@article{BassetCizekCuenoudetal.2015, author = {Basset, Yves and Cizek, Lukas and Cu{\´e}noud, Philippe and Didham, Raphael K. and Novotny, Vojtech and {\O}degaard, Frode and Roslin, Tomas and Tishechkin, Alexey K. and Schmidl, J{\"u}rgen and Winchester, Neville N. and Roubik, David W. and Aberlenc, Henri-Pierre and Bail, Johannes and Barrios, Hector and Bridle, Jonathan R. and Casta{\~n}o-Meneses, Gabriela and Corbara, Bruno and Curletti, Gianfranco and da Rocha, Wesley Duarte and De Bakker, Domir and Delabie, Jacques H. C. and Dejean, Alain and Fagan, Laura L. and Floren, Andreas and Kitching, Roger L. and Medianero, Enrique and de Oliveira, Evandro Gama and Orivel, Jerome and Pollet, Marc and Rapp, Mathieu and Ribeiro, Servio P. and Roisin, Yves and Schmidt, Jesper B. and S{\o}rensen, Line and Lewinsohn, Thomas M. and Leponce, Maurice}, title = {Arthropod Distribution in a Tropical Rainforest: Tackling a Four Dimensional Puzzle}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0144110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136393}, pages = {e0144110}, year = {2015}, abstract = {Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.}, language = {en} } @article{SinghKingstonGuptaetal.2015, author = {Singh, Amit K. and Kingston, Joseph J. and Gupta, Shishir K. and Batra, Harsh V.}, title = {Recombinant Bivalent Fusion Protein rVE Induces CD4+ and CD8+ T-Cell Mediated Memory Immune Response for Protection Against Yersinia enterocolitica Infection}, series = {Frontiers in Microbiology}, volume = {6}, journal = {Frontiers in Microbiology}, number = {1407}, doi = {10.3389/fmicb.2015.01407}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136114}, year = {2015}, abstract = {Studies investigating the correlates of immune protection against Yersinia infection have established that both humoral and cell mediated immune responses are required for the comprehensive protection. In our previous study, we established that the bivalent fusion protein (rVE) comprising immunologically active regions of Y pestis LcrV (100-270 aa) and YopE (50-213 aa) proteins conferred complete passive and active protection against lethal Y enterocolitica 8081 challenge. In the present study, cohort of BALB/c mice immunized with rVE or its component proteins rV, rE were assessed for cell mediated immune responses and memory immune protection against Y enterocolitica 8081 rVE immunization resulted in extensive proliferation of both CD4 and CD8 T cell subsets; significantly high antibody titer with balanced IgG1: IgG2a/IgG2b isotypes (1:1 ratio) and up regulation of both Th1 (INF-\(\alpha\), IFN-\(\gamma\), IL 2, and IL 12) and Th2 (IL 4) cytokines. On the other hand, rV immunization resulted in Th2 biased IgG response (11:1 ratio) and proliferation of CD4+ T-cell; rE group of mice exhibited considerably lower serum antibody titer with predominant Th1 response (1:3 ratio) and CD8+ T-cell proliferation. Comprehensive protection with superior survival (100\%) was observed among rVE immunized mice when compared to the significantly lower survival rates among rE (37.5\%) and rV (25\%) groups when IP challenged with Y enterocolitica 8081 after 120 days of immunization. Findings in this and our earlier studies define the bivalent fusion protein rVE as a potent candidate vaccine molecule with the capability to concurrently stimulate humoral and cell mediated immune responses and a proof of concept for developing efficient subunit vaccines against Gram negative facultative intracellular bacterial pathogens.}, language = {en} } @article{KuhnGrippFliederetal.2015, author = {Kuhn, Joachim and Gripp, Tatjana and Flieder, Tobias and Dittrich, Marcus and Hendig, Doris and Busse, Jessica and Knabbe, Cornelius and Birschmann, Ingvild}, title = {UPLC-MRM Mass Spectrometry Method for Measurement of the Coagulation Inhibitors Dabigatran and Rivaroxaban in Human Plasma and Its Comparison with Functional Assays}, series = {PLOS ONE}, volume = {10}, journal = {PLOS ONE}, number = {12}, doi = {10.1371/journal.pone.0145478}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136023}, pages = {e0145478}, year = {2015}, abstract = {Introduction The fast, precise, and accurate measurement of the new generation of oral anticoagulants such as dabigatran and rivaroxaban in patients' plasma my provide important information in different clinical circumstances such as in the case of suspicion of overdose, when patients switch from existing oral anticoagulant, in patients with hepatic or renal impairment, by concomitant use of interaction drugs, or to assess anticoagulant concentration in patients' blood before major surgery. Methods Here, we describe a quick and precise method to measure the coagulation inhibitors dabigatran and rivaroxaban using ultra-performance liquid chromatography electrospray ionization-tandem mass spectrometry in multiple reactions monitoring (MRM) mode (UPLC-MRM MS). Internal standards (ISs) were added to the sample and after protein precipitation; the sample was separated on a reverse phase column. After ionization of the analytes the ions were detected using electrospray ionization-tandem mass spectrometry. Run time was 2.5 minutes per injection. Ion suppression was characterized by means of post-column infusion. Results The calibration curves of dabigatran and rivaroxaban were linear over the working range between 0.8 and 800 mu g/L (r > 0.99). Limits of detection (LOD) in the plasma matrix were 0.21 mu