TY - JOUR A1 - Mueller, Thomas D. A1 - Fiebig, Juliane E. A1 - Weidauer, Stella E. A1 - Qiu, Li-Yan A1 - Bauer, Markus A1 - Schmieder, Peter A1 - Beerbaum, Monika A1 - Zhang, Jin-Li A1 - Oschkinat, Hartmut A1 - Sebald, Walter T1 - The Clip-Segment of the von Willebrand Domain 1 of the BMP Modulator Protein Crossveinless 2 Is Preformed JF - Molecules N2 - Bone Morphogenetic Proteins (BMPs) are secreted protein hormones that act as morphogens and exert essential roles during embryonic development of tissues and organs. Signaling by BMPs occurs via hetero-oligomerization of two types of serine/threonine kinase transmembrane receptors. Due to the small number of available receptors for a large number of BMP ligands ligand-receptor promiscuity presents an evident problem requiring additional regulatory mechanisms for ligand-specific signaling. Such additional regulation is achieved through a plethora of extracellular antagonists, among them members of the Chordin superfamily, that modulate BMP signaling activity by binding. The key-element in Chordin-related antagonists for interacting with BMPs is the von Willebrand type C (VWC) module, which is a small domain of about 50 to 60 residues occurring in many different proteins. Although a structure of the VWC domain of the Chordin-member Crossveinless 2 (CV2) bound to BMP-2 has been determined by X-ray crystallography, the molecular mechanism by which the VWC domain binds BMPs has remained unclear. Here we present the NMR structure of the Danio rerio CV2 VWC1 domain in its unbound state showing that the key features for high affinity binding to BMP-2 is a pre-oriented peptide loop. KW - bone morphogenetic proteins KW - TGF-β superfamily KW - BMP antagonist KW - protein-protein recognition KW - NMR spectroscopy KW - von Willebrand type C domain Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97196 ER - TY - JOUR A1 - Winter, Patrick A1 - Kampf, Thomas A1 - Helluy, Xavier A1 - Gutjahr, Fabian T. A1 - Meyer, Cord B. A1 - Rommel, Eberhard A1 - Bauer, Wolfgang R. A1 - Jakob, Peter M. A1 - Herold, Volker T1 - Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory JF - Journal of Cardiovascular Magnetic Resonance N2 - Background The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed. Methods The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence. Results In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method. Conclusion With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware. KW - pulse-wave velocity KW - mouse KW - self-gating KW - phase-contrast CMR KW - non-triggered KW - retrospective KW - radial KW - aorta Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96602 UR - http://jcmr-online.com/content/15/1/88 ER - TY - JOUR A1 - Sepahi, Ilnaz A1 - Faust, Ulrike A1 - Sturm, Marc A1 - Bosse, Kristin A1 - Kehrer, Martin A1 - Heinrich, Tilman A1 - Grundman-Hauser, Kathrin A1 - Bauer, Peter A1 - Ossowski, Stephan A1 - Susak, Hana A1 - Varon, Raymonda A1 - Schröck, Evelin A1 - Niederacher, Dieter A1 - Auber, Bernd A1 - Sutter, Christian A1 - Arnold, Norbert A1 - Hahnen, Eric A1 - Dworniczak, Bernd A1 - Wang-Gorke, Shan A1 - Gehrig, Andrea A1 - Weber, Bernhard H. F. A1 - Engel, Christoph A1 - Lemke, Johannes R. A1 - Hartkopf, Andreas A1 - Huu Phuc, Nguyen A1 - Riess, Olaf A1 - Schroeder, Christopher T1 - Investigating the effects of additional truncating variants in DNA-repair genes on breast cancer risk in BRCA1-positive women JF - BMC Cancer N2 - Background Inherited pathogenic variants in BRCA1 and BRCA2 are the most common causes of hereditary breast and ovarian cancer (HBOC). The risk of developing breast cancer by age 80 in women carrying a BRCA1 pathogenic variant is 72%. The lifetime risk varies between families and even within affected individuals of the same family. The cause of this variability is largely unknown, but it is hypothesized that additional genetic factors contribute to differences