@article{KarunakaranSubramanianJinetal.2023, author = {Karunakaran, Mohindar M. and Subramanian, Hariharan and Jin, Yiming and Mohammed, Fiyaz and Kimmel, Brigitte and Juraske, Claudia and Starick, Lisa and N{\"o}hren, Anna and L{\"a}nder, Nora and Willcox, Carrie R. and Singh, Rohit and Schamel, Wolfgang W. and Nikolaev, Viacheslav O. and Kunzmann, Volker and Wiemer, Andrew J. and Willcox, Benjamin E. and Herrmann, Thomas}, title = {A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41938-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358179}, year = {2023}, abstract = {Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.}, language = {en} } @article{BarileBerryBlaauboeretal.2021, author = {Barile, Frank A. and Berry, Colin and Blaauboer, Bas and Boobis, Alan and Bolt, Herrmann M. and Borgert, Christopher and Dekant, Wolfgang and Dietrich, Daniel and Domingo, Jose L. and Galli, Corrado L. and Gori, Gio Batta and Greim, Helmut and Hengstler, Jan G. and Heslop-Harrison, Pat and Kacew, Sam and Marquardt, Hans and Mally, Angela and Pelkonen, Olavi and Savolainen, Kai and Testai, Emanuela and Tsatsakis, Aristides and Vermeulen, Nico P.}, title = {The EU chemicals strategy for sustainability: in support of the BfR position}, series = {Archives of Toxicology}, volume = {95}, journal = {Archives of Toxicology}, number = {9}, issn = {0340-5761}, doi = {10.1007/s00204-021-03125-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307154}, pages = {3133-3136}, year = {2021}, abstract = {The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved. A continuous process of improvement in consumer protection is clearly desirable but any initiative directed towards this objective must be based on scientific knowledge. It must not confound risk with other factors in determining policy. This conclusion is fully supported in the present Commentary including the request to improve both, data collection and the time-consuming and bureaucratic procedures that delay the publication of regulations.}, language = {en} } @article{ZeinerSchroederMetzneretal.2023, author = {Zeiner, Carsten and Schr{\"o}der, Malte and Metzner, Selina and Herrmann, Johannes and Notz, Quirin and Hottenrott, Sebastian and R{\"o}der, Daniel and Meybohm, Patrick and Lepper, Philipp M. and Lotz, Christopher}, title = {High-dose methylprednisolone pulse therapy during refractory COVID-19 acute respiratory distress syndrome: a retrospective observational study}, series = {BMC Pulmonary Medicine}, volume = {23}, journal = {BMC Pulmonary Medicine}, doi = {10.1186/s12890-023-02664-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357231}, year = {2023}, abstract = {Background Current COVID-19 guidelines recommend the early use of systemic corticoids for COVID-19 acute respiratory distress syndrome (ARDS). It remains unknown if high-dose methylprednisolone pulse therapy (MPT) ameliorates refractory COVID-19 ARDS after many days of mechanical ventilation or rapid deterioration with or without extracorporeal membrane oxygenation (ECMO). Methods This is a retrospective observational study. Consecutive patients with COVID-19 ARDS treated with a parenteral high-dose methylprednisolone pulse therapy at the intensive care units (ICU) of two University Hospitals between January 1st 2021 and November 30st 2022 were included. Clinical data collection was at ICU admission, start of MPT, 3-, 10- and 14-days post MPT. Results Thirty-seven patients (mean age 55 ± 12 years) were included in the study. MPT started at a mean of 17 ± 12 days after mechanical ventilation. Nineteen patients (54\%) received ECMO support when commencing MPT. Mean paO2/FiO2 significantly improved 3- (p = 0.034) and 10 days (p = 0.0313) post MPT. The same applied to the necessary FiO2 10 days after MPT (p = 0.0240). There were no serious infectious complications. Twenty-four patients (65\%) survived to ICU discharge, including 13 out of 20 (65\%) needing ECMO support. Conclusions Late administration of high-dose MPT in a critical subset of refractory COVID-19 ARDS patients improved respiratory function and was associated with a higher-than-expected survival of 65\%. These data suggest that high-dose MPT may be a viable salvage therapy in refractory COVID-19 ARDS.}, language = {en} } @article{BreunFlockFeldheimetal.2023, author = {Breun, Maria and Flock, Katharina and Feldheim, Jonas and Nattmann, Anja and Monoranu, Camelia M. and Herrmann, Pia and Ernestus, Ralf-Ingo and L{\"o}hr, Mario and Hagemann, Carsten and Stein, Ulrike}, title = {Metastasis associated in colorectal cancer 1 (MACC1) mRNA expression is enhanced in sporadic vestibular schwannoma and correlates to deafness}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {16}, issn = {2072-6694}, doi = {10.3390/cancers15164089}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-362543}, year = {2023}, abstract = {Vestibular schwannoma (VS) are benign cranial nerve sheath tumors of the vestibulocochlear nerve. Their incidence is mostly sporadic, but they can also be associated with NF2-related schwannomatosis (NF2), a hereditary tumor syndrome. Metastasis associated in colon cancer 1 (MACC1) is known to contribute to angiogenesis, cell growth, invasiveness, cell motility and metastasis of solid malignant cancers. In addition, MACC1 may be associated with nonsyndromic hearing impairment. Therefore, we evaluated whether MACC1 may be involved in the pathogenesis of VS. Sporadic VS, recurrent sporadic VS, NF2-associated VS, recurrent NF2-associated VS and healthy vestibular nerves were analyzed for MACC1 mRNA and protein expression by quantitative polymerase chain reaction and immunohistochemistry. MACC1 expression levels were correlated with the patients' clinical course and symptoms. MACC1 mRNA expression was significantly higher in sporadic VS compared to NF2-associated VS (p \< 0.001). The latter expressed similar MACC1 concentrations as healthy vestibular nerves. Recurrent tumors resembled the MACC1 expression of the primary tumors. MACC1 mRNA expression was significantly correlated with deafness in sporadic VS patients (p = 0.034). Therefore, MACC1 might be a new molecular marker involved in VS pathogenesis.}, language = {en} } @article{WiedenmannBocquillonDeaconetal.2016, author = {Wiedenmann, J. and Bocquillon, E. and Deacon, R.S. and Hartinger, S. and Herrmann, O. and Klapwijk, T.M. and Maier, L. and Ames, C. and Br{\"u}ne, C. and Gould, C. and Oiwa, A. and Ishibashi, K. and Tarucha, S. and Buhmann, H. and Molenkamp, L.W.}, title = {4π-periodic Josephson supercurrent in HgTe-based topological Josephson junctions}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms10303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175353}, year = {2016}, abstract = {The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.}, 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} }