@article{KleinschnitzLinkerMagnusetal.2015, author = {Kleinschnitz, Christoph and Linker, Ralf A. and Magnus, Tim and Korn, Thomas and Meuth, Sven G.}, title = {Report on the 6th scientific meeting of the "Verein zur F{\"o}rderung des Wissenschaftlichen Nachwuchses in der Neurologie" (NEUROWIND e.V.) held in Motzen, Germany, Oct. 31th - Nov. 2nd, 2014}, series = {Experimental \& Translational Stroke Medicine}, volume = {7}, journal = {Experimental \& Translational Stroke Medicine}, number = {1}, organization = {on behalf of the speakers at the 6'th NEUROWIND e.V. scientific meeting}, doi = {10.1186/s13231-014-0013-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125049}, year = {2015}, abstract = {From October 31th - November 2nd, 2014, the 6th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. 70 doctoral students and postdocs from over 25 different groups working in German and Swiss university hospitals or research institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. The meeting was regarded as a very well organized platform to support research of young investigators in Germany and all participants enjoyed the stimulating environment for lively in depth discussions. According to the major aim of NEUROWIND e.V. to support younger researchers in Germany the 4th NEUROWIND YOUNG SCIENTIST AWARD for experimental neurology was awarded to Michael Breckwoldt on his work in the group of Thomas Misgeld (Institute of Neuronal Cell Biology, Technische Universit{\"a}t M{\"u}nchen, Germany). The successful project was published in Nature Medicine entitled "Multiparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo". This outstanding paper deals with a molecular imaging approach in living mice to optically analyze the role of mitochondrial redox signals in axons in health and disease. The award is endowed with 20.000 Euro sponsored by Merck Serono GmbH, Darmstadt, Germany (unrestricted educational grant). This year's keynote lecture was given by Bernhard Hemmer, Head of the Department of Neurology at the Klinikum rechts der Isar, Technische Universit{\"a}t M{\"u}nchen. Dr. Hemmer highlighted the particular role of B cells and (auto)antibodies in multiple sclerosis (MS). As a new highlight Dr. Urbahns, head of global discovery technologies at Merck research laboratories, gave insights from research practice in the pharmaceutical industry and introduced a shift in the view on present-day drug discovery paradigms.}, language = {en} } @article{KleinGrohWeishauptetal.2015, author = {Klein, Dennis and Groh, Janos and Weishaupt, Andreas and Martini, Rudolf}, title = {Endogenous antibodies contribute to macrophage-mediated demyelination in a mouse model for CMT1B}, series = {Journal of Neuroinflammation}, volume = {12}, journal = {Journal of Neuroinflammation}, number = {49}, doi = {10.1186/s12974-015-0267-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125036}, year = {2015}, abstract = {Background We could previously identify components of both the innate and the adaptive immune system as disease modifiers in the pathogenesis of models for Charcot-Marie-Tooth (CMT) neuropathies type 1B and 1X. As part of the adaptive immune system, here we investigated the role of antibodies in a model for CMT1B. Methods Antibodies were localized and characterized in peripheral nerves of the CMT1B model by immunohistochemistry and Western blot analysis. Experimental ablation of antibodies was performed by cross breeding the CMT1B models with mutants deficient in B-lymphocytes (JHD-/- mutants). Ameliorated demyelination by antibody deficiency was reverted by intravenous injection of mouse IgG fractions. Histopathological analysis was performed by immunocytochemistry and light and quantitative electron microscopy. Results We demonstrate that in peripheral nerves of a mouse model for CMT1B, endogenous antibodies strongly decorate endoneurial tubes of peripheral nerves. These antibodies comprise IgG and IgM subtypes and are preferentially, but not exclusively, associated with nerve fiber aspects nearby the nodes of Ranvier. In the absence of antibodies, the early demyelinating phenotype is substantially ameliorated. Reverting the neuropathy by reconstitution with murine