@phdthesis{Fischer2011, author = {Fischer, Michael Johannes}, title = {K{\"o}rperliche Leistungsf{\"a}higkeit bei Patienten mit HLA B27 positiver juveniler idiopathischer Arthritis in Remission}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67301}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2011}, abstract = {Mit dieser Arbeit sollte untersucht werden, ob es eine Beeintr{\"a}chtigung der k{\"o}rperlichen Leistungsf{\"a}higkeit bei Patienten bis zum 20. Lebensjahr mit inaktiver juveniler idiopathischer Arthritis bzw. einer Arthritis in Remission im Vergleich zu gesunden Gleichaltrigen gibt und wenn ja, ob ein Zusammenhang zu dem Eiweißk{\"o}rper HLA B27 besteht.}, subject = {Juvenile chronische Arthritis}, language = {de} } @article{PetersenKuntzerFischeretal.2015, author = {Petersen, Jens A. and Kuntzer, Thierry and Fischer, Dirk and von der Hagen, Maja and Veronika, Angela and Lobrinus, Johannes A. and Kress, Wolfram and Rushing, Elisabeth J. and Sinnreich, Michael and Jung, Hans H.}, title = {Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects}, series = {BMC Neurology}, volume = {15}, journal = {BMC Neurology}, number = {182}, doi = {10.1186/s12883-015-0449-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139920}, year = {2015}, abstract = {Background: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. Methods: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. Results: Thirteen patients from 6 non-related families were included. Age of onset was 18.8 +/- 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869C>T (p.Gln957Stop), c.5928G>A (p.Trp1976Stop)). Conclusions: Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c.3031 + 2T>C) suggested a possible founder effect.}, language = {en} } @article{GrabenhenrichReichFischeretal.2014, author = {Grabenhenrich, Linus B. and Reich, Andreas and Fischer, Felix and Zepp, Fred and Forster, Johannes and Schuster, Antje and Bauer, Carl-Peter and Bergmann, Renate L. and Bergmann, Karl E. and Wahn, Ulrich and Keil, Thomas and Lau, Susanne}, title = {The Novel 10-Item Asthma Prediction Tool: External Validation in the German MAS Birth Cohort}, series = {PLOS ONE}, volume = {9}, journal = {PLOS ONE}, number = {12}, issn = {1932-6203}, doi = {10.1371/journal.pone.0115852}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114202}, pages = {e115852}, year = {2014}, abstract = {Background: A novel non-invasive asthma prediction tool from the Leicester Cohort, UK, forecasts asthma at age 8 years based on 10 predictors assessed in early childhood, including current respiratory symptoms, eczema, and parental history of asthma. Objective: We aimed to externally validate the proposed asthma prediction method in a German birth cohort. Methods: The MAS-90 study (Multicentre Allergy Study) recorded details on allergic diseases prospectively in about yearly follow-up assessments up to age 20 years in a cohort of 1,314 children born 1990. We replicated the scoring method from the Leicester cohort and assessed prediction, performance and discrimination. The primary outcome was defined as the combination of parent-reported wheeze and asthma drugs (both in last 12 months) at age 8. Sensitivity analyses assessed model performance for outcomes related to asthma up to age 20 years. Results: For 140 children parents reported current wheeze or cough at age 3 years. Score distribution and frequencies of later asthma resembled the Leicester cohort: 9\% vs. 16\% (MAS-90 vs. Leicester) of children at low risk at 3 years had asthma at 8 years, at medium risk 45\% vs. 48\%. Performance of the asthma prediction tool in the MAS-90 cohort was similar (Brier score 0.22 vs. 0.23) and discrimination slightly better than in the original cohort (area under the curve, AUC 0.83 vs. 0.78). Prediction and discrimination were robust against changes of inclusion criteria, scoring and outcome definitions. The secondary outcome 'physicians' diagnosed asthma at 20 years' showed the highest discrimination (AUC 0.89). Conclusion: The novel asthma prediction tool from the Leicester cohort, UK, performed well in another population, a German birth cohort, supporting its use and further development as a simple aid to predict asthma risk in clinical settings.