@article{PetrovGentschevVyalkovaetal.2020, author = {Petrov, Ivan and Gentschev, Ivaylo and Vyalkova, Anna and Elashry, Mohamed I. and Klymiuk, Michele C. and Arnhold, Stefan and Szalay, Aladar A.}, title = {Canine Adipose-Derived Mesenchymal Stem Cells (cAdMSCs) as a "Trojan Horse" in Vaccinia Virus Mediated Oncolytic Therapy against Canine Soft Tissue Sarcomas}, series = {Viruses}, volume = {12}, journal = {Viruses}, number = {7}, doi = {10.3390/v12070750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236007}, year = {2020}, abstract = {Several oncolytic viruses (OVs) including various human and canine adenoviruses, canine distemper virus, herpes-simplex virus, reovirus, and members of the poxvirus family, such as vaccinia virus and myxoma virus, have been successfully tested for canine cancer therapy in preclinical and clinical settings. The success of the cancer virotherapy is dependent on the ability of oncolytic viruses to overcome the attacks of the host immune system, to preferentially infect and lyse cancer cells, and to initiate tumor-specific immunity. To date, several different strategies have been developed to overcome the antiviral host defense barriers. In our study, we used canine adipose-derived mesenchymal stem cells (cAdMSCs) as a "Trojan horse" for the delivery of oncolytic vaccinia virus Copenhagen strain to achieve maximum oncolysis against canine soft tissue sarcoma (CSTS) tumors. A single systemic administration of vaccinia virus-loaded cAdMSCs was found to be safe and led to the significant reduction and substantial inhibition of tumor growth in a CSTS xenograft mouse model. This is the first example that vaccinia virus-loaded cAdMSCs could serve as a therapeutic agent against CSTS tumors.}, language = {en} } @article{BoschertKlenkAbtetal.2020, author = {Boschert, Verena and Klenk, Nicola and Abt, Alexander and Raman, Sudha Janaki and Fischer, Markus and Brands, Roman C. and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Bischler, Thorsten and Hartmann, Stefan}, title = {The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {2}, issn = {1422-0067}, doi = {10.3390/ijms21020471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235995}, year = {2020}, abstract = {Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.}, language = {en} } @article{ClassenEardleyHempetal.2020, author = {Classen, Alice and Eardley, Connal D. and Hemp, Andreas and Peters, Marcell K. and Peters, Ralph S. and Ssymank, Axel and Steffan-Dewenter, Ingolf}, title = {Specialization of plant-pollinator interactions increases with temperature at Mt. Kilimanjaro}, series = {Ecology and Evolution}, volume = {10}, journal = {Ecology and Evolution}, number = {4}, doi = {10.1002/ece3.6056}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235959}, pages = {2182-2195}, year = {2020}, abstract = {Aim: Species differ in their degree of specialization when interacting with other species, with significant consequences for the function and robustness of ecosystems. In order to better estimate such consequences, we need to improve our understanding of the spatial patterns and drivers of specialization in interaction networks. Methods: Here, we used the extensive environmental gradient of Mt. Kilimanjaro (Tanzania, East Africa) to study patterns and drivers of specialization, and robustness of plant-pollinator interactions against simulated species extinction with standardized sampling methods. We studied specialization, network robustness and other network indices of 67 quantitative plant-pollinator networks consisting of 268 observational hours and 4,380 plant-pollinator interactions along a 3.4 km elevational gradient. Using path analysis, we tested whether resource availability, pollinator richness, visitation rates, temperature, and/or area explain average specialization in pollinator communities. We further linked pollinator specialization to different pollinator taxa, and species traits, that is, proboscis length, body size, and species elevational ranges. Results: We found that specialization decreased with increasing elevation at different levels of biological organization. Among all variables, mean annual temperature was the best predictor of average specialization in pollinator communities. Specialization differed between pollinator taxa, but was not related to pollinator traits. Network robustness against simulated species extinctions