@article{BerntRangrezEdenetal.2016,
  author    = {Bernt, Alexander and Rangrez, Ashraf Y. and Eden, Matthias and Jungmann, Andreas and Katz, Sylvia and Rohr, Claudia and M{\"u}ller, Oliver J. and Katus, Hugo A. and Sossalla, Samuel T. and Williams, Tatjana and Ritter, Oliver and Frank, Derk and Frey, Norbert},
  title     = {Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  number    = {35758},
  doi       = {10.1038/srep35758},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167525},
  year      = {2016},
  abstract  = {The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway.},
  language  = {en}
}
@article{BittnerBobakFeuchtenbergeretal.2011,
  author    = {Bittner, Stefan and Bobak, Nicole and Feuchtenberger, Martin and Herrmann, Alexander M and G{\"o}bel, Kerstin and Kinne, Raimund W and Hansen, Anker J and Budde, Thomas and Kleinschnitz, Christoph and Frey, Oliver and Tony, Hans-Peter and Wiendl, Heinz and Meuth, Sven G},
  title     = {Expression of K\(_2\)\(_P\)5.1 potassium channels on CD4\(^+\)T lymphocytes correlates with disease activity in rheumatoid arthritis patients},
  series = {Arthritis Research \& Therapy},
  volume    = {13},
  journal   = {Arthritis Research \& Therapy},
  number    = {R21},
  doi       = {10.1186/ar3245},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139334},
  year      = {2011},
  abstract  = {Introduction CD4+ T cells express K2P5.1 (TWIK-related acid-sensitive potassium channel 2 (TASK2); KCNK5), a member of the two-pore domain potassium channel family, which has been shown to influence T cell effector functions. Recently, it was shown that K2P5.1 is upregulated upon (autoimmune) T cell stimulation. The aim of this study was to correlate expression levels of K2P5.1 on T cells from patients with rheumatoid arthritis (RA) to disease activity in these patients. Methods Expression levels of K2P5.1 were measured by RT-PCR in the peripheral blood of 58 patients with RA and correlated with disease activity parameters (C-reactive protein levels, erythrocyte sedimentation rates, disease activity score (DAS28) scores). Twenty patients undergoing therapy change were followed-up for six months. Additionally, synovial fluid and synovial biopsies were investigated for T lymphocytes expressing K2P5.1. Results K2P5.1 expression levels in CD4+ T cells show a strong correlation to DAS28 scores in RA patients. Similar correlations were found for serological inflammatory parameters (erythrocyte sedimentation rate, C-reactive protein). In addition, K2P5.1 expression levels of synovial fluid-derived T cells are higher compared to peripheral blood T cells. Prospective data in individual patients show a parallel behaviour of K2P5.1 expression to disease activity parameters during a longitudinal follow-up for six months. Conclusions Disease activity in RA patients correlates strongly with K2P5.1 expression levels in CD4+ T lymphocytes in the peripheral blood in cross-sectional as well as in longitudinal observations. Further studies are needed to investigate the exact pathophysiological mechanisms and to evaluate the possible use of K2P5.1 as a potential biomarker for disease activity and differential diagnosis.},
  language  = {en}
}
@article{ReuschWagenhaeuserGabeletal.2022,
  author    = {Reusch, Julia and Wagenh{\"a}user, Isabell and Gabel, Alexander and Eggestein, Annika and H{\"o}hn, Anna and L{\^a}m, Thi{\^e}n-Tr{\´i} and Frey, Anna and Schubert-Unkmeir, Alexandra and D{\"o}lken, Lars and Frantz, Stefan and Kurzai, Oliver and Vogel, Ulrich and Krone, Manuel and Petri, Nils},
  title     = {Influencing factors of anti-SARS-CoV-2-spike-IgG antibody titers in healthcare workers: A cross-section study},
  series = {Journal of Medical Virology},
  volume    = {95},
  journal   = {Journal of Medical Virology},
  number    = {1},
  doi       = {10.1002/jmv.28300},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318659},
  year      = {2022},
  abstract  = {Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination. anti-SARS-CoV-2-spike IgG titers were determined by SERION ELISA agile SARS-CoV-2 IgG. Mean anti-SARS-CoV-2-spike IgG levels increased significantly by number of COVID-19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID-19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti-SARS-CoV-2-spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS-CoV-2 immunity, adding to the risk of severe infections within this already health impaired collective.},
  language  = {en}
}