@article{GratwohlPfirrmannZanderetal.2016, author = {Gratwohl, A and Pfirrmann, M and Zander, A and Kr{\"o}ger, N and Beelen, D and Novotny, J and Nerl, C and Scheid, C and Spiekermann, K and Mayer, J and Sayer, HG and Falge, C and Bunjes, D and D{\"o}hner, H and Ganser, A and Schmidt-Wolf, I and Schwerdtfeger, R and Baurmann, H and Kuse, R and Schmitz, N and Wehmeier, A and Fischer, J Th and Ho, AD and Wilhelm, M and Goebeler, M-E and Lindemann, HW and Bormann, M and Hertenstein, B and Schlimok, G and Baerlocher, GM and Aul, C and Pfreundschuh, M and Fabian, M and Staib, P and Edinger, M and Schatz, M and Fauser, A and Arnold, R and Kindler, T and Wulf, G and Rosselet, A and Hellmann, A and Sch{\"a}fer, E and Pr{\"u}mmer, O and Schenk, M and Hasford, J and Heimpel, H and Hossfeld, DK and Kolb, H-J and B{\"u}sche, G and Haferlach, C and Schnittger, S and M{\"u}ller, MC and Reiter, A and Berger, U and Saußele, S and Hochhaus, A and Hehlmann, R}, title = {Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment}, series = {Leukemia}, volume = {30}, journal = {Leukemia}, doi = {10.1038/leu.2015.281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150368}, pages = {562-569}, year = {2016}, abstract = {Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95\% confidence interval (CI): 0.69-0.82) vs 0.69 (95\% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56\% vs 39\%; P = 0.005) and free of drug treatment (56\% vs 6\%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.}, language = {en} } @article{WohlfarthSchmitteckertHaertleetal.2017, author = {Wohlfarth, Carolin and Schmitteckert, Stefanie and H{\"a}rtle, Janina D. and Houghton, Lesley A. and Dweep, Harsh and Fortea, Marina and Assadi, Ghazaleh and Braun, Alexander and Mederer, Tanja and P{\"o}hner, Sarina and Becker, Philip P. and Fischer, Christine and Granzow, Martin and M{\"o}nnikes, Hubert and Mayer, Emeran A. and Sayuk, Gregory and Boeckxstaens, Guy and Wouters, Mira M. and Simr{\´e}n, Magnus and Lindberg, Greger and Ohlsson, Bodil and Schmidt, Peter Thelin and Dlugosz, Aldona and Agreus, Lars and Andreasson, Anna and D'Amato, Mauro and Burwinkel, Barbara and Bermejo, Justo Lorenzo and R{\"o}th, Ralph and Lasitschka, Felix and Vicario, Maria and Metzger, Marco and Santos, Javier and Rappold, Gudrun A. and Martinez, Cristina and Niesler, Beate}, title = {miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-13982-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173478}, year = {2017}, abstract = {Irritable bowel syndrome (IBS) is a gut-brain disorder involving alterations in intestinal sensitivity and motility. Serotonin 5-HT4 receptors are promising candidates in IBS pathophysiology since they regulate gut motor function and stool consistency, and targeted 5-HT4R selective drug intervention has been proven beneficial in subgroups of patients. We identified a single nucleotide polymorphism (SNP) (rs201253747) c.*61 T > C within the 5-HT4 receptor gene \(HTR4\) to be predominantly present in diarrhoea-IBS patients (IBS-D). It affects a binding site for the miR-16 family and miR-103/miR-107 within the isoforms \({HTR4b/i}\) and putatively impairs \(HTR4\) expression. Subsequent miRNA profiling revealed downregulation of miR-16 and miR-103 in the jejunum of IBS-D patients correlating with symptoms. \(In\) \(vitro\) assays confirmed expression regulation via three 3′UTR binding sites. The novel isoform \(HTR4b\_2\) lacking two of the three miRNA binding sites escapes miR-16/103/107 regulationin SNP carriers. We provide the first evidence that \(HTR4\) expression is fine-tuned by miRNAs, and that this regulation is impaired either by the SNP c.*61 T > C or bydiminished levels of miR-16 and miR-103 suggesting that \(HTR4\) might be involved in the development of IBS-D.}, language = {en} } @article{PetersenKuntzerFischeretal.2015, author = {Petersen, Jens A. and Kuntzer, Thierry and Fischer, Dirk and von der Hagen, Maja and Veronika, Angela and Lobrinus, Johannes A. and Kress, Wolfram and Rushing, Elisabeth J. and Sinnreich, Michael and Jung, Hans H.