuchungen}, doi = {10.25972/OPUS-23093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230939}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Angsterkrankungen sind h{\"a}ufige Krankheitsbilder mit bislang nicht vollst{\"a}ndig gekl{\"a}rter multifaktorieller {\"A}tiologie. Neben Umwelt- und psychosozialen Faktoren zeigen Studien eine signifikante famili{\"a}re H{\"a}ufung und lassen eine genetische Komponente mit einer Heritabilit{\"a}t in einem Bereich von 30-60 \% vermuten. Da hierbei am ehesten von einem komplexen Zusammenspiel verschiedenster Gene mit unterschiedlicher Relevanz auszugehen ist, stellen miRNAs eine bedeutende Gr{\"o}ße dar, da sie es verm{\"o}gen auf transkriptioneller Ebene Einfluss auf die Regulierung einer Vielzahl von Genen zu nehmen. Verschiedene Aspekte liefern Hinweise darauf, dass eine Neurotransmitterdysregulation eine wichtige Komponente in der Pathogenese von Angsterkrankungen einnimmt - insbesondere ver{\"a}nderte noradrenerge Signalwege sind hierbei entscheidend beteiligt. Dies macht den Noradrenalin-Transporter bzw. SLC6A2 zu einem interessanten Kandidatengen, und stellt die Bezugsgr{\"o}ße der angestellten Untersuchungen in dieser Arbeit dar. miRNAs, welche die SLC6A2-Expression modulieren, k{\"o}nnen somit Einfluss auf zentrale Verarbeitungswege von Angst nehmen. Im ersten Teil der vorliegenden Arbeit wurden potentielle miRNA-Regulatoren von SLC6A2 in silico ermittelt und in einem weiteren Schritt in vitro {\"u}berpr{\"u}ft. Zehn der miRNAs (hsa-miR-378g, hsa-miR-330-5p, hsa-miR-4781-5p, hsa-miR664b-3p, hsa-miR-4715-3p, hsa-miR-579-3p, hsa-miR-3921, hsa-miR-3622b-5p, hsa-miR-4773, hsa-miR-532-3p) zeigten hierbei eine relevante Abnahme der Luciferase-Aktivit{\"a}t als Hinweis auf ihre funktionelle Relevanz und stellen damit die Basis der nachfolgenden Untersuchungen dar. Im zweiten Teil der Arbeit wurden Einzelbasenpolymorphismen im Bereich der zuvor ermittelten miRNA-Gene sowie eines SNP innerhalb der 3'-UTR von SLC6A2 mittels Fall-Kontroll-Studie in einer Population von Patienten mit Panikst{\"o}rung und entsprechenden Kontrollen untersucht. Eine nominelle Assoziation ließ sich f{\"u}r das (minor) T-Allel von rs2910931 (stromaufw{\"a}rts von MIR579) (p-allel = 0,004) sowie das (major) A-Allel von rs2582372 (p-allel = 0,023) feststellen. In Einklang hiermit ließ sich weiterhin f{\"u}r rs2910931 eine signifikante Assoziation zwischen der Anzahl der (minor) T-Allele und dem ASI-Wert (β = 0,371, p = 0,029, 95 \%-CI 0,039-0,702) sowie dem ACQ-Wert (β = 0,012, p = 0,041, 95 \%-CI 0,000-0,023) ermitteln. Somit zeigt sich eine Einflussnahme der genetischen Variante um MIR579 auf die Feinmodulation der Noradrenalin-Hom{\"o}ostase als m{\"o}glichem {\"a}tiopathogenetischen Faktor von Angsterkrankungen.}, subject = {Angsterkrankungen}, language = {de} } @phdthesis{Venturini2021, author = {Venturini, Elisa}, title = {Small proteins in \(Salmonella\): an updated annotation and a global analysis to find new regulators of virulence}, doi = {10.25972/OPUS-24702}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247029}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Small proteins, often defined as shorter than 50 amino acids, have been implicated in fundamental cellular processes. Despite this, they have been largely understudied throughout all domains of life, since their size often makes their identification and characterization challenging. This work addressed the knowledge gap surrounding small proteins with a focus on the model bacterial pathogen Salmonella Typhimurium. In a first step, new small proteins were identified with a combination of computational and experimental approaches. Infection-relevant datasets were then investigated with the updated Salmonella annotation to prioritize promising candidates involved in virulence. To implement the annotation of new small proteins, predictions from the algorithm sPepFinder were merged with those derived from Ribo-seq. These were added to the Salmonella annotation and used to (re)analyse different datasets. Information regarding expression during infection (dual RNA-seq) and requirement for virulence (TraDIS) was collected for each given coding sequence. In parallel, Grad-seq data were mined to identify small proteins engaged in intermolecular interactions. The combination of dual RNA-seq and TraDIS lead to the identification of small proteins with features of virulence factors, namely high intracellular induction and a virulence phenotype upon transposon insertion. As a proof of principle of the power of this approach in highlighting high confidence candidates, two small proteins were characterized in the context of Salmonella infection. MgrB, a known regulator of the PhoPQ two-component system, was shown to be essential for the infection of epithelial cells and macrophages, possibly via its stabilizing effect on flagella or by interacting with other sensor kinases of twocomponent systems. YjiS, so far uncharacterized in Salmonella, had an opposite role in infection, with its deletion rendering Salmonella hypervirulent. The mechanism underlying this, though still obscure, likely relies on the interaction with inner-membrane proteins. Overall, this work provides a global description of Salmonella small proteins in the context of infection with a combinatorial approach that expedites the identification of interesting candidates. Different high-throughput datasets available for a broad range of organisms can be analysed in a similar manner with a focus on small proteins. This will lead to the identification of key factors in the regulation of various processes, thus for example providing targets for the treatment of bacterial infections or, in the case of commensal bacteria, for the modulation of the microbiota composition.}, subject = {Salmonella Typhimurium}, language = {en} } @article{PernitzschAlzheimerBremeretal.2021, author = {Pernitzsch, Sandy R. and Alzheimer, Mona and Bremer, Belinda U. and Robbe-Saule, Marie and De Reuse, Hilde and Sharma, Cynthia M.