IgG fractions identified accumulating antibodies as potentially pathogenic at this early stage of disease. Conclusions Our study demonstrates that in a mouse model for CMT1B, endogenous antibodies contribute to early macrophage-mediated demyelination and disease progression. Thus, both the innate and adaptive immune system are mutually interconnected in a genetic model for demyelination. Since in Wallerian degeneration antibodies have also been shown to be involved in myelin phagocytosis, our study supports our view that inherited demyelination and Wallerian degeneration share common mechanisms, which are detrimental when activated under nonlesion conditions.}, language = {en} } @article{ZusanGiesekingZersonetal.2015, author = {Zusan, Andreas and Gieseking, Bj{\"o}rn and Zerson, Mario and Dyakonov, Vladimir and Magerle, Robert and Deibel, Carsten}, title = {The Effect of Diiodooctane on the Charge Carrier Generation in Organic Solar Cells Based on the Copolymer PBDTTT-C}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, doi = {10.1038/srep08286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125022}, pages = {8286}, year = {2015}, abstract = {Microstructural changes and the understanding of their effect on photocurrent generation are key aspects for improving the efficiency of organic photovoltaic devices. We analyze the impact of a systematically increased amount of the solvent additive diiodooctane (DIO) on the morphology of PBDTTT-C:PC71BM blends and related changes in free carrier formation and recombination by combining surface imaging, photophysical and charge extraction techniques. We identify agglomerates visible in AFM images of the 0\% DIO blend as PC71BM domains embedded in an intermixed matrix phase. With the addition of DIO, a decrease in the size of fullerene domains along with a demixing of the matrix phase appears for 0.6\% and 1\% DIO. Surprisingly, transient absorption spectroscopy reveals an efficient photogeneration already for the smallest amount of DIO, although the largest efficiency is found for 3\% DIO. It is ascribed to a fine-tuning of the blend morphology in terms of the formation of interpenetrating donor and acceptor phases minimizing geminate and nongeminate recombination as indicated by charge extraction experiments. An increase in the DIO content to 10\% adversely affects the photovoltaic performance, most probably due to an inefficient free carrier formation and trapping in a less interconnected donor-acceptor network.}, language = {en} } @article{SeyfriedvonRahdenMirasetal.2015, author = {Seyfried, Florian and von Rahden, Burkhard H. and Miras, Alexander D. and Gasser, Martin and Maeder, Uwe and Kunzmann, Volker and Germer, Christoph-Thomas and Pelz, J{\"o}rg O. W. and Kerscher, Alexander G.}, title = {Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin - a longitudinal experience from a prospectively collected database of 1108 patients}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {73}, doi = {10.1186/s12885-015-1081-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125014}, year = {2015}, abstract = {Background Comprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking. Methods Data from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively. Results Despite R0 D2 gastrectomy (n = 560), 49.6\% (±5.4\%) of the patients were diagnosed with tumour recurrence and 15.5\% (±1.8\%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100\% with a median survival of 3.0 months (2.1 - 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54). Conclusions Despite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.