@article{NiewaldaVoellerEschbachetal.2011,
  author    = {Niewalda, Thomas and V{\"o}ller, Thomas and Eschbach, Claire and Ehmer, Julia and Wen-Chuang, Chou and Timme, Marc and Fiala, Andr{\´e} and Gerber, Bertram},
  title     = {A Combined Perceptual, Physico-Chemical, and Imaging Approach to 'Odour-Distances' Suggests a Categorizing Function of the Drosophila Antennal Lobe},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0024300},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133510},
  pages     = {e24300},
  year      = {2011},
  abstract  = {How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.},
  language  = {en}
}
@article{NiewaldaVoellerEschbachetal.2011,
  author    = {Niewalda, Thomas and V{\"o}ller, Thomas and Eschbach, Claire and Ehmer, Julia and Chou, Wen-Chuang and Timme, Marc and Fiala, Andr{\´e} and Gerber, Bertram},
  title     = {A Combined Perceptual, Physico-Chemical, and ImagingApproach to 'Odour-Distances' Suggests a CategorizingFunction of the Drosophila Antennal Lobe},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74769},
  year      = {2011},
  abstract  = {How do physico-chemical stimulus features, perception, and physiology relate? Given the multi-layered and parallel architecture of brains, the question specifically is where physiological activity patterns correspond to stimulus features and/ or perception. Perceived distances between six odour pairs are defined behaviourally from four independent odour recognition tasks. We find that, in register with the physico-chemical distances of these odours, perceived distances for 3-octanol and n-amylacetate are consistently smallest in all four tasks, while the other five odour pairs are about equally distinct. Optical imaging in the antennal lobe, using a calcium sensor transgenically expressed in only first-order sensory or only second-order olfactory projection neurons, reveals that 3-octanol and n-amylacetate are distinctly represented in sensory neurons, but appear merged in projection neurons. These results may suggest that within-antennal lobe processing funnels sensory signals into behaviourally meaningful categories, in register with the physico-chemical relatedness of the odours.},
  subject      = {Drosophila Antennal Lobe},
  language  = {en}
}
@article{SchrammFrauneNaumannetal.2011,
  author    = {Schramm, Sabine and Fraune, Johanna and Naumann, Ronald and Hernandez-Hernandez, Abrahan and H{\"o}{\"o}g, Christer and Cooke, Howard J. and Alsheimer, Manfred and Benavente, Ricardo},
  title     = {A Novel Mouse Synaptonemal Complex Protein Is Essential for Loading of Central Element Proteins, Recombination, and Fertility},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68895},
  year      = {2011},
  abstract  = {The synaptonemal complex (SC) is a proteinaceous, meiosis-specific structure that is highly conserved in evolution. During meiosis, the SC mediates synapsis of homologous chromosomes. It is essential for proper recombination and segregation of homologous chromosomes, and therefore for genome haploidization. Mutations in human SC genes can cause infertility. In order to gain a better understanding of the process of SC assembly in a model system that would be relevant for humans, we are investigating meiosis in mice. Here, we report on a newly identified component of the murine SC, which we named SYCE3. SYCE3 is strongly conserved among mammals and localizes to the central element (CE) of the SC. By generating a Syce3 knockout mouse, we found that SYCE3 is required for fertility in both sexes. Loss of SYCE3 blocks synapsis initiation and results in meiotic arrest. In the absence of SYCE3, initiation of meiotic recombination appears to be normal, but its progression is severely impaired resulting in complete absence of MLH1 foci, which are presumed markers of crossovers in wild-type meiocytes. In the process of SC assembly, SYCE3 is required downstream of transverse filament protein SYCP1, but upstream of the other previously described CE-specific proteins. We conclude that SYCE3 enables chromosome loading of the other CE-specific proteins, which in turn would promote synapsis between homologous chromosomes.},
  subject      = {Maus},
  language  = {en}
}
@article{KatjaLopezTillichetal.2011,
  author    = {Katja, Schulze and L{\´o}pez, Diana A. and Tillich, Ulrich M. and Frohme, Marcus},
  title     = {A simple viability analysis for unicellular cyanobacteria using a new autofluorescence assay, automated microscopy, and ImageJ},
  series = {BMC Biotechnology},
  volume    = {11},
  journal   = {BMC Biotechnology},
  number    = {118},
  doi       = {10.1186/1472-6750-11-118},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137735},
  year      = {2011},
  abstract  = {Background Currently established methods to identify viable and non-viable cells of cyanobacteria are either time-consuming (eg. plating) or preparation-intensive (eg. fluorescent staining). In this paper we present a new and fast viability assay for unicellular cyanobacteria, which uses red chlorophyll fluorescence and an unspecific green autofluorescence for the differentiation of viable and non-viable cells without the need of sample preparation. Results The viability assay for unicellular cyanobacteria using red and green autofluorescence was established and validated for the model organism Synechocystis sp. PCC 6803. Both autofluorescence signals could be observed simultaneously allowing a direct classification of viable and non-viable cells. The results were confirmed by plating/colony count, absorption spectra and chlorophyll measurements. The use of an automated fluorescence microscope and a novel ImageJ based image analysis plugin allow a semi-automated analysis. Conclusions The new method simplifies the process of viability analysis and allows a quick and accurate analysis. Furthermore results indicate that a combination of the new assay with absorption spectra or chlorophyll concentration measurements allows the estimation of the vitality of cells.},
  language  = {en}
}
@article{EckhardtAndersMuranyietal.2011,
  author    = {Eckhardt, Manon and Anders, Maria and Muranyi, Walter and Heilemann, Mike and Krijnse-Locker, Jacomine and M{\"u}ller, Barbara},
  title     = {A SNAP-Tagged Derivative of HIV-1-A Versatile Tool to Study Virus-Cell Interactions},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {7},
  doi       = {10.1371/journal.pone.0022007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133534},
  pages     = {e22007},
  year      = {2011},
  abstract  = {Fluorescently labeled human immunodeficiency virus (HIV) derivatives, combined with the use of advanced fluorescence microscopy techniques, allow the direct visualization of dynamic events and individual steps in the viral life cycle. HIV proteins tagged with fluorescent proteins (FPs) have been successfully used for live-cell imaging analyses of HIV-cell interactions. However, FPs display limitations with respect to their physicochemical properties, and their maturation kinetics. Furthermore, several independent FP-tagged constructs have to be cloned and characterized in order to obtain spectral variations suitable for multi-color imaging setups. In contrast, the so-called SNAP-tag represents a genetically encoded non-fluorescent tag which mediates specific covalent coupling to fluorescent substrate molecules in a self-labeling reaction. Fusion of the SNAP-tag to the protein of interest allows specific labeling of the fusion protein with a variety of synthetic dyes, thereby offering enhanced flexibility for fluorescence imaging approaches. Here we describe the construction and characterization of the HIV derivative HIV(SNAP), which carries the SNAP-tag as an additional domain within the viral structural polyprotein Gag. Introduction of the tag close to the C-terminus of the matrix domain of Gag did not interfere with particle assembly, release or proteolytic virus maturation. The modified virions were infectious and could be propagated in tissue culture, albeit with reduced replication capacity. Insertion of the SNAP domain within Gag allowed specific staining of the viral polyprotein in the context of virus producing cells using a SNAP reactive dye as well as the visualization of individual virions and viral budding sites by stochastic optical reconstruction microscopy. Thus, HIV(SNAP) represents a versatile tool which expands the possibilities for the analysis of HIV-cell interactions using live cell imaging and sub-diffraction fluorescence microscopy.},
  language  = {en}
}
@article{ChipperfieldDythamHovestadt2011,
  author    = {Chipperfield, Joseph D. and Dytham, Calvin and Hovestadt, Thomas},
  title     = {An Updated Algorithm for the Generation of Neutral Landscapes by Spectral Synthesis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68938},
  year      = {2011},
  abstract  = {Background: Patterns that arise from an ecological process can be driven as much from the landscape over which the process is run as it is by some intrinsic properties of the process itself. The disentanglement of these effects is aided if it possible to run models of the process over artificial landscapes with controllable spatial properties. A number of different methods for the generation of so-called 'neutral landscapes' have been developed to provide just such a tool. Of these methods, a particular class that simulate fractional Brownian motion have shown particular promise. The existing methods of simulating fractional Brownian motion suffer from a number of problems however: they are often not easily generalisable to an arbitrary number of dimensions and produce outputs that can exhibit some undesirable artefacts. Methodology: We describe here an updated algorithm for the generation of neutral landscapes by fractional Brownian motion that do not display such undesirable properties. Using Monte Carlo simulation we assess the anisotropic properties of landscapes generated using the new algorithm described in this paper and compare it against a popular benchmark algorithm. Conclusion/Significance: The results show that the existing algorithm creates landscapes with values strongly correlated in the diagonal direction and that the new algorithm presented here corrects this artefact. A number of extensions of the algorithm described here are also highlighted: we describe how the algorithm can be employed to generate landscapes that display different properties in different dimensions and how they can be combined with an environmental gradient to produce landscapes that combine environmental variation at the local and macro scales.},
  subject      = {Landschaft},
  language  = {en}
}
@article{StiebKelberWehneretal.2011,
  author    = {Stieb, Sara Mae and Kelber, Christina and Wehner, R{\"u}diger and R{\"o}ssler, Wolfgang},
  title     = {Antennal-Lobe Organization in Desert Ants of the Genus Cataglyphis},
  series = {Brain, Behavior and Evolution},
  volume    = {77},
  journal   = {Brain, Behavior and Evolution},
  number    = {3},
  issn      = {0006-8977},
  doi       = {10.1159/000326211},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196815},
  pages     = {136-146},
  year      = {2011},
  abstract  = {Desert ants of the genus Cataglyphis possess remarkable visual navigation capabilities. Although Cataglyphis species lack a trail pheromone system, Cataglyphis fortis employs olfactory cues for detecting nest and food sites. To investigate potential adaptations in primary olfactory centers of the brain of C. fortis, we analyzed olfactory glomeruli (odor processing units) in their antennal lobes and compared them to glomeruli in different Cataglyphis species. Using confocal imaging and 3D reconstruction, we analyzed the number, size and spatial arrangement of olfactory glomeruli in C. fortis, C.albicans, C.bicolor, C.rubra, and C.noda. Workers of all Cataglyphis species have smaller numbers of glomeruli (198-249) compared to those previously found in olfactory-guided ants. Analyses in 2 species of Formica - a genus closely related to Cataglyphis - revealed substantially higher numbers of olfactory glomeruli (c. 370), which is likely to reflect the importance of olfaction in these wood ant species. Comparisons between Cataglyphis species revealed 2 special features in C. fortis. First, with c. 198 C. fortis has the lowest number of glomeruli compared to all other species. Second, a conspicuously enlarged glomerulus is located close to the antennal nerve entrance. Males of C. fortis possess a significantly smaller number of glomeruli (c. 150) compared to female workers and queens. A prominent male-specific macroglomerulus likely to be involved in sex pheromone communication occupies a position different from that of the enlarged glomerulus in females. The behavioral significance of the enlarged glomerulus in female workers remains elusive. The fact that C. fortis inhabits microhabitats (salt pans) that are avoided by all other Cataglyphis species suggests that extreme ecological conditions may not only have resulted in adaptations of visual capabilities, but also in specializations of the olfactory system.},
  language  = {en}
}
@phdthesis{Azzami2011,
  author    = {Azzami, Klara},
  title     = {Antibakterielle und antivirale Abwehrreaktionen in unterschiedlichen Entwicklungsstadien der Honigbiene (Apis mellifera)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66452},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Das angeborene Immunsystem von Insekten besteht aus einer humoralen Komponente, einer zellul{\"a}ren Komponente und dem Prophenoloxidase-aktivierenden System. Fast alle Erkenntnisse {\"u}ber das angeborene Immunsystem stammen von Arbeiten mit Modellorganismen wie z.B. Drosophila oder Anopheles gambiae. Wie genau das Immunsystem der Honigbiene (Apis mellifera) funktioniert, ist jedoch noch relativ unbekannt. In der vorliegenden Arbeit wurden die unterschiedlichen Immunreaktionen aller drei Entwicklungsstadien der Honigbiene nach artifizieller Infektion mit Gram-negativen und Gram-positiven Bakterien (Escherichia coli und Micrococcus flavus) und dem Akuten Bienen Paralyse Virus (ABPV) untersucht und verglichen. Eine E. coli-Injektion zeigt bei Larven und adulten Arbeiterinnen nur wenig Auswirkung auf das {\"a}ußere Erscheinungsbild und die {\"U}berlebensrate. In beiden Entwicklungsstadien wird die humorale Immunantwort stark induziert, erkennbar an der Expression der antimikrobiellen Peptide (AMPs) Hymenoptaecin, Defensin1 und Abaecin. Zus{\"a}tzlich werden allein in Jungbienen nach bakterieller Infektion vier weitere immunspezifische Proteine exprimiert. Unter anderem eine Carboxylesterase (CE1) und das Immune-Responsive Protein 30 (IRp30). Die Expression von CE1 und IRp30 zeigt dabei den gleichen zeitlichen Verlauf wie die der AMPs. In Jungbienen kommt es zudem nach E. coli-Injektion zu einer raschen Abnahme an lebenden Bakterien in der H{\"a}molymphe, was auf eine Aktivierung der zellul{\"a}ren Immunantwort schließen l{\"a}sst. {\"A}ltere Bienen und Winterbienen zeigen eine st{\"a}rkere Immunkompetenz als Jungbienen. Selbst nicht-infizierte Winterbienen exprimieren geringe Mengen der immunspezifischen Proteine IRp30 und CE1. Die Expression von IRp30 kann dabei durch Verwundung oder Injektion von E. coli noch gesteigert werden. Eine weitere Besonderheit ist die im Vergleich zu Jungbienen raschere Abnahme an lebenden Bakterien in der H{\"a}molymphe bis hin zur vollst{\"a}ndigen Eliminierung. Die Reaktion von Puppen auf eine bakterielle Infektion war v{\"o}llig unerwartet. Nach Injektion von E. coli-Zellen kommt es innerhalb von 24 h p.i. zu einem t{\"o}dlichen Kollaps, der sich in einer Grauf{\"a}rbung des gesamten Puppenk{\"o}rpers {\"a}ußert. Da keine Expression von AMPs nachzuweisen war, wird die humorale Immunantwort offensichtlich nicht induziert. Auch die zellul{\"a}re Immunantwort scheint nicht aktiviert zu werden, denn es konnte keine Abnahme an lebenden E. coli-Zellen beobachtet werden. Aufgrund dieser fehlenden Immunreaktionen vermehrt sich E. coli im H{\"a}mocoel infizierter Puppen und scheint damit deren Tod herbeizuf{\"u}hren. Nach viraler Infektion wurden in allen drei Entwicklungsstadien der Honigbiene g{\"a}nzlich andere Reaktionen beobachtet als nach bakterieller Infektion. Bei dem verwendeten Akuten Bienen Paralyse Virus (ABPV) handelt es sich um ein Picorna-{\"a}hnliches Virus, dessen Vermehrung in der H{\"a}molymphe {\"u}ber die massive Synthese der Capsidproteine verfolgt werden kann. Eine Injektion von sehr wenigen ABPV-Partikeln ins H{\"a}mocoel hat dramatische Auswirkungen auf Larven. Nach Virusinjektion kommt es innerhalb weniger Stunden zu einer raschen Virusvermehrung und schon 24 h p.i. zum Tod, h{\"a}ufig begleitet von einer Schwarzf{\"a}rbung der gesamten Larve. Kurz vor dem Ableben kommt es neben dem Abbau hochmolekularer Speicherproteine zur Expression zahlreicher Proteine, die u.a. an der Translation oder dem Schutz vor oxidativem Stress beteiligt sind. Auf Jungbienen hat eine ABPV-Infektion keine so dramatischen Auswirkungen wie auf Larven. Sie zeigen lediglich Zeichen von Paralyse, zudem {\"u}berleben sie l{\"a}nger bei h{\"o}heren injizierten Partikelzahlen, die Virusvermehrung ist langsamer und es kommt zu keiner starken Ver{\"a}nderung des H{\"a}molymph-Proteinmusters. Es konnte gezeigt werden, dass es in ABPV-infizierten Larven oder adulten Bienen zu keiner erkennbaren Aktivierung des humoralen Immunsystems in Form von exprimierten AMPs kommt. Zudem scheint die humorale Immunantwort auch nicht unterdr{\"u}ckt zu werden, denn nach gleichzeitiger Injektion von E. coli und ABPV kommt es neben der Expression viraler Capsidproteine auch zur Expression von AMPs. Zus{\"a}tzlich konnte in Jungbienen nach Infektion mit ABPV eine zellul{\"a}re Immunantwort in Form von Nodulation ausgeschlossen werden. {\"A}ltere Bienen scheinen nicht nur mit bakteriellen Infektionen, sondern auch mit einer ABPV-Infektion besser zurechtzukommen. Bei einer Menge an ABPV-Partikeln, die in Jungbienen sp{\"a}testens 72 h p.i. zum Tod f{\"u}hrt, ist in Winterbienen eine Virusvermehrung erst ab 96 h p.i. erkennbar und diese beeintr{\"a}chtigt die {\"U}berlebensrate kaum. Puppen sind einer Virusinfektion genauso schutzlos ausgeliefert wie einer Bakterieninfektion. Es kommt zwar zu keiner starken {\"A}nderung des {\"a}ußeren Erscheinungsbildes, jedoch bleiben Puppen in ihrer Entwicklung komplett stehen. Das Virus muss sich daher stark vermehren, allerdings nicht {\"u}berwiegend - wie bei Larven und adulten Bienen - in der H{\"a}molymphe.},
