@article{BluemelZinkKlopockietal.2019, author = {Bl{\"u}mel, Rabea and Zink, Miriam and Klopocki, Eva and Liedtke, Daniel}, title = {On the traces of tcf12: Investigation of the gene expression pattern during development and cranial suture patterning in zebrafish (Danio rerio)}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0218286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201428}, pages = {e0218286}, year = {2019}, abstract = {The transcription factor 12 (tcf12) is a basic Helix-Loop-Helix protein (bHLH) of the E-protein family, proven to play an important role in developmental processes like neurogenesis, mesoderm formation, and cranial vault development. In humans, mutations in TCF12 lead to craniosynostosis, a congenital birth disorder characterized by the premature fusion of one or several of the cranial sutures. Current research has been primarily focused on functional studies of TCF12, hence the cellular expression profile of this gene during embryonic development and early stages of ossification remains poorly understood. Here we present the establishment and detailed analysis of two transgenic tcf12:EGFP fluorescent zebrafish (Danio rerio) reporter lines. Using these transgenic lines, we analyzed the general spatiotemporal expression pattern of tcf12 during different developmental stages and put emphasis on skeletal development and cranial suture patterning. We identified robust tcf12 promoter-driven EGFP expression in the central nervous system (CNS), the heart, the pronephros, and the somites of zebrafish embryos. Additionally, expression was observed inside the muscles and bones of the viscerocranium in juvenile and adult fish. During cranial vault development, the transgenic fish show a high amount of tcf12 expressing cells at the growth fronts of the ossifying frontal and parietal bones and inside the emerging cranial sutures. Subsequently, we tested the transcriptional activity of three evolutionary conserved non-coding elements (CNEs) located in the tcf12 locus by transient transgenic assays and compared their in vivo activity to the expression pattern determined in the transgenic tcf12:EGFP lines. We could validate two of them as tcf12 enhancer elements driving specific gene expression in the CNS during embryogenesis. Our newly established transgenic lines enhance the understanding of tcf12 gene regulation and open up the possibilities for further functional investigation of these novel tcf12 enhancer elements in zebrafish.}, language = {en} } @article{KunzmannNgyuenStahletal.2019, author = {Kunzmann, S. and Ngyuen, T. and Stahl, A. and Walz, J. M. and Nentwich, M. M. and Speer, C. P. and Ruf, K.}, title = {Necrotizing enterocolitis after intravitreal bevacizumab in an infant with Incontinentia Pigmenti - a case report}, series = {BMC Pediatrics}, volume = {19}, journal = {BMC Pediatrics}, doi = {10.1186/s12887-019-1732-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201024}, pages = {353}, year = {2019}, abstract = {Background Incontinentia Pigmenti is a rare disease affecting multiple organs. Fifty of patients show affection of the eye with retinopathy and possible amaurosis being the worst outcome. Treatment has commonly been panretinal laser coagulation but intravitreal application of bevacizumab as VEGF-inhibitor has shown to effectively suppress retinal neovascularization. Case presentation A six-week-old female infant with Incontinentia Pigmenti developed a foudroyant necrotizing enterocolitis shortly after intravitreal injection of bevazicumab due to a retinopathy with impending tractional detachment of the left eye. Since the onset of abdominal symptoms occurred immediately after the intravitreal application, a link between the two events seemed likely. Sequential analyses of the VEGF serum concentrations showed a massive suppression of endogenous VEGF with only a very slow recovery over weeks. Such a severe systemic adverse event has not been reported after intravitreal treatment with bevacizumab in an infant. Conclusion This case report shows a relevant systemic uptake of bevacizumab after intravitreal application as suppressed VEGF levels show. There seems to be a connection between suppressed VEGF levels and the onset of necrotizing enterocolitis. Therefore, treatment with bevacizumab should be carefully considered and further research is needed to assess this drug's safety profile.