@article{EisenhuthVellmerRauhetal.2021, author = {Eisenhuth, Nicole and Vellmer, Tim and Rauh, Elisa T. and Butter, Falk and Janzen, Christian J.}, title = {A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei}, series = {mbio}, volume = {12}, journal = {mbio}, number = {6}, doi = {10.1128/mBio.01352-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260698}, pages = {e01352-21}, year = {2021}, abstract = {The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.}, 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{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{RotherKraftSmithetal.2021, author = {Rother, Lisa and Kraft, Nadine and Smith, Dylan B. and El Jundi, Basil and Gill, Richard J. and Pfeiffer, Keram}, title = {A micro-CT-based standard brain atlas of the bumblebee}, series = {Cell and Tissue Research}, volume = {386}, journal = {Cell and Tissue Research}, number = {1}, issn = {1432-0878}, doi = {10.1007/s00441-021-03482-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267783}, pages = {29-45}, year = {2021}, abstract = {In recent years, bumblebees have become a prominent insect model organism for a variety of biological disciplines, particularly to investigate learning behaviors as well as visual performance. Understanding these behaviors and their underlying neurobiological principles requires a clear understanding of brain anatomy. Furthermore, to be able to compare neuronal branching patterns across individuals, a common framework is required, which has led to the development of 3D standard brain atlases in most of the neurobiological insect model species. Yet, no bumblebee 3D standard brain atlas has been generated. Here we present a brain atlas for the buff-tailed bumblebee Bombus terrestris using micro-computed tomography (micro-CT) scans as a source for the raw data sets, rather than traditional confocal microscopy, to produce the first ever micro-CT-based insect brain atlas. We illustrate the advantages of the micro-CT technique, namely, identical native resolution in the three cardinal planes and 3D structure being better preserved. Our Bombus terrestris brain atlas consists of 30 neuropils reconstructed from ten individual worker bees, with micro-CT allowing us to segment neuropils completely intact, including the lamina, which is a tissue structure often damaged when dissecting for immunolabeling. Our brain atlas can serve as a platform to facilitate future neuroscience studies in bumblebees and illustrates the advantages of micro-CT for specific applications in insect neuroanatomy.}, language = {en} } @article{YeWilhelmGentschevetal.2021, author = {Ye, Mingyu and Wilhelm, Martina and Gentschev, Ivaylo and Szalay, Alad{\´a}r}, title = {A modified limiting dilution method for monoclonal stable cell line selection using a real-time fluorescence imaging system: A practical workflow and advanced applications}, series = {Methods and Protocols}, volume = {4}, journal = {Methods and Protocols}, number = {1}, doi = {10.3390/mps4010016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228896}, year = {2021}, abstract = {Stable cell lines are widely used in laboratory research and pharmaceutical industry. They are mainly applied in recombinant protein and antibody productions, gene function studies, drug screens, toxicity assessments, and for cancer therapy investigation. There are two types of cell lines, polyclonal and monoclonal origin, that differ regarding their homogeneity and heterogeneity. Generating a high-quality stable cell line, which can grow continuously and carry a stable genetic modification without alteration is very important for most studies, because polyclonal cell lines of multicellular origin can be highly variable and unstable and lead to inconclusive experimental results. The most commonly used technologies of single cell originate monoclonal stable cell isolation in laboratory are fluorescence-activated cell sorting (FACS) sorting and limiting dilution cloning. Here, we describe a modified limiting dilution method of monoclonal stable cell line selection using the real-time fluorescence imaging system IncuCyte\(^®\)S3.}, language = {en} } @article{WalterDegenPfeifferetal.2021, author = {Walter, Thomas and Degen, Jacqueline and Pfeiffer, Keram and St{\"o}ckl, Anna and Montenegro, Sergio and Degen, Tobias}, title = {A new innovative real-time tracking method for flying insects applicable under natural conditions}, series = {BMC Zoology}, volume = {6}, journal = {BMC Zoology}, doi = {10.1186/s40850-021-00097-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265716}, year = {2021}, abstract = {Background Sixty percent of all species are insects, yet despite global efforts to monitor animal movement patterns, insects are continuously underrepresented. This striking difference between species richness and the number of species monitored is not due to a lack of interest but rather to the lack of technical solutions. Often the accuracy and speed of established tracking methods is not high enough to record behavior and react to it experimentally in real-time, which applies in particular to small flying animals. Results Our new method of real-time tracking relates to frequencies of solar radiation which are almost completely absorbed by traveling through the atmosphere. For tracking, photoluminescent tags with a peak emission (1400 nm), which lays in such a region of strong absorption through the atmosphere, were attached to the animals. The