@article{OnoSonoyamaNemaetal.2014,
  author    = {Ono, Mitsuaki and Sonoyama, Wataru and Nema, Kazuki and Hara, Emilio Satoshi and Oida, Yasutaka and Pham, Hai Thanh and Yamamoto, Katushi and Hirota, Kazuo and Sugama, Kazushige and Sebald, Walter and Kuboki, Takuo},
  title     = {Regeneration of calvarial defects with Escherichia coli-derived rhBMP-2 adsorbed in PLGA membrane},
  series = {Cells Tissues Organs},
  volume    = {198},
  journal   = {Cells Tissues Organs},
  number    = {5},
  issn      = {1422-6405},
  doi       = {10.1159/000356947},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196680},
  pages     = {367 -- 376},
  year      = {2014},
  abstract  = {Objective: Escherichia coli-derived recombinant human bone morphogenetic protein-2 (E-BMP-2) has been shown to be as effective as mammalian cell-derived BMP-2. However, several in vitro and in vivo experiments are still necessary to validate the effectiveness of E-BMP-2 due to the difference in synthesis process, mainly related to protein nonglycosylation. The objective of this study was to investigate whether biodegradable polylactide-co-glycolide (PLGA) membrane is a suitable carrier for E-BMP-2 delivery for bone regeneration of critical-sized defects in rat calvaria. Materials and Methods: First, the osteoinductive effect of E-BMP-2 was confirmed in vitro in mouse bone marrow stromal cells by analysis of osteocalcin mRNA levels, and calcium deposition was detected by alizarin red staining. Before in vivo experiments, the release profile of E-BMP-2 from PLGA membranes was determined by ELISA. E-BMP-2 (0, 1, 5 and 10 μg/μl) was applied for ectopic and orthotopic bone formation and was analyzed by X-ray, micro-CT and histology. Results: Release-profile testing showed that PLGA membrane could retain 94\% of the initially applied E-BMP-2. Ectopic bone formation assay revealed that combination of E-BMP-2/PLGA membrane strongly induced bone formation. Stronger osteoinductivity with complete repair of critical-sized defects was observed only with PLGA membranes adsorbed with 5 and 10 μg/μl of E-BMP-2, whereas no bone formation was observed in the groups that received no membrane or 0-μg/μl dose of E-BMP-2. Conclusion: PLGA membrane was shown to be a suitable carrier for sustained release of E-BMP-2, and the E-BMP-2/PLGA membrane combination was demonstrated to be efficient in bone regeneration in a model of critical-sized defects.},
  language  = {en}
}
@article{ChenGerber2014,
  author    = {Chen, Yi-chun and Gerber, Bertram},
  title     = {Generalization and discrimination tasks yield concordant measures of perceived distance between odours and their binary mixtures in larval Drosophila},
  series = {The Journal of Experimental Biology},
  volume    = {217},
  journal   = {The Journal of Experimental Biology},
  number    = {12},
  doi       = {10.1242/jeb.100966},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121625},
  pages     = {2071-7},
  year      = {2014},
  abstract  = {Similarity between odours is notoriously difficult to measure. Widely used behavioural approaches in insect olfaction research are cross-adaptation, masking, as well as associative tasks based on olfactory learning and the subsequent testing for how specific the established memory is. A concern with such memory-based approaches is that the learning process required to establish an odour memory may alter the way the odour is processed, such that measures of perception taken at the test are distorted. The present study was therefore designed to see whether behavioural judgements of perceptual distance are different for two different memory-based tasks, namely generalization and discrimination. We used odour-reward learning in larval Drosophila as a study case. In order to challenge the larvae's olfactory system, we chose to work with binary mixtures and their elements (1-octanol, n-amyl acetate, 3-octanol, benzaldehyde and hexyl acetate). We determined the perceptual distance between each mixture and its elements, first in a generalization task, and then in a discrimination task. It turns out that scores of perceptual distance are correlated between both tasks. A re-analysis of published studies looking at element-to-element perceptual distances in larval reward learning and in adult punishment learning confirms this result. We therefore suggest that across a given set of olfactory stimuli, associative training does not grossly alter the pattern of perceptual distances.},