  subject      = {Biene},
  language  = {de}
}
@article{SchmittKellerNourkamiTutdibietal.2011,
  author    = {Schmitt, Jana and Keller, Andreas and Nourkami-Tutdibi, Nasenien and Heisel, Sabrina and Habel, Nunja and Leidinger, Petra and Ludwig, Nicole and Gessler, Manfred and Graf, Norbert and Berthold, Frank and Lenhof, Hans-Peter and Meese, Eckart},
  title     = {Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0028951},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133794},
  pages     = {e28951},
  year      = {2011},
  abstract  = {Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8\%, a sensitivity of 87.0\% and a specificity of 86.7\%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8\%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.},
  language  = {en}
}
@phdthesis{Hokema2011,
  author    = {Hokema, Anna},
  title     = {Beeinflussung der Genexpression verschiedener Gene durch Xmrk in Pigmentzelltumoren bei Oryzias latipes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75616},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Ziel dieser Arbeit ist es ein besseres Verst{\"a}ndinis der molekularen Prozesse der Melanomentstehung und Tumorprogression zu gewinnen. Hierf{\"u}r wurde ein Tiermodell transgener Medakas (Oryzias latipes) verwendet, welche als stabiles Transgen das Konstrukt mitf::xmrk besitzen. Diese Fische entwickelten Pigmentzelltumore, welche f{\"u}r eine Microarrayanalyse herangezogen wurden. Aus diesem Microarraydatensatz wurden 11 Gene ausgew{\"a}hlt, welche in dieser Arbeit n{\"a}her untersucht wurden. Beobachtungen haben ergeben, dass sich bei transgenen Medakas, welche Xmrk exprimieren, verschiedene pigmentierte Hauttumore entwickeln. Diese Tumore wurden je nach ihrem verschiedenen Histiotyp klassifiziert und untersucht. Um einen Eindruck zu gewinnen, wie Xmrk die Transkription verschiedener Gene, welche in der Krebsentstehung und -progression eine wichtige Rolle spielen, beeinflusst, wurden pigmentierte Hauttumore transgener Medakas, so wie zu Vergleichszwecken hyperpigmentierte Haut transgener Medakas und Lymphome und gesunde Organe von Wildtyp-Medakas, untersucht. Mit Hilfe von Real-time-PCR's wurden die folgenden Gene untersucht: G6PC, GAMT, GM2A, MAPK3, NID1, SLC24A5, SPP1, PDIA4, RASL11B, TACC2 und ZFAND5. Dabei konnte festgestellt werden, dass die Expression der Gene GM2A, MAPK3, NID1, PDIA4, RASL11B, SLC24A5 und ZFAND5 von Xmrk beeinflusst wird, w{\"a}hrend dies f{\"u}r die Gene G6PC, GAMT, SPP1 und TACC2 nicht zutrifft. Im Vergleich zu gesunder Haut werden GM2A, MAPK3, PDIA4, RASL11B, SLC24A5 und ZFAND5 in Tumoren h{\"o}her exprimiert. Die Gene G6PC, GAMT, NID1, SPP1 und TACC2 werden dagegen verglichen mit gesunder Haut unver{\"a}ndert oder niedriger exprimiert. Die Bedeutung der erh{\"o}hten Genexpression l{\"a}sst sich in vielen F{\"a}llen zurzeit nur theoretisch erfassen. Eine h{\"o}here Expression von SLC24A5 beispielsweise l{\"a}sst vermuten, dass ein Zusammenhang zwischen der Melaninproduktion und der Zellproliferation besteht. Die {\"U}berexpression von GM2A weist dagegen auf eine Rolle von GM2A als Tumormarker hin. Dahingegen scheint die erniedrigte Expression von GAMT und G6PC Auskunft {\"u}ber den ver{\"a}nderten Stoffwechsel in Tumoren zu geben. Um diese Ergebnisse zu best{\"a}tigen und zu entschl{\"u}sseln wie genau Xmrk die Expression der getesteten Gene beeinflusst, sind allerdings noch weitere funktionelle Studien n{\"o}tig. Generell kommt man zu dem Schluss, dass die Genexpression sich in jedem Tumor unterscheidet. Daher scheint jeder Tumor seinen eigenen Evolutionsweg zu beschreiten.},
  subject      = {Japank{\"a}rpfling},
  language  = {de}
}
@article{OndruschKreft2011,
  author    = {Ondrusch, Nicolai and Kreft, J{\"u}rgen},
  title     = {Blue and Red Light Modulates SigB-Dependent Gene Transcription, Swimming Motility and Invasiveness in \(Listeria\) \(monocytogenes\)},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0016151},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134050},
  pages     = {e16151},
  year      = {2011},
  abstract  = {Background: In a number of gram-positive bacteria, including Listeria, the general stress response is regulated by the alternative sigma factor B (SigB). Common stressors which lead to the activation of SigB and the SigB-dependent regulon are high osmolarity, acid and several more. Recently is has been shown that also blue and red light activates SigB in Bacillus subtilis. Methodology/Principal Findings: By qRT-PCR we analyzed the transcriptional response of the pathogen L. monocytogenes to blue and red light in wild type bacteria and in isogenic deletion mutants for the putative blue-light receptor Lmo0799 and the stress sigma factor SigB. It was found that both blue (455 nm) and red (625 nm) light induced the transcription of sigB and SigB-dependent genes, this induction was completely abolished in the SigB mutant. The blue-light effect was largely dependent on Lmo0799, proving that this protein is a genuine blue-light receptor. The deletion of lmo0799 enhanced the red-light effect, the underlying mechanism as well as that of SigB activation by red light remains unknown. Blue light led to an increased transcription of the internalin A/B genes and of bacterial invasiveness for Caco-2 enterocytes. Exposure to blue light also strongly inhibited swimming motility of the bacteria in a Lmo0799- and SigB-dependent manner, red light had no effect there. Conclusions/Significance: Our data established that visible, in particular blue light is an important environmental signal with an impact on gene expression and physiology of the non-phototrophic bacterium L. monocytogenes. In natural environments these effects will result in sometimes random but potentially also cyclic fluctuations of gene activity, depending on the light conditions prevailing in the respective habitat.},
  language  = {en}
}
@article{OndruschKreft2011,
  author    = {Ondrusch, Nicolai and Kreft, J{\"u}rgen},
  title     = {Blue and Red Light Modulates SigB-Dependent Gene Transcription, Swimming Motility and Invasiveness in Listeria monocytogenes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75451},
  year      = {2011},
  abstract  = {Background: In a number of gram-positive bacteria, including Listeria, the general stress response is regulated by the alternative sigma factor B (SigB). Common stressors which lead to the activation of SigB and the SigB-dependent regulon are high osmolarity, acid and several more. Recently is has been shown that also blue and red light activates SigB in Bacillus subtilis. Methodology/Principal Findings: By qRT-PCR we analyzed the transcriptional response of the pathogen L. monocytogenes to blue and red light in wild type bacteria and in isogenic deletion mutants for the putative blue-light receptor Lmo0799 and the stress sigma factor SigB. It was found that both blue (455 nm) and red (625 nm) light induced the transcription of sigB and SigB-dependent genes, this induction was completely abolished in the SigB mutant. The blue-light effect was largely dependent on Lmo0799, proving that this protein is a genuine blue-light receptor. The deletion of lmo0799 enhanced the red-light effect, the underlying mechanism as well as that of SigB activation by red light remains unknown. Blue light led to an increased transcription of the internalin A/B genes and of bacterial invasiveness for Caco-2 enterocytes. Exposure to blue light also strongly inhibited swimming motility of the bacteria in a Lmo0799- and SigB-dependent manner, red light had no effect there. Conclusions/Significance: Our data established that visible, in particular blue light is an important environmental signal with an impact on gene expression and physiology of the non-phototrophic bacterium L. monocytogenes. In natural environments these effects will result in sometimes random but potentially also cyclic fluctuations of gene activity, depending on the light conditions prevailing in the respective habitat.},
  subject      = {Listeria monocytogenes},
  language  = {en}
}
@phdthesis{Schneider2011,
  author    = {Schneider, Matthias},
  title     = {Characterisation of Metalloprotease-mediated EGFR Signal Transactivation after GPCR Stimulation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65105},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {In the context of metalloprotease-mediated transactivation of the epidermal growth factor receptor, different monoclonal antibodies against ADAM17 / TACE were characterized for their ability to block the sheddase. Activity of some of them was observed at doses between 2µg/mL and 10µg/mL. Kinetic analyses showed their activity starting at around 30 minutes. In cellular assays performed with the antibodies, especially upon treatment of cells with sphingosine-1-phosphate a reduction in proliferation was observed with some candidates. Moreover this study provides potential new roles for ß-Arrestins. Their involvement in the triple membrane-passing signal pathway of EGFR transactivation was shown. Furthermore, in overexpressing cellular model systems, an interaction between ADAM17 and ß-Arrestin1 could be observed. Detailed analysis discovered that phosphorylation of ß-Arrestin1 is crucial for this interaction. Additionally, the novel mechanism of UV-induced EGFR transactivation was extended to squamous cell carcinoma. The mechanism happens in a dose dependent manner and requires a metalloprotease to shed the proligand Amphiregulin. The involvement of both ADAM9 and ADAM17, being the metalloproteases responsible for this cleavage, was shown for SCC9 cells.},
  subject      = {Epidermaler Wachstumsfaktor-Rezeptor},
  language  = {en}
}
@phdthesis{Schmull2011,
  author    = {Schmull, Sebastian},
  title     = {Charakterisierung der pathogenetisch-relevanten Rolle von SF1 beim Nebennierenrindenkarzinom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66398},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Tumore der Nebennieren stellen h{\"a}ufige Tumore dar, welche bei mindestens 3 \% der Population {\"u}ber 50-J{\"a}hriger vorkommen. Im Gegensatz dazu ist das Nebennierenrindenkarzinom mit einer Inzidenz von 1-2 Einwohner pro Million ein sehr seltener Tumor. Da seine Prognose allerdings ung{\"u}nstig, und diese maßgeblich davon abh{\"a}ngt wie fortgeschritten der Tumor bei Diagnosestellung ist, ist es wichtig, dass die richtige Diagnose fr{\"u}hzeitig gestellt wird. Bis heute ist kein zuverl{\"a}ssiger immunhistochemischer Nebennierenrindenkarzinom-spezifischer Marker etabliert um das Nebennierenrindenkarzinom von anderen retroperitonealen Tumoren zu differenzieren. Sasano et al. schlug bereits 1995 erstmalig den Transkriptionsfaktor Steroidogenic Factor 1 (SF1) als Marker zur Differenzierung von Nebennierenrinden- und Nicht-Nebennierenrindentumoren vor. Allerdings wurde die diagnostische Wertigkeit bisher nur in sehr kleinen Fallserien mit insgesamt nur 17 Nebennierenrindenkarzinomen untersucht. In der vorliegenden Arbeit wurde die SF1 Protein-Expression bei 163 Nebennierenrindenkarzinomen, 52 Nebennierenrinden-Adenomen, 12 normalen steroidogenen Geweben (6 Nebennieren und 6 Ovare), sowie 73 Nicht-Steroidtumoren immunhistochemisch untersucht. Hierbei zeigte sich, das SF1 bei 158 von 161 evaluierbaren Nebennierenrindenkarzinomen und bei allen Proben von normalen und gutartigen Geweben (n=64) nachweisbar war. Im Gegensatz dazu war keine der 73 Nicht-Steroidgeweben SF1 positiv, so dass die diagnostische Genauigkeit extrem gut ist (Sensitivit{\"a}t: 98.6 \%, Spezifit{\"a}t: 100 \%, positive und negative predictive value jeweils 100 \% und 97.3 \%). In einem zweiten Schritt wurde untersucht ob die Protein-Expression von SF1 beim Nebennierenrindenkarzinom auch prognostische Bedeutung hat. Hierbei zeigte sich, dass Patienten mit Tumoren mit starker SF1 F{\"a}rbung (30 \%) ein deutlich schlechteres tumorstadium-adjustiertes Rezidiffreies- und Gesamt-{\"U}berleben haben als Patienten mit geringer SF1 Expression (hazard ratio: 2.45). Zus{\"a}tzlich zu den immunhistochemischen Untersuchungen wurden FISH Analysen durchgef{\"u}hrt. Hierbei zeigte sich allerdings keine signifikante Korrelation zwischen SF1 Gendosis und der SF1 Protein-Expression, so dass zu vermuten ist, dass SF1 maßgeblich auf Transkriptions- und Translationsebene reguliert wird. In einem Versuch diese Frage zu beantworten wurden zwei mutmaßliche SF1 Interaktionspartner, FATE1 und DAX1, genauer immunhistochemisch untersucht. Hierbei wurde deutlich, dass FATE1 bei 62 von 141 evaluierbaren Nebenierenrindenkarzinomen und 12 von 62 normalen und gutartigen Geweben nachweisbar war. Im Gegensatz hierzu waren alle 9 Nicht-Steroidgewebe FATE1 negativ. Dies zeigt, das FATE1 nicht zur Diagnostik nutzbar ist (Sensitivit{\"a}t: 61 \%, Spezifit{\"a}t: 100 \%, positive und negative predictive value 100 \% bzw. 14 \%). Die DAX1 Analyse zeigte, dass alle 20 normalen und gutartigen Gewebe eine positive DAX1 F{\"a}rbereaktion zeigten. Von 126 Nebennierenrindenkarzinomen waren 71 DAX1 positiv. Von den 8 untersuchten Nicht-Steroidgeweben waren 6 DAX1 positiv. Diese Ergebnisse belegen, dass auch DAX1 keine diagnostische Genauigkeit besitzt (Sensitivit{\"a}t: 56 \%, Spezifit{\"a}t: 25 \%, positive und negative predictive value 92 \% bzw. 4 \%). Die Untersuchung der prognostischen F{\"a}higkeiten von FATE1 und DAX1 zeigte, dass Patienten mit Tumoren mit starker FATE1 F{\"a}rbung (39 \%) ein schlechteres tumorstadium-adjustiertes Gesamt- aber nicht Rezidiffreies-{\"U}berleben haben als Patienten mit niedriger FATE1 Protein-Expression (hazard ratio: 2.01). Weiterhin wurde deutlich, dass DAX1 keine deutlichen prognostischen F{\"a}higkeiten besitzt. Zusammenfassend l{\"a}ßt sich aus der vorliegenden Arbeit folgern, das SF1 aktuell der beste diagnostische Marker zur Diagnose von Tumoren der Nebennierenrinde ist und damit Eingang in die histopathologische Routine-Diagnostik von Nebennierentumoren finden wird. Zus{\"a}tzlich ist die SF1 Expression ein sehr guter prognostischer Marker beim Nebennierenrindenkarzinom, wobei sich die prognostische Aussage durch zus{\"a}tzliche F{\"a}rbung von FATE1 und DAX1 nur unwesentlich verbessern l{\"a}ßt.},
  subject      = {Nebennierenrindenkrebs},
  language  = {de}
}
@phdthesis{Keidel2011,
  author    = {Keidel, Kristina},
