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Institute
- Theodor-Boveri-Institut für Biowissenschaften (2281) (remove)
Sonstige beteiligte Institutionen
- Institut für Tierökologie und Tropenbiologie (2)
- Mildred-Scheel-Nachwuchszentrum (2)
- Ökologische Station Fabrikschleichach (2)
- Albert-Ludwigs-Universität Freiburg (1)
- Boehringer Ingelheim Pharma GmbH & Co. KG (1)
- Boston Children's Hospital (1)
- Center for Computational and Theoretical Biology (CCTB), Universität Würzburg (1)
- Chemical Biology Laboratory, National Cancer Institue, Frederick (USA) (1)
- Core Unit Systemmedizin (1)
- DNA Analytics Core Facility, Biocenter, University of Wuerzburg, Wuerzburg, Germany (1)
ResearcherID
- D-1221-2009 (1)
- J-8841-2015 (1)
- N-2030-2015 (1)
Milanese, Alessio ; Mende, Daniel R ; Paoli, Lucas ; Salazar, Guillem ; Ruscheweyh, Hans-Joachim ; Cuenca, Miguelangel ; Hingamp, Pascal ; Alves, Renato ; Costea, Paul I ; Coelho, Luis Pedro ; Schmidt, Thomas S. B. ; Almeida, Alexandre ; Mitchell, Alex L ; Finn, Robert D. ; Huerta-Cepas, Jaime ; Bork, Peer ; Zeller, Georg ; Sunagawa, Shinichi
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).
Krah, Franz-Sebastian ; Büntgen, Ulf ; Schaefer, Hanno ; Müller, Jörg ; Andrew, Carrie ; Boddy, Lynne ; Diez, Jeffrey ; Egli, Simon ; Freckleton, Robert ; Gange, Alan C. ; Halvorsen, Rune ; Heegaard, Einar ; Heideroth, Antje ; Heibl, Christoph ; Heilmann-Clausen, Jacob ; Høiland, Klaus ; Kar, Ritwika ; Kauserud, Håvard ; Kirk, Paul M. ; Kuyper, Thomas W. ; Krisai-Greilhuber, Irmgard ; Norden, Jenni ; Papastefanou, Phillip ; Senn-Irlet, Beatrice ; Bässler, Claus
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.
Woodcock, B. A. ; Garratt, M. P. D. ; Powney, G. D. ; Shaw, R. F. ; Osborne, J. L. ; Soroka, J. ; Lindström, S. A. M. ; Stanley, D. ; Ouvrard, P. ; Edwards, M. E. ; Jauker, F. ; McCracken, M. E. ; Zou, Y. ; Potts, S. G. ; Rundlöf, M. ; Noriega, J. A. ; Greenop, A. ; Smith, H. G. ; Bommarco, R. ; van der Werf, W. ; Stout, J. C. ; Steffan-Dewenter, I. ; Morandin, L. ; Bullock, J. M. ; Pywell, R. F.
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.
Wegert, Jenny ; Vokuhl, Christian ; Collord, Grace ; Del Castillo Velasco-Herrera, Martin ; Farndon, Sarah J. ; Guzzo, Charlotte ; Jorgensen, Mette ; Anderson, John ; Slater, Olga ; Duncan, Catriona ; Bausenwein, Sabrina ; Streitenberger, Heike ; Ziegler, Barbara ; Furtwängler, Rhoikos ; Graf, Norbert ; Stratton, Michael R. ; Campbell, Peter J. ; Jones, David TW ; Koelsche, Christian ; Pfister, Stefan M. ; Mifsud, William ; Sebire, Neil ; Sparber-Sauer, Monika ; Koscielniak, Ewa ; Rosenwald, Andreas ; Gessler, Manfred ; Behjati, Sam
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.
Vujanić, Gordan M. ; Gessler, Manfred ; Ooms, Ariadne H. A. G. ; Collini, Paola ; Coulomb-l'Hermine, Aurore ; D'Hooghe, Ellen ; de Krijger, Ronald R. ; Perotti, Daniela ; Pritchard-Jones, Kathy ; Vokuhl, Christian ; van den Heuvel-Eibrink, Marry M. ; Graf, Norbert
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.
Sommerfeld, Andreas ; Senf, Cornelius ; Buma, Brian ; D'Amato, Anthony W. ; Després, Tiphaine ; Díaz-Hormazábal, Ignacio ; Fraver, Shawn ; Frelich, Lee E. ; Gutiérrez, Álvaro G. ; Hart, Sarah J. ; Harvey, Brian J. ; He, Hong S. ; Hlásny, Tomáš ; Holz, Andrés ; Kitzberger, Thomas ; Kulakowski, Dominik ; Lindenmayer, David ; Mori, Akira S. ; Müller, Jörg ; Paritsis, Juan ; Perry, George L. W. ; Stephens, Scott L. ; Svoboda, Miroslav ; Turner, Monica G. ; Veblen, Thomas T. ; Seidl, Rupert
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.
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.
The Drosophila microbiome has a limited influence on sleep, activity, and courtship behaviors
(2018)
Selkrig, Joel ; Mohammad, Farhan ; Ng, Soon Hwee ; Chua, Jia Yi ; Tumkaya, Tayfun ; Ho, Joses ; Chiang, Yin Ning ; Rieger, Dirk ; Pettersson, Sven ; Helfrich-Förster, Charlotte ; Yew, Joanne Y. ; Claridge-Chang, Adam
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.
Nerreter, Thomas ; Letschert, Sebastian ; Götz, Ralph ; Doose, Sören ; Danhof, Sophia ; Einsele, Hermann ; Sauer, Markus ; Hudecek, Michael
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.
Müller, Laura S. M. ; Cosentino, Raúl O. ; Förstner, Konrad U. ; Guizetti, Julien ; Wedel, Carolin ; Kaplan, Noam ; Janzen, Christian J. ; Arampatzi, Panagiota ; Vogel, Jörg ; Steinbiss, Sascha ; Otto, Thomas D. ; Saliba, Antoine-Emmanuel ; Sebra, Robert P. ; Siegel, T. Nicolai
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.