@article{GeisingerRodriguezCasuriagaBenavente2021, author = {Geisinger, Adriana and Rodr{\´i}guez-Casuriaga, Rosana and Benavente, Ricardo}, title = {Transcriptomics of Meiosis in the Male Mouse}, series = {Frontiers in Cell and Developmental Biology}, volume = {9}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2021.626020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231032}, year = {2021}, abstract = {Molecular studies of meiosis in mammals have been long relegated due to some intrinsic obstacles, namely the impossibility to reproduce the process in vitro, and the difficulty to obtain highly pure isolated cells of the different meiotic stages. In the recent years, some technical advances, from the improvement of flow cytometry sorting protocols to single-cell RNAseq, are enabling to profile the transcriptome and its fluctuations along the meiotic process. In this mini-review we will outline the diverse methodological approaches that have been employed, and some of the main findings that have started to arise from these studies. As for practical reasons most studies have been carried out in males, and mostly using mouse as a model, our focus will be on murine male meiosis, although also including specific comments about humans. Particularly, we will center on the controversy about gene expression during early meiotic prophase; the widespread existing gap between transcription and translation in meiotic cells; the expression patterns and potential roles of meiotic long non-coding RNAs; and the visualization of meiotic sex chromosome inactivation from the RNAseq perspective.}, language = {en} } @article{HartmannReisslandMaieretal.2021, author = {Hartmann, Oliver and Reissland, Michaela and Maier, Carina R. and Fischer, Thomas and Prieto-Garcia, Cristian and Baluapuri, Apoorva and Schwarz, Jessica and Schmitz, Werner and Garrido-Rodriguez, Martin and Pahor, Nikolett and Davies, Clare C. and Bassermann, Florian and Orian, Amir and Wolf, Elmar and Schulze, Almut and Calzado, Marco A. and Rosenfeldt, Mathias T. and Diefenbacher, Markus E.}, title = {Implementation of CRISPR/Cas9 Genome Editing to Generate Murine Lung Cancer Models That Depict the Mutational Landscape of Human Disease}, series = {Frontiers in Cell and Developmental Biology}, volume = {9}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2021.641618}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230949}, year = {2021}, abstract = {Lung cancer is the most common cancer worldwide and the leading cause of cancer-related deaths in both men and women. Despite the development of novel therapeutic interventions, the 5-year survival rate for non-small cell lung cancer (NSCLC) patients remains low, demonstrating the necessity for novel treatments. One strategy to improve translational research is the development of surrogate models reflecting somatic mutations identified in lung cancer patients as these impact treatment responses. With the advent of CRISPR-mediated genome editing, gene deletion as well as site-directed integration of point mutations enabled us to model human malignancies in more detail than ever before. Here, we report that by using CRISPR/Cas9-mediated targeting of Trp53 and KRas, we recapitulated the classic murine NSCLC model Trp53fl/fl:lsl-KRasG12D/wt. Developing tumors were indistinguishable from Trp53fl/fl:lsl-KRasG12D/wt-derived tumors with regard to morphology, marker expression, and transcriptional profiles. We demonstrate the applicability of CRISPR for tumor modeling in vivo and ameliorating the need to use conventional genetically engineered mouse models. Furthermore, tumor onset was not only achieved in constitutive Cas9 expression but also in wild-type animals via infection of lung epithelial cells with two discrete AAVs encoding different parts of the CRISPR machinery. While conventional mouse models require extensive husbandry to integrate new genetic features allowing for gene targeting, basic molecular methods suffice to inflict the desired genetic alterations in vivo. Utilizing the CRISPR toolbox, in vivo cancer research and modeling is rapidly evolving and enables researchers to swiftly develop new, clinically relevant surrogate models for translational research.}, language = {en} } @article{YuWolfThuseketal.2021, author = {Yu, Yidong and Wolf, Ann-Katrin and Thusek, Sina and Heinekamp, Thorsten and Bromley, Michael and Krappmann, Sven and Terpitz, Ulrich and Voigt, Kerstin and Brakhage, Axel A. and Beilhack, Andreas}, title = {Direct Visualization of Fungal Burden in Filamentous Fungus-Infected Silkworms}, series = {Journal of Fungi}, volume = {7}, journal = {Journal of Fungi}, number = {2}, issn = {2309-608X}, doi = {10.3390/jof7020136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228855}, year = {2021}, abstract = {Invasive fungal infections (IFIs) are difficult to diagnose and to treat and, despite several available antifungal drugs, cause high mortality rates. In the past decades, the incidence of IFIs has continuously increased. More recently, SARS-CoV-2-associated lethal IFIs have been reported worldwide in critically ill patients. Combating IFIs requires a more profound understanding of fungal pathogenicity to facilitate the development of novel antifungal strategies. Animal models are indispensable for studying fungal infections and to develop new antifungals. However, using mammalian animal models faces various hurdles including ethical issues and high costs, which makes large-scale infection experiments extremely challenging. To overcome these limitations, we optimized an invertebrate model and introduced a simple calcofluor white (CW) staining protocol to macroscopically and microscopically monitor disease progression in silkworms (Bombyx mori) infected with the human pathogenic filamentous fungi Aspergillus fumigatus and Lichtheimia corymbifera. This advanced silkworm A. fumigatus infection model could validate knockout mutants with either attenuated, strongly attenuated or unchanged virulence. Finally, CW staining allowed us to efficiently visualize antifungal treatment outcomes in infected silkworms. Conclusively, we here present a powerful animal model combined with a straightforward staining protocol to expedite large-scale in vivo research of fungal pathogenicity and to investigate novel antifungal candidates.}, language = {en} } @article{HensgenEnglandHombergetal.2021, author = {Hensgen, Ronja and England, Laura and Homberg, Uwe and Pfeiffer, Keram}, title = {Neuroarchitecture of the central complex in the brain of the honeybee: Neuronal cell types}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, doi = {10.1002/cne.24941}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215566}, pages = {159-186}, year = {2021}, abstract = {The central complex (CX) in the insect brain is a higher order integration center that controls a number of behaviors, most prominently goal directed locomotion. The CX comprises the protocerebral bridge (PB), the upper division of the central body (CBU), the lower division of the central body (CBL), and the paired noduli (NO). Although spatial orientation has been extensively studied in honeybees at the behavioral level, most electrophysiological and anatomical analyses have been carried out in other insect species, leaving the morphology and physiology of neurons that constitute the CX in the honeybee mostly enigmatic. The goal of this study was to morphologically identify neuronal cell types of the CX in the honeybee Apis mellifera. By performing iontophoretic dye injections into the CX, we traced 16 subtypes of neuron that connect a subdivision of the CX with other regions in the bee's central brain, and eight subtypes that mainly interconnect different subdivisions of the CX. They establish extensive connections between the CX and the lateral complex, the superior protocerebrum and the posterior protocerebrum. Characterized neuron classes and subtypes are morphologically similar to those described in other insects, suggesting considerable conservation in the neural network relevant for orientation.}, language = {en} } @article{KunzRuehlingMoldovanetal.2021, author = {Kunz, Tobias C. and R{\"u}hling, Marcel and Moldovan, Adriana and Paprotka, Kerstin and Kozjak-Pavlovic, Vera and Rudel, Thomas and Fraunholz, Martin}, title = {The Expandables: Cracking the Staphylococcal Cell Wall for Expansion Microscopy}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {11}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2021.644750}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232292}, year = {2021}, abstract = {Expansion Microscopy (ExM) is a novel tool improving the resolution of fluorescence microscopy by linking the sample into a hydrogel that gets physically expanded in water. Previously, we have used ExM to visualize the intracellular Gram-negative pathogens Chlamydia trachomatis, Simkania negevensis, and Neisseria gonorrhoeae. Gram-positive bacteria have a rigid and thick cell wall that impedes classic expansion strategies. Here we developed an approach, which included a series of enzymatic treatments resulting in isotropic 4× expansion of the Gram-positive pathogen Staphylococcus aureus. We further demonstrate the suitability of the technique for imaging of planktonic bacteria as well as endocytosed, intracellular bacteria at a spatial resolution of approximately 60 nm with conventional confocal laser scanning microscopy.}, language = {en} } @article{DuMaYanez‐Serranoetal.2021, author = {Du, Baoguo and Ma, Yuhua and Y{\´a}{\~n}ez-Serrano, Ana Maria and Arab, Leila and Fasbender, Lukas and Alfarraj, Saleh and Albasher, Gadah and Hedrich, Rainer and White, Philip J. and Werner, Christiane and Rennenberg, Heinz}, title = {Physiological responses of date palm (Phoenix dactylifera) seedlings to seawater and flooding}, series = {New Phytologist}, volume = {229}, journal = {New Phytologist}, number = {6}, doi = {10.1111/nph.17123}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228226}, pages = {3318 -- 3329}, year = {2021}, abstract = {In their natural environment along coast lines, date palms are exposed to seawater inundation and, hence, combined stress by salinity and flooding. To elucidate the consequences of this combined stress on foliar gas exchange and metabolite abundances in leaves and roots, date palm seedlings were exposed to flooding with seawater and its major constituents under controlled conditions. Seawater flooding significantly reduced CO\(_{2}\) assimilation, transpiration and stomatal conductance, but did not affect isoprene emission. A similar effect was observed upon NaCl exposure. By contrast, flooding with distilled water or MgSO\(_{4}\) did not affect CO\(_{2}\)/H\(_{2}\)O gas exchange or stomatal conductance significantly, indicating that neither flooding itself, nor seawater sulfate, contributed greatly to stomatal closure. Seawater exposure increased Na and Cl contents in leaves and roots, but did not affect sulfate contents significantly. Metabolite analyses revealed reduced abundances of foliar compatible solutes, such as sugars and sugar alcohols, whereas nitrogen compounds accumulated in roots. Reduced transpiration upon seawater exposure may contribute to controlling the movement of toxic ions to leaves and, therefore, can be seen as a mechanism to cope with salinity. The present results indicate that date palm seedlings are tolerant towards seawater exposure to some extent, and highly tolerant to flooding.