}, title = {Small RNA mediated gradual control of lipopolysaccharide biosynthesis affects antibiotic resistance in Helicobacter pylori}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-24689-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261536}, year = {2021}, abstract = {The small, regulatory RNA RepG (Regulator of polymeric G-repeats) regulates the expression of the chemotaxis receptor TlpB in Helicobacter pylori by targeting a variable G-repeat in the tlpB mRNA leader. Here, we show that RepG additionally controls lipopolysaccharide (LPS) phase variation by also modulating the expression of a gene (hp0102) that is co-transcribed with tlpB. The hp0102 gene encodes a glycosyltransferase required for LPS O-chain biosynthesis and in vivo colonization of the mouse stomach. The G-repeat length defines a gradual (rather than ON/OFF) control of LPS biosynthesis by RepG, and leads to gradual resistance to a membrane-targeting antibiotic. Thus, RepG-mediated modulation of LPS structure might impact host immune recognition and antibiotic sensitivity, thereby helping H. pylori to adapt and persist in the host. The small RNA RepG modulates expression of chemotaxis receptor TlpB in Helicobacter pylori by targeting a length-variable G-repeat in the tlpB mRNA. Here, Pernitzsch et al. show that RepG also gradually controls lipopolysaccharide biosynthesis, antibiotic susceptibility, and in-vivo colonization of the stomach, by regulating a gene that is co-transcribed with tlpB.}, language = {en} } @article{LetunicKhedkarBork2021, author = {Letunic, Ivica and Khedkar, Supriya and Bork, Peer}, title = {SMART: recent updates, new developments and status in 2020}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, number = {D1}, doi = {10.1093/nar/gkaa937}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363816}, pages = {D458-D460}, year = {2021}, abstract = {SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available.}, language = {en} } @article{QiBruchKropetal.2021, author = {Qi, Yanyan and Bruch, Dorothee and Krop, Philipp and Herrmann, Martin J. and Latoschik, Marc E. and Deckert, J{\"u}rgen and Hein, Grit}, title = {Social buffering of human fear is shaped by gender, social concern, and the presence of real vs virtual agents}, series = {Translational Psychiatry}, volume = {11}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-021-01761-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265782}, year = {2021}, abstract = {The presence of a partner can attenuate physiological fear responses, a phenomenon known as social buffering. However, not all individuals are equally sociable. Here we investigated whether social buffering of fear is shaped by sensitivity to social anxiety (social concern) and whether these effects are different in females and males. We collected skin conductance responses (SCRs) and affect ratings of female and male participants when they experienced aversive and neutral sounds alone (alone treatment) or in the presence of an unknown person of the same gender (social treatment). Individual differences in social concern were assessed based on a well-established questionnaire. Our results showed that social concern had a stronger effect on social buffering in females than in males. The lower females scored on social concern, the stronger the SCRs reduction in the social compared to the alone treatment. The effect of social concern on social buffering of fear in females disappeared if participants were paired with a virtual agent instead of a real person. Together, these results showed that social buffering of human fear is shaped by gender and social concern. In females, the presence of virtual agents can buffer fear, irrespective of individual differences in social concern. These findings specify factors that shape the social modulation of human fear, and thus might be relevant for the treatment of anxiety disorders.}, language = {en} } @article{HeinGamerGalletal.2021, author = {Hein, Grit and Gamer, Matthias and Gall, Dominik and Gr{\"u}ndahl, Marthe and Domschke, Katharina and Andreatta, Marta and Wieser, Matthias J. and Pauli, Paul}, title = {Social cognitive factors outweigh negative emotionality in predicting COVID-19 related safety behaviors}, series = {Preventive Medicine Reports}, volume = {24}, journal = {Preventive Medicine Reports}, doi = {10.1016/j.pmedr.2021.101559}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265008}, year = {2021}, abstract = {Emotion-motivation models propose that behaviors, including health behaviors, should be predicted by the same variables that also predict negative affect since emotional reactions should induce a motivation to avoid threatening situations. In contrast, social cognitive models propose that safety behaviors are predicted by a different set of variables that mainly reflect cognitive and socio-structural aspects. Here, we directly tested these opposing hypotheses in young adults (N = 4134) in the context of COVID-19-related safety behaviors to prevent infections. In each participant, we collected measures of negative affect as well as cognitive and socio-structural variables during the lockdown in the first infection wave in Germany. We found a negative effect of the pandemic on emotional responses. However, this was not the main predictor for young adults' willingness to comply with COVID-19-related safety measures. Instead, individual differences in compliance were mainly predicted by cognitive and socio-structural variables. These results were confirmed in an independent data set. This study shows that individuals scoring high on negative affect during the pandemic are not necessarily more likely to comply with safety regulations. Instead, political measures should focus on cognitive interventions and the societal relevance of the health issue. These findings provide important insights into the basis of health-related concerns and feelings as well as behavioral adaptations.