TY - JOUR A1 - Milanese, Alessio A1 - Mende, Daniel R A1 - Paoli, Lucas A1 - Salazar, Guillem A1 - Ruscheweyh, Hans-Joachim A1 - Cuenca, Miguelangel A1 - Hingamp, Pascal A1 - Alves, Renato A1 - Costea, Paul I A1 - Coelho, Luis Pedro A1 - Schmidt, Thomas S. B. A1 - Almeida, Alexandre A1 - Mitchell, Alex L A1 - Finn, Robert D. A1 - Huerta-Cepas, Jaime A1 - Bork, Peer A1 - Zeller, Georg A1 - Sunagawa, Shinichi T1 - Microbial abundance, activity and population genomic profiling with mOTUs2 JF - Nature Communications N2 - Metagenomic sequencing has greatly improved our ability to profile the composition of environmental and host-associated microbial communities. However, the dependency of most methods on reference genomes, which are currently unavailable for a substantial fraction of microbial species, introduces estimation biases. We present an updated and functionally extended tool based on universal (i.e., reference-independent), phylogenetic marker gene (MG)-based operational taxonomic units (mOTUs) enabling the profiling of >7700 microbial species. As more than 30% of them could not previously be quantified at this taxonomic resolution, relative abundance estimates based on mOTUs are more accurate compared to other methods. As a new feature, we show that mOTUs, which are based on essential housekeeping genes, are demonstrably well-suited for quantification of basal transcriptional activity of community members. Furthermore, single nucleotide variation profiles estimated using mOTUs reflect those from whole genomes, which allows for comparing microbial strain populations (e.g., across different human body sites). KW - microbiome KW - software Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224089 VL - 10 ER - TY - JOUR A1 - Krah, Franz-Sebastian A1 - Büntgen, Ulf A1 - Schaefer, Hanno A1 - Müller, Jörg A1 - Andrew, Carrie A1 - Boddy, Lynne A1 - Diez, Jeffrey A1 - Egli, Simon A1 - Freckleton, Robert A1 - Gange, Alan C. A1 - Halvorsen, Rune A1 - Heegaard, Einar A1 - Heideroth, Antje A1 - Heibl, Christoph A1 - Heilmann-Clausen, Jacob A1 - Høiland, Klaus A1 - Kar, Ritwika A1 - Kauserud, Håvard A1 - Kirk, Paul M. A1 - Kuyper, Thomas W. A1 - Krisai-Greilhuber, Irmgard A1 - Norden, Jenni A1 - Papastefanou, Phillip A1 - Senn-Irlet, Beatrice A1 - Bässler, Claus T1 - European mushroom assemblages are darker in cold climates JF - Nature Communications N2 - Thermal melanism theory states that dark-colored ectotherm organisms are at an advantage at low temperature due to increased warming. This theory is generally supported for ectotherm animals, however, the function of colors in the fungal kingdom is largely unknown. Here, we test whether the color lightness of mushroom assemblages is related to climate using a dataset of 3.2 million observations of 3,054 species across Europe. Consistent with the thermal melanism theory, mushroom assemblages are significantly darker in areas with cold climates. We further show differences in color phenotype between fungal lifestyles and a lifestyle differentiated response to seasonality. These results indicate a more complex ecological role of mushroom colors and suggest functions beyond thermal adaption. Because fungi play a crucial role in terrestrial carbon and nutrient cycles, understanding the links between the thermal environment, functional coloration and species’ geographical distributions will be critical in predicting ecosystem responses to global warming. KW - evolutionary ecology KW - fungal ecology KW - fungal evolution KW - macroecology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224815 VL - 10 ER - TY - JOUR A1 - Woodcock, B. A. A1 - Garratt, M. P. D. A1 - Powney, G. D. A1 - Shaw, R. F. A1 - Osborne, J. L. A1 - Soroka, J. A1 - Lindström, S. A. M. A1 - Stanley, D. A1 - Ouvrard, P. A1 - Edwards, M. E. A1 - Jauker, F. A1 - McCracken, M. E. A1 - Zou, Y. A1 - Potts, S. G. A1 - Rundlöf, M. A1 - Noriega, J. A. A1 - Greenop, A. A1 - Smith, H. G. A1 - Bommarco, R. A1 - van der Werf, W. A1 - Stout, J. C. A1 - Steffan-Dewenter, I. A1 - Morandin, L. A1 - Bullock, J. M. A1 - Pywell, R. F. T1 - Meta-analysis reveals that pollinator functional diversity