@article{WaeldchenLehmannKleinetal.2015, author = {W{\"a}ldchen, Sina and Lehmann, Julian and Klein, Teresa and van de Linde, Sebastian and Sauer, Markus}, title = {Light-induced cell damage in live-cell super-resolution microscopy}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {15348}, doi = {10.1038/srep15348}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145207}, year = {2015}, abstract = {Super-resolution microscopy can unravel previously hidden details of cellular structures but requires high irradiation intensities to use the limited photon budget efficiently. Such high photon densities are likely to induce cellular damage in live-cell experiments. We applied single-molecule localization microscopy conditions and tested the influence of irradiation intensity, illumination-mode, wavelength, light-dose, temperature and fluorescence labeling on the survival probability of different cell lines 20-24 hours after irradiation. In addition, we measured the microtubule growth speed after irradiation. The photo-sensitivity is dramatically increased at lower irradiation wavelength. We observed fixation, plasma membrane permeabilization and cytoskeleton destruction upon irradiation with shorter wavelengths. While cells stand light intensities of similar to 1 kW cm\(^{-2}\) at 640 nm for several minutes, the maximum dose at 405 nm is only similar to 50 J cm\(^{-2}\), emphasizing red fluorophores for live-cell localization microscopy. We also present strategies to minimize phototoxic factors and maximize the cells ability to cope with higher irradiation intensities.}, language = {en} } @article{RemmeleLutherBalkenholetal.2015, author = {Remmele, Christian W. and Luther, Christian H. and Balkenhol, Johannes and Dandekar, Thomas and M{\"u}ller, Tobias and Dittrich, Marcus T.}, title = {Integrated inference and evaluation of host-fungi interaction networks}, series = {Frontiers in Microbiology}, volume = {6}, journal = {Frontiers in Microbiology}, number = {764}, doi = {10.3389/fmicb.2015.00764}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148278}, year = {2015}, abstract = {Fungal microorganisms frequently lead to life-threatening infections. Within this group of pathogens, the commensal Candida albicans and the filamentous fungus Aspergillus fumigatus are by far the most important causes of invasive mycoses in Europe. A key capability for host invasion and immune response evasion are specific molecular interactions between the fungal pathogen and its human host. Experimentally validated knowledge about these crucial interactions is rare in literature and even specialized host pathogen databases mainly focus on bacterial and viral interactions whereas information on fungi is still sparse. To establish large-scale host fungi interaction networks on a systems biology scale, we develop an extended inference approach based on protein orthology and data on gene functions. Using human and yeast intraspecies networks as template, we derive a large network of pathogen host interactions (PHI). Rigorous filtering and refinement steps based on cellular localization and pathogenicity information of predicted interactors yield a primary scaffold of fungi human and fungi mouse interaction networks. Specific enrichment of known pathogenicity-relevant genes indicates the biological relevance of the predicted PHI. A detailed inspection of functionally relevant subnetworks reveals novel host fungal interaction candidates such as the Candida virulence factor PLB1 and the anti-fungal host protein APP. Our results demonstrate the applicability of interolog-based prediction methods for host fungi interactions and underline the importance of filtering and refinement steps to attain biologically more relevant interactions. This integrated network framework can serve as a basis for future analyses of high-throughput host fungi transcriptome and proteome data.}, language = {en} } @article{KarlDandekar2015, author = {Karl, Stefan and Dandekar, Thomas}, title = {Convergence behaviour and control in non-linear biological networks}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {09746}, doi = {10.1038/srep09746}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148510}, year = {2015}, abstract = {Control of genetic regulatory networks is challenging to define and quantify. Previous control centrality metrics, which aim to capture the ability of individual nodes to control the system, have been found to suffer from plausibility and applicability problems. Here we present a new approach to control centrality based on network convergence behaviour, implemented as an extension of our genetic regulatory network simulation framework Jimena (http://stefan-karl.de/jimena). We