@article{GilbertKleinWengetal.2017, author = {Gilbert, Fabian and Klein, Detlef and Weng, Andreas Max and K{\"o}stler, Herbert and Schmitz, Benedikt and Schmalzl, Jonas and B{\"o}hm, Dirk}, title = {Supraspinatus muscle elasticity measured with real time shear wave ultrasound elastography correlates with MRI spectroscopic measured amount of fatty degeneration}, series = {BMC Muscoskeletal Disorders}, volume = {18}, journal = {BMC Muscoskeletal Disorders}, number = {549}, doi = {10.1186/s12891-017-1911-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159378}, year = {2017}, abstract = {Background: Fatty Degeneration (FD) of the rotator cuff muscles influences functional and anatomical outcome after rotator cuff repair. The MRI based estimation of fatty degeneration is the gold standard. There is some evidence that Ultrasound elastography (EUS) can detect local differences of tissue stiffness in muscles and tendons. Shear-wave elastography (SWE) was evaluated to determine the extent to which shear wave velocity was associated with measures of fatty degeneration. MRI-spectroscopic fat measurement was used as a reference to quantify the amount of fat in the muscle belly. Methods: Forty-two patients underwent SWE of the supraspinatus muscles at its thickest diameter. After ultrasound evaluation an MRI-spectroscopic fat measurement of the supraspinatus muscle was performed using the SPLASH-technique. A gel filled capsule was used to locate the measured area in the MRI. The values of shear wave velocity (SWV) measured with SWE and spectroscopic fat measurement were correlated statistically using Pearson's correlation test. Results: Correlation of the fat amount measured with MRI-spectroscopy and the SWV measured with SWE was ρ =0.82. Spectroscopic measured fat ratio of the supraspinatus muscle ranged from 0\% to 77.41\% and SWV from 1.59 m/s to 5.32 m/s. In 4 patients no sufficient SWE could be performed, these individuals showed a larger diameter of the overlying soft tissue. SWV measured with SWE showed a good correlation with MRI spectroscopic fat amount of the supraspinatus muscle. Conclusion: These preliminary data suggest that SWE may be a sufficient tool in detecting and estimating the amount of fatty degeneration in the supraspinatus muscle in real time. Large overlying soft tissue may be a limitation in performing sufficient EUS.}, language = {en} } @article{GilPulidoCochainLippertetal.2017, author = {Gil-Pulido, Jesus and Cochain, Clement and Lippert, Malte A. and Schneider, Nicole and Butt, Elke and Am{\´e}zaga, N{\´u}ria and Zernecke, Alma}, title = {Deletion of Batf3-dependent antigen-presenting cells does not affect atherosclerotic lesion formation in mice}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0181947}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170535}, pages = {e0181947}, year = {2017}, abstract = {Atherosclerosis is the main underlying cause for cardiovascular events such as myocardial infarction and stroke and its development might be influenced by immune cells. Dendritic cells (DCs) bridge innate and adaptive immune responses by presenting antigens to T cells and releasing a variety of cytokines. Several subsets of DCs can be discriminated that engage specific transcriptional pathways for their development. Basic leucine zipper transcription factor ATF-like 3 (Batf3) is required for the development of classical CD8α\(^{+}\) and CD103\(^{+}\) DCs. By crossing mice deficient in Batf3 with atherosclerosis-prone low density lipoprotein receptor (Ldlr\(^{-/-}\))-deficient mice we here aimed to further address the contribution of Batf3-dependent CD8α\(^{+}\) and CD103\(^{+}\) antigen-presenting cells to atherosclerosis. We demonstrate that deficiency in Batf3 entailed mild effects on the immune response in the spleen but did not alter atherosclerotic lesion formation in the aorta or aortic root, nor affected plaque phenotype in low density lipoprotein receptor-deficient mice fed a high fat diet. We thus provide evidence that Batf3-dependent antigen-presenting cells do not have a prominent role in atherosclerosis.