  title     = {Charakterisierung des Hfq-Regulons in Bordetella pertussis und Bordetella bronchiseptica},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66677},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Bordetellen sind Gram-negative Kokkobazillen, die phylogenetisch zu den β-Proteobakterien z{\"a}hlen und in der Familie der Alcaligenaceae eingeordnet sind. Der bedeutendste Vertreter der Gattung, die nach heutigem Kenntnisstand neun Arten umfasst, ist Bordetella pertussis, der Erreger des Keuchhustens. Der Keim ist obligat humanpathogen und besitzt zahlreiche Virulenzfaktoren, um die Epithelzellen des Respirationstraktes zu besiedeln und zu zerst{\"o}ren, wodurch es zu dem charakteristischen Krankheitsverlauf kommt. Neben B. pertussis werden noch B. bronchiseptica und B. parapertussis dem sogenannten B. bronchiseptica-Cluster zugeteilt. Alle Vertreter des B. bronchiseptica-Clusters sind in der Lage, bei verschiedenen Wirtsspezies respiratorische Erkrankungen mit unterschiedlichem Schweregrad auszul{\"o}sen. Dabei weist B. bronchiseptica ein breiteres Wirtsspektrum auf und kann Atemwegserkrankungen in einer Vielzahl von S{\"a}ugetieren ausl{\"o}sen, wohingegen B. parapertussis vornehmlich Schafe und Menschen infiziert und bei letzteren eine schw{\"a}chere Form des Keuchhustens bewirkt. Das Hfq-Protein wurde urspr{\"u}nglich als Wirtsfaktor identifiziert, welcher f{\"u}r die Replikation des RNA-Phagen Qβ in Escherichia coli ben{\"o}tigt wird (host factor for Qβ oder HF-1). Es ist in Struktur und Funktion homolog zu den Sm-Proteinen aus Eukaryoten, die am Splicing von mRNAs involviert sind. Die Beteiligung des Hfq-Proteins an regulatorischen Vorg{\"a}ngen, die durch kleine nicht-kodierende RNAs (sRNAs) vermittelt werden, wurde erstmals in einer Studie zum Mechanismus der rpoS-Regulation durch die kleine regulatorische RNA OxyS ersichtlich. Seitdem konnte f{\"u}r eine Vielzahl an sRNAs gezeigt werden, dass sie an Hfq gebunden vorliegen und die Hilfe des Proteins bei der post-transkriptionellen Kontrolle ihrer Ziel-mRNAs ben{\"o}tigen. In dieser Hinsicht {\"u}bernimmt Hfq die Rolle eines RNA-Chaperons, indem es trans-kodierte sRNAs stabilisiert und die Basenpaarung mit ihren Ziel-mRNAs f{\"o}rdert. Dabei beeinflusst die Bindung der sRNA-Regulatoren an ihre Ziel-mRNAs deren Translation, sowohl aktivierend als auch inhibierend. Bislang wurden Hfq-Homologe in der H{\"a}lfte aller sequenzierten Gram-positiven und Gram-negativen Bakterienarten gefunden. Eine BLAST-Analyse ergab, dass B. pertussis und B. bronchiseptica Homologe zum Hfq-Protein aufweisen und diese in der ver{\"o}ffentlichten Genomsequenz bereits als Hfq-Protein annotiert sind. Fokus dieser Arbeit war weitestgehend, die Funktion des Hfq-Proteins in B. pertussis und vergleichend in B. bronchiseptica zu charakterisieren. Mittels Primer Extension-Analyse konnte zun{\"a}chst der Startpunkt des hfq-Transkripts in B. pertussis und B. bronchiseptica unter logarithmischen Wachstumsbedingungen bestimmt werden. Dieser Startpunkt war zudem unter station{\"a}ren Wachstumsbedingungen und nach Hitzestress aktiv, was in Diskrepanz zur Beobachtung in E. coli steht. Ferner konnte festgestellt werden, dass die hfq-Transkription nach Induktion verschiedener Stressformen in beiden Organismen erh{\"o}ht war. Nach Generierung der jeweiligen Δhfq-Mutanten in beiden Organismen wurden diese charakterisiert. Die B. pertussis Δhfq-Mutante zeigte ein deutliches Wachstumsdefizit gegen{\"u}ber dem Wildtyp, im Gegensatz zu B. bronchiseptica Δhfq, die sich im Wachstum wie der Wildtyp verhielt. Beide Mutanten zeigten sich sensitiver gegen{\"u}ber H2O2-Stress als der Wildtyp, nicht jedoch gegen{\"u}ber weiteren oxidativen Stressbedingungen oder Membranstress induzierenden Substanzen. Die Δhfq-Mutante in B. pertussis war zudem in ihrer F{\"a}higkeit zur Biofilmbildung beeintr{\"a}chtigt, was jedoch nicht f{\"u}r B. bronchiseptica Δhfq galt. Da Hfq an sRNA-mRNA-Interaktionen, welche die Translation der mRNAs beeinflussen, beteiligt ist, sollte {\"u}ber 2D-Gelelektrophorese das Hfq-regulierte Proteom in B. pertussis und B. bronchiseptica bestimmt werden. Auff{\"a}llig war, dass viele periplasmatische Transport-bindeproteine von der Δhfq-Mutation betroffen waren. Es zeigten sich aber auch Stoffwechselenzyme und wichtige Housekeeping-Faktoren, wie z. B. der Elongationsfaktor EF-Tu und das Chaperon GroEL, in der Δhfq-Mutante dereguliert. Generell scheint das Hfq-regulierte Proteom in B. pertussis und B. bronchiseptica nur einen kleinen Teil des gesamten Proteoms auszumachen. Zudem ist das Hfq-regulierte Proteom variabel zwischen verschiedenen Wachstumsbedingungen, aber auch zwischen den beiden Organismen trotz der engen Verwandtschaft. Die Expression ausgew{\"a}hlter Virulenzfaktoren zeigte keinen Unterschied zwischen Δhfq-Mutante und B. pertussis-Wildtyp.},
  subject      = {Bordetella pertussis},
  language  = {de}
}
@article{EndesfelderMalkuschFlottmannetal.2011,
  author    = {Endesfelder, Ulrike and Malkusch, Sebastian and Flottmann, Benjamin and Mondry, Justine and Liguzinski, Piotr and Verveer, Peter J. and Heilemann, Mike},
  title     = {Chemically Induced Photoswitching of Fluorescent Probes - A General Concept for Super-Resolution Microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74896},
  year      = {2011},
  abstract  = {We review fluorescent probes that can be photoswitched or photoactivated and are suited for single-molecule localization based super-resolution microscopy. We exploit the underlying photochemical mechanisms that allow photoswitching of many synthetic organic fluorophores in the presence of reducing agents, and study the impact of these on the photoswitching properties of various photoactivatable or photoconvertible fluorescent proteins. We have identified mEos2 as a fluorescent protein that exhibits reversible photoswitching under various imaging buffer conditions and present strategies to characterize reversible photoswitching. Finally, we discuss opportunities to combine fluorescent proteins with organic fluorophores for dual-color photoswitching microscopy.},
  subject      = {Super-Resolution Microscopy},
  language  = {en}
}
@article{EndesfelderMalkuschFlottmannetal.2011,
  author    = {Endesfelder, Ulrike and Malkusch, Sebastian and Flottmann, Benjamin and Mondry, Justine and Liguzinski, Piotr and Verveer, Peter J. and Heilemann, Mike},
  title     = {Chemically Induced Photoswitching of Fluorescent Probes - A General Concept for Super-Resolution Microscopy},
  series = {Molecules},
  volume    = {16},
  journal   = {Molecules},
  number    = {4},
  doi       = {10.3390/molecules16043106},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134080},
  pages     = {3106-3118},
  year      = {2011},
  abstract  = {We review fluorescent probes that can be photoswitched or photoactivated and are suited for single-molecule localization based super-resolution microscopy. We exploit the underlying photochemical mechanisms that allow photoswitching of many synthetic organic fluorophores in the presence of reducing agents, and study the impact of these on the photoswitching properties of various photoactivatable or photoconvertible fluorescent proteins. We have identified mEos2 as a fluorescent protein that exhibits reversible photoswitching under various imaging buffer conditions and present strategies to characterize reversible photoswitching. Finally, we discuss opportunities to combine fluorescent proteins with organic fluorophores for dual-color photoswitching microscopy.},
  language  = {en}
}
@phdthesis{Batzilla2011,
  author    = {Batzilla, Julia},
  title     = {Complete genome sequence of Yersinia enterocolitica subspecies palearctica serotype O:3: Identification of novel virulence-associated genes and evolutionary aspects},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69668},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Yersinia enterocolitica subsp. palearctica Serobiotyp O:3/4 ist verantwortlich f{\"u}r 80-90 \% aller Yersiniosen beim Menschen in Deutschland und Europa. Y. enterocolitica Infektionen zeigen vielf{\"a}ltige Krankheitsbilder wie Gastroenteritis, Lymphadenitis und verschiedene Sp{\"a}tkomplikationen wie reaktive Arthritis. Das wichtigste Tierreservoir stellt das Hausschwein dar. Rohes Schweinefleisch in Metzgereien in Deutschland und anderen Regionen in Nord-Ost Europa ist h{\"a}ufig mit Yersinien kontaminiert (Bayern: 25 \%). Da sich Serobiotyp O:3/4-St{\"a}mme geografisch und phylogenetisch deutlich von dem bisher sequenzierten Serobiotyp O:8/1B Stamm 8081 unterscheiden, wurde eine komplette Genomsequenzierung des europ{\"a}ischen Serobiotyp O:3/4 DSMZ Referenzstammes Y11 (aus Patientenstuhl isoliert) durchgef{\"u}hrt. Um einen genaueren Einblick in die Y. enterocolitica subsp. palearctica Gruppe zu erhalten, wurden zus{\"a}tzlich zwei weitere Serobiotyp O:3/4 Isolate (Stamm Y8265, Patientenisolat, und Stamm Y5307, mit reaktiver Arthritis assoziiertes Patientenisolat), sowie ein eng verwandtes Y. enterocolitica subsp. palearctica Serobiotyp O:5,27/3 Isolat, Stamm Y527P, und zwei Biotyp 1A Isolate (ein Isolat nosokomialer Herkunft (Serogruppe O:5) und ein Umwelt-Isolat (O:36)) unvollst{\"a}ndig sequenziert. Die nicht mausvirulenten St{\"a}mme wurden mit dem mausvirulenten Y. enterocolitica subsp. enterocolitica Serobiotyp O:8/1B Stamm 8081 verglichen, um genetische Besonderheiten von Stamm Y11 und der Y. enterocolitica subsp. palearctica Gruppe zu identifizieren. Besonderer Fokus lag hierbei auf dem pathogenen Potential von Stamm Y11, um neue potentielle Virulenz Faktoren und Fitnessfaktoren zu identifizieren, darunter vor allem solche, die eine Rolle bei der Wirtsspezifit{\"a}t von Serobiotyp O:3/4 spielen k{\"o}nnten. Y. enterocolitica subsp. palearctica Serobiotyp O:3/4 St{\"a}mmen fehlen einige der Charakteristika der mausvirulenten Gruppe Y. enterocolitica subsp. enterocolitica, beispielsweise die Yersiniabactin kodierende‚ High-Pathogenicity Island (HPI), das Yts1 Typ 2 Sekretionssystem und das Ysa Typ 3 Sekretionssystem. Die Serobiotyp O:3/4-St{\"a}mme haben ein anderes Repertoir von Virulenz Faktoren erworben, darunter Gene bzw. genomische Inseln f{\"u}r das Ysp Typ 3 Sekretionssystem, Rtx-{\"a}hnliches putatives Toxin, Insektizid-Toxine und ein funktionelles PTS System f{\"u}r die Aufnahme von N-acetyl-galactosamin, dem aga-Operon. Nach dem Transfer des aga-Operons in Y. enterocolitica subsp. enterocolitica O:8/1B konnte Wachstum auf N-acetyl-galactosamin festgestellt werden. Neben diesen Genen k{\"o}nnen m{\"o}glicherweise auch zwei Prophagen (PhiYep-2 und PhiYep-3) und eine asn tRNA assoziierte genomische Insel (GIYep-01) zur Pathoadaptation von Y. enterocolitica subsp. palearctica Serobiotyp O:3/4 beitragen. Der PhiYep-3 Prophage und die GIYep-01 Insel weisen Rekombinationsaktivit{\"a}t auf, und PhiYep-3 wurde nicht in allen untersuchten Serobiotyp O:3/4 St{\"a}mmen gefunden. Y. enterocolitica subsp. palearctica Serobiotyp O:5,27/3 Stamm Y527P ist genetisch eng verwandt zu allen Serobiotyp O:3/4 Isolaten, wohingegen die Biotyp 1A Isolate ein mehr Mosaik-artiges Genom aufweisen und potentielle Virulenzgene sowohl mit Serobiotyp O:8/1B als auch O:3/4 gemeinsam haben, was einen gemeinsamen Vorfahren impliziert. Neben dem pYV Virulenz-Plasmid fehlen den Biotyp 1A Isolaten klassische Virulenzmarker wie das Ail Adhesin, das YstA Enterotoxin und das Virulenz-assoziierte Protein C (VapC). Interessanterweise gibt es keine betr{\"a}chtlichen Unterschiede zwischen den bekannten Virulenzfaktoren des nosokomialen Isolats und dem Umweltisolat der Biotyp 1A-Gruppe, abgesehen von einem verk{\"u}rzten Rtx Toxin-{\"a}hnlichem Genkluster und {\"U}berresten eines P2-{\"a}hnlichen Phagen im Krankenhausisolat der Serogruppe O:5.},
  subject      = {Genanalyse},
  language  = {en}
}
@article{PillaiHeidemannKumaretal.2011,
  author    = {Pillai, Deepu R. and Heidemann, Robin M. and Kumar, Praveen and Shanbhag, Nagesh and Lanz, Titus and Dittmar, Michael S. and Sandner, Beatrice and Beier, Christoph P. and Weidner, Norbert and Greenlee, Mark W. and Schuierer, Gerhard and Bogdahn, Ulrich and Schlachetzki, Felix},
  title     = {Comprehensive Small Animal Imaging Strategies on a Clinical 3 T Dedicated Head MR-Scanner; Adapted Methods and Sequence Protocols in CNS Pathologies},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0016091},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134193},
  pages     = {e16091},
  year      = {2011},
  abstract  = {Background: Small animal models of human diseases are an indispensable aspect of pre-clinical research. Being dynamic, most pathologies demand extensive longitudinal monitoring to understand disease mechanisms, drug efficacy and side effects. These considerations often demand the concomitant development of monitoring systems with sufficient temporal and spatial resolution. Methodology and Results: This study attempts to configure and optimize a clinical 3 Tesla magnetic resonance scanner to facilitate imaging of small animal central nervous system pathologies. The hardware of the scanner was complemented by a custom-built, 4-channel phased array coil system. Extensive modification of standard sequence protocols was carried out based on tissue relaxometric calculations. Proton density differences between the gray and white matter of the rodent spinal cord along with transverse relaxation due to magnetic susceptibility differences at the cortex and striatum of both rats and mice demonstrated statistically significant differences. The employed parallel imaging reconstruction algorithms had distinct properties dependent on the sequence type and in the presence of the contrast agent. The attempt to morphologically phenotype a normal healthy rat brain in multiple planes delineated a number of anatomical regions, and all the clinically relevant sequels following acute cerebral ischemia could be adequately characterized. Changes in blood-brain-barrier permeability following ischemia-reperfusion were also apparent at a later time. Typical characteristics of intracerebral haemorrhage at acute and chronic stages were also visualized up to one month. Two models of rodent spinal cord injury were adequately characterized and closely mimicked the results of histological studies. In the employed rodent animal handling system a mouse model of glioblastoma was also studied with unequivocal results. Conclusions: The implemented customizations including extensive sequence protocol modifications resulted in images of high diagnostic quality. These results prove that lack of dedicated animal scanners shouldn't discourage conventional small animal imaging studies.},
  language  = {en}
}
@article{CeteciXuCetecietal.2011,
  author    = {Ceteci, Fatih and Xu, Jiajia and Ceteci, Semra and Zanucco, Emanuele and Thakur, Chitra and Rapp, Ulf R.},
  title     = {Conditional Expression of Oncogenic C-RAF in Mouse Pulmonary Epithelial Cells Reveals Differential Tumorigenesis and Induction of Autophagy Leading to Tumor Regression},
  series = {Neoplasia},
  volume    = {13},
  journal   = {Neoplasia},
  number    = {11},
  doi       = {10.1593/neo.11652},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134347},
  pages     = {1005-1018},
  year      = {2011},
  abstract  = {Here we describe a novel conditional mouse lung tumor model for investigation of the pathogenesis of human lung cancer. On the basis of the frequent involvement of the Ras-RAF-MEK-ERK signaling pathway in human non-small cell lung carcinoma (NSCLC), we have explored the target cell availability, reversibility, and cell type specificity of transformation by oncogenic C-RAF. Targeting expression to alveolar type II cells or to Clara cells, the two likely precursors of human NSCLC, revealed differential tumorigenicity between these cells. Whereas expression of oncogenic C-RAF in alveolar type II cells readily induced multifocal macroscopic lung tumors independent of the developmental state, few tumors with type II pneumocytes features and incomplete penetrance were found when targeted to Clara cells. Induced tumors did not progress and were strictly dependent on the initiating oncogene. Deinduction of mice resulted in tumor regression due to autophagy rather than apoptosis. Induction of autophagic cell death in regressing lung tumors suggests the use of autophagy enhancers as a treatment choice for patients with NSCLC.},
  language  = {en}
}
@article{VogelLoeschbergerSaueretal.2011,
  author    = {Vogel, Benjamin and L{\"o}schberger, Anna and Sauer, Markus and Hock, Robert},
  title     = {Cross-linking of DNA through HMGA1 suggests a DNA scaffold},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68865},
  year      = {2011},
  abstract  = {Binding of proteins to DNA is usually considered 1D with one protein bound to one DNA molecule. In principle, proteins with multiple DNA binding domains could also bind to and thereby cross-link different DNA molecules. We have investigated this possibility using high-mobility group A1 (HMGA1) proteins, which are architectural elements of chromatin and are involved in the regulation of multiple DNA-dependent processes. Using direct stochastic optical reconstruction microscopy (dSTORM), we could show that overexpression of HMGA1a-eGFP in Cos-7 cells leads to chromatin aggregation. To investigate if HMGA1a is directly responsible for this chromatin compaction we developed a DNA cross-linking assay. We were able to show for the first time that HMGA1a can cross-link DNA directly. Detailed analysis using point mutated proteins revealed a novel DNA cross-linking domain. Electron microscopy indicates that HMGA1 proteins are able to create DNA loops and supercoils in linearized DNA confirming the cross-linking ability of HMGA1a. This capacity has profound implications for the spatial organization of DNA in the cell nucleus and suggests cross-linking activities for additional nuclear proteins.},
  subject      = {DNA},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery : A Web Tool for Easy Associative Querying of Transcriptome Data},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76088},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deepsequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  subject      = {CrossQuery},
  language  = {en}
}
@article{WagnerFischerThomaetal.2011,
  author    = {Wagner, Toni U. and Fischer, Andreas and Thoma, Eva C. and Schartl, Manfred},
  title     = {CrossQuery: A Web Tool for Easy Associative Querying of Transcriptome Data},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0028990},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134787},
  pages     = {e28990},
  year      = {2011},