g/L for dabigatran and 0.34 mu g/L for rivaroxaban, and lower limits of quantification (LLOQ) in the plasma matrix were 0.46 mu g/L for dabigatran and 0.54 mu g/L for rivaroxaban. The intraassay coefficients of variation (CVs) for dabigatran and rivaroxaban were < 4\% and 6\%; respectively, the interassay CVs were < 6\% for dabigatran and < 9\% for rivaroxaban. Inaccuracy was < 5\% for both substances. The mean recovery was 104.5\% (range 83.8-113.0\%) for dabigatran and 87.0\%(range 73.6-105.4\%) for rivaroxaban. No significant ion suppressions were detected at the elution times of dabigatran or rivaroxaban. Both coagulation inhibitors were stable in citrate plasma at -20 degrees C, 4 degrees C and even at RT for at least one week. A method comparison between our UPLC-MRM MS method, the commercially available automated Direct Thrombin Inhibitor assay (DTI assay) for dabigatran measurement from CoaChrom Diagnostica, as well as the automated anti-Xa assay for rivaroxaban measurement from Chromogenix both performed by ACL-TOP showed a high degree of correlation. However, UPLC-MRM MS measurement of dabigatran and rivaroxaban has a much better selectivity than classical functional assays measuring activities of various coagulation factors which are susceptible to interference by other coagulant drugs. Conclusions Overall, we developed and validated a sensitive and specific UPLC-MRM MS assay for the quick and specific measurement of dabigatran and rivaroxaban in human plasma.}, language = {en} } @article{GalluzziBravoSanPedroVitaleetal.2015, author = {Galluzzi, L. and Bravo-San Pedro, J. M. and Vitale, I. and Aaronson, S. A. and Abrams, J. M. and Adam, D. and Alnemri, E. S. and Altucci, L. and Andrews, D. and Annicchiarico-Petruzelli, M. and Baehrecke, E. H. and Bazan, N. G. and Bertrand, M. J. and Bianchi, K. and Blagosklonny, M. V. and Blomgren, K. and Borner, C. and Bredesen, D. E. and Brenner, C. and Campanella, M. and Candi, E. and Cecconi, F. and Chan, F. K. and Chandel, N. S. and Cheng, E. H. and Chipuk, J. E. and Cidlowski, J. A. and Ciechanover, A. and Dawson, T. M. and Dawson, V. L. and De Laurenzi, V. and De Maria, R. and Debatin, K. M. and Di Daniele, N. and Dixit, V. M. and Dynlacht, B. D. and El-Deiry, W. S. and Fimia, G. M. and Flavell, R. A. and Fulda, S. and Garrido, C. and Gougeon, M. L. and Green, D. R. and Gronemeyer, H. and Hajnoczky, G. and Hardwick, J. M. and Hengartner, M. O. and Ichijo, H. and Joseph, B. and Jost, P. J. and Kaufmann, T. and Kepp, O. and Klionsky, D. J. and Knight, R. A. and Kumar, S. and Lemasters, J. J. and Levine, B. and Linkermann, A. and Lipton, S. A. and Lockshin, R. A. and L{\´o}pez-Ot{\´i}n, C. and Lugli, E. and Madeo, F. and Malorni, W. and Marine, J. C. and Martin, S. J. and Martinou, J. C. and Medema, J. P. and Meier, P. and Melino, S. and Mizushima, N. and Moll, U. and Mu{\~n}oz-Pinedo, C. and Nu{\~n}ez, G. and Oberst, A. and Panaretakis, T. and Penninger, J. M. and Peter, M. E. and Piacentini, M. and Pinton, P. and Prehn, J. H. and Puthalakath, H. and Rabinovich, G. A. and Ravichandran, K. S. and Rizzuto, R. and Rodrigues, C. M. and Rubinsztein, D. C. and Rudel, T. and Shi, Y. and Simon, H. U. and Stockwell, B. R. and Szabadkai, G. and Tait, S. W. and Tang, H. L. and Tavernarakis, N. and Tsujimoto, Y. and Vanden Berghe, T. and Vandenabeele, P. and Villunger, A. and Wagner, E. F. and Walczak, H. and White, E. and Wood, W. G. and Yuan, J. and Zakeri, Z. and Zhivotovsky, B. and Melino, G. and Kroemer, G.}, title = {Essential versus accessory aspects of cell death: recommendations of the NCCD 2015}, series = {Cell Death and Differentiation}, volume = {22}, journal = {Cell Death and Differentiation}, doi = {10.1038/cdd.2014.137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121207}, pages = {58-73}, year = {2015}, abstract = {Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as 'accidental cell death' (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. 'Regulated cell death' (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.}, language = {en} } @article{StrubeBlossBrownSpaetheetal.2015, author = {Strube-Bloss, Martin F. and Brown, Austin and Spaethe, Johannes and Schmitt, Thomas and R{\"o}ssler, Wolfgang}, title = {Extracting the Behaviorally Relevant Stimulus: Unique Neural Representation of Farnesol, a Component of the Recruitment Pheromone of Bombus terrestris}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {9}, doi = {10.1371/journal.pone.0137413}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125875}, pages = {e0137413}, year = {2015}, abstract = {To trigger innate behavior, sensory neural networks are pre-tuned to extract biologically relevant stimuli. Many male-female or insect-plant interactions depend on this phenomenon. Especially communication among individuals within social groups depends on innate behaviors. One example is the efficient recruitment of nest mates by successful bumblebee foragers. Returning foragers release a recruitment pheromone in the nest while they perform a 'dance' behavior to activate unemployed nest mates. A major component of this pheromone is the sesquiterpenoid farnesol. How farnesol is processed and perceived by the olfactory system, has not yet been identified. It is much likely that processing farnesol involves an innate mechanism for the extraction of relevant information to trigger a fast and reliable behavioral response. To test this hypothesis, we used population response