}, language = {en} } @article{SeiboldHothornGossneretal.2021, author = {Seibold, Sebastian and Hothorn, Torsten and Gossner, Martin M. and Simons, Nadja K. and Bl{\"u}thgen, Nico and M{\"u}ller, J{\"o}rg and Ambarl{\i}, Didem and Ammer, Christian and Bauhus, J{\"u}rgen and Fischer, Markus and Habel, Jan C. and Penone, Caterina and Schall, Peter and Schulze, Ernst-Detlef and Weisser, Wolfgang W.}, title = {Insights from regional and short-term biodiversity monitoring datasets are valuable: a reply to Daskalova et al. 2021}, series = {Insect Conservation and Diversity}, volume = {14}, journal = {Insect Conservation and Diversity}, number = {1}, doi = {10.1111/icad.12467}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228309}, pages = {144 -- 148}, year = {2021}, abstract = {Reports of major losses in insect biodiversity have stimulated an increasing interest in temporal population changes. Existing datasets are often limited to a small number of study sites, few points in time, a narrow range of land-use intensities and only some taxonomic groups, or they lack standardised sampling. While new monitoring programs have been initiated, they still cover rather short time periods. Daskalova et al. 2021 (Insect Conservation and Diversity, 14, 1-18) argue that temporal trends of insect populations derived from short time series are biased towards extreme trends, while their own analysis of an assembly of shorter- and longer-term time series does not support an overall insect decline. With respect to the results of Seibold et al. 2019 (Nature, 574, 671-674) based on a 10-year multi-site time series, they claim that the analysis suffers from not accounting for temporal pseudoreplication. Here, we explain why the criticism of missing statistical rigour in the analysis of Seibold et al. (2019) is not warranted. Models that include 'year' as random effect, as suggested by Daskalova et al. (2021), fail to detect non-linear trends and assume that consecutive years are independent samples which is questionable for insect time-series data. We agree with Daskalova et al. (2021) that the assembly and analysis of larger datasets is urgently needed, but it will take time until such datasets are available. Thus, short-term datasets are highly valuable, should be extended and analysed continually to provide a more detailed understanding of insect population changes under the influence of global change, and to trigger immediate conservation actions.}, language = {en} } @article{BritzMarkertWitvlietetal.2021, author = {Britz, Sebastian and Markert, Sebastian Matthias and Witvliet, Daniel and Steyer, Anna Maria and Tr{\"o}ger, Sarah and Mulcahy, Ben and Kollmannsberger, Philip and Schwab, Yannick and Zhen, Mei and Stigloher, Christian}, title = {Structural Analysis of the Caenorhabditis elegans Dauer Larval Anterior Sensilla by Focused Ion Beam-Scanning Electron Microscopy}, series = {Frontiers in Neuroanatomy}, volume = {15}, journal = {Frontiers in Neuroanatomy}, issn = {1662-5129}, doi = {10.3389/fnana.2021.732520}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-249622}, year = {2021}, abstract = {At the end of the first larval stage, the nematode Caenorhabditis elegans developing in harsh environmental conditions is able to choose an alternative developmental path called the dauer diapause. Dauer larvae exhibit different physiology and behaviors from non-dauer larvae. Using focused ion beam-scanning electron microscopy (FIB-SEM), we volumetrically reconstructed the anterior sensory apparatus of C. elegans dauer larvae with unprecedented precision. We provide a detailed description of some neurons, focusing on structural details that were unknown or unresolved by previously published studies. They include the following: (1) dauer-specific branches of the IL2 sensory neurons project into the periphery of anterior sensilla and motor or putative sensory neurons at the sub-lateral cords; (2) ciliated endings of URX sensory neurons are supported by both ILso and AMso socket cells near the amphid openings; (3) variability in amphid sensory dendrites among dauers; and (4) somatic RIP interneurons maintain their projection into the pharyngeal nervous system. Our results support the notion that dauer larvae structurally expand their sensory system to facilitate searching for more favorable environments.}, language = {en} } @article{PauliPaulProppertetal.2021, author = {Pauli, Martin and Paul, Mila M. and Proppert, Sven and Mrestani, Achmed and Sharifi, Marzieh and Repp, Felix and K{\"u}rzinger, Lydia and Kollmannsberger, Philip and Sauer, Markus and Heckmann, Manfred and Sir{\´e}n, Anna-Leena}, title = {Targeted volumetric single-molecule localization microscopy of defined presynaptic structures in brain sections}, series = {Communications Biology}, volume = {4}, journal = {Communications Biology}, doi = {10.1038/s42003-021-01939-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259830}, pages = {407}, year = {2021}, abstract = {Revealing the molecular organization of anatomically precisely defined brain regions is necessary for refined understanding of synaptic plasticity. Although three-dimensional (3D) single-molecule localization microscopy can provide the required resolution, imaging more than a few micrometers deep into tissue remains challenging. To quantify presynaptic active zones (AZ) of entire, large, conditional detonator hippocampal mossy fiber (MF) boutons with diameters as large as 10 mu m, we developed a method for targeted volumetric direct stochastic optical reconstruction microscopy (dSTORM). An optimized protocol for fast repeated axial scanning and efficient sequential labeling of the AZ scaffold Bassoon and membrane bound GFP with Alexa Fluor 647 enabled 3D-dSTORM imaging of 25 mu m thick mouse brain sections and assignment of AZs to specific neuronal substructures. Quantitative data analysis revealed large differences in Bassoon cluster size and density for distinct hippocampal regions with largest clusters in MF boutons. Pauli et al. develop targeted volumetric dSTORM in order to image large hippocampal mossy fiber boutons (MFBs) in brain slices. They can identify synaptic targets of individual MFBs and measured size and density of Bassoon clusters within individual untruncated MFBs at nanoscopic resolution.}, language = {en} } @article{HurdGruebelWojciechowskietal.2021, author = {Hurd, Paul J. and Gr{\"u}bel, Kornelia and Wojciechowski, Marek and Maleszka, Ryszard and R{\"o}ssler, Wolfgang}, title = {Novel structure in the nuclei of honey bee brain neurons revealed by immunostaining}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, doi = {10.1038/s41598-021-86078-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260059}, pages = {6852}, year = {2021}, abstract = {In the course of a screen designed to produce antibodies (ABs) with affinity to proteins in the honey bee brain we found an interesting AB that detects a highly specific epitope predominantly in the nuclei of Kenyon cells (KCs). The observed staining pattern is unique, and its unfamiliarity indicates a novel previously unseen nuclear structure that does not colocalize with the cytoskeletal protein f-actin. A single rod-like assembly, 3.7-4.1 mu m long, is present in each nucleus of KCs in adult brains of worker bees and drones with the strongest immuno-labelling found in foraging bees. In brains of young queens, the labelling is more sporadic, and the rod-like structure appears to be shorter (similar to 2.1 mu m). No immunostaining is detectable in worker larvae. In pupal stage 5 during a peak of brain development only some occasional staining was identified. Although the cellular function of this unexpected structure has not been determined, the unusual distinctiveness of the revealed pattern suggests an unknown and potentially important protein assembly. One possibility is that this nuclear assembly is part of the KCs plasticity underlying the brain maturation in adult honey bees. Because no labelling with this AB is detectable in brains of the fly Drosophila melanogaster and the ant Camponotus floridanus, we tentatively named this antibody AmBNSab (Apis mellifera Brain Neurons Specific antibody). Here we report our results to make them accessible to a broader community and invite further research to unravel the biological role of this curious nuclear structure in the honey bee central brain.}, language = {en} } @article{KruegerMausKressetal.2021, author = {Kr{\"u}ger, Timothy and Maus, Katharina and Kreß, Verena and Meyer-Natus, Elisabeth and Engstler, Markus}, title = {Single-cell motile behaviour of Trypanosoma brucei in thin-layered fluid collectives}, series = {The European Physical Journal E}, volume = {44}, journal = {The European Physical Journal E}, number = {3}, issn = {1292-895X}, doi = {10.1140/epje/s10189-021-00052-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273022}, year = {2021}, abstract = {We describe a system for the analysis of an important unicellular eukaryotic flagellate in a confining and crowded environment. The parasite Trypanosoma brucei is arguably one of the most versatile microswimmers known. It has unique properties as a single microswimmer and shows remarkable adaptations (not only in motility, but prominently so), to its environment during a complex developmental cycle involving two different hosts. Specific life cycle stages show fascinating collective behaviour, as millions of cells can be forced to move together in extreme confinement. Our goal is to examine such motile behaviour directly in the context of the relevant environments. Therefore, for the first time, we analyse the motility behaviour of trypanosomes directly in a widely used assay, which aims to evaluate the parasites behaviour in collectives, in response to as yet unknown parameters. In a step towards understanding whether, or what type of, swarming behaviour of trypanosomes exists, we customised the assay for quantitative tracking analysis of motile behaviour on the single-cell level. We show that the migration speed of cell groups does not directly depend on single-cell velocity and that the system remains to be simplified further, before hypotheses about collective motility can be advanced.