@article{TauscherNakagawaVoelkeretal.2018, author = {Tauscher, Sabine and Nakagawa, Hitoshi and V{\"o}lker, Katharina and Werner, Franziska and Krebes, Lisa and Potapenko, Tamara and Doose, S{\"o}ren and Birkenfeld, Andreas L. and Baba, Hideo A. and Kuhn, Michaela}, title = {β Cell-specific deletion of guanylyl cyclase A, the receptor for atrial natriuretic peptide, accelerates obesity-induced glucose intolerance in mice}, series = {Cardiovascular Diabetology}, volume = {17}, journal = {Cardiovascular Diabetology}, number = {103}, doi = {10.1186/s12933-018-0747-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176322}, year = {2018}, abstract = {Background: The cardiac hormones atrial (ANP) and B-type natriuretic peptides (BNP) moderate arterial blood pressure and improve energy metabolism as well as insulin sensitivity via their shared cGMP-producing guanylyl cyclase-A (GC-A) receptor. Obesity is associated with impaired NP/GC-A/cGMP signaling, which possibly contributes to the development of type 2 diabetes and its cardiometabolic complications. In vitro, synthetic ANP, via GC-A, stimulates glucose-dependent insulin release from cultured pancreatic islets and β-cell proliferation. However, the relevance for systemic glucose homeostasis in vivo is not known. To dissect whether the endogenous cardiac hormones modulate the secretory function and/or proliferation of β-cells under (patho)physiological conditions in vivo, here we generated a novel genetic mouse model with selective disruption of the GC-A receptor in β-cells. Methods: Mice with a floxed GC-A gene were bred to Rip-CreTG mice, thereby deleting GC-A selectively in β-cells (β GC-A KO). Weight gain, glucose tolerance, insulin sensitivity, and glucose-stimulated insulin secretion were monitored in normal diet (ND)- and high-fat diet (HFD)-fed mice. β-cell size and number were measured by immunofluorescence-based islet morphometry. Results: In vitro, the insulinotropic and proliferative actions of ANP were abolished in islets isolated from β GC-A KO mice. Concordantly, in vivo, infusion of BNP mildly enhanced baseline plasma insulin levels and glucose-induced insulin secretion in control mice. This effect of exogenous BNP was abolished in β GC-A KO mice, corroborating the efficient inactivation of the GC-A receptor in β-cells. Despite this under physiological, ND conditions, fasted and fed insulin levels, glucose-induced insulin secretion, glucose tolerance and β-cell morphology were similar in β GC-A KO mice and control littermates. However, HFD-fed β GC-A KO animals had accelerated glucose intolerance and diminished adaptative β-cell proliferation. Conclusions: Our studies of β GC-A KO mice demonstrate that the cardiac hormones ANP and BNP do not modulate β-cell's growth and secretory functions under physiological, normal dietary conditions. However, endogenous NP/GC-A signaling improves the initial adaptative response of β-cells to HFD-induced obesity. Impaired β-cell NP/GC-A signaling in obese individuals might contribute to the development of type 2 diabetes.}, language = {en} } @article{KellerBrandelBeckeretal.2018, author = {Keller, Alexander and Brandel, Annette and Becker, Mira C. and Balles, Rebecca and Abdelmohsen, Usama Ramadan and Ankenbrand, Markus J. and Sickel, Wiebke}, title = {Wild bees and their nests host Paenibacillus bacteria with functional potential of avail}, series = {Microbiome}, volume = {6}, journal = {Microbiome}, number = {229}, doi = {10.1186/s40168-018-0614-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177554}, year = {2018}, abstract = {Background: In previous studies, the gram-positive firmicute genus Paenibacillus was found with significant abundances in nests of wild solitary bees. Paenibacillus larvae is well-known for beekeepers as a severe pathogen causing the fatal honey bee disease American foulbrood, and other members of the genus are either secondary invaders of European foulbrood or considered a threat to honey bees. We thus investigated whether Paenibacillus is a common bacterium associated with various wild bees and hence poses a latent threat to honey bees visiting the same flowers. Results: We collected 202 samples from 82 individuals or nests of 13 bee species at the same location and screened each for Paenibacillus using high-throughput sequencing-based 16S metabarcoding. We then isolated the identified strain Paenibacillus MBD-MB06 from a solitary bee nest and sequenced its genome. We did find conserved toxin genes and such encoding for chitin-binding proteins, yet none specifically related to foulbrood virulence or chitinases. Phylogenomic analysis revealed a closer relationship to strains of root-associated Paenibacillus rather than strains causing foulbrood or other accompanying diseases. We found anti-microbial evidence within the genome, confirmed by experimental bioassays with strong growth inhibition of selected fungi as well as gram-positive and gram-negative bacteria. Conclusions: The isolated wild bee associate Paenibacillus MBD-MB06 is a common, but irregularly occurring part of wild bee microbiomes, present on adult body surfaces and guts and within nests especially in megachilids. It was phylogenetically and functionally distinct from harmful members causing honey bee colony diseases, although it shared few conserved proteins putatively toxic to insects that might indicate ancestral predisposition for the evolution of insect pathogens within the group. By contrast, our strain showed anti-microbial capabilities and the genome further indicates abilities for chitin-binding and biofilm-forming, suggesting it is likely a useful associate to avoid fungal penetration of the bee cuticula and a beneficial inhabitant of nests to repress fungal threats in humid and nutrient-rich environments of wild bee nests.}, language = {en} } @article{RatHeibyBunzetal.2018, author = {Rat, Charlotte and Heiby, Julia C. and Bunz, Jessica P. and Neuweiler, Hannes}, title = {Two-step self-assembly of a spider silk molecular clamp}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-07227-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225016}, pages = {4779, 1-11}, year = {2018}, abstract = {Web spiders synthesize silk fibers of unique strength and extensibility through the controlled self-assembly of protein building blocks, so-called spidroins. The spidroin C-terminal domain is highly conserved and connects two polypeptide chains through formation of an all-helical, intertwined dimer. Here we use contact-induced fluorescence self-quenching and resonance energy transfer in combination with far-UV circular dichroism spectroscopy as three orthogonal structural probes to dissect the mechanism of folding and dimerization of a spidroin C-terminal domain from the major ampullate gland of the nursery web spider Euprosthenops australis. We show that helices forming the dimer core assemble very rapidly and fold on association. Subsequently, peripheral helices fold and dock slowly onto the preformed core. Lability of outer helices facilitates formation of a highly expanded, partially folded dimer. The high end-to-end distance of chain termini in the partially folded dimer suggests an extensibility module that contributes to elasticity of spider silk.}, language = {en} } @article{BatzkeBuechelHansenetal.2018, author = {Batzke, Katharina and B{\"u}chel, Gabriele and Hansen, Wiebke and Schramm, Alexander}, title = {TrkB-target Galectin-1 impairs immune activation and radiation responses in neuroblastoma: implications for tumour therapy}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms19030718}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285097}, year = {2018}, abstract = {Galectin-1 (Gal-1) has been described to promote tumour growth by inducing angiogenesis and to contribute to the tumour immune escape. We had previously identified up-regulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), the most common extracranial tumour of childhood. While Gal-1 did not confer a survival advantage in the absence of exogenous stressors, Gal-1 contributed to enhanced cell migratory and invasive properties. Here, we review these findings and extend them by analyzing Gal-1 mediated effects on immune cell regulation and radiation resistance. In line with previous results, cell autonomous effects as well as paracrine functions contribute to Gal-1 mediated pro-tumourigenic functions. Interfering with Gal-1 functions in vivo will add to a better understanding of the role of the Gal-1 axis in the complex tumour-host interaction during immune-, chemo- and radiotherapy of neuroblastoma.}, language = {en} } @article{RubioCosialsSchulzLambertsenetal.2018, author = {Rubio-Cosials, Anna and Schulz, Eike C. and Lambertsen, Lotte and Smyshlyaev, Georgy and Rojas-Cordova, Carlos and Forslund, Kristoffer and Karaca, Ezgi and Bebel, Aleksandra and Bork, Peer and Barabas, Orsolya}, title = {Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance}, series = {Cell}, volume = {173}, journal = {Cell}, number = {1}, doi = {10.1016/j.cell.2018.02.032}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227085}, pages = {e20, 208-220}, year = {2018}, abstract = {Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.}, language = {en} } @article{JarickBertscheStahletal.2018, author = {Jarick, Marcel and Bertsche, Ute and Stahl, Mark and Schultz, Daniel and Methling, Karen and Lalk, Michael and Stigloher, Christian and Steger, Mirco and Schlosser, Andreas and Ohlsen, Knut}, title = {The serine/threonine kinase Stk and the phosphatase Stp regulate cell wall synthesis in Staphylococcus aureus}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {13693}, doi = {10.1038/s41598-018-32109-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177333}, year = {2018}, abstract = {The cell wall synthesis pathway producing peptidoglycan is a highly coordinated and tightly regulated process. Although the major components of bacterial cell walls have been known for decades, the complex regulatory network controlling peptidoglycan synthesis and many details of the cell division machinery are not well understood. The eukaryotic-like serine/threonine kinase Stk and the cognate phosphatase Stp play an important role in cell wall biosynthesis and drug resistance in S. aureus. We show that stp deletion has a pronounced impact on cell wall synthesis. Deletion of stp leads to a thicker cell wall and decreases susceptibility to lysostaphin. Stationary phase Δstp cells accumulate peptidoglycan precursors and incorporate higher amounts of incomplete muropeptides with non-glycine, monoglycine and monoalanine interpeptide bridges into the cell wall. In line with this cell wall phenotype, we demonstrate that the lipid II:glycine glycyltransferase FemX can be phosphorylated by the Ser/Thr kinase Stk in vitro. Mass spectrometric analyses identify Thr32, Thr36 and Ser415 as phosphoacceptors. The cognate phosphatase Stp dephosphorylates these phosphorylation sites. Moreover, Stk interacts with FemA and FemB, but is unable to phosphorylate them. Our data indicate that Stk and Stp modulate cell wall synthesis and cell division at several levels.