analyses of 100 antennal lobe (AL) neurons recorded in alive bumblebee workers under repeated stimulation with four behaviorally different, but chemically related odorants (geraniol, citronellol, citronellal and farnesol). The analysis identified a unique neural representation of the recruitment pheromone component compared to the other odorants that are predominantly emitted by flowers. The farnesol induced population activity in the AL allowed a reliable separation of farnesol from all other chemically related odor stimuli we tested. We conclude that the farnesol induced population activity may reflect a predetermined representation within the AL-neural network allowing efficient and fast extraction of a behaviorally relevant stimulus. Furthermore, the results show that population response analyses of multiple single AL-units may provide a powerful tool to identify distinct representations of behaviorally relevant odors.}, language = {en} } @article{LichtensteinSommerlandtSpaethe2015, author = {Lichtenstein, Leonie and Sommerlandt, Frank M. J. and Spaethe, Johannes}, title = {Dumb and Lazy? A Comparison of Color Learning and Memory Retrieval in Drones and Workers of the Buff-Tailed Bumblebee, Bombus terrestris, by Means of PER Conditioning}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0134248}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125832}, pages = {e0134248}, year = {2015}, abstract = {More than 100 years ago, Karl von Frisch showed that honeybee workers learn and discriminate colors. Since then, many studies confirmed the color learning capabilities of females from various hymenopteran species. Yet, little is known about visual learning and memory in males despite the fact that in most bee species males must take care of their own needs and must find rewarding flowers to obtain food. Here we used the proboscis extension response (PER) paradigm to study the color learning capacities of workers and drones of the bumblebee, Bombus terrestris. Light stimuli were paired with sucrose reward delivered to the insects' antennae and inducing a reflexive extension of the proboscis. We evaluated color learning (i.e. conditioned PER to color stimuli) in absolute and differential conditioning protocols and mid-term memory retention was measured two hours after conditioning. Different monochromatic light stimuli in combination with neutral density filters were used to ensure that the bumblebees could only use chromatic and not achromatic (e.g. brightness) information. Furthermore, we tested if bees were able to transfer the learned information from the PER conditioning to a novel discrimination task in a Y-maze. Both workers and drones were capable of learning and discriminating between monochromatic light stimuli and retrieved the learned stimulus after two hours. Drones performed as well as workers during conditioning and in the memory test, but failed in the transfer test in contrast to workers. Our data clearly show that bumblebees can learn to associate a color stimulus with a sugar reward in PER conditioning and that both workers and drones reach similar acquisition and mid-term retention performances. Additionally, we provide evidence that only workers transfer the learned information from a Pavlovian to an operant situation.}, language = {en} } @article{SalatWinklerUrlaubetal.2015, author = {Salat, Daniela and Winkler, Anja and Urlaub, Henning and Gessler, Manfred}, title = {Hey bHLH Proteins Interact with a FBXO45 Containing SCF Ubiquitin Ligase Complex and Induce Its Translocation into the Nucleus}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0130288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125769}, pages = {e0130288}, year = {2015}, abstract = {The Hey protein family, comprising Hey1, Hey2 and HeyL in mammals, conveys Notch signals in many cell types. The helix-loop-helix (HLH) domain as well as the Orange domain, mediate homo- and heterodimerization of these transcription factors. Although distinct interaction partners have been identified so far, their physiological relevance for Hey functions is still largely unclear. Using a tandem affinity purification approach and mass spectrometry analysis we identified members of an ubiquitin E3-ligase complex consisting of FBXO45, PAM and SKP1 as novel Hey1 associated proteins. There is a direct interaction between Hey1 and FBXO45, whereas FBXO45 is needed to mediate indirect Hey1 binding to SKP1. Expression of Hey1 induces translocation of FBXO45 and PAM into the nucleus. Hey1 is a short-lived protein that is degraded by the proteasome, but there is no evidence for FBXO45-dependent ubiquitination of Hey1. On the contrary, Hey1 mediated nuclear translocation of FBXO45 and its associated ubiquitin ligase complex may extend its spectrum to additional nuclear targets triggering their ubiquitination. This suggests a novel mechanism of action for Hey bHLH factors.