  abstract  = {Enormous amounts of data are being generated by modern methods such as transcriptome or exome sequencing and microarray profiling. Primary analyses such as quality control, normalization, statistics and mapping are highly complex and need to be performed by specialists. Thereafter, results are handed back to biomedical researchers, who are then confronted with complicated data lists. For rather simple tasks like data filtering, sorting and cross-association there is a need for new tools which can be used by non-specialists. Here, we describe CrossQuery, a web tool that enables straight forward, simple syntax queries to be executed on transcriptome sequencing and microarray datasets. We provide deep-sequencing data sets of stem cell lines derived from the model fish Medaka and microarray data of human endothelial cells. In the example datasets provided, mRNA expression levels, gene, transcript and sample identification numbers, GO-terms and gene descriptions can be freely correlated, filtered and sorted. Queries can be saved for later reuse and results can be exported to standard formats that allow copy-and-paste to all widespread data visualization tools such as Microsoft Excel. CrossQuery enables researchers to quickly and freely work with transcriptome and microarray data sets requiring only minimal computer skills. Furthermore, CrossQuery allows growing association of multiple datasets as long as at least one common point of correlated information, such as transcript identification numbers or GO-terms, is shared between samples. For advanced users, the object-oriented plug-in and event-driven code design of both server-side and client-side scripts allow easy addition of new features, data sources and data types.},
  language  = {en}
}
@article{KraussGallenbergerSteffanDewenter2011,
  author    = {Krauss, Jochen and Gallenberger, Iris and Steffan-Dewenter, Ingolf},
  title     = {Decreased Functional Diversity and Biological Pest Control in Conventional Compared to Organic Crop Fields},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69005},
  year      = {2011},
  abstract  = {Organic farming is one of the most successful agri-environmental schemes, as humans benefit from high quality food, farmers from higher prices for their products and it often successfully protects biodiversity. However there is little knowledge if organic farming also increases ecosystem services like pest control. We assessed 30 triticale fields (15 organic vs. 15 conventional) and recorded vascular plants, pollinators, aphids and their predators. Further, five conventional fields which were treated with insecticides were compared with 10 non-treated conventional fields. Organic fields had five times higher plant species richness and about twenty times higher pollinator species richness compared to conventional fields. Abundance of pollinators was even more than one-hundred times higher on organic fields. In contrast, the abundance of cereal aphids was five times lower in organic fields, while predator abundances were three times higher and predator-prey ratios twenty times higher in organic fields, indicating a significantly higher potential for biological pest control in organic fields. Insecticide treatment in conventional fields had only a short-term effect on aphid densities while later in the season aphid abundances were even higher and predator abundances lower in treated compared to untreated conventional fields. Our data indicate that insecticide treatment kept aphid predators at low abundances throughout the season, thereby significantly reducing top-down control of aphid populations. Plant and pollinator species richness as well as predator abundances and predator-prey ratios were higher at field edges compared to field centres, highlighting the importance of field edges for ecosystem services. In conclusion organic farming increases biodiversity, including important functional groups like plants, pollinators and predators which enhance natural pest control. Preventative insecticide application in conventional fields has only short-term effects on aphid densities but long-term negative effects on biological pest control. Therefore conventional farmers should restrict insecticide applications to situations where thresholds for pest densities are reached.},
  subject      = {Landwirtschaft},
  language  = {en}
}
@phdthesis{Hauber2011,
  author    = {Hauber, Melanie Erika},
  title     = {Description and Improvement of the 'Whedo'-Aquaculture-System in Malanville (North of Benin)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57711},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {This work delves into the recently developed 'Whedo'-aquaculture-system in the rural community of Malanville (North Benin)and aims on providing a closer insight on this - for the area--recent system including the ecological but also the sociological and economical aspects in order to develop this extensive traditional fishery to a more productive semi-intensive aquaculture system. With the retreat of the flood 'Whedos' usually become infested with numerous hydato-and tenagophytes, while the presence and density of the free-floating macrophytes were positively related to the nutrient content of the 'Whedo'. Extensive plant infestation also affects water quality through the decomposition of organic material and its accumulation in thick mud layers on the pond bottom as well as through the nocturnal oxygen consumption. Unfavourable water quality, especially low dissolved oxygen as well as high conductivity and nitrite levels, was identified to be the main factor determining which fish species were able to survive the harsh conditions prevailing in the 'Whedos' during the dry season. With the deteriorating water quality with advancing dry season, fish diversity decreased significantly leaving only species that are highly adapted to such unfavourable conditions. The most abundant species were Clarias gariepinus, Heterotis niloticus, Oreochromis niloticus L., Hemichromis c.f. letourneauxi, Polypterus senegalus and Epiplatys spilargyreius. Besides, the investigations also concentrated on the fish diversity of the rivers Niger and Sota with the results that for three species distribution gaps could be closed and for further three species their already known distribution could be expanded. But otherwise it could also be detected that some economically important species that were abundant in the past. In regard to the 'Whedo'-management, the investigations showed that the owners lack most of the knowledge on appropriate management strategies, e.g. the feeding and stocking regime. The exploitation period depends on the extent of the previous annual flood and the location of the 'Whedo' within the floodplain, but the main season is from February to April. The biomass harvested on a hectare basis separated for each of the 'Whedos' averaged 17 tons/ha in 2008 and 8.6 tons/ha in 2009. However, 72 percent of the total biomass of Clarias only had an average weight of 40 grams. Therefore, two separated feeding trials were conducted and in total 6 supplementary feeds were tested on Clarias gariepinus. Groundnut cake, fish trash, rice bran, blood meal and azolla meal were used in different combination and rations to formulate the experimental diets. Diet containing 19 percent blood meal resulted in the best economical benefits showing that the use of high quality feed ingredients such as groundnut cake is not recommendable because local fish prices are too low to compensate the additional feeding costs. Instead of high quality feed farmers should focus on ingredients that are free of charge and easy to process. The supplementation based on 19 percent blood meal resulted in the doubling of the net profit compared to the income based on feeding only rice bran, thus provided higher additional income, enhancing the livelihood of the fish farmers. Concluding, the 'Whedo'-aquaculture system is still in its infancy but nevertheless is an attractive system for the rural population because of existing knowledge of post-flood wetland fisheries as well as the low investment needed for its installation. Additionally, the local fish supply will increase and hence not only contribute to a better provision of protein-rich food and reduced pressure on the wild fish stocks but might also prevent fish prices to increase in a way that the poor won't be able anymore to afford their most important source of animal protein. But fish farmers need more knowledge on appropriate management strategies and thus should be provided with technical support to guarantee a successful development and not to discourage the owners as a consequence of avoidable failures. Furthermore, the use of supplementary feed offers a cheap and effective means to increase the biomass production and thus enhance the extensive fishery to a semi-intensive aquaculture system.},
  subject      = {Aquakultur},
  language  = {en}
}
@phdthesis{Schneider2011,
  author    = {Schneider, Christof},
  title     = {Detecting the influence of different potential stress factors on the behavior of the honeybee Apis mellifera using Radiofrequency Identification (RFID)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71344},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {This study was conducted to determine the influence of different stress factors on the honeybee Apis mellifera. The investigation was motivated by previous experiments that suggested the existence of an unspecific defense mechanism causing a generalized change of flight behavior after the onset of different diseases. This mechanism is thought to impede the ability of flight bees to return to their respective colonies thereby removing the disease from the colony over time. During the last years, the existence of such a "suicidal behavior" was supported by further studies. Thus, an unnoticed, potentially highly effective defense mechanism of social insects was revealed whose spectrum of activity and physiological basics require further investigation. Suggesting that the reaction by the bees is unspecific to different diseases as well as to other potential stress factors, this study was designed to investigate the influence of pathogens, insecticides, and different brood rearing temperatures on different parameters like lifespan, foraging activity, and foraging trip duration of worker bees.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Donat2011,
  author    = {Donat, Ulrike},
  title     = {Detektion und Therapie von Metastasen des humanen Prostatakarzinoms durch das onkolytische Vaccinia-Virus GLV-1h68},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-56421},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Zurzeit sterben j{\"a}hrlich ca. 11.000 M{\"a}nner in Deutschland am Prostatakarzinom. Damit stellt dies die zweith{\"a}ufigste Krebstodesursache von M{\"a}nnern dar. Da das Prostatakarzinom h{\"a}ufig asymptomatisch verl{\"a}uft, wird die Erkrankung oftmals erst so sp{\"a}t erkannt, dass zum Zeitpunkt der Diagnose bereits eine Metastasierung stattgefunden hat. Durch metastasierende Prostatakarzinomzellen werden Lymphknoten, Knochen und Lungen befallen. Es sind zwei unterschiedliche Verbreitungsarten von metastasierenden Tumorzellen beschrieben. Zum einen kann eine Migration {\"u}ber Lymphgef{\"a}ße erfolgen, ein Prozess der als lymphatische Metastasierung bezeichnet wird. Zum anderen k{\"o}nnen Tumorzellen {\"u}ber das Blutsystem im K{\"o}rper zirkulieren: die h{\"a}matogene Metastasierung. In dieser Arbeit wurde die lymphatische Metastasierung der humanen Prostatakarzinomzellline PC-3 im Detail analysiert und Teilaspekte der h{\"a}matogenen Verteilung untersucht. Ausgangspunkt der Untersuchungen bildete die Vergr{\"o}ßerung lumbaler und renaler Lymphknoten in PC-3-Tumor-tragenden M{\"a}usen 60 Tage nach der Implantation von PC-3-Zellen. Es wurde daraufhin der zeitliche Verlauf der Vergr{\"o}ßerung untersucht und festgestellt, dass sowohl das Volumen als auch die Anzahl vergr{\"o}ßerter Lymphknoten von Woche zu Woche nach Implantation der PC-3-Tumore zunehmen. Anschließend wurden alle vergr{\"o}ßerten Lymphknoten bez{\"u}glich des Vorhandenseins von metastasierenden humanen PC-3-Zellen in den M{\"a}usen untersucht. Dies geschah mit Hilfe einer RT-PCR unter Verwendung von Primern f{\"u}r humanes β-Aktin. Sechs Wochen nach Implantation konnten in 90 \% der vergr{\"o}ßerten Lymphknoten PC-3-Zellen nachgewiesen werden. Weiterhin wurde durch lentivirale Transduktion das Gen f{\"u}r das rot fluoreszierende Protein (RFP) in die PC-3-Zellen inseriert, wodurch eine Visualisierung dieser Zellen in der Maus erm{\"o}glicht wurde. Es konnten metastasierende PC-3-RFP-Zellen in lumbalen und renalen Lymphknoten PC-3-RFP-Tumor-tragender M{\"a}use nachgewiesen werden. Ebenso konnte mittels RFP gezeigt werden, dass die Lymphknotenmetastasierung in Abh{\"a}ngigkeit von der Lokalisation des PC-3-RFP-Tumors erfolgt. Es kam zur Metastasierung jener Lymphknoten, in deren Einzugsgebiet sich der PC-3-Tumor befand. Es wurde eine PC-3-RFP-Zellmigration zwischen lumbalen und renalen Lymphknotenmetastasen nachgewiesen und bei immunhistologischen Untersuchungen stellte sich heraus, dass PC-3-RFP-Zellen tats{\"a}chlich in lymphatischen Bahnen zwischen lumbalen und renalen Lymphknotenmetastasen migrieren. Außerdem wurde gezeigt, dass es von Woche zu Woche nach Implantation von PC-3-Zellen zu einer Zunahme der Anzahl von Lymphgef{\"a}ßen in PC-3-Tumoren kommt. Die Zunahme der Lymphgef{\"a}ßdichte korrelierte hierbei positiv mit der Bildung von Lymphknotenmetastasen. Es konnten weiterhin neben Lymphknotenmetastasen h{\"a}matogene Mikrometastasen in den Lungen PC-3-RFP-Tumor-tragender M{\"a}use beobachtet werden. Da die Haupttodesursache von Prostatakarzinompatienten in der Bildung von Metastasen liegt, ist es von herausragender Bedeutung eine effektive Therapie gegen lymphatische und h{\"a}matogene Metastasen zu entwickeln. Aus diesem Grund erlangt die onkolytische Virustherapie große Bedeutung. Deshalb wurde als zweiter Aspekt in dieser Arbeit der Einfluss des onkolytischen Vaccinia-Virus GLV-1h68 auf den Prozess der PC-3-Zellmetastasierung untersucht. Dabei konnte zun{\"a}chst gezeigt werden, dass GLV-1h68 in der Lage ist, erfolgreich sowohl migrierende PC-3-Zellen als auch metastasierende PC-3-Zellen in Lymphknoten zu kolonisieren. In der Folge wurde deshalb ein m{\"o}glicher Metastasen-inhibierender Effekt von GLV-1h68 untersucht. Hierbei stellte sich heraus, dass GLV-1h68 drei Wochen nach intraven{\"o}ser Injektion eine signifikante Reduktion der Anzahl der f{\"u}r PC-3-Zellen positiven Lymphknoten bewirkt. Des Weiteren konnte ein inhibierender Effekt von GLV-1h68 auf die im Blut zirkulierenden PC-3-Zellen und auf h{\"a}matogene Metastasen in den Lungen beobachtet werden. Durch intraven{\"o}se Injektion von GLV-1h68 in PC-3-RFP-Tumor-tragenden M{\"a}usen konnte gezeigt werden, dass es zu einer pr{\"a}ferentiellen Virus-Kolonisierung der Lymphknotenmetastasen im Vergleich zu den Tumoren kommt. Auch nach intraperitonealer und intratumoraler Injektion von GLV-1h68 konnte eine pr{\"a}ferentielle Virus-Kolonisierung der Lymphknotenmetastasen gezeigt werden. Dar{\"u}ber hinaus wurden die Lymph- und Blutgef{\"a}ße von PC-3-Tumoren und Lymphknotenmetastasen analysiert. Hierbei wurde gezeigt, dass es sieben Tage nach intraven{\"o}ser Injektion von GLV-1h68 zu einer signifikanten Abnahme von beiden Gef{\"a}ßarten kam. Es wurde in dieser Arbeit somit gezeigt, dass GLV-1h68 in der Lage ist, sowohl lymphatische als auch h{\"a}matogene Metastasen der Prostatakarzinomzelllinie PC-3 erfolgreich zu eliminieren. Folglich d{\"u}rften onkolytische Vaccinia-Viren ein vielversprechendes Therapeutikum f{\"u}r die Behandlung des fortgeschrittenen Prostatakarzinoms darstellen.},
  subject      = {Prostatakrebs},
  language  = {de}
}
@phdthesis{Goeb2011,
  author    = {G{\"o}b, Eva},