}, language = {en} } @article{StelznerBoynyHertleinetal.2021, author = {Stelzner, Kathrin and Boyny, Aziza and Hertlein, Tobias and Sroka, Aneta and Moldovan, Adriana and Paprotka, Kerstin and Kessie, David and Mehling, Helene and Potempa, Jan and Ohlsen, Knut and Fraunholz, Martin J. and Rudel, Thomas}, title = {Intracellular Staphylococcus aureus employs the cysteine protease staphopain A to induce host cell death in epithelial cells}, series = {PLoS Pathogens}, volume = {17}, journal = {PLoS Pathogens}, number = {9}, doi = {10.1371/journal.ppat.1009874}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263908}, year = {2021}, abstract = {Staphylococcus aureus is a major human pathogen, which can invade and survive in non-professional and professional phagocytes. Uptake by host cells is thought to contribute to pathogenicity and persistence of the bacterium. Upon internalization by epithelial cells, cytotoxic S. aureus strains can escape from the phagosome, replicate in the cytosol and induce host cell death. Here, we identified a staphylococcal cysteine protease to induce cell death after translocation of intracellular S. aureus into the host cell cytoplasm. We demonstrated that loss of staphopain A function leads to delayed onset of host cell death and prolonged intracellular replication of S. aureus in epithelial cells. Overexpression of staphopain A in a non-cytotoxic strain facilitated intracellular killing of the host cell even in the absence of detectable intracellular replication. Moreover, staphopain A contributed to efficient colonization of the lung in a mouse pneumonia model. In phagocytic cells, where intracellular S. aureus is exclusively localized in the phagosome, staphopain A did not contribute to cytotoxicity. Our study suggests that staphopain A is utilized by S. aureus to exit the epithelial host cell and thus contributes to tissue destruction and dissemination of infection. Author summary Staphylococcus aureus is an antibiotic-resistant pathogen that emerges in hospital and community settings and can cause a variety of diseases ranging from skin abscesses to lung inflammation and blood poisoning. The bacterium can asymptomatically colonize the upper respiratory tract and skin of humans and take advantage of opportune conditions, like immunodeficiency or breached barriers, to cause infection. Although S. aureus was not regarded as intracellular bacterium, it can be internalized by human cells and subsequently exit the host cells by induction of cell death, which is considered to cause tissue destruction and spread of infection. The bacterial virulence factors and underlying molecular mechanisms involved in the intracellular lifestyle of S. aureus remain largely unknown. We identified a bacterial cysteine protease to contribute to host cell death of epithelial cells mediated by intracellular S. aureus. Staphopain A induced killing of the host cell after translocation of the pathogen into the cell cytosol, while bacterial proliferation was not required. Further, the protease enhanced survival of the pathogen during lung infection. These findings reveal a novel, intracellular role for the bacterial protease staphopain A.}, language = {en} } @article{KramerMeyerNatusStigloheretal.2021, author = {Kramer, Susanne and Meyer-Natus, Elisabeth and Stigloher, Christian and Thoma, Hanna and Schnaufer, Achim and Engstler, Markus}, title = {Parallel monitoring of RNA abundance, localization and compactness with correlative single molecule FISH on LR White embedded samples}, series = {Nucleic Acids Research}, volume = {49}, journal = {Nucleic Acids Research}, number = {3}, doi = {10.1093/nar/gkaa1142}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230647}, year = {2021}, abstract = {Single mRNA molecules are frequently detected by single molecule fluorescence in situ hybridization (smFISH) using branched DNA technology. While providing strong and background-reduced signals, the method is inefficient in detecting mRNAs within dense structures, in monitoring mRNA compactness and in quantifying abundant mRNAs. To overcome these limitations, we have hybridized slices of high pressure frozen, freeze-substituted and LR White embedded cells (LR White smFISH). mRNA detection is physically restricted to the surface of the resin. This enables single molecule detection of RNAs with accuracy comparable to RNA sequencing, irrespective of their abundance, while at the same time providing spatial information on RNA localization that can be complemented with immunofluorescence and electron microscopy, as well as array tomography. Moreover, LR White embedding restricts the number of available probe pair recognition sites for each mRNA to a small subset. As a consequence, differences in signal intensities between RNA populations reflect differences in RNA structures, and we show that the method can be employed to determine mRNA compactness. We apply the method to answer some outstanding questions related to trans-splicing, RNA granules and mitochondrial RNA editing in single-cellular trypanosomes and we show an example of differential gene expression in the metazoan Caenorhabditis elegans.}, language = {en} } @article{WohlwendCravenWeigeltetal.2021, author = {Wohlwend, Michael R. and Craven, Dylan and Weigelt, Patrick and Seebens, Hanno and Winter, Marten and Kreft, Holger and Zurell, Damaris and Sarmento Cabral, Juliano and Essl, Franz and van Kleunen, Mark and Pergl, Jan and Pyšek, Petr and Knight, Tiffany M.}, title = {Anthropogenic and environmental drivers shape diversity of naturalized plants across the Pacific}, series = {Diversity and Distributions}, volume = {27}, journal = {Diversity and Distributions}, number = {6}, doi = {10.1111/ddi.13260}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239925}, pages = {1120 -- 1133}, year = {2021}, abstract = {Aim The Pacific exhibits an exceptional number of naturalized plant species, but the drivers of this high diversity and the associated compositional patterns remain largely unknown. Here, we aim to (a) improve our understanding of introduction and establishment processes and (b) evaluate whether this information is sufficient to create scientific conservation tools, such as watchlists. Location Islands in the Pacific Ocean, excluding larger islands such as New Zealand, Japan, the Philippines and Indonesia. Methods We combined information from the most up-to-date data sources to quantify naturalized plant species richness and turnover across island groups and investigate the effects of anthropogenic, biogeographic and climate drivers on these patterns. In total, we found 2,672 naturalized plant species across 481 islands and 50 island groups, with a total of 11,074 records. Results Most naturalized species were restricted to few island groups, and most island groups have a low number of naturalized species. Island groups with few naturalized species were characterized by a set of widespread naturalized species. Several plant families that contributed many naturalized species globally also did so in the Pacific, particularly Fabaceae and Poaceae. However, many families were significantly over- or under-represented in the Pacific naturalized flora compared to other regions of the world. Naturalized species richness increased primarily with increased human activity and island altitude/area, whereas similarity between island groups in temperature along with richness differences was most important for beta diversity. Main conclusions The distribution and richness of naturalized species can be explained by a small set of drivers. The Pacific region contains many naturalized plant species also naturalized in other regions in the world, but our results highlight key differences such as a stronger role of anthropogenic drivers in shaping diversity patterns. Our results establish a basis for predicting and preventing future naturalizations in a threatened biodiversity hotspot.}, language = {en} } @article{PrietoGarciaTomaškovićShahetal.2021, author = {Prieto-Garcia, Cristian and Tomašković, Ines and Shah, Varun Jayeshkumar and Dikic, Ivan and Diefenbacher, Markus}, title = {USP28: oncogene or tumor suppressor? a unifying paradigm for squamous cell carcinoma}, series = {Cells}, volume = {10}, journal = {Cells}, number = {10}, issn = {2073-4409}, doi = {10.3390/cells10102652}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248409}, year = {2021}, abstract = {Squamous cell carcinomas are therapeutically challenging tumor entities. Low response rates to radiotherapy and chemotherapy are commonly observed in squamous patients and, accordingly, the mortality rate is relatively high compared to other tumor entities. Recently, targeting USP28 has been emerged as a potential alternative to improve the therapeutic response and clinical outcomes of squamous patients. USP28 is a catalytically active deubiquitinase that governs a plethora of biological processes, including cellular proliferation, DNA damage repair, apoptosis and oncogenesis. In squamous cell carcinoma, USP28 is strongly expressed and stabilizes the essential squamous transcription factor ΔNp63, together with important oncogenic factors, such as NOTCH1, c-MYC and c-JUN. It is presumed that USP28 is an oncoprotein; however, recent data suggest that the deubiquitinase also has an antineoplastic effect regulating important tumor suppressor proteins, such as p53 and CHK2. In this review, we discuss: (1) The emerging role of USP28 in cancer. (2) The complexity and mutational landscape of squamous tumors. (3) The genetic alterations and cellular pathways that determine the function of USP28 in squamous cancer. (4) The development and current state of novel USP28 inhibitors.}, language = {en} } @article{RajabBisminSchwarzeetal.2021, author = {Rajab, Suhaila and Bismin, Leah and Schwarze, Simone and Pinggera, Alexandra and Greger, Ingo H. and Neuweiler, Hannes}, title = {Allosteric coupling of sub-millisecond clamshell motions in ionotropic glutamate receptor ligand-binding domains}, series = {Communications Biology}, volume = {4}, journal = {Communications Biology}, number = {1}, doi = {10.1038/s42003-021-02605-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261678}, year = {2021}, abstract = {Ionotropic glutamate receptors (iGluRs) mediate signal transmission in the brain and are important drug targets. Structural studies show snapshots of iGluRs, which provide a mechanistic understanding of gating, yet the rapid motions driving the receptor machinery are largely elusive. Here we detect kinetics of conformational change of isolated clamshell-shaped ligand-binding domains (LBDs) from the three major iGluR sub-types, which initiate gating upon binding of agonists. We design fluorescence probes to measure domain motions through nanosecond fluorescence correlation spectroscopy. We observe a broad kinetic spectrum of LBD dynamics that underlie activation of iGluRs. Microsecond clamshell motions slow upon dimerization and freeze upon binding of full and partial agonists. We uncover allosteric coupling within NMDA LBD hetero-dimers, where binding of L-glutamate to the GluN2A LBD stalls clamshell motions of the glycine-binding GluN1 LBD. Our results reveal rapid LBD dynamics across iGluRs and suggest a mechanism of negative allosteric cooperativity in NMDA receptors.}, language = {en} } @article{SchmitzKodererElMeseryetal.2021, author = {Schmitz, Werner and Koderer, Corinna and El-Mesery, Mohamed and Gobik, Sebastian and Sampers, Rene and Straub, Anton and K{\"u}bler, Alexander Christian and Seher, Axel}, title = {Metabolic fingerprinting of murine L929 fibroblasts as a cell-based tumour suppressor model system for methionine restriction}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {6}, issn = {1422-0067}, doi = {10.3390/ijms22063039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259198}, year = {2021}, abstract = {Since Otto Warburg reported in 1924 that cancer cells address their increased energy requirement through a massive intake of glucose, the cellular energy level has offered a therapeutic anticancer strategy. Methionine restriction (MetR) is one of the most effective approaches for inducing low-energy metabolism (LEM) due to the central position in metabolism of this amino acid. However, no simple in vitro system for the rapid analysis of MetR is currently available, and this study establishes the murine cell line L929 as such a model system. L929 cells react rapidly and efficiently to MetR, and the analysis of more than 150 different metabolites belonging to different classes (amino acids, urea and tricarboxylic acid cycle (TCA) cycles, carbohydrates, etc.) by liquid chromatography/mass spectrometry (LC/MS) defines a metabolic fingerprint and enables the identification of specific metabolites representing normal or MetR conditions. The system facilitates the rapid and efficient testing of potential cancer therapeutic metabolic targets. To date, MS studies of MetR have been performed using organisms and yeast, and the current LC/MS analysis of the intra- and extracellular metabolites in the murine cell line L929 over a period of 5 days thus provides new insights into the effects of MetR at the cellular metabolic level.