}, language = {en} } @article{WutzlerKrogiasGrauetal.2019, author = {Wutzler, Alexander and Krogias, Christos and Grau, Anna and Veltkamp, Roland and Heuschmann, Peter U. and Haeusler, Karl Georg}, title = {Stroke prevention in patients with acute ischemic stroke and atrial fibrillation in Germany - a cross sectional survey}, series = {BMC Neurology}, volume = {19}, journal = {BMC Neurology}, doi = {10.1186/s12883-019-1249-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201078}, pages = {25}, year = {2019}, abstract = {Background Atrial fibrillation (AF) is present in 15-20\% of patients with acute ischemic stroke. Oral anticoagulation reduces the risk of AF-related recurrent stroke but clinical guideline recommendations are rather vague regarding its use in the acute phase of stroke. We aimed to assess the current clinical practice of medical stroke prevention in AF patients during the acute phase of ischemic stroke. Methods In April 2017, a standardized anonymous questionnaire was sent to clinical leads of all 298 certified stroke units in Germany. Results Overall, 154 stroke unit leads participated (response rate 52\%). Anticoagulation in the acute phase of stroke is considered feasible in more than 90\% of AF patients with ischemic stroke. Clinicians assume that about two thirds of all AF patients (range 20-100\%) are discharged on oral anticoagulation. According to local preferences, acetylsalicylic acid is given orally in the majority of patients with delayed initiation of oral anticoagulation. A non-vitamin K-dependent oral anticoagulant (NOAC) is more often prescribed than a vitamin K-dependent oral anticoagulant (VKA). VKA is more often chosen in patients with previous VKA intake than in VKA naive patients. In the minority of patients, stroke unit leads discuss the prescription of a specific oral anticoagulant with the treating general practitioner. Adherence to medical stroke prevention after hospital discharge is not assessed on a regular basis in any patient by the majority of participating stroke centers. Conclusions Early secondary stroke prevention in AF patients in German stroke units is based on OAC use but prescription modalities vary in clinical practice.}, language = {en} } @article{HeroldKampfJakob2019, author = {Herold, Volker and Kampf, Thomas and Jakob, Peter Michael}, title = {Dynamic magnetic resonance scattering}, series = {Communications Physics}, volume = {2}, journal = {Communications Physics}, doi = {10.1038/s42005-019-0136-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201091}, pages = {46}, year = {2019}, abstract = {Dynamic light scattering is a popular technique to determine the size distribution of small particles in the sub micrometer region. It operates in reciprocal space, by analyzing the signal fluctuations with the photon auto correlation function. Equally, pulsed field gradient magnetic resonance is a technique generating data in the reciprocal space of the density distribution of an object. Here we show the feasibility of employing a magnetic resonance imaging system as a dynamic scattering device similar to dynamic light scattering appliances. By acquiring a time series of single data points from reciprocal space, analogue to dynamic light scattering, we demonstrate the examination of motion patterns of microscopic particles. This method allows the examination of particle dynamics significantly below the spatial resolution of magnetic resonance imaging. It is not limited by relaxation times and covers a wide field of applications for particle or cell motion in opaque media.}, language = {en} } @article{WinterAndelovicKampfetal.2019, author = {Winter, Patrick and Andelovic, Kristina and Kampf, Thomas and Gutjahr, Fabian Tobias and Heidenreich, Julius and Zernecke, Alma and Bauer, Wolfgang Rudolf and Jakob, Peter Michael and Herold, Volker}, title = {Fast self-navigated wall shear stress measurements in the murine aortic archusing radial 4D-phase contrast cardiovascular magnetic resonance at 17.6 T}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {21}, journal = {Journal of Cardiovascular Magnetic Resonance}, doi = {10.1186/s12968-019-0566-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201120}, pages = {64}, year = {2019}, abstract = {Purpose 4D flow cardiovascular magnetic resonance (CMR) and the assessment of wall shear stress (WSS) are non-invasive tools to study cardiovascular risks in vivo. Major limitations of conventional triggered methods are the long measurement times needed for high-resolution data sets and the necessity of stable electrocardiographic (ECG) triggering. In this work an ECG-free retrospectively synchronized method is presented that enables accelerated high-resolution measurements of 4D flow and WSS in the aortic arch of mice. Methods 4D flow and WSS were measured in the aortic arch of 12-week-old wildtype C57BL/6 J mice (n = 7) with a radial 4D-phase-contrast (PC)-CMR sequence, which was validated in a flow phantom. Cardiac and respiratory motion signals were extracted from the radial CMR signal and were used for the reconstruction of 4D-flow data. Rigid motion correction and a first order B0 correction was used to improve the robustness of magnitude and velocity data. The aortic lumen was segmented semi-automatically. Temporally averaged and