distinguish three types of network control, and show how these mathematical concepts correspond to experimentally verified node functions and signalling pathways in immunity and cell differentiation: Total control centrality quantifies the impact of node mutations and identifies potential pharmacological targets such as genes involved in oncogenesis (e.g. zinc finger protein GLI2 or bone morphogenetic proteins in chondrocytes). Dynamic control centrality describes relaying functions as observed in signalling cascades (e.g. src kinase or Jak/Stat pathways). Value control centrality measures the direct influence of the value of the node on the network (e.g. Indian hedgehog as an essential regulator of proliferation in chondrocytes). Surveying random scale-free networks and biological networks, we find that control of the network resides in few high degree driver nodes and networks can be controlled best if they are sparsely connected.}, language = {en} } @article{MatosMachadoSchartletal.2015, author = {Matos, I and Machado, M. P. and Schartl, M. and Coelho, M. M.}, title = {Gene expression dosage regulation in an allopolyploid fish}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0116309}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143565}, pages = {e0116309}, year = {2015}, abstract = {How allopolyploids are able not only to cope but profit from their condition is a question that remains elusive, but is of great importance within the context of successful allopolyploid evolution. One outstanding example of successful allopolyploidy is the endemic Iberian cyprinid Squalius alburnoides. Previously, based on the evaluation of a few genes, it was reported that the transcription levels between diploid and triploid S. alburnoides were similar. If this phenomenon occurs on a full genomic scale, a wide functional "diploidization'' could be related to the success of these polyploids. We generated RNA-seq data from whole juvenile fish and from adult livers, to perform the first comparative quantitative transcriptomic analysis between diploid and triploid individuals of a vertebrate allopolyploid. Together with an assay to estimate relative expression per cell, it was possible to infer the relative sizes of transcriptomes. This showed that diploid and triploid S. alburnoides hybrids have similar liver transcriptome sizes. This in turn made it valid to directly compare the S. alburnoides RNA-seq transcript data sets and obtain a profile of dosage responses across the S. alburnoides transcriptome. We found that 64\% of transcripts in juveniles' samples and 44\% in liver samples differed less than twofold between diploid and triploid hybrids (similar expression). Yet, respectively 29\% and 15\% of transcripts presented accurate dosage compensation (PAA/PA expression ratio of 1 instead of 1.5). Therefore, an exact functional diploidization of the triploid genome does not occur, but a significant down regulation of gene expression in triploids was observed. However, for those genes with similar expression levels between diploids and triploids, expression is not globally strictly proportional to gene dosage nor is it set to a perfect diploid level. This quantitative expression flexibility may be a strong contributor to overcome the genomic shock, and be an immediate evolutionary advantage of allopolyploids.}, language = {en} } @article{AlizadehradKruegerEngstleretal.2015, author = {Alizadehrad, Davod and Kr{\"u}ger, Timothy and Engstler, Markus and Stark, Holger}, title = {Simulating the complex cell design of Trypanosoma brucei and its motility}, series = {PLOS Computational Biology}, volume = {11}, journal = {PLOS Computational Biology}, number = {1}, doi = {10.1371/journal.pcbi.1003967}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144610}, pages = {e1003967}, year = {2015}, abstract = {The flagellate Trypanosoma brucei, which causes the sleeping sickness when infecting a mammalian host, goes through an intricate life cycle. It has a rather complex propulsion mechanism and swims in diverse microenvironments. These continuously exert selective pressure, to which the trypanosome adjusts with its architecture and behavior. As a result, the trypanosome assumes a diversity of complex morphotypes during its life cycle. However, although cell biology has detailed form and function of most of them, experimental data on the dynamic behavior and development of most morphotypes is lacking. Here we show that simulation science can predict intermediate cell designs by conducting specific and controlled modifications of an accurate, nature-inspired cell model, which we developed using information from live cell analyses. The cell models account for