of both plants and pollinators was lowest in the most specialized interaction networks, that is, in the lowlands. Conclusions: Our study uncovers patterns in plant-pollinator specialization along elevational gradients. Mean annual temperature was closely linked to pollinator specialization. Energetic constraints, caused by short activity timeframes in cold highlands, may force ectothermic species to broaden their dietary spectrum. Alternatively or in addition, accelerated evolutionary rates might facilitate the establishment of specialization under warm climates. Despite the mechanisms behind the patterns have yet to be fully resolved, our data suggest that temperature shifts in the course of climate change may destabilize pollination networks by affecting network architecture.}, language = {en} } @article{DeLiraRamanSchulzeetal.2020, author = {De Lira, Maria Nathalia and Raman, Sudha Janaki and Schulze, Almut and Schneider-Schaulies, Sibylle and Avota, Elita}, title = {Neutral Sphingomyelinase-2 (NSM 2) Controls T Cell Metabolic Homeostasis and Reprogramming During Activation}, series = {Frontiers in Molecular Biosciences}, volume = {7}, journal = {Frontiers in Molecular Biosciences}, issn = {2296-889X}, doi = {10.3389/fmolb.2020.00217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211311}, year = {2020}, abstract = {Neutral sphingomyelinase-2 (NSM2) is a member of a superfamily of enzymes responsible for conversion of sphingomyelin into phosphocholine and ceramide at the cytosolic leaflet of the plasma membrane. Upon specific ablation of NSM2, T cells proved to be hyper-responsive to CD3/CD28 co-stimulation, indicating that the enzyme acts to dampen early overshooting activation of these cells. It remained unclear whether hyper-reactivity of NSM2-deficient T cells is supported by a deregulated metabolic activity in these cells. Here, we demonstrate that ablation of NSM2 activity affects metabolism of the quiescent CD4\(^+\) T cells which accumulate ATP in mitochondria and increase basal glycolytic activity. This supports enhanced production of total ATP and metabolic switch early after TCR/CD28 stimulation. Most interestingly, increased metabolic activity in resting NSM2-deficient T cells does not support sustained response upon stimulation. While elevated under steady-state conditions in NSM2-deficient CD4\(^+\) T cells, the mTORC1 pathway regulating mitochondria size, oxidative phosphorylation, and ATP production is impaired after 24 h of stimulation. Taken together, the absence of NSM2 promotes a hyperactive metabolic state in unstimulated CD4\(^+\) T cells yet fails to support sustained T cell responses upon antigenic stimulation.}, language = {en} } @article{YangHeydarianKozjakPavlovicetal.2020, author = {Yang, Tao and Heydarian, Motaharehsadat and Kozjak-Pavlovic, Vera and Urban, Manuela and Harbottle, Richard P. and Rudel, Thomas}, title = {Folliculin Controls the Intracellular Survival and Trans-Epithelial Passage of Neisseria gonorrhoeae}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {10}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {422}, issn = {2235-2988}, doi = {10.3389/fcimb.2020.00422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211372}, year = {2020}, abstract = {Neisseria gonorrhoeae, a Gram-negative obligate human pathogenic bacterium, infects human epithelial cells and causes sexually transmitted diseases. Emerging multi-antibiotic resistant gonococci and increasing numbers of infections complicate the treatment of infected patients. Here, we used an shRNA library screen and next-generation sequencing to identify factors involved in epithelial cell infection. Folliculin (FLCN), a 64 kDa protein with a tumor repressor function was identified as a novel host factor important for N. gonorrhoeae survival after uptake. We further determined that FLCN did not affect N. gonorrhoeae adherence and invasion but was essential for its survival in the cells by modulating autophagy. In addition, FLCN was also required to maintain cell to cell contacts in the epithelial layer. In an infection model with polarized cells, FLCN inhibited the polarized localization of E-cadherin and the transcytosis of gonococci across polarized epithelial cells. In conclusion, we demonstrate here the connection between FLCN and bacterial infection and in particular the role of FLCN in the intracellular survival and transcytosis of gonococci across polarized epithelial cell layers.