@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}
}
@article{BijuSchwarzLinkeetal.2011,
  author    = {Biju, Joseph and Schwarz, Roland and Linke, Burkhard and Blom, Jochen and Becker, Anke and Claus, Heike and Goesmann, Alexander and Frosch, Matthias and M{\"u}ller, Tobias and Vogel, Ulrich and Schoen, Christoph},
  title     = {Virulence Evolution of the Human Pathogen Neisseria meningitidis by Recombination in the Core and Accessory Genome},
  series = {PLoS One},
  volume    = {6},
  journal   = {PLoS One},
  number    = {4},
  doi       = {10.1371/journal.pone.0018441},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137960},
  pages     = {e18441},
  year      = {2011},
  abstract  = {Background Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. Principal Findings We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA) island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40\% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. Conclusions Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.},
  language  = {en}
}
@article{KuhnGrippFliederetal.2015,
  author    = {Kuhn, Joachim and Gripp, Tatjana and Flieder, Tobias and Dittrich, Marcus and Hendig, Doris and Busse, Jessica and Knabbe, Cornelius and Birschmann, Ingvild},
  title     = {UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays},
  series = {PLOS ONE},
  volume    = {10},
  journal   = {PLOS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0145478},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136023},
  pages     = {e0145478},
  year      = {2015},
  abstract  = {Introduction The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Methods Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. Results The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 mu g/L (r > 0.99). Limits of detection (LOD) in the plasma matrix were 0.21 mu g/L for dabigatran and 0.34 mu g/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 mu g/L for dabigatran and 0.54 mu g/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were < 4\% and 6\%; respectively, the interassay CVs were < 6\% for dabigatran and < 9\% for rivaroxaban. Inaccuracy was < 5\% for both substances. The mean recovery was 104.5\% (range 83.8-113.0\%) for dabigatran and 87.0\%(range 73.6-105.4\%) for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20 degrees C, 4 degrees C and even at RT for at least one week. A method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional assays measuring activities of various coagulation factors which are susceptible to interference by other coagulant drugs. Conclusions Overall, we developed and validated a sensitive and specific UPLC-MRM MS assay for the quick and specific measurement of dabigatran and rivaroxaban in human plasma.},
  language  = {en}
}
@article{SinghKingstonGuptaetal.2015,
  author    = {Singh, Amit K. and Kingston, Joseph J. and Gupta, Shishir K. and Batra, Harsh V.},
  title     = {Recombinant Bivalent Fusion Protein rVE Induces CD4+ and CD8+ T-Cell Mediated Memory Immune Response for Protection Against Yersinia enterocolitica Infection},
  series = {Frontiers in Microbiology},
  volume    = {6},
  journal   = {Frontiers in Microbiology},
  number    = {1407},
  doi       = {10.3389/fmicb.2015.01407},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136114},
  year      = {2015},
  abstract  = {Studies investigating the correlates of immune protection against Yersinia infection have established that both humoral and cell mediated immune responses are required for the comprehensive protection. In our previous study, we established that the bivalent fusion protein (rVE) comprising immunologically active regions of Y pestis LcrV (100-270 aa) and YopE (50-213 aa) proteins conferred complete passive and active protection against lethal Y enterocolitica 8081 challenge. In the present study, cohort of BALB/c mice immunized with rVE or its component proteins rV, rE were assessed for cell mediated immune responses and memory immune protection against Y enterocolitica 8081 rVE immunization resulted in extensive proliferation of both CD4 and CD8 T cell subsets; significantly high antibody titer with balanced IgG1: IgG2a/IgG2b isotypes (1:1 ratio) and up regulation of both Th1 (INF-\(\alpha\), IFN-\(\gamma\), IL 2, and IL 12) and Th2 (IL 4) cytokines. On the other hand, rV immunization resulted in Th2 biased IgG response (11:1 ratio) and proliferation of CD4+ T-cell; rE group of mice exhibited considerably lower serum antibody titer with predominant Th1 response (1:3 ratio) and CD8+ T-cell proliferation. Comprehensive protection with superior survival (100\%) was observed among rVE immunized mice when compared to the significantly lower survival rates among rE (37.5\%) and rV (25\%) groups when IP challenged with Y enterocolitica 8081 after 120 days of immunization. Findings in this and our earlier studies define the bivalent fusion protein rVE as a potent candidate vaccine molecule with the capability to concurrently stimulate humoral and cell mediated immune responses and a proof of concept for developing efficient subunit vaccines against Gram negative facultative intracellular bacterial pathogens.},
  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{StaigerCadotKooteretal.2012,
  author    = {Staiger, Christine and Cadot, Sidney and Kooter, Raul and Dittrich, Marcus and M{\"u}ller, Tobias and Klau, Gunnar W. and Wessels, Lodewyk F. A.},
  title     = {A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {4},
  doi       = {10.1371/journal.pone.0034796},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131323},
  pages     = {e34796},
  year      = {2012},
  abstract  = {Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single genes classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single genes classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single genes classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single genes sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single genes classifiers for predicting outcome in breast cancer.},
  language  = {en}
}
@article{RuczyńskiBartoń2012,
  author    = {Ruczyński, Ireneusz and Bartoń, Kamil A.},
  title     = {Modelling Sensory Limitation: The Role of Tree Selection, Memory and Information Transfer in Bats' Roost Searching Strategies},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0044897},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133963},
  pages     = {e44897},
  year      = {2012},
  abstract  = {Sensory limitation plays an important role in the evolution of animal behaviour. Animals have to find objects of interest (e.g. food, shelters, predators). When sensory abilities are strongly limited, animals adjust their behaviour to maximize chances for success. Bats are nocturnal, live in complex environments, are capable of flight and must confront numerous perceptual challenges (e.g. limited sensory range, interfering clutter echoes). This makes them an excellent model for studying the role of compensating behaviours to decrease costs of finding resources. Cavity roosting bats are especially interesting because the availability of tree cavities is often limited, and their quality is vital for bats during the breeding season. From a bat's sensory point of view, cavities are difficult to detect and finding them requires time and energy. However, tree cavities are also long lasting, allowing information transfer among conspecifics. Here, we use a simple simulation model to explore the benefits of tree selection, memory and eavesdropping (compensation behaviours) to searches for tree cavities by bats with short and long perception range. Our model suggests that memory and correct discrimination of tree suitability are the basic strategies decreasing the cost of roost finding, whereas perceptual range plays a minor role in this process. Additionally, eavesdropping constitutes a buffer that reduces the costs of finding new resources (such as roosts), especially when they occur in low density. We conclude that natural selection may promote different strategies of roost finding in relation to habitat conditions and cognitive skills of animals.},
  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 \(Listeria\) \(monocytogenes\)},
  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{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}
}
@article{TuChenLimetal.2012,
  author    = {Tu, Xiaolin and Chen, Jianquan and Lim, Joohyun and Karner, Courtney M. and Lee, Seung-Yon and Heisig, Julia and Wiese, Cornelia and Surendran, Kameswaran and Kopan, Raphael and Gessler, Manfred and Long, Fanxin},
  title     = {Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1},
  series = {PLoS Genetics},
  volume    = {8},
  journal   = {PLoS Genetics},
  number    = {3},
  doi       = {10.1371/journal.pgen.1002577},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133490},
  pages     = {e1002577},
  year      = {2012},
  abstract  = {Notch signaling between neighboring cells controls many cell fate decisions in metazoans both during embryogenesis and in postnatal life. Previously, we uncovered a critical role for physiological Notch signaling in suppressing osteoblast differentiation in vivo. However, the contribution of individual Notch receptors and the downstream signaling mechanism have not been elucidated. Here we report that removal of Notch2, but not Notch1, from the embryonic limb mesenchyme markedly increased trabecular bone mass in adolescent mice. Deletion of the transcription factor RBPjk, a mediator of all canonical Notch signaling, in the mesenchymal progenitors but not the more mature osteoblast-lineage cells, caused a dramatic high-bone-mass phenotype characterized by increased osteoblast numbers, diminished bone marrow mesenchymal progenitor pool, and rapid age-dependent bone loss. Moreover, mice deficient in Hey1 and HeyL, two target genes of Notch-RBPjk signaling, exhibited high bone mass. Interestingly, Hey1 bound to and suppressed the NFATc1 promoter, and RBPjk deletion increased NFATc1 expression in bone. Finally, pharmacological inhibition of NFAT alleviated the high-bone-mass phenotype caused by RBPjk deletion. Thus, Notch-RBPjk signaling functions in part through Hey1-mediated inhibition of NFATc1 to suppress osteoblastogenesis, contributing to bone homeostasis in vivo.},
  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{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{GassenBrechtefeldSchandryetal.2012,
  author    = {Gassen, Alwine and Brechtefeld, Doris and Schandry, Niklas and Arteaga-Salas, J. Manuel and Israel, Lars and Imhof, Axel and Janzen, Christian J.},
  title     = {DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei},
  series = {Nucleic Acids Research},
  volume    = {40},
  journal   = {Nucleic Acids Research},
  number    = {20},
  doi       = {10.1093/nar/gks801},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131449},
  pages     = {10302 - 10311},
  year      = {2012},
  abstract  = {Cell-cycle progression requires careful regulation to ensure accurate propagation of genetic material to the daughter cells. Although many cell-cycle regulators are evolutionarily conserved in the protozoan parasite Trypanosoma brucei, novel regulatory mechanisms seem to have evolved. Here, we analyse the function of the histone methyltransferase DOT1A during cell-cycle progression. Over-expression of DOT1A generates a population of cells with aneuploid nuclei as well as enucleated cells. Detailed analysis shows that DOT1A over-expression causes continuous replication of the nuclear DNA. In contrast, depletion of DOT1A by RNAi abolishes replication but does not prevent karyokinesis. As histone H3K76 methylation has never been associated with replication control in eukaryotes before, we have discovered a novel function of DOT1 enzymes, which might not be unique to trypanosomes.},
  language  = {en}
}
@article{RoesslerBrill2013,
  author    = {R{\"o}ssler, Wolfgang and Brill, Martin F.},
  title     = {Parallel processing in the honeybee olfactory pathway: structure, function, and evolution},
  series = {Journal of Comparative Physiology A},
  volume    = {199},
  journal   = {Journal of Comparative Physiology A},
  doi       = {10.1007/s00359-013-0821-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132548},
  pages     = {981-996},
  year      = {2013},
  abstract  = {Animals face highly complex and dynamic olfactory stimuli in their natural environments, which require fast and reliable olfactory processing. Parallel processing is a common principle of sensory systems supporting this task, for example in visual and auditory systems, but its role in olfaction remained unclear. Studies in the honeybee focused on a dual olfactory pathway. Two sets of projection neurons connect glomeruli in two antennal-lobe hemilobes via lateral and medial tracts in opposite sequence with the mushroom bodies and lateral horn. Comparative studies suggest that this dual-tract circuit represents a unique adaptation in Hymenoptera. Imaging studies indicate that glomeruli in both hemilobes receive redundant sensory input. Recent simultaneous multi-unit recordings from projection neurons of both tracts revealed widely overlapping response profiles strongly indicating parallel olfactory processing. Whereas lateral-tract neurons respond fast with broad (generalistic) profiles, medial-tract neurons are odorant specific and respond slower. In analogy to "what-" and "where" subsystems in visual pathways, this suggests two parallel olfactory subsystems providing "what-" (quality) and "when" (temporal) information. Temporal response properties may support across-tract coincidence coding in higher centers. Parallel olfactory processing likely enhances perception of complex odorant mixtures to decode the diverse and dynamic olfactory world of a social insect.},
  language  = {en}
}
@article{ElKeredySchleyerKoenigetal.2012,
  author    = {El-Keredy, Amira and Schleyer, Michael and K{\"o}nig, Christian and Ekim, Aslihan and Gerber, Bertram},
  title     = {Behavioural Analyses of Quinine Processing in Choice, Feeding and Learning of Larval Drosophila},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0040525},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130811},
  pages     = {e40525},
  year      = {2012},
  abstract  = {Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.},
  language  = {en}
}
@article{ZoephelReiherRexeretal.2012,
  author    = {Zoephel, Judith and Reiher, Wencke and Rexer, Karl-Heinz and Kahnt, J{\"o}rg and Wegener, Christian},
  title     = {Peptidomics of the Agriculturally Damaging Larval Stage of the Cabbage Root Fly Delia radicum (Diptera: Anthomyiidae)},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0041543},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131727},
  pages     = {e41543},
  year      = {2012},
  abstract  = {The larvae of the cabbage root fly induce serious damage to cultivated crops of the family Brassicaceae. We here report the biochemical characterisation of neuropeptides from the central nervous system and neurohemal organs, as well as regulatory peptides from enteroendocrine midgut cells of the cabbage maggot. By LC-MALDI-TOF/TOF and chemical labelling with 4-sulfophenyl isothiocyanate, 38 peptides could be identified, representing major insect peptide families: allatostatin A, allatostatin C, FMRFamide-like peptides, kinin, CAPA peptides, pyrokinins, sNPF, myosuppressin, corazonin, SIFamide, sulfakinins, tachykinins, NPLP1-peptides, adipokinetic hormone and CCHamide 1. We also report a new peptide (Yamide) which appears to be homolog to an amidated eclosion hormone-associated peptide in several Drosophila species. Immunocytochemical characterisation of the distribution of several classes of peptide-immunoreactive neurons and enteroendocrine cells shows a very similar but not identical peptide distribution to Drosophila. Since peptides regulate many vital physiological and behavioural processes such as moulting or feeding, our data may initiate the pharmacological testing and development of new specific peptide-based protection methods against the cabbage root fly and its larva.},
  language  = {en}
}
@article{SchneiderTautzGruenewaldetal.2012,
  author    = {Schneider, Christof W. and Tautz, J{\"u}rgen and Gr{\"u}newald, Bernd and Fuchs, Stefan},
  title     = {RFID Tracking of Sublethal Effects of Two Neonicotinoid Insecticides on the Foraging Behavior of Apis mellifera},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {1},
  doi       = {10.1371/journal.pone.0030023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131753},
  pages     = {e30023},
  year      = {2012},
  abstract  = {The development of insecticides requires valid risk assessment procedures to avoid causing harm to beneficial insects and especially to pollinators such as the honeybee Apis mellifera. In addition to testing according to current guidelines designed to detect bee mortality, tests are needed to determine possible sublethal effects interfering with the animal's vitality and behavioral performance. Several methods have been used to detect sublethal effects of different insecticides under laboratory conditions using olfactory conditioning. Furthermore, studies have been conducted on the influence insecticides have on foraging activity and homing ability which require time-consuming visual observation. We tested an experimental design using the radiofrequency identification (RFID) method to monitor the influence of sublethal doses of insecticides on individual honeybee foragers on an automated basis. With electronic readers positioned at the hive entrance and at an artificial food source, we obtained quantifiable data on honeybee foraging behavior. This enabled us to efficiently retrieve detailed information on flight parameters. We compared several groups of bees, fed simultaneously with different dosages of a tested substance. With this experimental approach we monitored the acute effects of sublethal doses of the neonicotinoids imidacloprid (0.15-6 ng/bee) and clothianidin (0.05-2 ng/bee) under field-like circumstances. At field-relevant doses for nectar and pollen no adverse effects were observed for either substance. Both substances led to a significant reduction of foraging activity and to longer foraging flights at doses of >= 0.5 ng/bee (clothianidin) and >= 1.5 ng/bee (imidacloprid) during the first three hours after treatment. This study demonstrates that the RFID-method is an effective way to record short-term alterations in foraging activity after insecticides have been administered once, orally, to individual bees. We contribute further information on the understanding of how honeybees are affected by sublethal doses of insecticides.},
  language  = {en}
}
@article{NaseemDandekar2012,
  author    = {Naseem, Muhammad and Dandekar, Thomas},
  title     = {The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions},
  series = {PLOS Pathogens},
  volume    = {8},
  journal   = {PLOS Pathogens},
  number    = {11},
  doi       = {10.1371/journal.ppat.1003026},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131901},
  pages     = {e1003026},
  year      = {2012},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KesslerHertelJungkunstetal.2012,
  author    = {Kessler, Michael and Hertel, Dietrich and Jungkunst, Hermann F. and Kluge, J{\"u}rgen and Abrahamczyk, Stefan and Bos, Merijn and Buchori, Damayanti and Gerold, Gerhard and Gradstein, S. Robbert and K{\"o}hler, Stefan and Leuschner, Christoph and Moser, Gerald and Pitopang, Ramadhanil and Saleh, Shahabuddin and Schulze, Christian H. and Sporn, Simone G. and Steffan-Dewenter, Ingolf and Tjitrosoedirdjo, Sri S. and Tscharntke, Teja},
  title     = {Can Joint Carbon and Biodiversity Management in Tropical Agroforestry Landscapes Be Optimized?},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0047192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132016},
  pages     = {e47192},
  year      = {2012},
  abstract  = {Managing ecosystems for carbon storage may also benefit biodiversity conservation, but such a potential 'win-win' scenario has not yet been assessed for tropical agroforestry landscapes. We measured above-and below-ground carbon stocks as well as the species richness of four groups of plants and eight of animals on 14 representative plots in Sulawesi, Indonesia, ranging from natural rainforest to cacao agroforests that have replaced former natural forest. The conversion of natural forests with carbon stocks of 227-362 Mg C ha\(^{-1}\) to agroforests with 82-211 Mg C ha\(^{-1}\) showed no relationships to overall biodiversity but led to a significant loss of forest-related species richness. We conclude that the conservation of the forest-related biodiversity, and to a lesser degree of carbon stocks, mainly depends on the preservation of natural forest habitats. In the three most carbon-rich agroforestry systems, carbon stocks were about 60\% of those of natural forest, suggesting that 1.6 ha of optimally managed agroforest can contribute to the conservation of carbon stocks as much as 1 ha of natural forest. However, agroforestry systems had comparatively low biodiversity, and we found no evidence for a tight link between carbon storage and biodiversity. Yet, potential win-win agroforestry management solutions include combining high shade-tree quality which favours biodiversity with cacao-yield adapted shade levels.},
  language  = {en}
}
@article{HolzschuhDormannTscharntkeetal.2013,
  author    = {Holzschuh, Andrea and Dormann, Carsten F. and Tscharntke, Teja and Steffan-Dewenter, Ingolf},
  title     = {Mass-flowering crops enhance wild bee abundance},
  series = {Oecologia},
  volume    = {172},
  journal   = {Oecologia},
  number    = {2},
  doi       = {10.1007/s00442-012-2515-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132149},
  pages     = {477-484},
  year      = {2013},
  abstract  = {Although agricultural habitats can provide enormous amounts of food resources for pollinator species, links between agricultural and (semi-)natural habitats through dispersal and foraging movements have hardly been studied. In 67 study sites, we assessed the interactions between mass-flowering oilseed rape fields and semi-natural grasslands at different spatial scales, and their effects on the number of brood cells of a solitary cavity-nesting bee. The probability that the bee Osmia bicornis colonized trap nests in oilseed rape fields increased from 12 to 59 \% when grassland was nearby, compared to fields isolated from grassland. In grasslands, the number of brood cells of O. bicornis in trap nests was 55 \% higher when adjacent to oilseed rape compared to isolated grasslands. The percentage of oilseed rape pollen in the larval food was higher in oilseed rape fields and grasslands adjacent to oilseed rape than in isolated grasslands. In both oilseed rape fields and grasslands, the number of brood cells was positively correlated with the percentage of oilseed rape pollen in the larval food. We show that mass-flowering agricultural habitats—even when they are intensively managed—can strongly enhance the abundance of a solitary bee species nesting in nearby semi-natural habitats. Our results suggest that positive effects of agricultural habitats have been underestimated and might be very common (at least) for generalist species in landscapes consisting of a mixture of agricultural and semi-natural habitats. These effects might also have—so far overlooked—implications for interspecific competition and mutualistic interactions in semi-natural habitats.},