  language  = {en}
}
@article{StefanovicBarnettvanDuijvenbodenetal.2014,
  author    = {Stefanovic, Sonia and Barnett, Phil and van Duijvenboden, Karel and Weber, David and Gessler, Manfred and Christoffels, Vincent M.},
  title     = {GATA-dependent regulatory switches establish atrioventricular canal specificity during heart development},
  series = {Nature Communications},
  volume    = {5},
  journal   = {Nature Communications},
  number    = {3680},
  issn      = {2041-1723},
  doi       = {10.1038/ncomms4680},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121437},
  year      = {2014},
  abstract  = {The embryonic vertebrate heart tube develops an atrioventricular canal that divides the atrial and ventricular chambers, forms atrioventricular conduction tissue and organizes valve development. Here we assess the transcriptional mechanism underlying this localized differentiation process. We show that atrioventricular canal-specific enhancers are GATA-binding site-dependent and act as switches that repress gene activity in the chambers. We find that atrioventricular canal-specific gene loci are enriched in H3K27ac, a marker of active enhancers, in atrioventricular canal tissue and depleted in H3K27ac in chamber tissue. In the atrioventricular canal, Gata4 activates the enhancers in synergy with Bmp2/Smad signalling, leading to H3K27 acetylation. In contrast, in chambers, Gata4 cooperates with pan-cardiac Hdac1 and Hdac2 and chamber-specific Hey1 and Hey2, leading to H3K27 deacetylation and repression. We conclude that atrioventricular canal-specific enhancers are platforms integrating cardiac transcription factors, broadly active histone modification enzymes and localized co-factors to drive atrioventricular canal-specific gene activity.},
  language  = {en}
}
@article{McCarthyMooreKraussetal.2014,
  author    = {McCarthy, Michael A. and Moore, Alana L. and Krauss, Jochen and Morgan, John W. and Clements, Christopher F.},
  title     = {Linking Indices for Biodiversity Monitoring to Extinction Risk Theory},
  series = {Conservation Biology},
  volume    = {28},
  journal   = {Conservation Biology},
  number    = {6},
  doi       = {10.1111/cobi.12308},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121218},
  pages     = {1575-83},
  year      = {2014},
  abstract  = {Biodiversity indices often combine data from different species when used in monitoring programs. Heuristic properties can suggest preferred indices, but we lack objective ways to discriminate between indices with similar heuristics. Biodiversity indices can be evaluated by determining how well they reflect management objectives that a monitoring program aims to support. For example, the Convention on Biological Diversity requires reporting about extinction rates, so simple indices that reflect extinction risk would be valuable. We developed 3 biodiversity indices that are based on simple models of population viability that relate extinction risk to abundance. We based the first index on the geometric mean abundance of species and the second on a more general power mean. In a third index, we integrated the geometric mean abundance and trend. These indices require the same data as previous indices, but they also relate directly to extinction risk. Field data for butterflies and woodland plants and experimental studies of protozoan communities show that the indices correlate with local extinction rates. Applying the index based on the geometric mean to global data on changes in avian abundance suggested that the average extinction probability of birds has increased approximately 1\% from 1970 to 2009.},
  language  = {en}
}
@article{ZhanStanciauskasStigloheretal.2014,
  author    = {Zhan, Hong and Stanciauskas, Ramunas and Stigloher, Christian and Dizon, Kevin K. and Jospin, Maelle and Bessereau, Jean-Luis and Pinaud, Fabien},
  title     = {In vivo single-molecule imaging identifies altered dynamics of calcium channels in dystrophin-mutant C. elegans},
  series = {Nature Communications},
  volume    = {5},
  journal   = {Nature Communications},
  number    = {4974},
  doi       = {10.1038/ncomms5974},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121125},
  year      = {2014},