}, language = {en} } @article{BalkenholKaltdorfMammadovaBachetal.2020, author = {Balkenhol, Johannes and Kaltdorf, Kristin V. and Mammadova-Bach, Elmina and Braun, Attila and Nieswandt, Bernhard and Dittrich, Marcus and Dandekar, Thomas}, title = {Comparison of the central human and mouse platelet signaling cascade by systems biological analysis}, series = {BMC Genomics}, volume = {21}, journal = {BMC Genomics}, doi = {10.1186/s12864-020-07215-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230377}, year = {2020}, abstract = {Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81\%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences.}, language = {en} } @article{UrbanRemmeleDittrichetal.2020, author = {Urban, Lara and Remmele, Christian W. and Dittrich, Marcus and Schwarz, Roland F. and M{\"u}ller, Tobias}, title = {covRNA: discovering covariate associations in large-scale gene expression data}, series = {BMC Reserach Notes}, volume = {13}, journal = {BMC Reserach Notes}, doi = {10.1186/s13104-020-04946-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229258}, year = {2020}, abstract = {Objective The biological interpretation of gene expression measurements is a challenging task. While ordination methods are routinely used to identify clusters of samples or co-expressed genes, these methods do not take sample or gene annotations into account. We aim to provide a tool that allows users of all backgrounds to assess and visualize the intrinsic correlation structure of complex annotated gene expression data and discover the covariates that jointly affect expression patterns. Results The Bioconductor package covRNA provides a convenient and fast interface for testing and visualizing complex relationships between sample and gene covariates mediated by gene expression data in an entirely unsupervised setting. The relationships between sample and gene covariates are tested by statistical permutation tests and visualized by ordination. The methods are inspired by the fourthcorner and RLQ analyses used in ecological research for the analysis of species abundance data, that we modified to make them suitable for the distributional characteristics of both, RNA-Seq read counts and microarray intensities, and to provide a high-performance parallelized implementation for the analysis of large-scale gene expression data on multi-core computational systems. CovRNA provides additional modules for unsupervised gene filtering and plotting functions to ensure a smooth and coherent analysis workflow.}, language = {en} } @article{StelznerWinklerLiangetal.2020, author = {Stelzner, Kathrin and Winkler, Ann-Cathrin and Liang, Chunguang and Boyny, Aziza and Ade, Carsten P. and Dandekar, Thomas and Fraunholz, Martin J. and Rudel, Thomas}, title = {Intracellular Staphylococcus aureus Perturbs the Host Cell Ca\(^{2+}\) Homeostasis To Promote Cell Death}, series = {mBio}, volume = {11}, journal = {mBio}, doi = {10.1128/mBio.02250-20}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231448}, year = {2020}, abstract = {The opportunistic human pathogen Staphylococcus aureus causes serious infectious diseases that range from superficial skin and soft tissue infections to necrotizing pneumonia and sepsis. While classically regarded as an extracellular pathogen, S. aureus is able to invade and survive within human cells. Host cell exit is associated with cell death, tissue destruction, and the spread of infection. The exact molecular mechanism employed by S. aureus to escape the host cell is still unclear. In this study, we performed a genome-wide small hairpin RNA (shRNA) screen and identified the calcium signaling pathway as being involved in intracellular infection. S. aureus induced a massive cytosolic Ca\(^{2+}\) increase in epithelial host cells after invasion and intracellular replication of the pathogen. This was paralleled by a decrease in endoplasmic reticulum Ca\(^{2+}\) concentration. Additionally, calcium ions from the extracellular space contributed to the cytosolic Ca2+ increase. As a consequence, we observed that the cytoplasmic Ca\(^{2+}\) rise led to an increase in mitochondrial Ca\(^{2+}\) concentration, the activation of calpains and caspases, and eventually to cell lysis of S. aureus-infected cells. Our study therefore suggests that intracellular S. aureus disturbs the host cell