}, language = {en} } @article{TrinksReinhardDrobnyetal.2021, author = {Trinks, Nora and Reinhard, Sebastian and Drobny, Matthias and Heilig, Linda and L{\"o}ffler, J{\"u}rgen and Sauer, Markus and Terpitz, Ulrich}, title = {Subdiffraction-resolution fluorescence imaging of immunological synapse formation between NK cells and A. fumigatus by expansion microscopy}, series = {Communications Biology}, volume = {4}, journal = {Communications Biology}, number = {1}, doi = {10.1038/s42003-021-02669-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264996}, year = {2021}, abstract = {Expansion microscopy (ExM) enables super-resolution fluorescence imaging on standard microscopes by physical expansion of the sample. However, the investigation of interactions between different organisms such as mammalian and fungal cells by ExM remains challenging because different cell types require different expansion protocols to ensure identical, ideally isotropic expansion of both partners. Here, we introduce an ExM method that enables super-resolved visualization of the interaction between NK cells and Aspergillus fumigatus hyphae. 4-fold expansion in combination with confocal fluorescence imaging allows us to resolve details of cytoskeleton rearrangement as well as NK cells' lytic granules triggered by contact with an RFP-expressing A. fumigatus strain. In particular, subdiffraction-resolution images show polarized degranulation upon contact formation and the presence of LAMP1 surrounding perforin at the NK cell-surface post degranulation. Our data demonstrate that optimized ExM protocols enable the investigation of immunological synapse formation between two different species with so far unmatched spatial resolution.}, language = {en} } @article{GrobTritscherGruebeletal.2021, author = {Grob, Robin and Tritscher, Clara and Gr{\"u}bel, Kornelia and Stigloher, Christian and Groh, Claudia and Fleischmann, Pauline N. and R{\"o}ssler, Wolfgang}, title = {Johnston's organ and its central projections in Cataglyphis desert ants}, series = {Journal of Comparative Neurology}, volume = {529}, journal = {Journal of Comparative Neurology}, number = {8}, doi = {10.1002/cne.25077}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225679}, pages = {2138 -- 2155}, year = {2021}, abstract = {The Johnston's organ (JO) in the insect antenna is a multisensory organ involved in several navigational tasks including wind-compass orientation, flight control, graviception, and, possibly, magnetoreception. Here we investigate the three dimensional anatomy of the JO and its neuronal projections into the brain of the desert ant Cataglyphis, a marvelous long-distance navigator. The JO of C. nodus workers consists of 40 scolopidia comprising three sensory neurons each. The numbers of scolopidia slightly vary between different sexes (female/male) and castes (worker/queen). Individual scolopidia attach to the intersegmental membrane between pedicel and flagellum of the antenna and line up in a ring-like organization. Three JO nerves project along the two antennal nerve branches into the brain. Anterograde double staining of the antennal afferents revealed that JO receptor neurons project to several distinct neuropils in the central brain. The T5 tract projects into the antennal mechanosensory and motor center (AMMC), while the T6 tract bypasses the AMMC via the saddle and forms collaterals terminating in the posterior slope (PS) (T6I), the ventral complex (T6II), and the ventrolateral protocerebrum (T6III). Double labeling of JO and ocellar afferents revealed that input from the JO and visual information from the ocelli converge in tight apposition in the PS. The general JO anatomy and its central projection patterns resemble situations in honeybees and Drosophila. The multisensory nature of the JO together with its projections to multisensory neuropils in the ant brain likely serves synchronization and calibration of different sensory modalities during the ontogeny of navigation in Cataglyphis.}, language = {en} } @article{SchmitzRiesKodereretal.2021, author = {Schmitz, Werner and Ries, Elena and Koderer, Corinna and V{\"o}lter, Maximilian Friedrich and W{\"u}nsch, Anna Chiara and El-Mesery, Mohamed and Frackmann, Kyra and K{\"u}bler, Alexander Christian and Linz, Christian and Seher, Axel}, title = {Cysteine restriction in murine L929 fibroblasts as an alternative strategy to methionine restriction in cancer therapy}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {21}, issn = {1422-0067}, doi = {10.3390/ijms222111630}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265486}, year = {2021}, abstract = {Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.}, language = {en} } @article{SprengerMuesseHartkeetal.2021, author = {Sprenger, Philipp P. and M{\"u}sse, Christian and Hartke, Juliane and Feldmeyer, Barbara and Schmitt, Thomas and Gebauer, Gerhard and Menzel, Florian}, title = {Dinner with the roommates: trophic niche differentiation and competition in a mutualistic ant-ant association}, series = {Ecological Entomology}, volume = {46}, journal = {Ecological Entomology}, number = {3}, doi = {10.1111/een.13002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228215}, pages = {562 -- 572}, year = {2021}, abstract = {1. The potential for competition is highest among species in close association. Despite net benefits for both parties, mutualisms can involve costs, including food competition. This might be true for the two neotropical ants Camponotus femoratus and Crematogaster levior, which share the same nest in a presumably mutualistic association (parabiosis). 2. While each nest involves one Crematogaster and one Camponotus partner, both taxa were recently found to comprise two cryptic species that show no partner preferences and seem ecologically similar. Since these cryptic species often occur in close sympatry, they might need to partition their niches to avoid competitive exclusion. 3. Here, we investigated first, is there interference competition between parabiotic Camponotus and Crematogaster, and do they prefer different food sources under competition? And second, is there trophic niche partitioning between the cryptic species of either genus? 4. Using cafeteria experiments, neutral lipid fatty acid and stable isotope analyses, we found evidence for interference competition, but also trophic niche partitioning between Camponotus and Crematogaster. Both preferred protein- and carbohydrate-rich baits, but at protein-rich baits Ca. femoratus displaced Cr. levior over time, suggesting a potential discovery-dominance trade-off between parabiotic partners. Only limited evidence was found for trophic differentiation between the cryptic species of each genus. 5. Although we cannot exclude differentiation in other niche dimensions, we argue that neutral dynamics might mediate the coexistence of cryptic species. This model system is highly suitable for further studies of the maintenance of species diversity and the role of mutualisms in promoting species coexistence.}, language = {en} } @article{BoffFriedel2021, author = {Boff, Samuel and Friedel, Anna}, title = {Dynamics of nest occupation and homing of solitary bees in painted trap nests}, series = {Ecological Entomology}, volume = {46}, journal = {Ecological Entomology}, number = {2}, doi = {10.1111/een.12965}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224605}, pages = {496 -- 499}, year = {2021}, abstract = {1. The oil-collecting bee Centris analis (Fabricius, 1804) is an important pollinator for the Neotropical region. The species can be attracted to nest in human-made cavities. Such trap nests or insect hotels offer the opportunity to study the behaviour of populations in semifield conditions. 2. We studied a newly established trap nest aggregation of C. analis in Mato Grosso do Sul, Brazil and tested the effect that differentially painted nesting options have on the rate of nest foundation, and on the ability of relocating the nest when returning from a foraging trip (homing behaviour). Moreover, we tested if the duration of foraging trips decreased with time. 3. We found that females preferred to nest in painted nests compared to unpainted nests, with blue nests being the most occupied ones, followed by purple, yellow, white, and green. Furthermore, bees improved their homing behaviour with time, however, nest colour did not seem to have an effect on this process. Moreover, we found that bees reduce the duration of their foraging trips with time. This could be an indicator of improved foraging efficiency through learning. 4. These findings could inform a new and fruitful line of research on the behaviour and ecology of trap nesting solitary bees.}, language = {en} } @article{SivarajanKessieOberwinkleretal.2021, author = {Sivarajan, Rinu and Kessie, David Komla and Oberwinkler, Heike and Pallmann, Niklas and Walles, Thorsten and Scherzad, Agmal and Hackenberg, Stephan and Steinke, Maria}, title = {Susceptibility of Human Airway Tissue Models Derived From Different Anatomical Sites to Bordetella pertussis and Its Virulence Factor Adenylate Cyclase Toxin}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {11}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2021.797491}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253302}, year = {2021}, abstract = {To study the interaction of human pathogens with their host target structures, human tissue models based on primary cells are considered suitable. Complex tissue models of the human airways have been used as infection models for various viral and bacterial pathogens. The Gram-negative bacterium Bordetella pertussis is of relevant clinical interest since whooping cough has developed into a resurgent infectious disease. In the present study, we created three-dimensional tissue models of the human ciliated nasal and tracheo-bronchial mucosa. We compared the innate immune response of these models towards the B. pertussis virulence factor adenylate cyclase toxin (CyaA) and its enzymatically inactive but fully pore-forming toxoid CyaA-AC\(^-\). Applying molecular biological, histological, and microbiological assays, we found that 1 µg/ml CyaA elevated the intracellular cAMP level but did not disturb the epithelial barrier integrity of nasal and tracheo-bronchial airway mucosa tissue models. Interestingly, CyaA significantly increased interleukin 6, interleukin 8, and human beta defensin 2 secretion in nasal tissue models, whereas tracheo-bronchial tissue models were not significantly affected compared to the controls. Subsequently, we investigated the interaction of B. pertussis with both differentiated primary nasal and tracheo-bronchial tissue models and demonstrated bacterial adherence and invasion without observing host cell type-specific significant differences. Even though the nasal and the tracheo-bronchial mucosa appear similar from a histological perspective, they are differentially susceptible to B. pertussis CyaA in vitro. Our finding that nasal tissue models showed an increased innate immune response towards the B. pertussis virulence factor CyaA compared to tracheo-bronchial tissue models may reflect the key role of the nasal airway mucosa as the first line of defense against airborne pathogens.