}, language = {en} } @article{LiuHuPelzeretal.2015, author = {Liu, Dan and Hu, Kai and Pelzer, Heinz-Theo and St{\"o}rk, Stefan and Weidemann, Frank}, title = {Journey of a patient with chronic thromboembolic pulmonary hypertension}, series = {European Journal of Medical Research}, volume = {20}, journal = {European Journal of Medical Research}, number = {20}, doi = {10.1186/s40001-015-0112-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125009}, year = {2015}, abstract = {Right ventricle (RV) dysfunction is a key outcome determinant and a leading cause of death for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In this report, we followed the 5-year clinical journey of a patient with CTEPH. The tricuspid pressure gradient was significantly increased in the early phase of CTEPH and "normalized" at the late phase of this patient's clinical journey, but this "normalized" gradient is not a positive treatment response but rather an ominous sign of advancing right heart failure owing to an exhaustion of RV contractile function. Thus, appropriate interpretation of the tricuspid pressure gradient change is of importance for assessing RV dysfunction and treatment outcome during follow-up in patients with CTEPH. Besides systolic pulmonary artery pressure (SPAP), other RV functional parameters such as tricuspid annular plane systolic excursion, RV fractional area change, and RV longitudinal strain, together with clinical markers, may provide additional guidance regarding functional improvement or progression in patients with CTEPH.}, language = {en} } @article{FrankMarcudeOliveiraAlmeidaPetersenetal.2015, author = {Frank, Benjamin and Marcu, Ana and de Oliveira Almeida Petersen, Antonio Luis and Weber, Heike and Stigloher, Christian and Mottram, Jeremy C. and Scholz, Claus J{\"u}rgen and Schurigt, Uta}, title = {Autophagic digestion of Leishmania major by host macrophages is associated with differential expression of BNIP3, CTSE, and the miRNAs miR-101c, miR-129, and miR-210}, series = {Parasites \& Vectors}, volume = {8}, journal = {Parasites \& Vectors}, number = {404}, doi = {10.1186/s13071-015-0974-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124997}, year = {2015}, abstract = {Background Autophagy participates in innate immunity by eliminating intracellular pathogens. Consequently, numerous microorganisms have developed strategies to impair the autophagic machinery in phagocytes. In the current study, interactions between Leishmania major (L. m.) and the autophagic machinery of bone marrow-derived macrophages (BMDM) were analyzed. Methods BMDM were generated from BALB/c mice, and the cells were infected with L. m. promastigotes. Transmission electron microscopy (TEM) and electron tomography were used to investigate the ultrastructure of BMDM and the intracellular parasites. Affymetrix® chip analyses were conducted to identify autophagy-related messenger RNAs (mRNAs) and microRNAs (miRNAs). The protein expression levels of autophagy related 5 (ATG5), BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 (BNIP3), cathepsin E (CTSE), mechanistic target of rapamycin (MTOR), microtubule-associated proteins 1A/1B light chain 3B (LC3B), and ubiquitin (UB) were investigated through western blot analyses. BMDM were transfected with specific small interfering RNAs (siRNAs) against autophagy-related genes and with mimics or inhibitors of autophagy-associated miRNAs. The infection rates of BMDM were determined by light microscopy after a parasite-specific staining. Results The experiments demonstrated autophagy induction in BMDM after in vitro infection with L. m.. The results suggested a putative MTOR phosphorylation-dependent counteracting mechanism in the early infection phase and indicated that intracellular amastigotes were cleared by autophagy in BMDM in the late infection phase. Transcriptomic analyses and specific downregulation of protein expression with siRNAs suggested there is an association between the infection-specific over expression of BNIP3, as well as CTSE, and the autophagic activity of BMDM. Transfection with mimics of mmu-miR-101c and mmu-miR-129-5p, as well as with an inhibitor of mmu-miR-210-5p, demonstrated direct effects of the respective miRNAs on parasite clearance in L. m.-infected BMDM. Furthermore, Affymetrix® chip analyses revealed a complex autophagy-related RNA network consisting of differentially expressed mRNAs and miRNAs in BMDM, which indicates high glycolytic and inflammatory activity in the host macrophages. Conclusions Autophagy in L. m.-infected host macrophages is a highly regulated cellular process at both the RNA level and the protein level. Autophagy has the potential to clear parasites from the host. The results obtained from experiments with murine host macrophages could be translated in the future to develop innovative and therapeutic antileishmanial strategies for human patients.