}, title = {Dysferlinopathy in Switzerland: clinical phenotypes and potential founder effects}, series = {BMC Neurology}, volume = {15}, journal = {BMC Neurology}, number = {182}, doi = {10.1186/s12883-015-0449-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139920}, year = {2015}, abstract = {Background: Dysferlin is reduced in patients with limb girdle muscular dystrophy type 2B, Miyoshi myopathy, distal anterior compartment myopathy, and in certain Ethnic clusters. Methods: We evaluated clinical and genetic patient data from three different Swiss Neuromuscular Centers. Results: Thirteen patients from 6 non-related families were included. Age of onset was 18.8 +/- 4.3 years. In all patients, diallelic disease-causing mutations were identified in the DYSF gene. Nine patients from 3 non-related families from Central Switzerland carried the identical homozygous mutation, c.3031 + 2T>C. A possible founder effect was confirmed by haplotype analysis. Three patients from two different families carried the heterozygous mutation, c.1064_1065delAA. Two novel mutations were identified (c.2869C>T (p.Gln957Stop), c.5928G>A (p.Trp1976Stop)). Conclusions: Our study confirms the phenotypic heterogeneity associated with DYSF mutations. Two mutations (c.3031 + 2T>C, c.1064_1065delAA) appear common in Switzerland. Haplotype analysis performed on one case (c.3031 + 2T>C) suggested a possible founder effect.}, language = {en} } @article{BenzMerkelOffneretal.2013, author = {Benz, Peter M. and Merkel, Carla J. and Offner, Kristin and Abeßer, Marco and Ullrich, Melanie and Fischer, Tobias and Bayer, Barbara and Wagner, Helga and Gambaryan, Stepan and Ursitti, Jeanine A. and Adham, Ibrahim M. and Linke, Wolfgang A. and Feller, Stephan M. and Fleming, Ingrid and Renn{\´e}, Thomas and Frantz, Stefan and Unger, Andreas and Schuh, Kai}, title = {Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy}, series = {Cell Communication and Signaling}, volume = {11}, journal = {Cell Communication and Signaling}, number = {56}, doi = {10.1186/1478-811X-11-56}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128760}, year = {2013}, abstract = {Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities.}, language = {en} } @article{TackeWagnerBrakmannetal.1993, author = {Tacke, Reinhold and Wagner, S. A. and Brakmann, S. and Wuttke, F. and Eilert, U. and Fischer, L. and Syldatk, C.}, title = {Synthesis of acetyldimethyl(phenyl)silane and its enantioselective conversion into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane by plant cell suspension culytures of Symphytum officinale L. and Ruta graveolens L.}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64299}, year = {1993}, abstract = {Starting from chlorodimethyl(phenyl)silane (3), acetyldimethyl(phenyl)silane (l) was prepared by a two-step synthesis in a total yield of 90\% [PhMe\(_2\)SiCl (3)-> PhMe\(_2\)SiCCOMe)=CH\(_2\) (4)-> PhMe\(_2\)SiC(O)Me (1)]. The prochiral acetylsilane 1 was transfonned enantioselectively into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane [(R)-2] using plant cell Suspension cultures of Symphytum officinale L. or Ruta graveolens L. Under preparative conditions (300-mg scale, not optimized), (R)-2 was isolated in 15\% (Symphytum) and 9\% yield (Ruta), respectively. The enantiomeric purities of the products were 81\% ee (Syrnphytum) and 60\% ee (Ruta), respectively.}, subject = {Anorganische Chemie}, language = {en} } @article{FlueggeFischerGrossetal.1989, author = {Fl{\"u}gge, U. I. and Fischer, K. and Gross, A. and Sebald, Walter and Lottspeich, F. and Eckerskorn, C.}, title = {The triose phosphate-3-phosphoglycerate-phosphate translocator from spinach chloroplasts: nucleotide sequence of a full-length cDNA clone and import of the in vitro synthesized precursor protein into chloroplasts}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62559}, year = {1989}, abstract = {No abstract available}, subject = {Biochemie}, language = {en} } @article{TsonevaStritzkerBedenketal.2015, author = {Tsoneva, Desislava and Stritzker, Jochen and Bedenk, Kristina and Zhang, Qian and Cappello, Joseph and Fischer, Utz and Szalay, Aladar A.