  language  = {en}
}
@article{RinawatiSteinLindner2013,
  author    = {Rinawati, Fitria and Stein, Katharina and Lindner, Andr{\´e}},
  title     = {Climate change impacts on biodiversity-the setting of a lingering global crisis},
  series = {Diversity},
  volume    = {5},
  journal   = {Diversity},
  number    = {1},
  doi       = {10.3390/d50100114},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131866},
  pages     = {114-123},
  year      = {2013},
  abstract  = {Climate change has created potential major threats to global biodiversity. The multiple components of climate change are projected to affect all pillars of biodiversity, from genes over species to biome level. Of particular concerns are "tipping points" where the exceedance of ecosystem thresholds will possibly lead to irreversible shifts of ecosystems and their functioning. As biodiversity underlies all goods and services provided by ecosystems that are crucial for human survival and wellbeing, this paper presents potential effects of climate change on biodiversity, its plausible impacts on human society as well as the setting in addressing a global crisis. Species affected by climate change may respond in three ways: change, move or die. Local species extinctions or a rapidly affected ecosystem as a whole respectively might move toward its particular "tipping point", thereby probably depriving its services to human society and ending up in a global crisis. Urgent and appropriate actions within various scenarios of climate change impacts on biodiversity, especially in tropical regions, are needed to be considered. Foremost a multisectoral approach on biodiversity issues with broader policies, stringent strategies and programs at international, national and local levels is essential to meet the challenges of climate change impacts on biodiversity.},
  language  = {en}
}
@phdthesis{Kunz2017,
  author    = {Kunz, Meik},
  title     = {Systembiologische Analysen von Interaktionen: Zytokinine (Pflanzenpathogene), 3D-Zellkulturen (Krebstherapie) und Drugtargets},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134911},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {Der Einsatz von computergest{\"u}tzten Analysen hat sich zu einem festen Bestandteil der biowissenschaftlichen Forschung etabliert. Im Rahmen dieser vorliegenden Arbeit wurden systembiologische Untersuchungen auf verschiedene biologische Themengebiete und Organismen angewendet. In diesem Zusammenhang liefert die Arbeit einen innovativen und interdisziplin{\"a}ren methodischen Ansatz. Die grundlegende Frage lautet: Wie verstehe und beschreibe ich Signalwege und wie kann ich sie beeinflussen? Der Ansatz verkn{\"u}pft verschiedene biologische Datens{\"a}tze und Datenebenen miteinander, beginnend vom Genom und Interaktionskontext {\"u}ber semiquantitative Simulationen hin zu neuen Interventionen und Experimenten, welche therapeutisch und biotechnologisch genutzt werden k{\"o}nnen. Die Analysen k{\"o}nnen auf diese Weise - zu einem besseren Verst{\"a}ndnis experimenteller Daten und biologischer Fragestellungen beitragen und erm{\"o}glichen ein systematisches Verst{\"a}ndnis der zugrunde liegenden Signalwege und Netzwerkeffekte (z.B. in Pflanzen). - Dar{\"u}ber hinaus erm{\"o}glichen sie die Identifizierung wichtiger funktioneller Hubproteine und die Entwicklung neuer therapeutischer Strategien f{\"u}r weitere experimentelle Testungen (z.B. Tumormodelle), - stellen zudem einen hilfreichen Schritt auf dem Weg zur personalisierten Medizin (z.B. lncRNAs und Tumormodelle) und Medikamentenentwicklung (z.B. Datenbank DrumPID) dar. (i) Als Grundlage wurde hierzu eine integrierte systembiologische Methode entwickelt, welche experimentelle Daten (z.B. Transkriptomdaten) hinsichtlich ihrer biologischen Funktionen untersucht und die Identifizierung relevanter funktioneller Cluster und Hubproteine erm{\"o}glicht. In einem ersten Teil wurden Analysen zum pflanzlichen Immunsystem durchgef{\"u}hrt. Mithilfe der entwickelten Methode wurden Genexpressionsdatens{\"a}tze von A. thaliana, die mit dem Pathogen Pst DC3000 infiziert wurden, untersucht, um den Einfluss verschiedener Virulenzfaktoren auf das Interaktom der Wirtspflanze zu untersuchen und neue Modulatoren einer CK-vermittelten Immunabwehr zu finden. In diesem Zusammenhang konnte gezeigt werden, dass die von Pst DC3000 sekretierten Abwehrstoffe wichtige pflanzliche Hormonsignalwege f{\"u}r die Immunabwehr in A. thaliana beeinflussen. Die Ergebnisse zeigen zudem, dass sich der Einfluss auf das Netzwerkverhalten der Effektorproteine und COR-Phytotoxine von dem der PAMPs unterscheidet, sich jedoch auch eine Regulierung gemeinsamer Signalwege und eine {\"U}berlappung der beiden Phasen der Immunantwort (PTI und ETI) in A. thaliana finden lassen. Die komplexe Immunantwort auf eine Infektion spiegelt sich zudem in einer h{\"o}heren Anzahl an funktionellen Clustern und Hubproteinen in Pst DC3000 gegen{\"u}ber den beiden untersuchten Mutanten wider, wobei sich f{\"u}r Pst DC3000 insbesondere ein stark vernetztes immunrelevantes Cluster um den JA-Signalweg zeigt. Weiterhin wurden anhand der entwickelten Methode wichtige Hubproteine f{\"u}r die Immunabwehr identifiziert. Als bedeutende Vertreter sind AHK2 und AAR14 zu nennen, welche Teil des Zweikomponentensystems der Signal{\"u}bertragung von CK sind und hierbei wichtige Modulatoren f{\"u}r eine CK-vermittelte Immunabwehr darstellen. (ii) Im zweiten Teil der Arbeit schließen sich Untersuchungen an einem in vitro-Experiment einer 2D- und 3D-Zellkultur einer HSP90-Behandlung in einem Lungentumormodell an. In diesem Zusammenhang wurden mithilfe der entwickelten Methode Unterschiede zwischen den beiden Zellkultursystemen gefunden, die das unterschiedliche Behandlungsansprechen erkl{\"a}ren, und f{\"u}r die beiden KRAS-mutierten Zelllinien A549 und H441 des 3D-Testsystems neue prognostische und therapeutische Kandidaten identifiziert. Hierbei haben die durchgef{\"u}hrten Analysen zwei funktionelle Cluster von Protein-Interaktionen um p53 und die STAT-Familie gefunden, welche eine Verbindung zu HSP90 haben und die entsprechenden Behandlungsunterschiede nach einer HSP90-Inhibierung zwischen den beiden Zellkultursystemen erkl{\"a}ren k{\"o}nnen. Unter Ber{\"u}cksichtigung des zelllinien-spezifischen Mutationshintergrunds wurde eine prognostische Markersignatur und daraus abgeleitet HIF1A f{\"u}r die H441-Zelllinie und AMPK f{\"u}r die A549-Zelllinie als neue therapeutische Targets gefunden, wobei die anschließend durchgef{\"u}hrten in silico-Simulationen einen potentiellen therapeutischen Effekt aufzeigen konnten. Weiterhin wurden wichtige experimentelle Readout-Parameter in ein in silico-Lungentumormodell integriert, wobei unter Einbeziehung des Mutationshintergrunds f{\"u}r die verwendeten Zelllinien die HSP90-Behandlung des 3D-Testsystems computergest{\"u}tzt abgebildet werden konnte. Im weiteren Verlauf wurden im in silico-Lungentumormodell Resistenzmechanismen nach einer Gefitinib-Behandlung mit bekanntem Mutationsstatus f{\"u}r die Zelllinien HCC827 und A549 untersucht und daraus folgend neue Therapieans{\"a}tze abgeleitet, die von potentieller klinischer Bedeutung sein k{\"o}nnen. Die durchgef{\"u}hrten in silico-Simulationen f{\"u}r HCC827 konnten hierbei zeigen, dass eine EGFR- und c-MET-Koaktivierung zu einer Gefitinib-Resistenz f{\"u}hren kann, wohingegen bei den A549 eine Komutation von KRAS und IGF-1R zu einem geringen Behandlungsansprechen beitr{\"a}gt. Die Simulationen lassen zudem erkennen, dass eine direkte Inhibierung der an der Resistenzentwicklung beteiligten Rezeptoren c-MET und IGF-1R in beiden F{\"a}llen nicht die bestm{\"o}gliche Therapiestrategie darstellt. In beiden Zelllinien konnte gezeigt werden, dass eine kombinierte Inhibierung von PI3K und MEK den bestm{\"o}glichen therapeutischen Effekt liefert, was demnach einen vielversprechenden Therapieansatz bei Gefitinib-resistenten Lungentumorpatienten darstellt. In einem weiteren Schritt wurde das therapeutische Potential der miRNA-21 im in silico-Modell f{\"u}r die HCC827-Zelllinie untersucht. Die durchgef{\"u}hrten Simulationen zeigen, dass eine miRNA-21-{\"U}berexpression zu einer Resistenzentwickung nach Gefitinib-Behandlung beitragen kann, wobei eine Inhibierung der miRNA-21 diesen Effekt umkehren kann. Die Ergebnisse lassen zudem erkennen, dass eine PTEN-Aktivierung als potentieller Marker einer erfolgreichen therapeutischen Inhibierung der miRNA-21 fungieren kann, wohingegen eine reduzierte miRNA-21-Expression als m{\"o}glicher Marker f{\"u}r eine erfolgreiche Gefitinib-Behandlung dienen kann. (iii) Im dritten Teil der Arbeit wurden systematisch RNA- und Protein-Interaktionen untersucht. Hierzu wurden integrierte systembiologische Analysen an neu identifizierten und funktionell bislang unbekannten lncRNAs durchgef{\"u}hrt. Die Analysen f{\"u}r die infolge einer Herzhypertrophie hochregulierte lncRNA Chast haben umfassend gezeigt, dass diese Proteine und Transkriptionsfaktoren regulieren und binden kann, welche die Signal{\"u}bertragung und Genexpression regulieren, aber auch eine Verbindung zum kardiovaskul{\"a}ren System und stressinduzierter Herzhypertrophie besitzt. Anhand der Ergebnisse l{\"a}sst sich schlussfolgern, dass Chast direkt und indirekt (a) Proteine binden und die Translation beeinflussen kann, zudem eine Chromatin-modifizierende Funktion besitzt und so die Transkription, z.B. f{\"u}r herz- und stress-assoziierte Gene, reguliert, und/oder (b) in einem negativen Feedbackloop seine eigene Transkription reguliert. Obwohl lncRNAs meist eine geringe Konservierung aufweisen, konnten die durchgef{\"u}hrten Analysen f{\"u}r Chast eine Sequenz-Struktur-Konservierung in S{\"a}ugetieren aufzeigen. Weiterhin haben die Untersuchungen an zwei hypoxie-induzierten lncRNAs in Endothelzellen gezeigt, dass die lncRNA MIR503HG eine hohe Sequenz-Struktur-Konservierung in S{\"a}ugetieren besitzt, wohingegen die LINC00323-003 eine geringe Konservierung aufzeigt. Dies untermauert die Tatsache, dass lncRNAs h{\"a}ufig eine geringe Konservierung aufweisen, was Untersuchungen in Modellorganismen hinsichtlich einer therapeutischen Nutzung schwierig machen. Da sich zahlreiche Untersuchungen auf Interaktionen und Signalwege konzentriert haben, wurde abschließend eine Datenbank entwickelt, welche Analysen von Protein-Interaktionen und Signalwegen nachhaltig voranbringt. Die entwickelte DrumPID-Datenbank stellt insbesondere die Interaktion zwischen einem Medikament und seinem Target in den Fokus und erm{\"o}glicht Analysen einzelner Interaktionen und beteiligter Signalwege, bietet zus{\"a}tzlich aber auch verschiedene Links zu anderen Datenbanken f{\"u}r individuelle weiterf{\"u}hrende Analysen. DrumPID erm{\"o}glicht ein geeignetes Medikament u. a. f{\"u}r ein vorgegebenes Zielprotein zu finden und dessen Wirkmechanismus und Interaktionskontext zu untersuchen, was zu einem besseren experimentellen Verst{\"a}ndnis beitragen kann. Zudem erlaubt DrumPID eine potentielle chemische Leitstruktur f{\"u}r ein Zielprotein zu entwickeln, was z.B. spezifisch ein parasitisches Protein inhibiert, ohne dabei einen toxischen Effekt im Menschen zu haben. Zahlreiche weitere Pharmakabeispiele belegen, dass DrumPID f{\"u}r den t{\"a}glichen wissenschaftlichen Gebrauch auf dem Gebiet der Analyse von Protein-Pharmaka-Interaktionen und der Medikamentenentwicklung geeignet ist. Die beschriebenen Ergebnisse der Promotionsarbeit wurden in f{\"u}nf Originalarbeiten, zwei {\"U}bersichtsartikeln und einem Buchteil, u. a. in Science Translational Medicine, ver{\"o}ffentlicht, sechs dieser Publikationen erfolgten im Rahmen von Erstautorschaften.},
  subject      = {Systembiologie},
  language  = {de}
}
@article{VieiraJonesDanonetal.2012,
  author    = {Vieira, Jacqueline and Jones, Alex R. and Danon, Antoine and Sakuma, Michiyo and Hoang, Nathalie and Robles, David and Tait, Shirley and Heyes, Derren J. and Picot, Marie and Yoshii, Taishi and Helfrich-F{\"o}rster, Charlotte and Soubigou, Guillaume and Coppee, Jean-Yves and Klarsfeld, Andr{\´e} and Rouyer, Francois and Scrutton, Nigel S. and Ahmad, Margaret},
  title     = {Human Cryptochrome-1 Confers Light Independent Biological Activity in Transgenic Drosophila Correlated with Flavin Radical Stability},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {3},
  doi       = {10.1371/journal.pone.0031867},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134513},
  pages     = {e31867},
  year      = {2012},
  abstract  = {Cryptochromes are conserved flavoprotein receptors found throughout the biological kingdom with diversified roles in plant development and entrainment of the circadian clock in animals. Light perception is proposed to occur through flavin radical formation that correlates with biological activity in vivo in both plants and Drosophila. By contrast, mammalian (Type II) cryptochromes regulate the circadian clock independently of light, raising the fundamental question of whether mammalian cryptochromes have evolved entirely distinct signaling mechanisms. Here we show by developmental and transcriptome analysis that Homo sapiens cryptochrome - 1 (HsCRY1) confers biological activity in transgenic expressing Drosophila in darkness, that can in some cases be further stimulated by light. In contrast to all other cryptochromes, purified recombinant HsCRY1 protein was stably isolated in the anionic radical flavin state, containing only a small proportion of oxidized flavin which could be reduced by illumination. We conclude that animal Type I and Type II cryptochromes may both have signaling mechanisms involving formation of a flavin radical signaling state, and that light independent activity of Type II cryptochromes is a consequence of dark accumulation of this redox form in vivo rather than of a fundamental difference in signaling mechanism.},
  language  = {en}
}
@article{HeddergottKruegerBabuetal.2012,
  author    = {Heddergott, Niko and Kr{\"u}ger, Timothy and Babu, Sujin B. and Wei, Ai and Stellamanns, Erik and Uppaluri, Sravanti and Pfohl, Thomas and Stark, Holger and Engstler, Markus},
  title     = {Trypanosome Motion Represents an Adaptation to the Crowded Environment of the Vertebrate Bloodstream},
  series = {PLoS Pathogens},
  volume    = {8},
  journal   = {PLoS Pathogens},
  number    = {11},
  doi       = {10.1371/journal.ppat.1003023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134595},
  pages     = {e1003023},
  year      = {2012},
  abstract  = {Blood is a remarkable habitat: it is highly viscous, contains a dense packaging of cells and perpetually flows at velocities varying over three orders of magnitude. Only few pathogens endure the harsh physical conditions within the vertebrate bloodstream and prosper despite being constantly attacked by host antibodies. African trypanosomes are strictly extracellular blood parasites, which evade the immune response through a system of antigenic variation and incessant motility. How the flagellates actually swim in blood remains to be elucidated. Here, we show that the mode and dynamics of trypanosome locomotion are a trait of life within a crowded environment. Using high-speed fluorescence microscopy and ordered micro-pillar arrays we show that the parasites mode of motility is adapted to the density of cells in blood. Trypanosomes are pulled forward by the planar beat of the single flagellum. Hydrodynamic flow across the asymmetrically shaped cell body translates into its rotational movement. Importantly, the presence of particles with the shape, size and spacing of blood cells is required and sufficient for trypanosomes to reach maximum forward velocity. If the density of obstacles, however, is further increased to resemble collagen networks or tissue spaces, the parasites reverse their flagellar beat and consequently swim backwards, in this way avoiding getting trapped. In the absence of obstacles, this flagellar beat reversal occurs randomly resulting in irregular waveforms and apparent cell tumbling. Thus, the swimming behavior of trypanosomes is a surprising example of micro-adaptation to life at low Reynolds numbers. For a precise physical interpretation, we compare our high-resolution microscopic data to results from a simulation technique that combines the method of multi-particle collision dynamics with a triangulated surface model. The simulation produces a rotating cell body and a helical swimming path, providing a functioning simulation method for a microorganism with a complex swimming strategy.},
  language  = {en}
}
@article{NanguneriFlottmannHorstmannetal.2012,
  author    = {Nanguneri, Siddharth and Flottmann, Benjamin and Horstmann, Heinz and Heilemann, Mike and Kuner, Thomas},
  title     = {Three-Dimensional, Tomographic Super-Resolution Fluorescence Imaging of Serially Sectioned Thick Samples},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0038098},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134434},
  pages     = {e38098},
  year      = {2012},
  abstract  = {Three-dimensional fluorescence imaging of thick tissue samples with near-molecular resolution remains a fundamental challenge in the life sciences. To tackle this, we developed tomoSTORM, an approach combining single-molecule localization-based super-resolution microscopy with array tomography of structurally intact brain tissue. Consecutive sections organized in a ribbon were serially imaged with a lateral resolution of 28 nm and an axial resolution of 40 nm in tissue volumes of up to 50 \(\mu\)mx50\(\mu\)mx2.5\(\mu\)m. Using targeted expression of membrane bound (m)GFP and immunohistochemistry at the calyx of Held, a model synapse for central glutamatergic neurotransmission, we delineated the course of the membrane and fine-structure of mitochondria. This method allows multiplexed super-resolution imaging in large tissue volumes with a resolution three orders of magnitude better than confocal microscopy.},
  language  = {en}
}
@article{SchokraieWarnkenHotzWagenblattetal.2012,
  author    = {Schokraie, Elham and Warnken, Uwe and Hotz-Wagenblatt, Agnes and Grohme, Markus A. and Hengherr, Steffen and F{\"o}rster, Frank and Schill, Ralph O. and Frohme, Marcus and Dandekar, Thomas and Schn{\"o}lzer, Martina},
  title     = {Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0045682},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134447},
  pages     = {e45682},
  year      = {2012},
  abstract  = {Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.},
  language  = {en}
}
@phdthesis{Koenig2016,
  author    = {K{\"o}nig, Sebastian},
  title     = {Spatially selective visual attention in Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134452},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Finding the right behavior at the right time is one of the major tasks of brains. In a natural scenery there is often an abundance of stimuli present and the brain has to separate the relevant from the irrelevant ones. Selective visual attention (SVA) is a property of higher visual systems that achieves this separation, as it allows to '[…] focus on one source of sensory input to the exclusion of others' (Luck and Mangun, 1996). There are probably several forms of SVA depending upon the criteria used for the separation, such as salience, color, location in space, novelty, or motion. Many studies have investigated SVA in humans and non-human primates. However, complex functions like attention were initially not expected to be already implemented in the brains of simple organisms like Drosophila. After a first demonstration of selective attention in the fly (Wolf and Heisenberg, 1980), it took some time until other studies included attentional mechanisms in their argumentation to explain certain behaviors of Drosophila. However, their definition and characterization of attention differed and often was ambiguous. Here, one particular form, spatially selective visual attention in the fly Drosophila is investigated. It has been shown earlier that the fly spontaneously may restrict its behavioral responses in stationary flight to the visual stimuli on one side of the visual field. On the basis of experiments of Sareen et al., (2011) it has been conjectured that the fly has a focus of attention (FoA) and that the fly responds to the visual stimuli within this area of the visual field. Whether the FoA is the adequate concept for this spatial property of SVA in the fly needs to be further discussed and is a subject also of the present study. At this stage, the concept will be used in the description of the new results expanding the characterization of SVA. This study continued the investigation of SVA during tethered flight with variable but controlled visual input and an automated primary data evaluation. This standardized paradigm allowed for analysis of wild-type behavior as well as for a comparison of several mutant and pharmacologically manipulated strains to the wild-type. Some properties of human SVA like the occurrence of externally as well as internally caused shifts of attention were found in Drosophila and it could be shown, that SVA in the fly can be externally guided and has an attention span. Additionally, a neurotransmitter and proteins, which play a significant role in SVA were discovered. Based on this, the genetic tools available for Drosophila provided the means to a first examination of cells and circuits involved in SVA. Finally, the free walk behavior of flies that had been shown to have compromised SVA was characterized. The results suggested that the observed phenotypes of SVA were not behavior specific. Covert shifts of the FoA were investigated. The FoA can be externally guided by visual cues to one or the other side of the visual field and even after the cue has disappeared it remains there for <4s. An intriguing finding of this study is the fact, that the quality of the cue determines whether it is attractive or repellent. For example a cue can be changed from being repellent (negative) to being attractive (positive) by changing its oscillation amplitude from 4° to 2°. Testing the effectiveness of cues in the upper and lower visual field separately, revealed that the perception of a cue by the fly is not exclusively based on a sum of its specifications. Because positive cueing did not have an after-effect in each of the two half-fields alone, but did so if the cue was shown in both, the fly seems to evaluate the cue for each combination of parameters specifically. Whether this evaluation of the cue changed on a trial-to-trial basis or if the cue in some cases failed to shift the FoA can at this point not be determined. Looking at the responses of the fly to the displacement of a black vertical stripe showed that they can be categorized as no responses, syn-directional responses (following the direction of motion of the stripe) and anti-directional responses (in the opposite direction of the motion of the stripe). The yaw-torque patterns of the latter bared similarities with spontaneous body saccades and they most likely represented escape attempts of the fly. Syn-directional responses, however, were genuine object responses, distinguishable by a longer latency until they were elicited and a larger amplitude. These properties as well as the distribution of response polarities were not influenced by the presence or absence of a cue. When two stripes were displaced simultaneously in opposite directions the rate of no responses increased in comparison to the displacement of a single stripe. If one of the stripes was cued, both, the responses towards and away