}, language = {en} } @phdthesis{Aydinli2021, author = {Aydinli, Muharrem}, title = {Software unterst{\"u}tzte Analyse von regulatorischen Elementen in Promotoren mittels AIModules}, doi = {10.25972/OPUS-24802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248025}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {Die Regulation der Genexpression steht am Anfang vieler zellbiologischer Prozesse wie beispielsweise dem Zellwachstum oder der Differenzierung. Gene werden an Promotoren transkribiert, wobei ein Promotor selbst aus vielen logischen Einheiten aufgebaut ist, den Transkriptionsfaktorbindestellen (TFBSs). Diese k{\"o}nnen sehr nah beieinander liegen, aber auch weit entfernt voneinander sein. Sie werden spezifisch von Transkriptionsfaktoren (TFs) gebunden, die die Transkritptionsrate z.B. verst{\"a}rken (Enhancer) oder schw{\"a}chen (Silencer) k{\"o}nnen. Zwei oder mehr dieser TFBSs mit bestimmtem Abstand werden als "Module" zusammengefasst, die {\"u}ber Spezies hinweg konserviert sein k{\"o}nnen. Typischerweise findet man Module in Zellen mit einem Zellkern. Spezies mit gemeinsamen Modulen k{\"o}nnen ein Hinweis auf die gemeinsame phylogenetische Abstammung darstellen, aber auch gemeinsame Funktionsmechanismen von TFs {\"u}ber Gene hinweg aufdecken. Heutzutage sind verschiedene Anwendungen verf{\"u}gbar, mit denen nach TFBSs in DNA gesucht werden kann. Zum Zeitpunkt des Verfassens dieser Arbeit sind aber nur zwei kommerzielle Produkte bekannt, die nicht nur TFBSs, sondern auch Module erkennen. Deshalb stellen wir hier die freie und quelloffene L{\"o}sung "AIModules" vor, die diese L{\"u}cke f{\"u}llt und einen Webservice zur Verf{\"u}gung stellt, der es erlaubt nach TFBSs sowie nach Modulen auf DNA- und auf RNA-Abschnitten zu suchen. F{\"u}r die Motivesuche werden entweder Matrizen aus der Jaspar Datenbank oder Matrizen vom Anwender verwendet. Dar{\"u}berhinaus zeigen wir, dass unser Tool f{\"u}r die TF Suche nur Sekunden ben{\"o}tigt, wohingegen conTraV3 mindestens eine Stunde f{\"u}r dieselbe Analyse braucht. Zus{\"a}tzlich kann der Anwender bei unserem Tool den Grad der Konserviertheit f{\"u}r TFs mit angeben und wir zeigen, dass wir mit unserer L{\"o}sung, die die Jaspar Datenbank heranzieht, mehr Module finden, als ein kommerziell verf{\"u}gbares Produkt. Weiterhin kann mit unserer L{\"o}sung auch auf RNA-Sequenzen nach regulatorischen Motiven gesucht werden, wenn der Anwender die daf{\"u}r n{\"o}tigen Matrizen liefert. Wir zeigen dies am Beispiel von Polyadenylierungsstellen. Zusammenfassend stellen wir ein Werkzeug vor, das erstens frei und quelloffen ist und zweitens entweder auf Servern ver{\"o}ffentlicht werden kann oder On-Site auf einem Notebook l{\"a}uft. Unser Tool erlaubt es Promotoren zu analysieren und nach konservierten Modulen sowie TFBSs in Genfamilien sowie nach regulatorischen Elementen in mRNA wie z.B. Polyadenylierungsstellen oder andere regulatorische Elemente wie beispielsweise Enhancern oder Silencern in genomischer DNA zu suchen.}, subject = {Genregulation}, language = {de} } @article{TurkinHolzapfelAgarwaletal.2021, author = {Turkin, Arthur and Holzapfel, Marco and Agarwal, Mohit and Fischermeier, David and Mitric, Roland and Schweins, Ralf and Gr{\"o}hns, Franziska and Lambert, Christoph}, title = {Solvent Induced Helix Folding of Defined Indolenine Squaraine Oligomers}, series = {Chemistry—A European Journal}, volume = {27}, journal = {Chemistry—A European Journal}, number = {32}, doi = {10.1002/chem.202101063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256869}, pages = {8380-8389}, year = {2021}, abstract = {A protecting group strategy was employed to synthesise a series of indolenine squaraine dye oligomers up to the nonamer. The longer oligomers show a distinct solvent dependence of the absorption spectra, that is, either a strong blue shift or a strong red shift of the lowest energy bands in the near infrared spectral region. This behaviour is explained by exciton coupling theory as being due to H- or J-type coupling of transition moments. The H-type coupling is a consequence of a helix folding in solvents with a small Hansen dispersity index. DOSY NMR, small angle neutron scattering (SANS), quantum chemical and force field calculations agree upon a helix structure with an unusually large pitch and open voids that are filled with solvent molecules, thereby forming a kind of clathrate. The thermodynamic parameters of the folding process were determined by temperature dependent optical absorption spectra.}, language = {en} } @article{HergetBoetzl2021, author = {Herget, Ann-Kristin and B{\"o}tzl, Franziska}, title = {Sounds Like Respect. The Impact of Background Music on the Acceptance of Gay Men in Audio-Visual Advertising}, series = {Frontiers in Psychology}, volume = {12}, journal = {Frontiers in Psychology}, issn = {1664-1078}, doi = {10.3389/fpsyg.2021.645533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237236}, year = {2021}, abstract = {Companies increasingly seek to use gay protagonists in audio-visual commercials to attract a new affluent target group. There is also growing demand for the diversity present in society to be reflected in media formats such as advertising. Studies have shown, however, that heterosexual consumers (especially men), who may be part of the company's loyal consumer base, tend to react negatively to gay-themed advertising campaigns. Searching for an instrument to mitigate this unwanted effect, the present study investigated whether carefully selected background music can shape the perceived gender of gay male advertising protagonists. In a 2 × 2 between-subjects online experiment (musical connotation × gender of the participant), 218 heterosexual participants watched a commercial promoting engagement rings that featured gay male protagonists, scored with feminine- or masculine-connoted background music. As expected, women generally reacted more positively than men to the advertising. Men exposed to the masculine-connoted background music rated the promoted brand more positively, and masculine music also enhanced (at least in the short term) these men's acceptance of gay men in general (low and medium effect sizes) more than was the case for feminine background music. Carefully selected background music affecting the perceived gender of gay male advertising protagonists may prevent negative reactions from heterosexual audiences and, therefore, motivate companies to use gay protagonists in television commercials on a more regular basis.