}, language = {en} } @article{DirksFischerHaaseetal.2021, author = {Dirks, Johannes and Fischer, Jonas and Haase, Gabriele and Holl-Wieden, Annette and Hofmann, Christine and Girschick, Hermann and Morbach, Henner}, title = {CD21\(^{lo/-}\)CD27\(^-\)IgM\(^-\) Double-Negative B Cells Accumulate in the Joints of Patients With Antinuclear Antibody-Positive Juvenile Idiopathic Arthritis}, series = {Frontiers in Pediatrics}, volume = {9}, journal = {Frontiers in Pediatrics}, issn = {2296-2360}, doi = {10.3389/fped.2021.635815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236286}, year = {2021}, abstract = {Juvenile idiopathic arthritis (JIA) encompasses a heterogeneous group of diseases. The appearance of antinuclear antibodies (ANAs) in almost half of the patients suggests B cell dysregulation as a distinct pathomechanism in these patients. Additionally, ANAs were considered potential biomarkers encompassing a clinically homogenous subgroup of JIA patients. However, in ANA+ JIA patients, the site of dysregulated B cell activation as well as the B cell subsets involved in this process is still unknown. Hence, in this cross-sectional study, we aimed in an explorative approach at characterizing potential divergences in B cell differentiation in ANA+ JIA patients by assessing the distribution of peripheral blood (PB) and synovial fluid (SF) B cell subpopulations using flow cytometry. The frequency of transitional as well as switched-memory B cells was higher in PB of JIA patients than in healthy controls. There were no differences in the distribution of B cell subsets between ANA- and ANA+ patients in PB. However, the composition of SF B cells was different between ANA- and ANA+ patients with increased frequencies of CD21\(^{lo/-}\)CD27\(^-\)IgM\(^-\) "double negative" (DN) B cells in the latter. DN B cells might be a characteristic subset expanding in the joints of ANA+ JIA patients and are potentially involved in the antinuclear immune response in these patients. The results of our explorative study might foster further research dissecting the pathogenesis of ANA+ JIA patients.}, language = {en} } @article{FischerDirksKlaussneretal.2022, author = {Fischer, Jonas and Dirks, Johannes and Klaussner, Julia and Haase, Gabriele and Holl-Wieden, Annette and Hofmann, Christine and Hackenberg, Stephan and Girschick, Hermann and Morbach, Henner}, title = {Effect of clonally expanded PD-1\(^h\)\(^i\)\(^g\)\(^h\) CXCR5-CD4+ peripheral T Helper cells on B cell differentiation in the joints of patients with antinuclear antibody-positive juvenile idiopathic arthritis}, series = {Arthritis \& Rheumatology}, volume = {74}, journal = {Arthritis \& Rheumatology}, number = {1}, doi = {10.1002/art.41913}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256607}, pages = {150-162}, year = {2022}, abstract = {Objective Antinuclear antibody (ANA)-positive juvenile idiopathic arthritis (JIA) is characterized by synovial B cell hyperactivity, but the precise role of CD4+ T cells in promoting local B cell activation is unknown. This study was undertaken to determine the phenotype and function of synovial CD4+ T cells that promote aberrant B cell activation in JIA. Methods Flow cytometry was performed to compare the phenotype and cytokine patterns of PD-1\(^h\)\(^i\)\(^g\)\(^h\)CD4+ T cells in the synovial fluid (SF) of patients with JIA and T follicular helper cells in the tonsils of control individuals. TCRVB next-generation sequencing was used to analyze T cell subsets for signs of clonal expansion. The functional impact of these T cell subsets on B cells was examined in cocultures in vitro. Results Multidimensional flow cytometry revealed the expansion of