@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} }