  title     = {Die Kernh{\"u}lle in Keimzellen: Strukturelle Besonderheiten, dynamische Prozesse und die Umgestaltung des Zellkerns w{\"a}hrend der Spermatogenese der Maus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-56839},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Die Kernh{\"u}lle umgibt als geschlossenes Membransystem einen jeden Zellkern und ist damit ein gemeinsames Merkmal aller eukaryotischen Zellen. Sie besteht aus einer inneren und einer {\"a}ußeren Kernmembran sowie der nukleoplasmatischen Kernlamina, die aufgrund zahlreicher assoziierter Proteine in enger Wechselbeziehung mit der inneren Kernmembran steht. Neben der rein r{\"a}umlichen Trennung nukle{\"a}rer und zytoplasmatischer Strukturen hat die Kernh{\"u}lle bedeutenden regulatorischen Einfluss auf die gesamte Zelle. So ist sie unter anderem an der Steuerung der genomischen Aktivit{\"a}t, an der nukleo- und zytoplasmatischen Signal{\"u}bertragung und in hohem Maße an der Positionierung und Formerhaltung des Zellkerns beteiligt. Es mehren sich die Hinweise, dass die Kernh{\"u}lle auch w{\"a}hrend der Gametogenese, der Differenzierung befruchtungsf{\"a}higer Keimzellen, eine zentrale Rolle einnimmt und folglich auch mit bislang ungekl{\"a}rten Ursachen humaner Infertilit{\"a}t in Kontext stehen k{\"o}nnte. Um die Bedeutung der Kernh{\"u}lle f{\"u}r die Keimbahn der S{\"a}uger generell besser verstehen zu k{\"o}nnen, wurden in dieser Arbeit ausgew{\"a}hlte Bestandteile der Keimzellkernh{\"u}lle untersucht. Dadurch sollte der Kenntnisstand erweitert werden, in welcher Weise die Kernh{\"u}lle dynamische, morphologische und vor allem f{\"u}r die Keimbahn essentielle Prozesse beeinflusst; insbesondere w{\"a}hrend der meiotischen und der postmeiotischen Differenzierungsphase bei m{\"a}nnlichen M{\"a}usen. Im Mittelpunkt stand dabei einerseits Lamin C2, ein meiosespezifisches A-Typ Lamin, dessen Verlust zu einer schwer gesch{\"a}digten Meiose und infolgedessen zu vollst{\"a}ndiger m{\"a}nnlicher Infertilit{\"a}t f{\"u}hrt. Es zeigte sich, dass Lamin C2-defiziente m{\"a}nnliche M{\"a}use schwerwiegende Defekte bei der Paarung und Synapsis der homologen Chromosomen in der meiotischen Prophase I aufweisen und aufgrund apoptotischer Spermatocyten keine reifen Spermien bilden k{\"o}nnen. Es wird angenommen, dass die Assoziation homologer Chromosomen bzw. die Abstoßung nicht-homologer durch gerichtete Telomerbewegungen entlang der Kernh{\"u}llenperipherie vorangetrieben bzw. verhindert wird. Da Lamin C2 seinerseits diese Wanderung der Telomere durch eine Flexibilisierung der Spermatocytenkernh{\"u}lle vereinfachen soll, ist es durchaus vorstellbar, dass sein Verlust verlangsamte Telomerbewegungen, eine gest{\"o}rte Homologenfindung und folglich Fehlpaarungen zur Folge hat. Ein weiteres zentrales Thema war die Erforschung potentieller LINC-Komplexe w{\"a}hrend der Differenzierungs- und morphologischen Umgestaltungsphase postmeiotischer Keimzellen. LINC-Komplexe sind kernh{\"u}llendurchspannende Proteingebilde aus SUN-Proteinen in der inneren und Nesprinen in der {\"a}ußeren Kernmembran, die nukle{\"a}re Strukturen an das Zytoskelett binden. Da sie aufgrund dieser strukturellen Eigenschaft die Kernmorphologie beeinflussen k{\"o}nnen, erscheinen sie als {\"a}ußerst geeignet, an der Formierung des Spermienkopfes beteiligt zu sein. Die detaillierte Untersuchung spermiogeneserelevanter LINC-Komplex-Bestandteile ergab, dass w{\"a}hrend der Spermiogenese tats{\"a}chlich zwei neue, strukturell einzigartige LINC-Komplexe gebildet werden, die dar{\"u}ber hinaus auf den entgegengesetzten Seiten differenzierender Spermatiden polarisieren. Da sie den Kern dort an jeweils spezielle Zytoskelettelemente binden k{\"o}nnten, wurde in dieser Arbeit das Modell der LINC-Komplex vermittelten Umformung des Spermienkopfes aufgestellt. Insgesamt tr{\"a}gt diese Arbeit durch die funktionelle Analyse von Lamin C2 und die Identifizierung neuer LINC-Komplexe dazu bei, die Wichtigkeit der Kernh{\"u}lle f{\"u}r die Spermatogenese zu vertiefen und auszuweiten.},
  subject      = {Spermatogenese},
  language  = {de}
}
@phdthesis{Schuelein2011,
  author    = {Sch{\"u}lein, Christina},
  title     = {Die Regulation von Fbw7 durch PI3K-abh{\"a}ngige Phosphorylierung und Charakterisierung eines konditionalen Usp28-Knockout-Mausmodells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-70963},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Das Proto-Onkoprotein Myc ist an der Entstehung und Aufrechterhaltung einer Vielzahl humaner Tumore entscheidend beteiligt. In der vorliegenden Arbeit wurde Serin 227 in Fbw7 als Ziel f{\"u}r eine PI3K-abh{\"a}ngige Phosphorylierung identifiziert. Diese Phosphorylierung f{\"u}hrt zur Stabilisierung von Fbw7 und steigert die F{\"a}higkeit von Fbw7, Substratproteine zu ubiquitinieren und abzubauen. Um die Bedeutung von Usp28 in der Myc-induzierten Tumorentstehung und in der normalen Gewebehom{\"o}ostase zu untersuchen, wurde ein konditionales Knockout-Mausmodell f{\"u}r Usp28 charakterisiert. M{\"a}use mit einer Keimbahndeletion von Usp28 sind lebensf{\"a}hig, fertil und ph{\"a}notypisch unauff{\"a}llig. Weder in Organen der Usp28-negativen Tiere, noch in entsprechenden murinen embryonalen Fibroblasten kann eine Destabilisierung von Myc festgestellt werden. Allerdings zeigen Fibroblasten mit heterozygotem Usp28-Verlust einen Proliferationsdefekt und in Eμ-Myc-Lymphomen dieses Genotyps werden tendenziell niedrigere Myc-Proteinmengen gefunden. Das tumorfreie {\"U}berleben ist bei den Eμ-Myc; Usp28 +/- Tieren verl{\"a}ngert.},
  subject      = {Myc},
  language  = {de}
}
@phdthesis{Pillai2011,
  author    = {Pillai, Deepu},
  title     = {Differential effects of Pigment epithelium derived factor and epidermal growth factor on Ischemia-reperfusion injury in rats - a magnetic resonance imaging study at 3 tesla},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57341},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Stroke, after myocardial infarction and cancer is the third most common cause of death worldwide and 1/6th of all human beings will suffer at least one stroke in their lives. Furthermore, it is the leading cause for adult disability with approximately one third of patients who survive for the next 6 months are dependent on others. Because of its huge socioeconomic burden absorbing 6\% of all health care budgets and with the fact that life expectancy increases globally, one can assume that stroke is already, and will continue to be, the most challenging disease. Ischemic stroke accounts for approximately 80\% of all strokes and results from a thrombotic or embolic occlusion of a major cerebral artery (most often the middle cerebral artery, MCA) or its branches Following acute ischemic stroke, the most worrisome outcome is the rapidly increasing intra-cranial pressure due to the formation of space-occupying vasogenic oedema which can have lethal consequences. Permeability changes at the Blood-Brain Barrier (BBB) usually accompanies the oedematous development and their time course can provide invaluable insight into the nature of the insult, activation of compensatory mechanisms followed by long term repair. Rodent models of focal cerebral ischemia have been developed and optimized to mimic human stroke conditions and serve as indispensable tools in the field of stroke research. The presented work constituting of three separate but complete works by themselves are sequential, where, the first part was dedicated to the establishment of non-invasive small animal imaging strategies on a 3 tesla clinical magnetic resonance scanner. This facilitated the longitudinal monitoring of pathological outcomes following stroke where identical animals can serve as its own control. Tissue relaxometric estimations were carried out initially to derive the transverse (T2), longitudinal (T1) and the transverse relaxation time due to magnetic susceptibility effects (T2*) at the cortical and striatal regions of the rodent brain. Statistically significant differences in T2*-values could be found between the cortex and striatal regions of the rodent brain. The derived tissue relaxation values were considered to modify the existing imaging protocols to facilitate the study of the rodent model of ischemic stroke. The modified sequence protocols adequately characterized all the clinically relevant sequels following acute ischemic stroke, like, the altered perfusion and diffusion characteristics. Subsequent to this, serial magnetic resonance imaging was performed to investigate the temporal and spatial relationship between the biphasic nature of BBB opening and, in parallel, the oedema formation after I/R injury in rats. T2-relaxometry for oedema assessment was performed at 1 h after ischemia, immediately following reperfusion, and at 4, 24 and 48 hours post reperfusion. Post-contrast T1-weighted imaging was performed at the last three time points to assess BBB integrity. The biphasic course of BBB opening with significant reduction in BBB permeability at 24 hours after reperfusion was associated with a progressive expansion of leaky BBB volume, accompanied by a peak ipsilateral oedema formation. At 48 hours, the reduction in T2-value indicated oedema resorption accompanied by a second phase of BBB opening. In addition, at 4 hours after reperfusion, oedema formation could also be detected at the contralateral striatum which persisted to varying degrees throughout the study, indicative of widespread effects of I/R injury. The observations of this study may indicate a dynamic temporal shift in the mechanisms responsible for biphasic BBB permeability changes, with non-linear relations to oedema formation. Two growth factor peptides namely pigment epithelium derived factor (PEDF) and epidermal growth factor (EGF) with widely different trophic properties were considered for their beneficial effects, if any, in the established rodent model of I/R injury and studied up to one week employing magnetic resonance imaging. Both the selected, trophic factors demonstrated significant neuroprotection as demonstrated by a reduction in infarct volume, even though PEDF was found to be the most potent one. PEDF also demonstrated significant attenuation of oedema formation in comparison to both the control and EGF groups, even though EGF could also demonstrate oedema suppression. In the present work, we noticed that interventions with macromolecule protein/peptides by itself could mediate remote oedema at distant sites even though the significance of such an observation is not clear at present. Susceptibility (T2*) weighted tissue relaxometric estimations were considered at the infarct region to detect any metabolic changes arising out of any neuroprotection and/or cellular proliferation / neurogenesis. PEDF group demonstrated a striking reduction of the T2*-values, which is indicative of an increased metabolic activity. Moreover, all the groups (Control, EGF and PEDF) demonstrated significantly elevated T2*-values at the contralateral striatum, which is indicative of widespread metabolic suppression usually associated with a variety of traumatic brain conditions. Moreover, as expected from the properties of PEDF, it demonstrated an extended BBB permeability suppression throughout the duration of the study. This study underlines the merits of considering non-invasive imaging strategies without which it was not possible to study the required parameters in a longitudinal fashion. All the observations are adequately supported by reasonably well defined mechanisms and needs to be further verified and confirmed by an immunohistochemical study. These results also need to be complemented by a functional study to evaluate the behavioural outcome of animals following these treatments. These studies are progressing at our laboratory and the results will be duly published afterwards.},
  subject      = {Schlaganfall},
  language  = {en}
}
@article{VandenHoveJakobSchrautetal.2011,
  author    = {Van den Hove, Daniel and Jakob, Sissi Brigitte and Schraut, Karla-Gerlinde and Kenis, Gunter and Schmitt, Angelika Gertrud and Kneitz, Susanne and Scholz, Claus-J{\"u}rgen and Wiescholleck, Valentina and Ortega, Gabriela and Prickaerts, Jos and Steinbusch, Harry and Lesch, Klaus-Peter},
  title     = {Differential Effects of Prenatal Stress in 5-Htt Deficient Mice: Towards Molecular Mechanisms of Gene x Environment Interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75795},
  year      = {2011},
  abstract  = {Prenatal stress (PS) has been shown to influence the development of the fetal brain and to increase the risk for the development of psychiatric disorders in later life. Furthermore, the variation of human serotonin transporter (5-HTT, SLC6A4) gene was suggested to exert a modulating effect on the association between early life stress and the risk for depression. In the present study, we used a 5-Htt6PS paradigm to investigate whether the effects of PS are dependent on the 5-Htt genotype. For this purpose, the effects of PS on cognition, anxiety- and depression-related behavior were examined using a maternal restraint stress paradigm of PS in C57BL6 wild-type (WT) and heterozygous 5-Htt deficient (5-Htt +/2) mice. Additionally, in female offspring, a genome-wide hippocampal gene expression profiling was performed using the Affymetrix GeneChipH Mouse Genome 430 2.0 Array. 5-Htt +/2 offspring showed enhanced memory performance and signs of reduced anxiety as compared to WT offspring. In contrast, exposure of 5-Htt +/2 mice to PS was associated with increased depressive-like behavior, an effect that tended to be more pronounced in female offspring. Further, 5-Htt genotype, PS and their interaction differentially affected the expression of numerous genes and related pathways within the female hippocampus. Specifically, MAPK and neurotrophin signaling were regulated by both the 5-Htt +/2 genotype and PS exposure, whereas cytokine and Wnt signaling were affected in a 5-Htt genotype6PS manner, indicating a gene6environment interaction at the molecular level. In conclusion, our data suggest that although the 5-Htt +/2 genotype shows clear adaptive capacity, 5-Htt +/2 mice -particularly females- at the same time appear to be more vulnerable to developmental stress exposure when compared to WT offspring. Moreover, hippocampal gene expression profiles suggest that distinct molecular mechanisms mediate the behavioral effects of the 5-Htt genotype, PS exposure, and their interaction.},
  subject      = {Medizin},
  language  = {en}
}
@phdthesis{Thoma2011,
  author    = {Thoma, Eva Christina},
  title     = {Directed differentiation of pluripotent stem cells induced by single genes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-54706},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Pluripotency describes the ability of stem cells to form every cell type of the body.. Pluripotent stem cells are e.g. embryonic stem cells (ESCs), but also the so called induced pluripotent stem cells (IPS cells), that are generated by reprogramming differentiated somatic cells into a pluripotent state. Furthermore, it has been shown that spermatogonia (SG) derived from adult testes of mouse or human are pluripotent. Because of their ability to differentiate into every somatic cell type, pluripotent stem cells have a unique status in research and regenerative medicine. For the latter, they offer a valuable opportunity to replace destroyed tissues or organs. For basic research, stem cells represent a useful system to study differentiation or developmental processes that are difficult to access in the physiological situation e.g. during embryogenesis. Both applications, however, require methods that allow efficient and directed differentiation of stem cells into defined specialized cell types. This study first aims to investigate the differentiation potential of SG derived from the teleost fish medaka (Oryzias latipes). My results demonstrate that medaka SG are able to form different somatic cell types, namely adipocytes, melanocytes, osteoblasts, and neurons. This indicates that medake SG have retained a broad differentiation potential suggesting that pluripotency is not restricted to mouse and human SG but might be conserved among vertebrates. Next, I wanted to establish a differentiation method that is solely based on ectopic expression of genes known to be essential for the formation of certain somatic cell types - so called master regulators (MRs). My findings show that ectopic expression of the melanocyte-specific transcription factor mitf-m that has previously been shown to induce differentiation of medaka ESCs into pigment cells resulted in the formation of the same cell type in medaka SG. This approach could be used to generate other somatic cell types. Thus, ectopic expression of the MRs cbfa1 and mash1 in MF-SG was sufficient to induce differentiation into osteoblasts and neurons, respectively. Interestingly, these differentiation processes included the activation of genes that are expressed earlier during embryogenesis than the differentiation-inducing MR. Furthermore, my findings show that the approach of MR-induced differentiation can be transferred to mammalian stem cell systems. Ectopic expression of the neural transcription factor ngn2 was sufficient to induce efficient and rapid differentiation of neurons in mouse ESCs. This differentiation process also included the induction of genes that in vivo are activated at earlier stages that ngn2. By generating a transgenic cell line allowing induction of ectopic ngn2 expression, it was possible to obtain a relatively pure culture of functional neurons. Ngn2-induced differentiation did not require any additional signals and occurred even under pluripotency promoting conditions. Moreover, ectopic expression of ngn2 did also induce the formation of cells with neuronal morphology in IPS cells indicating that MR-induced differentiation is operative in different stem cell types. Furthermore, protein transduction of Ngn2 into mouse ESCs also resulted in a neuronal differentiation process up to the appearance of neural precursor cells. Last, my results show that MR-induced differentiation can also be used to generate other cell types than neurons from mouse ESCs. Myoblasts and macrophage-like cells were generated by ectopic expression of the MRs myoD and cebpa, respectively. Using transgenic cell lines enabling induction of MR expression it was possible to obtain mixed cultures with two different differentiation processes occurring in parallel. Altogether this study shows that ectopic expression of single genes is sufficient to induce directed differentiation of stem cells into defined cell types. The feasibility of this approach was demonstrated for different MRs and consequently different somatic cell types. Furthermore, MR induced differentiation was operative in different stem cell types from fish and mouse. Thus, one can conclude that certain genes are able to define cell fates in in vitro stem cell systems and that this cell fate defining potential appears to be a conserved feature in vertebrates. These findings therefore provide new insights in the role of MRs in cell commitment and differentiation processes. Furthermore, this study presents a new method to induce directed differentiation of stem cells that offers several advantages regarding efficiency, rapidness, and reproducibility. MR-induced differentiation therefore represents a promising tool for both stem cell research and regenerative medicine.},