several important characteristics of the real trypanosomal morphotypes, such as the geometry and elastic properties of the cell body, and their swimming mechanism using an eukaryotic flagellum. We introduce an elastic network model for the cell body, including bending rigidity and simulate swimming in a fluid environment, using the mesoscale simulation technique called multi-particle collision dynamics. The in silico trypanosome of the bloodstream form displays the characteristic in vivo rotational and translational motility pattern that is crucial for survival and virulence in the vertebrate host. Moreover, our model accurately simulates the trypanosome's tumbling and backward motion. We show that the distinctive course of the attached flagellum around the cell body is one important aspect to produce the observed swimming behavior in a viscous fluid, and also required to reach the maximal swimming velocity. Changing details of the flagellar attachment generates less efficient swimmers. We also simulate different morphotypes that occur during the parasite's development in the tsetse fly, and predict a flagellar course we have not been able to measure in experiments so far.}, language = {en} } @article{SchartlShenMaurusetal.2015, author = {Schartl, Manfred and Shen, Yingjia and Maurus, Katja and Walter, Ron and Tomlinson, Chad and Wilson, Richard K. and Postlethwait, John and Warren, Wesley C.}, title = {Whole body melanoma transcriptome response in medaka}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0143057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144714}, pages = {e0143057}, year = {2015}, abstract = {The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.}, language = {en} } @article{TuchscherrBischoffLattaretal.2015, author = {Tuchscherr, Lorena and Bischoff, Markus and Lattar, Santiago M. and Noto Llana, Mariangeles and Pf{\"o}rtner, Henrike and Niemann, Silke and Geraci, Jennifer and Van de Vyver, H{\´e}l{\`e}ne and Fraunholz, Martin J. and Cheung, Ambrose L. and Herrmann, Mathias and V{\"o}lker, Uwe and Sordelli, Daniel O. and Peters, Georg and Loeffler, Bettina}, title = {Sigma factor SigB is crucial to mediate Staphylococcus aureus adaptation during chronic infections}, series = {PLoS Pathogens}, volume = {11}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1004870}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143419}, pages = {e1004870}, year = {2015}, abstract = {Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs), which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, \(\Delta\)sigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy-refractory infections.}, language = {en} } @article{LamatschAdolfssonSenioretal.2015, author = {Lamatsch, Dunja K. and Adolfsson, Sofia and Senior, Alistair M. and Christiansen, Guntram and Pichler, Maria and Ozaki, Yuichi and Smeds, Linnea and Schartl, Manfred and Nakagawa, Shinichi}, title = {A transcriptome derived female-specific marker from the invasive Western mosquitofish (Gambusia affinis)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0118214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144004}, pages = {e0118214}, year = {2015}, abstract = {Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3' UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes.}, language = {en} } @article{KangManousakiFranchinietal.2015, author = {Kang, Ji Hyoun and Manousaki, Tereza and Franchini, Paolo and Kneitz, Susanne and Schartl, Manfred and Meyer, Axel}, title = {Transcriptomics of two evolutionary novelties: how to make a sperm-transfer organ out of an anal fin and a sexually selected "sword" out of a caudal fin}, series = {Ecology and Evolution}, volume = {5}, journal = {Ecology and Evolution}, number = {4}, doi = {10.1002/ece3.1390}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144139}, pages = {848-864}, year = {2015}, abstract = {Swords are exaggerated male ornaments of swordtail fishes that have been of great interest to evolutionary biologists ever since Darwin described them in the Descent of Man (1871). They are a novel sexually selected trait derived from modified ventral caudal fin rays and are only found in the genus Xiphophorus. Another phylogenetically more widespread and older male trait is the gonopodium, an intromittent organ found in all poeciliid fishes, that is derived from a modified anal fin. Despite many evolutionary and behavioral studies on both traits, little is known so far about the molecular mechanisms underlying their development. By investigating transcriptomic changes (utilizing a RNA-Seq approach) in response to testosterone treatment in the swordtail fish, Xiphophorus hellerii, we aimed to better understand the architecture