}, language = {en} } @article{BoertleinDraegerSchoenaueretal.2018, author = {B{\"o}rtlein, Charlene and Draeger, Annette and Schoenauer, Roman and Kuhlemann, Alexander and Sauer, Markus and Schneider-Schaulies, Sybille and Avota, Elita}, title = {The neutral sphingomyelinase 2 is required to polarize and sustain T Cell receptor signaling}, series = {Frontiers in Immunology}, volume = {9}, journal = {Frontiers in Immunology}, number = {815}, doi = {10.3389/fimmu.2018.00815}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176572}, year = {2018}, abstract = {By promoting ceramide release at the cytosolic membrane leaflet, the neutral sphingomyelinase 2 (NSM) is capable of organizing receptor and signalosome segregation. Its role in T cell receptor (TCR) signaling remained so far unknown. We now show that TCR-driven NSM activation is dispensable for TCR clustering and initial phosphorylation, but of crucial importance for further signal amplification. In particular, at low doses of TCR stimulatory antibodies, NSM is required for Ca\(^{2+}\) mobilization and T cell proliferation. NSM-deficient T cells lack sustained CD3ζ and ZAP-70 phosphorylation and are unable to polarize and stabilize their microtubular system. We identified PKCζ as the key NSM downstream effector in this second wave of TCR signaling supporting dynamics of microtubule-organizing center (MTOC). Ceramide supplementation rescued PKCζ membrane recruitment and MTOC translocation in NSM-deficient cells. These findings identify the NSM as essential in TCR signaling when dynamic cytoskeletal reorganization promotes continued lateral and vertical supply of TCR signaling components: CD3ζ, Zap70, and PKCζ, and functional immune synapses are organized and stabilized via MTOC polarization.}, language = {en} } @article{KohlRutschmann2018, author = {Kohl, Patrick Laurenz and Rutschmann, Benjamin}, title = {The neglected bee trees: European beech forests as a home for feral honey bee colonies}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e4602}, doi = {10.7717/peerj.4602}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176512}, year = {2018}, abstract = {It is a common belief that feral honey bee colonies (Apis mellifera L.) were eradicated in Europe through the loss of habitats, domestication by man and spread of pathogens and parasites. Interestingly, no scientific data are available, neither about the past nor the present status of naturally nesting honeybee colonies. We expected near-natural beech (Fagus sylvatica L.) forests to provide enough suitable nest sites to be a home for feral honey bee colonies in Europe. Here, we made a first assessment of their occurrence and density in two German woodland areas based on two methods, the tracing of nest sites based on forager flight routes (beelining technique), and the direct inspection of potential cavity trees. Further, we established experimental swarms at forest edges and decoded dances for nest sites performed by scout bees in order to study how far swarms from beekeeper-managed hives would potentially move into a forest. We found that feral honey bee colonies regularly inhabit tree cavities in near-natural beech forests at densities of at least 0.11-0.14 colonies/km\(^{2}\). Colonies were not confined to the forest edges; they were also living deep inside the forests. We estimated a median distance of 2,600 m from the bee trees to the next apiaries, while scout bees in experimental swarms communicated nest sites in close distances (median: 470 m). We extrapolate that there are several thousand feral honey bee colonies in German woodlands. These have to be taken in account when assessing the role of forest areas in providing pollination services to the surrounding land, and their occurrence has implications for the species' perception among researchers, beekeepers and conservationists. This study provides a starting point for investigating the life-histories and the ecological interactions of honey bees in temperate European forest environments.}, language = {en} } @article{KruegerEngstler2018, author = {Kr{\"u}ger, Timothy and Engstler, Markus}, title = {The fantastic voyage of the trypanosome: a protean micromachine perfected during 500 million years of engineering}, series = {Micromachines}, volume = {9}, journal = {Micromachines}, number = {2}, doi = {10.3390/mi9020063}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175944}, pages = {63}, year = {2018}, abstract = {The human body is constantly attacked by pathogens. Various lines of defence have evolved, among which the immune system is principal. In contrast to most pathogens, the African trypanosomes thrive freely in the blood circulation, where they escape immune destruction by antigenic variation and incessant motility. These unicellular parasites are flagellate microswimmers that also withstand the harsh mechanical forces prevailing in the bloodstream. They undergo complex developmental cycles in the bloodstream and organs of the mammalian host, as well as the disease-transmitting tsetse fly. Each life cycle stage has been shaped by evolution for manoeuvring in distinct microenvironments. Here, we introduce trypanosomes as blueprints for nature-inspired design of trypanobots, micromachines that, in the future, could explore the human body without affecting its physiology. We review cell biological and biophysical aspects of trypanosome motion. While this could provide a basis for the engineering of microbots, their actuation and control still appear more like fiction than science. Here, we discuss potentials and challenges of trypanosome-inspired microswimmer robots.}, language = {en} } @article{HofrichterMojaradDolletal.2018, author = {Hofrichter, Michaela A. H. and Mojarad, Majid and Doll, Julia and Grimm, Clemens and Eslahi, Atiye and Hosseini, Neda Sadat and Rajati, Mohsen and M{\"u}ller, Tobias and Dittrich, Marcus and Maroofian, Reza and Haaf, Thomas and Vona, Barbara}, title = {The conserved p.Arg108 residue in S1PR2 (DFNB68) is fundamental for proper hearing: evidence from a consanguineous Iranian family}, series = {BMC Medical Genetics}, volume = {19}, journal = {BMC Medical Genetics}, number = {81}, doi = {10.1186/s12881-018-0598-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175755}, year = {2018}, abstract = {Background: Genetic heterogeneity and consanguineous marriages make recessive inherited hearing loss in Iran the second most common genetic disorder. Only two reported pathogenic variants (c.323G>C, p.Arg108Pro and c.419A>G, p.Tyr140Cys) in the S1PR2 gene have previously been linked to autosomal recessive hearing loss (DFNB68) in two Pakistani families. We describe a segregating novel homozygous c.323G>A, p.Arg108Gln pathogenic variant in S1PR2 that was identified in four affected individuals from a consanguineous five generation Iranian family. Methods: Whole exome sequencing and bioinformatics analysis of 116 hearing loss-associated genes was performed in an affected individual from a five generation Iranian family. Segregation analysis and 3D protein modeling of the p.Arg108 exchange was performed. Results: The two Pakistani families previously identified with S1PR2 pathogenic variants presented profound hearing loss that is also observed in the affected Iranian individuals described in the current study. Interestingly, we confirmed mixed hearing loss in one affected individual. 3D protein modeling suggests that the p.Arg108 position plays a key role in ligand receptor interaction, which is disturbed by the p.Arg108Gln change. Conclusion: In summary, we report the third overall mutation in S1PR2 and the first report outside the Pakistani population. Furthermore, we describe a novel variant that causes an amino acid exchange (p.Arg108Gln) in the same amino acid residue as one of the previously reported Pakistani families (p.Arg108Pro). This finding emphasizes the importance of the p.Arg108 amino acid in normal hearing and confirms and consolidates the role of S1PR2 in autosomal recessive hearing loss.}, language = {en} } @article{KottlerSchartl2018, author = {Kottler, Verena A. and Schartl, Manfred}, title = {The colorful sex chromosomes of teleost fish}, series = {Genes}, volume = {9}, journal = {Genes}, number = {5}, doi = {10.3390/genes9050233}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176587}, pages = {233}, year = {2018}, abstract = {Teleost fish provide some of the most intriguing examples of sexually dimorphic coloration, which is often advantageous for only one of the sexes. Mapping studies demonstrated that the genetic loci underlying such color patterns are frequently in tight linkage to the sex-determining locus of a species, ensuring sex-specific expression of the corresponding trait. Several genes affecting color synthesis and pigment cell development have been previously described, but the color loci on the sex chromosomes have mostly remained elusive as yet. Here, we summarize the current knowledge about the genetics of such color loci in teleosts, mainly from studies on poeciliids and cichlids. Further studies on these color loci will certainly provide important insights into the evolution of sex chromosomes.}, language = {en} } @article{FujiwaraHermannLuiblKatsuraetal.2018, author = {Fujiwara, Yuri and Hermann-Luibl, Christiane and Katsura, Maki and Sekiguchi, Manabu and Ida, Takanori and Helfrich-F{\"o}rster, Charlotte and Yoshii, Taishi}, title = {The CCHamide1 Neuropeptide Expressed in the Anterior Dorsal Neuron 1 Conveys a Circadian Signal to the Ventral Lateral Neurons in Drosophila melanogaster}, series = {Frontiers in Physiology}, volume = {09}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2018.01276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195940}, year = {2018}, abstract = {The fruit fly Drosophila melanogaster possesses approximately 150 brain clock neurons that control circadian behavioral rhythms. Even though individual clock neurons have self-sustaining oscillators, they interact and synchronize with each other through a network. However, little is known regarding the factors responsible for these network interactions. In this study, we investigated the role of CCHamide1 (CCHa1), a neuropeptide expressed in the anterior dorsal neuron 1 (DN1a), in intercellular communication of the clock neurons. We observed that CCHa1 connects the DN1a clock neurons to the ventral lateral clock neurons (LNv) via the CCHa1 receptor, which is a homolog of the gastrin-releasing peptide receptor playing a role in circadian intercellular communications in mammals. CCHa1 knockout or knockdown flies have a generally low activity level with a special reduction of morning activity. In addition, they exhibit advanced morning activity under light-dark cycles and delayed activity under constant dark conditions, which correlates with an advance/delay of PAR domain Protein 1 (PDP1) oscillations in the small-LNv (s-LNv) neurons that control morning activity. The terminals of the s-LNv neurons show rather high levels of Pigment-dispersing factor (PDF) in the evening, when PDF is low in control flies, suggesting that the knockdown of CCHa1 leads to increased PDF release; PDF signals the other clock neurons and evidently increases the amplitude of their PDP1 cycling. A previous study showed that high-amplitude PDP1 cycling increases the siesta of the flies, and indeed, CCHa1 knockout or knockdown flies exhibit a longer siesta than control flies. The DN1a neurons are known to be receptive to PDF signaling from the s-LNv neurons; thus, our results suggest that the DN1a and s-LNv clock neurons are reciprocally coupled via the neuropeptides CCHa1 and PDF, and this interaction fine-tunes the timing of activity and sleep.