  subject      = {Stammzelle},
  language  = {en}
}
@phdthesis{Duechs2011,
  author    = {D{\"u}chs, Matthias},
  title     = {Effects of Toll-like receptor agonists on the pathogenesis of atopic asthma in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66369},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {In the last decades, both the incidence and the severity of asthma have steadily increased. Furthermore, available therapies only treat the symptoms but do not cure the disease. Immune modulation induced by TLR agonists may be a promising novel approach to effectively treat asthma as it targets the underlying immunopathology directly rather than one mediator alone. The aim of this thesis was to investigate if the immunostimulatory properties of Toll-like receptor (TLR) agonists can be utilized to develop novel therapeutic intervention strategies for the treatment of asthma using murine models of allergic inflammation. For this purpose five different TLR agonists were tested in preclinical mouse models of acute and chronic asthma, both in preventive and therapeutic settings. Firstly, TLR-2, 3, 4, 7/8 and 9 agonists were delivered intratracheally at different doses before pulmonary allergen exposure in the asthma model of acute inflammation. TLR9 agonist CpG-containing oligodeoxynucleotides (CpG) > TLR7 agonist Resiquimod (R848) > TLR3 agonists poly(I:C) strongly reduced allergen induced airway eosinophilia and IL-4 levels in a dose-dependent manner. All TLR agonists increased neutrophil numbers, TLR4 agonist lipopolysaccharide (LPS) > TLR2 agonist lipoteichonic acid (LTA) > poly(I:C) > CpG > R848 and, with the exception of R848, the amount of pro-inflammatory cytokines in the airways. Suppressive effects were not dependent upon IFN-γ and IL-10 or associated with increased numbers of regulatory T cells in the airways. All TLR agonists, except LTA, similarly reduced airway eosinophilia and IL-4 levels when applied therapeutically after allergen challenge. These results show that the TLR agonists have different suppressive effects on TH2 responses in the airways which further depend on the dose and the experimental setup in which they were tested. Interestingly, all agonists induced airway neutrophilia, albeit to different degrees, raising the question if TLR ligands are safe for human use when applied directly into the lung. Different TLR agonists are also being developed for human use as adjuvants combined with allergen in specific immunotherapy. Recent clinical data suggest that this may be achieved by induction of allergen-specific TH1 responses. For this reason, the ability of different TLR agonists to induce allergen-specific TH1 and suppress allergen-specific TH2 responses in a preclinical setting was investigated in this thesis. Different doses of the TLR agonists were applied together with allergen, then mice were exposed to allergen aerosol. CpG > LPS >LTA dose-dependently strongly suppressed the development of airway eosinophilia with poly(I:C) and R848 having no effect. The decrease in eosinophilic numbers was associated withincreased neutrophils present in the airways. IL-4 and IL-5 levels in the bronchoalveolar lavage fluid were also decreased when poly(I:C), LPS, and CpG were used. All TLR agonists increased allergen-specific IgG2a, and with the exception of poly(I:C), reduced allergen-specific IgE levels in the serum. Cutaneous anaphylaxis to allergen was completely prevented when LPS or CpG were given as adjuvant. The strongest TH1 responses were induced by CpG and poly(I:C), characterized by the presence of IFN-γ in the bronchoalveolar lavage and the highest allergen-specific IgG2a levels in the serum. This data supports approaches to use TLR9 or TLR4 agonists for human therapy as adjuvant in combination with allergen in novel specific immunotherapy formulations. In the last part of the thesis, it was investigated if TLR activation can also affect the pathology of severe chronic asthma. Therapeutic administration of R848 or CpG reduced features of inflammation and remodeling. Both agonists showed superior effects to dexamethasone, with CpG being more efficient than R848. This result again supports a TLR9-based therapy as a viable option for the treatment of severe chronic asthma which may present a potential alternative for anti-inflammatory therapy with steroids. Taken together, the results of this thesis support the use of TLR agonists to treat asthma. The most favorable efficacy/safety ratio is to be expected from TLR-based therapies combining TLR4 or TLR9 agonists with allergen in specific immunotherapy. In regard to TLR agonist monotherapy, R848 and CpG showed the most promising profiles, CpG particularly in a model of severe chronic asthma. However, since all TLR agonists used in this study also showed pro-inflammatory potential, the safety aspect of such an approach needs to be taken into account.},
  subject      = {Toll-like Rezeptor},
  language  = {en}
}
@phdthesis{Wang2011,
  author    = {Wang, Huiqiang},
  title     = {Enhanced Replication of Vaccinia Virus GLV-1h68 in Cancer Stem-like Cells of Human Breast Cancer Cell Preparations},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64750},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {There is more and more evidence for the cancer stem cell hypothesis which believes that cancers are driven by a cellular subcomponent that has stem cell properties which is self-renewal, tumorigenicity and multilineage differentiation capacity. Cancer stem cells have been connected to the initiation of tumors and are even found to be responsible for relapses after apparently curative therapies have been undertaken. This hypothesis changes our conceptual approach of oncogenesis and shall have implications in breast cancer prevention, detection and treatment, especially in metastatic breast cancer for which no curative treatment exists. Given the specific stem cell features, novel therapeutic pathways can be targeted. Since the value of vaccinia virus as a vaccination virus against smallpox was discovered by E. Jenner at 18th century, it plays an important role in human medicine and molecular biology. After smallpox was successfully eradicated, vaccinia virus is mainly used as a viral vector in molecular biology and increasingly in cancer therapy. The outstanding capability to specifically target and destroy cancer cells makes it a perfect agent for oncolytic virotherapy. Furthermore, the virus can easily be modified by inserting genes which encode therapeutic or diagnostic proteins to be expressed when a tumor is infected. The emphasis in this study was the establishment of methods for the enrichment of human breast cancer stem-like cells from cancer cell lines and characterization of those cancer stem-like cells in vitro and in vivo. Furthermore, by using the Genelux Corporation vaccinia virus strain GLV-1h68, the isolated cancer stem-like cells can be targeted not only in vitro but also in vivo more efficiently. Side-population (SP) cells within cancers and cell lines are rare cell populations known to be enriched cancer stem-like cells. In this study, we used Hoechst 33342 staining and flow cytometry to identify SP cells from the human breast cancer cell lines MCF-7 and GI-101A as models for cancer stem-like cells. Considering the cytotoxicity of Hoechst dye and the restriction of instrument, we did not carry out further studies by this method. Utilizing in vitro and in vivo experimental systems, we showed that human breast cancer cell line GI-101A with aldehyde dehydrogenase activity (ALDH) have stemlike properties. Higher ALDH activity identifies the tumorigenic cell fraction which is capable of self-renewal and of generating tumors that could recapitulate the heterogeneity of the parental tumor. Furthermore, the cells with higher ALDH activity display significant resistance to chemotherapy and ionizing radiation, which proves their stem-like properties again. The cells which have higher ALDH activity also are more invasive compared to cells which have lower ALDH activity, which connects the cancer stem-like cells with cancer metastases. By analyzing the popular human breast cancer stem cells surface markers CD44, CD49f and CD24, it was discovered that the cells with higher ALDH activity have stronger CD44 and CD49f expression than in those cells with lower ALDH activity, which further confirms their stem-like properties. Finally, the cells with higher ALDH activity and lower ALDH activity were infected in vitro and used in virotherapy in a mouse xenograft model was performed. The results indicated that the vaccinia virus GLV-1h68 can replicate in cells with higher ALDH activity more efficiently than cells with lower ALDH activity. GLV-1h68 also can selectively target and eradicate the xenograft tumors which were derived from cells with higher ALDH activity. The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastases. EMT was induced in immortalized human mammary epithelial cells (HMLEs) and in GI-101A cells, which results in the acquisition of mesenchymal traits and in the expression of stem cell markers. Furthermore, the EMT-induced GI-101A cells showed resistance to chemotherapy and invasion capacity. CD44+/CD24- cells were enriched during the EMT induction. Following flow cytometry sorting by using CD44, CD24 and ESA surface marker, the sorted cells were tested in a mouse model regarding tumorigenicity. Unexpectedly, we found that CD44+/CD24+/ESA+ cells could initiate tumors more efficiently rather than CD44+/CD24-/ESA+ and other fractions in EMTinduced GI-101A cells. We also infected the CD44+/CD24+/ESA+ and CD44+/CD24- /ESA+ cells in vitro and performed virotherapy in a mouse xenograft model. The results indicated that the vaccinia virus GLV-1h68 is able to replicate in CD44+/CD24+/ESA+ cells more efficiently than in CD44+/CD24-/ESA+ cells. GLV-1h68 was also capable to selectively target and eradicate the xenograft tumors which derived from CD44+/CD24+/ESA+ cells. Moreover, CD44- cells have much lower tumorigenicity in the mouse model and CD44- cells derived-tumors are not responsive to vaccinia virotherapy. In summary, we have successfully established an in vitro and in vivo system for the identification, characterization and isolation of cancer stem-like cells from the human breast cancer cell line GI-101A by using the ALDEFLUOR assay. The vaccinia virus GLV-1h68 was able to efficiently target and eradicate the higher ALDH activity cells and tumors derived from those cells. Although contrary to the current assumption, CD44+/CD24+/ESA+ cells in the EMT-induced GI-101A cell line showed stem-like properties and GLV-1h68 was able to efficiently target and eradicate the CD44+/CD24+/ESA+ cells and tumors which derived from those cells. Finally, improved understanding of cancer stem cells may have tremendous relevance for how cancer should be treated. It is menacing that cancer stem cells are resistant to almost all anti-tumor approaches which have already been established for the treatment of metastatic diseases such as ionizing radiation, hormonal therapy, chemotherapy, and small molecular inhibitors. Therefore, it is promising that our results suggest that these cancer stem cells may be susceptible to treatment with oncolytic vaccinia virus.},
  subject      = {Vaccinia Virus},
  language  = {en}
}
@phdthesis{ElHajj2011,
  author    = {El Hajj, Nady},
  title     = {Epimutations in Germ-Cell and Embryo Development: Possible Consequences for Assisted Reproduction},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65995},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Assisted reproductive technologies (ART) emerged in the late 1970's as a therapy for human infertility. Up till now more than 3 million babies have been conceived through ART, demonstrating the safety and efficiency of the technique. Published reports showed an increase in the rate of imprinting disorders (Beckwith Wiedemann Syndrome, Angelman Syndrome, etc.) in babies born after ART. What are the effects imposed through ART and should researchers reassess its safety and implications on the future offspring? Throughout this thesis, I analyzed the methylation patterns of germ cells and embryos to determine whether in vitro maturation and in vitro fertilization have a negative impact on the epigenetic patterns. Furthermore, DNA methylation was compared between sperm of infertile and presumably fertile controls in order to understand whether epigenetic disturbances lead to infertility at the first place. The occurrence of methylation aberrations in germ cells of infertile patients could be transmitted to new-borns and then cause epigenetic disorders. In order to elucidate the imprinting status within single cells, I developed a new technique based on limiting dilution where bisulfite treated DNA is distributed across several wells before amplification. This allowed methylation measurement at the single allele level as well parent of origin detection. In a total of 141 sperm samples from couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) including 106 with male factor or combined infertility and 28 with female infertility, I detected a significant correlation between lower quality of semen parameters (sperm count, percentage of abnormal sperm, and percentage of motile sperm) and the rate of imprinting errors. ALU repeats displayed a higher methylation in sperm DNA of patients leading to a pregnancy and live birth, compared to patients in which pregnancy was not achieved or a spontaneous abortion occurred. A discriminant analysis based on ALU methylation allowed correct classification of >70\% of cases. Preliminary data from illumina methylation arrays where more than 27,000 CpGs were analyzed determined that only a single CpG site from the open reading frame C14orf93 was significantly different between the infertile and presumably fertile control group. However, further improvements on data normalization might permit detection of other differentially methylated regions. Comparison of embryos after natural conception, in vitro fertilized embryos from superovulated oocytes, and embryos achieved through fertilization of in vitro cultured oocytes revealed no dramatic effect on the imprinting patterns of Igf2r, H19, and Snrpn. Oocyte cryotop vitrification did not result in a dramatic increase of imprinting mutations in oocytes even though the rate of sporadic methylation errors in single Snrpn CpGs were higher within the in-vitrified group. Collectively, the results I will present within this thesis suggest an increase in the rate of imprinting errors within the germ cells of infertile patients, in addition to a decrease in genome wide methylation of ALU repetitive elements. I did not observe a detrimental effect on the methylation patterns of oocytes and the resulting embryos using in vitro maturation of oocytes and/or standard IVF with in vivo grown superovulated oocytes.},
  subject      = {Reproduktionsmedizin},
  language  = {en}
}
@phdthesis{Kroker2011,
  author    = {Kroker, Katja},