from the side of cue resembled the syn-directional responses. Significant progress was made with the elucidation of the neuronal underpinnings of SVA. Ablation of the mushroom bodies (MB) demonstrated their requirement for SVA. Furthermore, it was shown that dopamine signaling has to be balanced between too much and too little. Either inhibiting the synthesis of dopamine or its re-uptake at the synapse via the dDAT impaired the flies' susceptibility to cueing. Using the Gal4/UAS system, cell specific expression or knockdown of the dDAT was used to scrutinize the role of MB sub-compartments in SVA. The αβ-lobes turned out to be necessary and sufficient to maintain SVA. The Gal4-line c708a labels only a subset of Kenyon cells (KC) within the αβ-lobes, αβposterior. These cells stand out, because of (A) the mesh-like arrangement of their fibers within the lobes and (B) the fact that unlike the other KCs they bypass the calyx and thereby the main source of olfactory input to the MBs, forming connections only in the posterior accessory calyx (Tanaka et al., 2008). This structure receives no or only marginal olfactory input, suggesting for it a role in tasks other than olfaction. This study shows their requirement in a visual task by demonstrating that they are necessary to uphold SVA. Restoring dDAT function in these approximately only 90 cells was probably insufficient to lower the dopamine concentration at the relevant synapses and hence a rescue failed. Alternatively, the processes mediating SVA at the αβ-lobes might require an interplay between all of their KCs. In conclusion, the results provide an initial point for future research to fully understand the localization of and circuitry required for SVA in the brain. In the experiments described so far, attention has been externally guided. However, flies are also able to internally shift their FoA without any cues from the outside world. In a set of 60 consecutive simultaneous displacements of two stripes, they were more likely to produce a response with the same polarity as the preceding one than a random polarity selection predicted. This suggested a dwelling of the FoA on one side of the visual field. Assuming that each response was influenced by the previous one in a way that the probability to repeat the response polarity was increased by a certain factor (dwelling factor, df), a random selection of response type including a df was computed. Implementation of the df removed the difference between observed probability of polarity repetition and the one suggested by random selection. When the interval between displacements was iteratively increased to 5s, no significant df could be detected anymore for pauses longer than 4s. In conclusion, Drosophila has an attention span of approximately 4s. Flies with a mutation in the radish gene expressed no after-effect of cueing and had a shortened attention span of about 1s. The dDAT inhibitor methylphenidate is able to rescue the first, but does not affect the latter phenotype. Probably, radish is differently involved in the two mechanisms. This study showed, that endogenous (covert) shifts of spatially selective visual attention in the fly Drosophila can be internally and externally guided. The variables determining the quality of a cue turned out to be multifaceted and a more systematic approach is needed for a better understanding of what property or feature of the cue changes the way it is evaluated by the fly. A first step has been made to demonstrate that SVA is a fundamental process and compromising it can influence the characteristics of other behaviors like walking. The existence of an attention span, the dependence of SVA on dopamine as well as the susceptibility to pharmacological manipulations, which in humans are used to treat respective diseases, point towards striking similarities between SVA in humans and Drosophila.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Heidinger2015,
  author    = {Heidinger, Ina M. M.},
  title     = {Beyond metapopulation theory: Determinants of the dispersal capacity of bush crickets and grasshoppers},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135068},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {Habitat fragmentation and destruction due to anthropogenic land use are the major causes of the increasing extinction risk of many species and have a detrimental impact on animal populations in numerous ways. The long-term survival and stability of spatially structured populations in fragmented landscapes largely depends on the colonisation of habitat patches and the exchange of individuals and genes between patches. The degree of inter-patch dispersal, in turn, depends on the dispersal ability of a species (i.e. the combination of physiological and morphological factors that facilitate dispersal) and the landscape structure (i.e. the nature of the landscape matrix or the spatial configuration of habitat patches). As fragmentation of landscapes is increasing and the number of species is continuously declining, a thorough understanding of the causes and consequences of dispersal is essential for managing natural populations and developing effective conservation strategies. In the context of animal dispersal, movement behaviour is intensively investigated with capture-mark-recapture studies. For the analysis of such experiments, the influence of marking technique, handling and translocation of marked animals on movement pattern is of crucial importance since it may mask the effects of the main research question. Chapter 2 of this thesis presents a capture-mark-recapture study investigating the effect of translocation on the movement behaviour of the blue-winged grasshopper Oedipoda caerulescens. Transferring individuals of this grasshopper species to suitable but unfamilliar sites has a significant influence on their movement behaviour. Translocated individuals moved longer distances, showed smaller daily turning angles, and thus their movements were more directed than those of resident individuals. The effect of translocation was most pronounced on the first day of the experiment, but may persist for longer. On average, daily moved distances of translocated individuals were about 50 \% longer than that of resident individuals because they have been transferred to an unfamiliar habitat patch. Depending on experiment duration, this leads to considerable differences in net displacement between translocated and resident individuals. In summary, the results presented in chapter 2 clearly point out that translocation effects should not be disregarded in future studies on arthropod movement, respectively dispersal. Studies not controlling for possible translocation effects may result in false predictions of dispersal behaviour, habitat detection capability or habitat preferences. Beside direct field observations via capture-mark-recapture methods, genetic markers can be used to investigate animal dispersal. Chapter 3 presents data on the genetic structure of populations of Metrioptera bicolor, a wing-dimorphic bush cricket, in a spatially structured landscape with patches of suitable habitat distributed within a diverse matrix of different habitat types. Using microsatellite markers, the effects of geographic distance and different matrix types on the genetic differentiation among 24 local populations was assessed. The results of this study clearly indicate that for M. bicolor the isolation of local populations severely depends on the type of surrounding matrix. The presence of forest and a river running through the study area was positively correlated with the extent of genetic differentiation between populations. This indicates that both matrix types severely impede gene flow and the exchange of individuals between local populations of this bush cricket. In addition, for a subsample of populations which were separated only by arable land or settlements, a significant positive correlation between pairwise genetic and geographic distances exists. For the complete data set, this correlation could not be found. This is most probably due to the adverse effect of forest and river on gene flow which dominates the effect of geographic distance in the limited set of patches investigated in this study. The analyses in chapter 3 clearly emphasize the differential resistance of different habitat types on dispersal and the importance of a more detailed view on matrix 'quality' in metapopulation studies. Studies that focus on the specific dispersal resistance of different matrix types may provide much more detailed information on the dispersal capacity of species than a mere analysis of isolation by distance. Such information is needed to improve landscape oriented models for species conservation. In addition to direct effects on realised dispersal (see chapter 3), landscape structure on its own is known to act as an evolutionary selection agent because it determines the costs and benefits of dispersal. Both morphological and behavioural traits of individuals and the degree to which a certain genotype responds to environmental variation have heritable components, and are therefore expected to be able to respond to selection pressures. Chapter 4 analyses the influence of patch size, patch connectivity (isolation of populations) and sand dynamics (stability of habitat) on thorax- and wing length as proxies for dispersal ability of O. caerulescens in coastal grey dunes. This study revealed clear and sex-specific effects of landscape dynamics and patch configuration on dispersal-related morphology. Males of this grasshopper species were smaller and had shorter wings if patches were larger and less connected. In addition, both sexes were larger in habitat patches with high sand dynamics compared to those in patches with lower dynamics. The investments in wing length were only larger in connected populations when sand dynamics were low, indicating that both landscape and patch-related environmental factors are of importance. These results are congruent with theoretical predictions on the evolution of dispersal in metapopulations. They add to the evidence that dispersal-related morphology varies and is selected upon in recently structured populations even at small spatial scales. Dispersal involves different individual fitness costs like increased predation risk, energy expenditure, costs of developing dispersal-related traits, failure to find new suitable habitat as well as reproductive costs. Therefore, the decision to disperse should not be random but depend on the developmental stage or the physiological condition of an individual just as on actual environmental conditions (context-dependent dispersal, e.g. sex- and wing morph-biased dispersal). Biased dispersal is often investigated by comparing the morphology, physiology and behaviour of females and males or sedentary and dispersive individuals. Studies of biased dispersal in terms of capture-mark-recapture experiments, investigating real dispersal and not routine movements, and genetic proofs of biased dispersal are still rare for certain taxa, especially for orthopterans. However, information on biased dispersal is of great importance as for example, undetected biased dispersal may lead to false conclusions from genetic data. In chapter 5 of this thesis, a combined approach of morphological and genetic analyses was used to investigate biased dispersal of M. bicolor. The presented results not only show that macropterous individuals are predestined for dispersal due to their morphology, the genetic data also indicate that macropters are more dispersive than micropters. Furthermore, even within the group of macropterous individuals, males are supposed to be more dispersive than females. To get an idea of the flight ability of M. bicolor, the morphological data were compared with that of Locusta migratoria and Schistocerca gregaria, which are proved to be very good flyers. Based on the morphological data presented here, one can assume a good flight ability for macropters of M. bicolor, although flying individuals of this species are seldom observed in natural populations.},
  subject      = {Heuschrecken <{\"U}berfamilie>},
  language  = {en}
}
@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}
}
@article{GrafePreiningerSztatecsnyetal.2012,
  author    = {Grafe, T. Ulmar and Preininger, Doris and Sztatecsny, Marc and Kasah, Rosli and Dehling, J. Maximilian and Proksch, Sebastian and H{\"o}dl, Walter},
  title     = {Multimodal Communication in a Noisy Environment: A Case Study of the Bornean Rock Frog Staurois parvus},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0037965},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133718},
  year      = {2012},
  abstract  = {High background noise is an impediment to signal detection and perception. We report the use of multiple solutions to improve signal perception in the acoustic and visual modality by the Bornean rock frog, Staurois parvus. We discovered that vocal communication was not impaired by continuous abiotic background noise characterised by fast-flowing water. Males modified amplitude, pitch, repetition rate and duration of notes within their advertisement call. The difference in sound pressure between advertisement calls and background noise at the call dominant frequency of 5578 Hz was 8 dB, a difference sufficient for receiver detection. In addition, males used several visual signals to communicate with conspecifics with foot flagging and foot flashing being the most common and conspicuous visual displays, followed by arm waving, upright posture, crouching, and an open-mouth display. We used acoustic playback experiments to test the efficacy-based alerting signal hypothesis of multimodal communication. In support of the alerting hypothesis, we found that acoustic signals and foot flagging are functionally linked with advertisement calling preceding foot flagging. We conclude that S. parvus has solved the problem of continuous broadband low-frequency noise by both modifying its advertisement call in multiple ways and by using numerous visual signals. This is the first example of a frog using multiple acoustic and visual solutions to communicate in an environment characterised by continuous noise.},
  language  = {en}
}
@article{HarringtonScelsiHarteletal.2012,
  author    = {Harrington, John M. and Scelsi, Chris and Hartel, Andreas and Jones, Nicola G. and Engstler, Markus and Capewell, Paul and MacLeod, Annette and Hajduk, Stephen},
  title     = {Novel African Trypanocidal Agents: Membrane Rigidifying Peptides},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {9},
  doi       = {10.1371/journal.pone.0044384},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135179},
  pages     = {e44384},
  year      = {2012},
  abstract  = {The bloodstream developmental forms of pathogenic African trypanosomes are uniquely susceptible to killing by small hydrophobic peptides. Trypanocidal activity is conferred by peptide hydrophobicity and charge distribution and results from increased rigidity of the plasma membrane. Structural analysis of lipid-associated peptide suggests a mechanism of phospholipid clamping in which an internal hydrophobic bulge anchors the peptide in the membrane and positively charged moieties at the termini coordinate phosphates of the polar lipid headgroups. This mechanism reveals a necessary phenotype in bloodstream form African trypanosomes, high membrane fluidity, and we suggest that targeting the plasma membrane lipid bilayer as a whole may be a novel strategy for the development of new pharmaceutical agents. Additionally, the peptides we have described may be valuable tools for probing the biosynthetic machinery responsible for the unique composition and characteristics of African trypanosome plasma membranes.},
  language  = {en}
}
@article{RoierLeitnerIwashkiwetal.2012,
  author    = {Roier, Sandro and Leitner, Deborah R. and Iwashkiw, Jeremy and Schild-Pr{\"u}fert, Kristina and Feldman, Mario F. and Krohne, Georg and Reidl, Joachim and Schild, Stefan},
  title     = {Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {8},
  doi       = {10.1371/journal.pone.0042664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135201},
  pages     = {e42664},
  year      = {2012},
  abstract  = {Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.},
  language  = {en}
}
@article{AsoHerbOguetaetal.2012,
  author    = {Aso, Yoshinori and Herb, Andrea and Ogueta, Maite and Siwanowicz, Igor and Templier, Thomas and Friedrich, Anja B. and Ito, Kei and Scholz, Henrike and Tanimoto, Hiromu},
  title     = {Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability},
  series = {PLoS Genetics},
  volume    = {8},
  journal   = {PLoS Genetics},
  number    = {7},
  doi       = {10.1371/journal.pgen.1002768},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130631},
  pages     = {e1002768},
  year      = {2012},
  abstract  = {Animals acquire predictive values of sensory stimuli through reinforcement. In the brain of Drosophila melanogaster, activation of two types of dopamine neurons in the PAM and PPL1 clusters has been shown to induce aversive odor memory. Here, we identified the third cell type and characterized aversive memories induced by these dopamine neurons. These three dopamine pathways all project to the mushroom body but terminate in the spatially segregated subdomains. To understand the functional difference of these dopamine pathways in electric shock reinforcement, we blocked each one of them during memory acquisition. We found that all three pathways partially contribute to electric shock memory. Notably, the memories mediated by these neurons differed in temporal stability. Furthermore, combinatorial activation of two of these pathways revealed significant interaction of individual memory components rather than their simple summation. These results cast light on a cellular mechanism by which a noxious event induces different dopamine signals to a single brain structure to synthesize an aversive memory.},
  language  = {en}
}
@article{BugaScholzKumaretal.2012,
  author    = {Buga, Ana-Maria and Scholz, Claus J{\"u}rgen and Kumar, Senthil and Herndon, James G. and Alexandru, Dragos and Cojocaru, Gabriel Radu and Dandekar, Thomas and Popa-Wagner, Aurel},
  title     = {Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {12},
  doi       = {10.1371/journal.pone.0050985},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130657},
  pages     = {e50985},
  year      = {2012},
  abstract  = {Background: Because most human stroke victims are elderly, studies of experimental stroke in the aged rather than the young rat model may be optimal for identifying clinically relevant cellular responses, as well for pinpointing beneficial interventions. Methodology/Principal Findings: We employed the Affymetrix platform to analyze the whole-gene transcriptome following temporary ligation of the middle cerebral artery in aged and young rats. The correspondence, heat map, and dendrogram analyses independently suggest a differential, age-group-specific behaviour of major gene clusters after stroke. Overall, the pattern of gene expression strongly suggests that the response of the aged rat brain is qualitatively rather than quantitatively different from the young, i.e. the total number of regulated genes is comparable in the two age groups, but the aged rats had great difficulty in mounting a timely response to stroke. Our study indicates that four genes related to neuropathic syndrome, stress, anxiety disorders and depression (Acvr1c, Cort, Htr2b and Pnoc) may have impaired response to stroke in aged rats. New therapeutic options in aged rats may also include Calcrl, Cyp11b1, Prcp, Cebpa, Cfd, Gpnmb, Fcgr2b, Fcgr3a, Tnfrsf26, Adam 17 and Mmp14. An unexpected target is the enzyme 3-hydroxy-3-methylglutaryl-Coenzyme A synthase 1 in aged rats, a key enzyme in the cholesterol synthesis pathway. Post-stroke axonal growth was compromised in both age groups. Conclusion/Significance: We suggest that a multi-stage, multimodal treatment in aged animals may be more likely to produce positive results. Such a therapeutic approach should be focused on tissue restoration but should also address other aspects of patient post-stroke therapy such as neuropathic syndrome, stress, anxiety disorders, depression, neurotransmission and blood pressure.},
  language  = {en}
}
@article{WeisseHeddergottHeydtetal.2012,
  author    = {Weiße, Sebastian and Heddergott, Niko and Heydt, Matthias and Pfl{\"a}sterer, Daniel and Maier, Timo and Haraszti, Tamas and Grunze, Michael and Engstler, Markus and Rosenhahn, Axel},
  title     = {A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {5},
  doi       = {10.1371/journal.pone.0037296},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130666},
  pages     = {e37296},
  year      = {2012},
  abstract  = {We present a quantitative 3D analysis of the motility of the blood parasite Trypanosoma brucei. Digital in-line holographic microscopy has been used to track single cells with high temporal and spatial accuracy to obtain quantitative data on their behavior. Comparing bloodstream form and insect form trypanosomes as well as mutant and wildtype cells under varying external conditions we were able to derive a general two-state-run-and-tumble-model for trypanosome motility. Differences in the motility of distinct strains indicate that adaption of the trypanosomes to their natural environments involves a change in their mode of swimming.},
  language  = {en}
}
@phdthesis{Beck2016,
  author    = {Beck, Katherina},