Ca\(^{2+}\) homeostasis and induces cytoplasmic Ca\(^{2+}\) overload, which results in both apoptotic and necrotic cell death in parallel or succession. IMPORTANCE Despite being regarded as an extracellular bacterium, the pathogen Staphylococcus aureus can invade and survive within human cells. The intracellular niche is considered a hideout from the host immune system and antibiotic treatment and allows bacterial proliferation. Subsequently, the intracellular bacterium induces host cell death, which may facilitate the spread of infection and tissue destruction. So far, host cell factors exploited by intracellular S. aureus to promote cell death are only poorly characterized. We performed a genome-wide screen and found the calcium signaling pathway to play a role in S. aureus invasion and cytotoxicity. The intracellular bacterium induces a cytoplasmic and mitochondrial Ca\(^{2+}\) overload, which results in host cell death. Thus, this study first showed how an intracellular bacterium perturbs the host cell Ca\(^{2+}\) homeostasis."}, language = {en} } @article{NaseemOthmanFathyetal.2020, author = {Naseem, Muhammad and Othman, Eman M. and Fathy, Moustafa and Iqbal, Jibran and Howari, Fares M. and AlRemeithi, Fatima A. and Kodandaraman, Geema and Stopper, Helga and Bencurova, Elena and Vlachakis, Dimitrios and Dandekar, Thomas}, title = {Integrated structural and functional analysis of the protective effects of kinetin against oxidative stress in mammalian cellular systems}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-70253-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231317}, year = {2020}, abstract = {Metabolism and signaling of cytokinins was first established in plants, followed by cytokinin discoveries in all kingdoms of life. However, understanding of their role in mammalian cells is still scarce. Kinetin is a cytokinin that mitigates the effects of oxidative stress in mammalian cells. The effective concentrations of exogenously applied kinetin in invoking various cellular responses are not well standardized. Likewise, the metabolism of kinetin and its cellular targets within the mammalian cells are still not well studied. Applying vitality tests as well as comet assays under normal and hyper-oxidative states, our analysis suggests that kinetin concentrations of 500 nM and above cause cytotoxicity as well as genotoxicity in various cell types. However, concentrations below 100 nM do not cause any toxicity, rather in this range kinetin counteracts oxidative burst and cytotoxicity. We focus here on these effects. To get insights into the cellular targets of kinetin mediating these pro-survival functions and protective effects we applied structural and computational approaches on two previously testified targets for these effects. Our analysis deciphers vital residues in adenine phosphoribosyltransferase (APRT) and adenosine receptor (A2A-R) that facilitate the binding of kinetin to these two important human cellular proteins. We finally discuss how the therapeutic potential of kinetin against oxidative stress helps in various pathophysiological conditions.}, language = {en} } @article{SajkoGrishkovskayaKostanetal.2020, author = {Sajko, Sara and Grishkovskaya, Irina and Kostan, Julius and Graewert, Melissa and Setiawan, Kim and Tr{\"u}bestein, Linda and Niederm{\"u}ller, Korbinian and Gehin, Charlotte and Sponga, Antonio and Puchinger, Martin and Gavin, Anne-Claude and Leonard, Thomas A. and Svergun, Dimitri I. and Smith, Terry K. and Morriswood, Brooke and Djinovic-Carugo, Kristina}, title = {Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {23}, doi = {10.1371/journal.pone.0242677}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231261}, year = {2020}, abstract = {MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats-Trypanosoma brucei MORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein from Trypanosoma brucei and homologous proteins from the parasites Toxoplasma gondii and Plasmodium falciparum were obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This enabled a first structure-based definition of the MORN repeat itself. Furthermore, all three structures dimerised via their C-termini in an antiparallel configuration. The dimers could form extended or V-shaped quaternary structures depending on the presence of specific interface residues. This work provides a new perspective on MORN repeats, showing that they are protein-protein interaction modules capable of mediating both dimerisation and oligomerisation.