}, language = {en} } @article{WienrichKommaVogtetal.2021, author = {Wienrich, Carolin and Komma, Philipp and Vogt, Stephanie and Latoschik, Marc E.}, title = {Spatial Presence in Mixed Realities - Considerations About the Concept, Measures, Design, and Experiments}, series = {Frontiers in Virtual Reality}, volume = {2}, journal = {Frontiers in Virtual Reality}, doi = {10.3389/frvir.2021.694315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260328}, year = {2021}, abstract = {Plenty of theories, models, measures, and investigations target the understanding of virtual presence, i.e., the sense of presence in immersive Virtual Reality (VR). Other varieties of the so-called eXtended Realities (XR), e.g., Augmented and Mixed Reality (AR and MR) incorporate immersive features to a lesser degree and continuously combine spatial cues from the real physical space and the simulated virtual space. This blurred separation questions the applicability of the accumulated knowledge about the similarities of virtual presence and presence occurring in other varieties of XR, and corresponding outcomes. The present work bridges this gap by analyzing the construct of presence in mixed realities (MR). To achieve this, the following presents (1) a short review of definitions, dimensions, and measurements of presence in VR, and (2) the state of the art views on MR. Additionally, we (3) derived a working definition of MR, extending the Milgram continuum. This definition is based on entities reaching from real to virtual manifestations at one time point. Entities possess different degrees of referential power, determining the selection of the frame of reference. Furthermore, we (4) identified three research desiderata, including research questions about the frame of reference, the corresponding dimension of transportation, and the dimension of realism in MR. Mainly the relationship between the main aspects of virtual presence of immersive VR, i.e., the place-illusion, and the plausibility-illusion, and of the referential power of MR entities are discussed regarding the concept, measures, and design of presence in MR. Finally, (5) we suggested an experimental setup to reveal the research heuristic behind experiments investigating presence in MR. The present work contributes to the theories and the meaning of and approaches to simulate and measure presence in MR. We hypothesize that research about essential underlying factors determining user experience (UX) in MR simulations and experiences is still in its infancy and hopes this article provides an encouraging starting point to tackle related questions.}, language = {en} } @article{BrodehlMiltingGerull2021, author = {Brodehl, Andreas and Milting, Hendrik and Gerull, Brenda}, title = {Special Issue "Cardiovascular Genetics"}, series = {Genes}, volume = {12}, journal = {Genes}, number = {4}, issn = {2073-4425}, doi = {10.3390/genes12040479}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234229}, year = {2021}, abstract = {No abstract available}, language = {en} } @article{MeintrupBorgmannSeidletal.2021, author = {Meintrup, David and Borgmann, Stefan and Seidl, Karlheinz and Stecher, Melanie and Jakob, Carolin E. M. and Pilgram, Lisa and Spinner, Christoph D. and Rieg, Siegbert and Isberner, Nora and Hower, Martin and Vehreschild, Maria and G{\"o}pel, Siri and Hanses, Frank and Nowak-Machen, Martina}, title = {Specific risk factors for fatal outcome in critically ill COVID-19 patients: results from a European multicenter study}, series = {Journal of Clinical Medicine}, volume = {10}, journal = {Journal of Clinical Medicine}, number = {17}, issn = {2077-0383}, doi = {10.3390/jcm10173855}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245191}, year = {2021}, abstract = {(1) Background: The aim of our study was to identify specific risk factors for fatal outcome in critically ill COVID-19 patients. (2) Methods: Our data set consisted of 840 patients enclosed in the LEOSS registry. Using lasso regression for variable selection, a multifactorial logistic regression model was fitted to the response variable survival. Specific risk factors and their odds ratios were derived. A nomogram was developed as a graphical representation of the model. (3) Results: 14 variables were identified as independent factors contributing to the risk of death for critically ill COVID-19 patients: age (OR 1.08, CI 1.06-1.10), cardiovascular disease (OR 1.64, CI 1.06-2.55), pulmonary disease (OR 1.87, CI 1.16-3.03), baseline Statin treatment (0.54, CI 0.33-0.87), oxygen saturation (unit = 1\%, OR 0.94, CI 0.92-0.96), leukocytes (unit 1000/μL, OR 1.04, CI 1.01-1.07), lymphocytes (unit 100/μL, OR 0.96, CI 0.94-0.99), platelets (unit 100,000/μL, OR 0.70, CI 0.62-0.80), procalcitonin (unit ng/mL, OR 1.11, CI 1.05-1.18), kidney failure (OR 1.68, CI 1.05-2.70), congestive heart failure (OR 2.62, CI 1.11-6.21), severe liver failure (OR 4.93, CI 1.94-12.52), and a quick SOFA score of 3 (OR 1.78, CI 1.14-2.78). The nomogram graphically displays the importance of these 14 factors for mortality. (4) Conclusions: There are risk factors that are specific to the subpopulation of critically ill COVID-19 patients.