}, language = {en} } @article{KirscherDeanBenScadengetal.2015, author = {Kirscher, Lorenz and De{\´a}n-Ben, Xos{\´e} Luis and Scadeng, Miriam and Zaremba, Angelika and Zhang, Qian and Kober, Christina and Fehm, Thomas Felix and Razansky, Daniel and Ntziachristos, Vasilis and Stritzker, Jochen and Szalay, Aladar A.}, title = {Doxycycline Inducible Melanogenic Vaccinia Virus as Theranostic Anti-Cancer Agent}, series = {Theranostics}, volume = {5}, journal = {Theranostics}, number = {10}, doi = {10.7150/thno.12533}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124987}, pages = {1045-1057}, year = {2015}, abstract = {We reported earlier the diagnostic potential of a melanogenic vaccinia virus based system in magnetic resonance (MRI) and optoacoustic deep tissue imaging (MSOT). Since melanin overproduction lead to attenuated virus replication, we constructed a novel recombinant vaccinia virus strain (rVACV), GLV-1h462, which expressed the key enzyme of melanogenesis (tyrosinase) under the control of an inducible promoter-system. In this study melanin production was detected after exogenous addition of doxycycline in two different tumor xenograft mouse models. Furthermore, it was confirmed that this novel vaccinia virus strain still facilitated signal enhancement as detected by MRI and optoacoustic tomography. At the same time we demonstrated an enhanced oncolytic potential compared to the constitutively melanin synthesizing rVACV system.}, language = {en} } @article{HamoudaOezkurSinhaetal.2015, author = {Hamouda, Khaled and Oezkur, Mehmet and Sinha, Bhanu and Hain, Johannes and Menkel, Hannah and Leistner, Marcus and Leyh, Rainer and Schimmer, Christoph}, title = {Different duration strategies of perioperative antibiotic prophylaxis in adult patients undergoing cardiac surgery: an observational study}, series = {Journal of Cardiothoracic Surgery}, volume = {10}, journal = {Journal of Cardiothoracic Surgery}, number = {25}, doi = {10.1186/s13019-015-0225-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124977}, year = {2015}, abstract = {Background All international guidelines recommend perioperative antibiotic prophylaxis (PAB) should be routinely administered to patients undergoing cardiac surgery. However, the duration of PAB is heterogeneous and controversial. Methods Between 01.01.2011 and 31.12.2011, 1096 consecutive cardiac surgery patients were assigned to one of two groups receiving PAB with a second-generation cephalosporin for either 56 h (group I) or 32 h (group II). Patients' characteristics, intraoperative data, and the in-hospital follow-up were analysed. Primary endpoint was the incidence of surgical site infection (deep and superficial sternal wound-, and vein harvesting site infection; DSWI/SSWI/VHSI). Secondary endpoints were the incidence of respiratory-, and urinary tract infection, as well as the mortality rate. Results 615/1096 patients (56,1\%) were enrolled (group I: n = 283 versus group II: n = 332). There were no significant differences with regard to patient characteristics, comorbidities, and procedure-related variables. No statistically significant differences were demonstrated concerning primary and secondary endpoints. The incidence of DSWI/SSWI/VHSI were 4/283 (1,4\%), 5/283 (1,7\%), and 1/283 (0,3\%) in group I versus 6/332 (1,8\%), 9/332 (2,7\%), and 3/332 (0,9\%) in group II (p = 0,76/0,59/0,63). In univariate analyses female gender, age, peripheral arterial obstructive disease, operating-time, ICU-duration, transfusion, and respiratory insufficiency were determinants for nosocomial infections (all ≤ 0,05). Subgroup analyses of these high-risk patients did not show any differences between the two regimes (all ≥ 0,05). Conclusions Reducing the duration of PAB from 56 h to 32 h in adult cardiac surgery patients was not associated with an increase of nosocomial infection rate, but contributes to reduce antibiotic resistance and health care costs.