}, language = {en} } @article{GoetzKunzFinketal.2020, author = {G{\"o}tz, Ralph and Kunz, Tobias C. and Fink, Julian and Solger, Franziska and Schlegel, Jan and Seibel, J{\"u}rgen and Kozjak-Pavlovic, Vera and Rudel, Thomas and Sauer, Markus}, title = {Nanoscale imaging of bacterial infections by sphingolipid expansion microscopy}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-19897-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231248}, year = {2020}, abstract = {Expansion microscopy (ExM) enables super-resolution imaging of proteins and nucleic acids on conventional microscopes. However, imaging of details of the organization of lipid bilayers by light microscopy remains challenging. We introduce an unnatural short-chain azide- and amino-modified sphingolipid ceramide, which upon incorporation into membranes can be labeled by click chemistry and linked into hydrogels, followed by 4x to 10x expansion. Confocal and structured illumination microscopy (SIM) enable imaging of sphingolipids and their interactions with proteins in the plasma membrane and membrane of intracellular organelles with a spatial resolution of 10-20nm. As our functionalized sphingolipids accumulate efficiently in pathogens, we use sphingolipid ExM to investigate bacterial infections of human HeLa229 cells by Neisseria gonorrhoeae, Chlamydia trachomatis and Simkania negevensis with a resolution so far only provided by electron microscopy. In particular, sphingolipid ExM allows us to visualize the inner and outer membrane of intracellular bacteria and determine their distance to 27.6 +/- 7.7nm. Imaging of lipid bilayers using light microscopy is challenging. Here the authors label cells using a short chain click-compatible ceramide to visualize mammalian and bacterial membranes with expansion microscopy.}, language = {en} } @article{MarkertSkoruppaYuetal.2020, author = {Markert, Sebastian M. and Skoruppa, Michael and Yu, Bin and Mulcahy, Ben and Zhen, Mai and Gao, Shangbang and Sendtner, Michael and Stigloher, Christian}, title = {Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission}, series = {Biology Open}, volume = {9}, journal = {Biology Open}, doi = {10.1242/bio.055129}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230662}, year = {2020}, abstract = {The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization.}, language = {en} } @article{VogelGossnerMergneretal.2020, author = {Vogel, Sebastian and Gossner, Martin M. and Mergner, Ulrich and M{\"u}ller, J{\"o}rg and Thorn, Simon}, title = {Optimizing enrichment of deadwood for biodiversity by varying sun exposure and tree species: An experimental approach}, series = {Journal of Applied Ecology}, volume = {57}, journal = {Journal of Applied Ecology}, number = {10}, doi = {10.1111/1365-2664.13648}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214614}, pages = {2075 -- 2085}, year = {2020}, abstract = {The enrichment of deadwood is essential for the conservation of saproxylic biodiversity in managed forests. However, existing strategies focus on a cost-intensive increase of deadwood amount, while largely neglecting increasing deadwood diversity. Deadwood objects, that is logs and branches, from six tree species were experimentally sun exposed, canopy shaded and artificially shaded for 4 years, after which the alpha-, beta- and gamma-diversity of saproxylic beetles, wood-inhabiting fungi and spiders were analysed. Analyses of beta-diversity included the spatial distance between exposed deadwood objects. A random-drawing procedure was used to identify the combination of tree species and sun exposure that yielded the highest gamma-diversity at a minimum of exposed deadwood amount. In sun-exposed plots, species numbers in logs were higher than in shaded plots for all taxa, while in branches we observed the opposite for saproxylic beetles. Tree species affected the species numbers only of saproxylic beetles and wood-inhabiting fungi. The beta-diversity of saproxylic beetles and wood-inhabiting fungi among logs was influenced by sun exposure and tree species, but beta-diversity of spiders by sun exposure only. For all saproxylic taxa recorded in logs, differences between communities increased with increasing spatial distance. A combination of canopy-shaded Carpinus logs and sun-exposed