@article{HerrmannBeierSimonsetal.2016, author = {Herrmann, Martin J. and Beier, Jennifer S. and Simons, Bibiane and Polak, Thomas}, title = {Transcranial Direct Current Stimulation (tDCS) of the Right Inferior Frontal Gyrus Attenuates Skin Conductance Responses to Unpredictable Threat Conditions}, series = {Frontiers in Human Neuroscience}, volume = {10}, journal = {Frontiers in Human Neuroscience}, number = {352}, doi = {10.3389/fnhum.2016.00352}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146486}, year = {2016}, abstract = {Patients with panic and post-traumatic stress disorders seem to show increased psychophysiological reactions to conditions of unpredictable (U) threat, which has been discussed as a neurobiological marker of elevated levels of sustained fear in these disorders. Interestingly, a recent study found that the right inferior frontal gyrus (rIFG) is correlated to the successful regulation of sustained fear during U threat. Therefore this study aimed to examine the potential use of non-invasive brain stimulation to foster the rIFG by means of anodal transcranial direct current stimulation (tDCS) in order to reduce psychophysiological reactions to U threat. Twenty six participants were randomly assigned into an anodal and sham stimulation group in a double-blinded manner. Anodal and cathodal electrodes (7 * 5 cm) were positioned right frontal to target the rIFG. Stimulation intensity was I = 2 mA applied for 20 min during a task including U threat conditions (NPU-task). The effects of the NPU paradigm were measured by assessing the emotional startle modulation and the skin conductance response (SCR) at the outset of the different conditions. We found a significant interaction effect of condition × tDCS for the SCR (F(2,48) = 6.3, p < 0.01) without main effects of condition and tDCS. Post hoc tests revealed that the increase in SCR from neutral (N) to U condition was significantly reduced in verum compared to the sham tDCS group (t(24) = 3.84, p < 0.001). Our results emphasize the causal role of rIFG for emotional regulation and the potential use of tDCS to reduce apprehension during U threat conditions and therefore as a treatment for anxiety disorders.}, language = {en} } @article{TuchscherrBischoffLattaretal.2015, author = {Tuchscherr, Lorena and Bischoff, Markus and Lattar, Santiago M. and Noto Llana, Mariangeles and Pf{\"o}rtner, Henrike and Niemann, Silke and Geraci, Jennifer and Van de Vyver, H{\´e}l{\`e}ne and Fraunholz, Martin J. and Cheung, Ambrose L. and Herrmann, Mathias and V{\"o}lker, Uwe and Sordelli, Daniel O. and Peters, Georg and Loeffler, Bettina}, title = {Sigma factor SigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections}, series = {PLoS Pathogens}, volume = {11}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1004870}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143419}, pages = {e1004870}, year = {2015}, abstract = {Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, \(\Delta\)sigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections.}, language = {en} } @article{HennessenMiethkeZaburannyietal.2020, author = {Hennessen, Fabienne and Miethke, Marcus and Zaburannyi, Nestor and Loose, Maria and Lukežič, Tadeja and Bernecker, Steffen and H{\"u}ttel, Stephan and Jansen, Rolf and Schmiedel, Judith and Fritzenwanker, Moritz and Imirzalioglu, Can and Vogel, J{\"o}rg and Westermann, Alexander J. and Hesterkamp, Thomas and Stadler, Marc and Wagenlehner, Florian and Petković, Hrvoje and Herrmann, Jennifer and M{\"u}ller, Rolf}, title = {Amidochelocardin overcomes resistance mechanisms exerted on tetracyclines and natural chelocardin}, series = {Antibiotics}, volume = {9}, journal = {Antibiotics}, number = {9}, issn = {2079-6382}, doi = {10.3390/antibiotics9090619}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213149}, year = {2020}, abstract = {The reassessment of known but neglected natural compounds is a vital strategy for providing novel lead structures urgently needed to overcome antimicrobial