  title     = {Einfluss von RSK auf die Aktivit{\"a}t von ERK, den axonalen Transport und die synaptische Funktion in Motoneuronen von \(Drosophila\) \(melanogaster\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130717},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {In dieser Arbeit sollte die Funktion von RSK in Motoneuronen von Drosophila untersucht werden. Mutationen im RSK2-Gen verursachen das Coffin-Lowry-Syndrom (CLS), das durch mentale Retardierung charakterisiert ist. RSK2 ist haupts{\"a}chlich in Regionen des Gehirns exprimiert, in denen Lernen und Ged{\"a}chtnisbildung stattfinden. In M{\"a}usen und Drosophila, die als Modellorganismen f{\"u}r CLS dienen, konnten auf makroskopischer Ebene keine Ver{\"a}nderungen in den Hirnstrukturen gefunden werden, dennoch wurden in verschiedenen Verhaltensstudien Defekte im Lernen und der Ged{\"a}chtnisbildung beobachtet. Die synaptische Plastizit{\"a}t und die einhergehenden Ver{\"a}nderungen in den Eigenschaften der Synapse sind fundamental f{\"u}r adaptives Verhalten. Zur Analyse der synaptischen Plastizit{\"a}t eignet sich das neuromuskul{\"a}re System von Drosophila als Modell wegen des stereotypen Innervierungsmusters und der Verwendung ionotroper Glutamatrezeptoren, deren Untereinheiten homolog sind zu den Untereinheiten der Glutamatrezeptoren des AMPA-Typs aus S{\"a}ugern, die wesentlich f{\"u}r die Bildung von LTP im Hippocampus sind. Zun{\"a}chst konnte gezeigt werden, dass RSK in den Motoneuronen von Drosophila an der pr{\"a}synaptischen Seite lokalisiert ist, wodurch RSK eine Synapsen-spezifische Funktion aus{\"u}ben k{\"o}nnte. Morphologische Untersuchungen der Struktur der neuromuskul{\"a}ren Synapsen konnten aufzeigen, dass durch den Verlust von RSK die Gr{\"o}ße der neuromuskul{\"a}ren Synapse, der Boutons sowie der Aktiven Zonen und Glutamatrezeptorfelder reduziert ist. Obwohl mehr Boutons gebildet werden, sind weniger Aktive Zonen und Glutamatrezeptorfelder in der neuromuskul{\"a}ren Synapse enthalten. RSK reguliert die synaptische Transmission, indem es die postsynaptische Sensitivit{\"a}t, nicht aber die Freisetzung der Neurotransmitter an der pr{\"a}synaptischen Seite beeinflusst, obwohl in immunhistochemischen Analysen eine postsynaptische Lokalisierung von RSK nicht nachgewiesen werden konnte. RSK ist demnach an der Regulation der synaptischen Plastizit{\"a}t glutamaterger Synapsen beteiligt. Durch immunhistochemische Untersuchungen konnte erstmals gezeigt werden, dass aktiviertes ERK an der pr{\"a}synaptischen Seite lokalisiert ist und diese synaptische Lokalisierung von RSK reguliert wird. Dar{\"u}ber hinaus konnte in dieser Arbeit nachgewiesen werden, dass durch den Verlust von RSK hyperaktiviertes ERK in den Zellk{\"o}rpern der Motoneurone vorliegt. RSK wird durch den ERK/MAPK-Signalweg aktiviert und {\"u}bernimmt eine Funktion sowohl als Effektorkinase als auch in der Negativregulation des Signalwegs. Demnach dient RSK in den Zellk{\"o}rpern der Motoneurone als Negativregulator des ERK/MAPK-Signalwegs. Dar{\"u}ber hinaus k{\"o}nnte RSK die Verteilung von aktivem ERK in den Subkompartimenten der Motoneurone regulieren. Da in vorangegangenen Studien gezeigt werden konnte, dass ERK an der Regulation der synaptischen Plastizit{\"a}t beteiligt ist, indem es die Insertion der AMPA-Rezeptoren zur Bildung der LTP reguliert, sollte in dieser Arbeit aufgekl{\"a}rt werden, ob der Einfluss von RSK auf die synaptische Plastizit{\"a}t durch seine Funktion als Negativregulator von ERK zustande kommt. Untersuchungen der genetischen Interaktion von rsk und rolled, dem Homolog von ERK in Drosophila, zeigten, dass die durch den Verlust von RSK beobachtete reduzierte Gesamtzahl der Aktiven Zonen und Glutamatrezeptorfelder der neuromuskul{\"a}ren Synapse auf die Funktion von RSK als Negativregulator von ERK zur{\"u}ckzuf{\"u}hren ist. Die Gr{\"o}ße der neuromuskul{\"a}ren Synapse sowie die Gr{\"o}ße der Aktiven Zonen und Glutamatrezeptorfelder beeinflusst RSK allerdings durch seine Funktion als Effektorkinase des ERK/MAPK-Signalwegs. Studien des axonalen Transports von Mitochondrien zeigten, dass dieser in vielen neuropathologischen Erkrankungen beeintr{\"a}chtigt ist. Die durchgef{\"u}hrten Untersuchungen des axonalen Transports in Motoneuronen konnten eine neue Funktion von RSK in der Regulation des axonalen Transports aufdecken. In den Axonen der Motoneurone von RSK-Nullmutanten wurden BRP- und CSP-Agglomerate nachgewiesen. RSK k{\"o}nnte an der Regulation des axonalen Transports von pr{\"a}synaptischem Material beteiligt sein. Durch den Verlust von RSK wurden weniger Mitochondrien in anterograder Richtung entlang dem Axon transportiert, daf{\"u}r verweilten mehr Mitochondrien in station{\"a}ren Phasen. Diese Ergebnisse zeigen, dass auch der anterograde Transport von Mitochondrien durch den Verlust von RSK beeintr{\"a}chtigt ist.},
  subject      = {Taufliege},
  language  = {de}
}
@article{KarlDandekar2013,
  author    = {Karl, Stefan and Dandekar, Thomas},
  title     = {Jimena: Efficient computing and system state identification for genetic regulatory networks},
  series = {BMC Bioinformatics},
  volume    = {14},
  journal   = {BMC Bioinformatics},
  doi       = {10.1186/1471-2105-14-306},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128671},
  year      = {2013},
  abstract  = {Background: Boolean networks capture switching behavior of many naturally occurring regulatory networks. For semi-quantitative modeling, interpolation between ON and OFF states is necessary. The high degree polynomial interpolation of Boolean genetic regulatory networks (GRNs) in cellular processes such as apoptosis or proliferation allows for the modeling of a wider range of node interactions than continuous activator-inhibitor models, but suffers from scaling problems for networks which contain nodes with more than ~10 inputs. Many GRNs from literature or new gene expression experiments exceed those limitations and a new approach was developed. Results: (i) As a part of our new GRN simulation framework Jimena we introduce and setup Boolean-tree-based data structures; (ii) corresponding algorithms greatly expedite the calculation of the polynomial interpolation in almost all cases, thereby expanding the range of networks which can be simulated by this model in reasonable time. (iii) Stable states for discrete models are efficiently counted and identified using binary decision diagrams. As application example, we show how system states can now be sampled efficiently in small up to large scale hormone disease networks (Arabidopsis thaliana development and immunity, pathogen Pseudomonas syringae and modulation by cytokinins and plant hormones). Conclusions: Jimena simulates currently available GRNs about 10-100 times faster than the previous implementation of the polynomial interpolation model and even greater gains are achieved for large scale-free networks. This speed-up also facilitates a much more thorough sampling of continuous state spaces which may lead to the identification of new stable states. Mutants of large networks can be constructed and analyzed very quickly enabling new insights into network robustness and behavior.},
  language  = {en}
}
@article{HuserRohwedderApostolopoulouetal.2012,
  author    = {Huser, Annina and Rohwedder, Astrid and Apostolopoulou, Anthi A. and Widmann, Annekathrin and Pfitzenmaier, Johanna E. and Maiolo, Elena M. and Selcho, Mareike and Pauls, Dennis and von Essen, Alina and Gupta, Tript and Sprecher, Simon G. and Birman, Serge and Riemensperger, Thomas and Stocker, Reinhard F. and Thum, Andreas S.},
  title     = {The Serotonergic Central Nervous System of the Drosophila Larva: Anatomy and Behavioral Function},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {10},
  doi       = {10.1371/journal.pone.0047518},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130437},
  pages     = {e47518},
  year      = {2012},
  abstract  = {The Drosophila larva has turned into a particularly simple model system for studying the neuronal basis of innate behaviors and higher brain functions. Neuronal networks involved in olfaction, gustation, vision and learning and memory have been described during the last decade, often up to the single-cell level. Thus, most of these sensory networks are substantially defined, from the sensory level up to third-order neurons. This is especially true for the olfactory system of the larva. Given the wealth of genetic tools in Drosophila it is now possible to address the question how modulatory systems interfere with sensory systems and affect learning and memory. Here we focus on the serotonergic system that was shown to be involved in mammalian and insect sensory perception as well as learning and memory. Larval studies suggested that the serotonergic system is involved in the modulation of olfaction, feeding, vision and heart rate regulation. In a dual anatomical and behavioral approach we describe the basic anatomy of the larval serotonergic system, down to the single-cell level. In parallel, by expressing apoptosis-inducing genes during embryonic and larval development, we ablate most of the serotonergic neurons within the larval central nervous system. When testing these animals for naive odor, sugar, salt and light perception, no profound phenotype was detectable; even appetitive and aversive learning was normal. Our results provide the first comprehensive description of the neuronal network of the larval serotonergic system. Moreover, they suggest that serotonin per se is not necessary for any of the behaviors tested. However, our data do not exclude that this system may modulate or fine-tune a wide set of behaviors, similar to its reported function in other insect species or in mammals. Based on our observations and the availability of a wide variety of genetic tools, this issue can now be addressed.},
  language  = {en}
}
@article{HendriksmaKuetingHaerteletal.2013,
  author    = {Hendriksma, Harmen P. and K{\"u}ting, Meike and H{\"a}rtel, Stephan and N{\"a}ther, Astrid and Dohrmann, Anja B. and Steffan-Dewenter, Ingolf and Tebbe, Christoph C.},
  title     = {Effect of Stacked Insecticidal Cry Proteins from Maize Pollen on Nurse Bees (Apis mellifera carnica) and Their Gut Bacteria},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0059589},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131025},
  pages     = {e59589},
  year      = {2013},
  abstract  = {Honey bee pollination is a key ecosystem service to nature and agriculture. However, biosafety research on genetically modified crops rarely considers effects on nurse bees from intact colonies, even though they receive and primarily process the largest amount of pollen. The objective of this study was to analyze the response of nurse bees and their gut bacteria to pollen from Bt maize expressing three different insecticidal Cry proteins (Cry1A.105, Cry2Ab2, and Cry3Bb1). Naturally Cry proteins are produced by bacteria (Bacillus thuringiensis). Colonies of Apis mellifera carnica were kept during anthesis in flight cages on field plots with the Bt maize, two different conventionally bred maize varieties, and without cages, 1-km outside of the experimental maize field to allow ad libitum foraging to mixed pollen sources. During their 10-days life span, the consumption of Bt maize pollen had no effect on their survival rate, body weight and rates of pollen digestion compared to the conventional maize varieties. As indicated by ELISA-quantification of Cry1A.105 and Cry3Bb1, more than 98\% of the recombinant proteins were degraded. Bacterial population sizes in the gut were not affected by the genetic modification. Bt-maize, conventional varieties and mixed pollen sources selected for significantly different bacterial communities which were, however, composed of the same dominant members, including Proteobacteria in the midgut and Lactobacillus sp. and Bifidobacterium sp. in the hindgut. Surprisingly, Cry proteins from natural sources, most likely B. thuringiensis, were detected in bees with no exposure to Bt maize. The natural occurrence of Cry proteins and the lack of detectable effects on nurse bees and their gut bacteria give no indication for harmful effects of this Bt maize on nurse honey bees.},
  language  = {en}
}
@article{KatoLuRapaportetal.2013,
  author    = {Kato, Hiroki and Lu, Qiping and Rapaport, Doron and Kozjak-Pavlovic, Vera},
  title     = {Tom70 Is Essential for PINK1 Import into Mitochondria},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0058435},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131061},
  pages     = {e58435},
  year      = {2013},
  abstract  = {PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a responsible gene of Parkinson's disease (PD). The precursor of PINK1 is synthesized in the cytosol and then imported into the mitochondria via the translocase of the OMM (TOM) complex. However, a large part of PINK1 import mechanism remains unclear. In this study, we examined using cell-free system the mechanism by which PINK1 is targeted to and assembled into mitochondria. Surprisingly, the main component of the import channel, Tom40 was not necessary for PINK1 import. Furthermore, we revealed that the import receptor Tom70 is essential for PINK1 import. In addition, we observed that although PINK1 has predicted mitochondrial targeting signal, it was not processed by the mitochondrial processing peptidase. Thus, our results suggest that PINK1 is imported into mitochondria by a unique pathway that is independent of the TOM core complex but crucially depends on the import receptor Tom70.},
  language  = {en}
}
@article{ScharmannThornhamGrafeetal.2013,
  author    = {Scharmann, Mathias and Thornham, Daniel G. and Grafe, T. Ulmar and Federle, Walter},
  title     = {A Novel Type of Nutritional Ant-Plant Interaction: Ant Partners of Carnivorous Pitcher Plants Prevent Nutrient Export by Dipteran Pitcher Infauna},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0063556},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130952},
  pages     = {e63556},
  year      = {2013},
  abstract  = {Many plants combat herbivore and pathogen attack indirectly by attracting predators of their herbivores. Here we describe a novel type of insect-plant interaction where a carnivorous plant uses such an indirect defence to prevent nutrient loss to kleptoparasites. The ant Camponotus schmitzi is an obligate inhabitant of the carnivorous pitcher plant Nepenthes bicalcarata in Borneo. It has recently been suggested that this ant-plant interaction is a nutritional mutualism, but the detailed mechanisms and the origin of the ant-derived nutrient supply have remained unexplained. We confirm that N. bicalcarata host plant leaves naturally have an elevated \(^{15}N/^{14}N\) stable isotope abundance ratio (\(\delta ^{15}N\)) when colonised by C. schmitzi. This indicates that a higher proportion of the plants' nitrogen is insect-derived when C. schmitzi ants are present (ca. 100\%, vs. 77\% in uncolonised plants) and that more nitrogen is available to them. We demonstrated direct flux of nutrients from the ants to the host plant in a \(^{15}N\) pulse-chase experiment. As C. schmitzi ants only feed on nectar and pitcher contents of their host, the elevated foliar \(\delta ^{15}N\) cannot be explained by classic ant-feeding (myrmecotrophy) but must originate from a higher efficiency of the pitcher traps. We discovered that C. schmitzi ants not only increase the pitchers' capture efficiency by keeping the pitchers' trapping surfaces clean, but they also reduce nutrient loss from the pitchers by predating dipteran pitcher inhabitants (infauna). Consequently, nutrients the pitchers would have otherwise lost via emerging flies become available as ant colony waste. The plants' prey is therefore conserved by the ants. The interaction between C. schmitzi, N. bicalcarata and dipteran pitcher infauna represents a new type of mutualism where animals mitigate the damage by nutrient thieves to a plant.},
  language  = {en}
}
@article{SporbertCseresnyesHeidbrederetal.2013,
  author    = {Sporbert, Anje and Cseresnyes, Zoltan and Heidbreder, Meike and Domaing, Petra and Hauser, Stefan and Kaltschmidt, Barbara and Kaltschmidt, Christian and Heilemann, Mike and Widera, Darius},
  title     = {Simple Method for Sub-Diffraction Resolution Imaging of Cellular Structures on Standard Confocal Microscopes by Three-Photon Absorption of Quantum Dots},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0064023},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130963},
  pages     = {e64023},
  year      = {2013},
  abstract  = {This study describes a simple technique that improves a recently developed 3D sub-diffraction imaging method based on three-photon absorption of commercially available quantum dots. The method combines imaging of biological samples via tri-exciton generation in quantum dots with deconvolution and spectral multiplexing, resulting in a novel approach for multi-color imaging of even thick biological samples at a 1.4 to 1.9-fold better spatial resolution. This approach is realized on a conventional confocal microscope equipped with standard continuous-wave lasers. We demonstrate the potential of multi-color tri-exciton imaging of quantum dots combined with deconvolution on viral vesicles in lentivirally transduced cells as well as intermediate filaments in three-dimensional clusters of mouse-derived neural stem cells (neurospheres) and dense microtubuli arrays in myotubes formed by stacks of differentiated C2C12 myoblasts.},
  language  = {en}
}
@article{WolfAkrapMargetal.2013,
  author    = {Wolf, Annette and Akrap, Nina and Marg, Berenice and Galliardt, Helena and Heiligentag, Martyna and Humpert, Fabian and Sauer, Markus and Kaltschmidt, Barbara and Kaltschmidt, Christian and Seidel, Thorsten},
  title     = {Elements of Transcriptional Machinery Are Compatible among Plants and Mammals},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0053737},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131203},
  pages     = {e53737},
  year      = {2013},
  abstract  = {In the present work, the objective has been to analyse the compatibility of plant and human transcriptional machinery. The experiments revealed that nuclear import and export are conserved among plants and mammals. Further it has been shown that transactivation of a human promoter occurs by human transcription factor NF-\(\kappa\) B in plant cells, demonstrating that the transcriptional machinery is highly conserved in both kingdoms. Functionality was also seen for regulatory elements of NF-\(\kappa\) B such as its inhibitor I\(\kappa\)B isoform \(\alpha\) that negatively regulated the transactivation activity of the p50/RelA heterodimer by interaction with NF-\(\kappa\)B in plant cells. Nuclear export of RelA could be demonstrated by FRAP-measurements so that RelA shows nucleo-cytoplasmic shuttling as reported for RelA in mammalian cells. The data reveals the high level of compatibility of human transcriptional elements with the plant transcriptional machinery. Thus, Arabidopsis thaliana mesophyll protoplasts might provide a new heterologous expression system for the investigation of the human NF-\(\kappa\)B signaling pathways. The system successfully enabled the controlled manipulation of NF-\(\kappa\)B activity. We suggest the plant protoplast system as a tool for reconstitution and analyses of mammalian pathways and for direct observation of responses to e. g. pharmaceuticals. The major advantage of the system is the absence of interference with endogenous factors that affect and crosstalk with the pathway.},
  language  = {en}
}
@article{MollRocesFederle2013,
  author    = {Moll, Karin and Roces, Flavio and Federle, Walter},
  title     = {How Load-Carrying Ants Avoid Falling Over: Mechanical Stability during Foraging in Atta vollenweideri Grass-Cutting Ants},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {1},
  doi       = {10.1371/journal.pone.0052816},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131211},
  pages     = {e52816},
  year      = {2013},
  abstract  = {Background: Foraging workers of grass-cutting ants (Atta vollenweideri) regularly carry grass fragments larger than their Fragment length has been shown to influence the ants' running speed and thereby the colony's food intake rate. We investigated whether and how grass-cutting ants maintain stability when carrying fragments of two different lengths but identical mass. Principal Findings: Ants carried all fragments in an upright, backwards-tilted position, but held long fragments more vertically than short ones. All carrying ants used an alternating tripod gait, where mechanical stability was increased by overlapping stance phases of consecutive steps. The overlap was greatest for ants carrying long fragments, resulting in more legs contacting the ground simultaneously. For all ants, the projection of the total centre of mass (ant and fragment) was often outside the supporting tripod, i.e. the three feet that would be in stance for a non-overlapping tripod gait. Stability was only achieved through additional legs in ground contact. Tripod stability (quantified as the minimum distance of the centre of mass to the edge of the supporting tripod) was significantly smaller for ants with long fragments. Here, tripod stability was lowest at the beginning of each step, when the center of mass was near the posterior margin of the supporting tripod. By contrast, tripod stability was lowest at the end of each step for ants carrying short fragments. Consistently, ants with long fragments mainly fell backwards, whereas ants carrying short fragments mainly fell forwards or to the side. Assuming that transporting ants adjust neither the fragment angle nor the gait, they would be less stable and more likely to fall over. Conclusions: In grass-cutting ants, the need to maintain static stability when carrying long grass fragments has led to multiple kinematic adjustments at the expense of a reduced material transport rate.},
  language  = {en}
}
@article{RodriguesPopovKayeetal.2013,
  author    = {Rodrigues, L{\´e}nia and Popov, Nikita and Kaye, Kenneth M. and Simas, J. Pedro},
  title     = {Stabilization of Myc through Heterotypic Poly-Ubiquitination by mLANA Is Critical for \(\gamma\)-Herpesvirus Lymphoproliferation},
  series = {PLoS PATHOGENS},
  volume    = {9},
  journal   = {PLoS PATHOGENS},
  number    = {8},
  doi       = {10.1371/journal.ppat.1003554},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131227},
  pages     = {e1003554},
  year      = {2013},
  abstract  = {Host colonization by lymphotropic \(\gamma\)-herpesviruses depends critically on expansion of viral genomes in germinal center (GC) B-cells. Myc is essential for the formation and maintenance of GCs. Yet, the role of Myc in the pathogenesis of \(\gamma\)-cherpesviruses is still largely unknown. In this study, Myc was shown to be essential for the lymphotropic \(\gamma\)-herpesvirus MuHV- 4 biology as infected cells exhibited increased expression of Myc signature genes and the virus was unable to expand in Myc defficient GC B- cells. We describe a novel strategy of a viral protein activating Myc through increased protein stability resulting in increased progression through the cell cycle. This is acomplished by modulating a physiological posttranslational regulatory pathway of Myc. The molecular mechanism involves Myc heterotypic poly- ubiquitination mediated via the viral E3 ubiquitin- ligase mLANA protein. \(EC_5S^{mLANA}\) modulates cellular control of Myc turnover by antagonizing \(SCF^{Fbw7}\) mediated proteasomal degradation of Myc, mimicking \(SCF^{\beta-TrCP}\). The findings here reported reveal that modulation of Myc is essential for \(\gamma\)-herpesvirus persistent infection, establishing a link between virus induced lymphoproliferation and disease.},
  language  = {en}
}
@article{MuranyiMalkuschMuelleretal.2013,
  author    = {Muranyi, Walter and Malkusch, Sebastian and M{\"u}ller, Barbara and Heilemann, Mike and Kr{\"a}usslich, Hans-Georg},
  title     = {Super-Resolution Microscopy Reveals Specific Recruitment of HIV-1 Envelope Proteins to Viral Assembly Sites Dependent on the Envelope C-Terminal Tail},
  series = {PLoS Pathogens},
  volume    = {9},
  journal   = {PLoS Pathogens},
  number    = {2},
  doi       = {10.1371/journal.ppat.1003198},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131235},
  pages     = {e1003198},
  year      = {2013},
  abstract  = {The inner structural Gag proteins and the envelope (Env) glycoproteins of human immunodeficiency virus (HIV-1) traffic independently to the plasma membrane, where they assemble the nascent virion. HIV-1 carries a relatively low number of glycoproteins in its membrane, and the mechanism of Env recruitment and virus incorporation is incompletely understood. We employed dual-color super-resolution microscopy visualizing Gag assembly sites and HIV-1 Env proteins in virus-producing and in Env expressing cells. Distinctive HIV-1 Gag assembly sites were readily detected and were associated with Env clusters that always extended beyond the actual Gag assembly site and often showed enrichment at the periphery and surrounding the assembly site. Formation of these Env clusters depended on the presence of other HIV-1 proteins and on the long cytoplasmic tail (CT) of Env. CT deletion, a matrix mutation affecting Env incorporation or Env expression in the absence of other HIV-1 proteins led to much smaller Env clusters, which were not enriched at viral assembly sites. These results show that Env is recruited to HIV-1 assembly sites in a CT-dependent manner, while Env\((\Delta CT)\) appears to be randomly incorporated. The observed Env accumulation surrounding Gag assemblies, with a lower density on the actual bud, could facilitate viral spread in vivo. Keeping Env molecules on the nascent virus low may be important for escape from the humoral immune response, while cell-cell contacts mediated by surrounding Env molecules could promote HIV-1 transmission through the virological synapse.},
