TY - JOUR A1 - El-Helou, Sabine M. A1 - Biegner, Anika-Kerstin A1 - Bode, Sebastian A1 - Ehl, Stephan R. A1 - Heeg, Maximilian A1 - Maccari, Maria E. A1 - Ritterbusch, Henrike A1 - Speckmann, Carsten A1 - Rusch, Stephan A1 - Scheible, Raphael A1 - Warnatz, Klaus A1 - Atschekzei, Faranaz A1 - Beider, Renata A1 - Ernst, Diana A1 - Gerschmann, Stev A1 - Jablonka, Alexandra A1 - Mielke, Gudrun A1 - Schmidt, Reinhold E. A1 - Schürmann, Gesine A1 - Sogkas, Georgios A1 - Baumann, Ulrich H. A1 - Klemann, Christian A1 - Viemann, Dorothee A1 - Bernuth, Horst von A1 - Krüger, Renate A1 - Hanitsch, Leif G. A1 - Scheibenbogen, Carmen M. A1 - Wittke, Kirsten A1 - Albert, Michael H. A1 - Eichinger, Anna A1 - Hauck, Fabian A1 - Klein, Christoph A1 - Rack-Hoch, Anita A1 - Sollinger, Franz M. A1 - Avila, Anne A1 - Borte, Michael A1 - Borte, Stephan A1 - Fasshauer, Maria A1 - Hauenherm, Anja A1 - Kellner, Nils A1 - Müller, Anna H. A1 - Ülzen, Anett A1 - Bader, Peter A1 - Bakhtiar, Shahrzad A1 - Lee, Jae-Yun A1 - Heß, Ursula A1 - Schubert, Ralf A1 - Wölke, Sandra A1 - Zielen, Stefan A1 - Ghosh, Sujal A1 - Laws, Hans-Juergen A1 - Neubert, Jennifer A1 - Oommen, Prasad T. A1 - Hönig, Manfred A1 - Schulz, Ansgar A1 - Steinmann, Sandra A1 - Klaus, Schwarz A1 - Dückers, Gregor A1 - Lamers, Beate A1 - Langemeyer, Vanessa A1 - Niehues, Tim A1 - Shai, Sonu A1 - Graf, Dagmar A1 - Müglich, Carmen A1 - Schmalzing, Marc T. A1 - Schwaneck, Eva C. A1 - Tony, Hans-Peter A1 - Dirks, Johannes A1 - Haase, Gabriele A1 - Liese, Johannes G. A1 - Morbach, Henner A1 - Foell, Dirk A1 - Hellige, Antje A1 - Wittkowski, Helmut A1 - Masjosthusmann, Katja A1 - Mohr, Michael A1 - Geberzahn, Linda A1 - Hedrich, Christian M. A1 - Müller, Christiane A1 - Rösen-Wolff, Angela A1 - Roesler, Joachim A1 - Zimmermann, Antje A1 - Behrends, Uta A1 - Rieber, Nikolaus A1 - Schauer, Uwe A1 - Handgretinger, Rupert A1 - Holzer, Ursula A1 - Henes, Jörg A1 - Kanz, Lothar A1 - Boesecke, Christoph A1 - Rockstroh, Jürgen K. A1 - Schwarze-Zander, Carolynne A1 - Wasmuth, Jan-Christian A1 - Dilloo, Dagmar A1 - Hülsmann, Brigitte A1 - Schönberger, Stefan A1 - Schreiber, Stefan A1 - Zeuner, Rainald A1 - Ankermann, Tobias A1 - Bismarck, Philipp von A1 - Huppertz, Hans-Iko A1 - Kaiser-Labusch, Petra A1 - Greil, Johann A1 - Jakoby, Donate A1 - Kulozik, Andreas E. A1 - Metzler, Markus A1 - Naumann-Bartsch, Nora A1 - Sobik, Bettina A1 - Graf, Norbert A1 - Heine, Sabine A1 - Kobbe, Robin A1 - Lehmberg, Kai A1 - Müller, Ingo A1 - Herrmann, Friedrich A1 - Horneff, Gerd A1 - Klein, Ariane A1 - Peitz, Joachim A1 - Schmidt, Nadine A1 - Bielack, Stefan A1 - Groß-Wieltsch, Ute A1 - Classen, Carl F. A1 - Klasen, Jessica A1 - Deutz, Peter A1 - Kamitz, Dirk A1 - Lassy, Lisa A1 - Tenbrock, Klaus A1 - Wagner, Norbert A1 - Bernbeck, Benedikt A1 - Brummel, Bastian A1 - Lara-Villacanas, Eusebia A1 - Münstermann, Esther A1 - Schneider, Dominik T. A1 - Tietsch, Nadine A1 - Westkemper, Marco A1 - Weiß, Michael A1 - Kramm, Christof A1 - Kühnle, Ingrid A1 - Kullmann, Silke A1 - Girschick, Hermann A1 - Specker, Christof A1 - Vinnemeier-Laubenthal, Elisabeth A1 - Haenicke, Henriette A1 - Schulz, Claudia A1 - Schweigerer, Lothar A1 - Müller, Thomas G. A1 - Stiefel, Martina A1 - Belohradsky, Bernd H. A1 - Soetedjo, Veronika A1 - Kindle, Gerhard A1 - Grimbacher, Bodo T1 - The German national registry of primary immunodeficiencies (2012-2017) JF - Frontiers in Immunology N2 - 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. KW - registry for primary immunodeficiency