}, language = {en} } @article{BrunkhorstKanaanTrautmannSchreiberetal.2021, author = {Brunkhorst-Kanaan, Nathalie and Trautmann, Sandra and Schreiber, Yannick and Thomas, Dominique and Kittel-Schneider, Sarah and Gurke, Robert and Geisslinger, Gerd and Reif, Andreas and Tegeder, Irmgard}, title = {Sphingolipid and endocannabinoid profiles in adult attention deficit hyperactivity disorder}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {9}, issn = {2227-9059}, doi = {10.3390/biomedicines9091173}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246080}, year = {2021}, abstract = {Genes encoding endocannabinoid and sphingolipid metabolism pathways were suggested to contribute to the genetic risk towards attention deficit hyperactivity disorder (ADHD). The present pilot study assessed plasma concentrations of candidate endocannabinoids, sphingolipids and ceramides in individuals with adult ADHD in comparison with healthy controls and patients with affective disorders. Targeted lipid analyses of 23 different lipid species were performed in 71 mental disorder patients and 98 healthy controls (HC). The patients were diagnosed with adult ADHD (n = 12), affective disorder (major depression, MD n = 16 or bipolar disorder, BD n = 6) or adult ADHD with comorbid affective disorders (n = 37). Canonical discriminant analysis and CHAID analyses were used to identify major components that predicted the diagnostic group. ADHD patients had increased plasma concentrations of sphingosine-1-phosphate (S1P d18:1) and sphinganine-1-phosphate (S1P d18:0). In addition, the endocannabinoids, anandamide (AEA) and arachidonoylglycerol were increased. MD/BD patients had increased long chain ceramides, most prominently Cer22:0, but low endocannabinoids in contrast to ADHD patients. Patients with ADHD and comorbid affective disorders displayed increased S1P d18:1 and increased Cer22:0, but the individual lipid levels were lower than in the non-comorbid disorders. Sphingolipid profiles differ between patients suffering from ADHD and affective disorders, with overlapping patterns in comorbid patients. The S1P d18:1 to Cer22:0 ratio may constitute a diagnostic or prognostic tool.}, language = {en} } @article{SchneiderSchauliesSchumacherWiggeretal.2021, author = {Schneider-Schaulies, Sibylle and Schumacher, Fabian and Wigger, Dominik and Sch{\"o}l, Marie and Waghmare, Trushnal and Schlegel, Jan and Seibel, J{\"u}rgen and Kleuser, Burkhard}, title = {Sphingolipids: effectors and Achilles heals in viral infections?}, series = {Cells}, volume = {10}, journal = {Cells}, number = {9}, issn = {2073-4409}, doi = {10.3390/cells10092175}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245151}, year = {2021}, abstract = {As viruses are obligatory intracellular parasites, any step during their life cycle strictly depends on successful interaction with their particular host cells. In particular, their interaction with cellular membranes is of crucial importance for most steps in the viral replication cycle. Such interactions are initiated by uptake of viral particles and subsequent trafficking to intracellular compartments to access their replication compartments which provide a spatially confined environment concentrating viral and cellular components, and subsequently, employ cellular membranes for assembly and exit of viral progeny. The ability of viruses to actively modulate lipid composition such as sphingolipids (SLs) is essential for successful completion of the viral life cycle. In addition to their structural and biophysical properties of cellular membranes, some sphingolipid (SL) species are bioactive and as such, take part in cellular signaling processes involved in regulating viral replication. It is especially due to the progress made in tools to study accumulation and dynamics of SLs, which visualize their compartmentalization and identify interaction partners at a cellular level, as well as the availability of genetic knockout systems, that the role of particular SL species in the viral replication process can be analyzed and, most importantly, be explored as targets for therapeutic intervention.}, language = {en} } @article{GottschollDiezSoltamovetal.2021, author = {Gottscholl, Andreas and Diez, Matthias and Soltamov, Victor and Kasper, Christian and Krauße, Dominik and Sperlich, Andreas and Kianinia, Mehran and Bradac, Carlo and Aharonovich, Igor and Dyakonov, Vladimir}, title = {Spin defects in hBN as promising temperature, pressure and magnetic field quantum sensors}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-24725-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261581}, year = {2021}, abstract = {Spin defects in solid-state materials are strong candidate systems for quantum information technology and sensing applications. Here we explore in details the recently discovered negatively charged boron vacancies (V\(_B\)\(^-\)) in hexagonal boron nitride (hBN) and demonstrate their use as atomic scale sensors for temperature, magnetic fields and externally applied pressure. These applications are possible due to the high-spin triplet ground state and bright spin-dependent photoluminescence of the V\(_B\)\(^-\). Specifically, we find that the frequency shift in optically detected magnetic resonance measurements is not only sensitive to static magnetic fields, but also to temperature and pressure changes which we relate to crystal lattice parameters. We show that spin-rich hBN films are potentially applicable as intrinsic sensors in heterostructures made of functionalized 2D materials.