interleukin-21 (IL-21) and interferon-γ (IFNγ)-coexpressing PD-1\(^h\)\(^i\)\(^g\)\(^h\)CXCR5-HLA-DR+CD4+ T cells that accumulate in the joints of ANA-positive JIA patients. These T cells exhibited signs of clonal expansion with restricted T cell receptor clonotypes. The phenotype resembled peripheral T helper (Tph) cells with an extrafollicular chemokine receptor pattern and high T-bet and B lymphocyte-induced maturation protein 1 expression, but low B cell lymphoma 6 expression. SF Tph cells, by provision of IL-21 and IFNy, skewed B cell differentiation toward a CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+ phenotype in vitro. Additionally, SF Tph cell frequencies correlated with the appearance of SF CD21\(^l\)\(^o\)\(^w\)\(^/\)\(^-\)CD11c+CD27-IgM- double-negative (DN) B cells in situ.}, language = {en} } @article{JarauschNeuenrothAndagetal.2022, author = {Jarausch, Johannes and Neuenroth, Lisa and Andag, Reiner and Leha, Andreas and Fischer, Andreas and Asif, Abdul R. and Lenz, Christof and Eidizadeh, Abass}, title = {Influence of shear stress, inflammation and BRD4 inhibition on human endothelial cells: a holistic proteomic approach}, series = {Cells}, volume = {11}, journal = {Cells}, number = {19}, issn = {2073-4409}, doi = {10.3390/cells11193086}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-289872}, year = {2022}, abstract = {Atherosclerosis is an important risk factor in the development of cardiovascular diseases. In addition to increased plasma lipid concentrations, irregular/oscillatory shear stress and inflammatory processes trigger atherosclerosis. Inhibitors of the transcription modulatory bromo- and extra-terminal domain (BET) protein family (BETi) could offer a possible therapeutic approach due to their epigenetic mechanism and anti-inflammatory properties. In this study, the influence of laminar shear stress, inflammation and BETi treatment on human endothelial cells was investigated using global protein expression profiling by ion mobility separation-enhanced data independent acquisition mass spectrometry (IMS-DIA-MS). For this purpose, primary human umbilical cord derived vascular endothelial cells were treated with TNFα to mimic inflammation and exposed to laminar shear stress in the presence or absence of the BRD4 inhibitor JQ1. IMS-DIA-MS detected over 4037 proteins expressed in endothelial cells. Inflammation, shear stress and BETi led to pronounced changes in protein expression patterns with JQ1 having the greatest effect. To our knowledge, this is the first proteomics study on primary endothelial cells, which provides an extensive database for the effects of shear stress, inflammation and BETi on the endothelial proteome.}, language = {en} } @article{HoffmannEtzrodtWillkommetal.2015, author = {Hoffmann, Linda S. and Etzrodt, Jennifer and Willkomm, Lena and Sanyal, Abhishek and Scheja, Ludger and Fischer, Alexander W. C. and Stasch, Johannes-Peter and Bloch, Wilhelm and Friebe, Andreas and Heeren, Joerg and Pfeifer, Alexander}, title = {Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7235}, doi = {10.1038/ncomms8235}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143127}, year = {2015}, abstract = {Obesity is characterized by a positive energy balance and expansion of white adipose tissue (WAT). In contrast, brown adipose tissue (BAT) combusts energy to produce heat. Here we show that a small molecule stimulator (BAY 41-8543) of soluble guanylyl cyclase (sGC), which produces the second messenger cyclic GMP (cGMP), protects against diet-induced weight gain, induces weight loss in established obesity, and also improves the diabetic phenotype. Mechanistically, the haeme-dependent sGC stimulator BAY 41-8543 enhances lipid uptake into BAT and increases whole-body energy expenditure, whereas ablation of the haeme-containing \(\beta\)\(_{1}\)-subunit of sGC severely impairs BAT function. Notably, the sGC stimulator enhances differentiation of human brown adipocytes as well as induces 'browning' of primary white adipocytes. Taken together, our data suggest that sGC is a potential pharmacological target for the treatment of obesity and its comorbidities.