}, language = {en} } @article{ReisSchwebsDietzetal.2018, author = {Reis, Helena and Schwebs, Marie and Dietz, Sabrina and Janzen, Christian J. and Butter, Falk}, title = {TelAP1 links telomere complexes with developmental expression site silencing in African trypanosomes}, series = {Nucleic Acids Research}, volume = {46}, journal = {Nucleic Acids Research}, number = {6}, doi = {10.1093/nar/gky028}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225180}, pages = {2820-2833}, year = {2018}, abstract = {During its life cycle, Trypanosoma brucei shuttles between a mammalian host and the tsetse fly vector. In the mammalian host, immune evasion of T. brucei bloodstream form (BSF) cells relies on antigenic variation, which includes monoallelic expression and periodic switching of variant surface glycoprotein (VSG) genes. The active VSG is transcribed from only 1 of the 15 subtelomeric expression sites (ESs). During differentiation from BSF to the insect-resident procyclic form (PCF), the active ES is transcriptionally silenced. We used mass spectrometry-based interactomics to determine the composition of telomere protein complexes in T. brucei BSF and PCF stages to learn more about the structure and functions of telomeres in trypanosomes. Our data suggest a different telomere complex composition in the two forms of the parasite. One of the novel telomere-associated proteins, TelAP1, forms a complex with telomeric proteins TbTRF, TbRAP1 and TbTIF2 and influences ES silencing kinetics during developmental differentiation.}, language = {en} } @article{BeckYuStrzelczykPaulsetal.2018, author = {Beck, Sebastian and Yu-Strzelczyk, Jing and Pauls, Dennis and Constantin, Oana M. and Gee, Christine E. and Ehmann, Nadine and Kittel, Robert J. and Nagel, Georg and Gao, Shiqiang}, title = {Synthetic light-activated ion channels for optogenetic activation and inhibition}, series = {Frontiers in Neuroscience}, volume = {12}, journal = {Frontiers in Neuroscience}, number = {643}, doi = {10.3389/fnins.2018.00643}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177520}, year = {2018}, abstract = {Optogenetic manipulation of cells or living organisms became widely used in neuroscience following the introduction of the light-gated ion channel channelrhodopsin-2 (ChR2). ChR2 is a non-selective cation channel, ideally suited to depolarize and evoke action potentials in neurons. However, its calcium (Ca2\(^{2+}\)) permeability and single channel conductance are low and for some applications longer-lasting increases in intracellular Ca\(^{2+}\) might be desirable. Moreover, there is need for an efficient light-gated potassium (K\(^{+}\)) channel that can rapidly inhibit spiking in targeted neurons. Considering the importance of Ca\(^{2+}\) and K\(^{+}\) in cell physiology, light-activated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels would be welcome additions to the optogenetic toolbox. Here we describe the engineering of novel light-gated Ca\(^{2+}\)-permeant and K\(^{+}\)-specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high permeability for Ca\(^{2+}\) or for K\(^{+}\), respectively. Optimized fusion constructs showed strong light-gated conductance in Xenopus laevis oocytes and in rat hippocampal neurons. These constructs could also be used to control the motility of Drosophila melanogaster larvae, when expressed in motoneurons. Illumination led to body contraction when motoneurons expressed the light-sensitive Ca\(^{2+}\)-permeant channel, and to body extension when expressing the light-sensitive K\(^{+}\) channel, both effectively and reversibly paralyzing the larvae. Further optimization of these constructs will be required for application in adult flies since both constructs led to eclosion failure when expressed in motoneurons.}, language = {en} } @article{RangerBiedermannPhuntumartetal.2018, author = {Ranger, Christopher M. and Biedermann, Peter HW and Phuntumart, Vipaporn and Beligala, Gayathri U. and Ghosh, Satyaki and Palmquist, Debra E. and Mueller, Robert and Barnett, Jenny and Schultz, Peter B. and Reding, Michael E. and Benz, J. Philipp}, title = {Symbiont selection via alcohol benefits fungus farming by ambrosia beetles}, series = {Proceedings of the National Academy of Sciences}, volume = {115}, journal = {Proceedings of the National Academy of Sciences}, number = {17}, doi = {10.1073/pnas.1716852115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224953}, pages = {4447-4452}, year = {2018}, abstract = {Animal-microbe mutualisms are typically maintained by vertical symbiont transmission or partner choice. A third mechanism, screening of high-quality symbionts, has been predicted in theory, but empirical examples are rare. Here we demonstrate that ambrosia beetles rely on ethanol within host trees for promoting gardens of their fungal symbiont and producing offspring. Ethanol has long been known as the main attractant for many of these fungus-farming beetles as they select host trees in which they excavate tunnels and cultivate fungal gardens. More than 300 attacks by Xylosandrus germanus and other species were triggered by baiting trees with ethanol lures, but none of the foundresses established fungal gardens or produced broods unless tree tissues contained in vivo ethanol resulting from irrigation with ethanol solutions. More X. germanus brood were also produced in a rearing substrate containing ethanol. These benefits are a result of increased food supply via the positive effects of ethanol on food-fungus biomass. Selected Ambrosiella and Raffaelea fungal isolates from ethanol-responsive ambrosia beetles profited directly and indirectly by (i) a higher biomass on medium containing ethanol, (ii) strong alcohol dehydrogenase enzymatic activity, and (iii) a competitive advantage over weedy fungal garden competitors (Aspergillus, Penicillium) that are inhibited by ethanol. As ambrosia fungi both detoxify and produce ethanol, they may maintain the selectivity of their alcohol-rich habitat for their own purpose and that of other ethanol-resistant/producing microbes. This resembles biological screening of beneficial symbionts and a potentially widespread, unstudied benefit of alcohol-producing symbionts (e.g., yeasts) in other microbial symbioses.}, language = {en} } @article{RibitschPehamAdeetal.2018, author = {Ribitsch, Iris and Peham, Christian and Ade, Nicole and Duerr, Julia and Handschuh, Stephan and Schramel, Johannes Peter and Vogl, Claus and Walles, Heike and Egerbacher, Monika and Jenner, Florian}, title = {Structure-Function relationships of equine menisci}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0194052}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225214}, pages = {e0194052, 1-17}, year = {2018}, abstract = {Meniscal pathologies are among the most common injuries of the femorotibial joint in both human and equine patients. Pathological forces and ensuing injuries of the cranial horn of the equine medial meniscus are considered analogous to those observed in the human posterior medial horn. Biomechanical properties of human menisci are site-and depth-specific. However, the influence of equine meniscus topography and composition on its biomechanical properties is yet unknown. A better understanding of equine meniscus composition and biomechanics could advance not only veterinary therapies for meniscus degeneration or injuries, but also further substantiate the horse as suitable translational animal model for (human) meniscus tissue engineering. Therefore, the aim of this study was to investigate the composition and structure of the equine knee meniscus in a site-and age-specific manner and their relationship with potential site-specific biomechanical properties. The meniscus architecture was investigated histologically. Biomechanical testing included evaluation of the shore hardness (SH), stiffness and energy loss of the menisci. The SH was found to be subjected to both age and site-specific changes, with an overall higher SH of the tibial meniscus surface and increase in SH with age. Stiffness and energy loss showed neither site nor age related significant differences. The macroscopic and histologic similarities between equine and human menisci described in this study, support continued research in this field.}, language = {en} } @article{SchartlSchoriesWatamatsuetal.2018, author = {Schartl, Manfred and Schories, Susanne and Watamatsu, Yuko and Nagao, Yusuke and Hashimoto, Hisashi and Bertin, Chlo{\´e} and Mourot, Brigitte and Schmidt, Cornelia and Wilhelm, Dagmar and Centanin, Lazaro and Guiguen, Yann and Herpin, Amaury}, title = {Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements}, series = {BMC Biology}, volume = {16}, journal = {BMC Biology}, number = {16}, doi = {10.1186/s12915-018-0485-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175827}, year = {2018}, abstract = {Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination. Results: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal. Conclusions: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.}, language = {en} } @article{KaluzaWallaceHeardetal.2018, author = {Kaluza, Benjamin F. and Wallace, Helen M. and Heard, Tim A. and Minden, Vanessa and Klein, Alexandra and Leonhardt, Sara D.}, title = {Social bees are fitter in more biodiverse environments}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {12353}, doi = {10.1038/s41598-018-30126-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177231}, year = {2018}, abstract = {Bee population declines are often linked to human impacts, especially habitat and biodiversity loss, but empirical evidence is lacking. To clarify the link between biodiversity loss and bee decline, we examined how floral diversity affects (reproductive) fitness and population growth of a social stingless bee. For the first time, we related available resource diversity and abundance to resource (quality and quantity) intake and colony reproduction, over more than two years. Our results reveal plant diversity as key driver of bee fitness. Social bee colonies were fitter and their populations grew faster in more florally diverse environments due to a continuous supply of food resources. Colonies responded to high plant diversity with increased resource intake and colony food stores. Our findings thus point to biodiversity loss as main reason for the observed bee decline.