}, language = {en} } @phdthesis{EliasdosSantos2021, author = {Elias dos Santos, Graciely}, title = {Spin-Orbit Torques and Galvanomagnetic Effects Generated by the 3D Topological Insulator HgTe}, doi = {10.25972/OPUS-24797}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-247971}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {In meiner Dissertation besch{\"a}ftigte ich mich mit der Frage, ob der 3D topologische Isolator Quecksilbertellurid (3D TI HgTe) ein geeignetes Material f{\"u}r Spintronik-Anwendungen ist. Wir untersuchten Spin-Bahn-Drehmomente, die auf Elektronen beim Tunneln zwischen HgTe und einem angrenzenden Ferromagneten (Permalloy) einwirken. Zun{\"a}chst setzten wir die Methode der Ferromagnetresonanz (SOT-FMR) f{\"u}r diese Untersuchungen ein. Im ersten Teil der Dissertation werden die Leser in die mathematische Beschreibung von Spin- Bahn-Drehmomenten in einem Hybridsystem bestehend aus topologischem Isolator (TI) und Ferromagnet (FM) eingef{\"u}hrt. Des Weiteren werden die Probenherstellung und der Messaufbau f{\"u}r SOT-FMR Messungen besprochen. Unsere SOT-FMR Messungen ergaben, dass bei tiefen Temperaturen (T = 4.2 K) die Normalkomponente (bezogen auf der TI-Oberfl{\"a}che) des Drehmoments groß war. Bei Raumtemperatur konnten im Signal beide Komponenten (parallel und normal zur TI-Oberfl{\"a}che) beobachtet werden. Aus der Symmetrie der Mixing-Spannung (Abbildungen 3.14 und 3.15) schlossen wir, dass 3D TI HgTe ein Spin-Bahn-Drehmoment auf das Elektronensystem des Permalloys {\"u}bertr{\"a}gt. Unsere Untersuchungen zeigten dar{\"u}ber hinaus, dass die Effizienz dieser {\"U}bertragung mit der anderer vorhandener topologischen Isolatoren vergleichbar ist (siehe Abb. 3.17). Abschließend wurden parasit{\"a}re Effekte bei der Absch{\"a}tzung des Spin-Bahn-Drehmoments bzw. andere Interpretationen des Messsignals und seiner Komponenten (z.B., Thermospannungen) ausf{\"u}hrlich diskutiert. Obwohl die hier gezeigten Ergebnisse vermehrt darauf hinweisen, dass der 3D TI HgTe m{\"o}glicherweise effizient f{\"u}r die Anwendung von Spin-Drehmomenten in angrezenden Ferromagneten ist [1], wird dem Leser weiderholt klargemacht, dass parasit{\"a}re Effekte eventuelle das korrekte Schreiben und Lesen der Information in Ferromagneten verunreignigt. Diese sollten auch bei der Interpretation von publizierten Resultaten besonders hohen Spin-Bahn-Drehmoment{\"u}bertragungen in der Literatur ber{\"u}cksichtigt werden [1-3]. Die Nachteile der SOT-FMR-Messmethode f{\"u}hrten zu einerWeiterentwicklung unseres Messkonzepts, bei dem der Ferromagnet durch eine Spin-Valve-Struktur ersetzt wurde. In dieser Messanordnung ist der Stromfluss durch den 3D TI im Gegensatz zu den vorangegangenen Messungen bekannt und die Widerstands{\"a}nderung der Spin-Valve-Struktur kann durch den GMR-Effekt ausgelesen werden. Die Ausrichtung der Magnetisierung des Ferromagneten in den SOT-FMR-Experimenten erforderte es, ein magnetisches Feld von bis zu 300 mT parallel zur TI-Oberfl{\"a}che anzulegen. Motiviert durch diesen Umstand, untersuchten wir den Einfluss eines parallelen Magnetfelds auf den Magnetowiderstand in 3D TI HgTe. Die {\"u}berraschenden Resultate dieser Messungen werden im zweiten Teil der Dissertation beschrieben. Obwohl nichtmagnetisches Quecksilbertellurid untersucht wurde, oszillierte der transversale Magnetowiderstand (Rxy) mit dem Winkel � zwischen der Magnetfeldrichtung (parallel zur Oberfl{\"a}che) und der elektrischen Stromflussrichtung im topologischen Isolator. Dieser Effekt ist eine typische Eigenschaft von ferromagnetischen Materialien und wird planarer Hall-Effekt (PHE) genannt[4, 5]. Magnetowiderstands- (MR-)Oszillationen wurden ebenfalls sowohl im L{\"a}ngswiderstand (Rxx) und im transversalen Widerstand (Rxy) {\"u}ber einen weiten Bereich von magnetischen Feldst{\"a}rken und Ladungstr{\"a}gerdichten des topologischen Isolators beobachtet. Der PHE wurde bereits zuvor in einem anderen TI-Material (Bi2-xSbxTe3) beschrieben [6]. Als physikalischer Mechanismus wurde von den Autoren Elektronenstreuung an magnetisch polarisierten Streuzentren vorgeschlagen. Wir diskutierten sowohl diesen Erkl{\"a}rungsansatz als auch andere Theorievorschl{\"a}ge in der Literatur [7, 8] kritisch. In dieser Doktorarbeit haben wir versucht, der PHE des 3D TI HgTe durch die Asymmetrie in der Bandstruktur dieses Materials zu erkl{\"a}ren. In k.p Bandstrukturrechnungen mit einer 6-Orbital-Basis zeigten wir, dass das Zwischenspiel von Rashba- und Dresselhaus-Spin-Bahn- Wechselwirkung mit dem magnetischen Feld parallel zur TI-Oberfl{\"a}che zu einer Verformung der Fermikontur des Valenzbands von 3D TI-HgTe f{\"u}hrt, welche ihrerseits eine Anisotropie des Leitf{\"a}higkeit bedingt. Die ben{\"o}tigten Magnetfeldst{\"a}rken in diesem Modell waren mit bis zu 40 T jedoch etwa eine Gr{\"o}ßenordnung gr{\"o}ßer als jene in unseren Experimenten. Des Weiteren lieferte eine direkte Berechnung der Zustandsdichten f{\"u}r Bin k I und Bin ? I bisher keine klaren Resultate. Die komplizierte Abh{\"a}ngigkeit der Rashba-Spin-Bahn-Kopplung f{\"u}r p-leitendes HgTe [9] machte es außerdem schwierig, diesen Term in die Bandstrukturrechnung zu inkludieren. Trotz umfangreicher Bem{\"u}hungen, den Ursprung der galvanomagnetischen Effekte im 3D TI HgTe zu verstehen, konnte in dieser Arbeit der Mechanismus des PHE und der MR-Oszillationen nicht eindeutig bestimmt werden. Es gelang jedoch, einige aus der Literatur bekannte Theorien f{\"u}r den PHE und die MR-Oszillationseffekte in topologischen Isolatoren auszuschließen. Die Herausforderung, eine vollst{\"a}ndige theoretische Beschreibung zu entwickeln, die allen experimentellen Aspekten (PHE, Gatespannungsabh{\"a}ngigkeit und MR-Oszillationen) gerecht wird, bleibt weiter bestehen. Abschließend m{\"o}chte die Autorin ihre Hoffnung ausdr{\"u}cken, den Lesern die Komplexit{\"a}t der Fragestellung n{\"a}her gebracht zu haben und sie in die Kunst elektrischer Messungen an topologischen Isolatoren bei angelegtem parallelem Magnetfeld initiiert zu haben.