Populus logs resulted in the highest species numbers of all investigated saproxylic taxa among all possible combinations of tree species and sun-exposure treatments. Synthesis and applications. We recommend incorporating the enrichment of different tree species and particularly the variation in sun exposure into existing strategies of deadwood enrichment. Based on the results of our study, we suggest to combine the logs of softwood broadleaf tree species (e.g. Carpinus, Populus), hardwood broadleaf tree species (e.g. Quercus) and coniferous tree species (e.g. Pinus) under different conditions of sun exposure and distribute them spatially in a landscape to maximize the beneficial effects on overall diversity.}, language = {en} } @article{LealSchwebsBriggsetal.2020, author = {Leal, Andrea Zurita and Schwebs, Marie and Briggs, Emma and Weisert, Nadine and Reis, Helena and Lemgruber, Leondro and Luko, Katarina and Wilkes, Jonathan and Butter, Falk and McCulloch, Richard and Janzen, Christian J.}, title = {Genome maintenance functions of a putative Trypanosoma brucei translesion DNA polymerase include telomere association and a role in antigenic variation}, series = {Nucleic Acids Research}, volume = {48}, journal = {Nucleic Acids Research}, number = {17}, doi = {10.1093/nar/gkaa686}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230579}, pages = {9660-9680}, year = {2020}, abstract = {Maintenance of genome integrity is critical to guarantee transfer of an intact genome from parent to off-spring during cell division. DNA polymerases (Pols) provide roles in both replication of the genome and the repair of a wide range of lesions. Amongst replicative DNA Pols, translesion DNA Pols play a particular role: replication to bypass DNA damage. All cells express a range of translesion Pols, but little work has examined their function in parasites, including whether the enzymes might contribute to host-parasite interactions. Here, we describe a dual function of one putative translesion Pol in African trypanosomes, which we now name TbPolIE. Previously, we demonstrated that TbPolIE is associated with telomeric sequences and here we show that RNAi-mediated depletion of TbPolIE transcripts results in slowed growth, altered DNA content, changes in cell morphology, and increased sensitivity to DNA damaging agents. We also show that TbPolIE displays pronounced localization at the nuclear periphery, and that its depletion leads to chromosome segregation defects and increased levels of endogenous DNA damage. Finally, we demonstrate that TbPolIE depletion leads to deregulation of telomeric variant surface glycoprotein genes, linking the function of this putative translesion DNA polymerase to host immune evasion by antigenic variation.}, language = {en} } @article{FlorenvonRintelenHerbertetal.2020, author = {Floren, Andreas and von Rintelen, Thomas and Herbert, Paul D. N. and de Araujo, Bruno Cancian and Schmidt, Stefan and Balke, Michael and Narakusumo, Raden Pramesa and Peggie, Djunijanti and Ubaidillah, Rosichon and von Rintelen, Kristina and M{\"u}ller, Tobias}, title = {Integrative ecological and molecular analysis indicate high diversity and strict elevational separation of canopy beetles in tropical mountain forests}, series = {Scientific Reports}, volume = {10}, journal = {Scientific Reports}, doi = {10.1038/s41598-020-73519-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230565}, year = {2020}, abstract = {Tropical mountain forests contribute disproportionately to terrestrial biodiversity but little is known about insect diversity in the canopy and how it is distributed between tree species. We sampled tree-specific arthropod communities from 28 trees by canopy fogging and analysed beetle communities which were first morphotyped and then identified by their DNA barcodes. Our results show that communities from forests at 1100 and 1700 m a.s.l. are almost completely distinct. Diversity was much lower in the upper forest while community structure changed from many rare, less abundant species to communities with a pronounced dominance structure. We also found significantly higher beta-diversity between trees at the lower than higher elevation forest where community similarity was high. Comparisons on tree species found at both elevations reinforced these results. There was little species overlap between sites indicating limited elevational ranges. Furthermore, we exploited the advantage of DNA barcodes to patterns of haplotype diversity in some of the commoner species. Our results support the advantage of fogging and DNA barcodes for community studies and underline the need for comprehensive research aimed at the preservation of these last remaining pristine forests.