}, language = {en} } @article{CoelhoKultimaCosteaetal.2018, author = {Coelho, Luis Pedro and Kultima, Jens Roat and Costea, Paul Igor and Fournier, Coralie and Pan, Yuanlong and Czarnecki-Maulden, Gail and Hayward, Matthew Robert and Forslund, Sofia K. and Schmidt, Thomas Sebastian Benedikt and Descombes, Patrick and Jackson, Janet R. and Li, Qinghong and Bork, Peer}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet}, series = {Microbiome}, volume = {6}, journal = {Microbiome}, doi = {10.1186/s40168-018-0450-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223177}, year = {2018}, abstract = {Background Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. Results We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies. Conclusions We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, language = {en} } @article{ScheibBroserConstantinetal.2018, author = {Scheib, Ulrike and Broser, Matthias and Constantin, Oana M. and Yang, Shang and Gao, Shiqiang and Mukherjee, Shatanik and Stehfest, Katja and Nagel, Georg and Gee, Christine E. and Hegemann, Peter}, title = {Rhodopsin-cyclases for photocontrol of cGMP/cAMP and 2.3 {\AA} structure of the adenylyl cyclase domain}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-04428-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228517}, pages = {2046, 1-15}, year = {2018}, abstract = {The cyclic nucleotides cAMP and cGMP are important second messengers that orchestrate fundamental cellular responses. Here, we present the characterization of the rhodopsinguanylyl cyclase from Catenaria anguillulae (CaRhGC), which produces cGMP in response to green light with a light to dark activity ratio > 1000. After light excitation the putative signaling state forms with tau = 31 ms and decays with tau = 570 ms. Mutations (up to 6) within the nucleotide binding site generate rhodopsin-adenylyl cyclases (CaRhACs) of which the double mutated YFP-CaRhAC (E497K/C566D) is the most suitable for rapid cAMP production in neurons. Furthermore, the crystal structure of the ligand-bound AC domain (2.25 angstrom) reveals detailed information about the nucleotide binding mode within this recently discovered class of enzyme rhodopsin. Both YFP-CaRhGC and YFP-CaRhAC are favorable optogenetic tools for non-invasive, cell-selective, and spatio-temporally precise modulation of cAMP/cGMP with light.}, language = {en} } @article{ZielewskaBuettnerHeurichMuelleretal.2018, author = {Zielewska-B{\"u}ttner, Katarzyna and Heurich, Marco and M{\"u}ller, J{\"o}rg and Braunisch, Veronika}, title = {Remotely Sensed Single Tree Data Enable the Determination of Habitat Thresholds for the Three-Toed Woodpecker (Picoides tridactylus)}, series = {Remote Sensing}, volume = {10}, journal = {Remote Sensing}, number = {12}, issn = {2072-4292}, doi = {10.3390/rs10121972}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197565}, year = {2018}, abstract = {Forest biodiversity conservation requires precise, area-wide information on the abundance and distribution of key habitat structures at multiple spatial scales. We combined airborne laser scanning (ALS) data with color-infrared (CIR) aerial imagery for identifying individual tree characteristics and quantifying multi-scale habitat requirements using the example of the three-toed woodpecker (Picoides tridactylus) (TTW) in the Bavarian Forest National Park (Germany). This bird, a keystone species of boreal and mountainous forests, is highly reliant on bark beetles dwelling in dead or dying trees. While previous studies showed a positive relationship between the TTW presence and the amount of deadwood as a limiting resource, we hypothesized a unimodal response with a negative effect of very high deadwood amounts and tested for effects of substrate quality. Based on 104 woodpecker presence or absence locations, habitat selection was modelled at four spatial scales reflecting different woodpecker home range sizes. The abundance of standing dead trees was the most important predictor, with an increase in the probability of TTW occurrence up to a threshold of 44-50 dead trees per hectare, followed by a decrease in the probability of occurrence. A positive relationship with the deadwood crown size indicated the importance of fresh deadwood. Remote sensing data allowed both an area-wide prediction of species occurrence and the derivation of ecological threshold values for deadwood quality and quantity for more informed conservation management.}, language = {en} } @article{AnelliOrdasKneitzetal.2018, author = {Anelli, Viviana and Ordas, Anita and Kneitz, Susanne and Sagredo, Leonel Munoz and Gourain, Victor and Schartl, Manfred and Meijer, Annemarie H. and Mione, Marina}, title = {Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression}, series = {Frontiers in Genetics}, volume = {9}, journal = {Frontiers in Genetics}, number = {675}, issn = {1664-8021}, doi = {10.3389/fgene.2018.00675}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196963}, year = {2018}, abstract = {Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression. The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc\&acc=GSE37015.}, language = {en} } @article{AdamDeimelPardoMedinaetal.2018, author = {Adam, Alexander and Deimel, Stephan and Pardo-Medina, Javier and Garc{\´i}a-Mart{\´i}nez, Jorge and Konte, Tilen and Lim{\´o}n, M. Carmen and Avalos, Javier and Terpitz, Ulrich}, title = {Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus-plant interaction}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms19010215}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285125}, year = {2018}, abstract = {Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus.}, language = {en} } @article{AlbrechtClassenVollstaedtetal.2018, author = {Albrecht, J{\"o}rg and Classen, Alice and Vollst{\"a}dt, Maximilian G.R. and Mayr, Antonia and Mollel, Neduvoto P. and Schellenberger Costa, David and Dulle, Hamadi I. and Fischer, Markus and Hemp, Andreas and Howell, Kim M. and Kleyer, Michael and Nauss, Thomas and Peters, Marcell K. and Tschapka, Marco and Steffan-Dewenter, Ingolf and B{\"o}hning-Gaese, Katrin and Schleuning, Matthias}, title = {Plant and animal functional diversity drive mutualistic network assembly across an elevational gradient}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-05610-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221056}, pages = {1-10}, year = {2018}, abstract = {Species' functional traits set the blueprint for pair-wise interactions in ecological networks. Yet, it is unknown to what extent the functional diversity of plant and animal communities controls network assembly along environmental gradients in real-world ecosystems. Here we address this question with a unique dataset of mutualistic bird-fruit, bird-flower and insect-flower interaction networks and associated functional traits of 200 plant and 282 animal species sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show that plant functional diversity is mainly limited by precipitation, while animal functional diversity is primarily limited by temperature. Furthermore, shifts in plant and animal functional diversity along the elevational gradient control the niche breadth and partitioning of the respective other trophic level. These findings reveal that climatic constraints on the functional diversity of either plants or animals determine the relative importance of bottom-up and top-down control in plant-animal interaction networks.}, language = {en} } @article{PrustyChowdhuryGulveetal.2018, author = {Prusty, Bhupesh K. and Chowdhury, Suvagata R. and Gulve, Nitish and Rudel, Thomas}, title = {Peptidase Inhibitor 15 (PI15) Regulates Chlamydial CPAF Activity}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {8}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {183}, issn = {2235-2988}, doi = {10.3389/fcimb.2018.00183}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196918}, year = {2018}, abstract = {Obligate intracellular pathogenic Chlamydia trachomatis express several serine proteases whose roles in chlamydial development and pathogenicity are not completely understood. The chlamydial protease CPAF is expressed during the replicative phase of the chlamydial developmental cycle and is secreted into the lumen of the Chlamydia-containing vacuole called inclusion. How the secreted protease is activated in the inclusion lumen is currently not fully understood. We have identified human serine peptidase inhibitor PI15 as a potential host factor involved in the regulation of CPAF activation. Silencing expression as well as over expression of PI15 affected normal development of Chlamydia. PI15 was transported into the chlamydial inclusion lumen where it co-localized with CPAF aggregates. We show that PI15 binds to the CPAF zymogen and potentially induces CPAF protease activity at low concentrations. However, at high concentrations PI15 inhibits CPAF activity possibly by blocking its protease domain. Our findings shed light on a new aspect of chlamydial host co-evolution which involves the recruitment of host cell proteins into the inclusion to control the activation of bacterial proteases like CPAF that are important for the normal development of Chlamydia.}, language = {en} } @article{SchenkMitesserHovestadtetal.2018, author = {Schenk, Mariela and Mitesser, Oliver and Hovestadt, Thomas and Holzschuh, Andrea}, title = {Overwintering temperature and body condition shift emergence dates of spring-emerging solitary bees}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, doi = {10.7717/peerj.4721}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228544}, pages = {e4721, 1-17}, year = {2018}, abstract = {Solitary bees in seasonal environments must align their life-cycles with favorable environmental conditions and resources; the timing of their emergence is highly fitness relevant. In several bee species, overwintering temperature influences both emergence date and body weight at emergence. High variability in emergence dates among specimens overwintering at the same temperatures suggests that the timing of emergence also depends on individual body conditions. However, possible causes for this variability, such as individual differences in body size or weight, have been rarely studied. In a climate chamber experiment using two spring-emerging mason bees (Osmia cornuta and O. bicornis), we investigated the relationship between temperature, emergence date, body weight, and body size, the last of which is not affected by overwintering temperature. Our study showed that body weight declined during hibernation more strongly in warm than in cold overwintering temperatures. Although bees emerged earlier in warm than in cold overwintering temperatures, at the time of emergence, bees in warm overwintering temperatures had lower body weights than bees in cold overwintering temperatures (exception of male O. cornuta). Among specimens that experienced the same overwintering temperatures, small and light bees emerged later than their larger and heavier conspecifics. Using a simple mechanistic model we demonstrated that spring-emerging solitary bees use a strategic approach and emerge at a date that is most promising for their individual fitness expectations. Our results suggest that warmer overwintering temperatures reduce bee fitness by causing a decrease in body weight at emergence. We showed furthermore that in order to adjust their emergence dates, bees use not only temperature but also their individual body condition as triggers. This may explain differing responses to climate warming within and among bee populations and may have consequences for bee-plant interactions as well as for the persistence of bee populations under climate change.