resistance. Scaffolds with resistance-breaking properties represent the most promising candidates for a successful translation into future therapeutics. Our study focuses on chelocardin, a member of the atypical tetracyclines, and its bioengineered derivative amidochelocardin, both showing broad-spectrum antibacterial activity within the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) panel. Further lead development of chelocardins requires extensive biological and chemical profiling to achieve favorable pharmaceutical properties and efficacy. This study shows that both molecules possess resistance-breaking properties enabling the escape from most common tetracycline resistance mechanisms. Further, we show that these compounds are potent candidates for treatment of urinary tract infections due to their in vitro activity against a large panel of multidrug-resistant uropathogenic clinical isolates. In addition, the mechanism of resistance to natural chelocardin was identified as relying on efflux processes, both in the chelocardin producer Amycolatopsis sulphurea and in the pathogen Klebsiella pneumoniae. Resistance development in Klebsiella led primarily to mutations in ramR, causing increased expression of the acrAB-tolC efflux pump. Most importantly, amidochelocardin overcomes this resistance mechanism, revealing not only the improved activity profile but also superior resistance-breaking properties of this novel antibacterial compound.}, language = {en} } @article{HerrmannHildebrandMenzeletal.2019, author = {Herrmann, Marietta and Hildebrand, Maria and Menzel, Ursula and Fahy, Niamh and Alini, Mauro and Lang, Siegmund and Benneker, Lorin and Verrier, Sophie and Stoddart, Martin J. and Bara, Jennifer J.}, title = {Phenotypic characterization of bone marrow mononuclear cells and derived stromal cell populations from human iliac crest, vertebral body and femoral head}, series = {International Journal of Molecular Sciences}, volume = {20}, journal = {International Journal of Molecular Sciences}, number = {14}, issn = {1422-0067}, doi = {10.3390/ijms20143454}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285054}, year = {2019}, abstract = {(1) In vitro, bone marrow-derived stromal cells (BMSCs) demonstrate inter-donor phenotypic variability, which presents challenges for the development of regenerative therapies. Here, we investigated whether the frequency of putative BMSC sub-populations within the freshly isolated mononuclear cell fraction of bone marrow is phenotypically predictive for the in vitro derived stromal cell culture. (2) Vertebral body, iliac crest, and femoral head bone marrow were acquired from 33 patients (10 female and 23 male, age range 14-91). BMSC sub-populations were identified within freshly isolated mononuclear cell fractions based on cell-surface marker profiles. Stromal cells were expanded in monolayer on tissue culture plastic. Phenotypic assessment of in vitro derived cell cultures was performed by examining growth kinetics, chondrogenic, osteogenic, and adipogenic differentiation. (3) Gender, donor age, and anatomical site were neither predictive for the total yield nor the population doubling time of in vitro derived BMSC cultures. The abundance of freshly isolated progenitor sub-populations (CD45-CD34-CD73+, CD45-CD34-CD146+, NG2+CD146+) was not phenotypically predictive of derived stromal cell cultures in terms of growth kinetics nor plasticity. BMSCs derived from iliac crest and vertebral body bone marrow were more responsive to chondrogenic induction, forming superior cartilaginous tissue in vitro, compared to those isolated from femoral head. (4) The identification of discrete progenitor populations in bone marrow by current cell-surface marker profiling is not predictive for subsequently derived in vitro BMSC cultures. Overall, the iliac crest and the vertebral body offer a more reliable tissue source of stromal progenitor cells for cartilage repair strategies compared to femoral head.