TY - JOUR A1 - Staiger, Christine A1 - Cadot, Sidney A1 - Kooter, Raul A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Klau, Gunnar W. A1 - Wessels, Lodewyk F. A. T1 - A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer JF - PLoS One N2 - 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. KW - modules KW - protein-interaction networks KW - expression signature KW - classification KW - set KW - metastasis KW - stability KW - survival KW - database KW - markers Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131323 VL - 7 IS - 4 ER - TY - JOUR A1 - Weiße, Sebastian A1 - Heddergott, Niko A1 - Heydt, Matthias A1 - Pflästerer, Daniel A1 - Maier, Timo A1 - Haraszti, Tamas A1 - Grunze, Michael A1 - Engstler, Markus A1 - Rosenhahn, Axel T1 - A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy JF - PLoS One N2 - 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. KW - african trypanosomes KW - actin cortex KW - flagellum KW - tracking KW - surface KW - models Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130666 VL - 7 IS - 5 ER - TY - JOUR A1 - Jahn, Daniel A1 - Schramm, Sabine A1 - Schnölzer, Martina A1 - Heilmann, Clemens J. A1 - de Koster, Chris G. A1 - Schütz, Wolfgang A1 - Benavente, Ricardo A1 - Alsheimer, Manfred T1 - A truncated lamin A in the Lmna\(^{−/−}\) mouse line: Implications for the understanding of laminopathies JF - Nucleus N2 - During recent years a number of severe clinical syndromes, collectively termed laminopathies, turned out to be caused by various, distinct mutations in the human LMNA gene. Arising from this, remarkable progress has been made to unravel the molecular pathophysiology underlying these disorders. A great benefit in this context was the generation of an A-type lamin deficient mouse line (Lmna\(^{−/−}\)) by Sullivan and others,1 which has become one of the most frequently used models in the field and provided profound insights to many different aspects of A-type lamin function. Here, we report the unexpected finding that these mice express a truncated Lmna gene product on both transcriptional and protein level. Combining different approaches including mass spectrometry, we precisely define this product as a C-terminally truncated lamin A mutant that lacks domains important for protein interactions and post-translational processing. Based on our findings we discuss implications for the interpretation of previous studies using Lmna\(^{−/−}\) mice and the concept of human laminopathies. KW - nuclear organization KW - A-type lamins KW - LMNA mutations KW - laminopathies KW - nuclear envelope KW - nuclear lamina Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127281 VL - 3 IS - 5 ER - TY - JOUR A1 - Zirkel, J. A1 - Cecil, A. A1 - Schäfer, F. A1 - Rahlfs, S. A1 - Ouedraogo, A. A1 - Xiao, K. A1 - Sawadogo, S. A1 - Coulibaly, B. A1 - Becker, K. A1 - Dandekar, T. T1 - Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling JF - Bioinformatics and Biology Insights N2 - BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data. RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs. CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas. KW - methylene blue KW - malaria KW - elementary mode analysis KW - drug KW - resistance KW - combination therapy KW - pathway KW - metabolic flux Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123751 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - JOUR A1 - Tomei, Sara A1 - Adams, Sharon A1 - Uccellini, Lorenzo A1 - Bedognetti, Davide A1 - De Giorgi, Valeria A1 - Erdenebileg, Narnygerel A1 - Libera Ascierto, Maria A1 - Reinboth, Jennifer A1 - Liu, Qiuzhen A1 - Bevilacqua, Generoso A1 - Wang, Ena A1 - Mazzanti, Chiara A1 - Marincola, Francesco M. T1 - Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of melanoma in the North American population JF - Medical Oncology N2 - HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case–control study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83, p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR = 0.5, p = 0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690. KW - HRAS KW - polymorphism KW - melanoma KW - rs12628 KW - rs112587690 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126834 VL - 29 IS - 5 ER - TY - JOUR A1 - El-Keredy, Amira A1 - Schleyer, Michael A1 - König, Christian A1 - Ekim, Aslihan A1 - Gerber, Bertram T1 - Behavioural Analyses of Quinine Processing in Choice, Feeding and Learning of Larval Drosophila JF - PLoS One N2 - 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. KW - honeybees KW - chemosensory system KW - bitter taste KW - melanogaster KW - receptor KW - reward KW - brain KW - organization KW - architecture KW - perception Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130811 VL - 7 IS - 7 ER - TY - JOUR A1 - Kessler, Michael A1 - Hertel, Dietrich A1 - Jungkunst, Hermann F. A1 - Kluge, Jürgen A1 - Abrahamczyk, Stefan A1 - Bos, Merijn A1 - Buchori, Damayanti A1 - Gerold, Gerhard A1 - Gradstein, S. Robbert A1 - Köhler, Stefan A1 - Leuschner, Christoph A1 - Moser, Gerald A1 - Pitopang, Ramadhanil A1 - Saleh, Shahabuddin A1 - Schulze, Christian H. A1 - Sporn, Simone G. A1 - Steffan-Dewenter, Ingolf A1 - Tjitrosoedirdjo, Sri S. A1 - Tscharntke, Teja T1 - Can Joint Carbon and Biodiversity Management in Tropical Agroforestry Landscapes Be Optimized? JF - PLoS One N2 - 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. KW - forest soils KW - stocks KW - diversity KW - sequestration KW - conversion KW - balance KW - root Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132016 VL - 7 IS - 10 ER - TY - JOUR A1 - Schokraie, Elham A1 - Warnken, Uwe A1 - Hotz-Wagenblatt, Agnes A1 - Grohme, Markus A. A1 - Hengherr, Steffen A1 - Förster, Frank A1 - Schill, Ralph O. A1 - Frohme, Marcus A1 - Dandekar, Thomas A1 - Schnölzer, Martina T1 - Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state JF - PLoS One N2 - 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. KW - life-span regulation KW - genes KW - Yolk protein KW - water stress KW - expression KW - tolerance KW - richtersius coronifer KW - superoxide-dismutase KW - caenorhabditis elegans KW - arabidopsis thaliana KW - vitellogenin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134447 VL - 7 IS - 9 ER - TY - JOUR A1 - Schartl, Manfred A1 - Kneitz, Susanne A1 - Wilde, Brigitta A1 - Wagner, Toni A1 - Henkel, Christiaan V. A1 - Spaink, Hermann P. A1 - Meierjohann, Svenja T1 - Conserved expression signatures between medaka and human pigment cell tumors N2 - Aberrations in gene expression are a hallmark of cancer cells. Differential tumor-specific transcript levels of single genes or whole sets of genes may be critical for the neoplastic phenotype and important for therapeutic considerations or useful as biomarkers. As an approach to filter out such relevant expression differences from the plethora of changes noted in global expression profiling studies, we searched for changes of gene expression levels that are conserved. Transcriptomes from massive parallel sequencing of different types of melanoma from medaka were generated and compared to microarray datasets from zebrafish and human melanoma. This revealed molecular conservation at various levels between fish models and human tumors providing a useful strategy for identifying expression signatures strongly associated with disease phenotypes and uncovering new melanoma molecules. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75848 ER - TY - JOUR A1 - Krueger, Beate A1 - Friedrich, Torben A1 - Förster, Frank A1 - Bernhardt, Jörg A1 - Gross, Roy A1 - Dandekar, Thomas T1 - Different evolutionary modifications as a guide to rewire two-component systems JF - Bioinformatics and Biology Insights N2 - Two-component systems (TCS) are short signalling pathways generally occurring in prokaryotes. They frequently regulate prokaryotic stimulus responses and thus are also of interest for engineering in biotechnology and synthetic biology. The aim of this study is to better understand and describe rewiring of TCS while investigating different evolutionary scenarios. Based on large-scale screens of TCS in different organisms, this study gives detailed data, concrete alignments, and structure analysis on three general modification scenarios, where TCS were rewired for new responses and functions: (i) exchanges in the sequence within single TCS domains, (ii) exchange of whole TCS domains; (iii) addition of new components modulating TCS function. As a result, the replacement of stimulus and promotor cassettes to rewire TCS is well defined exploiting the alignments given here. The diverged TCS examples are non-trivial and the design is challenging. Designed connector proteins may also be useful to modify TCS in selected cases. KW - histidine kinase KW - connector KW - Mycoplasma KW - engineering KW - promoter KW - sensor KW - response regulator KW - synthetic biology KW - sequence alignment Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123647 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - JOUR A1 - Gassen, Alwine A1 - Brechtefeld, Doris A1 - Schandry, Niklas A1 - Arteaga-Salas, J. Manuel A1 - Israel, Lars A1 - Imhof, Axel A1 - Janzen, Christian J. T1 - DOT1A-dependent H3K76 methylation is required for replication regulation in Trypanosoma brucei JF - Nucleic Acids Research N2 - 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. KW - variants KW - cell-cycle regulation KW - blood-stream forms KW - african trypanosomes KW - mammalian cells KW - DNA replication KW - DOT1 KW - protein KW - transcription KW - cultivation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131449 VL - 40 IS - 20 ER - TY - JOUR A1 - Rakosy, Demetra A1 - Streinzer, Martin A1 - Paulus, Hannes F. A1 - Spaethe, Johannes T1 - Floral visual signal increases reproductive success in a sexually deceptive orchid JF - Arthropod-Plant Interactions N2 - Sexually deceptive orchids mimic signals emitted by female insects in order to attract mate-searching males. Specific attraction of the targeted pollinator is achieved by sex pheromone mimicry, which constitutes the major attraction channel. In close vicinity of the flower, visual signals may enhance attraction, as was shown recently in the sexually deceptive orchid Ophrys heldreichii. Here, we conducted an in situ manipulation experiment in two populations of O. heldreichii on Crete to investigate whether the presence/absence of the conspicuous pink perianth affects reproductive success in two natural orchid populations. We estimated reproductive success of three treatment groups (with intact, removed and artificial perianth) throughout the flowering period as pollinaria removal (male reproductive success) and massulae deposition (female reproductive success). Reproductive success was significantly increased by the presence of a strong visual signal—the conspicuous perianth—in one study population, however, not in the second, most likely due to the low pollinator abundance in the latter population. This study provides further evidence that the coloured perianth in O. heldreichii is adaptive and thus adds to the olfactory signal to maximise pollinator attraction and reproductive success. KW - sexual deception KW - eucera berlandi KW - male bees KW - ophrys heldreichii KW - pollination Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127209 VL - 6 IS - 4 ER - TY - JOUR A1 - Owen, Dylan M. A1 - Sauer, Markus A1 - Gaus, Katharina T1 - Fluorescence localization microscopy JF - Communicative & Integrative Biology N2 - Localization microscopy techniques are super-resolution fluorescence imaging methods based on the detection of individual molecules. Despite the relative simplicity of the microscope setups and the availability of commercial instruments, localization microscopy faces unique challenges. While achieving super-resolution is now routine, issues concerning data analysis and interpretation mean that revealing novel biological insights is not. Here, we outline why data analysis and the design of robust test samples may hold the key to harness the full potential of localization microscopy. Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124416 VL - 5 IS - 4 ER - TY - JOUR A1 - Sturm, Julia B. A1 - Hess, Michael A1 - Weibel, Stephanie A1 - Chen, Nanhei G. A1 - Yu, Yong A. A1 - Zhang, Quian A1 - Donat, Ulrike A1 - Reiss, Cora A1 - Gambaryan, Stepan A1 - Krohne, Georg A1 - Stritzker, Jochen A1 - Szalay, Aladar A. T1 - Functional hyper-IL-6 from vaccinia virus-colonized tumors triggers platelet formation and helps to alleviate toxicity of mitomycin C enhanced virus therapy N2 - Background: Combination of oncolytic vaccinia virus therapy with conventional chemotherapy has shown promise for tumor therapy. However, side effects of chemotherapy including thrombocytopenia, still remain problematic. Methods: Here, we describe a novel approach to optimize combination therapy of oncolytic virus and chemotherapy utilizing virus-encoding hyper-IL-6, GLV-1h90, to reduce chemotherapy-associated side effects. Results: We showed that the hyper-IL-6 cytokine was successfully produced by GLV-1h90 and was functional both in cell culture as well as in tumor-bearing animals, in which the cytokine-producing vaccinia virus strain was well tolerated. When combined with the chemotherapeutic mitomycin C, the anti-tumor effect of the oncolytic virotherapy was significantly enhanced. Moreover, hyper-IL-6 expression greatly reduced the time interval during which the mice suffered from chemotherapy-induced thrombocytopenia. Conclusion: Therefore, future clinical application would benefit from careful investigation of additional cytokine treatment to reduce chemotherapy-induced side effects. KW - Biologie KW - vaccinia virus KW - cancer KW - cytokine KW - hyper-IL-6 KW - oncolysis KW - chemotherapy Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75224 ER - TY - JOUR A1 - Agoston, Zsuzsa A1 - Li, Naixin A1 - Haslinger, Anja A1 - Wizenmann, Andrea A1 - Schulte, Dorothea T1 - Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development JF - BMC Developmental Biology N2 - Background: During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid-and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced. Results: Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage. Conclusion: The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7. KW - dosage KW - quali-chick chimeras KW - drosophila embryo KW - neural crest KW - transcription activation KW - hindbrain boundary KW - isthmic oragnizer KW - sonic hedghog KW - expression KW - induction Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132626 VL - 12 IS - 10 ER - TY - JOUR A1 - Vieira, Jacqueline A1 - Jones, Alex R. A1 - Danon, Antoine A1 - Sakuma, Michiyo A1 - Hoang, Nathalie A1 - Robles, David A1 - Tait, Shirley A1 - Heyes, Derren J. A1 - Picot, Marie A1 - Yoshii, Taishi A1 - Helfrich-Förster, Charlotte