}, language = {en} } @article{LichtensteinGruebelSpaethe2018, author = {Lichtenstein, Leonie and Gr{\"u}bel, Kornelia and Spaethe, Johannes}, title = {Opsin expression patterns coincide with photoreceptor development during pupal development in the honey bee, Apis mellifera}, series = {BMC Developmental Biology}, volume = {18}, journal = {BMC Developmental Biology}, number = {1}, doi = {10.1186/s12861-018-0162-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175665}, year = {2018}, abstract = {Background: The compound eyes of insects allow them to catch photons and convert the energy into electric signals. All compound eyes consist of numerous ommatidia, each comprising a fixed number of photoreceptors. Different ommatidial types are characterized by a specific set of photoreceptors differing in spectral sensitivity. In honey bees, males and females possess different ommatidial types forming distinct retinal mosaics. However, data are lacking on retinal ontogeny and the mechanisms by which the eyes are patterned. In this study, we investigated the intrinsic temporal and circadian expression patterns of the opsins that give rise to the ultraviolet, blue and green sensitive photoreceptors, as well as the morphological maturation of the retina during pupal development of honey bees. Results: qPCR and histological labeling revealed that temporal opsin mRNA expression differs between sexes and correlates with rhabdom elongation during photoreceptor development. In the first half of the pupal stage, when the rhabdoms of the photoreceptors are still short, worker and (dorsal) drone retinae exhibit similar expression patterns with relatively high levels of UV (UVop) and only marginal levels of blue (BLop) and green (Lop1) opsin mRNA. In the second half of pupation, when photoreceptors and rhabdoms elongate, opsin expression in workers becomes dominated by Lop1 mRNA. In contrast, the dorsal drone eye shows high expression levels of UVop and BLop mRNA, whereas Lop1 mRNA level decreases. Interestingly, opsin expression levels increase up to 22-fold during early adult life. We also found evidence that opsin expression in adult bees is under the control of the endogenous clock. Conclusions: Our data indicate that the formation of the sex-specific retinal composition of photoreceptors takes place during the second half of the pupal development, and that opsin mRNA expression levels continue to increase in young bees, which stands in contrast to Drosophila, where the highest expression levels are found during the late pupal stage and remain constant in adults. From an evolutionary perspective, we hypothesize that the delayed retinal maturation during the early adult phase is linked to the delayed transition from indoor to outdoor activities in bees, when vision becomes important.}, language = {en} } @article{PelzWagnerLichthardtetal.2018, author = {Pelz, J{\"o}rg O. W. and Wagner, Johanna and Lichthardt, Sven and Baur, Johannes and Kastner, Caroline and Matthes, Niels and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Laparoscopic right-sided colon resection for colon cancer - has the control group so far been chosen correctly?}, series = {World Journal of Surgical Oncology}, volume = {16}, journal = {World Journal of Surgical Oncology}, number = {117}, doi = {10.1186/s12957-018-1417-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176186}, year = {2018}, abstract = {Background: The treatment strategies for colorectal cancer located in the right side of the colon have changed dramatically during the last decade. Due to the introduction of complete mesocolic excision (CME) with central ligation of the vessels and systematic lymph node dissection, the long-term survival of affected patients has increased significantly. It has also been proposed that right-sided colon resection can be performed laparoscopically with the same extent of resection and equal long-term results. Methods: A retrospective evaluation of a prospectively expanded database on right-sided colorectal cancer or adenoma treated at the University Hospital of Wuerzburg between 2009 and 2016 was performed. All patients underwent CME. This data was analyzed alone and in comparison to the published data describing laparoscopic right-sided colon resection for colon cancer. Results: The database contains 279 patients, who underwent right-sided colon resection due to colorectal cancer or colorectal adenoma (255 open; 24 laparoscopic). Operation data (time, length of stay, time on ICU) was equal or superior to laparoscopy, which is comparable to the published results. Surprisingly, the surrogate parameter for correct CME (the number of removed lymph nodes) was significantly higher in the open group. In a subgroup analysis only including patients who were feasible for laparoscopic resection and had been operated with an open procedure by an experienced surgeon, operation time was significantly shorter and the number of removed lymph nodes is significantly higher in the open group. Conclusion: So far, several studies demonstrate that laparoscopic right-sided colon resection is comparable to open resection. Our data suggests that a consequent CME during an open operation leads to significantly more removed lymph nodes than in laparoscopically resected patients and in several so far published data of open control groups from Europe. Further prospective randomized trials comparing the long-term outcome are urgently needed before laparoscopy for right-sided colon resection can be recommended ubiquitously.}, language = {en} } @article{RedlichMartinWendeetal.2018, author = {Redlich, Sarah and Martin, Emily A. and Wende, Beate and Steffan-Dewenter, Ingolf}, title = {Landscape heterogeneity rather than crop diversity mediates bird diversity in agricultural landscapes}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0200438}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177110}, pages = {e0200438}, year = {2018}, abstract = {Crop diversification has been proposed as farm management tool that could mitigate the externalities of conventional farming while reducing productivity-biodiversity trade-offs. Yet evidence for the acclaimed biodiversity benefits of landscape-level crop diversity is ambiguous. Effects may strongly depend on spatial scale and the level of landscape heterogeneity (e.g. overall habitat diversity). At the same time, contrasting within-taxon responses obscure benefits to specific functional groups (i.e. species with shared characteristics or requirements) if studied at the community level. The objectives of this study were to 1) disentangle the relative effects of crop diversity and landscape heterogeneity on avian species richness across five spatial scales ranging from 250 to 3000 m radii around focal winter wheat fields; and 2) assess whether functional groups (feeding guild, conservation status, habitat preference, nesting behaviour) determine the strength and direction of responses to crop diversity and landscape heterogeneity. In central Germany, 14 landscapes were selected along independent gradients of crop diversity (annual arable crops) and landscape heterogeneity. Bird species richness in each landscape was estimated using four point counts throughout the breeding season. We found no effects of landscape-level crop diversity on bird richness and functional groups. Instead, landscape heterogeneity was strongly associated with increased total bird richness across all spatial scales. In particular, insect-feeding and non-farmland birds were favoured in heterogeneous landscapes, as were species not classified as endangered or vulnerable on the regional Red List. Crop-nesting farmland birds, however, were less species-rich in these landscapes. Accordingly, crop diversification may be less suitable for conserving avian diversity and associated ecosystem services (e.g. biological pest control), although confounding interactions with management intensity need yet to be confirmed. In contrast, enhancement of landscape heterogeneity by increasing perennial habitat diversity, reducing field sizes and the amount of cropland has the potential to benefit overall bird richness. Specialist farmland birds, however, may require more targeted management approaches.}, language = {en} } @article{KoenigGuerreiroPeršohetal.2018, author = {K{\"o}nig, Julia and Guerreiro, Marco Alexandre and Peršoh, Derek and Begerow, Dominik and Krauss, Jochen}, title = {Knowing your neighbourhood - the effects of Epichlo{\"e} endophytes on foliar fungal assemblages in perennial ryegrass in dependence of season and land-use intensity}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e4660}, doi = {10.7717/peerj.4660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176814}, year = {2018}, abstract = {Epichlo{\"e} endophytes associated with cool-season grass species can protect their hosts from herbivory and can suppress mycorrhizal colonization of the hosts' roots. However, little is known about whether or not Epichlo{\"e} endophyte infection can also change the foliar fungal assemblages of the host. We tested 52 grassland study sites along a land-use intensity gradient in three study regions over two seasons (spring vs. summer) to determine whether Epichlo{\"e} infection of the host grass Lolium perenne changes the fungal community structure in leaves. Foliar fungal communities were assessed by Next Generation Sequencing of the ITS rRNA gene region. Fungal community structure was strongly affected by study region and season in our study, while land-use intensity and infection with Epichlo{\"e} endophytes had no significant effects. We conclude that effects on non-systemic endophytes resulting from land use practices and Epichlo{\"e} infection reported in other studies were masked by local and seasonal variability in this study's grassland sites.}, language = {en} } @article{BoetzlRiesSchneideretal.2018, author = {Boetzl, Fabian A. and Ries, Elena and Schneider, Gudrun and Krauss, Jochen}, title = {It's a matter of design - how pitfall trap design affects trap samples and possible predictions}, series = {PeerJ}, volume = {6}, journal = {PeerJ}, number = {e5078}, doi = {10.7717/peerj.5078}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176870}, year = {2018}, abstract = {Background: Pitfall traps are commonly used to assess ground dwelling arthropod communities. The effects of different pitfall trap designs on the trapping outcome are poorly investigated however they might affect conclusions drawn from pitfall trap data greatly. Methods: We tested four pitfall trap types which have been used in previous studies for their effectiveness: a simple type, a faster exchangeable type with an extended plastic rim plate and two types with guidance barriers (V- and X-shaped). About 20 traps were active for 10 weeks and emptied biweekly resulting in 100 trap samples. Results: Pitfall traps with guidance barriers were up to five times more effective than simple pitfall traps and trap samples resulted in more similar assemblage approximations. Pitfall traps with extended plastic rim plates did not only perform poorly but also resulted in distinct carabid assemblages with less individuals of small species and a larger variation. Discussion: Due to the obvious trait filtering and resulting altered assemblages, we suggest not to use pitfall traps with extended plastic rim plates. In comprehensive biodiversity inventories, a smaller number of pitfall traps with guidance barriers and a larger number of spatial replicates is of advantage, while due to comparability reasons, the use of simple pitfall traps will be recommended in most other cases.}, language = {en} } @article{MallLarsenMartin2018, author = {Mall, David and Larsen, Ashley E. and Martin, Emily A.