and abundance enhance crop pollination and yield JF - Nature Communications N2 - How insects promote crop pollination remains poorly understood in terms of the contribution of functional trait differences between species. We used meta-analyses to test for correlations between community abundance, species richness and functional trait metrics with oilseed rape yield, a globally important crop. While overall abundance is consistently important in predicting yield, functional divergence between species traits also showed a positive correlation. This result supports the complementarity hypothesis that pollination function is maintained by non-overlapping trait distributions. In artificially constructed communities (mesocosms), species richness is positively correlated with yield, although this effect is not seen under field conditions. As traits of the dominant species do not predict yield above that attributed to the effect of abundance alone, we find no evidence in support of the mass ratio hypothesis. Management practices increasing not just pollinator abundance, but also functional divergence, could benefit oilseed rape agriculture. KW - agroecology KW - agriculture KW - ecosystem services KW - environmental sciences Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233787 VL - 10 ER - TY - JOUR A1 - Wegert, Jenny A1 - Vokuhl, Christian A1 - Collord, Grace A1 - Del Castillo Velasco-Herrera, Martin A1 - Farndon, Sarah J. A1 - Guzzo, Charlotte A1 - Jorgensen, Mette A1 - Anderson, John A1 - Slater, Olga A1 - Duncan, Catriona A1 - Bausenwein, Sabrina A1 - Streitenberger, Heike A1 - Ziegler, Barbara A1 - Furtwängler, Rhoikos A1 - Graf, Norbert A1 - Stratton, Michael R. A1 - Campbell, Peter J. A1 - Jones, David TW A1 - Koelsche, Christian A1 - Pfister, Stefan M. A1 - Mifsud, William A1 - Sebire, Neil A1 - Sparber-Sauer, Monika A1 - Koscielniak, Ewa A1 - Rosenwald, Andreas A1 - Gessler, Manfred A1 - Behjati, Sam T1 - Recurrent intragenic rearrangements of EGFR and BRAF in soft tissue tumors of infants JF - Nature Communications N2 - Soft tissue tumors of infancy encompass an overlapping spectrum of diseases that pose unique diagnostic and clinical challenges. We studied genomes and transcriptomes of cryptogenic congenital mesoblastic nephroma (CMN), and extended our findings to five anatomically or histologically related soft tissue tumors: infantile fibrosarcoma (IFS), nephroblastomatosis, Wilms tumor, malignant rhabdoid tumor, and clear cell sarcoma of the kidney. A key finding is recurrent mutation of EGFR in CMN by internal tandem duplication of the kinase domain, thus delineating CMN from other childhood renal tumors. Furthermore, we identify BRAF intragenic rearrangements in CMN and IFS. Collectively these findings reveal novel diagnostic markers and therapeutic strategies and highlight a prominent role of isolated intragenic rearrangements as drivers of infant tumors. KW - cancer KW - genetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233446 VL - 9 ER - TY - JOUR A1 - Vujanić, Gordan M. A1 - Gessler, Manfred A1 - Ooms, Ariadne H. A. G. A1 - Collini, Paola A1 - Coulomb-l'Hermine, Aurore A1 - D'Hooghe, Ellen A1 - de Krijger, Ronald R. A1 - Perotti, Daniela A1 - Pritchard-Jones, Kathy A1 - Vokuhl, Christian A1 - van den Heuvel-Eibrink, Marry M. A1 - Graf, Norbert T1 - The UMBRELLA SIOP–RTSG 2016 Wilms tumour pathology and molecular biology protocol JF - Nature Reviews Urology N2 - On the basis of the results of previous national and international trials and studies, the Renal Tumour Study Group of the International Society of Paediatric Oncology (SIOP–RTSG) has developed a new study protocol for paediatric renal tumours: the UMBRELLA SIOP–RTSG 2016 protocol (the UMBRELLA protocol). Currently, the overall outcomes of patients with Wilms tumour are excellent, but subgroups with poor prognosis and increased relapse rates still exist. The identification of these subgroups is of utmost importance to improve treatment stratification, which might lead to reduction of the direct and late effects of chemotherapy. The UMBRELLA protocol aims to validate new prognostic factors, such