}, language = {en} } @article{AdolfiDuKneitzetal.2021, author = {Adolfi, Mateus C. and Du, Kang and Kneitz, Susanne and Cabau, C{\´e}dric and Zahm, Margot and Klopp, Christophe and Feron, Romain and Paix{\~a}o, R{\^o}mulo V. and Varela, Eduardo S. and de Almeida, Fernanda L. and de Oliveira, Marcos A. and N{\´o}brega, Rafael H. and Lopez-Roques, C{\´e}line and Iampietro, Carole and Lluch, J{\´e}r{\^o}me and Kloas, Werner and Wuertz, Sven and Schaefer, Fabian and St{\"o}ck, Matthias and Guiguen, Yann and Schartl, Manfred}, title = {A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-01066-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265672}, year = {2021}, abstract = {Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.}, language = {en} } @article{RothHackerHeidrichetal.2021, author = {Roth, Nicolas and Hacker, Herrmann Heinrich and Heidrich, Lea and Friess, Nicolas and Garc{\´i}a-Barroas, Enrique and Habel, Jan Christian and Thorn, Simon and M{\"u}ler, J{\"o}rg}, title = {Host specificity and species colouration mediate the regional decline of nocturnal moths in central European forests}, series = {Ecography}, volume = {44}, journal = {Ecography}, number = {6}, doi = {10.1111/ecog.05522}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258731}, pages = {941-952}, year = {2021}, abstract = {The high diversity of insects has limited the volume of long-term community data with a high taxonomic resolution and considerable geographic replications, especially in forests. Therefore, trends and causes of changes are poorly understood. Here we analyse trends in species richness, abundance and biomass of nocturnal macro moths in three quantitative data sets collected over four decades in forests in southern Germany. Two local data sets, one from coppiced oak forests and one from high oak forests included 125K and 48K specimens from 559 and 532 species, respectively. A third regional data set, representing all forest types in the temperate zone of central Europe comprised 735K specimens from 848 species. Generalized additive mixed models revealed temporal declines in species richness (-38\%), abundance (-53\%) and biomass (-57\%) at the regional scale. These were more pronounced in plant host specialists and in dark coloured species. In contrast, the local coppiced oak forests showed an increase, in species richness (+62\%), while the high oak forests showed no clear trends. Left and right censoring as well as cross validation confirmed the robustness of the analyses, which led to four conclusions. First, the decline in insects appears in hyper diverse insect groups in forests and affects species richness, abundance and biomass. Second, the pronounced decline in host specialists suggests habitat loss as an important driver of the observed decline. Third, the more severe decline in dark species might be an indication of global warming as a potential driver. Fourth, the trends in coppiced oak forests indicate that maintaining complex and diverse forest ecosystems through active management may be a promising conservation strategy in order to counteract negative trends in biodiversity, alongside rewilding approaches.}, language = {en} } @article{HepbasliGredyUllrichetal.2021, author = {Hepbasli, Denis and Gredy, Sina and Ullrich, Melanie and Reigl, Amelie and Abeßer, Marco and Raabe, Thomas and Schuh, Kai}, title = {Genotype- and Age-Dependent Differences in Ultrasound Vocalizations of SPRED2 Mutant Mice Revealed by Machine Deep Learning}, series = {Brain Sciences}, volume = {11}, journal = {Brain Sciences}, number = {10}, issn = {2076-3425}, doi = {10.3390/brainsci11101365}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248525}, year = {2021}, abstract = {Vocalization is an important part of social communication, not only for humans but also for mice. Here, we show in a mouse model that functional deficiency of Sprouty-related EVH1 domain-containing 2 (SPRED2), a protein ubiquitously expressed in the brain, causes differences in social ultrasound vocalizations (USVs), using an uncomplicated and reliable experimental setting of a short meeting of two individuals. SPRED2 mutant mice show an OCD-like behaviour, accompanied by an increased release of stress hormones from the hypothalamic-pituitary-adrenal axis, both factors probably influencing USV usage. To determine genotype-related differences in USV usage, we analyzed call rate, subtype profile, and acoustic parameters (i.e., duration, bandwidth, and mean peak frequency) in young and old SPRED2-KO mice. We recorded USVs of interacting male and female mice, and analyzed the calls with the deep-learning DeepSqueak software, which was trained to recognize and categorize the emitted USVs. Our findings provide the first classification of SPRED2-KO vs. wild-type mouse USVs using neural networks and reveal significant differences in their development and use of calls. Our results show, first, that simple experimental settings in combination with deep learning are successful at identifying genotype-dependent USV usage and, second, that SPRED2 deficiency negatively affects the vocalization usage and social communication of mice.}, language = {en} } @article{HabensteinSchmittLiessemetal.2021, author = {Habenstein, Jens and Schmitt, Franziska and Liessem, Sander and Ly, Alice and Trede, Dennis and Wegener, Christian and Predel, Reinhard and R{\"o}ssler, Wolfgang and Neupert, Susanne}, title = {Transcriptomic, peptidomic, and mass spectrometry imaging analysis of the brain in the ant Cataglyphis nodus}, series = {Journal of Neurochemistry}, volume = {158}, journal = {Journal of Neurochemistry}, number = {2}, doi = {10.1111/jnc.15346}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239917}, pages = {391 -- 412}, year = {2021}, abstract = {Behavioral flexibility is an important cornerstone for the ecological success of animals. Social Cataglyphis nodus ants with their age-related polyethism characterized by age-related behavioral phenotypes represent a prime example for behavioral flexibility. We propose neuropeptides as powerful candidates for the flexible modulation of age-related behavioral transitions in individual ants. As the neuropeptidome of C. nodus was unknown, we collected a comprehensive peptidomic data set obtained by transcriptome analysis of the ants' central nervous system combined with brain extract analysis by Q-Exactive Orbitrap mass spectrometry (MS) and direct tissue profiling of different regions of the brain by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS. In total, we identified 71 peptides with likely bioactive function, encoded on 49 neuropeptide-, neuropeptide-like, and protein hormone prepropeptide genes, including a novel neuropeptide-like gene (fliktin). We next characterized the spatial distribution of a subset of peptides encoded on 16 precursor proteins with high resolution by MALDI MS imaging (MALDI MSI) on 14 µm brain sections. The accuracy of our MSI data were confirmed by matching the immunostaining patterns for tachykinins with MSI ion images from consecutive brain sections. Our data provide a solid framework for future research into spatially resolved qualitative and quantitative peptidomic changes associated with stage-specific behavioral transitions and the functional role of neuropeptides in Cataglyphis ants.}, language = {en} } @article{MuellerKoehlerHendricksetal.2021, author = {M{\"u}ller, Sophie and K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and B{\"o}rner, Kevin and Diers, Johannes and Lock, Johan F. and Petritsch, Bernhard and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Brain metastases from colorectal cancer: a systematic review of the literature and meta-analysis to establish a guideline for daily treatment}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {4}, issn = {2072-6694}, doi = {10.3390/cancers13040900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228883}, year = {2021}, abstract = {Colorectal cancer (CRC) is the third most common malignancy worldwide. Most patients with metastatic CRC develop liver or lung metastases, while a minority suffer from brain metastases. There is little information available regarding the presentation, treatment, and overall survival of brain metastases (BM) from CRC. This systematic review and meta-analysis includes data collected from three major databases (PubMed, Cochrane, and Embase) based on the key words "brain", "metastas*", "tumor", "colorectal", "cancer", and "malignancy". In total, 1318 articles were identified in the search and 86 studies matched the inclusion criteria. The incidence of BM varied between 0.1\% and 11.5\%. Most patients developed metastases at other sites prior to developing BM. Lung metastases and KRAS mutations were described as risk factors for additional BM. Patients with BM suffered from various symptoms, but up to 96.8\% of BM patients were asymptomatic at the time of BM diagnosis. Median survival time ranged from 2 to 9.6 months, and overall survival (OS) increased up to 41.1 months in patients on a multimodal therapy regimen. Several factors including age, blood levels of carcinoembryonic antigen (CEA), multiple metastases sites, number of brain lesions, and presence of the KRAS mutation were predictors of OS. For BM diagnosis, MRI was considered to be state of the art. Treatment consisted of a combination of surgery, radiation, or systemic treatment.}, language = {en} } @article{DjuzenovaFischerKatzeretal.2021, author = {Djuzenova, Cholpon S. and Fischer, Thomas and Katzer, Astrid and Sisario, Dmitri and Korsa, Tessa and Streussloff, Gudrun and Sukhorukov, Vladimir L. and Flentje, Michael}, title = {Opposite effects of the triple target (DNA-PK/PI3K/mTOR) inhibitor PI-103 on the radiation sensitivity of glioblastoma cell lines proficient and deficient in DNA-PKcs}, series = {BMC Cancer}, volume = {21}, journal = {BMC Cancer}, doi = {10.1186/s12885-021-08930-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265826}, year = {2021}, abstract = {Background: Radiotherapy is routinely used to combat glioblastoma (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells. Methods: Two GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by gamma H2AX and 53BP1, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations. Results: We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. Treatment of MO59K cells with PI-103 lead to protraction of the DNA damage repair as compared to drug-free irradiated cells. In PI-103-treated and irradiated MO59J cells the foci numbers of both proteins was higher than in the drug-free samples, but a large portion of DNA damage was quickly repaired. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP and increased subG1 fraction. Moreover, irradiation induced a strong G2 arrest in MO59J cells (similar to 80\% vs. similar to 50\% in MO59K), which was, however, partially reduced in the presence of PI-103. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells. Conclusions: The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism.}, language = {en} } @article{KoehlerHendricksKastneretal.2021, author = {K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Boerner, Kevin and Wagner, Johanna C. and Lock, Johan F. and Wiegering, Armin}, title = {Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review}, series = {International Journal of Colorectal Disease}, volume = {36}, journal = {International Journal of Colorectal Disease}, number = {10}, issn = {1432-1262}, doi = {10.1007/s00384-021-03927-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266616}, pages = {2283-2286}, year = {2021}, abstract = {Background Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis. Methods The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications. Results No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis. Conclusions To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.}, language = {en} } @article{OthmanBekhitAnanyetal.2021, author = {Othman, Eman M. and Bekhit, Amany A. and Anany, Mohamed A. and Dandekar, Thomas and Ragab, Hanan M. and Wahid, Ahmed}, title = {Design, Synthesis, and Anticancer Screening for Repurposed Pyrazolo[3,4-d]pyrimidine Derivatives on Four Mammalian Cancer Cell Lines}, series = {Molecules}, volume = {26}, journal = {Molecules}, number = {10}, issn = {1420-3049}, doi = {10.3390/molecules26102961}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239734}, year = {2021}, abstract = {The present study reports the synthesis of new purine bioisosteres comprising a pyrazolo[3,4-d]pyrimidine scaffold linked to mono-, di-, and trimethoxy benzylidene moieties through hydrazine linkages. First, in silico docking experiments of the synthesized compounds against Bax, Bcl-2, Caspase-3, Ki67, p21, and p53 were performed in a trial to rationalize the observed cytotoxic activity for the tested compounds. The anticancer activity of these compounds was evaluated in vitro against Caco-2, A549, HT1080, and Hela cell lines. Results revealed that two (5 and 7) of the three synthesized compounds (5, 6, and 7) showed high cytotoxic activity against all tested cell lines with IC50 values in the micro molar concentration. Our in vitro results show that there is no significant apoptotic effect for the treatment with the experimental compounds on the viability of cells against A549 cells. Ki67 expression was found to decrease significantly following the treatment of cells with the most promising candidate: drug 7. The overall results indicate that these pyrazolopyrimidine derivatives possess anticancer activity at varying doses. The suggested mechanism of action involves the inhibition of the proliferation of cancer cells.}, language = {en} } @article{BohnertReinertTrellaetal.2021, author = {Bohnert, Simone and Reinert, Christoph and Trella, Stefanie and Schmitz, Werner and Ondruschka, Benjamin and Bohnert, Michael}, title = {Metabolomics in postmortem cerebrospinal fluid diagnostics: a state-of-the-art method to interpret central nervous system-related pathological processes}, series = {International Journal of Legal Medicine}, volume = {135}, journal = {International Journal of Legal Medicine}, issn = {0937-9827}, doi = {10.1007/s00414-020-02462-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235724}, pages = {183-191}, year = {2021}, abstract = {In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples.}, language = {en} } @article{KessieLodesOberwinkleretal.2021, author = {Kessie, David K. and Lodes, Nina and Oberwinkler, Heike and Goldman, William E. and Walles, Thorsten and Steinke, Maria and Gross, Roy}, title = {Activity of Tracheal Cytotoxin of Bordetella pertussis in a Human Tracheobronchial 3D Tissue Model}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {10}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2020.614994}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222736}, year = {2021}, abstract = {Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.}, language = {en} } @article{LiPradaDaminelietal.2021, author = {Li, Kunkun and Prada, Juan and Damineli, Daniel S. C. and Liese, Anja and Romeis, Tina and Dandekar, Thomas and Feij{\´o}, Jos{\´e} A. and Hedrich, Rainer and Konrad, Kai Robert}, title = {An optimized genetically encoded dual reporter for simultaneous ratio imaging of Ca\(^{2+}\) and H\(^{+}\) reveals new insights into ion signaling in plants}, series = {New Phytologist}, volume = {230}, journal = {New Phytologist}, number = {6}, doi = {10.1111/nph.17202}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239847}, pages = {2292 -- 2310}, year = {2021}, abstract = {Whereas the role of calcium ions (Ca\(^{2+}\)) in plant signaling is well studied, the physiological significance of pH-changes remains largely undefined. Here we developed CapHensor, an optimized dual-reporter for simultaneous Ca\(^{2+}\) and pH ratio-imaging and studied signaling events in pollen tubes (PTs), guard cells (GCs), and mesophyll cells (MCs). Monitoring spatio-temporal relationships between membrane voltage, Ca\(^{2+}\)- and pH-dynamics revealed interconnections previously not described. In tobacco PTs, we demonstrated Ca\(^{2+}\)-dynamics lag behind pH-dynamics during oscillatory growth, and pH correlates more with growth than Ca\(^{2+}\). In GCs, we demonstrated abscisic acid (ABA) to initiate stomatal closure via rapid cytosolic alkalization followed by Ca2+ elevation. Preventing the alkalization blocked GC ABA-responses and even opened stomata in the presence of ABA, disclosing an important pH-dependent GC signaling node. In MCs, a flg22-induced membrane depolarization preceded Ca2+-increases and cytosolic acidification by c. 2 min, suggesting a Ca\(^{2+}\)/pH-independent early pathogen signaling step. Imaging Ca2+ and pH resolved similar cytosol and nuclear signals and demonstrated flg22, but not ABA and hydrogen peroxide to initiate rapid membrane voltage-, Ca\(^{2+}\)- and pH-responses. We propose close interrelation in Ca\(^{2+}\)- and pH-signaling that is cell type- and stimulus-specific and the pH having crucial roles in regulating PT growth and stomata movement.}, language = {en} } @article{DapergolaMenegazziRaabeetal.2021, author = {Dapergola, Eleni and Menegazzi, Pamela and Raabe, Thomas and Hovhanyan, Anna}, title = {Light Stimuli and Circadian Clock Affect Neural Development in Drosophila melanogaster}, series = {Frontiers in Cell and Developmental Biology}, volume = {9}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2021.595754}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231049}, year = {2021}, abstract = {Endogenous clocks enable organisms to adapt cellular processes, physiology, and behavior to daily variation in environmental conditions. Metabolic processes in cyanobacteria to humans are under the influence of the circadian clock, and dysregulation of the circadian clock causes metabolic disorders. In mouse and Drosophila, the circadian clock influences translation of factors involved in ribosome biogenesis and synchronizes protein synthesis. Notably, nutrition signals are mediated by the insulin receptor/target of rapamycin (InR/TOR) pathways to regulate cellular metabolism and growth. However, the role of the circadian clock in Drosophila brain development and the potential impact of clock impairment on neural circuit formation and function is less understood. Here we demonstrate that changes in light stimuli or disruption of the molecular circadian clock cause a defect in neural stem cell growth and proliferation. Moreover, we show that disturbed cell growth and proliferation are accompanied by reduced nucleolar size indicative of impaired ribosomal biogenesis. Further, we define that light and clock independently affect the InR/TOR growth regulatory pathway due to the effect on regulators of protein biosynthesis. Altogether, these data suggest that alterations in InR/TOR signaling induced by changes in light conditions or disruption of the molecular clock have an impact on growth and proliferation properties of neural stem cells in the developing Drosophila brain.}, language = {en} } @article{HoehneProkopovKuhletal.2021, author = {H{\"o}hne, Christin and Prokopov, Dmitry and Kuhl, Heiner and Du, Kang and Klopp, Christophe and Wuertz, Sven and Trifonov, Vladimir and St{\"o}ck, Matthias}, title = {The immune system of sturgeons and paddlefish (Acipenseriformes): a review with new data from a chromosome-scale sturgeon genome}, series = {Reviews in Aquaculture}, volume = {13}, journal = {Reviews in Aquaculture}, number = {3}, doi = {10.1111/raq.12542}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239865}, pages = {1709 -- 1729}, year = {2021}, abstract = {Sturgeon immunity is relevant for basic evolutionary and applied research, including caviar- and meat-producing aquaculture, protection of wild sturgeons and their re-introduction through conservation aquaculture. Starting from a comprehensive overview of immune organs, we discuss pathways of innate and adaptive immune systems in a vertebrate phylogenetic and genomic context. The thymus as a key organ of adaptive immunity in sturgeons requires future molecular studies. Likewise, data on immune functions of sturgeon-specific pericardial and meningeal tissues are largely missing. Integrating immunological and endocrine functions, the sturgeon head kidney resembles that of teleosts. Recently identified pattern recognition receptors in sturgeon require research on downstream regulation. We review first acipenseriform data on Toll-like receptors (TLRs), type I transmembrane glycoproteins expressed in membranes and endosomes, initiating inflammation and host defence by molecular pattern-induced activation. Retinoic acid-inducible gene-I-like (RIG-like) receptors of sturgeons present RNA and key sensors of virus infections in most cell types. Sturgeons and teleosts share major components of the adaptive immune system, including B cells, immunoglobulins, major histocompatibility complex and the adaptive cellular response by T cells. The ontogeny of the sturgeon innate and onset of adaptive immune genes in different organs remain understudied. In a genomics perspective, our new data on 100 key immune genes exemplify a multitude of evolutionary trajectories after the sturgeon-specific genome duplication, where some single-copy genes contrast with many duplications, allowing tissue specialization, sub-functionalization or both. Our preliminary conclusion should be tested by future evolutionary bioinformatics, involving all >1000 immunity genes. This knowledge update about the acipenseriform immune system identifies several important research gaps and presents a basis for future applications.}, language = {en} } @article{SchubertSchulzeProdromouetal.2021, author = {Schubert, Jonathan and Schulze, Andrea and Prodromou, Chrisostomos and Neuweiler, Hannes}, title = {Two-colour single-molecule photoinduced electron transfer fluorescence imaging microscopy of chaperone dynamics}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, doi = {10.1038/s41467-021-27286-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265754}, year = {2021}, abstract = {Many proteins are molecular machines, whose function is dependent on multiple conformational changes that are initiated and tightly controlled through biochemical stimuli. Their mechanistic understanding calls for spectroscopy that can probe simultaneously such structural coordinates. Here we present two-colour fluorescence microscopy in combination with photoinduced electron transfer (PET) probes as a method that simultaneously detects two structural coordinates in single protein molecules, one colour per coordinate. This contrasts with the commonly applied resonance energy transfer (FRET) technique that requires two colours per coordinate. We demonstrate the technique by directly and simultaneously observing three critical structural changes within the Hsp90 molecular chaperone machinery. Our results reveal synchronicity of conformational motions at remote sites during ATPase-driven closure of the Hsp90 molecular clamp, providing evidence for a cooperativity mechanism in the chaperone's catalytic cycle. Single-molecule PET fluorescence microscopy opens up avenues in the multi-dimensional exploration of protein dynamics and allosteric mechanisms.