}, language = {en} } @article{MatthesDiersSchlegeletal.2020, author = {Matthes, Niels and Diers, Johannes and Schlegel, Nicolas and Hankir, Mohammed and Haubitz, Imme and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Validation of MTL30 as a quality indicator for colorectal surgery}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0238473}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230530}, year = {2020}, abstract = {Background Valid indicators are required to measure surgical quality. These ideally should be sensitive and selective while being easy to understand and adjust. We propose here the MTL30 quality indicator which takes into account 30-day mortality, transfer within 30 days, and a length of stay of 30 days as composite markers of an uneventful operative/postoperative course. Methods Patients documented in the StuDoQ|Colon and StuDoQ|Rectal carcinoma register of the German Society for General and Visceral Surgery (DGAV) were analyzed with regard to the effects of patient and tumor-related risk factors as well as postoperative complications on the MTL30. Results In univariate analysis, the MTL30 correlated significantly with patient and tumor-related risk factors such as ASA score (p<0.001), age (p<0.001), or UICC stage (p<0.001). There was a high sensitivity for the postoperative occurrence of complications such as re-operations (p<0.001) or subsequent bleeding (p<0.001), as well as a significant correlation with the CDC classification (p<0.001). In multivariate analysis, patient-related risk factors and postoperative complications significantly increased the odds ratio for a positive MTL30. A negative MTL30 showed a high specify for an uneventful operative and postoperative course. Conclusion The MTL30 is a valid indicator of colorectal surgical quality.}, language = {en} } @article{ThornChaoGeorgievetal.2020, author = {Thorn, Simon and Chao, Anne and Georgiev, Konstadin B. and M{\"u}ller, J{\"o}rg and B{\"a}ssler, Claus and Campbell, John L. and Jorge, Castro and Chen, Yan-Han and Choi, Chang-Yong and Cobb, Tyler P. and Donato, Daniel C. and Durska, Ewa and Macdonald, Ellen and Feldhaar, Heike and Fontaine, Jospeh B. and Fornwalt, Paula J. and Hern{\´a}ndez Hern{\´a}ndez, Raquel Mar{\´i}a and Hutto, Richard L. and Koivula, Matti and Lee, Eun-Jae and Lindenmayer, David and Mikusinski, Grzegorz and Obrist, Martin K. and Perl{\´i}k, Michal and Rost, Josep and Waldron, Kaysandra and Wermelinger, Beat and Weiß, Ingmar and Zmihorski, Michal and Leverkus, Alexandro B.}, title = {Estimating retention benchmarks for salvage logging to protect biodiversity}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-18612-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230512}, year = {2020}, abstract = {Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757\% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90\% richness of its unique species, whereas retaining 50\% of a naturally disturbed forest unlogged maintains 73 +/- 12\% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75\% of the naturally disturbed forest should be left unlogged to maintain 90\% of the species unique to the area.}, language = {en} } @article{GromaHorstDasetal.2020, author = {Groma, Michaela and Horst, Sarah A. and Das, Sudip and Huettel, Bruno and Klepsch, Maximilian and Rudel, Thomas and Medina, Eva and Fraunholz, Martin}, title = {Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection}, series = {mbio}, volume = {11}, journal = {mbio}, number = {4}, doi = {10.1128/mBio.01646-20}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230473}, year = {2020}, abstract = {Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used an S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used an S. aureus strain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched-chain amino acid biosynthesis, a methionine sulfoxide reductase, and a copper transporter as well as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, is induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enables a rapid adaptation of S. aureus to the changing host microenvironment. IMPORTANCE Staphylococcus aureus is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a Staphylococcus aureus transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by S. aureus for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of S. aureus to the host microenvironment found in secondary infection sites.