time-resolved WSS and oscillatory shear index (OSI) were calculated from the spatial velocity gradients at the lumen surface at 14 locations along the aortic arch. Reproducibility was tested in 3 animals and the influence of subsampling was investigated. Results Volume flow, cross-sectional areas, WSS and the OSI were determined in a measurement time of only 32 min. Longitudinal and circumferential WSS and radial stress were assessed at 14 analysis planes along the aortic arch. The average longitudinal, circumferential and radial stress values were 1.52 ± 0.29 N/m2, 0.28 ± 0.24 N/m2 and - 0.21 ± 0.19 N/m2, respectively. Good reproducibility of WSS values was observed. Conclusion This work presents a robust measurement of 4D flow and WSS in mice without the need of ECG trigger signals. The retrospective approach provides fast flow quantification within 35 min and a flexible reconstruction framework.}, language = {en} } @article{MatosMachadoSchartletal.2019, author = {Matos, Isa and Machado, Miguel P. and Schartl, Manfred and Coelho, Maria Manuela}, title = {Allele-specific expression variation at different ploidy levels in Squalius alburnoides}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-40210-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200910}, pages = {3688}, year = {2019}, abstract = {Allopolyploid plants are long known to be subject to a homoeolog expression bias of varying degree. The same phenomenon was only much later suspected to occur also in animals based on studies of single selected genes in an allopolyploid vertebrate, the Iberian fish Squalius alburnoides. Consequently, this species became a good model for understanding the evolution of gene expression regulation in polyploid vertebrates. Here, we analyzed for the first time genome-wide allele-specific expression data from diploid and triploid hybrids of S. alburnoides and compared homoeolog expression profiles of adult livers and of juveniles. Co-expression of alleles from both parental genomic types was observed for the majority of genes, but with marked homoeolog expression bias, suggesting homoeolog specific reshaping of expression level patterns in hybrids. Complete silencing of one allele was also observed irrespective of ploidy level, but not transcriptome wide as previously speculated. Instead, it was found only in a restricted number of genes, particularly ones with functions related to mitochondria and ribosomes. This leads us to hypothesize that allelic silencing may be a way to overcome intergenomic gene expression interaction conflicts, and that homoeolog expression bias may be an important mechanism in the achievement of sustainable genomic interactions, mandatory to the success of allopolyploid systems, as in S. alburnoides.}, language = {en} } @article{DrescherKleinSchmittetal.2019, author = {Drescher, Nora and Klein, Alexandra-Maria and Schmitt, Thomas and Leonhardt, Sara Diana}, title = {A clue on bee glue: New insight into the sources and factors driving resin intake in honeybees (Apis mellifera)}, series = {PLoS ONE}, volume = {14}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0210594}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200935}, pages = {e0210594}, year = {2019}, abstract = {Honeybees (Apis mellifera) are threatened by numerous pathogens and parasites. To prevent infections they apply cooperative behavioral defenses, such as allo-grooming and hygiene, or they use antimicrobial plant resin. Resin is a chemically complex and highly variable mixture of many bioactive compounds. Bees collect the sticky material from different plant species and use it for nest construction and protection. Despite its importance for colony health, comparatively little is known about the precise origins and variability in resin spectra collected by honeybees. To identify the botanical resin sources of A. mellifera in Western Europe we chemically compared resin loads of individual foragers and tree resins. We further examined the resin intake of 25 colonies from five different apiaries to assess the effect of location on variation in the spectra of collected resin. Across all colonies and apiaries, seven distinct resin types were categorized according to their color and chemical composition. Matches between bee-collected resin and tree resin indicated that bees used poplar (Populus balsamifera, P. x canadensis), birch (Betula alba), horse chestnut (Aesculus hippocastanum) and coniferous trees (either Picea abies or Pinus sylvestris) as resin sources. Our data reveal that honeybees collect a comparatively broad and variable spectrum of resin sources, thus assuring protection against a variety of antagonists sensitive to different resins and/or compounds. We further unravel distinct preferences for specific resins and resin chemotypes, indicating that honeybees selectively search for bioactive resin compounds.