}, language = {en} } @article{SickelAnkenbrandGrimmeretal.2015, author = {Sickel, Wiebke and Ankenbrand, Markus J. and Grimmer, Gudrun and Holzschuh, Andrea and H{\"a}rtel, Stephan and Lanzen, Jonathan and Steffan-Dewenter, Ingolf and Keller, Alexander}, title = {Increased efficiency in identifying mixed pollen samples by meta-barcoding with a dual-indexing approach}, series = {BMC Ecology}, volume = {15}, journal = {BMC Ecology}, number = {20}, doi = {10.1186/s12898-015-0051-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125730}, year = {2015}, abstract = {Background Meta-barcoding of mixed pollen samples constitutes a suitable alternative to conventional pollen identification via light microscopy. Current approaches however have limitations in practicability due to low sample throughput and/or inefficient processing methods, e.g. separate steps for amplification and sample indexing. Results We thus developed a new primer-adapter design for high throughput sequencing with the Illumina technology that remedies these issues. It uses a dual-indexing strategy, where sample-specific combinations of forward and reverse identifiers attached to the barcode marker allow high sample throughput with a single sequencing run. It does not require further adapter ligation steps after amplification. We applied this protocol to 384 pollen samples collected by solitary bees and sequenced all samples together on a single Illumina MiSeq v2 flow cell. According to rarefaction curves, 2,000-3,000 high quality reads per sample were sufficient to assess the complete diversity of 95\% of the samples. We were able to detect 650 different plant taxa in total, of which 95\% were classified at the species level. Together with the laboratory protocol, we also present an update of the reference database used by the classifier software, which increases the total number of covered global plant species included in the database from 37,403 to 72,325 (93\% increase). Conclusions This study thus offers improvements for the laboratory and bioinformatical workflow to existing approaches regarding data quantity and quality as well as processing effort and cost-effectiveness. Although only tested for pollen samples, it is furthermore applicable to other research questions requiring plant identification in mixed and challenging samples.}, language = {en} } @article{Meierjohann2015, author = {Meierjohann, Svenja}, title = {Hypoxia independent drivers of melanoma angiogenesis}, series = {Frontiers in Oncology}, volume = {5}, journal = {Frontiers in Oncology}, number = {120}, doi = {10.3389/fonc.2015.00102}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125586}, year = {2015}, abstract = {Tumor angiogenesis is a process which is traditionally regarded as the tumor's response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a pre-requisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia-independent mechanisms of tumor angiogenesis in melanoma.}, language = {en} } @article{SubbarayalKarunakaranWinkleretal.2015, author = {Subbarayal, Prema and Karunakaran, Karthika and Winkler, Ann-Cathrin and Rother, Marion and Gonzalez, Erik and Meyer, Thomas F. and Rudel, Thomas}, title = {EphrinA2 Receptor (EphA2) Is an Invasion and Intracellular Signaling Receptor for Chlamydia trachomatis}, series = {PLoS Pathogens}, volume = {11}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1004846}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125566}, pages = {e1004846}, year = {2015}, abstract = {The obligate intracellular bacterium Chlamydia trachomatis invades into host cells to replicate inside a membrane-bound vacuole called inclusion. Multiple different host proteins are recruited to the inclusion and are functionally modulated to support chlamydial development. Invaded and replicating Chlamydia induces a long-lasting activation of the PI3 kinase signaling pathway that is required for efficient replication. We identified the cell surface tyrosine kinase EphrinA2 receptor (EphA2) as a chlamydial adherence and invasion receptor that induces PI3 kinase (PI3K) activation, promoting chlamydial replication. Interfering with binding of C. trachomatis serovar L2 (Ctr) to EphA2, downregulation of EphA2 expression or inhibition of EphA2 activity significantly reduced Ctr infection. Ctr interacts with and activates EphA2 on the cell surface resulting in Ctr and receptor internalization. During chlamydial replication, EphA2 remains active accumulating around the inclusion and interacts with the p85 regulatory subunit of PI3K to support the activation of the PI3K/Akt signaling pathway that is required for normal chlamydial development. Overexpression of full length EphA2, but not the mutant form lacking the intracellular cytoplasmic domain, enhanced PI3K activation and Ctr infection. Despite the depletion of EphA2 from the cell surface, Ctr infection induces upregulation of EphA2 through the activation of the ERK pathway, which keeps the infected cell in an apoptosis-resistant state. The significance of EphA2 as an entry and intracellular signaling receptor was also observed with the urogenital C. trachomatis-serovar D. Our findings provide the first evidence for a host cell surface receptor that is exploited for invasion as well as for receptor-mediated intracellular signaling to facilitate chlamydial replication. In addition, the engagement of a cell surface receptor at the inclusion membrane is a new mechanism by which Chlamydia subverts the host cell and induces apoptosis resistance.