of the gene regulatory networks underpinning the development of these two evolutionary novelties. Large numbers of genes with tissue-specific expression patterns were identified. Among the sword genes those involved in embryonic organ development, sexual character development and coloration were highly expressed, while in the gonopodium rather more morphogenesis-related genes were found. Interestingly, many genes and genetic pathways are shared between both developing novel traits derived from median fins: the sword and the gonopodium. Our analyses show that a larger set of gene networks was co-opted during the development and evolution of the older gonopodium than in the younger, and morphologically less complex trait, the sword. We provide a catalog of candidate genes for future efforts to dissect the development of those sexually selected exaggerated male traits in swordtails.}, language = {en} } @article{SimonRauskolbGunnersenetal.2015, author = {Simon, Christian M. and Rauskolb, Stefanie and Gunnersen, Jennifer M. and Holtmann, Bettina and Drepper, Carsten and Dombert, Benjamin and Braga, Massimiliano and Wiese, Stefan and Jablonka, Sibylle and P{\"u}hringer, Dirk and Zielasek, J{\"u}rgen and Hoeflich, Andreas and Silani, Vincenzo and Wolf, Eckhard and Kneitz, Susanne and Sommer, Claudia and Toyka, Klaus V. and Sendtner, Michael}, title = {Dysregulated IGFBP5 expression causes axon degeneration and motoneuron loss in diabetic neuropathy}, series = {Acta Neuropathologica}, volume = {130}, journal = {Acta Neuropathologica}, doi = {10.1007/s00401-015-1446-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154569}, pages = {373 -- 387}, year = {2015}, abstract = {Diabetic neuropathy (DNP), afflicting sensory and motor nerve fibers, is a major complication in diabetes.The underlying cellular mechanisms of axon degeneration are poorly understood. IGFBP5, an inhibitory binding protein for insulin-like growth factor 1 (IGF1) is highly up-regulated in nerve biopsies of patients with DNP. We investigated the pathogenic relevance of this finding in transgenic mice overexpressing IGFBP5 in motor axons and sensory nerve fibers. These mice develop motor axonopathy and sensory deficits similar to those seen in DNP. Motor axon degeneration was also observed in mice in which the IGF1 receptor(IGF1R) was conditionally depleted in motoneurons, indicating that reduced activity of IGF1 on IGF1R in motoneurons is responsible for the observed effect. These data provide evidence that elevated expression of IGFBP5 in diabetic nerves reduces the availability of IGF1 for IGF1R on motor axons, thus leading to progressive neurodegeneration. Inhibition of IGFBP5 could thus offer novel treatment strategies for DNP.}, language = {en} } @article{KarulinKaracsonyZhangetal.2015, author = {Karulin, Alexey Y. and Karacsony, Kinga and Zhang, Wenji and Targoni, Oleg S. and Moldova, Ioana and Dittrich, Marcus and Sundararaman, Srividya and Lehmann, Paul V.}, title = {ELISPOTs produced by CD8 and CD4 cells follow Log Normal size distribution permitting objective counting}, series = {Cells}, volume = {4}, journal = {Cells}, number = {1}, doi = {10.3390/cells4010056}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149648}, pages = {56-70}, year = {2015}, abstract = {Each positive well in ELISPOT assays contains spots of variable sizes that can range from tens of micrometers up to a millimeter in diameter. Therefore, when it comes to counting these spots the decision on setting the lower and the upper spot size thresholds to discriminate between non-specific background noise, spots produced by individual T cells, and spots formed by T cell clusters is critical. If the spot sizes follow a known statistical distribution, precise predictions on minimal and maximal spot sizes, belonging to a given T cell population, can be made. We studied the size distributional properties of IFN-γ, IL-2, IL-4, IL-5 and IL-17 spots elicited in ELISPOT assays with PBMC from 172 healthy donors, upon stimulation with 32 individual viral peptides representing defined HLA Class I-restricted epitopes for CD8 cells, and with protein antigens of CMV and EBV activating CD4 cells. A total of 334 CD8 and 80 CD4 positive T cell responses were analyzed. In 99.7\% of the test cases, spot size distributions followed Log Normal function. These data formally demonstrate that it is possible to establish objective, statistically validated parameters for counting T cell ELISPOTs.