A1 - Soubigou, Guillaume A1 - Coppee, Jean-Yves A1 - Klarsfeld, André A1 - Rouyer, Francois A1 - Scrutton, Nigel S. A1 - Ahmad, Margaret T1 - Human Cryptochrome-1 Confers Light Independent Biological Activity in Transgenic Drosophila Correlated with Flavin Radical Stability JF - PLoS One N2 - 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. KW - arabidopsi KW - dependent magnetosensitvity KW - protein KW - clock KW - gene KW - mechanism KW - rhythm KW - oscillator KW - circadian photoreception KW - mammalian CRY1 Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134513 VL - 7 IS - 3 ER - TY - JOUR A1 - Buga, Ana-Maria A1 - Scholz, Claus Jürgen A1 - Kumar, Senthil A1 - Herndon, James G. A1 - Alexandru, Dragos A1 - Cojocaru, Gabriel Radu A1 - Dandekar, Thomas A1 - Popa-Wagner, Aurel T1 - Identification of New Therapeutic Targets by Genome-Wide Analysis of Gene Expression in the Ipsilateral Cortex of Aged Rats after Stroke JF - PLoS One N2 - 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. KW - gamma KW - corticotropin-releasing hormone KW - colony-stimulating factor KW - cerebral ischemia KW - receptor KW - brain KW - protein KW - inhibitor KW - mouse KW - differentiation Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130657 VL - 7 IS - 12 ER - TY - JOUR A1 - Prusty, Bhupesh K. A1 - Böhme, Linda A1 - Bergmann, Birgit A1 - Siegl, Christine A1 - Krause, Eva A1 - Mehlitz, Adrian A1 - Rudel, Thomas T1 - Imbalanced oxidative stress causes chlamydial persistence during non-productive Human Herpes Virus co-infection N2 - Both human herpes viruses and Chlamydia are highly prevalent in the human population and are detected together in different human disorders. Here, we demonstrate that co-infection with human herpes virus 6 (HHV6) interferes with the developmental cycle of C. trachomatis and induces persistence. Induction of chlamydial persistence by HHV6 is independent of productive virus infection, but requires the interaction and uptake of the virus by the host cell. On the other hand, viral uptake is strongly promoted under co-infection conditions. Host cell glutathione reductase activity was suppressed by HHV6 causing NADPH accumulation, decreased formation of reduced glutathione and increased oxidative stress. Prevention of oxidative stress restored infectivity of Chlamydia after HHV6-induced persistence. We show that co-infection with Herpes simplex virus 1 or human Cytomegalovirus also induces chlamydial persistence by a similar mechanism suggesting that Chlamydia -human herpes virus co-infections are evolutionary shaped interactions with a thus far unrecognized broad significance. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76215 ER - TY - JOUR A1 - Dosso, Kanvaly A1 - Yeo, Kolo A1 - Konate, Souleymane A1 - Linsenmair, Karl Eduard T1 - Importance of protected areas for biodiversity conservation in central Cote d'Ivoire: Comparison of termite assemblages between two neighboring areas under differing levels of disturbance JF - Journal of Insect Science N2 - To highlight human impact on biodiversity in the Lamto region, termites were studied with regard to their use as bio-indicators of habitat change in the tropics. Using a standardized method, termites were sampled in the three most common habitat types, i.e., in semi-deciduous forest, savanna woodland, and annually burned savanna, all inside Lamto Reserve and its surrounding rural domain. Termite species richness fell from 25 species in the Lamto forest to 13 species in the rural area, involving strong modification in the species composition (species turnover = 59 %). In contrast, no significant change in diversity was found between the Lamto savannas and the rural ones. In addition, the relative abundance of termites showed a significantly greater decline in the rural domain, even in the species Ancistrotermes cavithorax (Sjostedt) (Isoptera: Termitidae), which is known to be ecologically especially versatile. Overall, the findings of this study suggest further investigation around Lamto Reserve on the impact of human activities on biodiversity, focusing on forest conversion to land uses (e.g. agricultural and silvicultural systems). KW - species richness KW - Savanna KW - trinervitermes KW - rural domain KW - ant communities KW - gradient KW - Amazonia KW - forest disturbance KW - diversity KW - soil macrofauna KW - West Africa KW - land use KW - burned savanna KW - forest KW - Lamto Reserve KW - relative abundance KW - savanna woodland KW - species composition Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133218 VL - 12 IS - 131 ER - TY - JOUR A1 - Azzami, Klara A1 - Ritter, Wolfgang A1 - Tautz, Jürgen A1 - Beier, Hildburg T1 - Infection of honey bees with acute bee paralysis virus does not trigger humoral or cellular immune responses JF - Archives of Virology N2 - We have studied the responses of honey bees at different life stages (Apis mellifera) to controlled infection with acute bee paralysis virus and have identified the haemolymph of infected larvae and adult worker bees as the compartment where massive propagation of ABPV occurs. Insects respond with a broad spectrum of induced innate immune reactions to bacterial infections, whereas defence mechanisms based on RNA interference play a major role in antiviral immunity. In this study, we have determined that honey bee larvae and adult workers do not produce a humoral immune reaction upon artificial infection with ABPV, in contrast to control individuals challenged with Escherichia coli. ABPV-infected bees produced neither elevated levels of specific antimicrobial peptides (AMPs), such as hymenoptaecin and defensin, nor any general antimicrobial activity, as revealed by inhibition-zone assays. Additionally, adult bees did not generate melanised nodules upon ABPV infection, an important cellular immune function activated by bacteria and viruses in some insects. Challenge of bees with both ABPV and E. coli showed that innate humoral and cellular immune reactions are induced in mixed infections, albeit at a reduced level. KW - chemosensory protein KW - bee larva KW - adult bee KW - honey bee KW - larva KW - work bee KW - infected bee KW - immune response KW - young work bee KW - capsid protein KW - abdominal KW - tergite KW - haemolymph KW - sample KW - Imd pathway KW - worker bee larva KW - antimicrobial KW - peptide Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126863 VL - 157 IS - 4 ER - TY - JOUR A1 - Beisser, Daniela A1 - Grohme, Markus A. A1 - Kopka, Joachim A1 - Frohme, Marcus A1 - Schill, Ralph O. A1 - Hengherr, Steffen A1 - Dandekar, Thomas A1 - Klau, Gunnar W. A1 - Dittrich, Marcus A1 - Müller, Tobias T1 - Integrated pathway modules using time-course metabolic profiles and EST data from Milnesium tardigradum N2 - Background: Tardigrades are multicellular organisms, resistant to extreme environmental changes such as heat, drought, radiation and freezing. They outlast these conditions in an inactive form (tun) to escape damage to cellular structures and cell death. Tardigrades are apparently able to prevent or repair such damage and are therefore a crucial model organism for stress tolerance. Cultures of the tardigrade Milnesium tardigradum were dehydrated by removing the surrounding water to induce tun formation. During this process and the subsequent rehydration, metabolites were measured in a time series by GC-MS. Additionally expressed sequence tags are available, especially