@article{MuellerSienerthDietzHoltzetal.2011, author = {M{\"u}ller-Sienerth, Nicole and Dietz, Lena and Holtz, Philipp and Kapp, Markus and Grigoleit, G{\"o}tz Ulrich and Schmuck, Carsten and Wajant, Harald and Siegmund, Daniela}, title = {SMAC Mimetic BV6 Induces Cell Death in Monocytes and Maturation of Monocyte-Derived Dendritic Cells}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0021556}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142415}, pages = {e21556}, year = {2011}, abstract = {Background: Compounds mimicking the inhibitory effect of SMAC / DIABLO on X-linked inhibitor of apoptosis (XIAP) have been developed with the aim to achieve sensitization for apoptosis of tumor cells resistant due to deregulated XIAP expression. It turned out that SMAC mimetics also have complex effects on the NF kappa B system and TNF signaling. In view of the overwhelming importance of the NF kappa B transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells. Principal Findings: BV6 induced apoptotic and necrotic cell death in monocytes while T-cells, dendritic cells and macrophages were largely protected against BV6-induced cell death. In immature dendritic cells BV6 treatment resulted in moderate activation of the classical NF kappa B pathway, but it also diminished the stronger NF kappa B-inducing effect of TNF and CD40L. Despite its inhibitory effect on TNF- and CD40L signaling, BV6 was able to trigger maturation of immature DCs as indicated by upregulation of CD83, CD86 and IL12. Significance: The demonstrated effects of SMAC mimetics on immune cells may complicate the development of tumor therapeutic concepts based on these compounds but also arise the possibility to exploit them for the development of immune stimulatory therapies.}, language = {en} } @article{MuellerSienerthDietzHoltzetal.2011, author = {M{\"u}ller-Sienerth, Nicole and Dietz, Lena and Holtz, Philipp and Kapp, Markus and Grigoleit, G{\"o}tz Ulrich and Schmuck, Carsten and Wajant, Harald and Siegmund, Siegmund}, title = {SMAC Mimetic BV6 Induces Cell Death in Monocytes and Maturation of Monocyte-Derived Dendritic Cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76106}, year = {2011}, abstract = {Background: Compounds mimicking the inhibitory effect of SMAC / DIABLO on X-linked inhibitor of apoptosis (XIAP) have been developed with the aim to achieve sensitization for apoptosis of tumor cells resistant due to deregulated XIAP expression. It turned out that SMAC mimetics also have complex effects on the NFkB system and TNF signaling. In view of the overwhelming importance of the NFkB transcription factors in the immune system, we analyzed here the effects of the SMAC mimetic BV6 on immune cells. Principal Findings: BV6 induced apoptotic and necrotic cell death in monocytes while T-cells, dendritic cells and macrophages were largely protected against BV6-induced cell death. In immature dendritic cells BV6 treatment resulted in moderate activation of the classical NFkB pathway, but it also diminished the stronger NFkB-inducing effect of TNF and CD40L. Despite its inhibitory effect on TNF- and CD40L signaling, BV6 was able to trigger maturation of immature DCs as indicated by upregulation of CD83, CD86 and IL12. Significance: The demonstrated effects of SMAC mimetics on immune cells may complicate the development of tumor therapeutic concepts based on these compounds but also arise the possibility to exploit them for the development of immune stimulatory therapies.}, subject = {Medizin}, language = {en} } @inproceedings{SchwaneckGlosBofingeretal.2008, author = {Schwaneck, Stefan and Glos, Michael and Bofinger, Peter and Straubhaar, Thomas and Haase, Axel and Pinkwart, Andreas and Kunze, Mario and {\"O}sterle, Irene and Seubert, Marc and Nowak, Matthias and Rosen, Holga and Steinle, Andreas and Schorr, Leander and Fichtner, Caroline and Fischl, Bernd and Wittrock, Max and G{\"u}nther, Niclas and Roth, Isabelle and Verburg, Erik and Sextl, Gerhard and Heitm{\"u}ller, Lars and M{\"u}ller, Norman and Frashek, Andr{\´e} and Stetter, Ulrich}, title = {Innovationen - Performancetreiber und nachhaltiger Wirtschaftsmotor in Deutschland? Festschrift zum 5. W{\"u}rzburger Wirtschaftssymposium}, organization = {5. W{\"u}rzburger Wirtschaftssymposium 2008}, isbn = {978-3-923959-58-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-53559}, year = {2008}, abstract = {5. W{\"u}rzburger