}, title = {Investigating the (mis)match between natural pest control knowledge and the intensity of pesticide use}, series = {Insects}, volume = {9}, journal = {Insects}, number = {1}, doi = {10.3390/insects9010002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158977}, pages = {2}, year = {2018}, abstract = {Transforming modern agriculture towards both higher yields and greater sustainability is critical for preserving biodiversity in an increasingly populous and variable world. However, the intensity of agricultural practices varies strongly between crop systems. Given limited research capacity, it is crucial to focus efforts to increase sustainability in the crop systems that need it most. In this study, we investigate the match (or mismatch) between the intensity of pesticide use and the availability of knowledge on the ecosystem service of natural pest control across various crop systems. Using a systematic literature search on pest control and publicly available pesticide data, we find that pest control literature is not more abundant in crops where insecticide input per hectare is highest. Instead, pest control literature is most abundant, with the highest number of studies published, in crops with comparatively low insecticide input per hectare but with high world harvested area. These results suggest that a major increase of interest in agroecological research towards crops with high insecticide input, particularly cotton and horticultural crops such as citrus and high value-added vegetables, would help meet knowledge needs for a timely ecointensification of agriculture.}, language = {en} } @article{NadellaMohantySharmaetal.2018, author = {Nadella, Vinod and Mohanty, Aparna and Sharma, Lalita and Yellaboina, Sailu and Mollenkopf, Hans-Joachim and Mazumdar, Varadendra Balaji and Palaparthi, Ramesh and Mylavarapu, Madhavi B. and Maurya, Radheshyam and Kurukuti, Sreenivasulu and Rudel, Thomas and Prakash, Hridayesh}, title = {Inhibitors of Apoptosis Protein Antagonists (Smac Mimetic Compounds) Control Polarization of Macrophages during Microbial Challenge and Sterile Inflammatory Responses}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {1792}, issn = {1664-3224}, doi = {10.3389/fimmu.2017.01792}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197484}, year = {2018}, abstract = {Apoptosis is a physiological cell death process essential for development, tissue homeostasis, and for immune defense of multicellular animals. Inhibitors of apoptosis proteins (IAPs) regulate apoptosis in response to various cellular assaults. Using both genetic and pharmacological approaches we demonstrate here that the IAPs not only support opportunistic survival of intracellular human pathogens like Chlamydia pneumoniae but also control plasticity of iNOS+ M1 macrophage during the course of infection and render them refractory for immune stimulation. Treatment of Th1 primed macrophages with birinapant (IAP-specific antagonist) inhibited NO generation and relevant proteins involved in innate immune signaling. Accordingly, birinapant promoted hypoxia, angiogenesis, and tumor-induced M2 polarization of iNOS+ M1 macrophages. Interestingly, birinapant-driven changes in immune signaling were accompanied with changes in the expression of various proteins involved in the metabolism, and thus revealing the new role of IAPs in immune metabolic reprogramming in committed macrophages. Taken together, our study reveals the significance of IAP targeting approaches (Smac mimetic compounds) for the management of infectious and inflammatory diseases relying on macrophage plasticity.}, language = {en} } @article{KropfRoessler2018, author = {Kropf, Jan and R{\"o}ssler, Wolfgang}, title = {In-situ recording of ionic currents in projection neurons and Kenyon cells in the olfactory pathway of the honeybee}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0191425}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175869}, pages = {e0191425}, year = {2018}, abstract = {The honeybee olfactory pathway comprises an intriguing pattern of convergence and divergence: ~60.000 olfactory sensory neurons (OSN) convey olfactory information on ~900 projection neurons (PN) in the antennal lobe (AL). To transmit this information reliably, PNs employ relatively high spiking frequencies with complex patterns. PNs project via a dual olfactory pathway to the mushroom bodies (MB). This pathway comprises the medial (m-ALT) and the lateral antennal lobe tract (l-ALT). PNs from both tracts transmit information from a wide range of similar odors, but with distinct differences in coding properties. In the MBs, PNs form synapses with many Kenyon cells (KC) that encode odors in a spatially and temporally sparse way. The transformation from complex information coding to sparse coding is a well-known phenomenon in insect olfactory coding. Intrinsic neuronal properties as well as GABAergic inhibition are thought to contribute to this change in odor representation. In the present study, we identified intrinsic neuronal properties promoting coding differences between PNs and KCs using in-situ patch-clamp recordings in the intact brain. We found very prominent K+ currents in KCs clearly differing from the PN currents. This suggests that odor coding differences between PNs and KCs may be caused by differences in their specific ion channel properties. Comparison of ionic currents of m- and l-ALT PNs did not reveal any differences at a qualitative level.}, language = {en} } @article{SarukhanyanShityakovDandekar2018, author = {Sarukhanyan, Edita and Shityakov, Sergey and Dandekar, Thomas}, title = {In silico designed Axl receptor blocking drug candidates against Zika virus infection}, series = {ACS Omega}, volume = {3}, journal = {ACS Omega}, number = {5}, doi = {10.1021/acsomega.8b00223}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176739}, pages = {5281-5290}, year = {2018}, abstract = {After a large outbreak in Brazil, novel drugs against Zika virus became extremely necessary. Evaluation of virus-based pharmacological strategies concerning essential host factors brought us to the idea that targeting the Axl receptor by blocking its dimerization function could be critical for virus entry. Starting from experimentally validated compounds, such as RU-301, RU-302, warfarin, and R428, we identified a novel compound 2′ (R428 derivative) to be the most potent for this task amongst a number of alternative compounds and leads. The improved affinity of compound 2′ was confirmed by molecular docking as well as molecular dynamics simulation techniques using implicit solvation models. The current study summarizes a new possibility for inhibition of the Axl function as a potential target for future antiviral therapies.}, language = {en} } @article{BencurovaGuptaSarukhanyanetal.2018, author = {Bencurova, Elena and Gupta, Shishir K. and Sarukhanyan, Edita and Dandekar, Thomas}, title = {Identification of antifungal targets based on computer modeling}, series = {Journal of Fungi}, volume = {4}, journal = {Journal of Fungi}, number = {3}, issn = {2309-608X}, doi = {10.3390/jof4030081}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197670}, pages = {81}, year = {2018}, abstract = {Aspergillus fumigatus is a saprophytic, cosmopolitan fungus that attacks patients with a weak immune system. A rational solution against fungal infection aims to manipulate fungal metabolism or to block enzymes essential for Aspergillus survival. Here we discuss and compare different bioinformatics approaches to analyze possible targeting strategies on fungal-unique pathways. For instance, phylogenetic analysis reveals fungal targets, while domain analysis allows us to spot minor differences in protein composition between the host and fungi. Moreover, protein networks between host and fungi can be systematically compared by looking at orthologs and exploiting information from host-pathogen interaction databases. Further data—such as knowledge of a three-dimensional structure, gene expression data, or information from calculated metabolic fluxes—refine the search and rapidly put a focus on the best targets for antimycotics. We analyzed several of the best targets for application to structure-based drug design. Finally, we discuss general advantages and limitations in identification of unique fungal pathways and protein targets when applying bioinformatics tools.}, language = {en} } @article{BrunkSputhDooseetal.2018, author = {Brunk, Michael and Sputh, Sebastian and Doose, S{\"o}ren and van de Linde, Sebastian and Terpitz, Ulrich}, title = {HyphaTracker: An ImageJ toolbox for time-resolved analysis of spore germination in filamentous fungi}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-19103-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221691}, year = {2018}, abstract = {The dynamics of early fungal development and its interference with physiological signals and environmental factors is yet poorly understood. Especially computational analysis tools for the evaluation of the process of early spore germination and germ tube formation are still lacking. For the time-resolved analysis of conidia germination of the filamentous ascomycete Fusarium fujikuroi we developed a straightforward toolbox implemented in ImageJ. It allows for processing of microscopic acquisitions (movies) of conidial germination starting with drift correction and data reduction prior to germling analysis. From the image time series germling related region of interests (ROIs) are extracted, which are analysed for their area, circularity, and timing. ROIs originating from germlings crossing other hyphae or the image boundaries are omitted during analysis. Each conidium/hypha is identified and related to its origin, thus allowing subsequent categorization. The efficiency of HyphaTracker was proofed and the accuracy was tested on simulated germlings at different signal-to-noise ratios. Bright-field microscopic images of conidial germination of rhodopsin-deficient F. fujikuroi mutants and their respective control strains were analysed with HyphaTracker. Consistent with our observation in earlier studies the CarO deficient mutant germinated earlier and grew faster than other, CarO expressing strains.}, language = {en} } @article{HesselbachScheiner2018, author = {Hesselbach, Hannah and Scheiner, Ricarda}, title = {Effects of the novel pesticide flupyradifurone (Sivanto) on honeybee taste and cognition}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {4954}, doi = {10.1038/s41598-018-23200-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175853}, year = {2018}, abstract = {Due to intensive agriculture honeybees are threatened by various pesticides. The use of one group of them, the neonicotinoids, was recently restricted by the European Union. These chemicals bind to the nicotinic acetylcholine receptor (nAchR) in the honeybee brain. Recently, Bayer AG released a new pesticide by the name of "Sivanto" against sucking insects. It is assumed to be harmless for honeybees, although its active ingredient, flupyradifurone, binds nAchR similar to the neonicotinoids. We investigated if this pesticide affects the taste for sugar and cognitive performance in honeybee foragers. These bees are directly exposed to the pesticide while foraging for pollen or nectar. Our results demonstrate that flupyradifurone can reduce taste and appetitive learning performance in honeybees foraging for pollen and nectar, although only the highest concentration had significant effects. Most likely, honeybee foragers will not be exposed to these high concentrations. Therefore, the appropriate use of this pesticide is considered safe for honeybees, at least with respect to the behaviors studied here.