in age at onset (AAO). Here we investigated whether truncating and rare missense variants in genes of different DNA-repair pathways contribute to this phenomenon. Methods We used extreme phenotype sampling to recruit 133 BRCA1-positive patients with either early breast cancer onset, below 35 (early AAO cohort) or cancer-free by age 60 (controls). Next Generation Sequencing (NGS) was used to screen for variants in 311 genes involved in different DNA-repair pathways. Results Patients with an early AAO (73 women) had developed breast cancer at a median age of 27 years (interquartile range (IQR); 25.00–27.00 years). A total of 3703 variants were detected in all patients and 43 of those (1.2%) were truncating variants. The truncating variants were found in 26 women of the early AAO group (35.6%; 95%-CI 24.7 - 47.7%) compared to 16 women of controls (26.7%; 95%-CI 16.1 to 39.7%). When adjusted for environmental factors and family history, the odds ratio indicated an increased breast cancer risk for those carrying an additional truncating DNA-repair variant to BRCA1 mutation (OR: 3.1; 95%-CI 0.92 to 11.5; p-value = 0.07), although it did not reach the conventionally acceptable significance level of 0.05. Conclusions To our knowledge this is the first time that the combined effect of truncating variants in DNA-repair genes on AAO in patients with hereditary breast cancer is investigated. Our results indicate that co-occurring truncating variants might be associated with an earlier onset of breast cancer in BRCA1-positive patients. Larger cohorts are needed to confirm these results. KW - breast cancer KW - age at onset KW - DNA-repair genes KW - next-generation-sequencing KW - panel sequencing KW - extreme phenotypes KW - hereditary breast and ovarian cancer KW - BRCA1 KW - DNA-repair Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-237676 VL - 19 ER - TY - JOUR A1 - Winter, Patrick M. A1 - Andelovic, Kristina A1 - Kampf, Thomas A1 - Hansmann, Jan A1 - Jakob, Peter Michael A1 - Bauer, Wolfgang Rudolf A1 - Zernecke, Alma A1 - Herold, Volker T1 - Simultaneous measurements of 3D wall shear stress and pulse wave velocity in the murine aortic arch JF - Journal of Cardiovascular Magnetic Resonance N2 - 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. KW - 4D flow KW - pulse wave velocity KW - wall shear stress KW - radial KW - self-navigation KW - mouse KW - aortic arch KW - atherosclerosis KW - mice KW - flow KW - plaque KW - CMR KW - quantification KW - microscopy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259152 VL - 23 IS - 1 ER - TY - JOUR A1 - Forchert, Leandra A1 - Potapova, Ekaterina A1 - Panetta, Valentina A1 - Dramburg, Stephanie A1 - Perna, Serena A1 - Posa, Daniela A1 - Resch‐Marat, Yvonne A1 - Lupinek, Christian A1 - Rohrbach, Alexander A1 - Grabenhenrich, Linus A1 - Icke, Katja A1 - Bauer, Carl‐Peter A1 - Hoffman, Ute A1 - Forster, Johannes A1 - Zepp, Fred A1 - Schuster, Antje A1 - Wahn, Ulrich A1 - Keil, Thomas A1 - Lau, Susanne A1 - Vrtala, Susanne A1 - Valenta, Rudolf A1 - Matricardi, Paolo Maria T1 - Der p 23‐specific IgE response throughout childhood and its association with allergic disease: A birth cohort study JF - Pediatric Allergy and Immunology N2 - Background The Dermatophagoides pteronyssinus molecule Der p 23 is a major allergen whose clinical relevance has been shown in cross‐sectional studies. We longitudinally analysed the trajectory of Der p 23‐specific IgE antibody (sIgE) levels throughout childhood and youth, their early‐life determinants and their clinical relevance for allergic rhinitis and asthma. Methods We obtained sera and clinical data of 191 participants of the German Multicentre Allergy Study, a prospective birth cohort. Serum samples from birth to 20 years of age with sIgE reactivity to Der p 23 in a customised semiquantitative microarray were newly analysed with a singleplex quantitative assay. Early mite exposure