}, language = {en} } @article{FischhaberFaberBakircietal.2021, author = {Fischhaber, Natalie and Faber, Jessica and Bakirci, Ezgi and Dalton, Paul D. and Budday, Silvia and Villmann, Carmen and Schaefer, Natascha}, title = {Spinal Cord Neuronal Network Formation in a 3D Printed Reinforced Matrix-A Model System to Study Disease Mechanisms}, series = {Advanced Healthcare Materials}, volume = {10}, journal = {Advanced Healthcare Materials}, number = {19}, doi = {10.1002/adhm.202100830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256353}, year = {2021}, abstract = {3D cell cultures allow a better mimicry of the biological and mechanical environment of cells in vivo compared to 2D cultures. However, 3D cell cultures have been challenging for ultrasoft tissues such as the brain. The present study uses a microfiber reinforcement approach combining mouse primary spinal cord neurons in Matrigel with melt electrowritten (MEW) frames. Within these 3D constructs, neuronal network development is followed for 21 days in vitro. To evaluate neuronal development in 3D constructs, the maturation of inhibitory glycinergic synapses is analyzed using protein expression, the complex mechanical properties by assessing nonlinearity, conditioning, and stress relaxation, and calcium imaging as readouts. Following adaptation to the 3D matrix-frame, mature inhibitory synapse formation is faster than in 2D demonstrated by a steep increase in glycine receptor expression between days 3 and 10. The 3D expression pattern of marker proteins at the inhibitory synapse and the mechanical properties resemble the situation in native spinal cord tissue. Moreover, 3D spinal cord neuronal networks exhibit intensive neuronal activity after 14 days in culture. The spinal cord cell culture model using ultrasoft matrix reinforced by MEW fibers provides a promising tool to study and understand biomechanical mechanisms in health and disease.}, language = {en} } @article{BunzmannKrugmannWeissenseeletal.2021, author = {Bunzmann, Nikolai and Krugmann, Benjamin and Weissenseel, Sebastian and Kudriashova, Liudmila and Ivaniuk, Khrystyna and Stakhira, Pavlo and Cherpak, Vladyslav and Chapran, Marian and Grybauskaite-Kaminskiene, Gintare and Grazulevicius, Juozas Vidas and Dyakonov, Vladimir and Sperlich, Andreas}, title = {Spin- and Voltage-Dependent Emission from Intra- and Intermolecular TADF OLEDs}, series = {Advanced Electronic Materials}, volume = {7}, journal = {Advanced Electronic Materials}, number = {3}, doi = {10.1002/aelm.202000702}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224434}, year = {2021}, abstract = {Organic light emitting diodes (OLEDs) based on thermally activated delayed fluorescence (TADF) utilize molecular systems with a small energy splitting between singlet and triplet states. This can either be realized in intramolecular charge transfer states of molecules with near-orthogonal donor and acceptor moieties or in intermolecular exciplex states formed between a suitable combination of individual donor and acceptor materials. Here, 4,4′-(9H,9′H-[3,3′-bicarbazole]-9,9′-diyl)bis(3-(trifluoromethyl) benzonitrile) (pCNBCzoCF\(_{3}\)) is investigated, which shows intramolecular TADF but can also form exciplex states in combination with 4,4′,4′′-tris[phenyl(m-tolyl)amino]triphenylamine (m-MTDATA). Orange emitting exciplex-based OLEDs additionally generate a sky-blue emission from the intramolecular emitter with an intensity that can be voltage-controlled. Electroluminescence detected magnetic resonance (ELDMR) is applied to study the thermally activated spin-dependent triplet to singlet up-conversion in operating devices. Thereby, intermediate excited states involved in OLED operation can be investigated and the corresponding activation energy for both, intra- and intermolecular based TADF can be derived. Furthermore, a lower estimate is given for the extent of the triplet wavefunction to be ≥ 1.2 nm. Photoluminescence detected magnetic resonance (PLDMR) reveals the population of molecular triplets in optically excited thin films. Overall, the findings allow to draw a comprehensive picture of the spin-dependent emission from intra- and intermolecular TADF OLEDs.}, language = {en} } @article{NguemeniHiewKoegleretal.2021, author = {Nguemeni, Carine and Hiew, Shawn and K{\"o}gler, Stefanie and Homola, Gy{\"o}rgy A. and Volkmann, Jens and Zeller, Daniel}, title = {Split-belt training but not cerebellar anodal tDCS improves stability control and reduces risk of fall in patients with multiple sclerosis}, series = {Brain Sciences}, volume = {12}, journal = {Brain Sciences}, number = {1}, issn = {2076-3425}, doi = {10.3390/brainsci12010063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252179}, year = {2021}, abstract = {The objective of this study was to examine the therapeutic potential of multiple sessions of training on a split-belt treadmill (SBT) combined with cerebellar anodal transcranial direct current stimulation (tDCS) on gait and balance in People with Multiple Sclerosis (PwMS). Twenty-two PwMS received six sessions of anodal (PwMS\(_{real}\), n = 12) or sham (PwMS\(_{sham}\), n = 10) tDCS to the cerebellum prior to performing the locomotor adaptation task on the SBT. To evaluate the effect of the intervention, functional gait assessment (FGA) scores and distance walked in 2 min (2MWT) were measured at the baseline (T0), day 6 (T5), and at the 4-week follow up (T6). Locomotor performance and changes of motor outcomes were similar in PwMS\(_{real}\) and PwMS\(_{sham}\) independently from tDCS mode applied to the cerebellum (anodal vs. sham, on FGA, p = 0.23; and 2MWT, p = 0.49). When the data were pooled across the groups to investigate the effects of multiple sessions of SBT training alone, significant improvement of gait and balance was found on T5 and T6, respectively, relative to baseline (FGA, p < 0.001 for both time points). The FGA change at T6 was significantly higher than at T5 (p = 0.01) underlining a long-lasting improvement. An improvement of the distance walked during the 2MWT was also observed on T5 and T6 relative to T0 (p = 0.002). Multiple sessions of SBT training resulted in a lasting improvement of gait stability and endurance, thus potentially reducing the risk of fall as measured by FGA and 2MWT. Application of cerebellar tDCS during SBT walking had no additional effect on locomotor outcomes.