}, language = {en} } @article{GarciaMartinezBrunkAvalosetal.2015, author = {Garc{\´i}a-Mart{\´i}nez, Jorge and Brunk, Michael and Avalos, Javier and Terpitz, Ulrich}, title = {The CarO rhodopsin of the fungus Fusarium fujikuroi is a light-driven proton pump that retards spore germination}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {7798}, doi = {10.1038/srep07798}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149049}, year = {2015}, abstract = {Rhodopsins are membrane-embedded photoreceptors found in all major taxonomic kingdoms using retinal as their chromophore. They play well-known functions in different biological systems, but their roles in fungi remain unknown. The filamentous fungus Fusarium fujikuroi contains two putative rhodopsins, CarO and OpsA. The gene carO is light-regulated, and the predicted polypeptide contains all conserved residues required for proton pumping. We aimed to elucidate the expression and cellular location of the fungal rhodopsin CarO, its presumed proton-pumping activity and the possible effect of such function on F. fujikuroi growth. In electrophysiology experiments we confirmed that CarO is a green-light driven proton pump. Visualization of fluorescent CarO-YFP expressed in F. fujikuroi under control of its native promoter revealed higher accumulation in spores (conidia) produced by light-exposed mycelia. Germination analyses of conidia from carO\(^{-}\) mutant and carO\(^{+}\) control strains showed a faster development of light-exposed carO-germlings. In conclusion, CarO is an active proton pump, abundant in light-formed conidia, whose activity slows down early hyphal development under light. Interestingly, CarO-related rhodopsins are typically found in plant-associated fungi, where green light dominates the phyllosphere. Our data provide the first reliable clue on a possible biological role of a fungal rhodopsin.}, language = {en} } @article{LeikamHufnagelOttoetal.2015, author = {Leikam, C and Hufnagel, AL and Otto, C and Murphy, DJ and M{\"u}hling, B and Kneitz, S and Nanda, I and Schmid, M and Wagner, TU and Haferkamp, S and Br{\"o}cker, E-B and Schartl, M and Meierjohann, S}, title = {In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells}, series = {Cell Death and Disease}, volume = {6}, journal = {Cell Death and Disease}, number = {e1711}, doi = {10.1038/cddis.2015.71}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148718}, year = {2015}, abstract = {Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi-or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS\(^{61K}\) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.}, language = {en} } @article{EhmannSauerKittel2015, author = {Ehmann, Nadine and Sauer, Markus and Kittel, Robert J.}, title = {Super-resolution microscopy of the synaptic active zone}, series = {Frontiers in Cellular Neuroscience}, volume = {9}, journal = {Frontiers in Cellular Neuroscience}, number = {7}, doi = {10.3389/fncel.2015.00007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148997}, year = {2015}, abstract = {Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ) a variety of specialized proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission. Calcium channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modeling approaches has provided predictions of channel properties, numbers and even positions on the nanometer scale. However, elucidating the nanoscopic organization of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy (SRM) techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how SRM can be used to obtain information on the organization of AZ proteins}, language = {en} } @article{DandekarEisenreich2015, author = {Dandekar, Thomas and Eisenreich, Wolfgang}, title = {Host-adapted metabolism and its regulation in bacterial pathogens}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {5}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {28}, issn = {2235-2988}, doi = {10.3389/fcimb.2015.00028}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196876}, year = {2015}, abstract = {No abstract available.}, language = {en} } @article{DandekarFieselmannFischeretal.2015, author = {Dandekar, Thomas and Fieselmann, Astrid and Fischer, Eva and Popp, Jasmin and Hensel, Michael and Noster, Janina}, title = {Salmonella - how a metabolic generalist adopts an intracellular lifestyle during infection}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {4}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {191}, doi = {10.3389/fcimb.2014.00191}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149029}, year = {2015}, abstract = {The human-pathogenic bacterium Salmonella enterica adjusts and adapts to different environments while attempting colonization. In the course of infection nutrient availabilities change drastically. New techniques, "-omics" data and subsequent integration by systems biology improve our understanding of these changes. We review changes in metabolism focusing on amino acid and carbohydrate metabolism. Furthermore, the adaptation process is associated with the activation of genes of the Salmonella pathogenicity islands (SPIs). Anti-infective strategies have to take these insights into account and include metabolic and other strategies. Salmonella infections will remain a challenge for infection biology.