KW - primary immunodeficiency (PID) KW - German PID-NET registry KW - PID prevalence KW - European Society for Immunodeficiencies (ESID) KW - IgG substitution therapy KW - CVID Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629 VL - 10 ER - TY - THES A1 - Friedrich, Maria T1 - Neue metallreiche [n]Metalloarenophane: Synthese, Struktur und katalytische Aktivität T1 - New metal-enriched [n]Metalloarenophanes: Synthesis, Structure and Catalytic Activity N2 - Ausgehend von den dilithiierten Verbindungen [Cr(C6H5Li)2]·(tmeda), [Cr(C5H4Li)(C7H6Li)]·(tmeda) und [Mn(C5H4Li)(C6H5Li)]·(tmeda) konnten durch Umsetzung mit Elementdihalogeniden der Gruppe 4 neue [1]Metalloarenophane synthetisiert werden. Aufgrund des großen Kovalenzradius von Zirkon weisen diese Spezies erwartungsgemäß nur sehr geringe Molekülspannungen auf, weshalb deren intensive Färbung nicht allein auf eine mit der Verbrückung einhergehende Verkleinerung des HOMO-LUMO-Abstandes zurückgeführt werden konnte. Die UV-Vis-spektroskopischen Untersuchungen zeigten ein nicht einheitliches Verhalten, so dass deren Hintergrund mittels zeitabhängiger DFT-Rechnungen (B3LYP/BP86) untersucht wurden. Den Rechnungen zufolge muss bei der niederenergetischsten Anregung dieser [1]Metalloarenophane ein starker elektronischer Einfluss der ansa-Brücke mit berücksichtigt werden. Die Übergänge finden demnach aus dem metallzentrierten HOMO in das LUMO statt, welches hauptsächlich an der Zr-Brücke lokalisiert ist. Des Weiteren ist es gelungen, heteroleptische 1,1 ́-Bis(phosphanyl)trochrocenderivate darzustellen. Neben NMR-spektroskopischen Experimenten belegen auch Kristallstrukturanalysen die Gegenwart nahezu ungespannter Systeme. Die Reaktivität dieser 1,1 ́-Bis(phosphane) in Hinblick auf deren Verwendung als Chelatliganden wurde durch deren Umsetzung mit Metallcarbonylen der Gruppe 6 sowie mit geeigneten Palladium- und Platinkomplexen untersucht. Auf diese Weise konnten bimetallische [3]Trochrocenophane erhalten werden. Durch Umsetzung mit MeLi bzw. M-C≡C-Ph (M = Li, Na) ist es in weiterführenden Experimenten gelungen, die disubstituierten Spezies darzustellen, welche eine deutlich erhöhte Löslichkeit als die entsprechenden MCl2-verbrückten Ausgangsverbindungen zeigten und konnten isoliert und in Lösung vollständig durch NMR-Spektroskopie charakterisiert werden. Die Ergebnisse dieser Studien stehen erwartungsgemäß im Einklang mit der Gegenwart ungespannter Systeme, was weiterhin durch Röntgenstrukturanalysen belegt werden konnte. Die Eignung der PdCl2-verbrückten 1,1´-Bis(phosphanyl)trochrocene als Katalysator für die Heck-Reaktion wurde weiterhin untersucht. Katalysestudien zur Umsetzung von Brombenzol mit Styrol zu trans- und cis-Stilben belegen eindeutig die katalytische Aktivität dieser Spezies. N2 - Based on the reaction of the dilithiated species [Cr(C6H5Li)2]·(tmeda), [Cr(C5H4Li)(C7H6Li)]·(tmeda) and [Mn(C5H4Li)(C6H5Li)]·(tmeda) with group 4 metal dichlorides new [1]metalloarenophanes were obtained. Due to the large covalent radius of the zirconium atom all species exhibit, as expected, little molecular ring strain. Therefore their intense colouration can not arise merely by the reduction of the HOMO-LUMO gap due to tilting. UV-Vis spectroscopy show an irregular trend, for which reason time-dependent DFT calculations (B3LYP/BP86) were conducted. According to these, the ansa-bridge executes a strong electronic influence on the lowest-energy transition in these [1]metalloarenophanes. These transitions arise