  title     = {Establishment and validation of hippocampal LTP for characterization of memory enhancing drugs as potential treatment of Alzheimer's disease},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85412},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Die Alzheimer'sche Erkrankung ist eine neurodegenerative Erkrankung des Gehirns. Um geeignete Medikamente f{\"u}r die Behandlung der Alzheimer'schen Erkrankung zu finden, werden experimentelle Modellsysteme zur Erforschung von Substanzkandidaten verwendet. Ein solches experimentelles System ist die hippocampale Langzeitpotenzierung (LTP), welche ein anerkanntes in vitro Modell f{\"u}r die Erforschung der zugrundeliegenden zellul{\"a}ren Prozesse der Ged{\"a}chtnisbildung ist. Die vorliegende Arbeit besch{\"a}ftigt sich mit der Etablierung und Validierung von LTP in hippocampalen Hirnschnitten der Ratte um ged{\"a}chtnissteigernde Substanzen zur potentiellen Behandlung der Alzheimer'schen Erkrankung zu charakterisieren. Dazu wurde zun{\"a}chst ein Messsystem zur parallelen Charakterisierung mehrerer Schnitte aufgebaut, das Messungen bis zu sieben Stunden erlaubt (Kapitel 2). Dann wurden unterschiedliche Protokolle etabliert um Fr{\"u}h- und Sp{\"a}tphasen-LTP zu generieren. Dabei w{\"u}rde Fr{\"u}hphasen-LTP konzeptionell eher mit dem Kurzzeitged{\"a}chtnis einhergehen, w{\"a}hrend Sp{\"a}tphasen-LTP dem Langzeitged{\"a}chtnis gleichkommen w{\"u}rde (Kapitel 3). Da in Alzheimer-Patienten haupts{\"a}chlich ein Defizit cholinerger und glutamaterger Neurone vorliegt, wurden die validierten LTP Formen benutzt, um solche Substanzen zu analysieren, die potentiell cholinerge und/oder glutamaterge neuronale Funktion erh{\"o}hen. Die Effekte zweier ausschließlich cholinerge Funktion erh{\"o}hender Substanzen wurden analysiert: Der α4β2 nicotinische Acetylcholin-Rezeptor Agonist TC-1827 (Kapitel 4) und der Acetylcholinesterase-Inhibitor Donepezil (Kapitel 5). Beide Substanzen erh{\"o}hten Fr{\"u}hphasen-LTP, aber hatten keinen Effekt auf Sp{\"a}tphasen-LTP. Desweiteren wurden zwei Substanzen getestet, die ausschließlich mit glutamaterger Funktion interferieren: Der metabotrope Glutamatrezeptor 5 positiv allosterische Modulator ADX-47273 (Kapitel 3) und der Phosphodiesterase (PDE) 9A-Inhibitor BAY 73-6691 (Kapitel 5). ADX-47273 erh{\"o}hte Sp{\"a}tphasen-LTP, aber hatte keinen Effekt auf Fr{\"u}hphasen-LTP, wohingegen BAY 73-6691 eine erh{\"o}hende Wirkung auf beide LTP Formen aufwies und sogar Fr{\"u}h- in Sp{\"a}tphasen-LTP umwandelte. Die gleichen Effekte, wie bei dem PDE9A-Inhibitor, konnten auch mit dem partiellen α7 nicotinische Acetylcholin-Rezeptor Agonisten SSR180711 (Kapitel 4) demonstriert werden. SSR180711 wirkt sowohl auf cholinerge, als auch auf glutamaterge neuronale Funktion. Dann wurde die F{\"a}higkeit der Substanzen {\"u}berpr{\"u}ft, durch l{\"o}sliche Aβ Oligomere verschlechtertes LTP zu verbessern (Kapitel 6). L{\"o}sliche Aβ Oligomere, auch als amyloid-β derived diffusible ligands (ADDLs) bezeichnet, werden zurzeit als eine mutmaßliche Ursache der Alzheimer'schen Erkrankung angesehen. In der vorliegenden Arbeit wurde gezeigt, dass ADDLs Fr{\"u}h- und Sp{\"a}tphasen-LTP in verschiedenem Ausmaß vermindern. Donepezil und TC-1827 konnten die durch ADDLs induzierten Defizite bei Fr{\"u}hphasen-LTP geringf{\"u}gig wiederherstellen, aber sie hatten keinen Einfluss auf das durch ADDLs verschlechterte Sp{\"a}tphasen-LTP. Im Gegensatz dazu, konnten sowohl SSR180711 als auch BAY 73-6691 ein durch ADDLs verschlechtertes Fr{\"u}h- und Sp{\"a}tphasen-LTP komplett wiederherstellen. ADX-47273 hatte keinen positiven Effekt auf Fr{\"u}hphasen-LTP, welches durch ADDLs verschlechtert worden war, konnte aber ein durch ADDLs verschlechtertes Sp{\"a}tphasen-LTP teilweise wiederherstellen. Somit wurde der vorherige Befund der Arbeit best{\"a}tigt: Substanzen, welche die glutamaterge Funktion verbessern, scheinen nicht nur wirksamer im Bezug auf LTP-Erh{\"o}hung zu sein als Substanzen die ausschließlich cholinerge Funktion erh{\"o}hen, sondern sie sind auch in der Lage, durch l{\"o}sliche Aβ Oligomere verursachte Defizite bei LTP zu verbessern. Aus einem pr{\"a}klinischen Blickwinkel und basierend auf den Ergebnissen der vorliegenden Arbeit weisen demnach Substanzen, die glutamaterge Funktionen verbessern, ein hohes therapeutisches Potential als alternative Ans{\"a}tze bez{\"u}glich kognitiver Defizite auf. M{\"o}glicherweise k{\"o}nnten sie sogar wirksamere Ans{\"a}tze f{\"u}r die symptomatische Behandlung der Alzheimer'schen Erkrankung darstellen, als derzeitige Behandlungen, die ausschließlich cholinerge Funktion verbessern.},
  subject      = {Alzheimerkrankheit},
  language  = {en}
}
@article{KarunakaranMehlitzRudel2011,
  author    = {Karunakaran, Karthika and Mehlitz, Adrian and Rudel, Thomas},
  title     = {Evolutionary conservation of infection-induced cell death inhibition among Chlamydiales},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68978},
  year      = {2011},
  abstract  = {Control of host cell death is of paramount importance for the survival and replication of obligate intracellular bacteria. Among these, human pathogenic Chlamydia induces the inhibition of apoptosis in a variety of different host cells by directly interfering with cell death signaling. However, the evolutionary conservation of cell death regulation has not been investigated in the order Chlamydiales, which also includes Chlamydia-like organisms with a broader host spectrum. Here, we investigated the apoptotic response of human cells infected with the Chlamydia-like organism Simkania negevensis (Sn). Simkania infected cells exhibited strong resistance to apoptosis induced by intrinsic stress or by the activation of cell death receptors. Apoptotic signaling was blocked upstream of mitochondria since Bax translocation, Bax and Bak oligomerisation and cytochrome c release were absent in these cells. Infected cells turned on pro-survival pathways like cellular Inhibitor of Apoptosis Protein 2 (cIAP-2) and the Akt/PI3K pathway. Blocking any of these inhibitory pathways sensitized infected host cell towards apoptosis induction, demonstrating their role in infection-induced apoptosis resistance. Our data support the hypothesis of evolutionary conserved signaling pathways to apoptosis resistance as common denominators in the order Chlamydiales.},
  subject      = {Chlamydiales},
  language  = {en}
}
@article{GoebMeyerNatusBenaventeetal.2011,
  author    = {G{\"o}b, Eva and Meyer-Natus, Elisabeth and Benavente, Ricardo and Alsheimer, Manfred},
  title     = {Expression of individual mammalian Sun1 isoforms depends on the cell type},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68750},
  year      = {2011},
  abstract  = {Mammalian Sun1 belongs to an evolutionarily conserved family of inner nuclear membrane proteins, which are known as SUN domain proteins. SUN domain proteins interact with KASH domain partners to form bridging complexes, so-called LINC complexes, that physically connect the nuclear interior to the cytoskeleton. LINC complexes are critical for nuclear integrity and play fundamental roles in nuclear positioning, shaping and movement. The mammalian genome codes for at least five different SUN domain proteins used for the formation of a number of different LINC complexes. Recently, we reported on the identification of everal Sun1 isoforms, which tremendously enlarges the alternatives to form functional LINC complexes. We now confirmed that Sun1 actually exists in at least seven distinct splice variants. Besides that, we observed that expression of individual Sun1 isoforms remarkably depends on the cell type, suggesting a cell type-specific adaption of Sun1 dependent LINC complexes to specific cellular and physiological requirements.},
  subject      = {Biologie},
  language  = {en}
}
@article{SchleuningFarwigPetersetal.2011,
  author    = {Schleuning, Matthias and Farwig, Nina and Peters, Marcell K. and Bergsdorf, Thomas and Bleher, B{\"a}rbel and Brandl, Roland and Dalitz, Helmut and Fischer, Georg and Freund, Wolfram and Gikungu, Mary W. and Hagen, Melanie and Garcia, Francisco Hita and Kagezi, Godfrey H. and Kaib, Manfred and Kraemer, Manfred and Lung, Tobias and Naumann, Clas M. and Schaab, Gertrud and Templin, Mathias and Uster, Dana and W{\"a}gele, J. Wolfgang and B{\"o}hning-Gaese, Katrin},
  title     = {Forest Fragmentation and Selective Logging Have Inconsistent Effects on Multiple Animal-Mediated Ecosystem Processes in a Tropical Forest},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0027785},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140093},
  pages     = {e27785},
  year      = {2011},
  abstract  = {Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the functionality of tropical forests can be maintained in moderately disturbed forest fragments. Conservation concepts for tropical forests should thus include not only remaining pristine forests but also functionally viable forest remnants.},
  language  = {en}
}
@phdthesis{Schaefer2011,
  author    = {Sch{\"a}fer, Ingo},
  title     = {Fremdgenexpression in humanen Mitochondrien},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85202},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Bei einer Vielzahl neuromuskul{\"a}rer und neurodegenerativer Erkrankungen spielen Fehlfunktionen der Mitochondrien eine wichtige Rolle. Da die Proteine der Atmungsketten-komplexe sowohl durch die mitochondriale DNA als auch durch das Kerngenom codiert werden, k{\"o}nnen Mutationen in beiden Genomen die Ausl{\"o}ser dieser Erkrankungen darstellen. Ver{\"a}nderungen der mitochondrialen DNA lassen sich - im Gegensatz zum Kerngenom - bisher nicht korrigieren, weshalb bei einem großen Teil der Erkrankungen nur die Symptome und nicht die Ausl{\"o}ser behandelt werden k{\"o}nnen. Das grundlegende Problem stellt dabei der Transport der DNA in die Mitochondrien dar. Ziel dieser Arbeit war es, mit Hilfe von physikalischen Transfektionsmethoden exogene DNA in die Mitochondrien menschlicher Kulturzellen einzubringen. Dazu wurden unterschiedliche Vektoren hergestellt, die in Mitochondrien das an die Mitochondrien angepasste gr{\"u}n fluoreszierende mtEGFP exprimieren sollen. Die Expressionsf{\"a}higkeit und Prozessierung dieser Konstrukte konnte in in-vitro-Assays mit einem Mitochondrienextrakt nachgewiesen werden. Bei Transfektionsversuchen mit der Gene Gun gelang es erstmals, exogene Plasmid-DNA in die Mitochondrien menschlicher Zellen einzubringen. Das durch die transfizierten Vektoren exprimierte mtEGFP konnte am Fluoreszenzmikroskop eindeutig in den Mitochondrien der Zellen lokalisiert werden. Eine Transfektion mit Hilfe magnetischer Partikel erwies sich jedoch nicht als zielf{\"u}hrend, da die die Partikel eine Eigenfluoreszenz aufwiesen, die eine Detektion der mtEGFP-Expression verhinderten. Eine wichtige Voraussetzung f{\"u}r die Transfektion von Mitochondrien durch mechanische Methoden wie die Mikroinjektion ist die reversible Induktion von Megamitochondrien, da sie erst in diesem Zustand penetriert werden k{\"o}nnen. Durch eine Ans{\"a}uerung des Kulturmediums mit Natriumacetat bzw. Essigs{\"a}ure konnten Mitochondrien erzeugt werden, die beinahe die Gr{\"o}ße des Zellkerns aufwiesen und somit ideale Bedingungen f{\"u}r die Mikroinjektion darstellen. Bei den anschließenden Mikroinjektionsversuchen mit den hergestellten mitochondrialen Expressionsvektoren wurden wiederum Zellen mit eindeutig gr{\"u}n fluoreszierenden Mitochondrien gefunden. Zusammenfassend wurden im Rahmen dieser Arbeit erstmalig menschliche Mitochondrien mit exogener DNA transfiziert. Dies stellt einen grundlegenden Schritt f{\"u}r die Entwicklung neuer Therapieformen bei mitochondrialen Myopathien dar. Zuvor m{\"u}ssen die Transfektionsmethoden jedoch noch weiter optimiert werden, um eine h{\"o}here Transfektionseffizienz zu erreichen.},
  subject      = {Mitochondrium},
  language  = {de}
}
@article{BrandstaetterRoesslerKleineidam2011,
  author    = {Brandst{\"a}tter, Andreas and R{\"o}ssler, W. and Kleineidam, C. J.},
  title     = {Friends and foes from an ant brain's point of view - neuronal correlates of colony odors in a social insect},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69046},
  year      = {2011},
  abstract  = {Background: Successful cooperation depends on reliable identification of friends and foes. Social insects discriminate colony members (nestmates/friends) from foreign workers (non-nestmates/foes) by colony-specific, multi-component colony odors. Traditionally, complex processing in the brain has been regarded as crucial for colony recognition. Odor information is represented as spatial patterns of activity and processed in the primary olfactory neuropile, the antennal lobe (AL) of insects, which is analogous to the vertebrate olfactory bulb. Correlative evidence indicates that the spatial activity patterns reflect odor-quality, i.e., how an odor is perceived. For colony odors, alternatively, a sensory filter in the peripheral nervous system was suggested, causing specific anosmia to nestmate colony odors. Here, we investigate neuronal correlates of colony odors in the brain of a social insect to directly test whether they are anosmic to nestmate colony odors and whether spatial activity patterns in the AL can predict how odor qualities like ''friend'' and ''foe'' are attributed to colony odors. Methodology/Principal Findings: Using ant dummies that mimic natural conditions, we presented colony odors and investigated their neuronal representation in the ant Camponotus floridanus. Nestmate and non-nestmate colony odors elicited neuronal activity: In the periphery, we recorded sensory responses of olfactory receptor neurons (electroantennography), and in the brain, we measured colony odor specific spatial activity patterns in the AL (calcium imaging). Surprisingly, upon repeated stimulation with the same colony odor, spatial activity patterns were variable, and as variable as activity patterns elicited by different colony odors. Conclusions: Ants are not anosmic to nestmate colony odors. However, spatial activity patterns in the AL alone do not provide sufficient information for colony odor discrimination and this finding challenges the current notion of how odor quality is coded. Our result illustrates the enormous challenge for the nervous system to classify multi-component odors and indicates that other neuronal parameters, e.g., precise timing of neuronal activity, are likely necessary for attribution of odor quality to multi-component odors.},
  subject      = {Ameisen},
  language  = {en}
}
@phdthesis{Weiss2011,
  author    = {Weiß, Sabine},
  title     = {Function of the Spir actin nucleators in intracellular vesicle transport processes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-64589},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Spir proteins are the founding members of the novel class of WH2-actin nucleators. A C-terminal modified FYVE zinc finger motif is necessary to target Spir proteins towards intracellular membranes. The function and regulation of the Spir actin organizers at vesicular membranes is almost unknown. Live cell imaging analyses performed in this study show that Spir-2 is localized at tubular vesicles. Cytoplasmic Spir-2-associated vesicles branch and form protrusions, which can make contacts to the microtubule network, where the Spir-2 vesicles stretch and slide along the microtubule filaments. The analysis of living HeLa cells expressing eGFP-tagged Spir-2, Spir-2-ΔKIND and Spir-2-ΔKW (lacking the 4 WH2 domains and the KIND domain) showed Spir-2-associated tubular structures which differ in their length and motility. Throughout the course of that study it could be shown that the tail domain of the actin motor protein myosin Vb, as a force-generating molecule, is colocalizing and co-immunoprecipitating with Spir-2-ΔKW. By using the tail domain of myosin Vb as a dominant negative mutant for myosin Vb-dependent vesicle transport processes it could be shown that Spir-2-ΔKW/MyoVb-cc-tail- associated vesicles exhibit an increased elongation. Moreover, using the microtubule depolymerizing drug nocodazole it could be shown that the elongation and the motility of Spir-2-ΔKW-associated vesicles depends on an intact microtubule cytoskeleton. Motility and morphological dynamics of Spir-2-associated vesicles is therefore dependent on actin, actin motorproteins and microtubule filaments. These results propose a model in which myosin/F-actin forces mediate vesicle branching, allowing the vesicles to move to and in between the microtubule filaments and thereby providing a new degree of freedom in vesicular motility. To determine the exact subcellular localization of Spir-2, colocalization studies were performed. It could be shown that Spir-2 shows a partial colocalization to Rab11a-positive compartments. Furthermore, Spir-2 exhibits an almost identical localization to Arf1 and the Arf1 small G protein but not Rab11a could be immunoprecipitated with Spir-2-ΔKW. This suggests, that Arf1 recruits Spir-2 to Arf1/Rab11a-positive membranes. Another important function of the Spir-2 C-terminus is the membrane targeting by the FYVE domain. By performing a protein-lipid overlay assay, it has been shown that purified GST- and 6xHis-tagged Spir-2-ΔKW bind phosphatidic acid suggesting a mechanism in which Spir-2 is recruited to phosphatidic acid-enriched membranes. To further elucidate the mechanism in which Spir-2 membrane-targeting could be regulated, interaction studies of C-terminal parts of Spir-2 revealed that the Spir-2 proteins interact directly.},
  subject      = {Aktin},
  language  = {en}
}
@phdthesis{Homola2011,
  author    = {Homola, Gy{\"o}rgy {\´A}d{\´a}m},
  title     = {Functional and Microstructural MRI of the Human Brain Revealing a Cerebral Network Processing the Age of Faces},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-56740},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Although age is one of the most salient and fundamental aspects of human faces, its processing in the brain has not yet been studied by any neuroimaging experiment. Automatic assessment of temporal changes across faces is a prerequisite to identifying persons over their life-span, and age per se is of biological and social relevance. Using a combination of evocative face morphs controlled for global optical flow and functional magnetic resonance imaging (fMRI), we segregate two areas that process changes of facial age in both hemispheres. These areas extend beyond the previously established face-sensitive network and are centered on the posterior inferior temporal sulcus (pITS) and the posterior angular gyrus (pANG), an evolutionarily new formation of the human brain. Using probabilistic tractography and by calculating spatial cross-correlations as well as creating minimum intersection maps between activation and connectivity patterns we demonstrate a hitherto unrecognized link between structure and function in the human brain on the basis of cognitive age processing. According to our results, implicit age processing involves the inferior temporal sulci and is, at the same time, closely tied to quantity decoding by the presumed neural systems devoted to magnitudes in the human parietal lobes. The ventral portion of Wernicke's largely forgotten perpendicular association fasciculus is shown not only to interconnect these two areas but to relate to their activations, i.e. to transmit age-relevant information. In particular, post-hoc age-rating competence is shown to be associated with high response levels in the left angular gyrus. Cortical activation patterns related to changes of facial age differ from those previously elicited by other fixed as well as changeable face aspects such as gender (used for comparison), ethnicity and identity as well as eye gaze or facial expressions. We argue that this may be due to the fact that individual changes of facial age occur ontogenetically, unlike the instant changes of gaze direction or expressive content in faces that can be "mirrored" and require constant cognitive monitoring to follow. Discussing the ample evidence for distinct representations of quantitative age as opposed to categorical gender varied over continuous androgyny levels, we suggest that particular face-sensitive regions interact with additional object-unselective quantification modules to obtain individual estimates of facial age.},