  abstract  = {Single-molecule (SM) fluorescence microscopy allows the imaging of biomolecules in cultured cells with a precision of a few nanometres but has yet to be implemented in living adult animals. Here we used split-GFP (green fluorescent protein) fusions and complementation-activated light microscopy (CALM) for subresolution imaging of individual membrane proteins in live Caenorhabditis elegans (C. elegans). In vivo tissue-specific SM tracking of transmembrane CD4 and voltage-dependent Ca(2+) channels (VDCC) was achieved with a precision of 30 nm within neuromuscular synapses and at the surface of muscle cells in normal and dystrophin-mutant worms. Through diffusion analyses, we reveal that dystrophin is involved in modulating the confinement of VDCC within sarcolemmal membrane nanodomains in response to varying tonus of C. elegans body-wall muscles. CALM expands the applications of SM imaging techniques beyond the petri dish and opens the possibility to explore the molecular basis of homeostatic and pathological cellular processes with subresolution precision, directly in live animals.},
  language  = {en}
}
@article{WirthGlushakovaScheuermayeretal.2014,
  author    = {Wirth, Christine C. and Glushakova, Svetlana and Scheuermayer, Matthias and Repnik, Urska and Garg, Swatl and Schaack, Dominik and Kachman, Marika M. and Weißbach, Tim and Zimmerberg, Joshua and Dandekar, Thomas and Griffiths, Gareth and Chitnis, Chetan E. and Singh, Shallja and Fischer, Rainer and Pradel, Gabriele},
  title     = {Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes},
  series = {Cellular Microbiology},
  volume    = {16},
  journal   = {Cellular Microbiology},
  number    = {5},
  doi       = {10.1111/cmi.12288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120895},
  pages     = {709-33},
  year      = {2014},
  abstract  = {Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.},
  language  = {en}
}
@article{KlattHolzschuhWestphaletal.2014,
  author    = {Klatt, Bj{\"o}rn K. and Holzschuh, Andrea and Westphal, Catrin and Clough, Yann and Smit, Inga and Pawelzik, Elke and Tscharntke, Teja},
  title     = {Bee pollination improves crop quality, shelf life and commercial value},
  series = {Proceedings of the Royal Society B: Biological Sciences},
  volume    = {281},
  journal   = {Proceedings of the Royal Society B: Biological Sciences},
  number    = {1775},
  doi       = {10.1098/rspb.2013.2440},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120797},
  year      = {2014},
  abstract  = {Pollination improves the yield of most crop species and contributes to one-third of global crop production, but comprehensive benefits including crop quality are still unknown. Hence, pollination is underestimated by international policies, which is particularly alarming in times of agricultural intensification and diminishing pollination services. In this study, exclusion experiments with strawberries showed bee pollination to improve fruit quality, quantity and market value compared with wind and self-pollination. Bee-pollinated fruits were heavier, had less malformations and reached higher commercial grades. They had increased redness and reduced sugar-acid-ratios and were firmer, thus improving the commercially important shelf life. Longer shelf life reduced fruit loss by at least 11\%. This is accounting for 0.32 billion US\$ of the 1.44 billion US\$ provided by bee pollination to the total value of 2.90 billion US\$ made with strawberry selling in the European Union 2009. The fruit quality and yield effects are driven by the pollination-mediated production of hormonal growth regulators, which occur in several pollination-dependent crops. Thus, our comprehensive findings should be transferable to a wide range of crops and demonstrate bee pollination to be a hitherto underestimated but vital and economically important determinant of fruit quality.},
  language  = {en}
}
@article{DandekarFieselmannFischeretal.2014,
  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},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2014.00191},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120686},
  year      = {2014},
  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{HaydnHufnagelGrimmetal.2014,
  author    = {Haydn, Johannes M. and Hufnagel, Anita and Grimm, Johannes and Maurus, Katja and Schartl, Manfred and Meierjohann, Svenja},
  title     = {The MAPK pathway as an apoptosis enhancer in melanoma},
  series = {Oncotarget},
  volume    = {5},
  journal   = {Oncotarget},
  number    = {13},
  issn      = {1949-2553},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120649},
  pages     = {5040-53},
  year      = {2014},