}, language = {en} } @phdthesis{Fischer2022, author = {Fischer, Johannes}, title = {Die Garantenstellung aus Ingerenz : Untersuchungen zur Dogmatik des unechten Unterlassungsdelikts, \S 13 StGB}, series = {Strafrechtliche Fragen der Gegenwart ; Band 13}, journal = {Strafrechtliche Fragen der Gegenwart ; Band 13}, publisher = {Logos Verlag}, address = {Berlin}, isbn = {978-3-8325-5533-7}, issn = {1614-4260}, doi = {10.25972/OPUS-29899}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298992}, school = {Universit{\"a}t W{\"u}rzburg}, pages = {XV, 860 Seiten}, year = {2022}, abstract = {Das unechte Unterlassungsdelikt gilt seit langem als das "dunkelste Ka- pitel" in der Dogmatik des Allgemeinen Teils des StGB. Gesetzlicher Anhaltspunkt der Strafbarkeit ist allein, dass der Unterlassende "recht- lich daf{\"u}r einzustehen hat, daß der Erfolg nicht eintritt", \S 13 Abs. 1 StGB, also Garant ist. Innerhalb der herkommlich diskutierten Garan- tenstellungen ist die aus Ingerenz besonders umstritten. Hat derjenige, der eine Gefahr f{\"u}r fremde Rechtsg{\"u}ter geschaffen hat, eine Garantenstellung im Hinblick auf dieses schadenstr{\"a}chtige Gesche- hen, sodass er gem{\"a}ß \S 13 Abs. 1 StGB f{\"u}r das Unterlassen der Erfolgs- abwendung gleich einem Begehungst{\"a}ter bestraft wird? Welche rechtli- chen Anforderungen w{\"a}ren in diesem Fall an das die Garantenstellung begr{\"u}ndende Handeln zu stellen? Die regelm{\"a}ßig diskutierten Alternati- ven sind, ob nur pflichtwidriges Tun eine Ingerenzgarantenstellung nach sich zieht oder auch rechtm{\"a}ßiges ("qualifiziert riskantes") Vorverhalten gen{\"u}gt. Die vorliegende Arbeit kommt zu dem Ergebnis, dass sich das Einste- henm{\"u}ssen des Ingerenten auf der Grundlage des geltenden Rechts be- gr{\"u}nden l{\"a}sst. Hinsichtlich der Voraussetzungen der Garantenstellung will sie aufzeigen, dass es nicht auf die aus der unsicheren Entschei- dungsperspektive ex ante zu treffende Verhaltensbewertung ankommen kann. Vorgeschlagen wird stattdessen eine vermittelnde L{\"o}sung, die die Bewertungsgrundlage mit einem Maximum an Objektivit{\"a}t versieht.}, subject = {Unterlassungsdelikt}, language = {de} } @article{LeProvostThieleWestphaletal.2021, author = {Le Provost, Ga{\"e}tane and Thiele, Jan and Westphal, Catrin and Penone, Caterina and Allan, Eric and Neyret, Margot and van der Plas, Fons and Ayasse, Manfred and Bardgett, Richard D. and Birkhofer, Klaus and Boch, Steffen and Bonkowski, Michael and Buscot, Francois and Feldhaar, Heike and Gaulton, Rachel and Goldmann, Kezia and Gossner, Martin M. and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Renner, Swen and Scherreiks, Pascal and Sikorski, Johannes and Baulechner, Dennis and Bl{\"u}thgen, Nico and Bolliger, Ralph and B{\"o}rschig, Carmen and Busch, Verena and Chist{\´e}, Melanie and Fiore-Donno, Anna Maria and Fischer, Markus and Arndt, Hartmut and Hoelzel, Norbert and John, Katharina and Jung, Kirsten and Lange, Markus and Marzini, Carlo and Overmann, J{\"o}rg and Paŝalić, Esther and Perović, David J. and Prati, Daniel and Sch{\"a}fer, Deborah and Sch{\"o}ning, Ingo and Schrumpf, Marion and Sonnemann, Ilja and Steffan-Dewenter, Ingolf and Tschapka, Marco and T{\"u}rke, Manfred and Vogt, Juliane and Wehner, Katja and Weiner, Christiane and Weisser, Wolfgang and Wells, Konstans and Werner, Michael and Wolters, Volkmar and Wubet, Tesfaye and Wurst, Susanne and Zaitsev, Andrey S. and Manning, Peter}, title = {Contrasting responses of above- and belowground diversity to multiple components of land-use intensity}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-23931-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-371552}, year = {2021}, abstract = {Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.}, language = {en} }