}, language = {en} } @phdthesis{Leipold2015, author = {Leipold, Winfried}, title = {Der deutsch-franz{\"o}sische Krieg von 1870/71. Die Konfrontation zweier Kulturen im Spiegelbild von Zeitzeugen und Zeitzeugnissen}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125434}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Der Fokus dieser Studie liegt auf dem punktuellen Ausleuchten themenrelevanter Aspekte des deutsch-franz{\"o}sischen Krieges von 1870/71. Somit ist die Einhaltung einer chronologischen Abfolge der Kriegsgenese, wie sie g{\"a}ngigen Publikationen zu eigen ist, nicht gegeben. Es sollen vielmehr der Einfluss und die Bedeutung jener kulturell-mentaler und soziomorpher Prozesse recherchiert werden, die sich auf den Fortgang »dieses von vornherein verlorenen Krieges« (»une guerre perdue d'avance«) beziehen und welche in der traditionellen Kriegsliteratur kaum gewichtet bzw. nur marginal gestreift werden. Die Arbeit wird dokumentiert durch eine Vielzahl von Quellen aus der Feder zeitgen{\"o}ssischer Kriegsteilnehmer, Historiker, Politiker und Literaten, von Theodor Fontane bis L{\´e}on Gambetta, von Baron de la Belle-Croix bis Napoleon III., von Hans v. Kretschman bis Alfred Duquet, von Karl Tanera bis General Chancy. Zudem konnten in die Arbeit zus{\"a}tzlich Analysen und Erkenntnisse gegenw{\"a}rtiger Historiker und Milit{\"a}rs mit einbezogen werden, welche, unisono und in aller Offenheit, die eigentlichen Gr{\"u}nde der franz{\"o}sischen Niederlage von 1870/71 darlegen. Des Weiteren wird sichtbar, weshalb die franz{\"o}sische Nation nicht f{\"a}hig und willens war, vom Elfenbeinturm ihrer Selbst{\"u}bersch{\"a}tzung in die Niederungen der Realit{\"a}t hinabzusteigen. Hier seien Autoren wie Audouin-Rouzeau, Henninger, Battesti, Fr{\`e}rejean, David, Guelton, Serman, Bern{\`e}de oder Dreyfus genannt. Letztendlich runden Besuche des Verfassers an den Kriegsschaupl{\"a}tzen sowie Gespr{\"a}che mit Menschen aus der Region das Bild des Kriegsgeschehens ab, wobei deren Rekurs auf tradierte Erinnerungen an diesen nahezu 150 Jahre zur{\"u}ckliegenden Krieg in Erstaunen versetzt. Neben der Gliederung in Kapitel ist diese Arbeit in 4 {\"u}bergeordnete Themengebiete eingeteilt: Der erste, gr{\"o}ßte Teil (Kapitel 1-22) behandelt das Kriegsgeschehen im Allgemeinen, w{\"a}hrend sich der zweite Teil (Kapitel 23-24) explizit der Rolle der zeitgen{\"o}ssischen Medien und der dritte Teil (Kapitel 25-27) der Resonanz des Kriegs in der zeitgen{\"o}ssischen Literatur widmen. Der vierte Teil ist als separater Abbildungsteil konzipiert, der die vorherigen Teile erg{\"a}nzt.}, subject = {Rezeption}, language = {de} } @article{HerterStauchGallantetal.2015, author = {Herter, Eva K. and Stauch, Maria and Gallant, Maria and Wolf, Elmar and Raabe, Thomas and Gallant, Peter}, title = {snoRNAs are a novel class of biologically relevant Myc targets}, series = {BMC Biology}, volume = {13}, journal = {BMC Biology}, number = {25}, doi = {10.1186/s12915-015-0132-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124956}, year = {2015}, abstract = {Background Myc proteins are essential regulators of animal growth during normal development, and their deregulation is one of the main driving factors of human malignancies. They function as transcription factors that (in vertebrates) control many growth- and proliferation-associated genes, and in some contexts contribute to global gene regulation. Results We combine chromatin immunoprecipitation-sequencing (ChIPseq) and RNAseq approaches in Drosophila tissue culture cells to identify a core set of less than 500 Myc target genes, whose salient function resides in the control of ribosome biogenesis. Among these genes we find the non-coding snoRNA genes as a large novel class of Myc targets. All assayed snoRNAs are affected by Myc, and many of them are subject to direct transcriptional activation by Myc, both in Drosophila and in vertebrates. The loss of snoRNAs impairs growth during normal development, whereas their overexpression increases tumor mass in a model for neuronal tumors. Conclusions This work shows that Myc acts as a master regulator of snoRNP biogenesis. In addition, in combination with recent observations of snoRNA involvement in human cancer, it raises the possibility that Myc's transforming effects are partially mediated by this class of non-coding transcripts.}, language = {en} }