}, language = {en} } @article{GiampaoloWojcikSerflingetal.2017, author = {Giampaolo, Sabrina and W{\´o}jcik, Gabriela and Serfling, Edgar and Patra, Amiya K.}, title = {Interleukin-2-regulatory T cell axis critically regulates maintenance of hematopoietic stem cells}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, number = {18}, doi = {10.18632/oncotarget.16377}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170947}, pages = {29625-29642}, year = {2017}, abstract = {The role of IL-2 in HSC maintenance is unknown. Here we show that Il2\(^{-/-}\) mice develop severe anomalies in HSC maintenance leading to defective hematopoiesis. Whereas, lack of IL-2 signaling was detrimental for lympho- and erythropoiesis, myelopoiesis was enhanced in Il2\(^{-/-}\) mice. Investigation of the underlying mechanisms of dysregulated hematopoiesis in Il2\(^{-/-}\) mice shows that the IL-2-T\(_{reg}\) cell axis is indispensable for HSC maintenance and normal hematopoiesis. Lack of T\(_{reg}\) activity resulted in increased IFN-γ production by activated T cells and an expansion of the HSCs in the bone marrow (BM). Though, restoring T\(_{reg}\) population successfully rescued HSC maintenance in Il2\(^{-/-}\) mice, preventing IFN-γ activity could do the same even in the absence of T\(_{reg}\) cells. Our study suggests that equilibrium in IL-2 and IFN-γ activity is critical for steady state hematopoiesis, and in clinical conditions of BM failure, IL-2 or anti-IFN-γ treatment might help to restore hematopoiesis.}, language = {en} } @article{GhoshHoenscheidDueckersetal.2017, author = {Ghosh, Sujal and H{\"o}nscheid, Andrea and D{\"u}ckers, Gregor and Ginzel, Sebastian and Gohlke, Holger and Gombert, Michael and Kempkes, Bettina and Klapper, Wolfram and Kuhlen, Michaela and Laws, Hans-J{\"u}rgen and Linka, Ren{\´e} Martin and Meisel, Roland and Mielke, Christian and Niehues, Tim and Schindler, Detlev and Schneider, Dominik and Schuster, Friedhelm R. and Speckmann, Carsten and Borkhardt, Arndt}, title = {Human RAD52 - a novel player in DNA repair in cancer and immunodeficiency}, series = {Haematologica}, volume = {102}, journal = {Haematologica}, number = {2}, doi = {10.3324/haematol.2016.155838}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180862}, pages = {e69-e72}, year = {2017}, abstract = {No abstract available.}, language = {en} } @article{GenheimerAndreattaAsanetal.2017, author = {Genheimer, Hannah and Andreatta, Marta and Asan, Esther and Pauli, Paul}, title = {Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {17886}, doi = {10.1038/s41598-017-18183-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169892}, year = {2017}, abstract = {Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX-). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX-, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.}, language = {en} } @article{GeigerHirtlerGottfriedetal.2017, author = {Geiger, Julia and Hirtler, Daniel and Gottfried, Kristina and Rahman, Ozair and Bollache, Emilie and Barker, Alex J. and Markl, Michael and Stiller, Brigitte}, title = {Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {19}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {33}, doi = {10.1186/s12968-017-0347-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171119}, year = {2017}, abstract = {Background The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). Methods 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. Results Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m\(^{2}\)) at baseline t1 (0.60 ± 0.18 N/m\(^{2}\); p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m\(^{2}\); p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = -0.64) and helix/vortex pattern grading (r = -0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen's k = 0.71). Conclusions MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time.