  subject      = {Gesicht},
  language  = {en}
}
@article{SeherNickelMuelleretal.2011,
  author    = {Seher, Axel and Nickel, Joachim and Mueller, Thomas D. and Kneitz, Susanne and Gebhardt, Susanne and Meyer ter Vehn, Tobias and Schlunck, Guenther and Sebald, Walter},
  title     = {Gene expression profiling of connective tissue growth factor (CTGF) stimulated primary human tenon fibroblasts reveals an inflammatory and wound healing response in vitro},
  series = {Molecular Vision},
  volume    = {17},
  journal   = {Molecular Vision},
  number    = {08. Okt},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140189},
  pages     = {53-62},
  year      = {2011},
  abstract  = {Purpose: The biologic relevance of human connective tissue growth factor (hCTGF) for primary human tenon fibroblasts (HTFs) was investigated by RNA expression profiling using affymetrix (TM) oligonucleotide array technology to identify genes that are regulated by hCTGF. Methods: Recombinant hCTGF was expressed in HEK293T cells and purified by affinity and gel chromatography. Specificity and biologic activity of hCTGF was confirmed by biosensor interaction analysis and proliferation assays. For RNA expression profiling HTFs were stimulated with hCTGF for 48h and analyzed using affymetrix (TM) oligonucleotide array technology. Results were validated by real time RT-PCR. Results: hCTGF induces various groups of genes responsible for a wound healing and inflammatory response in HTFs. A new subset of CTGF inducible inflammatory genes was discovered (e.g., chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-X-C motif] ligand 6 [CXCL6], interleukin 6 [IL6], and interleukin 8 [IL8]). We also identified genes that can transmit the known biologic functions initiated by CTGF such as proliferation and extracellular matrix remodelling. Of special interest is a group of genes, e.g., osteoglycin (OGN) and osteomodulin (OMD), which are known to play a key role in osteoblast biology. Conclusions: This study specifies the important role of hCTGF for primary tenon fibroblast function. The RNA expression profile yields new insights into the relevance of hCTGF in influencing biologic processes like wound healing, inflammation, proliferation, and extracellular matrix remodelling in vitro via transcriptional regulation of specific genes. The results suggest that CTGF potentially acts as a modulating factor in inflammatory and wound healing response in fibroblasts of the human eye.},
  language  = {en}
}
@article{KraeusslingWagnerSchartl2011,
  author    = {Kraeussling, Michael and Wagner, Toni Ulrich and Schartl, Manfred},
  title     = {Highly Asynchronous and Asymmetric Cleavage Divisions Accompany Early Transcriptional Activity in Pre-Blastula Medaka Embryos},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68906},
  year      = {2011},
  abstract  = {In the initial phase of development of fish embryos, a prominent and critical event is the midblastula transition (MBT). Before MBT cell cycle is rapid, highly synchronous and zygotic gene transcription is turned off. Only during MBT the cell cycle desynchronizes and transcription is activated. Multiple mechanisms, primarily the nucleocytoplasmic ratio, are supposed to control MBT activation. Unexpectedly, we find in the small teleost fish medaka (Oryzias latipes) that at very early stages, well before midblastula, cell division becomes asynchronous and cell volumes diverge. Furthermore, zygotic transcription is extensively activated already after the 64-cell stage. Thus, at least in medaka, the transition from maternal to zygotic transcription is uncoupled from the midblastula stage and not solely controlled by the nucleocytoplasmic ratio.},
  subject      = {Fische},
  language  = {en}
}
@phdthesis{Pahl2011,
  author    = {Pahl, Mario},
  title     = {Honeybee Cognition: Aspects of Learning, Memory and Navigation in a Social Insect},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66165},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Honeybees (Apis mellifera) forage on a great variety of plant species, navigate over large distances to crucial resources, and return to communicate the locations of food sources and potential new nest sites to nest mates using a symbolic dance language. In order to achieve this, honeybees have evolved a rich repertoire of adaptive behaviours, some of which were earlier believed to be restricted to vertebrates. In this thesis, I explore the mechanisms involved in honeybee learning, memory, numerical competence and navigation. The findings acquired in this thesis show that honeybees are not the simple reflex automats they were once believed to be. The level of sophistication I found in the bees' memory, their learning ability, their time sense, their numerical competence and their navigational abilities are surprisingly similar to the results obtained in comparable experiments with vertebrates. Thus, we should reconsider the notion that a bigger brain automatically indicates higher intelligence.},
  subject      = {Biene},
  language  = {en}
}
@article{KronauerPetersSchoningetal.2011,
  author    = {Kronauer, Daniel J. C. and Peters, Marcell K. and Schoning, Caspar and Boomsma, Jacobus J.},
  title     = {Hybridization in East African swarm-raiding army ants},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68798},
  year      = {2011},
  abstract  = {Background: Hybridization can have complex effects on evolutionary dynamics in ants because of the combination of haplodiploid sex-determination and eusociality. While hybrid non-reproductive workers have been found in a range of species, examples of gene-flow via hybrid queens and males are rare. We studied hybridization in East African army ants (Dorylus subgenus Anomma) using morphology, mitochondrial DNA sequences, and nuclear microsatellites. Results: While the mitochondrial phylogeny had a strong geographic signal, different species were not recovered as monophyletic. At our main study site at Kakamega Forest, a mitochondrial haplotype was shared between a "Dorylus molestus-like" and a "Dorylus wilverthi-like" form. This pattern is best explained by introgression following hybridization between D. molestus and D. wilverthi. Microsatellite data from workers showed that the two morphological forms correspond to two distinct genetic clusters, with a significant proportion of individuals being classified as hybrids. Conclusions: We conclude that hybridization and gene-flow between the two army ant species D. molestus and D. wilverthi has occurred, and that mating between the two forms continues to regularly produce hybrid workers. Hybridization is particularly surprising in army ants because workers have control over which males are allowed to mate with a young virgin queen inside the colony.},
  subject      = {Zoologie},
  language  = {en}
}
@phdthesis{Halder2011,
  author    = {Halder, Partho},
  title     = {Identification and characterization of synaptic proteins of Drosophila melanogaster using monoclonal antibodies of the Wuerzburg Hybridoma Library},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67325},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {For a large fraction of the proteins expressed in the human brain only the primary structure is known from the genome project. Proteins conserved in evolution can be studied in genetic models such as Drosophila. In this doctoral thesis monoclonal antibodies (mAbs) from the Wuerzburg Hybridoma library are produced and characterized with the aim to identify the target antigen. The mAb ab52 was found to be an IgM which recognized a cytosolic protein of Mr ~110 kDa on Western blots. The antigen was resolved by two-dimensional gel electrophoresis (2DE) as a single distinct spot. Mass spectrometric analysis of this spot revealed EPS-15 (epidermal growth factor receptor pathway substrate clone 15) to be a strong candidate. Another mAb from the library, aa2, was already found to recognize EPS-15, and comparison of the signal of both mAbs on Western blots of 1D and 2D electrophoretic separations revealed similar patterns, hence indicating that both antigens could represent the same protein. Finally absence of the wild-type signal in homozygous Eps15 mutants in a Western blot with ab52 confirmed the ab52 antigen to be EPS-15. Thus both the mAbs aa2 and ab52 recognize the Drosophila homologue of EPS-15. The mAb aa2, being an IgG, is more suitable for applications like immunoprecipitation (IP). It has already been submitted to the Developmental Studies Hybridoma Bank (DSHB) to be easily available for the entire research community. The mAb na21 was also found to be an IgM. It recognizes a membrane associated antigen of Mr ~10 kDa on Western blots. Due to the membrane associated nature of the protein, it was not possible to resolve it by 2DE and due to the IgM nature of the mAb it was not possible to enrich the antigen by IP. Preliminary attempts to biochemically purify the endogenously expressed protein from the tissue, gave promising results but could not be completed due to lack of time. Thus biochemical purification of the protein seems possible in order to facilitate its identification by mass spectrometry. Several other mAbs were studied for their staining pattern on cryosections and whole mounts of Drosophila brains. However, many of these mAbs stained very few structures in the brain, which indicated that only a very limited amount of protein would be available as starting material. Because these antibodies did not produce signals on Western blots, which made it impossible to enrich the antigens by electrophoretic methods, we did not attempt their purification. However, the specific localization of these proteins makes them highly interesting and calls for their further characterization, as they may play a highly specialized role in the development and/or function of the neural circuits they are present in. The purification and identification of such low expression proteins would need novel methods of enrichment of the stained structures.},
  subject      = {Taufliege},
  language  = {en}
}
@article{ParthoChenBrauckhoffetal.2011,
  author    = {Partho, Halder and Chen, Yi-chun and Brauckhoff, Janine and Hofbauer, Alois and Dabauvalle, Marie-Christine and Lewandrowski, Urs and Winkler, Christiane and Sickmann, Albert and Buchner, Erich},
  title     = {Identification of Eps15 as Antigen Recognized by the Monoclonal Antibodies aa2 and ab52 of the Wuerzburg Hybridoma Library against Drosophila Brain},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0029352},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137957},
  pages     = {e29352},
  year      = {2011},
  abstract  = {The Wuerzburg Hybridoma Library against the Drosophila brain represents a collection of around 200 monoclonal antibodies that bind to specific structures in the Drosophila brain. Here we describe the immunohistochemical staining patterns, the Western blot signals of one- and two-dimensional electrophoretic separation, and the mass spectrometric characterization of the target protein candidates recognized by the monoclonal antibodies aa2 and ab52 from the library. Analysis of a mutant of a candidate gene identified the Drosophila homolog of the Epidermal growth factor receptor Pathway Substrate clone 15 (Eps15) as the antigen for these two antibodies.},
  language  = {en}
}
@phdthesis{Heisig2011,
  author    = {Heisig, Julia},
  title     = {Identifizierung neuer Zielgene der Hey bHLH Transkriptionsfaktoren},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65053},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Der Notch Signalweg spielt w{\"a}hrend der Embryonalentwicklung eine zentrale Rolle in der Spezifizierung des Zellschicksales, der Proliferation und der Kommunikation benachbarter Zellen. Die Hey bHLH Transkriptionsfaktoren sind Zielgene des Notch-Signalweges und besitzen wichtige Funktionen in der kardiovaskul{\"a}ren Entwicklung. Hey2 Knockout (KO) M{\"a}use und Hey1/HeyL Doppelknockout-M{\"a}use (DKO) sind gekennzeichnet durch eine fehlerhafte Ausbildung der Herzscheidewand und der Herzklappen und durch eine unzureichende Differenzierung w{\"a}hrend der Blutgef{\"a}ßentwicklung. Ziel dieser Arbeit war es, neue Zielgene der Hey Proteine zu finden, um ihre Funktion in der Organentwicklung und die Auspr{\"a}gung der Hey KO Maus-Ph{\"a}notypen besser verstehen zu k{\"o}nnen. Dazu wurde als Methode eine Kombination aus Microarray-Analyse und Chromatinimmunpr{\"a}zipitation (ChIP) gew{\"a}hlt, um gleichzeitig einen {\"U}berblick {\"u}ber die regulierten Zielgene und der direkt gebundenen Promotoren zu gewinnen. Als Zellkulturmodell wurden HEK293-Zellen genutzt, die doxyzyklin-induzierbar Flag-markiertes Hey1, bzw. Hey2 Protein {\"u}berexprimieren. Eine Microarray-Analyse nach {\"U}berexpression von Hey1, bzw. Hey2 ergab insgesamt ca. 100 bis zu 5-fach herunterregulierte Zielgene und nur f{\"u}r Hey2 15 Gene, die st{\"a}rker als 2-fach hochreguliert waren. Eine ChIP mit αFlag-Antik{\"o}rper zeigte eine direkte DNA-Bindung von Hey1, bzw. Hey2, im proximalen Promotorbereich von 4 herunterregulierten Zielgenen (HEY1, BMP2, KLF10 und FOXC1). Ist jedoch die DNA-bindende basische Dom{\"a}ne des Hey1-Proteins deletiert, bzw. durch Aminos{\"a}ureaustausche (3 Arginine zu 3 Lysine) vermutlich nicht mehr DNA-bindend, kann eine Herunterregulation der Zielgene nach {\"U}berexpression der Hey1-Mutanten nicht mehr festgestellt werden. Ebenso kann eine Bindung der Hey1-Mutanten an die ausgew{\"a}hlten Promotoren von HEY1, BMP2, KLF10 oder FOXC1 mit ChIP nicht mehr nachgewiesen werden. Dies deutet darauf hin, dass die basische Dom{\"a}ne essentiell f{\"u}r die DNA-Bindung und f{\"u}r die Funktion der Hey Proteine ist. Mit ChIP-PET und anschließender Hochdurchsatz-Sequenzierung wurde ein genomweiter Screen der Hey1- und der Hey2-Bindungsstellen in HEK293-Zellen durchgef{\"u}hrt. F{\"u}r Hey1 wurden 1453 Zielgene, f{\"u}r Hey2 4288 Zielgene bestimmt, wobei 1147 Gene gemeinsame Zielgene von Hey1 und Hey2 waren. Obwohl die Bindungsstellen in 5'- und 3'-Richtung von kodierenden Sequenzen und auch in Exons und Introns lokalisiert waren, waren 55 \%, bzw. 49 \% aller Bindungsstellen f{\"u}r Hey1, bzw. Hey2 im proximalen Promotorbereich von -0,5 kb und im ersten Exon lokalisiert. Eine in silico Analyse des Bindemotivs deutete auf eine repetitive GC-haltige Sequenz hin, die vermutlich in CpG Inseln lokalisiert ist. Diese Ergebnisse weisen auf eine direkte Regulation der Transkriptionsmaschinerie durch die Hey Proteine hin. Ein Vergleich der Zielgene aus den Microarray-Analysen mit den ChIP-PET Daten zeigte einen hohen Anteil an herunterregulierten Genen mit Bindestellen, die direkt von Hey gebunden waren. W{\"a}hrend 60 \% der herunterregulierten Hey2 Zielgene in der ChIP-PET Analyse eine direkte DNA-Bindung zeigen, weisen nur 20 \% der hochregulierten Gene Bindestellen f{\"u}r Hey2 auf. Dies spricht f{\"u}r eine {\"u}berwiegende Repressorfunktion der Hey Proteine. Um zu {\"u}berpr{\"u}fen, inwieweit die Hey Proteine zelltypspezifisch verschiedene Zielgene regulieren, wurden embryonale Stammzellen (ES-Zellen) generiert, die ebenfalls doxyzyklin-induzierbar Hey1, bzw. Hey2 {\"u}berexprimieren. Diese ES-Zellen konnten effektiv zu Kardiomyozyten differenziert werden, so dass auch in diesen Zellen eine Hey {\"U}berexpression induziert und somit eine Genexpressionsanalyse durchgef{\"u}hrt werden konnte. Microarray Analysen der ES-Zellen und Kardiomyozyten ergaben mehr hoch- als herunterregulierte Gene im Vergleich zu HEK293-Zellen. Die {\"U}berlappung an gemeinsam regulierten Zielgenen in HEK293, ES-Zellen und Kardiomyozyten war sehr gering. Nur zwei Hey2-Zielgene wurden gleichzeitig in HEK293 und ES-Zellen st{\"a}rker als 2-fach reguliert (Hes1, Zic2). Diese geringe {\"U}berlappung deutet auf ein enges zelltypspezifische Regulationspotential hin. Eine Genontologie-Analyse aller Zielgene zeigte Interaktionen der Hey Proteine mit verschiedenen Signalwegen (z.B. TGFβ-, Id- oder Wnt-Signalweg), die alle unersetzlich in fr{\"u}hen Entwicklungsprozessen sind. Diese Ergebnisse deuten darauf hin, dass die Hey Proteine zelltypspezifisch die Expression von Genen aus verschiedenen Signalwegen beeinflussen und modulieren k{\"o}nnen. Weiterhin er{\"o}ffnen diese Daten neue M{\"o}glichkeiten f{\"u}r zuk{\"u}nftige Forschung, um die Rolle der Hey Proteine in der fr{\"u}hen Organentwicklung genauer ergr{\"u}nden.},
  subject      = {Gen notch},
  language  = {de}
}