libraries generated from the active and inactive state. The aim of this integrated analysis is to trace changes in tardigrade metabolism and identify pathways responsible for their extreme resistance against physical stress. Results: In this study we propose a novel integrative approach for the analysis of metabolic networks to identify modules of joint shifts on the transcriptomic and metabolic levels. We derive a tardigrade-specific metabolic network represented as an undirected graph with 3,658 nodes (metabolites) and 4,378 edges (reactions). Time course metabolite profiles are used to score the network nodes showing a significant change over time. The edges are scored according to information on enzymes from the EST data. Using this combined information, we identify a key subnetwork (functional module) of concerted changes in metabolic pathways, specific for de- and rehydration. The module is enriched in reactions showing significant changes in metabolite levels and enzyme abundance during the transition. It resembles the cessation of a measurablemetabolism (e.g. glycolysis and amino acid anabolism) during the tun formation, the production of storage metabolites and bioprotectants, such as DNA stabilizers, and the generation of amino acids and cellular components from monosaccharides as carbon and energy source during rehydration. Conclusions: The functional module identifies relationships among changed metabolites (e.g. spermidine) and reactions and provides first insights into important altered metabolic pathways. With sparse and diverse data available, the presented integrated metabolite network approach is suitable to integrate all existing data and analyse it in a combined manner. KW - Milnesium tardigradum KW - Integrated network analysis KW - Functional modules KW - Metabolic profiles KW - Metabolic pathways KW - Trend test Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75241 ER - TY - JOUR A1 - Fraunholz, Martin A1 - Sinha, Bhanu T1 - Intracellular staphylococcus aureus: Live-in and let die JF - Frontiers in Cellular and Infection Microbiology N2 - Staphylococcus aureus uses a plethora of virulence factors to accommodate a diversity of niches in its human host. Aside from the classical manifestations of S. aureus-induced diseases, the pathogen also invades and survives within mammalian host cells. The survival strategies of the pathogen are as diverse as strains or host cell types used. S. aureus is able to replicate in the phagosome or freely in the cytoplasm of its host cells. It escapes the phagosome of professional and non-professional phagocytes, subverts autophagy, induces cell death mechanisms such as apoptosis and pyronecrosis, and even can induce anti-apoptotic programs in phagocytes. The focus of this review is to present a guide to recent research outlining the variety of intracellular fates of S. aureus. KW - staphylococcus aureus KW - bacterial persistence KW - host cell death KW - autophagy KW - phagocytosis KW - phagosomalescape Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123374 VL - 2 IS - 43 ER - TY - JOUR A1 - Roier, Sandro A1 - Leitner, Deborah R. A1 - Iwashkiw, Jeremy A1 - Schild-Prüfert, Kristina A1 - Feldman, Mario F. A1 - Krohne, Georg A1 - Reidl, Joachim A1 - Schild, Stefan T1 - Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice JF - PLoS One N2 - 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. KW - conjugate KW - obstructive pulmonary disease KW - vaccine KW - vibrio cholerae KW - detoxified lipooligosaccharide KW - nasopharyngeal colonization KW - functional characterization KW - growing escherichia coli KW - DNA-binding vesicles KW - otitis media KW - hemophilus influenzae Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135201 VL - 7 IS - 8 ER - TY - JOUR A1 - Menescal, Luciana A1 - Schmidt, Cornelia A1 - Liedtke, Daniel A1 - Schartl, Manfred T1 - Liver hyperplasia after tamoxifen induction of Myc in a transgenic medaka model N2 - Myc is a global transcriptional regulator and one of the most frequently overexpressed oncoproteins in human tumors. It is well established that activation of Myc leads to enhanced cell proliferation but can also lead to increased apoptosis. The use of animal models expressing deregulated levels of Myc has helped to both elucidate its function in normal cells and give insight into how Myc initiates and maintains tumorigenesis. Analyses of the medaka (Oryzias latipes) genome uncovered the unexpected presence of two Myc gene copies in this teleost species. Comparison of these Myc versions to other vertebrate species revealed that one gene, myc17, differs by the loss of some conserved regulatory protein motifs present in all other known Myc genes. To investigate how such differences might affect the basic biological functions of Myc, we generated a tamoxifeninducible in vivo model utilizing a natural, fish-specific Myc gene. Using this model we show that, when activated, Myc17 leads to increased proliferation and to apoptosis in a dose-dependent manner, similar to human Myc. We have also shown that long-term Myc17 activation triggers liver hyperplasia in adult fish, allowing this newly established transgenic medaka model to be used to study the transition from hyperplasia to liver cancer and to identify Myc-induced tumorigenesis modifiers. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75316 ER - TY - JOUR A1 - Jazbutyte, Virginija A1 - Fiedler, Jan A1 - Kneitz, Susanne A1 - Galuppo, Paolo A1 - Just, Annette A1 - Holzmann, Angelika A1 - Bauersachs, Johann A1 - Thum, Thomas T1 - MicroRNA-22 increases senescence and activates cardiac fibroblasts in the aging heart JF - AGE N2 - MicroRNAs (miRs) are small non- coding RNA molecules controlling a plethora of biological processes such as development, cellular survival and senescence. We here determined miRs differentially regulated during cardiac postnatal development and aging. Cardiac function, morphology and miR expression profiles were determined in neonatal, 4 weeks, 6 months and 19 months old normotensive male healthy C57/Bl6N mice. MiR-22 was most prominently upregulated during cardiac aging. Cardiac expression of its bioinformatically predicted target mimecan (osteoglycin, OGN) was gradually decreased with advanced age. Luciferase reporter assays validated mimecan as a bona fide miR-22 target. Both, miR-22 and its target mimecan were co- expressed in cardiac fibroblasts and smooth muscle cells. Functionally, miR-22 overexpression induced cellular senescence and promoted migratory activity of cardiac fibroblasts. Small interference RNA-mediated silencing of mimecan in cardiac fibroblasts mimicked the miR-22-mediated effects. Rescue experiments revealed that the effects of miR-22 on cardiac fibroblasts were only partially mediated by mimecan. In conclusion, miR-22 upregulation in the aging heart contributed at least partly to accelerated cardiac fibroblast senescence and increased migratory activity. Our results suggest an involvement of miR-22 in age-associated cardiac changes, such as cardiac fibrosis. KW - cardiac fibrosis KW - cardiac aging KW - microRNAs KW - miR-22 KW - mimecan KW - osteoglycin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126745 VL - 35 IS - 3 ER - TY - JOUR A1 - Hönnemann, Jan A1 - Sanz-Moreno, Adrian A1 - Wolf, Elmar A1 - Eilers, Martin A1 - Elsässer, Hans-Peter T1 - Miz1 Is a Critical Repressor of cdkn1a during Skin Tumorigenesis JF - PLoS One N2 - The