from metal-centered orbitals (HOMO) to acceptor orbitals, predominately located at the zirconium bridge (LUMO). Furthermore, heteroleptic 1,1 ́-bis(phosphanyl)trochrocene derivatives could be obtained. In addition to solution NMR spectroscopic characterisation, the nonstrained character was further validated by X-ray diffraction analysis. The suitability of these 1,1 ́-bis(phosphanyles) to act as chelating ligands was subsequently evaluated by reactivity studies toward group 6 metalcarbonyls and adequate palladium- and platinum complexes. By this way the bimetallic [3]trochrocenophanes could be obtained. By further reaction with MeLi or M-C≡C-Ph (M = Li, Na) the disubstituted species could be synthesised. In contrast to their MCl2-precursors they show an increased solubility were isolated and fully characterised by solution NMR spectroscopy. Results of these studies suggest, as expected, the non-strained character of these systems, which is further validated by X-ray diffraction analysis. The applicability of the PdCl2-bridged 1,1´-bis(phosphanyl)trochrocenes to act as catalysts in the Heck reaction was investigated. Catalytic studies on the reaction of bromobenzene with styrene to trans- and cis-stilbene demonstrate the activity of these species. KW - Metallocene KW - Sandwich-Verbindungen KW - Heck-Reaktion KW - Metalloarenophane KW - Bis(phosphanyle) KW - Metalloarenophanes KW - Bis(phosphanyles) Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-66893 ER - TY - JOUR A1 - Wiegering, Armin A1 - Pfann, Christina A1 - Uthe, Friedrich Wilhelm A1 - Otto, Christoph A1 - Rycak, Lukas A1 - Mäder, Uwe A1 - Gasser, Martin A1 - Waaga-Gasser, Anna-Maria A1 - Eilers, Martin A1 - Germer, Christoph-Thomas T1 - CIP2A Influences Survival in Colon Cancer and Is Critical for Maintaining Myc Expression JF - PLoS ONE N2 - The cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic factor that stabilises the c-Myc protein. CIP2A is overexpressed in several tumours, and expression levels are an independent marker for long-term outcome. To determine whether CIP2A expression is elevated in colon cancer and whether it might serve as a prognostic marker for survival, we analysed CIP2A mRNA expression by real-time PCR in 104 colon cancer samples. CIP2A mRNA was overexpressed in colon cancer samples and CIP2A expression levels correlated significantly with tumour stage. We found that CIP2A serves as an independent prognostic marker for disease-free and overall survival. Further, we investigated CIP2A-dependent effects on levels of c-Myc, Akt and on cell proliferation in three colon cancer cell lines by silencing CIP2A using small interfering (si) and short hairpin (sh) RNAs. Depletion of CIP2A substantially inhibited growth of colon cell lines and reduced c-Myc levels without affecting expression or function of the upstream regulatory kinase, Akt. Expression of CIP2A was found to be dependent on MAPK activity, linking elevated c-Myc expression to deregulated signal transduction in colon cancer. KW - caco-2 cells KW - carcinomas KW - colon KW - colorectal cancer KW - MAPK signaling cascades KW - metastasis KW - protein expression KW - small interferring RNA Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97252 ER - TY - JOUR A1 - Benoit, Joshua B. A1 - Adelman, Zach N. A1 - Reinhardt, Klaus A1 - Dolan, Amanda A1 - Poelchau, Monica A1 - Jennings, Emily C. A1 - Szuter, Elise M. A1 - Hagan, Richard W. A1 - Gujar, Hemant A1 - Shukla, Jayendra Nath A1 - Zhu, Fang A1 - Mohan, M. A1 - Nelson, David R. A1 - Rosendale, Andrew J. A1 - Derst, Christian A1 - Resnik, Valentina A1 - Wernig, Sebastian A1 - Menegazzi, Pamela A1 - Wegener, Christian A1 - Peschel, Nicolai A1 - Hendershot, Jacob M. A1 - Blenau, Wolfgang A1 - Predel, Reinhard A1 - Johnston, Paul R. A1 - Ioannidis, Panagiotis A1 - Waterhouse, Robert M. A1 - Nauen, Ralf A1 - Schorn, Corinna A1 - Ott, Mark-Christoph A1 - Maiwald, Frank A1 - Johnston, J. Spencer A1 - Gondhalekar, Ameya D. A1 - Scharf, Michael E. A1 - Raje, Kapil R. A1 - Hottel, Benjamin A. A1 - Armisén, David A1 - Crumière, Antonin Jean Johan A1 - Refki, Peter Nagui A1 - Santos, Maria Emilia A1 - Sghaier, Essia A1 - Viala, Sèverine A1 - Khila, Abderrahman A1 - Ahn, Seung-Joon A1 - Childers, Christopher A1 - Lee, Chien-Yueh A1 - Lin, Han A1 - Hughes, Daniel S.T. A1 - Duncan, Elizabeth J. A1 - Murali, Shwetha C. A1 - Qu, Jiaxin A1 - Dugan, Shannon A1 - Lee, Sandra L. A1 - Chao, Hsu A1 - Dinh, Huyen A1 - Han, Yi A1 - Doddapaneni, Harshavardhan A1 - Worley, Kim C. A1 - Muzny, Donna M. A1 - Wheeler, David A1 - Panfilio, Kristen A. A1 - Jentzsch, Iris M. Vargas A1 - Jentzsch, IMV A1 - Vargo, Edward L. A1 - Booth, Warren A1 - Friedrich, Markus A1 - Weirauch, Matthew T. A1 - Anderson, Michelle A.E. A1 - Jones, Jeffery W. A1 - Mittapalli, Omprakash A1 - Zhao, Chaoyang A1 - Zhou, Jing-Jiang A1 - Evans, Jay D. A1 - Attardo, Geoffrey M. A1 - Robertson, Hugh M. A1 - Zdobnov, Evgeny M. A1 - Ribeiro, Jose M.C. A1 - Gibbs, Richard A. A1 - Werren, John H. A1 - Palli, Subba R. A1 - Schal, Coby A1 - Richards, Stephen T1 - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome JF - Nature Communications N2 - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. KW - human ectoparasite KW - bed bug KW - Cimex lectularius KW - genome Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221 VL - 7 IS - 10165 ER - TY - JOUR A1 - Schmitt, Elke A1 - Meybohm, Patrick A1 - Neef, Vanessa A1 - Baumgarten, Peter A1 - Bayer, Alexandra A1 - Choorapoikayil, Suma A1 - Friederich, Patrick A1 - Friedrich, Jens A1 - Geisen, Christof A1 - Güresir, Erdem A1 - Grünewald, Matthias A1 - Gutjahr, Martin A1 - Helmer, Philipp A1 - Herrmann, Eva A1 - Müller, Markus A1 - Narita, Diana A1 - Raadts, Ansgar A1 - Schwendner, Klaus A1 - Seifried, Erhard A1 - Stark, Patrick A1 - Steinbicker, Andrea U. A1 - Thoma, Josef A1 - Velten, Markus A1 - Weigt, Henry A1 - Wiesenack, Christoph A1 - Wittmann, Maria A1 - Zacharowski, Kai A1 - Piekarski, Florian T1 - Preoperative anaemia and red blood cell transfusion in patients with aneurysmal subarachnoid and intracerebral haemorrhage - a multicentre subanalysis of the German PBM Network Registry JF - Acta Neurochirurgica N2 - Purpose Anaemia is common in patients presenting with aneurysmal subarachnoid (aSAH) and intracerebral haemorrhage (ICH). In surgical patients, anaemia was identified as an idenpendent risk factor for postoperative mortality, prolonged hospital length of stay (LOS) and increased risk of red blood cell (RBC) transfusion. This multicentre cohort observation study describes the incidence and effects of preoperative anaemia in this critical patient collective for a 10-year period. Methods This multicentre observational study included adult in-hospital surgical patients diagnosed with aSAH or ICH of 21 German hospitals (discharged from 1 January 2010 to 30 September 2020). Descriptive, univariate and multivariate analyses were performed to investigate the incidence and association of preoperative anaemia with RBC