as blastemal tumour volume and molecular markers, to further improve outcome. To achieve this aim, large, international, high-quality databases are needed, which dictate optimization and international harmonization of specimen handling and comprehensive sampling of biological material, refine definitions and improve logistics for expert review. To promote broad implementation of the UMBRELLA protocol, the updated SIOP–RTSG pathology and molecular biology protocol for Wilms tumours has been outlined, which is a consensus from the SIOP–RTSG pathology panel. KW - molecular biology KW - paediatric cancer KW - pathology KW - renal cancer Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233265 VL - 15 ER - TY - JOUR A1 - Sommerfeld, Andreas A1 - Senf, Cornelius A1 - Buma, Brian A1 - D'Amato, Anthony W. A1 - Després, Tiphaine A1 - Díaz-Hormazábal, Ignacio A1 - Fraver, Shawn A1 - Frelich, Lee E. A1 - Gutiérrez, Álvaro G. A1 - Hart, Sarah J. A1 - Harvey, Brian J. A1 - He, Hong S. A1 - Hlásny, Tomáš A1 - Holz, Andrés A1 - Kitzberger, Thomas A1 - Kulakowski, Dominik A1 - Lindenmayer, David A1 - Mori, Akira S. A1 - Müller, Jörg A1 - Paritsis, Juan A1 - Perry, George L. W. A1 - Stephens, Scott L. A1 - Svoboda, Miroslav A1 - Turner, Monica G. A1 - Veblen, Thomas T. A1 - Seidl, Rupert T1 - Patterns and drivers of recent disturbances across the temperate forest biome JF - Nature Communications N2 - Increasing evidence indicates that forest disturbances are changing in response to global change, yet local variability in disturbance remains high. We quantified this considerable variability and analyzed whether recent disturbance episodes around the globe were consistently driven by climate, and if human influence modulates patterns of forest disturbance. We combined remote sensing data on recent (2001–2014) disturbances with in-depth local information for 50 protected landscapes and their surroundings across the temperate biome. Disturbance patterns are highly variable, and shaped by variation in disturbance agents and traits of prevailing tree species. However, high disturbance activity is consistently linked to warmer and drier than average conditions across the globe. Disturbances in protected areas are smaller and more complex in shape compared to their surroundings affected by human land use. This signal disappears in areas with high recent natural disturbance activity, underlining the potential of climate-mediated disturbance to transform forest landscapes. KW - forest ecology KW - forestry Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239157 VL - 9 ER - TY - JOUR A1 - Snaebjornsson, Marteinn T A1 - Schulze, Almut T1 - Non-canonical functions of enzymes facilitate cross-talk between cell metabolic and regulatory pathways JF - Experimental & Molecular Medicine N2 - The metabolic rewiring that occurs during cell transformation is a hallmark of cancer. It is diverse in different cancers as it reflects different combinations of oncogenic drivers, tumor suppressors, and the microenvironment. Metabolic rewiring is essential to cancer as it enables uncontrolled proliferation and adaptation to the fluctuating availability of nutrients and oxygen caused by poor access to the vasculature due to tumor growth and a foreign microenvironment encountered during metastasis. Increasing evidence now indicates that the metabolic state in cancer cells also plays a causal role in tumor growth and metastasis, for example through the action of oncometabolites, which modulate cell signaling and epigenetic pathways to promote malignancy. In addition to altering the metabolic state in cancer cells, some multifunctional enzymes possess non-metabolic functions that also contribute to cell transformation. Some multifunctional enzymes that are highly expressed in cancer, such as pyruvate kinase M2 (PKM2), have non-canonical functions that are co-opted by oncogenic signaling to drive proliferation and inhibit apoptosis. Other multifunctional enzymes that are frequently downregulated in cancer, such as fructose-bisphosphatase 1 (FBP1), are tumor suppressors, directly opposing mitogenic signaling via their non-canonical