}, language = {en} } @article{HerterStauchGallantetal.2015, author = {Herter, Eva K. and Stauch, Maria and Gallant, Maria and Wolf, Elmar and Raabe, Thomas and Gallant, Peter}, title = {snoRNAs are a novel class of biologically relevant Myc targets}, series = {BMC Biology}, volume = {13}, journal = {BMC Biology}, number = {25}, doi = {10.1186/s12915-015-0132-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124956}, year = {2015}, abstract = {Background Myc proteins are essential regulators of animal growth during normal development, and their deregulation is one of the main driving factors of human malignancies. They function as transcription factors that (in vertebrates) control many growth- and proliferation-associated genes, and in some contexts contribute to global gene regulation. Results We combine chromatin immunoprecipitation-sequencing (ChIPseq) and RNAseq approaches in Drosophila tissue culture cells to identify a core set of less than 500 Myc target genes, whose salient function resides in the control of ribosome biogenesis. Among these genes we find the non-coding snoRNA genes as a large novel class of Myc targets. All assayed snoRNAs are affected by Myc, and many of them are subject to direct transcriptional activation by Myc, both in Drosophila and in vertebrates. The loss of snoRNAs impairs growth during normal development, whereas their overexpression increases tumor mass in a model for neuronal tumors. Conclusions This work shows that Myc acts as a master regulator of snoRNP biogenesis. In addition, in combination with recent observations of snoRNA involvement in human cancer, it raises the possibility that Myc's transforming effects are partially mediated by this class of non-coding transcripts.}, language = {en} } @article{AdolfiCarreiraJesusetal.2015, author = {Adolfi, Mateus C. and Carreira, Ana C. O. and Jesus, L{\´a}zaro W. O. and Bogerd, Jan and Funes, Rejane M. and Schartl, Manfred and Sogayar, Mari C. and Borella, Maria I.}, title = {Molecular cloning and expression analysis of dmrt1 and sox9 during gonad development and male reproductive cycle in the lambari fish, Astyanax altiparanae}, series = {Reproductive Biology and Endocrinology}, volume = {13}, journal = {Reproductive Biology and Endocrinology}, number = {2}, doi = {10.1186/1477-7827-13-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126486}, year = {2015}, abstract = {Background The dmrt1 and sox9 genes have a well conserved function related to testis formation in vertebrates, and the group of fish presents a great diversity of species and reproductive mechanisms. The lambari fish (Astyanax altiparanae) is an important Neotropical species, where studies on molecular level of sex determination and gonad maturation are scarce. Methods Here, we employed molecular cloning techniques to analyze the cDNA sequences of the dmrt1 and sox9 genes, and describe the expression pattern of those genes during development and the male reproductive cycle by qRT-PCR, and related to histology of the gonad. Results Phylogenetic analyses of predicted amino acid sequences of dmrt1 and sox9 clustered A. altiparanae in the Ostariophysi group, which is consistent with the morphological phylogeny of this species. Studies of the gonad development revealed that ovary formation occurred at 58 days after hatching (dah), 2 weeks earlier than testis formation. Expression studies of sox9 and dmrt1 in different tissues of adult males and females and during development revealed specific expression in the testis, indicating that both genes also have a male-specific role in the adult. During the period of gonad sex differentiation, dmrt1 seems to have a more significant role than sox9. During the male reproductive cycle dmrt1 and sox9 are down-regulated after spermiation, indicating a role of these genes in spermatogenesis. Conclusions For the first time the dmrt1 and sox9 were cloned in a Characiformes species. We show that both genes have a conserved structure and expression, evidencing their role in sex determination, sex differentiation and the male reproductive cycle in A. altiparanae. These findings contribute to a better understanding of the molecular mechanisms of sex determination and differentiation in fish.}, language = {en} } @article{LakovicPoethkeHovestadt2015, author = {Lakovic, Milica and Poethke, Hans-Joachim and Hovestadt, Thomas}, title = {Dispersal timing: Emigration of insects living in patchy environments}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {7}, doi = {10.1371/journal.pone.0128672}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126466}, pages = {e0128672}, year = {2015}, abstract = {Dispersal is a life-history trait affecting dynamics and persistence of populations; it evolves under various known selective pressures. Theoretical studies on dispersal typically assume 'natal dispersal', where individuals emigrate right after birth. But emigration may also occur during a later moment within a reproductive season ('breeding dispersal'). For example, some female butterflies first deposit eggs in their natal patch before migrating to other site(s) to continue egg-laying there. How breeding compared to natal dispersal influences the evolution of dispersal has not been explored. To close this gap we used an individual-based simulation approach to analyze (i) the evolution of timing of breeding dispersal in annual organisms, (ii) its influence on dispersal (compared to natal dispersal). Furthermore, we tested (iii) its performance in direct evolutionary contest with individuals following a natal dispersal strategy. Our results show that evolution should typically result in lower dispersal under breeding dispersal, especially when costs of dispersal are low and population size is small. By distributing offspring evenly across two patches, breeding dispersal allows reducing direct sibling competition in the next generation whereas natal dispersal can only reduce trans-generational kin competition by producing highly dispersive offspring in each generation. The added benefit of breeding dispersal is most prominent in patches with small population sizes. Finally, the evolutionary contests show that a breeding dispersal strategy would universally out-compete natal dispersal.