  language  = {en}
}
@article{KlampCampsNietoetal.2013,
  author    = {Klamp, Tobias and Camps, Marta and Nieto, Benjamin and Guasch, Francesc and Ranasinghe, Rohan T. and Wiedemann, Jens and Petr{\´a}šek, Zdeněk and Schwille, Petra and Klenerman, David and Sauer, Markus},
  title     = {Highly Rapid Amplification-Free and Quantitative DNA Imaging Assay},
  series = {Scientific Reports},
  volume    = {3},
  journal   = {Scientific Reports},
  number    = {1852},
  doi       = {10.1038/srep01852},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130500},
  year      = {2013},
  abstract  = {There is an urgent need for rapid and highly sensitive detection of pathogen-derivedDNAin a point-of-care (POC) device for diagnostics in hospitals and clinics. This device needs to work in a 'sample-in-result-out' mode with minimum number of steps so that it can be completely integrated into a cheap and simple instrument. We have developed a method that directly detects unamplified DNA, and demonstrate its sensitivity on realistically sized 5 kbp targetDNA fragments of Micrococcus luteus in small sample volumes of 20 mL. The assay consists of capturing and accumulating of target DNA on magnetic beads with specific capture oligonucleotides, hybridization of complementary fluorescently labeled detection oligonucleotides, and fluorescence imaging on a miniaturized wide-field fluorescence microscope. Our simple method delivers results in less than 20 minutes with a limit of detection (LOD) of,5 pMand a linear detection range spanning three orders of magnitude.},
  language  = {en}
}
@phdthesis{Kluever2007,
  author    = {Kl{\"u}ver, Nils},
  title     = {Molecular analysis of gonad development in medaka (Oryzias latipes) and Oryzias celebensis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25105},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {The process of sex-determination can be better understood through examinations of developing organs and cells, which are involved in the formation of undifferentiated gonad. This mechanisms show in fish a broad variety, ranging from hermaphroditism to gonochorism and environmental to genetic sex determination. Hormones and abiotic factors such as temperature and pH can influence teleost development and reproductive traits. These factors are vulnerable to pollutants and climate changes. Therefore, it is important to examine gonad development and sex-determination/differentiation in teleost fish. Teleost fish are the largest known group of vertebrates with approximately 25,000 species and are used for such kind of examinations as model organisms. Recently, in Oryzias latipes (medaka), dmrt1bY (or dmy), a member of the Dmrt gene family, has been described as testis-determining gene. However, this gene is not the universal master sex-determining gene in teleost fish. Although dmrt1bY is present in the most closely related species of the genus, namely Oryzias curvinotous, it is absent from other Oryzias species, like Oryzias celebensis, and other fish. During my thesis, I studied gonad development in medaka and in the closely related species Oryzias celebensis. Germ cell specification in medaka seems to be dependent on maternally provided cytoplasmatic determinants, so called germ plasm. Nanos and vasa are such germ cell specific genes. In zebrafish they are asymmetrically localized in the early embryo. I have shown that nanos mRNA is evenly distributed in the early embryo of medaka. A similar pattern has been already described for the medaka vasa homolog, olvas. This suggests differences in PGC specification in zebrafish and medaka. Further, the vasa homolog was isolated and the expression pattern examined in O. celebensis. The results show that it can be used as a germ cell specific marker. Additionally, the primordial germ cell migration in O. celebensis was followed, which is similar to medaka PGC migration. Primordial germ cell migration in vertebrates is dependent on the chemokine stromal cell-derived factor 1 (Sdf-1). Medaka has two different sdf-1 genes, sdf-1a and sdf-1b. Both genes are expressed in the lateral plate mesoderm (LPM). During late embryonic development, I could show that sdf-1a is expressed in newly formed somites and not longer in the LPM. Sdf-1b expression persisted in the posterior part of the lateral plate mesoderm in the developing gonad. In terms of early and late functions, this suggests subfunctionalization of sdf-1a and sdf-1b. In "higher" vertebrates, genes that are involved in the process of gonad development have been studied in detail, e.g. Wt1, Sox9, and Amh. I have analyzed the expression pattern of wt1 and sox9 co-orthologs and amh. In both, the medaka and O. celebensis, wt1a transcripts were localized in the LPM and its expression was similar to sdf-1a gene expression in medaka. Wt1b expression was restricted to the developing pronephric region. During later embryonic development, wt1a is specifically expressed in the somatic cells of the gonad primordium in both sexes. This is the first time that in fish wt1 gene expression in developing gonads has been described. Therefore, this result suggests that wt1a is involved in the formation of the bipotential gonad. Furthermore, I have analyzed the gonad specific function of the wt1 co-orthologs in medaka. I could show that a conditional co-regulation mechanism between Wt1a and Wt1b ensures PGC maintenance and/or survival. The expression of sox9 genes in medaka and sox9b in O. celebensis were detected in the somatic cells of the gonad primordium of both sexes. Additionally, I have shown that amh and amhrII in medaka are expressed in somatic cells of the gonad primordium of both sexes. This suggests that sox9b, amh and amhrII are involved in gonad development and have specific functions in the adult gonad. In O. celebensis I could detect an expression of dmrt1 already six days after fertilization in half of the embryos, which is similar to the dmrt1bY expression in medaka. Whether the expression of dmrt1 is male specific in O. celebensis is currently under investigation. Altogether, the obtained results provide new insights into gene expression patterns during the processes of gonad development. Furthermore, no differences in the expression pattern of wt1a and sox9b during gonad development between the medaka and O. celebensis could be detected. This might indicate that the genetic mechanisms during gonad development are similar in both species.},
  subject      = {Japank{\"a}rpfling},
  language  = {en}
}
@phdthesis{Palanichamy2007,
  author    = {Palanichamy, Arumugam},
  title     = {Influence of transient B cell depletion on recirculating B cells and plasma cells in rheumatoid arthritis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25132},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Die zentrale Rolle der B-Zellen in der Pathogenese von Autoimmunerkrankungen hat in den letzten Jahren zu unterschiedlichen therapeutischen Ans{\"a}tzen gef{\"u}hrt, B-Zellen direkt oder indirekt zu targetieren. Ein Beispiel hierf{\"u}r stellt der monoklonale anti-CD20 Antik{\"o}rper Rituximab dar. Derzeit ist wenig {\"u}ber das Regenerationsverhalten von B-Zellen nach Therapie mit Rituximab bekannt. Daher untersuchten wir die fr{\"u}he Regnerationsphase und die Ver{\"a}nderungen des B-Zellrepertoirs. Am Beispiel der VH4 Familie der Immunglobulin schweren Ketten analysierten wir die Modulation des Immunglobulinrezeptor Repertoires durch die passagere B-Zelldepletion. Insgesamt wurden bei 5 Patienten 3 Zeitpunkte analysiert: vor Therapie, in der fr{\"u}hen Regenerationsphase (ERP- early regeneration period, mit einem B-Zellanteil > 1\% im peripheren Blut) und in der sp{\"a}ten Regenerationsphase (LRP- late regeneration period, 2-3 Monate nach der fr{\"u}hen Regenerationsphase). Bei 3 Patienten (A-C) wurden die Ig-VH4 Gene aus genomischer DNA amplifiziert und zu o.g. Zeitpunkten analysiert. Bei weiteren 2 Patienten (D und E) erfolgte die Analyse der Ig Gene in einzelnen B-Zellen mittels Einzelzellsortierung und Einzelzell RT-PCR. Die B-Zellregeneration nach Therapie mit Rituximab zeigte ein charakteristisches Regenerationsmuster mit einer Dominanz von unreifen CD10+ B-Zellen und CD38hi Plasmazellen w{\"a}hrend der fr{\"u}hen Phase der B-Zellrekonstitution. Im weiteren Verlauf kam es zu einer Abnahme dieser Zellen und einem Anstieg von naiven B-Zellen. Auf der molekularen Ebene zeigte sich vor und nach B-Zelldepletion eine unterschiedliche Nutzung der Ig-VH4 Gene. Mini Gene wie VH4-34 und VH4-39, die in Verbindung mit Autoimmunit{\"a}t stehen, waren vor Einleitung der Therapie {\"u}berexprimiert. Durch die Behandlung mit Rituximab kam es zu einer Ver{\"a}nderung des Repertoires der regenerierenden B-Zellen mit einer reduzierten Benutzung der VH4-39 Gene im B-Zellpool. Tief greifende Ver{\"a}nderungen fanden sich im regenerierenden Repertoire, mit einem relativen Anstieg von stark mutierten (>=9 Mutationen / Ig Sequenz) B-Zellen.. Die Immunph{\"a}notypisierung zeigte, dass diese hochmutierten B-Zellen den Ig-klassengeswitchten Ged{\"a}chtnis B-Zellkompartiment, insbesondere den Plasmazellen zugh{\"o}rig sind. Um diese Hypothese zu untermauern, erfolgte bei 2 Patienten eine Einzelzellsortierung dieser Plasmazellen w{\"a}hrend der fr{\"u}hen Regenerationsphase, welche einen vergleichbaren Mutationsstatus zeigte. Da Plasmazellen kein CD20 Molek{\"u}l exprimieren, werden sie durch eine Therapie mit Rituximab nicht direkt eliminiert. Allerdings zirkulieren sie nicht im peripheren Blut w{\"a}hrend der Phase der B-Zelldepletion. W{\"a}hrend der fr{\"u}hen Regenerationsphase (ERP) lassen sie sich in der Peripherie erneut nachweisen. Es wurde deshalb untersucht ob auch Plasmazellen durch die Therapie moduliert werden, obwohl sie nicht direkt durch Rituximab targetiert werden. In diesem Zusammenhang erfolgte eine detaillierte Analyse des Mutationsmusters der Plasmazellen vor Therapie und w{\"a}hrend der fr{\"u}hen Regenerationsphase. Die Analyse der Mutationsh{\"a}ufigkeit in RGYW/WRCY Hotspot Motive (R=purine, Y=pyrimidine, W=A/T) erlaubt Absch{\"a}tzung in wieweit die somatische Hypermutation der B-Zellen durch T-Zell abh{\"a}ngige Differenzierung erfolgte. Die Plasmazellen vor Therapie zeigten einem verminderten Targeting der RGYW/WRCY Motive. Im Gegensatz hierzu zeigte sich in den rezirkulierenden Plasmazellen w{\"a}hrend der fr{\"u}hen Regenerationsphase ein zunehmendes Targeting der RGYW/WRCY Motive. Dies spricht f{\"u}r einen Repertoire Shift zu mehr T-Zellabh{\"a}ngigen B-Zell Mutation. Ein Zusatand, wie er bei Gesunden beobachtet wird. Um die Hypothese der Rituximab-induzierten Plasmazell Modulation zu st{\"u}tzen wurde die R/S- Ratio (replacement to silent mutations ratio) der hypervariablen Regionen (CDRs) der Plasmazell Ig Sequenzen bestimmt. In unserer Studie war die mittlere R/S Ratio der CDRs der Plasmazellen vor Therapie entsprechend relativ niedrig (1.87). Interessanterweise kam es in der fr{\"u}hen und sp{\"a}ten Regenerationsphase zu einer signifikant erh{\"o}hten R/S Ration in den rezirkulierenden Plasmazellen mit Werten von 2.67 bzw. 3.60. Die verminderte R/S Ratio in den CDRs der Plasmazellen kann als Entwicklung des Ig-Repertoires durch positive Antigenselektion interpretiert werden und weist damit eine Therapie induzierte Ver{\"a}nderung auf, die dem entspricht wie man sie bei Gesunden findet. Zusammenfassend zeigt unsere Studie, dass die passagere B-Zelldepletion mit Rituximab zu einer Modulation des Plasmalzellkompartimentes f{\"u}hrt, welches nicht direkt durch die Therapie targetiert wird. Die Modulation der Plasmazellen bei der RA kann eventuell auch als m{\"o}glicher Biomarker entwickelt werden, um ein Ansprechen auf die Therapie vorherzusagen. Dies muss im Weiteren untersucht werden, um tiefer greifende Einblicke in Prozesse zu erlangen, die durch zuk{\"u}nftige Therapien beeinflussbar werden.},
  subject      = {B-zellen},
  language  = {en}
}
@phdthesis{Schultheis2007,
  author    = {Schultheis, Christina},
  title     = {Die geschlechtsbestimmende Region des Platyfisches Xiphophorus maculatus auf den Geschlechtschromosomen X und Y: Molekulare Analyse der genomischen Struktur und molekulargenetische Untersuchung von Genkandidaten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25170},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Mit {\"u}ber 24.000 Arten sind etwa die H{\"a}lfte aller heute lebenden Wirbeltiere Fische. Im Gegensatz zu V{\"o}geln oder S{\"a}ugetieren weisen Fische eine erstaunliche Vielfalt und Variabilit{\"a}t der Geschlechtsbestimmungsmechanismen auf. S{\"a}mtliche Formen von Zwittrigkeit sowie umweltbedingte und genetische Geschlechtsbestimmung sind beschrieben worden. Die molekularen Grundlagen der genetischen Geschlechtsbestimmung bei Fischen sind jedoch weitgehend unbekannt. F{\"u}r einige Fischarten, wie etwa der Zebrafisch, die beliebte Modellorganismen zur Untersuchung z.B. von Krankheiten sind, liegen bereits sequenzierte Genome vor. Dennoch sind diese Modellorganismen aufgrund bisher nicht identifizierbarer Geschlechtschromosomen oder fehlender geschlechtsgebundener molekularer Marker als Modellorganismen zur Untersuchung der genetischen Geschlechtsbestimmung und der Evolution der Geschlechtschromosomen ungeeignet. Bei Stichling und Medaka, ebenfalls Fische mit vollst{\"a}ndig sequenzierten Genomen, konnte hingegen die geschlechtsbestimmende Region identifiziert werden. Im Medaka ist bereits das geschlechtsbestimmende Gen identifiziert worden, eine Y-spezifische Kopie des Gens dmrt1. Dmrt1bY konnte aber lediglich in einigen Medaka Arten nachgewiesen werden und stellt somit keinesfalls das universelle geschlechtsbestimmende Gen der Fische dar. Da die geschlechtsbestimmenden Regionen von Medaka und Stichling evolution{\"a}r gesehen relativ jung und linienspezifisch sind, spiegeln sie nur begrenzt den evolution{\"a}ren Verlauf der Entstehung von Geschlechtschromosomen und Geschlechtsbestimmungsmechanismen wider. Der Platyfisch Xiphophorus maculatus ist ein hervorragender Modellorganismus zur Untersuchung der Geschlechtsbestimmung und Evolution von Geschlechtschromosomen. Er wird seit Ende 1920 zur Untersuchung von malignen Melanomen verwendet. Interspezifische Hybride bilden durch die kreuzungsbedingte Aktivierung eines Tumorlocus erbliche Melanome aus. Der Tumorlocus konnte bereits molekular identifiziert werden. Er entspricht dem Onkogen Xmrk, das durch eine Xiphophorus-spezifische Duplikation des Protoonkogens egfrb gebildet worden ist. Onkogen und Protoonkogen, die beide f{\"u}r epidermale Wachstumsfaktorrezeptoren codieren, befinden sich in der Subtelomerregion auf den Geschlechtschromosomen des Platyfisches. Sie flankieren die etwa 1 Mb große geschlechtsbestimmende Region. Neben dem geschlechtsbestimmenden Locus sind verschiedene pigmentzelldefinierende Loci in dieser Region vorzufinden. Die Geschlechtschromosomen X und Y des Platyfisches sind sehr homolog, lassen sich aber sowohl cytogenetisch als auch genetisch gut voneinander unterscheiden. Zur Untersuchung der genetischen Struktur der geschlechtsbestimmenden Region und zur Identifizierung des geschlechtsbestimmenden Gens mittels positioneller Klonierung, wurde eine artifizielle Bakterienchromosom-(BAC) Bibliothek aus m{\"a}nnlichen Platyfischen (Genotyp XY) angelegt. Onkogen und Protoonkogen sowie verschiedene andere X- und Y-chromosomale molekulare Marker wurden als Startpunkte f{\"u}r „Chromosomen-Walking" und den Aufbau von X- und Y-chromosomalen artifizielle Bakterienchromosom (BAC)-Contigs verwendet. Hauptaufgabe meiner Doktorarbeit war die Erweiterung und physikalische Verkn{\"u}pfung verschiedener X- und Y-chromosomaler Contigs mittels molekularbiologischer und cytogenetischer Methoden sowie die Identifizierung von Genen mittels Bioinformatik und funktioneller Analyse. Bis zum jetzigen Zeitpunkt decken die BAC-Contigs 3,1 Mb auf dem Y-Chromosom und 3,8 Mb auf dem X-Chromosom in der geschlechtsbestimmenden Region ab. Sie stellen mitunter die gr{\"o}ßten geschlechtschromosomalen Contigs bei Fischen dar. Die X- und Y-chromosomalen Contigs werden derzeit in Kollaboration mit dem Sequenzierungszentrum Genoscope in Frankreich komplett durchsequenziert. Erste Sequenzanalysen weisen auf eine molekulare Differenzierung zwischen den X- und Y-Geschlechtschromosomen in der geschlechtsbestimmenden Region hin. Es konnten ein duplizierter Bereich auf dem Y Chromosom sowie eine Inversion in der geschlechtsbestimmenden Region identifiziert werden. Nichthomologe Rekombinationsereignisse zwischen transponierbaren Elementen und wiederholende Sequenzen sind mutmaßlich an dieser molekularen Umordnung beteiligt. Solche transponierbaren und sich wiederholenden Elemente akkumulieren in der geschlechtsbestimmenden Region und erschwerten auch maßgeblich Aufbau und Ausweitung der geschlechtschromosomalen Contigs. W{\"a}hrend die meisten Elemente auf beiden Geschlechtschromosomen zu finden sind, konnten auch Y-spezifische Kopien nachgewiesen werden, wie beispielsweise der endogene Retrovirus foamy. Eine Reihe von Genkandidaten wurden in der geschlechtsbestimmenden Region identifiziert. Einige stellen aussichtsreiche Kandidaten f{\"u}r den geschlechtsbestimmenden Locus dar. So ist das Gen fredi, das f{\"u}r einen putativen Transkriptionsfaktor mit Helix-Turn-Helix Motiv codiert, im Hoden stark exprimiert. Verschiedene fredi Kopien sind auf dem X und Y Chromosom in der geschlechtsbestimmenden Region identifiziert worden. Interessanterweise ist die codierende Sequenz der X-chromosomalen fredi Kopien durch ein transponierbares Element zerst{\"o}rt. Die Y-chromosomalen Kopien sind hingegen scheinbar nicht beeintr{\"a}chtigt. Zwei weitere miteinander verwandter Genkandidaten namens fah und tan, die bislang f{\"u}r Genprodukte mit unbekannten Eigenschaften codieren, liegen nebeneinander in der geschlechtsbestimmenden Region vor. Expressionsanalysen beider Gene weisen eine spezifische Expression im Ovar und zwar in der vegetativen Hemisph{\"a}re der Oocyten auf. Orthologe Gene wurden in Medaka und Zebrafisch identifiziert und kloniert. Expressionsanalysen in Medaka zeigten eine Ovar-spezifische Transkription wie in Xiphophorus, w{\"a}hrend im Zebrafisch fah und tan ubiquit{\"a}r exprimiert sind. Interessanterweise konnte im Platyfisch eine Spleißvariante von fah identifiziert werden, die auch im Hoden exprimiert ist. Dies macht fah zu einem vielversprechenden Kandidaten f{\"u}r den geschlechtsbestimmenden Locus. Die genomischen Regionen, in der fah und tan bei anderen Fischarten wie Medaka, Zebrafisch und Kugelfisch identifiziert wurden, zeigen hohe Syntenie zur geschlechtsbestimmenden Region des Platyfisches und k{\"o}nnten auch bei diesen Fischarten eine Rolle in der Geschlechtsbestimmung spielen. Ein einziges Gen, das mit fah und tan verwandt ist, konnte auch in Maus, Huhn und Frosch nachgewiesen werden. Interessanterweise konnte auf dem menschlichen X-Chromosom eine mit Stoppcodons durchzogene, zu fah/tan homologe Pseudogene Sequenz identifiziert werden. Diese Syntenie zwischen Geschlechtschromosomen von Fischen und S{\"a}ugern k{\"o}nnte auf eine evolution{\"a}r sehr alte geschlechtsbestimmende Region der Wirbeltiere hindeuten. Zusammenfassend hat diese Arbeit neben neuen Erkenntnissen {\"u}ber die Evolution der Geschlechtschromosomen bei Fischen verschiedene Genkandidaten f{\"u}r den geschlechtsbestimmenden Locus geliefert, die nun auch funktionell analysiert werden m{\"u}ssen.},
  subject      = {Geschlechtsbestimmung},
  language  = {de}
}
@phdthesis{Weniger2007,
  author    = {Weniger, Markus},
  title     = {Genome Expression Pathway Analysis Tool - Analyse und Visualisierung von Microarray Genexpressionsdaten unter genomischen, proteomischen und metabolischen Gesichtspunkten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25392},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Die Messung der Genexpression ist f{\"u}r viele Bereiche der Biologie und Medizin wichtig geworden und unterst{\"u}tzt Studien {\"u}ber Behandlung, Krankheiten und Entwicklungsstadien. Microarrays k{\"o}nnen verwendet werden, um die Expression von tausenden mRNA-Molek{\"u}len gleichzeitig zu messen und erm{\"o}glichen so einen Einblick und einen Vergleich der verschiedenen zellul{\"a}ren Bedingungen. Die Daten, die durch Microarray-Experimente gewonnen werden, sind hochdimensional und verrauscht, eine Interpretation der Daten ist deswegen nicht einfach. Obwohl Programme f{\"u}r die statistische Auswertung von Microarraydaten existieren, fehlt vielen eine Integration der Analyseergebnisse mit einer automatischen Interpretationsm{\"o}glichkeit. In dieser Arbeit wurde GEPAT, Genome Expression Pathway Analysis Tool, entwickelt, das eine Analyse der Genexpression unter dem Gesichtspunkten der Genomik, Proteomik und Metabolik erm{\"o}glicht. GEPAT integriert statistische Methoden zum Datenimport und -analyse mit biologischer Interpretation f{\"u}r Genmengen oder einzelne Gene, die auf dem Microarray gemessen werden. Verschiedene Typen von Oligonukleotid- und cDNAMicroarrays k{\"o}nnen importiert werden, unterschiedliche Normalisierungsmethoden k{\"o}nnen auf diese Daten angewandt werden, anschließend wird eine Datenannotation durchgef{\"u}hrt. Nach dem Import k{\"o}nnen mit GEPAT verschiedene statische Datenanalysemethoden wie hierarchisches, k-means und PCA-Clustern, ein auf einem linearen Modell basierender t-Test, oder ein Vergleich chromosomaler Profile durchgef{\"u}hrt werden. Die Ergebnisse der Analysen k{\"o}nnen auf H{\"a}ufungen biologischer Begriffe und Vorkommen in Stoffwechselwegen oder Interaktionsnetzwerken untersucht werden. Verschiedene biologische Datenbanken wurden integriert, um zu jeder Gensonde auf dem Array Informationen zur Verf{\"u}gung stellen zu k{\"o}nnen. GEPAT bietet keinen linearen Arbeitsablauf, sondern erlaubt die Benutzung von beliebigen Teilmengen von Genen oder biologischen Proben als Startpunkt einer neuen Analyse oder Interpretation. Dabei verl{\"a}sst es sich auf bew{\"a}hrte Datenanalyse-Pakete, bietet einen modularen Ansatz zur einfachen Erweiterung und kann auf einem verteilten Computernetzwerk installiert werden, um eine große Zahl an Benutzern zu unterst{\"u}tzen. Es ist unter der LGPL Open-Source Lizenz frei verf{\"u}gbar und kann unter http://gepat.sourceforge.net heruntergeladen werden.},
  subject      = {Microarray},
  language  = {de}
}
@phdthesis{Tischner2007,
  author    = {Tischner, Denise},
  title     = {Mechanistische Untersuchungen zur Therapie von Multipler Sklerose am Beispiel der Experimentellen Autoimmunen Encephalomyelitis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-25258},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {No abstract available},
  subject      = {Autoimmunit{\"a}t},
  language  = {de}
}
@phdthesis{Golitschek2007,
  author    = {Golitschek, Robert von},