  abstract  = {Inhibition of RAF/MEK/ERK signaling is beneficial for many patients with BRAFV600E-mutated melanoma. However, primary and secondary resistances restrict long-lasting therapy success. Combination therapies are therefore urgently needed. Here, we evaluate the cellular effect of combining a MEK inhibitor with a genotoxic apoptosis inducer. Strikingly, we observed that an activated MAPK pathway promotes in several melanoma cell lines the pro-apoptotic response to genotoxic stress, and MEK inhibition reduces intrinsic apoptosis. This goes along with MEK inhibitor induced increased RAS and P-AKT levels. The protective effect of the MEK inhibitor depends on PI3K signaling, which prevents the induction of pro-apoptotic PUMA that mediates apoptosis after DNA damage. We could show that the MEK inhibitor dependent feedback loop is enabled by several factors, including EGF receptor and members of the SPRED family. The simultaneous knockdown of SPRED1 and SPRED2 mimicked the effects of MEK inhibitor such as PUMA repression and protection from apoptosis. Our data demonstrate that MEK inhibition of BRAFV600E-positive melanoma cells can protect from genotoxic stress, thereby achieving the opposite of the intended anti-tumorigenic effect of the combination of MEK inhibitor with inducers of intrinsic apoptosis.},
  language  = {en}
}
@article{NaseemKunzDandekar2014,
  author    = {Naseem, Muhammad and Kunz, Meik and Dandekar, Thomas},
  title     = {Probing the unknowns in cytokinin-mediated immune defense in Arabidopsis with systems biology approaches},
  series = {Bioinformatics and Biology Insights},
  volume    = {8},
  journal   = {Bioinformatics and Biology Insights},
  issn      = {1177-9322},
  doi       = {10.4137/bbi.s13462},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120199},
  pages     = {35-44},
  year      = {2014},
  abstract  = {Plant hormones involving salicylic acid (SA), jasmonic acid (JA), ethylene (Et), and auxin, gibberellins, and abscisic acid (ABA) are known to regulate host immune responses. However, plant hormone cytokinin has the potential to modulate defense signaling including SA and JA. It promotes plant pathogen and herbivore resistance; underlying mechanisms are still unknown. Using systems biology approaches, we unravel hub points of immune interaction mediated by cytokinin signaling in Arabidopsis. High-confidence Arabidopsis protein-protein interactions (PPI) are coupled to changes in cytokinin-mediated gene expression. Nodes of the cellular interactome that are enriched in immune functions also reconstitute sub-networks. Topological analyses and their specific immunological relevance lead to the identification of functional hubs in cellular interactome. We discuss our identified immune hubs in light of an emerging model of cytokinin-mediated immune defense against pathogen infection in plants.},
  language  = {en}
}
@article{AhmedZeeshanHuberetal.2014,
  author    = {Ahmed, Zeeshan and Zeeshan, Saman and Huber, Claudia and Hensel, Michael and Schomburg, Dietmar and M{\"u}nch, Richard and Eylert, Eva and Eisenreich, Wolfgang and Dandekar, Thomas},
  title     = {'Isotopo' a database application for facile analysis and management of mass isotopomer data},
  series = {Database},
  volume    = {2014},
  journal   = {Database},
  number    = {bau077},
  doi       = {10.1093/database/bau077},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120102},
  year      = {2014},
  abstract  = {The composition of stable-isotope labelled isotopologues/isotopomers in metabolic products can be measured by mass spectrometry and supports the analysis of pathways and fluxes. As a prerequisite, the original mass spectra have to be processed, managed and stored to rapidly calculate, analyse and compare isotopomer enrichments to study, for instance, bacterial metabolism in infection. For such applications, we provide here the database application 'Isotopo'. This software package includes (i) a database to store and process isotopomer data, (ii) a parser to upload and translate different data formats for such data and (iii) an improved application to process and convert signal intensities from mass spectra of \(^{13}C\)-labelled metabolites such as tertbutyldimethylsilyl-derivatives of amino acids. Relative mass intensities and isotopomer distributions are calculated applying a partial least square method with iterative refinement for high precision data. The data output includes formats such as graphs for overall enrichments in amino acids. The package is user-friendly for easy and robust data management of multiple experiments.},