}, language = {en} } @article{WeissSchultz2015, author = {Weiß, Clemens Leonard and Schultz, J{\"o}rg}, title = {Identification of divergent WH2 motifs by HMM-HMM alignments}, series = {BMC Research Notes}, volume = {8}, journal = {BMC Research Notes}, number = {18}, doi = {10.1186/s13104-015-0981-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126413}, year = {2015}, abstract = {Background The actin cytoskeleton is a hallmark of eukaryotic cells. Its regulation as well as its interaction with other proteins is carefully orchestrated by actin interaction domains. One of the key players is the WH2 motif, which enables binding to actin monomers and filaments and is involved in the regulation of actin nucleation. Contrasting conserved domains, the identification of this motif in protein sequences is challenging, as it is short and poorly conserved. Findings To identify divergent members, we combined Hidden-Markov-Model (HMM) to HMM alignments with orthology predictions. Thereby, we identified nearly 500 proteins containing so far not annotated WH2 motifs. This included shootin-1, an actin binding protein involved in neuron polarization. Among others, WH2 motifs of 'proximal to raf' (ptr)-orthologs, which are described in the literature, but not annotated in genome databases, were identified. Conclusion In summary, we increased the number of WH2 motif containing proteins substantially. This identification of candidate regions for actin interaction could steer their experimental characterization. Furthermore, the approach outlined here can easily be adapted to the identification of divergent members of further domain families.}, language = {en} } @article{AndronicShirakashiPickeletal.2015, author = {Andronic, Joseph and Shirakashi, Ryo and Pickel, Simone U. and Westerling, Katherine M. and Klein, Teresa and Holm, Thorge and Sauer, Markus and Sukhorukov, Vladimir L.}, title = {Hypotonic Activation of the Myo-Inositol Transporter SLC5A3 in HEK293 Cells Probed by Cell Volumetry, Confocal and Super-Resolution Microscopy}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0119990}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126408}, year = {2015}, abstract = {Swelling-activated pathways for myo-inositol, one of the most abundant organic osmolytes in mammalian cells, have not yet been identified. The present study explores the SLC5A3 protein as a possible transporter of myo-inositol in hyponically swollen HEK293 cells. To address this issue, we examined the relationship between the hypotonicity-induced changes in plasma membrane permeability to myo-inositol Pino [m/s] and expression/localization of SLC5A3. Pino values were determined by cell volumetry over a wide tonicity range (100-275 mOsm) in myo-inositol-substituted solutions. While being negligible under mild hypotonicity (200-275 mOsm), Pino grew rapidly at osmolalities below 200 mOsm to reach a maximum of ∼3 nm/s at 100-125 mOsm, as indicated by fast cell swelling due to myo-inositol influx. The increase in Pino resulted most likely from the hypotonicity-mediated incorporation of cytosolic SLC5A3 into the plasma membrane, as revealed by confocal fluorescence microscopy of cells expressing EGFP-tagged SLC5A3 and super-resolution imaging of immunostained SLC5A3 by direct stochastic optical reconstruction microscopy (dSTORM). dSTORM in hypotonic cells revealed a surface density of membrane-associated SLC5A3 proteins of 200-2000 localizations/μm2. Assuming SLC5A3 to be the major path for myo-inositol, a turnover rate of 80-800 myo-inositol molecules per second for a single transporter protein was estimated from combined volumetric and dSTORM data. Hypotonic stress also caused a significant upregulation of SLC5A3 gene expression as detected by semiquantitative RT-PCR and Western blot analysis. In summary, our data provide first evidence for swelling-mediated activation of SLC5A3 thus suggesting a functional role of this transporter in hypotonic volume regulation of mammalian cells.}, language = {en} } @article{BrillMeyerRoessler2015, author = {Brill, Martin F. and Meyer, Anneke and Roessler, Wolfgang}, title = {It takes two—coincidence coding within the dual olfactory pathway of the honeybee}, series = {Frontiers in Physiology}, volume = {6}, journal = {Frontiers in Physiology}, number = {208}, doi = {10.3389/fphys.2015.00208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126179}, year = {2015}, abstract = {To rapidly process biologically relevant stimuli, sensory systems have developed a broad variety of coding mechanisms like parallel processing and coincidence detection. Parallel processing (e.g., in the visual system), increases both computational capacity and processing speed by simultaneously coding different aspects of the same stimulus. Coincidence detection is an efficient way to integrate information from different sources. Coincidence has been shown to promote associative learning and memory or stimulus feature detection (e.g., in auditory delay lines). Within the dual olfactory pathway of the honeybee both of these mechanisms might be implemented by uniglomerular projection neurons (PNs) that transfer information from the