TY  - JOUR
A1  - Too, Chin Chin
A1  - Keller, Alexander
A1  - Sickel, Wiebke
A1  - Lee, Sui Mae
A1  - Yule, Catherine M.
T1  - Microbial Community Structure in a Malaysian Tropical Peat Swamp Forest: The Influence of Tree Species and Depth
JF  - Frontiers in Microbiology
N2  - Tropical peat swamp forests sequester globally significant stores of carbon in deep layers of waterlogged, anoxic, acidic and nutrient-depleted peat. The roles of microbes in supporting these forests through the formation of peat, carbon sequestration and nutrient cycling are virtually unknown. This study investigated physicochemical peat properties and microbial diversity between three dominant tree species: Shorea uliginosa (Dipterocarpaceae), Koompassia malaccensis (legumes associated with nitrogen-fixing bacteria), Eleiodoxa conferta (palm) and depths (surface, 45 and 90 cm) using microbial 16S rRNA gene amplicon sequencing. Water pH, oxygen, nitrogen, phosphorus, total phenolic contents and C/N ratio differed significantly between depths, but not tree species. Depth also strongly influenced microbial diversity and composition, while both depth and tree species exhibited significant impact on the archaeal communities. Microbial diversity was highest at the surface, where fresh leaf litter accumulates, and nutrient supply is guaranteed. Nitrogen was the core parameter correlating to microbial communities, but the interactive effects from various environmental variables displayed significant correlation to relative abundance of major microbial groups. Proteobacteria was the dominant phylum and the most abundant genus, Rhodoplanes, might be involved in nitrogen fixation. The most abundant methanogens and methanotrophs affiliated, respectively, to families Methanomassiliicoccaceae and Methylocystaceae. Our results demonstrated diverse microbial communities and provide valuable insights on microbial ecology in these extreme ecosystems.
KW  - tropical peat swamp forest
KW  - metabarcoding
KW  - microbial diversity and composition
KW  - tree species
KW  - depth
KW  - methanogens
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229000
VL  - 9
ER  - 
TY  - JOUR
A1  - Prusty, Bhupesh K.
A1  - Gulve, Nitish
A1  - Govind, Sheila
A1  - Krueger, Gerhard R. F.
A1  - Feichtinger, Julia
A1  - Larcombe, Lee
A1  - Aspinall, Richard
A1  - Ablashi, Dharam V.
A1  - Toro, Carla T.
T1  - Active HHV-6 Infection of Cerebellar Purkinje Cells in Mood Disorders
JF  - Frontiers in Microbiology
N2  - Early-life infections and associated neuroinflammation is incriminated in the pathogenesis of various mood disorders. Infection with human roseoloviruses, HHV-6A and HHV-6B, allows viral latency in the central nervous system and other tissues, which can later be activated causing cognitive and behavioral disturbances. Hence, this study was designed to evaluate possible association of HHV-6A and HHV-6B activation with three different groups of psychiatric patients. DNA qPCR, immunofluorescence and FISH studies were carried out in post-mortem posterior cerebellum from 50 cases each of bipolar disorder (BPD), schizophrenia, 15 major depressive disorder (MDD) and 50 appropriate control samples obtained from two well-known brain collections (Stanley Medical Research Institute). HHV-6A and HHV-6B late proteins (indicating active infection) and viral DNA were detected more frequently (p < 0.001 for each virus) in human cerebellum in MDD and BPD relative to controls. These roseolovirus proteins and DNA were found less frequently in schizophrenia cases. Active HHV-6A and HHV-6B infection in cerebellar Purkinje cells were detected frequently in BPD and MDD cases. Furthermore, we found a significant association of HHV-6A infection with reduced Purkinje cell size, suggesting virus-mediated abnormal Purkinje cell function in these disorders. Finally, gene expression analysis of cerebellar tissue revealed changes in pathways reflecting an inflammatory response possibly to HHV-6A infection. Our results provide molecular evidence to support a role for active HHV-6A and HHV-6B infection in BPD and MDD.
KW  - HHV-6
KW  - bipolar disorder
KW  - schizophrenia
KW  - major depressive disorder
KW  - Purkinje cells
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-369222
VL  - 9
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  - 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  - 
TY  - JOUR
A1  - Kraus, Michael
A1  - Grimm, Clemens
A1  - Seibel, Jürgen
T1  - Reversibility of a Point Mutation Induced Domain Shift: Expanding the Conformational Space of a Sucrose Phosphorylase
JF  - Scientific Reports
N2  - Despite their popularity as enzyme engineering targets structural information about Sucrose Phosphorylases remains scarce. We recently clarified that the Q345F variant of Bifidobacterium adolescentis Sucrose Phosphorylase is able to accept large polyphenolic substrates like resveratrol via a domain shift. Here we present a crystal structure of this variant in a conformation suitable for the accommodation of the donor substrate sucrose in excellent agreement with the wild type structure. Remarkably, this conformation does not feature the previously observed domain shift which is therefore reversible and part of a dynamic process rather than a static phenomenon. This crystallographic snapshot completes our understanding of the catalytic cycle of this useful variant and will allow for a more rational design of further generations of Sucrose Phosphorylase variants.
KW  - biocatalysis
KW  - X-ray crystallography
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224845
VL  - 8
ER  - 
TY  - JOUR
A1  - Hines, Rochelle M.
A1  - Maric, Hans Michael
A1  - Hines, Dustin J.
A1  - Modgil, Amit
A1  - Panzanelli, Patrizia
A1  - Nakamura, Yasuko
A1  - Nathanson, Anna J.
A1  - Cross, Alan
A1  - Deeb, Tarek
A1  - Brandon, Nicholas J.
A1  - Davies, Paul
A1  - Fritschy, Jean-Marc
A1  - Schindelin, Hermann
A1  - Moss, Stephen J.
T1  - Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin
JF  - Nature Communications
N2  - Fast inhibitory synaptic transmission is mediated by γ-aminobutyric acid type A receptors (GABAARs) that are enriched at functionally diverse synapses via mechanisms that remain unclear. Using isothermal titration calorimetry and complementary methods we demonstrate an exclusive low micromolar binding of collybistin to the α2-subunit of GABAARs. To explore the biological relevance of collybistin-α2-subunit selectivity, we generate mice with a mutation in the α2-subunit-collybistin binding region (Gabra2-1). The mutation results in loss of a distinct subset of inhibitory synapses and decreased amplitude of inhibitory synaptic currents. Gabra2–1 mice have a striking phenotype characterized by increased susceptibility to seizures and early mortality. Surviving Gabra2-1 mice show anxiety and elevations in electroencephalogram δ power, which are ameliorated by treatment with the α2/α3-selective positive modulator, AZD7325. Taken together, our results demonstrate an α2-subunit selective binding of collybistin, which plays a key role in patterned brain activity, particularly during development.
KW  - cellular neuroscience
KW  - ion channels in the nervous system
KW  - neurotransmitters
KW  - synaptic development
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320719
VL  - 9
ER  -