was assessed by measuring the average content of Der p 1 in house dust at 6 and 18 months. Results Der p 23‐sIgE levels were detected at least once in 97/191 participants (51%). Prevalence of Der p 23 sensitisation and mean sIgE levels increased until age 10 years, plateaued until age 13 years and were lowest at age 20 years. Asthma, allergic rhinitis (AR) and atopic dermatitis (AD) were more prevalent in Der p 23‐sensitised children, including those with monomolecular but persistent sensitisation (11/97, 11%). A higher exposure to mites in infancy and occurrence of AD before 5 years of age preceded the onset of Der p 23 sensitisation, which in turn preceded a higher incidence of asthma. Conclusions Der p 23 sensitisation peaks in late childhood and then decreases. It is preceded by early mite exposure and AD. Asthma and AR can occur in patients persistently sensitised to Der p 23 as the only mite allergen, suggesting the inclusion of molecular testing of Der p 23‐sIgE for subjects with clinical suspicion of HDM allergy but without sIgE to other major D.pt. allergens. KW - asthma KW - birth cohort KW - childhood KW - Der p 23 KW - house dust mite allergy KW - IgE Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287181 VL - 33 IS - 7 ER - TY - JOUR A1 - Lüffe, Teresa M. A1 - D'Orazio, Andrea A1 - Bauer, Moritz A1 - Gioga, Zoi A1 - Schoeffler, Victoria A1 - Lesch, Klaus-Peter A1 - Romanos, Marcel A1 - Drepper, Carsten A1 - Lillesaar, Christina T1 - Increased locomotor activity via regulation of GABAergic signalling in foxp2 mutant zebrafish – implications for neurodevelopmental disorders JF - Translational Psychiatry N2 - Recent advances in the genetics of neurodevelopmental disorders (NDDs) have identified the transcription factor FOXP2 as one of numerous risk genes, e.g. in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). FOXP2 function is suggested to be involved in GABAergic signalling and numerous studies demonstrate that GABAergic function is altered in NDDs, thus disrupting the excitation/inhibition balance. Interestingly, GABAergic signalling components, including glutamate-decarboxylase 1 (Gad1) and GABA receptors, are putative transcriptional targets of FOXP2. However, the specific role of FOXP2 in the pathomechanism of NDDs remains elusive. Here we test the hypothesis that Foxp2 affects behavioural dimensions via GABAergic signalling using zebrafish as model organism. We demonstrate that foxp2 is expressed by a subset of GABAergic neurons located in brain regions involved in motor functions, including the subpallium, posterior tuberculum, thalamus and medulla oblongata. Using CRISPR/Cas9 gene-editing we generated a novel foxp2 zebrafish loss-of-function mutant that exhibits increased locomotor activity. Further, genetic and/or pharmacological disruption of Gad1 or GABA-A receptors causes increased locomotor activity, resembling the phenotype of foxp2 mutants. Application of muscimol, a GABA-A receptor agonist, rescues the hyperactive phenotype induced by the foxp2 loss-of-function. By reverse translation of the therapeutic effect on hyperactive behaviour exerted by methylphenidate, we note that application of methylphenidate evokes different responses in wildtype compared to foxp2 or gad1b loss-of-function animals. Together, our findings support the hypothesis that foxp2 regulates locomotor activity via GABAergic signalling. This provides one targetable mechanism, which may contribute to behavioural phenotypes commonly observed in NDDs. KW - comparative genomics KW - molecular neuroscience Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-264713 VL - 11 ER - TY - JOUR A1 - Prantl, Thomas A1 - Zeck, Timo A1 - Bauer, Andre A1 - Ten, Peter A1 - Prantl, Dominik A1 - Yahya, Ala Eddine Ben A1 - Ifflaender, Lukas A1 - Dmitrienko, Alexandra A1 - Krupitzer, Christian A1 - Kounev, Samuel T1 - A Survey on Secure Group Communication Schemes With Focus on