}, language = {en} } @article{BreitenbachHelfrichFoersterDandekar2021, author = {Breitenbach, Tim and Helfrich-F{\"o}rster, Charlotte and Dandekar, Thomas}, title = {An effective model of endogenous clocks and external stimuli determining circadian rhythms}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-95391-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261655}, pages = {16165}, year = {2021}, abstract = {Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/.}, language = {en} } @article{ShityakovSkorbFoersteretal.2021, author = {Shityakov, Sergey and Skorb, Ekaterina V. and F{\"o}rster, Carola Y. and Dandekar, Thomas}, title = {Scaffold Searching of FDA and EMA-Approved Drugs Identifies Lead Candidates for Drug Repurposing in Alzheimer's Disease}, series = {Frontiers in Chemistry}, volume = {9}, journal = {Frontiers in Chemistry}, issn = {2296-2646}, doi = {10.3389/fchem.2021.736509}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248703}, year = {2021}, abstract = {Clinical trials of novel therapeutics for Alzheimer's Disease (AD) have consumed a significant amount of time and resources with largely negative results. Repurposing drugs already approved by the Food and Drug Administration (FDA), European Medicines Agency (EMA), or Worldwide for another indication is a more rapid and less expensive option. Therefore, we apply the scaffold searching approach based on known amyloid-beta (Aβ) inhibitor tramiprosate to screen the DrugCentral database (n = 4,642) of clinically tested drugs. As a result, menadione bisulfite and camphotamide substances with protrombogenic and neurostimulation/cardioprotection effects were identified as promising Aβ inhibitors with an improved binding affinity (ΔGbind) and blood-brain barrier permeation (logBB). Finally, the data was also confirmed by molecular dynamics simulations using implicit solvation, in particular as Molecular Mechanics Generalized Born Surface Area (MM-GBSA) model. Overall, the proposed in silico pipeline can be implemented through the early stage rational drug design to nominate some lead candidates for AD, which will be further validated in vitro and in vivo, and, finally, in a clinical trial.}, language = {en} } @article{BakariSoaleIkengaScheibeetal.2021, author = {Bakari-Soale, Majeed and Ikenga, Nonso Josephat and Scheibe, Marion and Butter, Falk and Jones, Nicola G. and Kramer, Susanne and Engstler, Markus}, title = {The nucleolar DExD/H protein Hel66 is involved in ribosome biogenesis in Trypanosoma brucei}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-97020-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-263872}, year = {2021}, abstract = {The biosynthesis of ribosomes is a complex cellular process involving ribosomal RNA, ribosomal proteins and several further trans-acting factors. DExD/H box proteins constitute the largest family of trans-acting protein factors involved in this process. Several members of this protein family have been directly implicated in ribosome biogenesis in yeast. In trypanosomes, ribosome biogenesis differs in several features from the process described in yeast. Here, we have identified the DExD/H box helicase Hel66 as being involved in ribosome biogenesis. The protein is unique to Kinetoplastida, localises to the nucleolus and its depletion via RNAi caused a severe growth defect. Loss of the protein resulted in a decrease of global translation and accumulation of rRNA processing intermediates for both the small and large ribosomal subunits. Only a few factors involved in trypanosome rRNA biogenesis have been described so far and our findings contribute to gaining a more comprehensive picture of this essential process.}, language = {en} } @article{LaswayKinaboMremietal.2021, author = {Lasway, Julius V. and Kinabo, Neema R. and Mremi, Rudolf F. and Martin, Emanuel H. and Nyakunga, Oliver C. and Sanya, John J. and Rwegasira, Gration M. and Lesio, Nicephor and Gideon, Hulda and Pauly, Alain and Eardley, Connal and Peters, Marcell K. and Peterson, Andrew T. and Steffan-Dewenter, Ingolf and Njovu, Henry K.}, title = {A synopsis of the Bee occurrence data of northern Tanzania}, series = {Biodiversity Data Journal}, volume = {9}, journal = {Biodiversity Data Journal}, doi = {10.3897/BDJ.9.e68190}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265018}, year = {2021}, abstract = {Background Bees (Hymenoptera: Apoidea: Anthophila) are the most important group of pollinators with about 20,507 known species worldwide. Despite the critical role of bees in providing pollination services, studies aiming at understanding which species are present across disturbance gradients are scarce. Limited taxononomic information for the existing and unidentified bee species in Tanzania make their conservation haphazard. Here, we present a dataset of bee species records obtained from a survey in nothern Tanzania i.e. Kilimanjaro, Arusha and Manyara regions. Our findings serve as baseline data necessary for understanding the diversity and distribution of bees in the northern parts of the country, which is a critical step in devising robust conservation and monitoring strategies for their populations. New information In this paper, we present information on 45 bee species belonging to 20 genera and four families sampled using a combination of sweep-netting and pan trap methods. Most species (27, ~ 60\%) belong to the family Halictidae followed by 16 species (35.5\%) from the family Apidae. Megachilidae and Andrenidae were the least represented, each with only one species (2.2\%). Additional species of Apidae and Megachilidae sampled during this survey are not yet published on Global Biodiversity Information Facility (GBIF), once they will be available on GBIF, they will be published in a subsequent paper. From a total of 953 occurrences, highest numbers were recorded in Kilimanjaro Region (n = 511), followed by Arusha (n = 410) and Manyara (n = 32), but this pattern reflects the sampling efforts of the research project rather than real bias in the distributions of bee species in northern Tanzania.}, language = {en} } @article{KhayenkoMaric2021, author = {Khayenko, Vladimir and Maric, Hans Michael}, title = {Innovative affinit{\"a}tsbasierte Markierungen f{\"u}r die High-End-Mikroskopie}, series = {BIOspektrum}, volume = {27}, journal = {BIOspektrum}, doi = {10.1007/s12268-021-1672-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287377}, pages = {709-712}, year = {2021}, abstract = {Advanced tissue imaging techniques and super resolution microscopy are opening new avenues of investigations in life sciences. These mainly instrumentation-driven innovations require the development of appropriate molecular labelling tools. Here, we discuss currently used and upcoming manipulation-free protein labelling strategies and their potential for the precise and interference-free visualization of endogenous proteins.}, language = {de} } @article{MayrKellerPetersetal.2021, author = {Mayr, Antonia V. and Keller, Alexander and Peters, Marcell K. and Grimmer, Gudrun and Krischke, Beate and Geyer, Mareen and Schmitt, Thomas and Steffan-Dewenter, Ingolf}, title = {Cryptic species and hidden ecological interactions of halictine bees along an elevational gradient}, series = {Ecology and Evolution}, volume = {11}, journal = {Ecology and Evolution}, number = {12}, doi = {10.1002/ece3.7605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238853}, pages = {7700 -- 7712}, year = {2021}, abstract = {Changes of abiotic and biotic conditions along elevational gradients represent serious challenges to organisms which may promote the turnover of species, traits and biotic interaction partners. Here, we used molecular methods to study cuticular hydrocarbon (CHC) profiles, biotic interactions and phylogenetic relationships of halictid bees of the genus Lasioglossum along a 2,900 m elevational gradient at Mt. Kilimanjaro, Tanzania. We detected a strong species turnover of morphologically indistinguishable taxa with phylogenetically clustered cryptic species at high elevations, changes in CHC profiles, pollen resource diversity, and a turnover in the gut and body surface microbiome of bees. At high elevations, increased proportions of saturated compounds in CHC profiles indicate physiological adaptations to prevent desiccation. More specialized diets with higher proportions of low-quality Asteraceae pollen imply constraints in the availability of food resources. Interactive effects of climatic conditions on gut and surface microbiomes, CHC profiles, and pollen diet suggest complex feedbacks among abiotic conditions, ecological interactions, physiological adaptations, and phylogenetic constraints as drivers of halictid bee communities at Mt. Kilimanjaro.}, language = {en} } @article{DuquePoelmanSteffanDewenter2021, author = {Duque, Laura and Poelman, Erik H. and Steffan-Dewenter, Ingolf}, title = {Plant age at the time of ozone exposure affects flowering patterns, biotic interactions and reproduction of wild mustard}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-02878-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265742}, year = {2021}, abstract = {Exposure of plants to environmental stressors can modify their metabolism, interactions with other organisms and reproductive success. Tropospheric ozone is a source of plant stress. We investigated how an acute exposure to ozone at different times of plant development affects reproductive performance, as well as the flowering patterns and the interactions with pollinators and herbivores, of wild mustard plants. The number of open flowers was higher on plants exposed to ozone at earlier ages than on the respective controls, while plants exposed at later ages showed a tendency for decreased number of open flowers. The changes in the number of flowers provided a good explanation for the ozone-induced effects on reproductive performance and on pollinator visitation. Ozone exposure at earlier ages also led to either earlier or extended flowering periods. Moreover, ozone tended to increase herbivore abundance, with responses depending on herbivore taxa and the plant age at the time of ozone exposure. These results suggest that the effects of ozone exposure depend on the developmental stage of the plant, affecting the flowering patterns in different directions, with consequences for pollination and reproduction of annual crops and wild species.