}, language = {en} } @article{MartinReinekingSeoetal.2015, author = {Martin, Emily A. and Reineking, Bj{\"o}rn and Seo, Bumsuk and Steffan-Dewenter, Ingolf}, title = {Pest control of aphids depends on landscape complexity and natural enemy interactions}, series = {PeerJ}, volume = {3}, journal = {PeerJ}, number = {e1095}, doi = {10.7717/peerj.1095}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148393}, year = {2015}, abstract = {Aphids are a major concern in agricultural crops worldwide, and control by natural enemies is an essential component of the ecological intensification of agriculture. Although the complexity of agricultural landscapes is known to influence natural enemies of pests, few studies have measured the degree of pest control by different enemy guilds across gradients in landscape complexity. Here, we use multiple natural-enemy exclosures replicated in 18 fields across a gradient in landscape complexity to investigate (1) the strength of natural pest control across landscapes, measured as the difference between pest pressure in the presence and in the absence of natural enemies; (2) the differential contributions of natural enemy guilds to pest control, and the nature of their interactions across landscapes. We show that natural pest control of aphids increased up to six-fold from simple to complex landscapes. In the absence of pest control, aphid population growth was higher in complex than simple landscapes, but was reduced by natural enemies to similar growth rates across all landscapes. The effects of enemy guilds were landscape-dependent. Particularly in complex landscapes, total pest control was supplied by the combined contribution of flying insects and ground-dwellers. Birds had little overall impact on aphid control. Despite evidence for intraguild predation of flying insects by ground-dwellers and birds, the overall effect of enemy guilds on aphid control was complementary. Understanding pest control services at large spatial scales is critical to increase the success of ecological intensification schemes. Our results suggest that, where aphids are the main pest of concern, interactions between natural enemies are largely complementary and lead to a strongly positive effect of landscape complexity on pest control. Increasing the availability of seminatural habitats in agricultural landscapes may thus benefit not only natural enemies, but also the effectiveness of aphid natural pest control.}, language = {en} } @article{JoschinskiHovestadtKrauss2015, author = {Joschinski, Jens and Hovestadt, Thomas and Krauss, Jochen}, title = {Coping with shorter days: do phenology shifts constrain aphid fitness?}, series = {PeerJ}, volume = {3}, journal = {PeerJ}, number = {e1103}, doi = {10.7717/peerj.1103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148382}, year = {2015}, abstract = {Climate change can alter the phenology of organisms. It may thus lead seasonal organisms to face different day lengths than in the past, and the fitness consequences of these changes are as yet unclear. To study such effects, we used the pea aphid Acyrthosiphon pisum as a model organism, as it has obligately asexual clones which can be used to study day length effects without eliciting a seasonal response. We recorded life-history traits under short and long days, both with two realistic temperature cycles with means differing by 2 °C. In addition, we measured the population growth of aphids on their host plant Pisum sativum. We show that short days reduce fecundity and the length of the reproductive period of aphids. Nevertheless, this does not translate into differences at the population level because the observed fitness costs only become apparent late in the individual's life. As expected, warm temperature shortens the development time by 0.7 days/°C, leading to faster generation times. We found no interaction of temperature and day length. We conclude that day length changes cause only relatively mild costs, which may not decelerate the increase in pest status due to climate change.