transcription factor Miz1 forms repressive DNA-binding complexes with the Myc, Gfi-1 and Bcl-6 oncoproteins. Known target genes of these complexes encode the cyclin-dependent kinase inhibitors (CKIs) cdkn2b (p15\(^{Ink4}\)), cdkn1a (p21\(^{Cip1}\)), and cdkn1c (p57\(^{Kip2}\)). Whether Miz1-mediated repression is important for control of cell proliferation in vivo and for tumor formation is unknown. Here we show that deletion of the Miz1 POZ domain, which is critical for Miz1 function, restrains the development of skin tumors in a model of chemically-induced, Ras-dependent tumorigenesis. While the stem cell compartment appears unaffected, interfollicular keratinocytes lacking functional Miz1 exhibit a reduced proliferation and an accelerated differentiation of the epidermis in response to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). Tumorigenesis, proliferation and normal differentiation are restored in animals lacking cdkn1a, but not in those lacking cdkn2b. Our data demonstrate that Miz1-mediated attenuation of cell cycle arrest pathways via repression of cdkn1a has a critical role during tumorigenesis in the skin. KW - transcription factor MIZ-1 KW - cell-cycle arrest KW - c-myc KW - tumor suppressor KW - cancer cells KW - POZ domain KW - P21 KW - differentiation KW - P15(INK4B) KW - senescence Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133285 VL - 7 IS - 4 ER - TY - JOUR A1 - Ruczyński, Ireneusz A1 - Bartoń, Kamil A. T1 - Modelling Sensory Limitation: The Role of Tree Selection, Memory and Information Transfer in Bats' Roost Searching Strategies JF - PLoS One N2 - 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. KW - New Zealand KW - netcar-feeding bats KW - big brown bats KW - long-term reuse KW - nyctalus noctula KW - chalinolobus-tuberculatus KW - eptesicus-fuscus KW - social calls KW - dwelling bat KW - rain forest Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133963 VL - 7 IS - 9 ER - TY - JOUR A1 - Ratzka, Carolin A1 - Förster, Frank A1 - Liang, Chunguang A1 - Kupper, Maria A1 - Dandekar, Thomas A1 - Feldhaar, Heike A1 - Gross, Roy T1 - Molecular characterization of antimicrobial peptide genes of the carpenter ant Camponotus floridanus N2 - The production of antimicrobial peptides (AMPs) is a major defense mechanism against pathogen infestation and of particular importance for insects relying exclusively on an innate immune system. Here, we report on the characterization of three AMPs from the carpenter ant Camponotus floridanus. Due to sequence similarities and amino acid composition these peptides can be classified into the cysteine-rich (e.g. defensin) and glycine-rich (e.g. hymenoptaecin) AMP groups, respectively. The gene and cDNA sequences of these AMPs were established and their expression was shown to be induced by microbial challenge. We characterized two different defensin genes. The defensin-2 gene has a single intron, whereas the defensin-1 gene has two introns. The deduced amino acid sequence of the C. floridanus defensins is very similar to other known ant defensins with the exception of a short C-terminal extension of defensin-1. The hymenoptaecin gene has a single intron and a very peculiar domain structure. The corresponding precursor protein consists of a signal- and a pro-sequence followed by a hymenoptaecin-like domain and six directly repeated hymenoptaecin domains. Each of the hymenoptaecin domains is flanked by an EAEP-spacer sequence and a RR-site known to be a proteolytic processing site. Thus, proteolytic processing of the multipeptide precursor may generate several mature AMPs leading to an amplification of the immune response. Bioinformatical analyses revealed the presence of hymenoptaecin genes with similar multipeptide precursor structure in genomes of other ant species suggesting an evolutionary conserved important role of this gene in ant immunity. KW - Biologie KW - Camponotus floridanus Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75985 ER - TY - JOUR A1 - Grafe, T. Ulmar A1 - Preininger, Doris A1 - Sztatecsny, Marc A1 - Kasah, Rosli A1 - Dehling, J. Maximilian A1 - Proksch, Sebastian A1 - Hödl, Walter T1 - Multimodal Communication in a Noisy Environment: A Case Study of the Bornean Rock Frog Staurois parvus JF - PLoS One N2 - 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. KW - call KW - dart-poison frog KW - animal communication KW - auditory masking KW - acoustic communication KW - anthropogenic noise KW - courtship displays KW - traffic noise KW - higher pitch KW - signals Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133718 VL - 7 IS - 5 ER - TY - JOUR A1 - Harrington, John M. A1 - Scelsi, Chris A1 - Hartel, Andreas A1 - Jones, Nicola G. A1 - Engstler, Markus A1 - Capewell, Paul A1 - MacLeod, Annette A1 - Hajduk, Stephen T1 - Novel African Trypanocidal Agents: Membrane Rigidifying Peptides JF - PLoS One N2 - 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. KW - depth KW - trypanosome lytic factor KW - signal peptides KW - cell surface KW - protein KW - brucei KW - environment KW - bilayers KW - binding KW - probes Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135179 VL - 7 IS - 9 ER - TY - JOUR A1 - Patil, Sandeep S. A1 - Gentschev, Ivaylo A1 - Nolte, Ingo A1 - Ogilvie, Gregory A1 - Szalay, Aladar A. T1 - Oncolytic virotherapy in veterinary medicine: current status and future prospects for canine patients N2 - Oncolytic viruses refer to those that are able to eliminate malignancies by direct targeting and lysis of cancer cells, leaving non-cancerous tissues unharmed. Several oncolytic viruses including adenovirus strains, canine distemper virus and vaccinia virus strains have been used for canine cancer therapy in preclinical studies. However, in contrast to human studies, clinical trials with oncolytic viruses for canine cancer patients have not been reported. An ‘ideal’ virus has yet to be identified. This review is focused on the prospective use of oncolytic viruses in the treatment of canine tumors - a knowledge that will undoubtedly contribute to the development of oncolytic viral agents for canine cancer therapy in the future. KW - Medizin KW - cancer KW - canine cancer therapy KW - oncolytic virus KW - oncolysis KW - target molecule KW - combination therapy Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75128 ER - TY - JOUR A1 - Zoephel, Judith A1 - Reiher, Wencke A1 - Rexer, Karl-Heinz A1 - Kahnt, Jörg A1 - Wegener, Christian T1 - Peptidomics of the Agriculturally Damaging Larval Stage of the Cabbage Root Fly Delia radicum (Diptera: Anthomyiidae) JF - PLoS One N2 - 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. KW - adult drosophila KW - central-nervous-system KW - blowfly calliphora-vomitoria KW - drosophila melanogaster KW - mass spectometry KW - feeding behavior KW - fruit fly KW - functional characterization KW - immunoreactive neurons KW - neobellieria bullata Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131727 VL - 7 IS - 7 ER - TY - JOUR A1 - Cornelius, C. A1 - Leingärtner, A. A1 - Hoiss, B. A1 - Krauss, J. A1 - Steffan-Dewenter, I. A1 - Menzel, A. T1 - Phenological response of grassland species to manipulative snowmelt and drought along an altitudinal gradient N2 - Plant communities in the European Alps are assumed to be highly affected by climate change since temperature rise in this region is above the global average. It is predicted that higher temperatures will lead to advanced