}, language = {en} } @article{ElHelouBiegnerBodeetal.2019, author = {El-Helou, Sabine M. and Biegner, Anika-Kerstin and Bode, Sebastian and Ehl, Stephan R. and Heeg, Maximilian and Maccari, Maria E. and Ritterbusch, Henrike and Speckmann, Carsten and Rusch, Stephan and Scheible, Raphael and Warnatz, Klaus and Atschekzei, Faranaz and Beider, Renata and Ernst, Diana and Gerschmann, Stev and Jablonka, Alexandra and Mielke, Gudrun and Schmidt, Reinhold E. and Sch{\"u}rmann, Gesine and Sogkas, Georgios and Baumann, Ulrich H. and Klemann, Christian and Viemann, Dorothee and Bernuth, Horst von and Kr{\"u}ger, Renate and Hanitsch, Leif G. and Scheibenbogen, Carmen M. and Wittke, Kirsten and Albert, Michael H. and Eichinger, Anna and Hauck, Fabian and Klein, Christoph and Rack-Hoch, Anita and Sollinger, Franz M. and Avila, Anne and Borte, Michael and Borte, Stephan and Fasshauer, Maria and Hauenherm, Anja and Kellner, Nils and M{\"u}ller, Anna H. and {\"U}lzen, Anett and Bader, Peter and Bakhtiar, Shahrzad and Lee, Jae-Yun and Heß, Ursula and Schubert, Ralf and W{\"o}lke, Sandra and Zielen, Stefan and Ghosh, Sujal and Laws, Hans-Juergen and Neubert, Jennifer and Oommen, Prasad T. and H{\"o}nig, Manfred and Schulz, Ansgar and Steinmann, Sandra and Klaus, Schwarz and D{\"u}ckers, Gregor and Lamers, Beate and Langemeyer, Vanessa and Niehues, Tim and Shai, Sonu and Graf, Dagmar and M{\"u}glich, Carmen and Schmalzing, Marc T. and Schwaneck, Eva C. and Tony, Hans-Peter and Dirks, Johannes and Haase, Gabriele and Liese, Johannes G. and Morbach, Henner and Foell, Dirk and Hellige, Antje and Wittkowski, Helmut and Masjosthusmann, Katja and Mohr, Michael and Geberzahn, Linda and Hedrich, Christian M. and M{\"u}ller, Christiane and R{\"o}sen-Wolff, Angela and Roesler, Joachim and Zimmermann, Antje and Behrends, Uta and Rieber, Nikolaus and Schauer, Uwe and Handgretinger, Rupert and Holzer, Ursula and Henes, J{\"o}rg and Kanz, Lothar and Boesecke, Christoph and Rockstroh, J{\"u}rgen K. and Schwarze-Zander, Carolynne and Wasmuth, Jan-Christian and Dilloo, Dagmar and H{\"u}lsmann, Brigitte and Sch{\"o}nberger, Stefan and Schreiber, Stefan and Zeuner, Rainald and Ankermann, Tobias and Bismarck, Philipp von and Huppertz, Hans-Iko and Kaiser-Labusch, Petra and Greil, Johann and Jakoby, Donate and Kulozik, Andreas E. and Metzler, Markus and Naumann-Bartsch, Nora and Sobik, Bettina and Graf, Norbert and Heine, Sabine and Kobbe, Robin and Lehmberg, Kai and M{\"u}ller, Ingo and Herrmann, Friedrich and Horneff, Gerd and Klein, Ariane and Peitz, Joachim and Schmidt, Nadine and Bielack, Stefan and Groß-Wieltsch, Ute and Classen, Carl F. and Klasen, Jessica and Deutz, Peter and Kamitz, Dirk and Lassy, Lisa and Tenbrock, Klaus and Wagner, Norbert and Bernbeck, Benedikt and Brummel, Bastian and Lara-Villacanas, Eusebia and M{\"u}nstermann, Esther and Schneider, Dominik T. and Tietsch, Nadine and Westkemper, Marco and Weiß, Michael and Kramm, Christof and K{\"u}hnle, Ingrid and Kullmann, Silke and Girschick, Hermann and Specker, Christof and Vinnemeier-Laubenthal, Elisabeth and Haenicke, Henriette and Schulz, Claudia and Schweigerer, Lothar and M{\"u}ller, Thomas G. and Stiefel, Martina and Belohradsky, Bernd H. and Soetedjo, Veronika and Kindle, Gerhard and Grimbacher, Bodo}, title = {The German national registry of primary immunodeficiencies (2012-2017)}, series = {Frontiers in Immunology}, volume = {10}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2019.01272}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226629}, year = {2019}, abstract = {Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57\% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36\% of patients. Familial cases were observed in 21\% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74\%) and immune dysregulation (22\%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49\% of all patients received immunoglobulin G (IgG) substitution (70\%-subcutaneous; 29\%-intravenous; 1\%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.}, language = {en} }