}, language = {en} } @article{ClausHubertBecheretal.2019, author = {Claus, Heike and Hubert, Kerstin and Becher, D{\"o}rte and Otto, Andreas and Pawlik, Marie-Christin and Lappann, Ines and Strobel, Lea and Vogel, Ulrich and Johswich, Kay}, title = {A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis}, series = {Scientific Reports}, volume = {9}, journal = {Scientific Reports}, doi = {10.1038/s41598-019-39231-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200956}, pages = {2736}, year = {2019}, abstract = {Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39\% of disease isolates, but only in 3.4\% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes.}, language = {en} } @article{TiffeMorbachRueckeretal.2019, author = {Tiffe, Theresa and Morbach, Caroline and R{\"u}cker, Viktoria and Gelbrich, G{\"o}tz and Wagner, Martin and Faller, Hermann and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Impact of patient beliefs on blood pressure control in the general population: findings from the population-based STAAB cohort study}, series = {International Journal of Hypertension}, volume = {2019}, journal = {International Journal of Hypertension}, doi = {10.1155/2019/9385397}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200992}, pages = {9385397}, year = {2019}, abstract = {Background. Effective antihypertensive treatment depends on patient compliance regarding prescribed medications. We assessed the impact of beliefs related towards antihypertensive medication on blood pressure control in a population-based sample treated for hypertension. Methods. We used data from the Characteristics and Course of Heart Failure Stages A-B and Determinants of Progression (STAAB) study investigating 5000 inhabitants aged 30 to 79 years from the general population of W{\"u}rzburg, Germany. The Beliefs about Medicines Questionnaire German Version (BMQ-D) was provided in a subsample without established cardiovascular diseases (CVD) treated for hypertension. We evaluated the association between inadequately controlled hypertension (systolic RR >140/90 mmHg; >140/85 mmHg in diabetics) and reported concerns about and necessity of antihypertensive medication. Results. Data from 293 participants (49.5\% women, median age 64 years [quartiles 56.0; 69.0]) entered the analysis. Despite medication, half of the participants (49.8\%) were above the recommended blood pressure target. Stratified for sex, inadequately controlled hypertension was less frequent in women reporting higher levels of concerns (OR 0.36; 95\%CI 0.17-0.74), whereas no such association was apparent in men. We found no association for specific-necessity in any model. Conclusion. Beliefs regarding the necessity of prescribed medication did not affect hypertension control. An inverse association between concerns about medication and inappropriately controlled hypertension was found for women only. Our findings highlight that medication-related beliefs constitute a serious barrier of successful implementation of treatment guidelines and underline the role of educational interventions taking into account sex-related differences.}, language = {en} } @article{Puetz2019, author = {P{\"u}tz, Stephanie M.}, title = {Mbt/PAK4 together with SRC modulates N-Cadherin adherens junctions in the developing Drosophila eye}, series = {Biology Open}, volume = {8}, journal = {Biology Open}, doi = {10.1242/bio.038406}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200898}, pages = {bio038406}, year = {2019}, abstract = {Tissue morphogenesis is accompanied by changes of adherens junctions (AJ). During Drosophila eye development, AJ reorganization includes the formation of isolated N-Cadherin AJ between photoreceptors R3/R4. Little is known about how these N-Cadherin AJ are established and maintained. This study focuses on the kinases Mbt/PAK4 and SRC, both known to alter E-Cadherin AJ across phyla. Drosophila p21-activated kinase Mbt and the non-receptor tyrosine kinases Src64 and Src42 regulate proper N-Cadherin AJ. N-Cadherin AJ elongation depends on SRC kinase activity. Cell culture experiments demonstrate binding of both Drosophila SRC isoforms to N-Cadherin and its subsequent tyrosine phosphorylation. In contrast, Mbt stabilizes but does not bind N-Cadherin in vitro. Mbt is required in R3/R4 for zipping the N-Cadherin AJ between these cells, independent of its kinase activity and Cdc42-binding. The mbt phenotype can be reverted by mutations in Src64 and Src42. Because Mbt neither directly binds to SRC proteins nor has a reproducible influence on their kinase activity, the conclusion is that Mbt and SRC signaling converge on N-Cadherin. N-Cadherin AJ formation during eye development requires a proper balance between the promoting effects of Mbt and the inhibiting influences of SRC kinases.}, language = {en} }