snowmelt dates and that the number of extreme weather events will increase. The aims of this study were to determine the impacts of extreme climatic events on flower phenology and to assess whether those impacts differed between lower and higher altitudes. In 2010 an experiment simulating advanced and delayed snowmelt as well as drought event was conducted along an altitudinal transect ca. every 250m (600-2000 m a.s.l.) in the Berchtesgaden National Park, Germany. The study showed that flower phenology is strongly affected by altitude; however there were few effects of the manipulative treatments on flowering. The effects of advanced snowmelt were significantly greater at higher than at lower sites, but no significant difference was found between both altitudinal bands for the other treatments. The response of flower phenology to temperature declined through the season and the length of flowering duration was not significantly influenced by treatments. The stronger effect of advanced snowmelt at higher altitudes might be a response to differences in treatment intensity across the gradient. Consequently, shifts in the date of snowmelt due to global warming may affect species more at higher than at lower altitudes since changes may be more pronounced at higher altitudes. Our data indicate a rather low risk of drought events on flowering phenology in the Bavarian Alps. KW - Biologie KW - Advanced snowmelt KW - Alps KW - BBCH KW - Climate change KW - Delayed snowmelt KW - Flowering Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-77969 N1 - ist zugleich: IV. Kapitel der Dissertation von Bernhard Hoiß ER - TY - JOUR A1 - Tu, Xiaolin A1 - Chen, Jianquan A1 - Lim, Joohyun A1 - Karner, Courtney M. A1 - Lee, Seung-Yon A1 - Heisig, Julia A1 - Wiese, Cornelia A1 - Surendran, Kameswaran A1 - Kopan, Raphael A1 - Gessler, Manfred A1 - Long, Fanxin T1 - Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1 JF - PLoS Genetics N2 - 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. KW - expression KW - axial skeletal defects KW - transcription factor KW - alagille syndrome KW - osteoblast differentiation KW - human jagged1 KW - aortic-valve KW - T cells KW - mutations KW - mice Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133490 VL - 8 IS - 3 ER - TY - JOUR A1 - Lando, David A1 - Endesfelder, Ulrike A1 - Berger, Harald A1 - Subramanian, Lakxmi A1 - Dunne, Paul D. A1 - McColl, James A1 - Klenerman, David A1 - Carr, Antony M. A1 - Sauer, Markus A1 - Allshire, Robin C. A1 - Heilemann, Mike A1 - Laue, Ernest D. T1 - Quantitative single-molecule microscopy reveals that CENP-A\(^{Cnp1}\) deposition occurs during G2 in fission yeast JF - Open Biology N2 - The inheritance of the histone H3 variant CENP-A in nucleosomes at centromeres following DNA replication is mediated by an epigenetic mechanism. To understand the process of epigenetic inheritance, or propagation of histones and histone variants, as nucleosomes are disassembled and reassembled in living eukaryotic cells, we have explored the feasibility of exploiting photo-activated localization microscopy (PALM). PALM of single molecules in living cells has the potential to reveal new concepts in cell biology, providing insights into stochastic variation in cellular states. However, thus far, its use has been limited to studies in bacteria or to processes occurring near the surface of eukaryotic cells. With PALM, one literally observes and 'counts' individual molecules in cells one-by-one and this allows the recording of images with a resolution higher than that determined by the diffraction of light (the so-called super-resolution microscopy). Here, we investigate the use of different fluorophores and develop procedures to count the centromere-specific histone H3 variant CENP-A\(^{Cnp1}\) with single-molecule sensitivity in fission yeast (Schizosaccharomyces pombe). The results obtained are validated by and compared with ChIP-seq analyses. Using this approach, CENP-A\(^{Cnp1}\) levels at fission yeast (S. pombe) centromeres were followed as they change during the cell cycle. Our measurements show that CENP-A(Cnp1) is deposited solely during the G2 phase of the cell cycle. KW - nucleosome KW - fission yeast KW - identification KW - propagation KW - CSE4, CENP-A KW - CENP-A KW - schizosaccaromyces-pombe KW - fluorescent protein KW - centomeres KW - superresolution KW - chromatin KW - centromere KW - ingle-molecule microscopy Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134682 VL - 2 IS - 120078 ER - TY - JOUR A1 - Sanges, C. A1 - Scheuermann, C. A1 - Zahedi, R. P. A1 - Sickmann, A. A1 - Lamberti, A. A1 - Migliaccio, N. A1 - Baljuls, A. A1 - Marra, M. A1 - Zappavigna, S. A1 - Rapp, U. A1 - Abbruzzese, A. A1 - Caraglia, M. A1 - Arcari, P. T1 - Raf kinases mediate the phosphorylation of eukaryotic translation elongation factor 1A and regulate its stability in eukaryotic cells JF - Cell Death & Disease N2 - We identified eukaryotic translation elongation factor 1A (eEF1A) Raf-mediated phosphorylation sites and defined their role in the regulation of eEF1A half-life and of apoptosis of human cancer cells. Mass spectrometry identified in vitro S21 and T88 as phosphorylation sites mediated by B-Raf but not C-Raf on eEF1A1 whereas S21 was phosphorylated on eEF1A2 by both B-and C-Raf. Interestingly, S21 belongs to the first eEF1A GTP/GDP-binding consensus sequence. Phosphorylation of S21 was strongly enhanced when both eEF1A isoforms were preincubated prior the assay with C-Raf, suggesting that the eEF1A isoforms can heterodimerize thus increasing the accessibility of S21 to the phosphate. Overexpression of eEF1A1 in COS 7 cells confirmed the phosphorylation of T88 also in vivo. Compared with wt, in COS 7 cells overexpressed phosphodeficient (A) and phospho-mimicking (D) mutants of eEF1A1 (S21A/D and T88A/D) and of eEF1A2 (S21A/D), resulted less stable and more rapidly proteasome degraded. Transfection of S21 A/D eEF1A mutants in H1355 cells increased apoptosis in comparison with the wt isoforms. It indicates that the blockage of S21 interferes with or even supports C-Raf induced apoptosis rather than cell survival. Raf-mediated regulation of this site could be a crucial mechanism involved in the functional switching of eEF1A between its role in protein biosynthesis and its participation in other cellular processes. KW - signal transduction KW - mass spectrometry KW - elongation KW - protein docking KW - factor EEF1A2 KW - cancer-cells KW - lung cancer KW - EF-1A KW - Raf kinases KW - aminoacyl-transfer-RNA KW - tyrosine phosphorylation KW - factor 1-alpha KW - nucleotide exchange KW - polyarcylamide gels KW - chain KW - apoptosis KW - ubiquitin Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134673 VL - 3 IS - e276 ER - TY - JOUR A1 - Schneider, Christof W. A1 - Tautz, Jürgen A1 - Grünewald, Bernd A1 - Fuchs, Stefan T1 - RFID Tracking of Sublethal Effects of Two Neonicotinoid Insecticides on the Foraging Behavior of Apis mellifera JF - PLoS One N2 - 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. KW - memory KW - nicotinic acetylcholine-receptors KW - unpaired median neurons KW - honey bees KW - learning performances KW - toxicity KW - hymenoptera KW - pesticides KW - relevance KW - agonist Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131753 VL - 7 IS - 1 ER - TY - JOUR A1 - Dandekar, Thomas A1 - Fieselmann, Astrid A1 - Popp, Jasmin A1 - Hensel, Michael T1 - Salmonella enterica: a surprisingly well-adapted intracellular lifestyle JF - Frontiers in Microbiology N2 - The infectious intracellular lifestyle of Salmonella enterica relies on the adaptation to nutritional conditions within the Salmonella-containing vacuole (SCV) in host cells. We summarize latest results on metabolic requirements for Salmonella during infection. This includes intracellular phenotypes of mutant strains based on metabolic modeling and experimental tests, isotopolog profiling using (13)C-compounds in intracellular Salmonella, and complementation of metabolic defects for attenuated mutant strains towards a comprehensive understanding of the metabolic requirements of the intracellular lifestyle of Salmonella. Helpful for this are also genomic comparisons. We outline further recent studies and which analyses of intracellular phenotypes and improved metabolic simulations were done and comment on technical required steps as well as progress involved in the iterative refinement of metabolic flux models, analyses of mutant phenotypes, and isotopolog analyses. Salmonella lifestyle is well-adapted to the SCV and its specific metabolic requirements. Salmonella metabolism adapts rapidly to SCV conditions, the metabolic generalist Salmonella is quite successful in host infection. KW - Salmonella enterica KW - metabolism KW - Salmonella-containing vacuole KW - regulation KW - virulence Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123135 ER - TY - JOUR A1 - Hsieh, Yu-Lung A1 - Linsenmair, Karl Eduard T1 - Seasonal dynamics of arboreal spider diversity in a temperate forest N2 - Measuring and estimating biodiversity patterns is a fundamental task of the scientist working to support conservation and informmanagement decisions.Most biodiversity studies in temperate regions were often carried out over a very short period of time (e.g., a single season) and it is often—at least tacitly—assumed that these short-termfindings are representative of long-termgeneral patterns.However, should the studied biodiversity pattern in fact contain significant temporal dynamics, perhaps leading to contradictory conclusions. Here, we studied the seasonal diversity dynamics of arboreal spider communities dwelling in 216 European beeches (Fagus sylvatica L.) to assess the spider community composition in the following seasons: two cold seasons (I:November 2005–January 2006; II: February–April) and two warm seasons (III: May–July; IV: August–October). We show that the usually measured diversity of the warmseason community (IV: 58 estimated species) alone did not deliver a reliable image of the overall diversity present in these trees, and therefore, we recommend it should not be used for sampling protocols aimed at providing a full picture of a forest’s biodiversity in the temperate zones. In particular, when the additional samplings of other seasons (I, II, III) were included, the estimated species richness nearly doubled (108). Community I possessed the lowest diversity and evenness due to the harsh winter conditions: this community was comprised of one dominant species together with several species low in abundance. Similarity was lowest (38.6%) between seasonal communities I and III, indicating a significant species turnover due to recolonization, so that community III had the highest diversity. Finally, using nonparametric estimators, we found that further sampling in late winter (February–April) is most needed to complete our inventory. Our study clearly demonstrates that seasonal dynamics of communities should be taken into account when studying biodiversity patterns of spiders, and probably forest arthropods in general. KW - Biologie KW - Araneae KW - canopy fogging KW - European beech KW - recolonization KW - species richness estimation KW - true diversity Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75158 ER - TY - JOUR A1 - Heisig, Julia A1 - Weber, David A1 - Englberger, Eva A1 - Winkler, Anja A1 - Kneitz, Susanne A1 - Sung, Wing-Kin A1 - Wolf, Elmar A1 - Eilers, Martin A1 - Wei, Chia-Lin A1 - Gessler, Manfred T1 - Target Gene Analysis by Microarrays and Chromatin Immunoprecipitation Identifies HEY Proteins as Highly Redundant bHLH Repressors N2 - HEY bHLH transcription factors have been shown to regulate multiple key steps in cardiovascular development. They can be induced by activated NOTCH receptors, but other upstream stimuli mediated by TGFß and BMP receptors may elicit a similar response. While the basic and helix-loop-helix domains exhibit strong similarity, large parts of the proteins are still unique and may serve divergent functions. The striking overlap of cardiac defects in HEY2 and combined HEY1/HEYL knockout mice suggested that all three HEY genes fulfill overlapping function in target cells. We therefore sought to identify target genes for HEY proteins by microarray expression and ChIPseq analyses in HEK293 cells, cardiomyocytes, and murine hearts. HEY proteins were found to modulate expression of their target gene to a rather limited extent, but with striking functional interchangeability between HEY factors. Chromatin immunoprecipitation revealed a much greater number of potential binding sites that again largely overlap between HEY factors. Binding sites are clustered in the proximal promoter region especially of transcriptional regulators or developmental control genes. Multiple lines of evidence suggest that HEY proteins primarily act as direct transcriptional repressors, while gene activation seems to be due to secondary or indirect effects. Mutagenesis of putative DNA binding residues supports the notion of direct DNA binding. While class B E-box sequences (CACGYG) clearly represent preferred target sequences, there must be additional and more loosely defined modes of DNA binding since many of the target promoters that are efficiently bound by HEY proteins do not contain an Ebox motif. These data clearly establish the three HEY bHLH factors as highly redundant transcriptional repressors in vitro and in vivo, which explains the combinatorial action observed in different tissues with overlapping expression. KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75341 ER - TY - JOUR A1 - Merget, Benjamin A1 - Koetschan, Christian A1 - Hackl, Thomas A1 - Förster, Frank A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schultz, Jörg A1 - Wolf, Matthias T1 - The ITS2 Database JF - Journal of Visual Expression N2 - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses. KW - homology modeling KW - molecular systematics KW - internal transcribed spacer 2 KW - alignment KW - genetics KW - secondary structure KW - ribosomal RNA KW - phylogenetic tree KW - phylogeny Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600 VL - 61 IS - e3806 ER - TY - JOUR A1 - Rhiem, Kerstin A1 - Engel, Christoph A1 - Graeser, Monika A1 - Zachariae, Silke A1 - Kast, Karin A1 - Kiechle, Marion A1 - Ditsch, Nina A1 - Janni, Wolfgang A1 - Mundhenke, Christoph A1 - Golatta, Michael A1 - Varga, Dominic A1 - Preisler-Adams, Sabine A1 - Heinrich, Tilman A1 - Bick, Ulrich A1 - Gadzicki, Dorothea A1 - Briest, Susanne A1 - Meindl, Alfons A1 - Schmutzler, Rita K. T1 - The risk of contralateral breast cancer in patients from BRCA1/2 negative high risk families as compared to patients from BRCA1 or BRCA2 positive families: a retrospective cohort study JF - Breast Cancer Research N2 - Introduction: While it has been reported that the risk of contralateral