transfusion, in-hospital mortality and postoperative complications in patients with aSAH and ICH. Results A total of n = 9081 patients were analysed (aSAH n = 5008; ICH n = 4073). Preoperative anaemia was present at 28.3% in aSAH and 40.9% in ICH. RBC transfusion rates were 29.9% in aSAH and 29.3% in ICH. Multivariate analysis revealed that preoperative anaemia is associated with a higher risk for RBC transfusion (OR = 3.25 in aSAH, OR = 4.16 in ICH, p < 0.001), for in-hospital mortality (OR = 1.48 in aSAH, OR = 1.53 in ICH, p < 0.001) and for several postoperative complications. Conclusions Preoperative anaemia is associated with increased RBC transfusion rates, in-hospital mortality and postoperative complications in patients with aSAH and ICH. KW - aneurysmal subarachnoid haemorrhage KW - intracerebral haemorrhage KW - anaemia KW - red blood cell transfusion KW - patient blood management Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-346754 VL - 164 ER - TY - JOUR A1 - Nguyen, Minh-Thu A1 - Saising, Jongkon A1 - Tribelli, Paula Maria A1 - Nega, Mulugeta A1 - Diene, Seydina M. A1 - François, Patrice A1 - Schrenzel, Jacques A1 - Spröer, Cathrin A1 - Bunk, Boyke A1 - Ebner, Patrick A1 - Hertlein, Tobias A1 - Kumari, Nimerta A1 - Härtner, Thomas A1 - Wistuba, Dorothee A1 - Voravuthikunchai, Supayang P. A1 - Mäder, Ulrike A1 - Ohlsen, Knut A1 - Götz, Friedrich T1 - Inactivation of farR Causes High Rhodomyrtone Resistance and Increased Pathogenicity in Staphylococcus aureus JF - Frontiers in Microbiology N2 - Rhodomyrtone (Rom) is an acylphloroglucinol antibiotic originally isolated from leaves of Rhodomyrtus tomentosa. Rom targets the bacterial membrane and is active against a wide range of Gram-positive bacteria but the exact mode of action remains obscure. Here we isolated and characterized a spontaneous Rom-resistant mutant from the model strain Staphylococcus aureus HG001 (RomR) to learn more about the resistance mechanism. We showed that Rom-resistance is based on a single point mutation in the coding region of farR [regulator of fatty acid (FA) resistance] that causes an amino acid change from Cys to Arg at position 116 in FarR, that affects FarR activity. Comparative transcriptome analysis revealed that mutated farR affects transcription of many genes in distinct pathways. FarR represses for example the expression of its own gene (farR), its flanking gene farE (effector of FA resistance), and other global regulators such as agr and sarA. All these genes were consequently upregulated in the RomR clone. Particularly the upregulation of agr and sarA leads to increased expression of virulence genes rendering the RomR clone more cytotoxic and more pathogenic in a mouse infection model. The Rom-resistance is largely due to the de-repression of farE. FarE is described as an efflux pump for linoleic and arachidonic acids. We observed an increased release of lipids in the RomR clone compared to its parental strain HG001. If farE is deleted in the RomR clone, or, if native farR is expressed in the RomR strain, the corresponding strains become hypersensitive to Rom. Overall, we show here that the high Rom-resistance is mediated by overexpression of farE in the RomR clone, that FarR is an important regulator, and that the point mutation in farR (RomR clone) makes the clone hyper-virulent. KW - antibiotic KW - Gram-positive bacteria KW - rhodomyrtone KW - Staphylococcus KW - membrane active Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224117 VL - 10 ER -