primary olfactory centers, the antennal lobe (AL), to a multimodal integration center, the mushroom body (MB). PNs from anatomically distinct tracts respond to the same stimulus space, but have different physiological properties, characteristics that are prerequisites for parallel processing of different stimulus aspects. However, the PN pathways also display mirror-imaged like anatomical trajectories that resemble neuronal coincidence detectors as known from auditory delay lines. To investigate temporal processing of olfactory information, we recorded PN odor responses simultaneously from both tracts and measured coincident activity of PNs within and between tracts. Our results show that coincidence levels are different within each of the two tracts. Coincidence also occurs between tracts, but to a minor extent compared to coincidence within tracts. Taken together our findings support the relevance of spike timing in coding of olfactory information (temporal code).}, language = {en} } @article{KlammertMuellerHellmannetal.2015, author = {Klammert, Uwe and M{\"u}ller, Thomas D. and Hellmann, Tina V. and Wuerzler, Kristian K. and Kotzsch, Alexander and Schliermann, Anna and Schmitz, Werner and Kuebler, Alexander C. and Sebald, Walter and Nickel, Joachim}, title = {GDF-5 can act as a context-dependent BMP-2 antagonist}, series = {BMC Biology}, volume = {13}, journal = {BMC Biology}, number = {77}, doi = {10.1186/s12915-015-0183-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125550}, year = {2015}, abstract = {Background Bone morphogenetic protein (BMP)-2 and growth and differentiation factor (GDF)-5 are two related transforming growth factor (TGF)-β family members with important functions in embryonic development and tissue homeostasis. BMP-2 is best known for its osteoinductive properties whereas GDF-5—as evident from its alternative name, cartilage derived morphogenetic protein 1—plays an important role in the formation of cartilage. In spite of these differences both factors signal by binding to the same subset of BMP receptors, raising the question how these different functionalities are generated. The largest difference in receptor binding is observed in the interaction with the type I receptor BMPR-IA. GDF-5, in contrast to BMP-2, shows preferential binding to the isoform BMPR-IB, which is abrogated by a single amino acid (A57R) substitution. The resulting variant, GDF-5 R57A, represents a "BMP-2 mimic" with respect to BMP receptor binding. In this study we thus wanted to analyze whether the two growth factors can induce distinct signals via an identically composed receptor. Results Unexpectedly and dependent on the cellular context, GDF-5 R57A showed clear differences in its activity compared to BMP-2. In ATDC-5 cells, both ligands induced alkaline phosphatase (ALP) expression with similar potency. But in C2C12 cells, the BMP-2 mimic GDF-5 R57A (and also wild-type GDF-5) clearly antagonized BMP-2-mediated ALP expression, despite signaling in both cell lines occurring solely via BMPR-IA. The BMP-2- antagonizing properties of GDF-5 and GDF-5 R57A could also be observed in vivo when implanting BMP-2 and either one of the two GDF-5 ligands simultaneously at heterotopic sites. Conclusions Although comparison of the crystal structures of the GDF-5 R57A:BMPR-IAEC- and BMP-2:BMPR-IAEC complex revealed small ligand-specific differences, these cannot account for the different signaling characteristics because the complexes seem identical in both differently reacting cell lines. We thus predict an additional component, most likely a not yet identified GDF-5-specific co-receptor, which alters the output of the signaling complexes. Hence the presence or absence of this component then switches GDF-5′s signaling capabilities to act either similar to BMP-2 or as a BMP-2 antagonist. These findings might shed new light on the role of GDF-5, e.g., in cartilage maintenance and/or limb development in that it might act as an inhibitor of signaling events initiated by other BMPs.}, language = {en} } @article{FalibeneRocesRoessler2015, author = {Falibene, Agustina and Roces, Flavio and R{\"o}ssler, Wolfgang}, title = {Long-term avoidance memory formation is associated with a transient increase in mushroom body synaptic complexes in leaf-cutting ants}, series = {Frontiers in Behavioral Neuroscience}, volume = {9}, journal = {Frontiers in Behavioral Neuroscience}, number = {84}, doi = {10.3389/fnbeh.2015.00084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125522}, year = {2015}, abstract = {Long-term behavioral changes related to learning and experience have been shown to be associated with structural remodeling in the brain. Leaf-cutting ants learn to avoid previously preferred plants after they have proved harmful for their symbiotic fungus, a process that involves long-term olfactory memory. We studied the dynamics of brain microarchitectural changes after long-term olfactory memory formation following avoidance learning in Acromyrmex ambiguus. After performing experiments to control for possible neuronal changes related to age and body size, we quantified synaptic complexes (microglomeruli, MG) in olfactory regions of the mushroom bodies (MBs) at different times after learning. Long-term avoidance memory formation was associated with a transient change in MG densities. Two days after learning, MG density was higher than before learning. At days 4 and 15 after learning—when ants still showed plant avoidance—MG densities had decreased to the initial state. The structural reorganization of MG triggered by long-term avoidance memory formation clearly differed from changes promoted by pure exposure to and collection of novel plants with distinct odors. Sensory exposure by the simultaneous collection of several, instead of one, non-harmful plant species resulted in a decrease in MG densities in the olfactory lip. We hypothesize that while sensory exposure leads to MG pruning in the MB olfactory lip, the formation of long-term avoidance memory involves an initial growth of new MG followed by subsequent pruning.