}, language = {en} } @article{UhlerRedlichZhangetal.2021, author = {Uhler, Johannes and Redlich, Sarah and Zhang, Jie and Hothorn, Torsten and Tobisch, Cynthia and Ewald, J{\"o}rg and Thorn, Simon and Seibold, Sebastian and Mitesser, Oliver and Morin{\`e}re, J{\´e}r{\^o}me and Bozicevic, Vedran and Benjamin, Caryl S. and Englmeier, Jana and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Uphus, Lars and Schmidt, Stefan and Steffan-Dewenter, Ingolf and M{\"u}ller, J{\"o}rg}, title = {Relationships of insect biomass and richness with land use along a climate gradient}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-26181-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265058}, year = {2021}, abstract = {Recently reported insect declines have raised both political and social concern. Although the declines have been attributed to land use and climate change, supporting evidence suffers from low taxonomic resolution, short time series, a focus on local scales, and the collinearity of the identified drivers. In this study, we conducted a systematic assessment of insect populations in southern Germany, which showed that differences in insect biomass and richness are highly context dependent. We found the largest difference in biomass between semi-natural and urban environments (-42\%), whereas differences in total richness (-29\%) and the richness of threatened species (-56\%) were largest from semi-natural to agricultural environments. These results point to urbanization and agriculture as major drivers of decline. We also found that richness and biomass increase monotonously with increasing temperature, independent of habitat. The contrasting patterns of insect biomass and richness question the use of these indicators as mutual surrogates. Our study provides support for the implementation of more comprehensive measures aimed at habitat restoration in order to halt insect declines.}, language = {en} } @article{HartkeWaldvogelSprengeretal.2021, author = {Hartke, Juliane and Waldvogel, Ann-Marie and Sprenger, Philipp P. and Schmitt, Thomas and Menzel, Florian and Pfenninger, Markus and Feldmeyer, Barbara}, title = {Little parallelism in genomic signatures of local adaptation in two sympatric, cryptic sister species}, series = {Journal of Evolutionary Biology}, volume = {34}, journal = {Journal of Evolutionary Biology}, number = {6}, doi = {10.1111/jeb.13742}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228355}, pages = {937 -- 952}, year = {2021}, abstract = {Species living in sympatry and sharing a similar niche often express parallel phenotypes as a response to similar selection pressures. The degree of parallelism within underlying genomic levels is often unexplored, but can give insight into the mechanisms of natural selection and adaptation. Here, we use multi-dimensional genomic associations to assess the basis of local and climate adaptation in two sympatric, cryptic Crematogaster levior ant species along a climate gradient. Additionally, we investigate the genomic basis of chemical communication in both species. Communication in insects is mainly mediated by cuticular hydrocarbons (CHCs), which also protect against water loss and, hence, are subject to changes via environmental acclimation or adaptation. The combination of environmental and chemical association analyses based on genome-wide Pool-Seq data allowed us to identify single nucleotide polymorphisms (SNPs) associated with climate and with chemical differences. Within species, CHC changes as a response to climate seem to be driven by phenotypic plasticity, since there is no overlap between climate- and CHC-associated SNPs. The only exception is the odorant receptor OR22c, which may be a candidate for population-specific CHC recognition in one of the species. Within both species, climate is significantly correlated with CHC differences, as well as to allele frequency differences. However, associated candidate SNPs, genes and functions are largely species-specific and we find evidence for minimal parallel evolution only on the level of genomic regions (J = 0.04). This highlights that even closely related species may follow divergent evolutionary trajectories when expressing similar adaptive phenotypes.}, language = {en} } @article{YeKeicherGentschevetal.2021, author = {Ye, Mingyu and Keicher, Markus and Gentschev, Ivaylo and Szalay, Aladar A.}, title = {Efficient selection of recombinant fluorescent vaccinia virus strains and rapid virus titer determination by using a multi-well plate imaging system}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {8}, issn = {2227-9059}, doi = {10.3390/biomedicines9081032}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245104}, year = {2021}, abstract = {Engineered vaccinia virus (VACV) strains are used extensively as vectors for the development of novel cancer vaccines and cancer therapeutics. In this study, we describe for the first time a high-throughput approach for both fluorescent rVACV generation and rapid viral titer measurement with the multi-well plate imaging system, IncuCyte\(^®\)S3. The isolation of a single, well-defined plaque is critical for the generation of novel recombinant vaccinia virus (rVACV) strains. Unfortunately, current methods of rVACV engineering via plaque isolation are time-consuming and laborious. Here, we present a modified fluorescent viral plaque screening and selection strategy that allows one to generally obtain novel fluorescent rVACV strains in six days, with a minimum of just four days. The standard plaque assay requires chemicals for fixing and staining cells. Manual plaque counting based on visual inspection of the cell culture plates is time-consuming. Here, we developed a fluorescence-based plaque assay for quantifying the vaccinia virus that does not require a cell staining step. This approach is less toxic to researchers and is reproducible; it is thus an improvement over the traditional assay. Lastly, plaque counting by virtue of a fluorescence-based image is very convenient, as it can be performed directly on the computer.}, language = {en} } @article{LiangBencurovaPsotaetal.2021, author = {Liang, Chunguang and Bencurova, Elena and Psota, Eric and Neurgaonkar, Priya and Prelog, Martina and Scheller, Carsten and Dandekar, Thomas}, title = {Population-predicted MHC class II epitope presentation of SARS-CoV-2 structural proteins correlates to the case fatality rates of COVID-19 in different countries}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {5}, issn = {1422-0067}, doi = {10.3390/ijms22052630}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258936}, year = {2021}, abstract = {We observed substantial differences in predicted Major Histocompatibility Complex II (MHCII) epitope presentation of SARS-CoV-2 proteins for different populations but only minor differences in predicted MHCI epitope presentation. A comparison of this predicted epitope MHC-coverage revealed for the early phase of infection spread (till day 15 after reaching 128 observed infection cases) highly significant negative correlations with the case fatality rate. Specifically, this was observed in different populations for MHC class II presentation of the viral spike protein (p-value: 0.0733 for linear regression), the envelope protein (p-value: 0.023), and the membrane protein (p-value: 0.00053), indicating that the high case fatality rates of COVID-19 observed in some countries seem to be related with poor MHC class II presentation and hence weak adaptive immune response against these viral envelope proteins. Our results highlight the general importance of the SARS-CoV-2 structural proteins in immunological control in early infection spread looking at a global census in various countries and taking case fatality rate into account. Other factors such as health system and control measures become more important after the early spread. Our study should encourage further studies on MHCII alleles as potential risk factors in COVID-19 including assessment of local populations and specific allele distributions.}, language = {en} } @article{LatifiHolzwarthSkidmoreetal.2021, author = {Latifi, Hooman and Holzwarth, Stefanie and Skidmore, Andrew and Brůna, Josef and Červenka, Jaroslav and Darvishzadeh, Roshanak and Hais, Martin and Heiden, Uta and Homolov{\´a}, Lucie and Krzystek, Peter and Schneider, Thomas and Star{\´y}, Martin and Wang, Tiejun and M{\"u}ller, J{\"o}rg and Heurich, Marco}, title = {A laboratory for conceiving Essential Biodiversity Variables (EBVs)—The 'Data pool initiative for the Bohemian Forest Ecosystem'}, series = {Methods in Ecology and Evolution}, volume = {12}, journal = {Methods in Ecology and Evolution}, number = {11}, doi = {10.1111/2041-210X.13695}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262743}, pages = {2073-2083}, year = {2021}, abstract = {Effects of climate change-induced events on forest ecosystem dynamics of composition, function and structure call for increased long-term, interdisciplinary and integrated research on biodiversity indicators, in particular within strictly protected areas with extensive non-intervention zones. The long-established concept of forest supersites generally relies on long-term funds from national agencies and goes beyond the logistic and financial capabilities of state- or region-wide protected area administrations, universities and research institutes. We introduce the concept of data pools as a smaller-scale, user-driven and reasonable alternative to co-develop remote sensing and forest ecosystem science to validated products, biodiversity indicators and management plans. We demonstrate this concept with the Bohemian Forest Ecosystem Data Pool, which has been established as an interdisciplinary, international data pool within the strictly protected Bavarian Forest and Šumava National Parks and currently comprises 10 active partners. We demonstrate how the structure and impact of the data pool differs from comparable cases. We assessed the international influence and visibility of the data pool with the help of a systematic literature search and a brief analysis of the results. Results primarily suggest an increase in the impact and visibility of published material during the life span of the data pool, with highest visibilities achieved by research conducted on leaf traits, vegetation phenology and 3D-based forest inventory. We conclude that the data pool results in an efficient contribution to the concept of global biodiversity observatory by evolving towards a training platform, functioning as a pool of data and algorithms, directly communicating with management for implementation and providing test fields for feasibility studies on earth observation missions.}, language = {en} } @article{DandekarBencurovaOsmanogluetal.2021, author = {Dandekar, Thomas and Bencurova, Elena and Osmanoglu, {\"O}zge and Naseem, Muhammad}, title = {Klimapflanzen und biologische Wege zu negativen Kohlendioxidemissionen}, series = {BIOspektrum}, volume = {27}, journal = {BIOspektrum}, number = {7}, issn = {1868-6249}, doi = {10.1007/s12268-021-1677-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-270067}, pages = {769-772}, year = {2021}, abstract = {Climate plants are critical to prevent global warming as all efforts to save carbon dioxide are too slow and climate disasters on the rise. For best carbon dioxide harvesting we compare algae, trees and crop plants and use metagenomic analysis of environmental samples. We compare different pathways, carbon harvesting potentials of different plants as well as synthetic modifications including carbon dioxide flux balance analysis. For implementation, agriculture and modern forestry are important.}, language = {de} }