Wirtschaftssymposium, 20.11.2008 Deutsche Erfindungen ver{\"a}ndern die Welt - heute wie vor 500 Jahren. Von Buchdruck, {\"u}ber Dieselmotor, Gl{\"u}hbirne bis hin zu Airbag, Aspirin, D{\"u}bel, Fernseher und mp3-Format. Alleine dieser bescheidene {\"U}berblick des Ph{\"a}nomens "Made in Germany" l{\"a}sst den Betrachter die Bedeutung und das Potenzial von Innovationen am Standort Deutschland schnell erkennen. Experten aus Wirtschaft, Politik und Gesellschaft setzten sich am 20.11.2008 unter der Leitfrage: "Innovationen - Performancetreiber und nachhaltiger Wirtschaftsmotor in Deutschland?" mit der Bedeutung von Innovationen f{\"u}r den Standort Deutschland auseinander. Die Festschrift rundet - neben Interviews mit und Gastbeitr{\"a}gen von Referenten der Veranstaltung - das 5. W{\"u}rzburger Wirtschaftssymposium mit Stellungnahmen und Beitr{\"a}gen renommierter Experten ab. Zu Wort kommen dabei Jungunternehmer ebenso wie Wissenschaftler der Universit{\"a}t W{\"u}rzburg und Vertreter externer Organisationen.}, subject = {Innovationsforschung}, language = {de} } @article{BijuSchwarzLinkeetal.2011, author = {Biju, Joseph and Schwarz, Roland and Linke, Burkhard and Blom, Jochen and Becker, Anke and Claus, Heike and Goesmann, Alexander and Frosch, Matthias and M{\"u}ller, Tobias and Vogel, Ulrich and Schoen, Christoph}, title = {Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome}, series = {PLoS One}, volume = {6}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0018441}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137960}, pages = {e18441}, year = {2011}, abstract = {Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40\% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.}, language = {en} } @article{GentschevMuellerAdelfingeretal.2011, author = {Gentschev, Ivaylo and M{\"u}ller, Meike and Adelfinger, Marion and Weibel, Stephanie and Grummt, Friedrich and Zimmermann, Martina and Bitzer, Michael and Heisig, Martin and Zhang, Qian and Yu, Yong A. and Chen, Nanhai G. and Stritzker, Jochen and Lauer, Ulrich M. and Szalay, Aladar A.}, title = {Efficient Colonization and Therapy of Human Hepatocellular Carcinoma (HCC) Using the Oncolytic Vaccinia Virus Strain GLV-1h68}, series = {PLOS ONE}, volume = {6}, journal = {PLOS ONE}, number = {7}, doi = {10.1371/journal.pone.0022069}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135319}, pages = {e22069}, year = {2011}, abstract = {Virotherapy using oncolytic vaccinia virus strains is one of the most promising new strategies for cancer therapy. In this study, we analyzed for the first time the therapeutic efficacy of the oncolytic vaccinia virus GLV-1h68 in two human hepatocellular carcinoma cell lines HuH7 and PLC/PRF/5 (PLC) in cell culture and in tumor xenograft models. By viral proliferation assays and cell survival tests, we demonstrated that GLV-1h68 efficiently colonized, replicated in, and did lyse these cancer cells in culture. Experiments with HuH7 and PLC xenografts have revealed that a single intravenous injection (i.v.) of mice with GLV-1h68 resulted in a significant reduction of primary tumor sizes compared to uninjected controls. In addition, replication of GLV-1h68 in tumor cells led to strong inflammatory and oncolytic effects resulting in intense infiltration of MHC class II-positive cells like neutrophils, macrophages, B cells and dendritic cells and in up-regulation of 13 pro-inflammatory cytokines. Furthermore, GLV-1h68 infection of PLC tumors inhibited the formation of hemorrhagic structures which occur naturally in PLC tumors. Interestingly, we found a strongly reduced vascular density in infected PLC tumors only, but not in the non-hemorrhagic HuH7 tumor model. These data demonstrate that the GLV-1h68 vaccinia virus may have an enormous potential for treatment of human hepatocellular carcinoma in man.