}, language = {en} } @article{KleijnWinfreeBartomeusetal.2015, author = {Kleijn, David and Winfree, Rachael and Bartomeus, Ignasi and Carvalheiro, Lu{\´i}sa G. and Henry, Mickael and Isaacs, Rufus and Klein, Alexandra-Maria and Kremen, Claire and M'Gonigle, Leithen K. and Rader, Romina and Ricketts, Taylor H. and Williams, Neal M. and Adamson, Nancy Lee and Ascher, John S. and B{\´a}ldi, Andr{\´a}s and Bat{\´a}ry, P{\´e}ter and Benjamin, Faye and Biesmeijer, Jacobus C. and Blitzer, Eleanor J. and Bommarco, Riccardo and Brand, Mariette R. and Bretagnolle, Vincent and Button, Lindsey and Cariveau, Daniel P. and Chifflet, R{\´e}my and Colville, Jonathan F. and Danforth, Bryan N. and Elle, Elizabeth and Garratt, Michael P. D. and Herzog, Felix and Holzschuh, Andrea and Howlett, Brad G. and Jauker, Frank and Jha, Shalene and Knop, Eva and Krewenka, Kristin M. and Le F{\´e}on, Violette and Mandelik, Yael and May, Emily A. and Park, Mia G. and Pisanty, Gideon and Reemer, Menno and Riedinger, Verena and Rollin, Orianne and Rundl{\"o}f, Maj and Sardi{\~n}as, Hillary S. and Scheper, Jeroen and Sciligo, Amber R. and Smith, Henrik G. and Steffan-Dewenter, Ingolf and Thorp, Robbin and Tscharntke, Teja and Verhulst, Jort and Viana, Blandina F. and Vaissi{\`e}re, Bernard E. and Veldtman, Ruan and Ward, Kimiora L. and Westphal, Catrin and Potts, Simon G.}, title = {Delivery of crop pollination services is an insufficient argument for wild pollinator conservation}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {7414}, doi = {10.1038/ncomms8414}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151879}, year = {2015}, abstract = {There is compelling evidence that more diverse ecosystems deliver greater benefits to people, and these ecosystem services have become a key argument for biodiversity conservation. However, it is unclear how much biodiversity is needed to deliver ecosystem services in a cost- effective way. Here we show that, while the contribution of wild bees to crop production is significant, service delivery is restricted to a limited subset of all known bee species. Across crops, years and biogeographical regions, crop-visiting wild bee communities are dominated by a small number of common species, and threatened species are rarely observed on crops. Dominant crop pollinators persist under agricultural expansion and many are easily enhanced by simple conservation measures, suggesting that cost- effective management strategies to promote crop pollination should target a different set of species than management strategies to promote threatened bees. Conserving the biological diversity of bees therefore requires more than just ecosystem-service-based arguments.}, language = {en} } @article{AppelScholzMuelleretal.2015, author = {Appel, Mirjam and Scholz, Claus-J{\"u}rgen and M{\"u}ller, Tobias and Dittrich, Marcus and K{\"o}nig, Christian and Bockstaller, Marie and Oguz, Tuba and Khalili, Afshin and Antwi-Adjei, Emmanuel and Schauer, Tamas and Margulies, Carla and Tanimoto, Hiromu and Yarali, Ayse}, title = {Genome-Wide Association Analyses Point to Candidate Genes for Electric Shock Avoidance in Drosophila melanogaster}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0126986}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-152006}, pages = {e0126986}, year = {2015}, abstract = {Electric shock is a common stimulus for nociception-research and the most widely used reinforcement in aversive associative learning experiments. Yet, nothing is known about the mechanisms it recruits at the periphery. To help fill this gap, we undertook a genome-wide association analysis using 38 inbred Drosophila melanogaster strains, which avoided shock to varying extents. We identified 514 genes whose expression levels and/or sequences covaried with shock avoidance scores. We independently scrutinized 14 of these genes using mutants, validating the effect of 7 of them on shock avoidance. This emphasizes the value of our candidate gene list as a guide for follow-up research. In addition, by integrating our association results with external protein-protein interaction data we obtained a shock avoidance- associated network of 38 genes. Both this network and the original candidate list contained a substantial number of genes that affect mechanosensory bristles, which are hairlike organs distributed across the fly's body. These results may point to a potential role for mechanosensory bristles in shock sensation. Thus, we not only provide a first list of candidate genes for shock avoidance, but also point to an interesting new hypothesis on nociceptive mechanisms.