}, language = {en} } @article{GathunguBorzi2017, author = {Gathungu, Duncan Kioi and Borz{\`i}, Alfio}, title = {Multigrid Solution of an Elliptic Fredholm Partial Integro-Differential Equation with a Hilbert-Schmidt Integral Operator}, series = {Applied Mathematics}, volume = {8}, journal = {Applied Mathematics}, number = {7}, doi = {10.4236/am.2017.87076}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158525}, pages = {967-986}, year = {2017}, abstract = {An efficient multigrid finite-differences scheme for solving elliptic Fredholm partial integro-differential equations (PIDE) is discussed. This scheme combines a second-order accurate finite difference discretization of the PIDE problem with a multigrid scheme that includes a fast multilevel integration of the Fredholm operator allowing the fast solution of the PIDE problem. Theoretical estimates of second-order accuracy and results of local Fourier analysis of convergence of the proposed multigrid scheme are presented. Results of numerical experiments validate these estimates and demonstrate optimal computational complexity of the proposed framework.}, language = {en} } @article{GarciaBetancurGoniMorenoHorgeretal.2017, author = {Garc{\´i}a-Betancur, Juan-Carlos and Go{\~n}i-Moreno, Angel and Horger, Thomas and Schott, Melanie and Sharan, Malvika and Eikmeier, Julian and Wohlmuth, Barbara and Zernecke, Alma and Ohlsen, Knut and Kuttler, Christina and Lopez, Daniel}, title = {Cell differentiation defines acute and chronic infection cell types in Staphylococcus aureus}, series = {eLife}, volume = {6}, journal = {eLife}, number = {e28023}, doi = {10.7554/eLife.28023}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170346}, year = {2017}, abstract = {A central question to biology is how pathogenic bacteria initiate acute or chronic infections. Here we describe a genetic program for cell-fate decision in the opportunistic human pathogen Staphylococcus aureus, which generates the phenotypic bifurcation of the cells into two genetically identical but different cell types during the course of an infection. Whereas one cell type promotes the formation of biofilms that contribute to chronic infections, the second type is planktonic and produces the toxins that contribute to acute bacteremia. We identified a bimodal switch in the agr quorum sensing system that antagonistically regulates the differentiation of these two physiologically distinct cell types. We found that extracellular signals affect the behavior of the agr bimodal switch and modify the size of the specialized subpopulations in specific colonization niches. For instance, magnesium-enriched colonization niches causes magnesium binding to S. aureusteichoic acids and increases bacterial cell wall rigidity. This signal triggers a genetic program that ultimately downregulates the agr bimodal switch. Colonization niches with different magnesium concentrations influence the bimodal system activity, which defines a distinct ratio between these subpopulations; this in turn leads to distinct infection outcomes in vitro and in an in vivo murine infection model. Cell differentiation generates physiological heterogeneity in clonal bacterial infections and helps to determine the distinct infection types.}, language = {en} } @article{GarciaLarsenArthurPottsetal.2017, author = {Garcia-Larsen, Vanessa and Arthur, Rhonda and Potts, James F. and Howarth, Peter H. and Ahlstr{\"o}m, Matti and Haahtela, Tari and Loureiro, Carlos and Bom, Ana Todo and Brożek, Grzegorz and Makowska, Joanna and Kowalski, Marek L. and Thilsing, Trine and Keil, Thomas and Matricardi, Paolo M. and Tor{\´e}n, Kjell and van Zele, Thibaut and Bachert, Claus and Rymarczyk, Barbara and Janson, Christer and Forsberg, Bertil and Niżankowska-Mogilnicka, Ewa and Burney, Peter G. J.