  language  = {en}
}
@article{Schartl2014,
  author    = {Schartl, Manfred},
  title     = {Beyond the zebrafish: diverse fish species for modeling human disease},
  series = {Disease Models \& Mechanisms},
  volume    = {7},
  journal   = {Disease Models \& Mechanisms},
  number    = {2},
  issn      = {1754-8411},
  doi       = {10.1242/dmm.012245},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119919},
  year      = {2014},
  abstract  = {In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.},
  language  = {en}
}
@article{AndreskaAufmkolkSaueretal.2014,
  author    = {Andreska, Thomas and Aufmkolk, Sarah and Sauer, Markus and Blum, Robert},
  title     = {High abundance of BDNF within glutamatergic presynapses of cultured hippocampal neurons},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Cellular Neuroscience},
  number    = {107},
  issn      = {1662-5102},
  doi       = {10.3389/fncel.2014.00107},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119793},
  year      = {2014},
  abstract  = {In the mammalian brain, the neurotrophin brain-derived neurotrophic factor (BDNF) has emerged as a key factor for synaptic refinement, plasticity and learning. Although BDNF-induced signaling cascades are well known, the spatial aspects of the synaptic BDNF localization remained unclear. Recent data provide strong evidence for an exclusive presynaptic location and anterograde secretion of endogenous BDNF at synapses of the hippocampal circuit. In contrast, various studies using BDNF overexpression in cultured hippocampal neurons support the idea that postsynaptic elements and other dendritic structures are the preferential sites of BDNF localization and release. In this study we used rigorously tested anti-BDNF antibodies and achieved a dense labeling of endogenous BDNF close to synapses. Confocal microscopy showed natural BDNF close to many, but not all glutamatergic synapses, while neither GABAergic synapses nor postsynaptic structures carried a typical synaptic BDNF label. To visualize the BDNF distribution within the fine structure of synapses, we implemented super resolution fluorescence imaging by direct stochastic optical reconstruction microscopy (dSTORM). Two-color dSTORM images of neurites were acquired with a spatial resolution of ~20 nm. At this resolution, the synaptic scaffold proteins Bassoon and Homer exhibit hallmarks of mature synapses and form juxtaposed bars, separated by a synaptic cleft. BDNF imaging signals form granule-like clusters with a mean size of ~60 nm and are preferentially found within the fine structure of the glutamatergic presynapse. Individual glutamatergic presynapses carried up to 90\% of the synaptic BDNF immunoreactivity, and only a minor fraction of BDNF molecules was found close to the postsynaptic bars. Our data proof that hippocampal neurons are able to enrich and store high amounts of BDNF in small granules within the mature glutamatergic presynapse, at a principle site of synaptic plasticity.},
  language  = {en}
}
@article{ProppertWolterHolmetal.2014,
  author    = {Proppert, Sven and Wolter, Steve and Holm, Thorge and Klein, Theresa and van de Linde, Sebastian and Sauer, Markus},
  title     = {Cubic B-spline calibration for 3D super-resolution measurements using astigmatic imaging},
  series = {Optics Express},
  volume    = {22},
  journal   = {Optics Express},
  number    = {9},
  issn      = {1094-4087},
  doi       = {10.1364/OE.22.010304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119730},
  pages     = {10304-16},
  year      = {2014},
  abstract  = {In recent years three-dimensional (3D) super-resolution fluorescence imaging by single-molecule localization (localization microscopy) has gained considerable interest because of its simple implementation and high optical resolution. Astigmatic and biplane imaging are experimentally simple methods to engineer a 3D-specific point spread function (PSF), but existing evaluation methods have proven problematic in practical application. Here we introduce the use of cubic B-splines to model the relationship of axial position and PSF width in the above mentioned approaches and compare the performance with existing methods. We show that cubic B-splines are the first method that can combine precision, accuracy and simplicity.},
  language  = {en}
}
@article{BatramJonesJanzenetal.2014,