}, language = {en} } @article{FrankDengjelWilflingetal.2015, author = {Frank, Daniel O. and Dengjel, J{\"o}rn and Wilfling, Florian and Kozjak-Pavlovic, Vera and H{\"a}cker, Georg and Weber, Arnim}, title = {The Pro-Apoptotic BH3-Only Protein Bim Interacts with Components of the Translocase of the Outer Mitochondrial Membrane (TOM)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0123341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143301}, pages = {e0123341}, year = {2015}, abstract = {The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show that Bim is constitutively inserted in the outer mitochondrial membrane via a C-terminal transmembrane anchor from where it can activate the effector of cytochrome c-release, Bax. To identify regulators of Bim-activity, we conducted a search for proteins interacting with Bim at mitochondria. We found an interaction of Bim with Tom70, Tom20 and more weakly with Tom40, all components of the Translocase of the Outer Membrane (TOM). In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. However, RNAi against components of TOM (Tom40, Tom70, Tom22 or Tom20) by siRNA, individually or in combination, did not consistently change the amount of Bim on HeLa mitochondria, either at steady state or upon de novo-induction. In support of this, the individual or combined knockdowns of TOM receptors also failed to alter the susceptibility of HeLa cells to Bim-induced apoptosis. In isolated yeast mitochondria, lack of Tom70 or the TOM-components Tom20 or Tom22 alone did not affect the import of Bim into the outer mitochondrial membrane. In yeast, expression of Bim can sensitize the cells to Bax-dependent killing. This sensitization was unaffected by the absence of Tom70 or by an experimental reduction in Tom40. Although thus the physiological role of the Bim-TOM-interaction remains unclear, TOM complex components do not seem to be essential for Bim insertion into the OMM. Nevertheless, this association should be noted and considered when the regulation of Bim in other cells and situations is investigated.}, language = {en} } @article{HerwegHansmeierOttoetal.2015, author = {Herweg, Jo-Ana and Hansmeier, Nicole and Otto, Andreas and Geffken, Anna C. and Subbarayal, Prema and Prusty, Bhupesh K. and Becher, D{\"o}rte and Hensel, Michael and Schaible, Ulrich E. and Rudel, Thomas and Hilbi, Hubert}, title = {Purification and proteomics of pathogen-modified vacuoles and membranes}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {5}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {48}, doi = {10.3389/fcimb.2015.00048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151823}, year = {2015}, abstract = {Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.}, language = {en} } @article{Morriswood2015, author = {Morriswood, Brooke}, title = {Form, fabric, and function of a flagellum-associated cytoskeletal structure.}, series = {Cells}, volume = {4}, journal = {Cells}, number = {4}, doi = {10.3390/cells4040726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149467}, pages = {726-747}, year = {2015}, abstract = {Trypanosoma brucei is a uniflagellated protist and the causative agent of African trypanosomiasis, a neglected tropical disease. The single flagellum of T. brucei is essential to a number of cellular processes such as motility, and has been a longstanding focus of scientific enquiry. A number of cytoskeletal structures are associated with the flagellum in T. brucei, and one such structure—a multiprotein complex containing the repeat motif protein TbMORN1—is the focus of this review. The TbMORN1-containing complex, which was discovered less than ten years ago, is essential for the viability of the mammalian-infective form of T. brucei. The complex has an unusual asymmetric morphology, and is coiled around the flagellum to form a hook shape. Proteomic analysis using the proximity-dependent biotin identification (BioID) technique has elucidated a number of its components. Recent work has uncovered a role for TbMORN1 in facilitating protein entry into the cell, thus providing a link between the cytoskeleton and the endomembrane system. This review summarises the extant data on the complex, highlights the outstanding questions for future enquiry, and provides speculation as to its possible role in a size-exclusion mechanism for regulating protein entry. The review additionally clarifies the nomenclature associated with this topic, and proposes the adoption of the term "hook complex" to replace the former name "bilobe" to describe the complex.}, language = {en} } @article{DuehringGermerodtSkerkaetal.2015, author = {D{\"u}hring, Sybille and Germerodt, Sebastian and Skerka, Christine and Zipfel, Peter F. and Dandekar, Thomas and Schuster, Stefan}, title = {Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies}, series = {Frontiers in Microbiology}, volume = {6}, journal = {Frontiers in Microbiology}, number = {625}, doi = {10.3389/fmicb.2015.00625}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151621}, year = {2015}, abstract = {The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.}, language = {en} }