functions. In some cases, the enzymatic and non-canonical roles of these enzymes are functionally linked, making the modulation of non-metabolic cellular processes dependent on the metabolic state of the cell. KW - cancer metabolism Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238763 VL - 50 ER - TY - JOUR A1 - Selkrig, Joel A1 - Mohammad, Farhan A1 - Ng, Soon Hwee A1 - Chua, Jia Yi A1 - Tumkaya, Tayfun A1 - Ho, Joses A1 - Chiang, Yin Ning A1 - Rieger, Dirk A1 - Pettersson, Sven A1 - Helfrich-Förster, Charlotte A1 - Yew, Joanne Y. A1 - Claridge-Chang, Adam T1 - The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors JF - Scientific Reports N2 - In animals, commensal microbes modulate various physiological functions, including behavior. While microbiota exposure is required for normal behavior in mammals, it is not known how widely this dependency is present in other animal species. We proposed the hypothesis that the microbiome has a major influence on the behavior of the vinegar fly (Drosophila melanogaster), a major invertebrate model organism. Several assays were used to test the contribution of the microbiome on some well-characterized behaviors: defensive behavior, sleep, locomotion, and courtship in microbe-bearing, control flies and two generations of germ-free animals. None of the behaviors were largely influenced by the absence of a microbiome, and the small or moderate effects were not generalizable between replicates and/or generations. These results refute the hypothesis, indicating that the Drosophila microbiome does not have a major influence over several behaviors fundamental to the animal’s survival and reproduction. The impact of commensal microbes on animal behaviour may not be broadly conserved. KW - behavioural ecology KW - sleep Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235891 VL - 8 ER - TY - JOUR A1 - Nerreter, Thomas A1 - Letschert, Sebastian A1 - Götz, Ralph A1 - Doose, Sören A1 - Danhof, Sophia A1 - Einsele, Hermann A1 - Sauer, Markus A1 - Hudecek, Michael T1 - Super-resolution microscopy reveals ultra-low CD19 expression on myeloma cells that triggers elimination by CD19 CAR-T JF - Nature Communications N2 - Immunotherapy with chimeric antigen receptor-engineered T-cells (CAR-T) is under investigation in multiple myeloma. There are reports of myeloma remission after CD19 CAR-T therapy, although CD19 is hardly detectable on myeloma cells by flow cytometry (FC). We apply single molecule-sensitive direct stochastic optical reconstruction microscopy (dSTORM), and demonstrate CD19 expression on a fraction of myeloma cells (10.3–80%) in 10 out of 14 patients (density: 13–5,000 molecules per cell). In contrast, FC detects CD19 in only 2 of these 10 patients, on a smaller fraction of cells. Treatment with CD19 CAR-T in vitro results in elimination of CD19-positive myeloma cells, including those with <100 CD19 molecules per cell. Similar data are obtained by dSTORM analyses of CD20 expression on myeloma cells and CD20 CAR-T. These data establish a sensitivity threshold for CAR-T and illustrate how super-resolution microscopy can guide patient selection in immunotherapy to exploit ultra-low density antigens. KW - cancer imaging KW - cancer immunotherapy KW - imaging Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232258 VL - 10 ER - TY - JOUR A1 - Müller, Laura S. M. A1 - Cosentino, Raúl O. A1 - Förstner, Konrad U. A1 - Guizetti, Julien A1 - Wedel, Carolin A1 - Kaplan, Noam A1 - Janzen, Christian J. A1 - Arampatzi, Panagiota A1 - Vogel, Jörg A1 - Steinbiss, Sascha A1 - Otto, Thomas D. A1 - Saliba, Antoine-Emmanuel A1 - Sebra, Robert P. A1 - Siegel, T. Nicolai T1 - Genome organization and DNA accessibility control antigenic variation in trypanosomes JF - Nature N2 - Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses—Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing—that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation. KW - histone variants KW - genome architecture KW - single molecule real time (SMRT) KW - brucei genome KW - distance-dependent decay Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224265 VL - 563 ER -