}, language = {en} } @article{BeckHovhanyanMenegazzietal.2018, author = {Beck, Katherina and Hovhanyan, Anna and Menegazzi, Pamela and Helfrich-F{\"o}rster, Charlotte and Raabe, Thomas}, title = {Drosophila RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {122}, issn = {1662-5099}, doi = {10.3389/fnmol.2018.00122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196034}, year = {2018}, abstract = {Endogenous molecular circadian clocks drive daily rhythmic changes at the cellular, physiological, and behavioral level for adaptation to and anticipation of environmental signals. The core molecular system consists of autoregulatory feedback loops, where clock proteins inhibit their own transcription. A complex and not fully understood interplay of regulatory proteins influences activity, localization and stability of clock proteins to set the pace of the clock. This study focuses on the molecular function of Ribosomal S6 Kinase (RSK) in the Drosophila melanogaster circadian clock. Mutations in the human rsk2 gene cause Coffin-Lowry syndrome, which is associated with severe mental disabilities. Knock-out studies with Drosophila ortholog rsk uncovered functions in synaptic processes, axonal transport and adult behavior including associative learning and circadian activity. However, the molecular targets of RSK remain elusive. Our experiments provide evidence that RSK acts in the key pace maker neurons as a negative regulator of Shaggy (SGG) kinase activity, which in turn determines timely nuclear entry of the clock proteins Period and Timeless to close the negative feedback loop. Phosphorylation of serine 9 in SGG is mediated by the C-terminal kinase domain of RSK, which is in agreement with previous genetic studies of RSK in the circadian clock but argues against the prevailing view that only the N-terminal kinase domain of RSK proteins carries the effector function. Our data provide a mechanistic explanation how RSK influences the molecular clock and imply SGG S9 phosphorylation by RSK and other kinases as a convergence point for diverse cellular and external stimuli.}, language = {en} } @article{YankuBitmanLotanZoharetal.2018, author = {Yanku, Yifat and Bitman-Lotan, Eliya and Zohar, Yaniv and Kurant, Estee and Zilke, Norman and Eilers, Martin and Orian, Amir}, title = {Drosophila HUWE1 ubiquitin ligase regulates endoreplication and antagonizes JNK signaling during salivary gland development}, series = {Cells}, volume = {7}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells7100151}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197630}, pages = {151}, year = {2018}, abstract = {The HECT-type ubiquitin ligase HECT, UBA and WWE Domain Containing 1, (HUWE1) regulates key cancer-related pathways, including the Myc oncogene. It affects cell proliferation, stress and immune signaling, mitochondria homeostasis, and cell death. HUWE1 is evolutionarily conserved from Caenorhabditis elegance to Drosophila melanogaster and Humans. Here, we report that the Drosophila ortholog, dHUWE1 (CG8184), is an essential gene whose loss results in embryonic lethality and whose tissue-specific disruption establishes its regulatory role in larval salivary gland development. dHUWE1 is essential for endoreplication of salivary gland cells and its knockdown results in the inability of these cells to replicate DNA. Remarkably, dHUWE1 is a survival factor that prevents premature activation of JNK signaling, thus preventing the disintegration of the salivary gland, which occurs physiologically during pupal stages. This function of dHUWE1 is general, as its inhibitory effect is observed also during eye development and at the organismal level. Epistatic studies revealed that the loss of dHUWE1 is compensated by dMyc proeitn expression or the loss of dmP53. dHUWE1 is therefore a conserved survival factor that regulates organ formation during Drosophila development.}, language = {en} } @article{RuedenauerWoehrleSpaetheetal.2018, author = {Ruedenauer, Fabian A. and W{\"o}hrle, Christine and Spaethe, Johannes and Leonhardt, Sara D.}, title = {Do honeybees (Apis mellifera) differentiate between different pollen types?}, series = {PLoS ONE}, volume = {13}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0205821}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177537}, pages = {e0205821}, year = {2018}, abstract = {Bees receive nectar and pollen as reward for pollinating plants. Pollen of different plant species varies widely in nutritional composition. In order to select pollen of appropriate nutritional quality, bees would benefit if they could distinguish different pollen types. Whether they rely on visual, olfactory and/or chemotactile cues to distinguish between different pollen types, has however been little studied. In this study, we examined whether and how Apis mellifera workers differentiate between almond and apple pollen. We used differential proboscis extension response conditioning with olfactory and chemotactile stimulation, in light and darkness, and in summer and winter bees. We found that honeybees were only able to differentiate between different pollen types, when they could use both chemotactile and olfactory cues. Visual cues further improved learning performance. Summer bees learned faster than winter bees. Our results thus highlight the importance of multisensory information for pollen discrimination.}, language = {en} } @article{BuellesbachVetterSchmitt2018, author = {Buellesbach, Jan and Vetter, Sebastian G. and Schmitt, Thomas}, title = {Differences in the reliance on cuticular hydrocarbons as sexual signaling and species discrimination cues in parasitoid wasps}, series = {Frontiers in Zoology}, volume = {15}, journal = {Frontiers in Zoology}, doi = {10.1186/s12983-018-0263-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221702}, year = {2018}, abstract = {Background Cuticular hydrocarbons (CHC) have been documented to play crucial roles as species- and sex-specific cues in the chemical communication systems of a wide variety of insects. However, whether they are sufficient by themselves as the sole cue triggering sexual behavior as well as preference of con- over heterospecific mating partners is rarely assessed. We conducted behavioral assays in three representative species of parasitoid wasps (Hymenoptera: Pteromalidae) to determine their reliance on CHC as species-specific sexual signaling cues. Results We found a surprising degree of either unspecific or insufficient sexual signaling when CHC are singled out as recognition cues. Most strikingly, the cosmopolitan species Nasonia vitripennis, expected to experience enhanced selection pressure to discriminate against other co-occurring parasitoids, did not discriminate against CHC of a partially sympatric species from another genus, Trichomalopsis sarcophagae. Focusing on the latter species, in turn, it became apparent that CHC are even insufficient as the sole cue triggering conspecific sexual behavior, hinting at the requirement of additional, synergistic sexual cues particularly important in this species. Finally, in the phylogenetically and chemically most divergent species Muscidifurax uniraptor, we intriguingly found both CHC-based sexual signaling as well as species discrimination behavior intact although this species is naturally parthenogenetic with sexual reproduction only occurring under laboratory conditions. Conclusions Our findings implicate a discrepancy in the reliance on and specificity of CHC as sexual cues in our tested parasitioid wasps. CHC profiles were not sufficient for unambiguous discrimination and preference behavior, as demonstrated by clear cross-attraction between some of our tested wasp genera. Moreover, we could show that only in T. sarcophagae, additional behavioral cues need to be present for triggering natural mating behavior, hinting at an interesting shift in signaling hierarchy in this particular species. This demonstrates the importance of integrating multiple, potentially complementary signaling modalities in future studies for a better understanding of their individual contributions to natural sexual communication behavior.}, language = {en} } @article{SchenkKraussHolzschuh2018, author = {Schenk, Mariela and Krauss, Jochen and Holzschuh, Andrea}, title = {Desynchronizations in bee-plant interactions cause severe fitness losses in solitary bees}, series = {Journal of Animal Ecology}, volume = {87}, journal = {Journal of Animal Ecology}, number = {1}, doi = {10.1111/1365-2656.12694}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228533}, pages = {139-149}, year = {2018}, abstract = {1. Global warming can disrupt mutualistic interactions between solitary bees and plants when increasing temperature differentially changes the timing of interacting partners. One possible scenario is for insect phenology to advance more rapidly than plant phenology. 2. However, empirical evidence for fitness consequences due to temporal mismatches is lacking for pollinators and it remains unknown if bees have developed strategies to mitigate fitness losses following temporal mismatches. 3. We tested the effect of temporal mismatches on the fitness of three spring-emerging solitary bee species, including one pollen specialist. Using flight cages, we simulated (i) a perfect synchronization (from a bee perspective): bees and flowers occur simultaneously, (ii) a mismatch of 3days and (iii) a mismatch of 6days, with bees occurring earlier than flowers in the latter two cases. 4. A mismatch of 6days caused severe fitness losses in all three bee species, as few bees survived without flowers. Females showed strongly reduced activity and reproductive output compared to synchronized bees. Fitness consequences of a 3-day mismatch were species-specific. Both the early-spring species Osmia cornuta and the mid-spring species Osmia bicornis produced the same number of brood cells after a mismatch of 3days as under perfect synchronization. However, O.cornuta decreased the number of female offspring, whereas O.bicornis spread the brood cells over fewer nests, which may increase offspring mortality, e.g. due to parasitoids. The late-spring specialist Osmia brevicornis produced fewer brood cells even after a mismatch of 3days. Additionally, our results suggest that fitness losses after temporal mismatches are higher during warm than cold springs, as the naturally occurring temperature variability revealed that warm temperatures during starvation decreased the survival rate of O.bicornis. 5. We conclude that short temporal mismatches can cause clear fitness losses in solitary bees. Although our results suggest that bees have evolved species-specific strategies to mitigate fitness losses after temporal mismatches, the bees were not able to completely compensate for impacts on their fitness after temporal mismatches with their food resources.