}, language = {en} } @article{PetritschPannbeckerWengetal.2021, author = {Petritsch, Bernhard and Pannbecker, Pauline and Weng, Andreas M. and Grunz, Jan-Peter and Veldhoen, Simon and Bley, Thorsten A. and Kosmala, Aleksander}, title = {Split-filter dual-energy CT pulmonary angiography for the diagnosis of acute pulmonary embolism: a study on image quality and radiation dose}, series = {Quantitative Imaging in Medicine and Surgery}, volume = {11}, journal = {Quantitative Imaging in Medicine and Surgery}, number = {5}, doi = {10.21037/qims-20-740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231456}, pages = {1817-1827}, year = {2021}, abstract = {Background: Computed tomography (CT) pulmonary angiography is the diagnostic reference standard in suspected pulmonary embolism (PE). Favorable results for dual-energy CT (DECT) images have been reported for this condition. Nowadays, dual-energy data acquisition is feasible with different technical options, including a single-source split-filter approach. Therefore, the aim of this retrospective study was to investigate image quality and radiation dose of thoracic split-filter DECT in comparison to conventional single-energy CT in patients with suspected PE. Methods: A total of 110 CT pulmonary angiographies were accomplished either as standard single-energy CT with automatic tube voltage selection (ATVS) (n=58), or as split-filter DECT (n=52). Objective [pulmonary artery CT attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)] and subjective image quality [four-point Likert scale; three readers (R)] were compared among the two study groups. Size-specific dose estimates (SSDE), dose-length-product (DLP) and volume CT dose index (CTDIvol) were assessed for radiation dose analysis. Results: Split-filter DECT images yielded 67.7\% higher SNR (27.0 vs. 16.1; P<0.001) and 61.9\% higher CNR (22.5 vs. 13.9; P<0.001) over conventional single-energy images, whereas CT attenuation was significantly lower (344.5 vs. 428.2 HU; P=0.013). Subjective image quality was rated good or excellent in 93.0\%/98.3\%/77.6\% (R1/R2/R3) of the single-energy CT scans, and 84.6\%/82.7\%/80.8\% (R1/R2/R3) of the split-filter DECT scans. SSDE, DLP and CTDIvol were significantly lower for conventional single-energy CT compared to split-filter DECT (all P<0.05), which was associated with 26.7\% higher SSDE. Conclusions: In the diagnostic workup of acute PE, the split-filter allows for dual-energy data acquisition from single-source single-layer CT scanners. The existing opportunity to assess pulmonary "perfusion" based on analysis of iodine distribution maps is associated with higher radiation dose in terms of increased SSDE than conventional single-energy CT with ATVS. Moreover, a proportion of up to 3.8\% non-diagnostic examinations in the current reference standard test for PE is not negligible.}, language = {en} } @article{VoelkerVoelkerEngertetal.2021, author = {Voelker, Johannes and Voelker, Christine and Engert, Jonas and Goemann, Nikolas and Hagen, Rudolf and Rak, Kristen}, title = {Spontaneous Calcium Oscillations through Differentiation: A Calcium Imaging Analysis of Rat Cochlear Nucleus Neural Stem Cells}, series = {Cells}, volume = {10}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells10102802}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248482}, year = {2021}, abstract = {Causal therapies for the auditory-pathway and inner-ear diseases are still not yet available for clinical application. Regenerative medicine approaches are discussed and examined as possible therapy options. Neural stem cells could play a role in the regeneration of the auditory pathway. In recent years, neural stem and progenitor cells have been identified in the cochlear nucleus, the second nucleus of the auditory pathway. The current investigation aimed to analyze cell maturation concerning cellular calcium activity. Cochlear nuclei from PND9 CD rats were microscopically dissected and propagated as neurospheres in free-floating cultures in stem-cell medium (Neurobasal, B27, GlutaMAX, EGF, bFGF). After 30 days, the dissociation and plating of these cells took place under withdrawal of the growth factors and the addition of retinoic acid, which induces neural cell differentiation. Calcium imaging analysis with BAPTA-1/Oregon Green was carried out at different times during the differentiation phase. In addition, the influence of different voltage-dependent calcium channels was analyzed through the targeted application of inhibitors of the L-, N-, R- and T-type calcium channels. For this purpose, comparative examinations were performed on CN NSCs, and primary CN neurons. As the cells differentiated, a significant increase in spontaneous neuronal calcium activity was demonstrated. In the differentiation stage, specific frequencies of the spontaneous calcium oscillations were measured in different regions of the individual cells. Initially, the highest frequency of spontaneous calcium oscillations was ascertainable in the maturing somata. Over time, these were overtaken by calcium oscillations in the axons and dendrites. Additionally, in the area of the growth cones, an increasing activity was determined. By inhibiting voltage-dependent calcium channels, their expression and function in the differentiation process were confirmed. A comparable pattern of maturation of these channels was found in CN NSCs and primary CN neurons. The present results show that neural stem cells of the rat cochlear nucleus differentiated not only morphologically but also functionally. Spontaneous calcium activities are of great relevance in terms of neurogenesis and integration into existing neuronal structures. These functional aspects of neurogenesis within the auditory pathway could serve as future targets for the exogenous control of neuronal regeneration.}, language = {en} }