}, title = {Drug-encoded Biomarkers for Monitoring Biological Therapies}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0137573}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125265}, pages = {e0137573}, year = {2015}, abstract = {Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers.}, language = {en} } @article{WinklerFischerSchadeetal.2015, author = {Winkler, Karol and Fischer, Julian and Schade, Anne and Amthor, Matthias and Dall, Robert and Geßler, Jonas and Emmerling, Monika and Ostrovskaya, Elena A. and Kamp, Martin and Schneider, Christian and H{\"o}fling, Sven}, title = {A polariton condensate in a photonic crystal potential landscape}, series = {New Journal of Physics}, volume = {17}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/17/2/023001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125050}, pages = {023001}, year = {2015}, abstract = {The possibility of investigating macroscopic coherent quantum states in polariton condensates and of engineering polariton landscapes in semiconductors has triggered interest in using polaritonic systems to simulate complex many-body phenomena. However, advanced experiments require superior trapping techniques that allow for the engineering of periodic and arbitrary potentials with strong on-site localization, clean condensate formation, and nearest-neighbor coupling. Here we establish a technology that meets these demands and enables strong, potentially tunable trapping without affecting the favorable polariton characteristics. The traps are based on a locally elongated microcavity which can be formed by standard lithography. We observe polariton condensation with non-resonant pumping in single traps and photonic crystal square lattice arrays. In the latter structures, we observe pronounced energy bands, complete band gaps, and spontaneous condensation at the M-point of the Brillouin zone.}, language = {en} } @article{GrossHennardMasourisetal.2012, author = {Gross, Henrik and Hennard, Christine and Masouris, Ilias and Cassel, Christian and Barth, Stephanie and Stober-Gr{\"a}sser, Ute and Mamiani, Alfredo and Moritz, Bodo and Ostareck, Dirk and Ostareck-Lederer, Antje and Neuenkirchen, Nils and Fischer, Utz and Deng, Wen and Leonhardt, Heinrich and Noessner, Elfriede and Kremmer, Elisabeth and Gr{\"a}sser, Friedrich A.}, title = {Binding of the Heterogeneous Ribonucleoprotein K (hnRNP K) to the Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Enhances Viral LMP2A Expression}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0042106}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133707}, year = {2012}, abstract = {The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA-antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV-infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.}, language = {en} } @article{BrixnerAeschlimannFischeretal.2013, author = {Brixner, T. and Aeschlimann, M. and Fischer, A. and Geisler, P. and Goetz, S. and Hecht, B. and Huang, J. S. and Keitzl, T. and Kramer, C. and Melchior, P. and Pfeiffer, W. and Razinskas, G. and Rewitz, C. and Schneider, C. and Str{\"u}ber, C. and Tuchscherer, P. and Voronine, D. V.}, title = {Coherent spectroscopies on ultrashort time and length scales}, series = {EPJ Web of Conferences}, volume = {41}, journal = {EPJ Web of Conferences}, doi = {10.1051/epjconf/20134109017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129073}, pages = {09017}, year = {2013}, abstract = {Three spectroscopic techniques are presented that provide simultaneous spatial and temporal resolution: modified confocal microscopy with heterodyne detection, space-time-resolved spectroscopy using coherent control concepts, and coherent two-dimensional nano-spectroscopy. Latest experimental results are discussed.}, language = {en} }