  title     = {Charakterisierung von genomischer Instabilit{\"a}t mit Hilfe der Spektralen Karyotypisierung beim Werner-Syndrom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-24957},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Im Rahmen dieser Arbeit wurden erstmals Metaphasen von Fibroblastenkulturen (AA, WL, SCH, H-51) von Patienten mit der klinischen Verdachtsdiagnose Werner Syndrom (WS) mit der Spektralen Karyotypisierung (SKY) analysiert. Die Auswertung best{\"a}tigte in allen vier Zelllinien (ZLL) die zuvor mit konventionellen Methoden (z.B. mit G- und R-B{\"a}nderung) etablierten zytogenetischen Charakteristika des WS in Form des „Variegated Translocation Mosaicism" (VTM) und der im zeitlichen Verlauf einer Zellkultur vorherrschenden zytogenetischen, dominanten Klone, deren Eigenschaften mit den drei Schlagw{\"o}rtern „clonal attenuation", „clonal succession" und „clonal expansion" bereits durch Salk et al. [28] treffend umschrieben wurden. Alle ZLL wurden nach 7 oder 8 Passagen seneszent, einer f{\"u}r WS-Fibroblasten typischen, reduzierten Lebensspanne. In der genaueren Analyse der aberranten Metaphasen war SKY den konventionellen Methoden deutlich {\"u}berlegen. W{\"a}hrend bei Salk et al. in 1005 Metaphasen 271 Br{\"u}che entdeckt wurden, wurden mit SKY in 69 Metaphasen 108 Br{\"u}che eindeutig klassifiziert, was außerdem eine detailliertere Einteilung der Klone in unterschiedliche, teilweise singul{\"a}re Subklone erforderlich machte. Die bisher noch nie in WS-Zellen festgestellten trizyklischen Chromosomenaustausche und dreifach-rekombinanten Chromosomen zeigten die F{\"a}higkeit der SKY-Methode, komplexe genomische Ver{\"a}nderungen genau darzustellen. Zudem wurde erstmals ein pseudotetraploider Subklon T mit 87-90 Chromosomen entdeckt, der aus der Mutterkultur WL stammte und ein ungew{\"o}hnliches Wachstumspotential von etwa 45 Populationsverdoppelungen (PD) erreichte und die durchschnittlichen 20 PD von WS-Fibroblasten um mehr als das Doppelte {\"u}berschritt, aber unter den 54 PD von Kontrollfibroblasten lag. Eine Tetrasomie wurde f{\"u}r alle autosomalen Chromosomen außer den Chromosomen 4 und 6 festgestellt, die jeweils dreimal, die Geschlechtschromosomen X und Y jeweils zweimal vertreten waren. Die Translokationen waren identisch mit denen von Klon a aus WL, allerdings in jeweils zweifacher Ausf{\"u}hrung. 77 der 10 Chromosomen beinhalteten in den 69 Metaphasen \&\#8805;6 Br{\"u}che und waren in jeweils mindestens 3 der 4 ZLL an Chromosomenaberrationen beteiligt. V.a. Chromosom 16 war mit 17 Bruchpunkten bzw. in 23 von 78 aberranten Chromosomen am h{\"a}ufigsten involviert. Zudem war es an zwei der drei dreifach-rekombinierten Chromosomen und bei einem der zwei trizyklischen Chromosomenaustausche beteiligt. Dies weist auf eine m{\"o}glicherweise große Bedeutung von Chromosom 16 in Rekombinationsprozessen hin. Auff{\"a}llig war eine nicht-zuf{\"a}llige Bruchpunktverteilung. Die Bruchpunkte 3q11\&\#8594;q12, 9q13, 15q15, 16q12\&\#8594;q13 und 16q22 waren m{\"o}gliche hot spots f{\"u}r Bruchereignisse und trugen Rechnung f{\"u}r \&\#8776;21\% der Bruchereignisse. V.a. 16q22 brach am h{\"a}ufigsten (11mal), war als einziger Bruchpunkt in allen 4 Zelllinien vorhanden und maßgeblich f{\"u}r die hohe Beteiligung des Chromosoms 16 an strukturellen Aberrationen verantwortlich. 16q22 wurde in vorherigen Untersuchungen bisher noch nicht als einer der bevorzugten Bruchpunkte in WS festgestellt. Einige der bei Salk et al. genannten hot spots wurden in dieser Arbeit best{\"a}tigt, jedoch mit unterschiedlichem Verteilungsmuster. Dies h{\"a}ngt m{\"o}glicherweise mit der h{\"o}heren Sensitivit{\"a}t von SKY, aber auch mit der in dieser Arbeit relativ niedrigen Anzahl an Metaphasen zusammen. F{\"u}r SKY bestehen weitere mannigfaltige Anwendungsm{\"o}glichkeiten , die in der zytogenetischen Forschung nicht nur auf dem Gebiet des WS Fortschritte erzielen k{\"o}nnen. SKY ist zudem eine sichere Methode, erfordert jedoch einen hohen zeitlichen und materiellen Aufwand, die die Anwendungsm{\"o}glichkeiten wiederum limitieren. Als diagnostisches Instrument erscheint SKY daher nur in F{\"a}llen sinnvoll, in denen nach der Anwendung konventioneller Methoden weiterhin Unsicherheiten bez{\"u}glich der Diagnose bestehen. Mit der Eigenschaft komplexe Rearrangements mit hoher Sensitivit{\"a}t zweifelsfrei nachzuweisen, kann es jedoch als der Gold-Standard bei unklaren F{\"a}llen gelten.},
  subject      = {Progeria adultorum},
  language  = {de}
}
@article{SchwabSebaldWeiss1972,
  author    = {Schwab, A. J. and Sebald, Walter and Weiss, H.},
  title     = {Schnelle Markierung eines mitochondrial synthetisiertem Polypeptids einer Cytochromoxidasen-Pr{\"a}paration aus Neurospora},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-84206},
  year      = {1972},
  abstract  = {no abstracts available},
  subject      = {Physiologische Chemie},
  language  = {de}
}
@unpublished{Dandekar2007,
  author    = {Dandekar, Thomas},
  title     = {Some general system properties of a living observer and the environment he explores},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33537},
  year      = {2007},
  abstract  = {In a nice assay published in Nature in 1993 the physicist Richard God III started from a human observer and made a number of witty conclusions about our future prospects giving estimates for the existence of the Berlin Wall, the human race and all the rest of the universe. In the same spirit, we derive implications for "the meaning of life, the universe and all the rest" from few principles. Adams´ absurd answer "42" tells the lesson "garbage in / garbage out" - or suggests that the question is non calculable. We show that experience of "meaning" and to decide fundamental questions which can not be decided by formal systems imply central properties of life: Ever higher levels of internal representation of the world and an escalating tendency to become more complex. An observer, "collecting observations" and three measures for complexity are examined. A theory on living systems is derived focussing on their internal representation of information. Living systems are more complex than Kolmogorov complexity ("life is NOT simple") and overcome decision limits (G{\"o}del theorem) for formal systems as illustrated for cell cycle. Only a world with very fine tuned environments allows life. Such a world is itself rather complex and hence excessive large in its space of different states - a living observer has thus a high probability to reside in a complex and fine tuned universe.},
  subject      = {Komplex <Algebra>},
  language  = {en}
}
@phdthesis{Steigerwald2008,
  author    = {Steigerwald, Jutta},
  title     = {Der NK-Zellrezeptor NKG2D als Zielstruktur f{\"u}r eine Antik{\"o}rper-basierte therapeutische Immunmodulation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33446},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Das NKG2D (Natural Killer Group 2 Member D)-Protein, ist ein aktivierender Rezeptor, der es NK- und CD8+ T-Zellen erm{\"o}glicht, infizierte oder transformierte k{\"o}rpereigene Zellen zu erkennen und zu eliminieren. Eine Fehlregulation dieses Rezeptors auf Immunzellen scheint jedoch auch zur Ausbildung von Autoimmunerkrankungen wie Typ I Diabetes, Z{\"o}liakie und RA zu f{\"u}hren. Im Rahmen dieser Arbeit wurde ein humaner Antik{\"o}rper gegen hNKG2D f{\"u}r einen m{\"o}glichen therapeutischen Einsatz bei Autoimmunerkrankungen generiert. Basierend auf den Sequenzen von schwerer (VH) und leichter Kette (VL) der murinen monoklonalen Antik{\"o}rper 6H7 und 6E5A7, welche hNKG2D spezifisch binden und die Interaktion zwischen Ligand und Rezeptor blockieren, wurden scFv-Phagenbibliotheken hergestellt. Diese wurden anschließend zur Selektion im Phagen-Display eingesetzt. Der Humanisierungsprozess erfolgte hierbei mit Hilfe des Guided Selection-Verfahrens. Dazu wurde in einem ersten Phagen-Display-Durchgang die VH-Dom{\"a}ne des parentalen scFv mit einem humanen VL-Repertoire kombiniert. Die beiden daraus resultierenden humanen VL-Ketten wurden im darauf folgenden Schritt mit einem Repertoire an humanen VH-Dom{\"a}nen verkn{\"u}pft. Da hierbei kein humaner rekombinanter scFv mit hNKG2D-Bindungsaktivit{\"a}t identifiziert werden konnte, musste eine schrittweise Humanisierung der Framework-Regionen (FR) der VH unter Beibehaltung der murinen CDR-Bereiche erfolgen. Diese f{\"u}hrte zur Generierung des humanen scFv E1VLV71KVH, welcher neben den murinen CDR-Regionen lediglich noch drei Aminos{\"a}uren murinen Ursprungs im FR-Bereich besaß. Dessen biologische Aktivit{\"a}t wurde nach Konvertierung in das IgG1/lambda-Format in verschiedenen in vitro-Systemen analysiert. Anhand der Ergebnisse aus diesen Versuchen konnte ein deutlicher Verlust der Affinit{\"a}t und inhibitorischen Aktivit{\"a}t nach der Humanisierung festgestellt werden. Die dadurch erforderliche Affinit{\"a}tsmaturierung des E1VLV71KVH Antik{\"o}rpers mittels sequentieller Randomisierung des CDR3-Bereichs von E1VL und V71KVH resultierte in f{\"u}nf unterschiedlichen, hoch-affinen Anti-hNKG2D scFv. Zwei dieser generierten Konstrukte, B1VLB6VH und E4VLG10VH, wurden nach ihrer Herstellung als vollst{\"a}ndige IgG1/lambda-Antik{\"o}rper in vitro hinsichtlich ihrer Aktivierungs- und Neutralisierungsaktivit{\"a}t, sowie ihrer Stabilit{\"a}t und Internalisierung durch NK-Zellen untersucht. Beide Antik{\"o}rper wiesen nach der Affinit{\"a}tsmaturierung mit einem IC50 von ca. 3,4x 10-2 µg/ml ein wesentlich h{\"o}heres Inhibitionspotential als der murine Ursprungsantik{\"o}rper (ca. 3,3 µg/ml) auf und zeigten gegen{\"u}ber Hitzeeinwirkung und Serumproteasen eine hohe Stabilit{\"a}t. Mit Hilfe fluoreszenzmikroskopischer Untersuchungen konnten Internalisierungsvorg{\"a}nge der Antik{\"o}rper in die NK-Zelle beobachtet werden. F{\"u}r ein besseres Verst{\"a}ndnis NKG2D-abh{\"a}ngiger Regulationsvorg{\"a}nge und die Identifizierung NKG2D-spezifischer Zielgene wurde das Genexpressionsprofil von humanen NK-Zellen nach Interaktion mit dem NKG2D-Liganden ULBP-1Fc mittels Microarray untersucht. Infolge einer anschließenden Validierung der Ergebnisse auf RNA- und Proteinebene konnten mittels RT-qPCR, FACS, ELISA und CBA NKG2D-spezifische Biomarker wie CRTAM, TNFalpha, IFNgamma und GM-CSF etabliert werden. Erg{\"a}nzend zu 51Cr-Freisetzungs-Experimenten in zwei unterschiedlichen in vitro Zellkultursystemen erm{\"o}glichten diese Biomarker eine umfassende Charakterisierung neutralisierender und aktivierender Eigenschaften der beiden Antik{\"o}rper B1VLB6VH und E4VLG10VH. Anhand dieser Experimente konnte festgestellt werden, dass die humanen Anti-hNKG2D Antik{\"o}rper eine ambivalente Funktionalit{\"a}t aufweisen. In L{\"o}sung sind sie in der Lage, NKG2D-induzierte CRTAM-Expression, Zellyse und Zytokinfreisetzung zu inhibieren. Nach Kreuzvernetzung des NKG2D-Rezeptors {\"u}ber an Platten immobilisierte Anti-hNKG2D Antik{\"o}rper hingegen lassen sich aktivierende Eigenschaften wie Zellyse und Zytokinsekretion durch NK Zellen beobachten. Aufgrund ihrer ambivalenten Aktivit{\"a}t scheint ein therapeutischer Einsatz der beiden Antik{\"o}rper bei humanen Autoimmunerkrankungen zum jetzigen Zeitpunkt noch nicht m{\"o}glich. In der vorliegenden Arbeit wurden somit die Voraussetzungen geschaffen, um einen humanen, hoch affinen hNKG2D neutralisierenden Antik{\"o}rper in einem letzten Schritt in ein besser geeignetes Antik{\"o}rper-Format (scFv, Fab oder F(ab)2) zu konvertieren.},
  subject      = {Antik{\"o}rper},
  language  = {de}
}
@article{ScheerFrankeTrendelenburgetal.1976,
  author    = {Scheer, Ulrich and Franke, Werner W. and Trendelenburg, Michael F. and Spring, Herbert},
  title     = {Classification of loops of lampbrush chromosomes according to the arrangement of transcriptional complexes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32822},
  year      = {1976},
  abstract  = {The arrangement of transcriptional units in the loops of lampbrush chromosomes from oocyte nuclei of urodele amphibia and from primary nuclei of the green alga Acetabularia have been studied in the electron microscope using spread preparations. Loops with different patterns of arrangement of matrix units (i.e. to a first approximation, transcriptional units) can be distinguished: (i) loops consisting of one active transcriptional unit; (ii) loops containing one active transcriptional unit plus additional fibril-free, i.e. apparently untranscribed, intercepts that may include 'spacer' regions; (iii) loops containing two or more transcriptional units arranged in identical or changing polarities, with or without interspersed apparent spacer regions. Morphological details of the transcriptional complexes are described. The observations are not compatible with the concept that one loop reflects one and only one transcriptional unit but, rather, lead to a classification of loop types according to the arrangement of their transcriptional units. We propose that the lampbrush chromosome loop can represent a unit for the coordinate transcription of either one gene or a set of several (different) genes.},
  language  = {en}
}
@phdthesis{Li2009,
  author    = {Li, Naixin},
  title     = {Dorso-ventral Differentiation and Specification of the Mesencephalon in Early Chick Embryos},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32950},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {The chick midbrain is subdivided into functionally distinct ventral and dorsal domains, tegmentum and optic tectum. In the mature tectum, neurons are organized in layers, while they form discrete nuclei in the tegmentum. An interesting characteristic of the embryonic brain is the development of a large optic tectum, of which the growth becomes obvious at embryonic day 3 (E3). Dorsoventral (DV) specification of the early midbrain should thus play a crucial role for the organization of the neuronal circuitry in optic tectum and tegmentum. In the first part of my thesis, I investigated regional commitment and establishment of cellular differences along the midbrain DV axis. I examined the commitment of gene expression patterns in isolated ventral and dorsal tissue in vivo and in vitro, and studied their cell mixing properties. Explant cultures, and grafting of dorsal midbrain into a ventral environment or vice versa, revealed a gradual increase in the autonomy of region-specific gene regulation between, which was accompanied by a gradual increase in differential adhesive properties from E2 to E3, once the DV axis polarity was fixed. These events happened at a time-point when the majority of midbrain cells are not yet differentiated. Long-term transplantation (6 - 9 days) using quail cells from ventral midbrain as grafts showed the same result. Hence, the results suggest that progressive specification of the midbrain DV axis is accompanied by progressively reduced cell mixing between dorsal and ventral precursors, leading to a partial regionalization of midbrain tissue into autonomous units of precursor cell populations. In the second part I investigated the genes that might be involved in regulating the growth of the tectum. In particular, I focused on the role of Pax7 transcription factor, a paired domain protein. The results suggested that Pax7 was involved in regulating the medial-lateral extension of the tectum. Over expression of Pax7 in dorsal midbrain led to an enlarged tectum accompanied by a raise in cell division, while Pax7 knockdown by shrank caused a reduction in tectum. The overall pattern of neuronal differentiation was not disturbed by an up or down regulation of Pax7. Pax7 also positively regulated Pax3, another pair-ruled gene expressed dorsally. These results suggest that Pax7 very likely together with Pax3 could facilitate or maintain neural cell proliferation in the midbrain at early stages and that a regulation of the size in that region does not influence the neuronal patterning of the developmental field. I further checked the expression and function of a GFPase Rab 23, that was suggested to be involved in the DV patterning in mouse neural tube as a negative regulator of Shh signaling. Overexpression of Rab23 indicated that it facilitated the expression of Pax7 and Pax3 in the neural tube and suppressed ventral genes like Nkx6.1 cell autonomously, however, it did not disturb neuronal patterning. Interestingly, a thorough expression study of Rab 23 during chick early development revealed that Rab23 is already expressed very early and asymmetrically during gastrulation, suggesting a possible role of Rab23 on the left-right determination of Hensen's node. In combination with the result that Rab23 is expressed in the notochord early in development, I assume that both Rab23 and Shh exist in all neural progenitor cells initially, and when their expression patterns separate gradually the neural cells adopt a ventral or dorsal fate according to their location along the dorsoventral axis. The avian embryo is a classic system used widely to investigate questions of vertebrate development. The easy and cheap accessibility of the embryo for in ovo or ex ovo experiments all around the year make it an ideal animal model to work with. The only recently developed method of over expressing genes in specific cells or regions in the chick embryo by electroporation enabled me to study different ways of gene suppression using this way of gene transfection. Thus, I compared the effect of long-hairpin and short hairpin dsRNA in different vectors and antisense morpholino oligonucleotides. The results revealed that all hairpin dsRNA constructs did reduce gene and protein expression often accompanied by morphological changes. Most efficiently were shRNAi constructs cloned into a siRNA-specific vector - pSilencer 1.0-U6. Gene silencing was already well observed 36 hours after transfection. In comparison antisense morpholino oligonucleotides did not show such big gene reduction as the shRNA in pSilencer. Taken together, this methodical research proposes that the shRNA in the pSilencer vector was a good and effective tool to reduce gene and protein expression locally.},
  subject      = {Differenzierung},
  language  = {en}
}
@phdthesis{Wuest2008,
  author    = {W{\"u}st, Simone},
  title     = {Analyse des Wirkmechanismus von Kortikosteroiden bei der Therapie der Experimentellen Autoimmunen Enzephalomyelitis, einem Tiermodell f{\"u}r Multiple Sklerose},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32961},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {In der vorliegenden Arbeit wurden die Mechanismen der Hochdosis-GC-Pulstherapie im Zusammenhang mit akuten Sch{\"u}ben von MS-Patienten anhand des Tiermodells der MS, der Experimentellen Autoimmunen Enzephalomyelitis (EAE), untersucht. Die EAE wurde in C57Bl/6 M{\"a}usen und diversen GR-defizienten M{\"a}usen durch Immunisierung mit Myelinoligodendrozytenglykoprotein (MOG35-55) induziert. Es konnte gezeigt werden, dass die Gabe von Dexamethason (Dex) den Krankheitsverlauf dosisabh{\"a}ngig verbessert. Die Untersuchung heterozygoter GR Knock-out M{\"a}use und h{\"a}matopoetischer Stammzellchim{\"a}ren verdeutlichte, dass der zytosolische GR (cGR) f{\"u}r die Vermittlung therapeutischer GC-Effekte von sehr großer Bedeutung ist. Der Einsatz zelltyp-spezifischer GR-defizienter M{\"a}use zeigte auf zellul{\"a}rer Ebene, dass f{\"u}r die Vermittlung von GC-Wirkungen die Expression des GR vor allem in T-Zellen unabdingbar ist, wohingegen die GR-Expression in myeloiden Zellen in diesem Kontext keine Bedeutung hat. Durch die Analyse des molekularen Mechanismus konnte festgestellt werden, dass diese Effekte durch Apoptoseinduktion und Herunterregulieren von Adh{\"a}sionsmolek{\"u}len in peripheren, aber nicht ZNS-residenten T-Zellen erzielt wurden. {\"U}berdies wurde ersichtlich, dass Dex die T-Zellmigration in das ZNS verhinderte. Diese Beobachtung unterst{\"u}tzt die Hypothese, dass Dex durch Apoptoseinduktion und Immunmodulation haupts{\"a}chlich auf periphere T-Zellen wirkt und somit den st{\"a}ndigen Influx neuer Immunzellen in das ZNS verhindert. Ferner konnte in dieser Arbeit gezeigt werden, dass die therapeutische Gabe hochdosierten Methylprednisolons (MP) in diesem EAE-Modell ebenfalls zu einer dosisabh{\"a}ngigen Verbesserung der EAE f{\"u}hrte. Diese beruhte auf einer reduzierten Lymphozyteninfiltration in das ZNS, war allerdings im Vergleich zur Dex-Therapie aufgrund geringerer Wirkpotenz weniger stark ausgepr{\"a}gt. Im Gegensatz dazu f{\"u}hrte die pr{\"a}ventive MP-Applikation zu einem verst{\"a}rkten EAE-Verlauf, der nach der Beeinflussung peripherer, h{\"a}matopoetischer Immunzellen auf eine verst{\"a}rkte Proliferation autoreaktiver T-Zellen zur{\"u}ckzuf{\"u}hren ist. Im weiteren Verlauf der vorliegenden Arbeit wurde als m{\"o}glicher Ersatz f{\"u}r die Hochdosis-GC-Pulstherapie eine nicht-steroidale, antiinflammatorische Substanz im chronischen EAE-Modell der C57Bl/6 Maus etabliert. Erste tierexperimentelle Untersuchungen mit Compound A (CpdA) offenbarten eine lediglich geringe therapeutische Breite dieser Substanz, wobei innerhalb pharmakologischer Dosierungen dennoch therapeutische Wirkungen vermittelt werden konnten. Anhand von in vitro Experimenten konnte eindeutig nachgewiesen werden, dass CpdA GR-unabh{\"a}ngig Apoptose induzierte, wobei Immunzellen und neuronale Zellen gegen{\"u}ber CpdA besonders empfindlich reagierten. Der Einsatz T-Zell-spezifischer GR-defizienter M{\"a}use konnte zeigen, dass CpdA f{\"u}r die Vermittlung therapeutischer Wirkungen den cGR ben{\"o}tigt. Ferner wurde offensichtlich, dass CpdA in Abwesenheit des cGR in T-Zellen eine signifikante Verschlechterung der EAE verursachte. Durch die Anwendung physikochemischer Analysenmethoden, wie der Massenspektrometrie und 1H-NMR-Spektroskopie, konnte festgestellt werden, dass CpdA in vitro in gepufferten Medien in eine zyklische, chemisch sehr reaktive Verbindung (Aziridin) metabolisiert wird. Diese kann sehr wahrscheinlich f{\"u}r die Apoptose-Induktion in Zellen und die in M{\"a}usen beobachteten neurotoxischen Ausfallerscheinungen verantwortlich gemacht werden. Durch chemische Analysen konnte in vitro in w{\"a}ssriger CpdA-L{\"o}sung ein weiterer Metabolit, das sympathomimetisch wirksame Synephrin, identifiziert werden. Um die Wirksamkeit adrenerger Substanzen in vivo zu testen, wurde das ß1/2-Sympathomimetikum Isoproterenol appliziert. Dieses verbesserte die EAE-Symptomatik, was sehr wahrscheinlich auf eine reduzierte Antigenpr{\"a}sentation und einer damit verbundenen verminderten T-Zellinfiltration in das ZNS zur{\"u}ckzuf{\"u}hren ist.},
  subject      = {Multiple Sklerose},
  language  = {de}
}
@article{FrankeSpringScheeretal.1975,
  author    = {Franke, Werner W. and Spring, Herbert and Scheer, Ulrich and Zerban, Heide},
  title     = {Growth of the nuclear envelope in the vegetative phase of the green alga Acetabularia. Evidence for assembly from membrane components synthesized in the cytoplasm.},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32403},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@article{ScheerFrankeTrendelenburg1975,
  author    = {Scheer, Ulrich and Franke, Werner W. and Trendelenburg, Michael F.},
  title     = {Effects of actinomycin D on the association of newly formed ribonucleoproteins with the cistrons of ribosomal RNA in Triturus oocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32383},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@phdthesis{Le2008,
  author    = {Le, Thu Ha},