}, language = {en} } @article{RoemerCosarinskyRoces2020, author = {R{\"o}mer, Daniela and Cosarinsky, Marcela I. and Roces, Flavio}, title = {Selection and spatial arrangement of building materials during the construction of nest turrets by grass-cutting ants}, series = {Royal Society Open Science}, volume = {7}, journal = {Royal Society Open Science}, doi = {10.1098/rsos.201312}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230458}, year = {2020}, abstract = {Ants build complex nest structures by reacting to simple, local stimuli. While underground nests result from the space generated by digging, some leaf- and grass-cutting ants also construct conspicuous aboveground turrets around nest openings. We investigated whether the selection of specific building materials occurs during turret construction in Acromyrmex fracticornis grass-cutting ants, and asked whether single building decisions at the beginning can modify the final turret architecture. To quantify workers' material selection, the original nest turret was removed and a choice between two artificial building materials, thin and thick sticks, was offered for rebuilding. Workers preferred thick sticks at the very beginning of turret construction, showed varying preferences thereafter, and changed to prefer thin sticks for the upper, final part of the turret, indicating that they selected different building materials over time to create a stable structure. The impact of a single building choice on turret architecture was evaluated by placing artificial beams that divided a colony's nest entrance at the beginning of turret rebuilding. Splitting the nest entrance led to the self-organized construction of turrets with branched galleries ending in multiple openings, showing that the spatial location of a single building material can strongly influence turret morphology.}, language = {en} } @article{WhisnantJuergesHennigetal.2020, author = {Whisnant, Adam W. and J{\"u}rges, Christopher S. and Hennig, Thomas and Wyler, Emanuel and Prusty, Bhupesh and Rutkowski, Andrzej J. and L'hernault, Anne and Djakovic, Lara and G{\"o}bel, Margarete and D{\"o}ring, Kristina and Menegatti, Jennifer and Antrobus, Robin and Matheson, Nicholas J. and K{\"u}nzig, Florian W. H. and Mastrobuoni, Guido and Bielow, Chris and Kempa, Stefan and Liang, Chunguang and Dandekar, Thomas and Zimmer, Ralf and Landthaler, Markus and Gr{\"a}sser, Friedrich and Lehner, Paul J. and Friedel, Caroline C. and Erhard, Florian and D{\"o}lken, Lars}, title = {Integrative functional genomics decodes herpes simplex virus 1}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-15992-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229884}, year = {2020}, abstract = {The predicted 80 open reading frames (ORFs) of herpes simplex virus 1 (HSV-1) have been intensively studied for decades. Here, we unravel the complete viral transcriptome and translatome during lytic infection with base-pair resolution by computational integration of multi-omics data. We identify a total of 201 transcripts and 284 ORFs including all known and 46 novel large ORFs. This includes a so far unknown ORF in the locus deleted in the FDA-approved oncolytic virus Imlygic. Multiple transcript isoforms expressed from individual gene loci explain translation of the vast majority of ORFs as well as N-terminal extensions (NTEs) and truncations. We show that NTEs with non-canonical start codons govern the subcellular protein localization and packaging of key viral regulators and structural proteins. We extend the current nomenclature to include all viral gene products and provide a genome browser that visualizes all the obtained data from whole genome to single-nucleotide resolution. Here, using computational integration of multi-omics data, the authors provide a detailed transcriptome and translatome of herpes simplex virus 1 (HSV-1), including previously unidentified ORFs and N-terminal extensions. The study also provides a HSV-1 genome browser and should be a valuable resource for further research.}, language = {en} }