  author    = {Batram, Christopher and Jones, Nivola G. and Janzen, Christian J. and Markert, Sebastian M. and Engstler, Markus},
  title     = {Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei},
  series = {eLife},
  volume    = {3},
  journal   = {eLife},
  number    = {e02324},
  issn      = {2050-084X},
  doi       = {10.7554/eLife.02324},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119727},
  year      = {2014},
  abstract  = {We have discovered a new mechanism of monoallelic gene expression that links antigenic variation, cell cycle, and development in the model parasite Trypanosoma brucei. African trypanosomes possess hundreds of variant surface glycoprotein (VSG) genes, but only one is expressed from a telomeric expression site (ES) at any given time. We found that the expression of a second VSG alone is sufficient to silence the active VSG gene and directionally attenuate the ES by disruptor of telomeric silencing-1B (DOT1B)-mediated histone methylation. Three conserved expression-site-associated genes (ESAGs) appear to serve as signal for ES attenuation. Their depletion causes G1-phase dormancy and reversible initiation of the slender-to-stumpy differentiation pathway. ES-attenuated slender bloodstream trypanosomes gain full developmental competence for transformation to the tsetse fly stage. This surprising connection between antigenic variation and developmental progression provides an unexpected point of attack against the deadly sleeping sickness.},
  language  = {en}
}
@article{YilmazAksoyCamlitepeetal.2014,
  author    = {Yilmaz, Ayse and Aksoy, Volkan and Camlitepe, Yilmaz and Giurfa, Martin},
  title     = {Eye structure, activity rhythms, and visually-driven behavior are tuned to visual niche in ants},
  series = {Frontiers in Behavioral Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Behavioral Neuroscience},
  doi       = {10.3389/fnbeh.2014.00205},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119595},
  pages     = {205},
  year      = {2014},
  abstract  = {Insects have evolved physiological adaptations and behavioral strategies that allow them to cope with a broad spectrum of environmental challenges and contribute to their evolutionary success. Visual performance plays a key role in this success. Correlates between life style and eye organization have been reported in various insect species. Yet, if and how visual ecology translates effectively into different visual discrimination and learning capabilities has been less explored. Here we report results from optical and behavioral analyses performed in two sympatric ant species, Formica cunicularia and Camponotus aethiops. We show that the former are diurnal while the latter are cathemeral. Accordingly, F. cunicularia workers present compound eyes with higher resolution, while C. aethiops workers exhibit eyes with lower resolution but higher sensitivity. The discrimination and learning of visual stimuli differs significantly between these species in controlled dual-choice experiments: discrimination learning of small-field visual stimuli is achieved by F. cunicularia but not by C. aethiops, while both species master the discrimination of large-field visual stimuli. Our work thus provides a paradigmatic example about how timing of foraging activities and visual environment match the organization of compound eyes and visually-driven behavior. This correspondence underlines the relevance of an ecological/evolutionary framework for analyses in behavioral neuroscience.},
  language  = {en}
}
@article{DusikSenthilanMentzeletal.2014,
  author    = {Dusik, Verena and Senthilan, Pingkalai R. and Mentzel, Benjamin and Hartlieb, Heiko and W{\"u}lbeck, Corina and Yoshii, Taishi and Raabe, Thomas and Helfrich-F{\"o}rster, Charlotte},
  title     = {The MAP Kinase p38 Is Part of Drosophila melanogaster's Circadian Clock},
  series = {PLoS Genetics},
  volume    = {10},
  journal   = {PLoS Genetics},
  number    = {8},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1004565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119433},
  pages     = {e1004565},
  year      = {2014},
  abstract  = {All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. Here, we demonstrate by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, we found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining ∼ 24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed our Western Blot results and point to p38 as a potential "clock kinase" phosphorylating Period. Taken together, our findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways.},