}, language = {en} } @article{OttDorschFraunholzetal.2015, author = {Ott, Christine and Dorsch, Eva and Fraunholz, Martin and Straub, Sebastian and Kozjak-Pavlovic, Vera}, title = {Detailed Analysis of the Human Mitochondrial Contact Site Complex Indicate a Hierarchy of Subunits}, series = {PLoS One}, volume = {10}, journal = {PLoS One}, number = {3}, doi = {10.1371/journal.pone.0120213}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125347}, pages = {e0120213}, year = {2015}, abstract = {Mitochondrial inner membrane folds into cristae, which significantly increase its surface and are important for mitochondrial function. The stability of cristae depends on the mitochondrial contact site (MICOS) complex. In human mitochondria, the inner membrane MICOS complex interacts with the outer membrane sorting and assembly machinery (SAM) complex, to form the mitochondrial intermembrane space bridging complex (MIB). We have created knockdown cell lines of most of the MICOS and MIB components and have used them to study the importance of the individual subunits for the cristae formation and complex stability. We show that the most important subunits of the MIB complex in human mitochondria are Mic60/Mitofilin, Mic19/CHCHD3 and an outer membrane component Sam50. We provide additional proof that ApoO indeed is a subunit of the MICOS and MIB complexes and propose the name Mic23 for this protein. According to our results, Mic25/CHCHD6, Mic27/ApoOL and Mic23/ApoO appear to be periphery subunits of the MICOS complex, because their depletion does not affect cristae morphology or stability of other components.}, language = {en} } @article{GuptaKupperRatzkaetal.2015, author = {Gupta, Shishir K. and Kupper, Maria and Ratzka, Carolin and Feldhaar, Heike and Vilcinskas, Andreas and Gross, Roy and Dandekar, Thomas and F{\"o}rster, Frank}, title = {Scrutinizing the immune defence inventory of Camponotus floridanus applying total transcriptome sequencing}, series = {BMC Genomics}, volume = {16}, journal = {BMC Genomics}, number = {540}, doi = {10.1186/s12864-015-1748-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125279}, year = {2015}, abstract = {Background Defence mechanisms of organisms are shaped by their lifestyle, environment and pathogen pressure. Carpenter ants are social insects which live in huge colonies comprising genetically closely related individuals in high densities within nests. This lifestyle potentially facilitates the rapid spread of pathogens between individuals. In concert with their innate immune system, social insects may apply external immune defences to manipulate the microbial community among individuals and within nests. Additionally, carpenter ants carry a mutualistic intracellular and obligate endosymbiotic bacterium, possibly maintained and regulated by the innate immune system. Thus, different selective forces could shape internal immune defences of Camponotus floridanus. Results The immune gene repertoire of C. floridanus was investigated by re-evaluating its genome sequence combined with a full transcriptome analysis of immune challenged and control animals using Illumina sequencing. The genome was re-annotated by mapping transcriptome reads and masking repeats. A total of 978 protein sequences were characterised further by annotating functional domains, leading to a change in their original annotation regarding function and domain composition in about 8 \% of all proteins. Based on homology analysis with key components of major immune pathways of insects, the C. floridanus immune-related genes were compared to those of Drosophila melanogaster, Apis mellifera, and other hymenoptera. This analysis revealed that overall the immune system of carpenter ants comprises many components found in these insects. In addition, several C. floridanus specific genes of yet unknown functions but which are strongly induced after immune challenge were discovered. In contrast to solitary insects like Drosophila or the hymenopteran Nasonia vitripennis, the number of genes encoding pattern recognition receptors specific for bacterial peptidoglycan (PGN) and a variety of known antimicrobial peptide (AMP) genes is lower in C. floridanus. The comparative analysis of gene expression post immune-challenge in different developmental stages of C. floridanus suggests a stronger induction of immune gene expression in larvae in comparison to adults. Conclusions The comparison of the immune system of C. floridanus with that of other insects revealed the presence of a broad immune repertoire. However, the relatively low number of PGN recognition proteins and AMPs, the identification of Camponotus specific putative immune genes, and stage specific differences in immune gene regulation reflects Camponotus specific evolution including adaptations to its lifestyle.}, language = {en} }