photoluminescent properties of passivated lead sulphide quantum dots were responsible for the emission of light by the tags and provide a superb signal-to noise ratio. We developed prototype markers with a weight of 12.5 mg and a diameter of 5 mm. Furthermore, we developed a short wave infrared detection system which can record and determine the position of an animal in a heterogeneous environment with a delay smaller than 10 ms. With this method we were able to track tagged bumblebees as well as hawk moths in a flight arena that was placed outside on a natural meadow. Conclusion Our new method eliminates the necessity of a constant or predictable environment for many experimental setups. Furthermore, we postulate that the developed matrix-detector mounted to a multicopter will enable tracking of small flying insects, over medium range distances (>1000m) in the near future because: a) the matrix-detector equipped with an 70 mm interchangeable lens weighs less than 380 g, b) it evaluates the position of an animal in real-time and c) it can directly control and communicate with electronic devices.}, 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{VogelPrinzingBussleretal.2021, author = {Vogel, Sebastian and Prinzing, Andreas and Bußler, Heinz and M{\"u}ller, J{\"o}rg and Schmidt, Stefan and Thorn, Simon}, title = {Abundance, not diversity, of host beetle communities determines abundance and diversity of parasitoids in deadwood}, series = {Ecology and Evolution}, volume = {11}, journal = {Ecology and Evolution}, number = {11}, doi = {10.1002/ece3.7535}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-238892}, pages = {6881 -- 6888}, year = {2021}, abstract = {Most parasites and parasitoids are adapted to overcome defense mechanisms of their specific hosts and hence colonize a narrow range of host species. Accordingly, an increase in host functional or phylogenetic dissimilarity is expected to increase the species diversity of parasitoids. However, the local diversity of parasitoids may be driven by the accessibility and detectability of hosts, both increasing with increasing host abundance. Yet, the relative importance of these two mechanisms remains unclear. We parallelly reared communities of saproxylic beetle as potential hosts and associated parasitoid Hymenoptera from experimentally felled trees. The dissimilarity of beetle communities was inferred from distances in seven functional traits and from their evolutionary ancestry. We tested the effect of host abundance, species richness, functional, and phylogenetic dissimilarities on the abundance, species richness, and Shannon diversity of parasitoids. Our results showed an increase of abundance, species richness, and Shannon diversity of parasitoids with increasing beetle abundance. Additionally, abundance of parasitoids increased with increasing species richness of beetles. However, functional and phylogenetic dissimilarity showed no effect on the diversity of parasitoids. Our results suggest that the local diversity of parasitoids, of ephemeral and hidden resources like saproxylic beetles, is highest when resources are abundant and thereby detectable and accessible. Hence, in some cases, resources do not need to be diverse to promote parasitoid diversity.}, language = {en} } @article{GaritanoTrojaolaSanchoGoetzetal.2021, author = {Garitano-Trojaola, Andoni and Sancho, Ana and G{\"o}tz, Ralph and Eiring, Patrick and Walz, Susanne and Jetani, Hardikkumar and Gil-Pulido, Jesus and Da Via, Matteo Claudio and Teufel, Eva and Rhodes, Nadine and Haertle, Larissa and Arellano-Viera, Estibaliz and Tibes, Raoul and Rosenwald, Andreas and Rasche, Leo and Hudecek, Michael and Sauer, Markus and Groll, J{\"u}rgen and Einsele, Hermann and Kraus, Sabrina and Kort{\"u}m, Martin K.}, title = {Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia}, series = {Communications Biology}, volume = {4}, journal = {Communications Biology}, number = {1}, doi = {10.1038/s42003-021-02215-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260709}, year = {2021}, abstract = {The presence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate FLT3-ITD+AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1/N-WASP, through ARP2/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate FLT3-ITD+AML. Garitano-Trojaola et al. used a combination of human acute myeloid leukemia (AML) cell lines and primary samples to show that RAC1-dependent actin cytoskeleton remodeling through BCL2 family plays a key role in resistance to the FLT3 inhibitor, Midostaurin in AML. They showed that by targeting RAC1 and BCL2, Midostaurin resistance was diminished, which potentially paves the way for an innovate treatment approach for FLT3 mutant AML.}, language = {en} } @article{MrestaniPauliKollmannsbergeretal.2021, author = {Mrestani, Achmed and Pauli, Martin and Kollmannsberger, Philip and Repp, Felix and Kittel, Robert J. and Eilers, Jens and Doose, S{\"o}ren and Sauer, Markus and Sir{\´e}n, Anna-Leena and Heckmann, Manfred and Paul, Mila M.