  language  = {en}
}
@article{AdelfingerGentschevdeGuibertetal.2014,
  author    = {Adelfinger, Marion and Gentschev, Ivaylo and de Guibert, Julio Grimm and Weibel, Stephanie and Langbein-Laugwitz, Johanna and H{\"a}rtl, Barbara and Escobar, Hugo Murua and Nolte, Ingo and Chen, Nanhai G. and Aguilar, Richard J. and Yu, Yong A. and Zhang, Qian and Frentzen, Alexa and Szalay, Aladar A.},
  title     = {Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0104337},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119387},
  pages     = {e104337},
  year      = {2014},
  abstract  = {Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis. In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.},
  language  = {en}
}
@article{LeonhardtKaltenpoth2014,
  author    = {Leonhardt, Sara D. and Kaltenpoth, Martin},
  title     = {Microbial Communities of Three Sympatric Australian Stingless Bee Species},
  series = {PLoS ONE},
  volume    = {9},
  journal   = {PLoS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0105718},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119341},
  pages     = {e105718},
  year      = {2014},
  abstract  = {Bacterial symbionts of insects have received increasing attention due to their prominent role in nutrient acquisition and defense. In social bees, symbiotic bacteria can maintain colony homeostasis and fitness, and the loss or alteration of the bacterial community may be associated with the ongoing bee decline observed worldwide. However, analyses of microbiota associated with bees have been largely confined to the social honeybees (Apis mellifera) and bumblebees (Bombus spec.), revealing - among other taxa - host-specific lactic acid bacteria (LAB, genus Lactobacillus) that are not found in solitary bees. Here, we characterized the microbiota of three Australian stingless bee species (Apidae: Meliponini) of two phylogenetically distant genera (Tetragonula and Austroplebeia). Besides common plant bacteria, we find LAB in all three species, showing that LAB are shared by honeybees, bumblebees and stingless bees across geographical regions. However, while LAB of the honeybee-associated Firm4-5 clusters were present in Tetragonula, they were lacking in Austroplebeia. Instead, we found a novel clade of likely host-specific LAB in all three Australian stingless bee species which forms a sister clade to a large cluster of Halictidae-associated lactobacilli. Our findings indicate both a phylogenetic and geographical signal of host-specific LAB in stingless bees and highlight stingless bees as an interesting group to investigate the evolutionary history of the bee-LAB association.},
  language  = {en}
}
@article{NaseemSrivastavaDandekar2014,
  author    = {Naseem, Muhammad and Srivastava, Mugdha and Dandekar, Thomas},
  title     = {Stem-cell-triggered immunity safeguards cytokinin enriched plant shoot apexes from pathogen infection},
  series = {Frontiers in Plant Science},
  volume    = {5},
  journal   = {Frontiers in Plant Science},
  issn      = {1664-462X},
  doi       = {10.3389/fpls.2014.00588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118247},
  pages     = {588},
  year      = {2014},
  abstract  = {Intricate mechanisms discriminate between friends and foes in plants. Plant organs deploy overlapping and distinct protection strategies. Despite vulnerability to a plethora of pathogens, the growing tips of plants grow bacteria free. The shoot apical meristem (SAM) is among three stem cells niches, a self-renewable reservoir for the future organogenesis of leaf, stem, and flowers. How plants safeguard this high value growth target from infections was not known until now. Recent reports find the stem cell secreted 12-amino acid peptide CLV3p (CLAVATA3 peptide) is perceived by FLS2 (FLAGELLIN SENSING 2) receptor and activates the transcription of immunity and defense marker genes. No infection in the SAM of wild type plants and bacterial infection in clv3 and fls2 mutants illustrate this natural protection against infections. Cytokinins (CKs) are enriched in the SAM and regulate meristem activities by their involvement in stem cell signaling networks. Auxin mediates plant susceptibility to pathogen infections while CKs boost plant immunity. Here, in addition to the stem-cell-triggered immunity we also highlight a potential link between CK signaling and CLV3p mediated immune response in the SAM.},
  language  = {en}
}