breast cancer in patients from BRCA1 or BRCA2 positive families is elevated, little is known about contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations. Methods: A retrospective, multicenter cohort study was performed from 1996 to 2011 and comprised 6,235 women with unilateral breast cancer from 6,230 high risk families that had tested positive for BRCA1 (n = 1,154) or BRCA2 (n = 575) mutations or tested negative (n = 4,501). Cumulative contralateral breast cancer risks were calculated using the Kaplan-Meier product-limit method and were compared between groups using the log-rank test. Cox regression analysis was applied to assess the impact of the age at first breast cancer and the familial history stratified by mutation status. Results: The cumulative risk of contralateral breast cancer 25 years after first breast cancer was 44.1% (95%CI, 37.6% to 50.6%) for patients from BRCA1 positive families, 33.5% (95%CI, 22.4% to 44.7%) for patients from BRCA2 positive families and 17.2% (95%CI, 14.5% to 19.9%) for patients from families that tested negative for BRCA1/2 mutations. Younger age at first breast cancer was associated with a higher risk of contralateral breast cancer. For women who had their first breast cancer before the age of 40 years, the cumulative risk of contralateral breast cancer after 25 years was 55.1% for BRCA1, 38.4% for BRCA2, and 28.4% for patients from BRCA1/2 negative families. If the first breast cancer was diagnosed at the age of 50 or later, 25-year cumulative risks were 21.6% for BRCA1, 15.5% for BRCA2, and 12.9% for BRCA1/2 negative families. Conclusions: Contralateral breast cancer risk in patients from high risk families that tested negative for BRCA1/2 mutations is similar to the risk in patients with sporadic breast cancer. Thus, the mutation status should guide decision making for contralateral mastectomy. KW - contralateral breast cancer KW - BRCA1/2 negative KW - BRCA1 positive KW - BRCA2 positive Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135715 VL - 14 IS - 6 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Dandekar, Thomas T1 - The Role of Auxin-Cytokinin Antagonism in Plant-Pathogen Interactions JF - PLOS Pathogens N2 - No abstract available. KW - disease KW - pseudomas-syringae KW - arabidpsis thaliana KW - immunity KW - organogenesis KW - transcription KW - resistance KW - crosstalk Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131901 VL - 8 IS - 11 ER - TY - JOUR A1 - Huser, Annina A1 - Rohwedder, Astrid A1 - Apostolopoulou, Anthi A. A1 - Widmann, Annekathrin A1 - Pfitzenmaier, Johanna E. A1 - Maiolo, Elena M. A1 - Selcho, Mareike A1 - Pauls, Dennis A1 - von Essen, Alina A1 - Gupta, Tript A1 - Sprecher, Simon G. A1 - Birman, Serge A1 - Riemensperger, Thomas A1 - Stocker, Reinhard F. A1 - Thum, Andreas S. T1 - The Serotonergic Central Nervous System of the Drosophila Larva: Anatomy and Behavioral Function JF - PLoS One N2 - 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. KW - term memory KW - light avoidance KW - decision making KW - olfactory memory KW - immunoreactive neurons KW - containing neurons KW - moth manduca sexta KW - head involution KW - mushroom bodies KW - biogenic amines Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130437 VL - 7 IS - 10 ER - TY - JOUR A1 - Aso, Yoshinori A1 - Herb, Andrea A1 - Ogueta, Maite A1 - Siwanowicz, Igor A1 - Templier, Thomas A1 - Friedrich, Anja B. A1 - Ito, Kei A1 - Scholz, Henrike A1 - Tanimoto, Hiromu T1 - Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability JF - PLoS Genetics N2 - 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. KW - dynamics KW - serotonin KW - expression KW - melanogaster KW - neurons form KW - olfactory memory KW - long-term-memory KW - drosophila mushroom body KW - sensitization KW - localization Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130631 VL - 8 IS - 7 ER - TY - JOUR A1 - Nanguneri, Siddharth A1 - Flottmann, Benjamin A1 - Horstmann, Heinz A1 - Heilemann, Mike A1 - Kuner, Thomas T1 - Three-Dimensional, Tomographic Super-Resolution Fluorescence Imaging of Serially Sectioned Thick Samples JF - PLoS One N2 - 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. KW - architecture KW - rat calyx KW - in-vivo KW - microscopy KW - resolution KW - proteins KW - transmission KW - ultrastructure KW - reconstruction KW - localization Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134434 VL - 7 IS - 5 ER - TY - JOUR A1 - Förster, Frank A1 - Beisser, Daniela A1 - Grohme, Markus A. A1 - Liang, Chunguang A1 - Mali, Brahim A1 - Siegl, Alexander Matthias A1 - Engelmann, Julia C. A1 - Shkumatov, Alexander V. A1 - Schokraie, Elham A1 - Müller, Tobias A1 - Schnölzer, Martina A1 - Schill, Ralph O. A1 - Frohme, Marcus A1 - Dandekar, Thomas T1 - Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations JF - Bioinformatics and biology insights N2 - Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant. KW - RNA KW - expressed sequence tag KW - cluster KW - protein familiy KW - adaption KW - tardigrada KW - transcriptome Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123089 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - JOUR A1 - Schmitt, Jana A1 - Backes, Christina A1 - Nourkami-Tutdibi, Nasenien A1 - Leidinger, Petra A1 - Deutscher, Stephanie A1 - Beier, Markus A1 - Gessler, Manfred A1 - Graf, Norbert A1 - Lenhof, Hans-Peter A1 - Keller, Andreas A1 - Meese, Eckart T1 - Treatment-independent miRNA signature in blood of wilms tumor patients JF - BMC Genomics N2 - Background Blood-born miRNA signatures have recently been reported for various tumor diseases. Here, we compared the miRNA signature in Wilms tumor patients prior and after preoperative chemotherapy according to SIOP protocol 2001. Results We did not find a significant difference between miRNA signature of both groups. However both, Wilms tumor patients prior and after chemotherapy showed a miRNA signature different from healthy controls. The signature of Wilms tumor patients prior to chemotherapy showed an accuracy of 97.5% and of patients after chemotherapy an accuracy of 97.0%, each as compared to healthy controls. Conclusion Our results provide evidence for a blood-born Wilms tumor miRNA signature largely independent of four weeks preoperative chemotherapy treatment. KW - miRNA Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124034 VL - 13 IS - 379 ER - TY - JOUR A1 - Heddergott, Niko A1 - Krüger, Timothy A1 - Babu, Sujin B. A1 - Wei, Ai A1 - Stellamanns, Erik A1 - Uppaluri, Sravanti A1 - Pfohl, Thomas A1 - Stark, Holger A1 - Engstler, Markus T1 - Trypanosome Motion Represents an Adaptation to the Crowded Environment of the Vertebrate Bloodstream JF - PLoS Pathogens N2 - 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. KW - simulation KW - multiparticle collision dynamics KW - propulsion KW - viscosity KW - flagellar KW - motility KW - solvent KW - model KW - hydrodynamics KW - spiroplasma Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134595 VL - 8 IS - 11 ER - TY - JOUR A1 - Heddergott, Nico A1 - Krüger, Timothy A1 - Babu, Sujin B. A1 - Wei, Ai A1 - Stellamanns, Erik A1 - Uppaluri, Sravanti A1 - Pfohl, Thomas A1 - Stark, Holger A1 - Engstler, Markus T1 - Trypanosome Motion Represents an Adaptation to the Crowded Environment ofthe Vertebrate Bloodstream N2 - 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 KW - Biologie Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78421 ER -