  title     = {Protein dynamics in responder and non-responder solid tumor xenografts during oncolytic viral therapy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32016},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {VACV GLV-1h68 was reported as a diagnostic/therapeutic vector which enters, replicates in, and reveals the locations of tumors in mice. Furthermore, the effect on tumor colonization, on tumor growth, regression and eradication by VACV GLV-1h68 without the need of any known genes with anti-tumoral activities was determined. To investigate differential protein expression between infected tumor cells and corresponding tumors, as well as between infected tumor cells, between infected tumors, proteomics is particularly used, possibly contributing to the understanding oncolytic ability on the protein level of VACV GLV-1h68. The given effects of VACV GLV-1h68 infection on cellular protein expression support tumor cell killing. In this study, differential protein expression was analyzed at different time points with two-dimensional gel electrophoresis (2DE) followed by MALDI-TOF/TOF identification. Comparative analysis of multiple 2-DE gels revealed that the majority of protein expression changes appeared at 48 hours post infection in cell cultivation and at 42 days post infection in tumors. Mass spectrometry identified 68, 75, 159 altered cellular proteins in the GI-101A, HT-29, PC-3 infected cells, respectively, including 30, 23, 49 up-regulated proteins and 38, 52, 110 down-regulated proteins 12 to 48 hours after infection. For xenografts, mass spectrometry identified 270, 101, 91 altered cellular proteins in the infected GI-101A, HT-29, PC-3 tumors, respectively, including 89, 70, 40 up-regulated proteins and 181, 31, 51 down-regulated proteins 7 to 42 days after infection. In general, in the cell lines, the proteins found to be differentially regulated are most often associated with metabolic processes, in particular with primary energy metabolism (glucose catabolism, TCA and lactate production). VAVC GLV 1h68 infection results in hijacking of the host translation apparatus, alteration of cytoskeleton networks, induce ubiqitin proteasome pathway (UPP) disorders. Particularly in tumors, the responses cover a much broader panel of cellular processes, including signalling (e.g., cell death), transport (in particular of iron ions) and migration. A common pathway to be up-regulated in both tumors and cell lines is the "unfolded protein response". Notably, VACV GLV-1h68 affected the anti-apoptosis pathways in GI-101A and PC-3 cancer cells but not in HT-29 xenografts. For example, GI-101A xenografts in mice appear 12 proteins associated with anti-apoptosis function. They were found down-regulated, including tumor protein-translationally-controlled (H-TPT1), rho-GDP-dissociation inhibitor alpha (H-GDIa), ywhaq protein (M-1433T), H-PRDX4, serine/threonine-protein phosphatase-2A-catalytic subunit beta isoform PP2A (M-Ppp2cb), eukaryotic translation initiation factor 2-subunit 1 alpha-35kDa (H-eIF2), H-actinin-\&\#945;1 (ACTN1 ), Annexin A1 (H-A1), annexin A5 (H-A5), Mouse albumin 1 (M-Alb1), dimethylarginine dimethylaminohydrolase 2 (H-DDAH2). In PC-3 xenografts, anti-apoptosis expression is lesser than those in GI-101A cells, however 3 anti-apoptosis associated proteins were down-regulated such as ARP3 actin-related protein-3-homolog (H-ARP3), Human FLNA protein, Rho GDP dissociation inhibitor (GDI) alpha (H-GDIa). In contrast, in HT-29 xenografts, there are several anti-apoptosis-associated proteins that show even to be up-regulated; they mostly belong to peroxiredoxin proteins. Lesson from HT-29 had been given what various means the HT-29 cells use to escape their apoptosis fate. This suggests that VAVC GLV1h68 infection may induce unbalance of unfolded protein response (UPR) but tending to anti-apoptosis-mediated proteins and promote the destructive elements of UPR, including caspase-12 cleavage and apoptosis. Taken together in this thesis research I have tried to compare protein profiles obtained from responder cell line and from regressing solid tumors colonized by VAVC GLV-1h68 with that of non-responding tumors. I also compared these data with PC-3 prostate cell line and tumor data on intermediate responder which alter mouse protein profiling in tumors similarly to the highly efficacious GI-101A breast tumor cell line. From these comparisons I have deduced exciting protein pattern signature characteristic for a responder or distinctly different from non-responder system. Combining these few crucial genes involved with the transcriptional test data obtained by fellow graduate student at NIH a novel national designed VACV GLV-1h68 strains with enhanced efficacy in many today non-responder cancer cell lines will be available to be tested into ongoing clinical trials.},
  language  = {en}
}
@article{FrankeKartenbeckZentgrafetal.1971,
  author    = {Franke, Werner W. and Kartenbeck, J{\"u}rgen and Zentgraf, Hanswalter and Scheer, Ulrich and Falk, Heinz},
  title     = {Membrane-to-membrane cross-bridges. A means to orientation and interaction of membrane faces},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32122},
  year      = {1971},
  abstract  = {No abstract available},
  language  = {en}
}
@article{FrankeScheerFritsch1972,
  author    = {Franke, Werner W. and Scheer, Ulrich and Fritsch, Hansj{\"o}rg},
  title     = {Intranuclear and cytoplasmic annulate lamellae in plant cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32148},
  year      = {1972},
  abstract  = {No abstract available},
  language  = {en}
}
@article{Scheer1970,
  author    = {Scheer, Ulrich},
  title     = {The ultrastructure of the nuclear envelope of amphibian oocytes: a reinvestigation. III. Actinomycin D-induced decrease in central granules within the pores.},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32110},
  year      = {1970},
  abstract  = {No abstract available},
  language  = {en}
}
@article{WilkenKossnerSenecaletal.1993,
  author    = {Wilken, Norbert and Kossner, Ursula and Sen{\´e}cal, Jean-Luc and Scheer, Ulrich and Dabauvalle, Marie-Christine},
  title     = {Nup180, a novel nuclear pore complex protein localizing to the cytoplasmic ring and associated fibrils},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32049},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DabauvalleLoosMerkertetal.1991,
  author    = {Dabauvalle, Marie-Christine and Loos, Karin and Merkert, Hilde and Scheer, Ulrich},
  title     = {Spontaneous assembly of pore complex-containing membranes ("Annulate lamellae") in Xenopus egg extract in the absence of chromatin},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32797},
  year      = {1991},
  abstract  = {No abstract available},
  language  = {en}
}
@article{ScheerTrendelenburgFranke1976,
  author    = {Scheer, Ulrich and Trendelenburg, Michael F. and Franke, Werner W.},
  title     = {Regulation of transcription of genes of ribosomal RNA during amphibian oogenesis: a biochemical and morphological study},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32814},
  year      = {1976},
  abstract  = {Natural changes in the transcription of rRNA genes were studied in nucleoli from three oogenic stages of the newt Triturus alpestris with electron microscope, autoradiographic, and biochemical techniques. From determinations of the uridine triphosphate pool sizes and [3H]uridine uptake, phosphorylation, and incorporation into 28S and 18S rRNAs in vivo it was estimated that the rate of rRNA synthesis was about 0.01\% in previtellogenic oocytes and 13\% in mature oocytes when compared to midvitellogenesis. Spread preparations of nucleoli showed significant morphological changes in the transcriptional complexes. The total number of lateral fibrils, i.e., ribonucleoproteins containing the nascent rRNA precursor, were drastically decreased in stages of reduced synthetic activity. This indicates that rRNA synthesis is regulated primarily at the level of transcription. The resulting patterns of fibril coverage of the nucleolar chromatin axes revealed a marked heterogeneity. On the same nucleolar axis occurred matrix units that were completely devoid of lateral fibrils, matrix units that were almost fully covered with lateral fibrils, and various forms of matrix units with a range of lateral fibril densities intermediate between the two extremes. Granular particles that were tentatively identified as RNA polymerase molecules were not restricted to the transcription l complexes. They were observed, although less regularly and separated by greater distances, in untranscribed spacer regions as well as in untranscribed gene intercepts. The results show that the pattern of transcriptional control of rRNA genes differs widely in different genes, even in the same genetic unit.},
  language  = {en}
}
@article{KobeltLinsenmair1986,
  author    = {Kobelt, Frank and Linsenmair, Karl Eduard},
  title     = {Adaptations of the reed frog Hyperolius viridiflavus to its arid environment. I. The skin of Hyperolius viridiflavus nitidulus in wet and dry season conditions.},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30551},
  year      = {1986},
  abstract  = {Hyperolius viridiflavus nitidulus inhabits parts of the seasonally very hot and dry West African savanna. During the long lasting dry season, the small frog is sitting unhidden on mostly dry plants and has to deal with high solar radiation load (SRL), evaporative water loss (EWL) and small energy reserves. It seems to be very badly equipped to survive such harsh climatic conditions (unfavorable surface to volume ratio, very limited capacity to st{\"o}re energy and water). Therefore, it must have developed extraordinary efficient mechanisms to solve the mentioned Problems. Some of these mechanisms are to be looked for within the skin of the animal (e.g. protection against fast desiccation, deleterious effects of UV radiation and over-heating). The morphology of the wet season skin is, in most aspects, that of a "normal" anuran skin. It differs in the Organization of the processes of the melanophores and in the arrangement of the chromatophores in the Stratum spongiosum, forming no "Dermal Chromatophore Unit". During the adaptation to dry season conditions the number of iridophores in dorsal and ventral skin is increased 4-6 times compared to wet season skin. This increase is accompanied by a very conspicuous change of the wet season color pattern. Now, at air temperatures below 35° C the color becomes brownish white or grey and changes to a brilliant white at air temperatures near and over 40° C. Thus, in dry season State the frog retains its ability for rapid color change. In wet season State the platelets of the iridophores are irregularly distributed. In dry season State many platelets become arranged almost parallel to the surface. These purine crystals probably act as quarter-wave-length interference reflectors, reducing SRL by reflecting a considerable amount of the radiated energy input. EWL is as low as that of much larger xeric reptilians. The impermeability of the skin seems to be the result of several mechanisms (ground substance, iridophores, lipids, mucus) supplementing each other. The light red skin at the pelvic region and inner sides of the limbs is specialized for rapid uptake of water allowing the frog to replenish the unavoidable EWL by using single drops of dew or rain, available for only very short periods.},
  language  = {en}
}
@article{Scheer1975,
  author    = {Scheer, Ulrich},
  title     = {The rifamycin derivative AF/013 is cytolytic},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32429},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@inproceedings{TrendelenburgSpringScheeretal.1974,
  author    = {Trendelenburg, Michael F. and Spring, Herbert and Scheer, Ulrich and Franke, Werner W.},
  title     = {Morphology of nucleolar cistrons in a plant cell, Acetabularia mediterranea},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32213},
  year      = {1974},
  abstract  = {The structural organization of transcriptionally active DNA that contains cistrons for precursor molecules of ribosomal RNA is described in positively stained spread preparations from nuclei and nucleoli isolated from the green alga, Acetabularia mediterranea Lmx. These nuclei contain large aggregates of nucleolar subunits in which fibril-covered regions, the putative active cistrons for precursors of ribosomal RNA, alternate with fibril-free intercepts, the "spacers". The length distribution of the different intercepts of this DNA is given, and the pattern is compared with those shown in animal cell systems. The data are discussed in relation to problems of transcription and of amplification of ribosomal RNA genes.},
  language  = {en}
}
@article{ScheerFranke1972,
  author    = {Scheer, Ulrich and Franke, Werner W.},
  title     = {Annulate lamellae in plant cells: formation during microsporogenesis and pollen development in Canna generalis Bailey},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32160},
  year      = {1972},
  abstract  = {The occurrence of stacked annulate tamellae is documented for a plant cell system, namely for pollen mother cells and developing pollen grains of Canna generalis. Their structural subarchiteeture and relationship to endoplasmie reticulum (ER) and nuclear envelope cisternae is described in detail. The results demonstrate structural homology between plant and animal annulate lamellae and are compatible with, though do not prove, the view that annulate lamcllar cisternae may originate as a degenerative form of endoplasmic retieulum.},
  language  = {en}
}
@article{EckertFrankeScheer1975,
  author    = {Eckert, W. A. and Franke, Werner W. and Scheer, Ulrich},
  title     = {Nucleocytoplasmic translocation of RNA in Tetrahymena pyriformis and its inhibition by actinomycin D and cycloheximide},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32399},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@article{SpringScheerFrankeetal.1975,
  author    = {Spring, Herbert and Scheer, Ulrich and Franke, Werner W. and Trendelenburg, Michael F.},
  title     = {Lampbrush type chromosomes in the primary nucleus of the green alga Acetabularia mediterranea},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32370},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@article{ZentgrafScheerFranke1975,
  author    = {Zentgraf, Hanswalter and Scheer, Ulrich and Franke, Werner W.},
  title     = {Characterization and localization of the RNA synthesized in mature avian erythrocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32410},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DerksenTrendelenburgScheeretal.1973,
  author    = {Derksen, J. and Trendelenburg, Michael F. and Scheer, Ulrich and Franke, Werner W.},
  title     = {Spread chromosomal nucleoli of Chironomus salivary glands},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32209},
  year      = {1973},
  abstract  = {No abstract available},
  language  = {en}
}
@article{Linsenmair1972,
  author    = {Linsenmair, Karl Eduard},
  title     = {Die Bedeutung familienspezifischer "Abzeichen" f{\"u}r den Familienzusammenhalt bei der sozialen W{\"u}stenassel Hemilepistus reaumuri Audouin und Savigny},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32663},
  year      = {1972},
  abstract  = {No abstract available},
  language  = {de}
}
@misc{ScheerThiryGoessens1993,
  author    = {Scheer, Ulrich and Thiry, Marc and Goessens, Guy},
  title     = {Structure, function and assembly of the nucleolus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32057},
  year      = {1993},
  abstract  = {No abstract available},
  language  = {en}
}
@article{FrankeScheer1970,
  author    = {Franke, Werner W. and Scheer, Ulrich},
  title     = {The ultrastructure of the nuclear envelope of amphibian oocytes: a reinvestigation. II. The immature oocyte and dynamic aspects},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32102},
  year      = {1970},
  abstract  = {No abstract available},
  language  = {en}
}
@article{FrankeTrendelenburgScheer1973,
  author    = {Franke, Werner W. and Trendelenburg, Michael F. and Scheer, Ulrich},
  title     = {Natural segregation of nucleolar components in the course of plant cell differentiation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32182},
  year      = {1973},
  abstract  = {Segregation of the nucleolar components is described in the differentiated nucleus of the generative cell in the growing Clivia and Lilium pollen tubes. This finding of a natural nucleolar segregation is discussed against the background of current views of the correlations of nucleolar morphology and transcriptional activity.},
  language  = {en}
}
@article{ScheerTrendelenburgFranke1973,
  author    = {Scheer, Ulrich and Trendelenburg, Michael F. and Franke, Werner W.},
  title     = {Transcription of ribosomal RNA cistrons: Correlation of morphological and biochemical data},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32195},
  year      = {1973},
  abstract  = {Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibians are quantitatively evaluated and the length distributions of repeat-, matrix-, and spacer-units along the rRNA cistron containing axes are given. The correlation of the matrix unit data with the gel electrophoretic pattern of labelled nuclear RNA from the same oocytes is examined. The mean value of the matrix unit corresponds fairly well to a 2.6 million D peak of pre-rRNA but the distribution of both matrix units and labelled pre-rRNAs shows an asymmetrical heterogeneity indicating the existence of some larger primary transcription products of rDNA. Novel structural aspects are described in the spacer regions which suggest that transcription does also take place in DNP regions between the matrix units. A special "prelude piece" coding for approx. 0.5 million D of RNA is frequently visualized in the spacer segments at the beginning of a matrix unit. Possible artifacts resulting from the preparation, the relative congruence between the data obtained using both methods, and the functional meaning of the findings are discussed against the background of current concepts of structural organization and transcription products of nucleolar DNA.},
  language  = {en}
}
@article{DabauvalleLoosScheer1990,
  author    = {Dabauvalle, Marie-Christine and Loos, Karin and Scheer, Ulrich},
  title     = {Identification of a soluble precursor complex essential for nuclear pore assembly in vitro},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32801},
  year      = {1990},
  abstract  = {No abstract available},
  language  = {en}
}
@article{Linsenmair1994,
  author    = {Linsenmair, Karl Eduard},
  title     = {Biologische Vielfalt und {\"o}kologische Stabilit{\"a}t},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31157},
  year      = {1994},
  abstract  = {No abstract available},
  language  = {en}
}
@article{GrafeSchmuckLinsenmair1992,
  author    = {Grafe, T. Ulmar and Schmuck, Richard and Linsenmair, Karl Eduard},
  title     = {Reproductive energetics of the African Reed Frogs, Hyperolius viridiflavus and Hyperolius marmoratus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31187},
  year      = {1992},
  abstract  = {No abstract available},
  language  = {en}
}
@phdthesis{Schmit2008,
  author    = {Schmit, Fabienne},
  title     = {LINC, a novel protein complex involved in the regulation of G2/M genes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29336},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Regulated progression through the cell cycle is essential for ordered cell proliferation. One of the best characterized tumor suppressors is the retinoblastoma protein pRB, which together with the E2F transcription factors regulates cell cycle progression. In the model organisms Drosophila melanogaster and Caenorhabditis elegans, RB/E2F containing multiprotein complexes have been described as transcriptional regulators of gene expression. This work first describes a homologous complex in human cells named LINC (for LIN complex). It consists of a stable core complex containing LIN-9, LIN-37, LIN-52, LIN-54 and RbAp48. This core complex interacts cell cycle-dependently with different pocket proteins and transcription factors. In quiescent cells, LINC associates with p130 and E2F4. In S-phase cells these interactions are lost and LINC binds to B-MYB and p107. The transient knock-down of LIN-54 in primary fibroblasts, as the depletion of LIN-9, leads to cell cycle defects. The cells are delayed before the entry into mitosis. This effect is due to the fact that the knock-down of LINC components leads to the downregulation of cell cycle genes responsible for the entry into and exit from mitosis as well as for checkpoints during mitosis. These LINC target genes are known E2F G2/M target genes, which are expressed later than the classical G1/S E2F target genes. The transcriptional regulation by LINC is a direct effect as LINC binds to the promoters of its target genes throughout the cell cycle. LINC contains three DNA-binding proteins. E2F4 and B-MYB, which cell cycle-dependently bind to LINC, are known DNA-binding transcription factors. Additionally, it is show here that the LINC core complex member LIN-54 also directly binds to the promoter of a LINC target gene. Although the exact molecular mechanism of LINC function needs to be analyzed further, data in this work provide a model for the delayed activation of G2/M target genes. B-MYB, a G1/S E2F target gene, binds to LINC upon its expression in S-phase. Then only LINC is a transcriptional activator that induces the expression of the G2/M genes. This provides an explanation for the delayed expression of these E2F G2/M target genes.},
  subject      = {Zellzyklus},
  language  = {en}
}
@phdthesis{Klaeckta2009,
  author    = {Kl{\"a}ckta, Christian},
  title     = {Biochemische und -physikalische Charakterisierung von rekombinanten Porinen aus den beiden pathogenen Bakterien Nocardia farcinica und Vibrio cholerae sowie von nativen Porinen aus drei Streptomyces Arten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-38910},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Die vorliegende Dissertation beschreibt detaillierte biochemische und biophysikalische Untersuchungen von rekombinanten Porinen aus den beiden pathogenen Bakterien Nocardia farcinica und Vibrio cholerae sowie von nativen Porinen aus drei Streptomyces Arten. F{\"u}r die beiden pathogenen Vertreter sind bereits impermebable Zellwandstrukturen beschrieben worden (Daffe et al., 1993; Rodriguez-Torres et al., 1993). F{\"u}r Streptomyces Arten ist keine vergeichbare, definierte {\"a}ußere Zellwandbarriere bekannt. Im Fall von S. griseus konnten dennoch undefinierte, kovalente Lipidverkn{\"u}pfungen mit der Peptidoglykanschicht nachgewiesen werden (Kim et al., 2001). Daher besteht die Notwendigkeit des Transports von N{\"a}hrstoffen und anderer Molek{\"u}le auch bei Streptomyces Arten durch porenformende Proteine, so genannte Porine. Unter Porinen versteht man wassergef{\"u}llte Kan{\"a}le, die in zwei Klassen unterteilt werden k{\"o}nnen: allgemeine Diffusionsporen und substratspezifische Porine. Allgemeine Diffusionsporen filtern entsprechend der molekularen Masse der gel{\"o}sten Substrate und weisen ein lineares Verh{\"a}ltnis zwischen Translokationsrate und Substratkonzentrationsgradient auf. Dagegen kann der Transport bestimmter Substanzen durch spezifische Porine mit einer Substrat-Bindestelle im Kanal durch die Michaelis-Menten-{\"a}hnliche Kinetik beschrieben werden. Diese Kan{\"a}le erm{\"o}glichen den schnellen Influx bestimmter Klassen von Substraten.},
  subject      = {Porine},
  language  = {de}
}
@article{ScheerSchmidtZachmannHuegleetal.1984,