}, title = {Is fruit and vegetable intake associated with asthma or chronic rhino-sinusitis in European adults? Results from the Global Allergy and Asthma Network of Excellence (GA\(^2\)LEN) Survey}, series = {Clinical and Translational Allergy}, volume = {7}, journal = {Clinical and Translational Allergy}, doi = {10.1186/s13601-016-0140-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180887}, pages = {9}, year = {2017}, abstract = {Background: Fruits and vegetables are rich in compounds with proposed antioxidant, anti-allergic and anti-inflammatory properties, which could contribute to reduce the prevalence of asthma and allergic diseases. Objective: We investigated the association between asthma, and chronic rhino-sinusitis (CRS) with intake of fruits and vegetables in European adults. Methods: A stratified random sample was drawn from the Global Allergy and Asthma Network of Excellence (GA\(^2\)LEN) screening survey, in which 55,000 adults aged 15-75 answered a questionnaire on respiratory symptoms. Asthma score (derived from self-reported asthma symptoms) and CRS were the outcomes of interest. Dietary intake of 22 subgroups of fruits and vegetables was ascertained using the internationally validated GA\(^2\)LEN Food Frequency Questionnaire. Adjusted associations were examined with negative binomial and multiple regressions. Simes procedure was used to control for multiple testing. Results: A total of 3206 individuals had valid data on asthma and dietary exposures of interest. 22.8\% reported having at least 1 asthma symptom (asthma score ≥1), whilst 19.5\% had CRS. After adjustment for potential confounders, asthma score was negatively associated with intake of dried fruits (β-coefficient -2.34; 95\% confidence interval [CI] -4.09, -0.59), whilst CRS was statistically negatively associated with total intake of fruits (OR 0.73; 95\% CI 0.55, 0.97). Conversely, a positive association was observed between asthma score and alliums vegetables (adjusted β-coefficient 0.23; 95\% CI 0.06, 0.40). None of these associations remained statistically significant after controlling for multiple testing. Conclusion and clinical relevance: There was no consistent evidence for an association of asthma or CRS with fruit and vegetable intake in this representative sample of European adults.}, language = {en} } @article{FroehlichPinartKelleretal.2017, author = {Fr{\"o}hlich, M. and Pinart, M. and Keller, T. and Reich, A. and Cabieses, B. and Hohmann, C. and Postma, D. S. and Bousquet, J. and Ant{\´o}, J. M. and Keil, T. and Roll, S.}, title = {Is there a sex-shift in prevalence of allergic rhinitis and comorbid asthma from childhood to adulthood? A meta-analysis}, series = {Clinical and Translational Allergy}, volume = {7}, journal = {Clinical and Translational Allergy}, doi = {10.1186/s13601-017-0176-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172508}, year = {2017}, abstract = {Background: Allergic rhinitis and asthma as single entities affect more boys than girls in childhood but more females in adulthood. However, it is unclear if this prevalence sex-shift also occurs in allergic rhinitis and concurrent asthma. Thus, our aim was to compare sex-specifc differences in the prevalence of coexisting allergic rhinitis and asthma in childhood, adolescence and adulthood. Methods: Post-hoc analysis of systematic review with meta-analysis concerning sex-specific prevalence of allergic rhinitis. Using random-effects meta-analysis, we assessed male-female ratios for coexisting allergic rhinitis and asthma in children (0-10 years), adolescents (11-17) and adults (> 17). Electronic searches were performed using MEDLINE and EMBASE for the time period 2000-2014. We included population-based observational studies, reporting coexisting allergic rhinitis and asthma as outcome stratifed by sex. We excluded non-original or non-population-based studies, studies with only male or female participants or selective patient collectives. Results: From a total of 6539 citations, 10 studies with a total of 93,483 participants met the inclusion criteria. The male-female ratios (95\% CI) for coexisting allergic rhinitis and asthma were 1.65 (1.52; 1.78) in children (N = 6 studies), 0.61 (0.51; 0.72) in adolescents (N = 2) and 1.03 (0.79; 1.35) in adults (N = 2). Male-female ratios for allergic rhinitis only were 1.25 (1.19; 1.32, N = 5) in children, 0.80 (0.71; 0.89, N = 2) in adolescents and 0.98 (0.74; 1.30, N = 2) in adults, respectively. Conclusions: The prevalence of coexisting allergic rhinitis and asthma shows a clear male predominance in childhood and seems to switch to a female predominance in adolescents. This switch was less pronounced for allergic rhinitis only.}, language = {en} }