IoT Communication JF - IEEE Access N2 - A key feature for Internet of Things (IoT) is to control what content is available to each user. To handle this access management, encryption schemes can be used. Due to the diverse usage of encryption schemes, there are various realizations of 1-to-1, 1-to-n, and n-to-n schemes in the literature. This multitude of encryption methods with a wide variety of properties presents developers with the challenge of selecting the optimal method for a particular use case, which is further complicated by the fact that there is no overview of existing encryption schemes. To fill this gap, we envision a cryptography encyclopedia providing such an overview of existing encryption schemes. In this survey paper, we take a first step towards such an encyclopedia by creating a sub-encyclopedia for secure group communication (SGC) schemes, which belong to the n-to-n category. We extensively surveyed the state-of-the-art and classified 47 different schemes. More precisely, we provide (i) a comprehensive overview of the relevant security features, (ii) a set of relevant performance metrics, (iii) a classification for secure group communication schemes, and (iv) workflow descriptions of the 47 schemes. Moreover, we perform a detailed performance and security evaluation of the 47 secure group communication schemes. Based on this evaluation, we create a guideline for the selection of secure group communication schemes. KW - Internet of Things KW - encryption KW - secure group communication Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300257 VL - 10 SP - 99944 EP - 99962 ER - TY - JOUR A1 - Andelovic, Kristina A1 - Winter, Patrick A1 - Kampf, Thomas A1 - Xu, Anton A1 - Jakob, Peter Michael A1 - Herold, Volker A1 - Bauer, Wolfgang Rudolf A1 - Zernecke, Alma T1 - 2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis JF - Biomedicines N2 - Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe\(^{−/−}\), n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe\(^{−/−}\) mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability. KW - atherosclerosis KW - mouse KW - 4D flow MRI KW - aortic arch KW - flow dynamics KW - WSS KW - mapping KW - PWV KW - plaque characteristics Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-252164 SN - 2227-9059 VL - 9 IS - 12 ER - TY - JOUR A1 - Marx, Gernot A1 - Schindler, Achim W. A1 - Mosch, Christoph A1 - Albers, Joerg A1 - Bauer, Michael A1 - Gnass, Irmela A1 - Hobohm, Carsten A1 - Janssens, Uwe A1 - Kluge, Stefan A1 - Kranke, Peter A1 - Maurer, Tobias A1 - Merz, Waltraut A1 - Neugebauer, Edmund A1 - Quintel, Michael A1 - Senninger, Norbert A1 - Trampisch, Hans-Joachim A1 - Waydhas, Christian A1 - Wildenauer, Rene A1 - Zacharowski, Kai A1 - Eikermann, Michaela T1 - Intravascular volume therapy in adults guidelines from the association of the scientific medical societies in Germany JF - European Journal of Anaesthesiology N2 - No abstract available. KW - Predict fluid responsiveness KW - Randomized controlled-trial KW - 6-percent hydroxyethyl starch KW - Central venous-pressure KW - Elective cesarean-section KW - Critically-ill patients KW - Puls-pressure variation KW - Lactated ringers solution KW - Hypertonic saline 7.5-percent KW - Major abdominal surgery Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188223 VL - 33 IS - 7 ER - TY - JOUR A1 - Andelovic, Kristina A1 - Winter, Patrick A1 - Jakob, Peter Michael A1 - Bauer, Wolfgang Rudolf A1 - Herold, Volker A1 - Zernecke, Alma T1 - Evaluation of plaque characteristics and inflammation using magnetic resonance imaging JF - Biomedicines N2 - Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients. KW - atherosclerosis KW - mouse models KW - wall shear stress KW - pulse wave velocity KW - arterial elasticity KW - inflammation KW - magnetic resonance imaging Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228839 SN - 2227-9059 VL - 9 IS - 2 ER -