  author    = {Scheer, Ulrich and Schmidt-Zachmann, Marion S. and H{\"u}gle, Barbara and Franke, Werner W.},
  title     = {Identification and localization of a novel nucleolar protein of a high molecular weight by a monoclonal antibody},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39786},
  year      = {1984},
  abstract  = {A monoclonal murine antibody (No-I 14) is described which reacts specifically with a polypeptide of molecular weight (M,) 180000 present in low-speed nuclear pellets from oocytes and somatic cells of Xenopus laevis and X. borealis and in isolated amplified nucleoli. Two-dimensional gel electrophoresis has revealed the acidic nature of this polypeptide (isoelectric at pH of ca 4.2 in the presence of 9.5 M urea). A relatively large proportion of the protein is extracted at elevated ionic strength( i.e., at 0.4-0.5 M alkali salt) in a form sedimenting at approx. 7-8S , compatible with a monomeric state. It is also extracted by digestion with RNase but not with DNase. In immunofluorescence microscopy, antibody No-114 stains intensely nucleoli of oocytes and all somatic cells examined , including the residual nucleolar structure of Xenopus erythrocytes which are transcriptionally inactive. During mitosis the antigen does not remain associated with the nucleolar organizer regions (NOR) of chromosomes but is released and dispersed over the cytoplasm until telophase when it re-associates with the reforming interphase nucleoli. At higher resolution the immunofluorescent region is often resolved into a number of distinct subnucleolar components of varied size and shape. Immunoelectron microscopy using colloidal gold-coupled secondary antibodies reveals that the M, 180000 protein is confined to the dense fibrillar component of the nucleolus. This conclusion is also supported by its localization in the fibrillar part of segregated nucleoli of cells treated with actinomycin D. We conclude that nucleoli contain a prominent protein of M, 180000 which contributes to the general structure of the dense fibrillar component of the interphase nucleolus , independent of its specific transcriptional activity.},
  language  = {en}
}
@article{ScheerSommerville1981,
  author    = {Scheer, Ulrich and Sommerville, J.},
  title     = {Structural organization of nascent transcripts and hnRNA molecules in amphibian oocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39765},
  year      = {1981},
  abstract  = {Comparisons ofrelative lengths oflampbrush loops, nascent RNP transcripts and hnRNA molecules from oocytes of amphibia with different C-values show that there is an increasing trend in loop, and transcriptional unit, length with increase in genome size but no increasing trend with respect to RN A contour length.The formation of duplex regions and circles in RNP fibrils indicates that RNA processing may occur within the nascent fibrils. The hnRNA molecules from oocytes of the various amphibia readily form intermolecular duplex structures. These complementary sequences have a low kinetic complexity and are transcribed from highly repetitive sequences distributed throughout the genome. Their possible function is considered.},
  language  = {en}
}
@incollection{ScheerFranke1974,
  author    = {Scheer, Ulrich and Franke, Werner W.},
  title     = {Structures and functions of the nuclear envelope},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39777},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1974},
  abstract  = {No abstract available},
  subject      = {Zellkern},
  language  = {en}
}
@article{Scheer1978,
  author    = {Scheer, Ulrich},
  title     = {Changes of nucleosome frequency in nucleolar and non-nucleolar chromatin as a function of transcription: an electron microscopic study},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39750},
  year      = {1978},
  abstract  = {The morphology of nucleolar and non-nucleolar (Iampbrush chromosome loops) chromatin was studied in the electron microscope during states of reduced transcriptional activity in amphibian oocytes (Xenopus laevis, Triturus alpestris, T. cristatus). Reduced transcriptional activity was observed in maturing stages of oocyte development and after treatment with an inhibitor, actinomycin D. Strands of nucleolar chromatin appear smooth and thin, and contain only few, if any, nucleosomal particles in the transcribed units. This is true whether they are densely or only sparsely covered with lateral ribonucleoprotein fibrils. This smooth and non-nucleosomal character is also predominant in the interspersed, apparently nontranscribed rDNA spacer regions. During inactivation, however, nucleolar chromatin frequently and progressively assumes a beaded appearance in extended fibril-free-that is, apparently nontranscribed - regions. I n either fUll-grown 00- cytes or late after drug treatment, most of the nucleolar chromatin is no longer smooth and thin, but rather shows a beaded configuration indistinguishable from inactive non - nucleolar chromatin. In many chromatin strands, transitions of fibril-associated regions of smooth character into beaded regions wihout lateral fibrils are seen. Similarly, in the non-nucleolar chromatin of the retracting lampbrush chromosome loops, reduced transcriptional activity is correlated with a change from smooth to beaded morphology. Here, however, beaded regions are also commonly found interspersed between the more or less distant bases of the lateral fibrils, the putative transcriptional complexes. I n both sorts of chromatin, detergents (in particular Sarkosyl) that remove most of the chromatin proteins including histones from the DNA axis but leave the RNA polymerases of the transcriptional complexes attached were used to discriminate between polymerases and nucleosomal particles. The results suggest that nucleosomes are absent in heavily transcribed chromatin regions but are reformed after inactivation. In contrast to the findings with inactivated nucleolar genes, in lampbrush chromosome loops the beaded nucleosomal configuration appears to be assumed also in regions within transcriptional units that, perhaps temporarily, are not involved in transcription.},
  language  = {en}
}
@article{ScheerHansmannFalketal.1986,
  author    = {Scheer, Ulrich and Hansmann, Paul and Falk, Heinz and Sitte, Peter},
  title     = {Ultrastructural localization of DNA in two Cryptomonas species by use of a monoclonal DNA-antibody},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-39746},
  year      = {1986},
  abstract  = {Immunogold cytochemistry - DNA localization - Cryptomonas nucleomorph The distribution and subcellular localization of DNA in the unicellular alga Cryptomonas has been investigated electron-microscopically by indirect immunocytochemistry, using a monoclonal DNA antibody and a gold-Iabeled secondary antibody. This technique proved to be very sensitive and entirely specific. DNA could be demonstrated in four different compartments (nucleus, nucleomorph, plastid, and mitochondrion). Within the plastid, DNA is concentrated in stroma regions that are localized preferentially around the center of the organelle. The mitochondrion contains several isolated DNA-containing regions (nucleoids). Within the nucleus, most of the DNA is localized in the 'condensed' chromatin. DNA was also detectable in small areas of the nucleolus, whereas the interchromatin space of the nucleus appeared almost devoid of DNA. Within the nucleomorph, DNA is distributed inhomogeneously in the matrix. DNA could furthermore be detected in restricted areas of the 'fibrillogranular body' of the nucleomorph, resembling the situation encountered in the nucleol us. The presence of DNA and its characteristic distribution in the nucleomorph provide additional, strong evidence in favour of the interpretation of that organelle as the residual nucleus of a eukaryotic endosymbiont in Cryptomonas.},
  subject      = {Cytologie},
  language  = {en}
}
@article{RoseSzopaHanetal.1988,
  author    = {Rose, Kathleen M. and Szopa, Jan and Han, Fu-Sheng and Cheng, Yung-Chi and Richter, Arndt and Scheer, Ulrich},
  title     = {Association of DNA topoisomerase I and RNA polymerase I: A possible role for topoisomerase I in ribosomal gene transcription},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33901},
  year      = {1988},
  abstract  = {RNA polymerase I preparations purified from a rat hepatoma contained DNA topoisomerase activity. The DNA topoisomerase associated with the polymerase had an Mr of 110000, required Mg2+ but not ATP, and was recognized by anti-topoisomerase I antibodies. When added to RNA polymerase I preparations containing topoisomerase activity, anti-topoisomerase I antibodies were able to inhibit the DNA relaxing activity of the preparation as well as RNA synthesis in vitro. RNA polymerase II prepared by analogous procedures did not contain topoisomerase activity and was not recognized by the antibodies. The topoisomerase I: polymerase I complex was reversibly dissociated by column chromatography on Sephacryl S200 in the presence of 0.25 M (NH4hS04. Topoisomerase I was immunolocalized in the transcriptionally active ribosomal gene complex containing RNA polymerase I in situ. These data indicate that topoisomerase I and RNA polymerase I are tightly complexed both in vivo and in vitro, and suggest a role for DNA topoisomerase I in the transcription of ribosomal genes.},
  language  = {en}
}
@article{ScheerFranke1969,
  author    = {Scheer, Ulrich and Franke, Werner W.},
  title     = {Negative staining and adenosine triphosphatase activity of annulate lamellae of newt oocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32087},
  year      = {1969},
  abstract  = {Semi -iso la ted annul a te lamellae were prepared from single newt oocy tes (Triturus alpestris) by a modified Call a n-T omlin technique. Such preparations were examined with the electron mi croscope, and the negative sta ining a ppearance of th e a nnulate lamellae is described . The annul a te lamellae can be de tected either adhering to the nuclear envelope or being detached from it. Sometimes they a re obse rved to be connected with slender tubular-like structures interpreted as pa rts of the endoplasmic reti culum. The results obta ined from negativ e sta ining a re combined with those from sections. Especially, the structural data on th e a nnula te lamellae and the nuclear envelope of the very same cell were compa red . Evidence is presented th a t in the oocytes studied the two kinds of porous cisternae, n amely a nnul a te lamellae and nuclear envelope, a re markedly distinguished in that the annul a te lamellae ex hibit a much higher pore frequency (generally about twice tha t found for the corresponding nuclear envelope) and have al so a rela tive pore area occupying as much as 32 \% to 55 \% of th e cistern al surface (compa red with 13 \% to 22 \% in the nuclear envelopes). T he pore di ame ter a nd all other ultras tructural details of the pore complexes, however, a re equi valent in both kinds of porous cisternae. Like the annuli of the nuclear pore complexes of various a nimal and pl ant cells, the a nnuli of the a nnula te lamellae pores reveal al so an eightfold symmetry of their subunits in negatively stained as well as in ectioned ma teria l. Furthermore, th e a nnul a te lamellae a re shown to be a site of activity of the Mg-Na-Kstimul a ted ATPase.},
  language  = {en}
}
@article{Scheer1973,
  author    = {Scheer, Ulrich},
  title     = {Nuclear pore flow rate of ribosomal RNA and chain growth rate of its precursor during oogenesis of Xenopus laevis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32178},
  year      = {1973},
  abstract  = {The number of ribosomal RNA molecules which are transferred through an average nuclear pore complex per minute into the cytoplasm (nuclear pore flow rate, NPFR) during oocyte growth of Xenopus laevis is estimated. The NPFR calculations are based on determinations of the increase of cytoplasmic rRNA content during defined time intervals and of the total number of pore complexes in the respective oogenesis stages. In the mid-la mpbrush stage (500:"700 I'm oocyte diameter) the NPFR is maximal with 2.62 rRNA molecules/ pore/ minute. Then it decreases to zero at the end of oogenesis. The nucleocytoplasmic RNA f10w rates determined are compared with corresponding values of other cell types. The molecular weight of the rRNA precursor transcribed in the extrachromosomal nucleoli of Xenopus lampbrush stage oocytes is determined by acrylamide gel electrophoresis to be 2.5 x 10· daltons. From the temporal increase of cytoplasmic rRNA (3.8 I'g per oocyte in 38 days) and the known number of simultaneously growing precursor molecules in the nucleus the chain growth rate of the 40 S precursor RNA is estimated to be 34 nucleotides per second.},
  language  = {en}
}
@article{FrankeBergerFalketal.1974,
  author    = {Franke, Werner W. and Berger, S. and Falk, Heinz and Spring, H. and Scheer, Ulrich and Trendelenburg, Michael F. and Schweiger, H. G. and Herth, W.},
  title     = {Morphology of the nucleo-cytoplasmic interactions during the development of Acetabularia cells. I. The vegetative phase},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32363},
  year      = {1974},
  abstract  = {The ultrastructure of th e growin g and ma turing primary nucleus of Acetabularia medite rranea and Acetabularia major has been studied with the use of various fi xation procedures. Particular interest has been focused on the deta ils of the nuclear periphery and the perinuclear region. It is demonstrated that early in nuclear grow th a characteristic perinucl ear structura l complex is formed which is, among the eukaryotic cells, unique to Acetabularia and re lated genera. This perinuclear system consists essentially of a) the nuclear envelope with a very hi gh pore frequency and various pore complex assoc iat ion s w ith granular and/or threadlike structures some of which are continuous with the nucleolus; b) an approx imate ly 100 nm thick intermediate zone densely filled with a filam entOus material and occasional sma ll membraneous structures from which the typical cytOplasmic and nuclear organe lles and particles are excl ud ed ; c) an adjacent Iacunar labyrinthum which is interrupted by many plasmatic junction channels between the intermed iate zone and the free cytOplasm; d) numerous dense perinuclear bodies in the juxtanuclear cytOplasm which a re especia lly frequent at the junction channels and reveal a composition of aggregated fibrillar and granul ar structures; e) very dense exclusively fibrill ar agg regates which occur either in assoc iation with t he perinuclear region of the lacunar labyrinthum or, somewhat further out, in the cytOplasmic strands between the bra nches of the lacun ar labyrinthum in the form of slender, characteristic rods or "sausages".},
  language  = {en}
}
@article{BenaventeRoseReimeretal.1987,
  author    = {Benavente, Ricardo and Rose, Kathleen M. and Reimer, Georg and H{\"u}gle-D{\"o}rr, Barbara and Scheer, Ulrich},
  title     = {Inhibition of nucleolar reformation after microinjection of antibodies to RNA polymerase I into mitotic cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33247},
  year      = {1987},
  abstract  = {The formation of daughter nuclei and the reformation of nucleolar structures was studied after microinjection of antibodies to RNA polymerase I into dividing cultured cells (PtK2). The fate of several nucleolar proteins representing the three main structural subcomponents of the nucleolus was examined by immunofluorescence and electron microscopy. The results show that the RNA polymerase I antibodies do not interfere with normal mitotic progression or the early steps of nucleologenesis, i.e. , the aggregation of nucleolar material into prenucleolar bodies. However,they inhibit the telophasic coalescence of the prenucleolar bodies into the chromosomal nucleolar organizer regions, thus preventing the formation of new nucleoli. These prenucleolar bodies show a fibrillar organization that also compositionally resembles the dense fibrillar component of interphase nucleoli . We conclude that during normal nucleologenesis the dense fibrillar component forms from preformed entities around nucleolar organizer regions, and that this association seems to be dependent on the presence of an active form of RNA polymerase I.},
  language  = {en}
}
@article{SommervilleScheer1982,
  author    = {Sommerville, John and Scheer, Ulrich},
  title     = {Transcription of complementary repeat sequences in amphibian oocytes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33915},
  year      = {1982},
  abstract  = {Repeat sequences are transcribed in the germinal vesicles of amphibian oocytes. In the hnRNA population both complements of the repeats are found and can be readily detected because they form intermolecular duplex structures. The structure and formation of duplex regions have been studied in the hnRNA of Xenopus laevis, Triturus cristatus, Amphiuma means and Necturus maculosus, a series of amphibians of increasing genome size (C-value). In T. cristatus, the duplex structures are mostly 600- 1200 bp in length, whereas in X. laevis they are shorter and in N. maculosus they tend to be longer. Although the proportion of RNA sequence capable of rapidly forming duplex structures is different in different organisms, this property bears no relationship to C-value. However the sequence complexity of complementary repeats, as estimated from the rate of duplex formation, does show an increasing trend with C-value. The complementary repeats found in oocyte hnRNA are transcribed from families of DNA sequence that are each represented in the genome by thousands of copies. The extent of cross-species hybridization is low, indicating that the repeat sequences transcribed in different amphibian genera are not the same. In situ hybridization experiments indicate that the repeat sequences are spread throughout the genome. The evolution and possible function of complementary repeats are considered.},
  language  = {en}
}
@article{ReimerRaskaScheeretal.1988,
  author    = {Reimer, Georg and Raska, Ivan and Scheer, Ulrich and Tan, Eng M.},
  title     = {Immunolocalization of 7-2-ribonucleoprotein in the granular component of the nucleolus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33890},
  year      = {1988},
  abstract  = {Certain autoimmune sera contain antibodies against a nucleolar ribonucleoprotein particle associated with 7-2-RNA (R. Reddy et al. (1983) J. Bioi. Chem . 258, 1383; C. Hashimoto and J. A. Steitz (1983) J. Bioi. Chem. 258, 1379). In this study, we showed by immunofluorescence microscopy that antibodies reactive with 7-2-ribonucleoprotein immunolocalized in the granular regions of actinomycin D and 5,6-dichloro-I-j3-D-ribofuranosylbenzimidazole (DRB)-segregated nucleoli from Vero cells. By electron microscopic immunocytochemistry, antigen-antibody complexes were located in the granular component of transcriptionally active nucleoli from rat liver hepatocytes and HeLa cells. Anti-7- 2-RNP antibodies from two autoimmune sera immunoprecipitated a major protein of Mr 40,000 from e5S] methionine-Iabeled HeLa cell extract. The immunolocalization data suggest that 7-2-ribonucleoprotein may be involved in stages of ribosome biogenesis which take place in the granular component of the nucleolus, i.e., assembly, maturation, and/or transport of preribosomes},
  language  = {en}
}
@phdthesis{Bertolucci2008,
  author    = {Bertolucci, Franco},
  title     = {Operant and classical learning in Drosophila melanogaster: the ignorant gene (ign)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-33984},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {One of the major challenges in neuroscience is to understand the neuronal processes that underlie learning and memory. For example, what biochemical pathways underlie the coincidence detection between stimuli during classical conditioning, or between an action and its consequences during operant conditioning? In which neural substructures is this information stored? How similar are the pathways mediating these two types of associative learning and at which level do they diverge? The fly Drosophila melanogaster is an appropriate model organism to address these questions due to the availability of suitable learning paradigms and neurogenetic tools. It permits an extensive study of the functional role of the gene S6KII which in Drosophila had been found to be differentially involved in classical and operant conditioning (Bertolucci, 2002; Putz et al., 2004). Genomic rescue experiments showed that olfactory conditioning in the Tully machine, a paradigm for Pavlovian olfactory conditioning, depends on the presence of an intact S6KII gene. This rescue was successfully performed on both the null mutant and a partial deletion, suggesting that the removal of the phosphorylating unit of the kinase was the main cause of the functional defect. The GAL4/UAS system was used to achieve temporal and spatial control of S6KII expression. It was shown that expression of the kinase during the adult stage was essential for the rescue. This finding ruled out a developmental origin of the mutant learning phenotype. Furthermore, targeted spatial rescue of S6KII revealed a requirement in the mushroom bodies and excluded other brain structures like the median bundle, the antennal lobes and the central complex. This pattern is very similar to the one previously identified with the rutabaga mutant (Zars et al., 2000). Experiments with the double mutant rut, ign58-1 suggest that both rutabaga and S6KII operate in the same signalling pathway. Previous studies had already shown that deviating results from operant and classical conditioning point to different roles for S6KII in the two types of learning (Bertolucci, 2002; Putz, 2002). This conclusion was further strengthened by the defective performance of the transgenic lines in place learning and their normal behavior in olfactory conditioning. A novel type of learning experiment, called "idle experiment", was designed. It is based on the conditioning of the walking activity and represents a purely operant task, overcoming some of the limitations of the "standard" heat-box experiment, a place learning paradigm. The novel nature of the idle experiment allowed exploring "learned helplessness" in flies, unveiling astonishing similarities to more complex organisms such as rats, mice and humans. Learned helplessness in Drosophila is found only in females and is sensitive to antidepressants.},
  subject      = {Klassische Konditionierung},
  language  = {en}
}
@phdthesis{Mitesser2006,
  author    = {Mitesser, Oliver},
  title     = {The evolution of insect life history strategies in a social context},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22576},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {This thesis extends the classical theoretical work of Macevicz and Oster (1976, expanded by Oster and Wilson, 1978) on adaptive life history strategies in social insects. It focuses on the evolution of dynamic behavioural patterns (reproduction and activity) as a consequence of optimal allocation of energy and time resources. Mathematical modelling is based on detailed empirical observations in the model species Lasioglossum malachurum (Halictidae; Hymenoptera). The main topics are field observations, optimisation models for eusocial life histories, temporal variation in life history decisions, and annual colony cycles of eusocial insects.},
  subject      = {Schmalbienen},
  language  = {en}
}