}, subject = {pollination}, language = {en} } @article{ChristopherDUgelvigWiesenhoferetal.2018, author = {Christopher D., Pull and Ugelvig, Line V. and Wiesenhofer, Florian and Anna V., Grasse and Tragust, Simon and Schmitt, Thomas and Brown, Mark JF and Cremer, Sylvia}, title = {Destructive disinfection of infected brood prevents systemic disease spread in ant colonies}, series = {eLIFE}, volume = {7}, journal = {eLIFE}, doi = {10.7554/eLife.32073}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223728}, pages = {e 32073, 1-29}, year = {2018}, abstract = {In social groups, infections have the potential to spread rapidly and cause disease outbreaks. Here, we show that in a social insect, the ant Lasius neglectus, the negative consequences of fungal infections (Metarhizium brunneum) can be mitigated by employing an efficient multicomponent behaviour, termed destructive disinfection, which prevents further spread of the disease through the colony. Ants specifically target infected pupae during the pathogens non-contagious incubation period, utilising chemical 'sickness cues' emitted by pupae. They then remove the pupal cocoon, perforate its cuticle and administer antimicrobial poison, which enters the body and prevents pathogen replication from the inside out. Like the immune system of a metazoan body that specifically targets and eliminates infected cells, ants destroy infected brood to stop the pathogen completing its lifecycle, thus protecting the rest of the colony. Hence, in an analogous fashion, the same principles of disease defence apply at different levels of biological organisation.}, language = {en} } @article{SchlichtingRiegerCusumanoetal.2018, author = {Schlichting, Matthias and Rieger, Dirk and Cusumano, Paola and Grebler, Rudi and Costa, Rodolfo and Mazzotta, Gabriella M. and Helfrich-F{\"o}rster, Charlotte}, title = {Cryptochrome interacts with actin and enhances eye-mediated light sensitivity of the circadian clock in Drosophila melanogaster}, series = {Frontiers in Molecular Neuroscience}, volume = {11}, journal = {Frontiers in Molecular Neuroscience}, number = {238}, doi = {10.3389/fnmol.2018.00238}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177086}, year = {2018}, abstract = {Cryptochromes (CRYs) are a class of flavoproteins that sense blue light. In animals, CRYs are expressed in the eyes and in the clock neurons that control sleep/wake cycles and are implied in the generation and/or entrainment of circadian rhythmicity. Moreover, CRYs are sensing magnetic fields in insects as well as in humans. Here, we show that in the fruit fly Drosophila melanogaster CRY plays a light-independent role as "assembling" protein in the rhabdomeres of the compound eyes. CRY interacts with actin and appears to increase light sensitivity of the eyes by keeping the "signalplex" of the phototransduction cascade close to the membrane. By this way, CRY also enhances light-responses of the circadian clock.}, language = {en} } @article{ZoltnerKrienitzFieldetal.2018, author = {Zoltner, Martin and Krienitz, Nina and Field, Mark C. and Kramer, Susanne}, title = {Comparative proteomics of the two T. brucei PABPs suggests that PABP2 controls bulk mRNA}, series = {PLoS Neglected Tropical Diseases}, volume = {12}, journal = {PLoS Neglected Tropical Diseases}, number = {7}, doi = {10.1371/journal.pntd.0006679}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177126}, pages = {e0006679}, year = {2018}, abstract = {Poly(A)-binding proteins (PABPs) regulate mRNA fate by controlling stability and translation through interactions with both the poly(A) tail and eIF4F complex. Many organisms have several paralogs of PABPs and eIF4F complex components and it is likely that different eIF4F/PABP complex combinations regulate distinct sets of mRNAs. Trypanosomes have five eIF4G paralogs, six of eIF4E and two PABPs, PABP1 and PABP2. Under starvation, polysomes dissociate and the majority of mRNAs, most translation initiation factors and PABP2 reversibly localise to starvation stress granules. To understand this more broadly we identified a protein interaction cohort for both T. brucei PABPs by cryo-mill/affinity purification-mass spectrometry. PABP1 very specifically interacts with the previously identified interactors eIF4E4 and eIF4G3 and few others. In contrast PABP2 is promiscuous, with a larger set of interactors including most translation initiation factors and most prominently eIF4G1, with its two partners TbG1-IP and TbG1-IP2. Only RBP23 was specific to PABP1, whilst 14 RNA-binding proteins were exclusively immunoprecipitated with PABP2. Significantly, PABP1 and associated proteins are largely excluded from starvation stress granules, but PABP2 and most interactors translocate to granules on starvation. We suggest that PABP1 regulates a small subpopulation of mainly small-sized mRNAs, as it interacts with a small and distinct set of proteins unable to enter the dominant pathway into starvation stress granules and localises preferentially to a subfraction of small polysomes. By contrast PABP2 likely regulates bulk mRNA translation, as it interacts with a wide range of proteins, enters stress granules and distributes over the full range of polysomes.}, language = {en} } @article{RasaNoraKrukleHenningetal.2018, author = {Rasa, Santa and Nora-Krukle, Zaiga and Henning, Nina and Eliassen, Eva and Shikova, Evelina and Harrer, Thomas and Scheibenbogen, Carmen and Murovska, Modra and Prusty, Bhupesh K.}, title = {Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)}, series = {Journal of Translational Medicine}, volume = {16}, journal = {Journal of Translational Medicine}, number = {268}, doi = {10.1186/s12967-018-1644-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224960}, pages = {1-25}, year = {2018}, abstract = {Background and main text: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex and controversial clinical condition without having established causative factors. Increasing numbers of cases during past decade have created awareness among patients as well as healthcare professionals. Chronic viral infection as a cause of ME/CFS has long been debated. However, lack of large studies involving well-designed patient groups and validated experimental set ups have hindered our knowledge about this disease. Moreover, recent developments regarding molecular mechanism of pathogenesis of various infectious agents cast doubts over validity of several of the past studies. Conclusions: This review aims to compile all the studies done so far to investigate various viral agents that could be associated with ME/CFS. Furthermore, we suggest strategies to better design future studies on the role of viral infections in ME/CFS.}, language = {en} } @article{ReilingKrohneFriedrichetal.2018, author = {Reiling, Sarah J. and Krohne, Georg and Friedrich, Oliver and Geary, Timothy G. and Rohrbach, Petra}, title = {Chloroquine exposure triggers distinct cellular responses in sensitive versus resistant Plasmodium falciparum parasites}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {11137}, doi = {10.1038/s41598-018-29422-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225123}, pages = {1-11}, year = {2018}, abstract = {Chloroquine (CQ) treatment failure in Plasmodium falciparum parasites has been documented for decades, but the pharmacological explanation of this phenotype is not fully understood. Current concepts attribute CQ resistance to reduced accumulation of the drug at a given external CQ concentration ([CQ] ex) in resistant compared to sensitive parasites. The implication of this explanation is that the mechanisms of CQ-induced toxicity in resistant and sensitive strains are similar once lethal internal concentrations have been reached. To test this hypothesis, we investigated the mechanism of CQ-induced toxicity in CQ-sensitive (CQS) versus CQ-resistant (CQR) parasites by analyzing the time-course of cellular responses in these strains after exposure to varying [CQ] ex as determined in 72 h toxicity assays. Parasite killing was delayed in CQR parasites for up to 10 h compared to CQS parasites when exposed to equipotent [CQ] ex. In striking contrast, brief exposure (1 h) to lethal [CQ] ex in CQS but not CQR parasites caused the appearance of hitherto undescribed hemozoin (Hz)-containing compartments in the parasite cytosol. Hz-containing compartments were very rarely observed in CQR parasites even after CQ exposures sufficient to cause irreversible cell death. These findings challenge current concepts that CQ killing of malaria parasites is solely concentration-dependent, and instead suggest that CQS and CQR strains fundamentally differ in the consequences of CQ exposure.}, language = {en} } @article{GrimmHufnagelWobseretal.2018, author = {Grimm, Johannes and Hufnagel, Anita and Wobser, Marion and Borst, Andreas and Haferkamp, Sebastian and Houben, Roland and Meierjohann, Svenja}, title = {BRAF inhibition causes resilience of melanoma cell lines by inducing the secretion of FGF1}, series = {Oncogenesis}, volume = {7}, journal = {Oncogenesis}, number = {71}, doi = {10.1038/s41389-018-0082-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177261}, year = {2018}, abstract = {Approximately half of all melanoma patients harbour activating mutations in the serine/threonine kinase BRAF. This is the basis for one of the main treatment strategies for this tumor type, the targeted therapy with BRAF and MEK inhibitors. While the initial responsiveness to these drugs is high, resistance develops after several months, frequently at sites of the previously responding tumor. This indicates that tumor response is incomplete and that a certain tumor fraction survives even in drug-sensitive patients, e.g., in a therapy-induced senescence-like state. Here, we show in several melanoma cell lines that BRAF inhibition induces a secretome with stimulating effect on fibroblasts and naive melanoma cells. Several senescence-associated factors were found to be transcribed and secreted in response to BRAF or MEK inhibition, among them members of the fibroblast growth factor family. We identified the growth factor FGF1 as mediator of resilience towards BRAF inhibition, which limits the pro-apoptotic effects of the drug and activates fibroblasts to secrete HGF. FGF1 regulation was mediated by the PI3K pathway and by FRA1, a direct target gene of the MAPK pathway. When FGFR inhibitors were applied in parallel to BRAF inhibitors, resilience was broken, thus providing a rationale for combined therapeutical application.}, language = {en} } @article{Scheer2018, author = {Scheer, Ulrich}, title = {Boveri's research at the Zoological Station Naples: Rediscovery of his original microscope slides at the University of W{\"u}rzburg}, series = {Marine Genomics}, volume = {40}, journal = {Marine Genomics}, doi = {10.1016/j.margen.2018.01.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228453}, pages = {1-8}, year = {2018}, abstract = {Eric Davidson once wrote about Theodor Boveri: "From his own researches, and perhaps most important, his generalized interpretations, derive the paradigms that underlie modern inquiries into the genomic basis of embryogenesis" (Davidson, 1985). As luck would have it, the "primary data" of Boveri's experimental work, namely the microscope slides prepared by him and his wife Marcella during several stays at the Zoological Station in Naples (1901/02, 1911/12 and 1914), have survived at the University of Wurzburg. More than 600 slides exist and despite their age they are in a surprisingly good condition. The slides are labelled and dated in Boveri's handwriting and thus can be assigned to his published experimental work on sea urchin development. The results allowed Boveri to unravel the role of the cell nucleus and its chromosomes in development and inheritance. Here, I present an overview of the slides in the context of Boveri's work along with photographic images of selected specimens taken from the original slides. It is planned to examine the slides in more detail, take high-resolution focal image series of significant specimens and make them online available.}, language = {en} }