}, language = {en} } @article{ScheerSommervilleMueller1980, author = {Scheer, Ulrich and Sommerville, John and M{\"u}ller, Ulrike}, title = {DNA is assembled into globular supranucleosomal chromatin structures by nuclear contents of amphibian oocytes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39671}, year = {1980}, abstract = {The assembly of DNA into nucleosomal and supranucleosomal chromatin structures has been studied (i) by injection of circular DNA molecules (plasmids) into nuclei of Pleurodeles waltlii oocytes; and (ii) by in vitro incubation of plasmid molecules with the supernatant fraction from oocyte nuclei of Pleurodeles and Xenopus laevis, followed by purification of nucleoprotein structures formed with sucrose gradient centrifugation. [n both types of experiments , spread preparations of the newly assembled and transcriptionally inactive chromatin , examined by electron microscopy , show dense globular higher order (supranucleosomal) packing forms. Under partially relaxing (low salt) preparation conditions granular chromatin subunits of about 30 nm diameter can be seen either as widely spaced particles or in closely packed aggregates. The transcriptionally inactive endogenous chromatin of chromomeres of lampbrush chromosomes is arranged in similar higher order chromatin units. A correlation is found between the sizes of the DN A molecule probes used and the numbers of nucleosomes and higher order globules in the assembled chromatin structures. After prolonged dispersion in low salt buffers , these globular chromatin units unfold into chains of7-12 nucleosomes. The results support the concept that chromatin is arranged , under physiological ion concentrations as they are present in the nucleus , in supranucleosomal units of globular morphology.}, language = {en} } @article{ZentgrafTrendelenburgSpringetal.1979, author = {Zentgraf, Hanswalter and Trendelenburg, Michael F. and Spring, Herbert and Scheer, Ulrich and Franke, Werner W. and M{\"u}ller, Ulrike and Drury, Kenneth C. and Rungger, Duri}, title = {Mitochondrial DNA arranged into chromatin-like structures after injection into amphibian oocyte nuclei}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33174}, year = {1979}, abstract = {Purified mitochondrial DNA (mitDNA) from ovaries ofXenopus lae vis was injected into the nuclei (germinal vesicles) of large viteUogenic oocytes of the same organism and examined by electron microscopy ofthe spread nuclear contents. Normally located nuclei of untreated oocytes as weil as peripherally translocated nuclei of centrifuged oocytes were used. In addition, oocyte nuclei isolated and incubated under liquid paraffin oil were injected with DNA. The integrity oftranscriptional structures of endogenous chromosomal (Iampbrush chromosomes) and extrachromosomal (nucleoli) genes of the injected nuclei was demonstrated. Microinjected mitDN A was identified as circles of chromatin exhibiting polynucleosome-like organization and a me an contour length of 2.6 J.Lm, corresponding to a compaction ratio of the mitDN A of about 2 : I. This DNA packing ratio is similar to that observed after preparation of various kinds of native chromatin in low salt buffers. The chromatin circles formed from injected mitDNA only very rarely exhibited lateral fibrils suggestive of transcriptional activity. These results suggest that purified mitDNA can be transformed to normally structured chromatin when exposed to oocyte nuclear contents but is rarely , if at all , transcribed in this form and in this environment.}, language = {en} } @article{ZentgrafMuellerScheeretal.1981, author = {Zentgraf, H. and M{\"u}ller, U. and Scheer, Ulrich and Franke, W. W.}, title = {Evidence for the existence of globular units in the supranucleosomal organization of chromatin}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-34123}, year = {1981}, abstract = {No abstract available}, language = {en} } @article{MuellerThomasRudeliusRondaketal.2014, author = {M{\"u}ller-Thomas, Catharina and Rudelius, Martina and Rondak, Ina-Christine and Haferlach, Torsten and Schanz, Julie and Huberle, Christina and Schmidt, Burkard and Blaser, Rainer and Kremer, Marcus and Peschel, Christian and Germing, Ulrich and Platzbecker, Uwe and Goetze, Katharina}, title = {Response to azacitidine is independent of p53 expression in higher-risk myelodysplastic syndromes and secondary acute myeloid leukemia}, series = {HAEMATOLOGICA}, volume = {99}, journal = {HAEMATOLOGICA}, number = {10}, issn = {1592-8721}, doi = {10.3324/haematol.2014.104760}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115313}, pages = {E179-E181}, year = {2014}, abstract = {No abstract available.}, language = {en} } @article{MuellerScheer1970, author = {M{\"u}ller, R. and Scheer, Ulrich}, title = {Klangspektrographische Untersuchungen der Laut{\"a}ußerung beim Krallenfrosch, Xenopus laevis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40529}, year = {1970}, abstract = {No abstract available}, language = {de} }