}, title = {Active zone compaction correlates with presynaptic homeostatic potentiation}, series = {Cell Reports}, volume = {37}, journal = {Cell Reports}, number = {1}, doi = {10.1016/j.celrep.2021.109770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265497}, pages = {109770}, year = {2021}, abstract = {Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic homeostatic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement by incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction microscopy [dSTORM]) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) to study AZ plasticity during PHP at the synaptic mesoscale. We find compaction of individual AZs in acute philanthotoxin-induced and chronic genetically induced PHP but unchanged copy numbers of AZ proteins. Compaction even occurs at the level of Brp subclusters, which move toward AZ centers, and in Rab3 interacting molecule (RIM)-binding protein (RBP) subclusters. Furthermore, correlative confocal and dSTORM imaging reveals how AZ compaction in PHP translates into apparent increases in AZ area and Brp protein content, as implied earlier.}, 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{RiedmeierDecarolisHaubitzetal.2021, author = {Riedmeier, Maria and Decarolis, Boris and Haubitz, Imme and M{\"u}ller, Sophie and Uttinger, Konstantin and B{\"o}rner, Kevin and Reibetanz, Joachim and Wiegering, Armin and H{\"a}rtel, Christoph and Schlegel, Paul-Gerhardt and Fassnacht, Martin and Wiegering, Verena}, title = {Adrenocortical carcinoma in childhood: a systematic review}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {21}, issn = {2072-6694}, doi = {10.3390/cancers13215266}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248507}, year = {2021}, abstract = {Adrenocortical tumors are rare in children. This systematic review summarizes the published evidence on pediatric adrenocortical carcinoma (ACC) to provide a basis for a better understanding of the disease, investigate new molecular biomarkers and therapeutic targets, and define which patients may benefit from a more aggressive therapeutic approach. We included 137 studies with 3680 ACC patients (~65\% female) in our analysis. We found no randomized controlled trials, so this review mainly reflects retrospective data. Due to a specific mutation in the TP53 gene in ~80\% of Brazilian patients, that cohort was analyzed separately from series from other countries. Hormone analysis was described in 2569 of the 2874 patients (89\%). Most patients were diagnosed with localized disease, whereas 23\% had metastasis at primary diagnosis. Only 72\% of the patients achieved complete resection. In 334 children (23\%), recurrent disease was reported: 81\% — local recurrence, 19\% (n = 65) — distant metastases at relapse. Patients < 4 years old had a different distribution of tumor stages and hormone activity and better overall survival (p < 0.001). Although therapeutic approaches are typically multimodal, no consensus is available on effective standard treatments for advanced ACC. Thus, knowledge regarding pediatric ACC is still scarce and international prospective studies are needed to implement standardized clinical stratifications and risk-adapted therapeutic strategies.}, 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{GuptaSrivastavaMinochaetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Minocha, Rashmi and Akash, Aman and Dangwal, Seema and Dandekar, Thomas}, title = {Alveolar regeneration in COVID-19 patients: a network perspective}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {20}, issn = {1422-0067}, doi = {10.3390/ijms222011279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284307}, year = {2021}, abstract = {A viral infection involves entry and replication of viral nucleic acid in a host organism, subsequently leading to biochemical and structural alterations in the host cell. In the case of SARS-CoV-2 viral infection, over-activation of the host immune system may lead to lung damage. Albeit the regeneration and fibrotic repair processes being the two protective host responses, prolonged injury may lead to excessive fibrosis, a pathological state that can result in lung collapse. In this review, we discuss regeneration and fibrosis processes in response to SARS-CoV-2 and provide our viewpoint on the triggering of alveolar regeneration in coronavirus disease 2019 (COVID-19) patients.}, 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{AlnusaireSayedElmaidomyetal.2021, author = {Alnusaire, Taghreed S. and Sayed, Ahmed M. and Elmaidomy, Abeer H. and Al-Sanea, Mohammad M. and Albogami, Sarah and Albqmi, Mha and Alowaiesh, Bassam F. and Mostafa, Ehab M. and Musa, Arafa and Youssif, Khayrya A. and Refaat, Hesham and Othman, Eman M. and Dandekar, Thomas and Alaaeldin, Eman and Ghoneim, Mohammed M. and Abdelmohsen, Usama Ramadan}, title = {An in vitro and in silico study of the enhanced antiproliferative and pro-oxidant potential of Olea europaea L. cv. Arbosana leaf extract via elastic nanovesicles (spanlastics)}, series = {Antioxidants}, volume = {10}, journal = {Antioxidants}, number = {12}, issn = {2076-3921}, doi = {10.3390/antiox10121860}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250064}, year = {2021}, abstract = {The olive tree is a venerable Mediterranean plant and often used in traditional medicine. The main aim of the present study was to evaluate the effect of Olea europaea L. cv. Arbosana leaf extract (OLE) and its encapsulation within a spanlastic dosage form on the improvement of its pro-oxidant and antiproliferative activity against HepG-2, MCF-7, and Caco-2 human cancer cell lines. The LC-HRESIMS-assisted metabolomic profile of OLE putatively annotated 20 major metabolites and showed considerable in vitro antiproliferative activity against HepG-2, MCF-7, and Caco-2 cell lines with IC\(_{50}\) values of 9.2 ± 0.8, 7.1 ± 0.9, and 6.5 ± 0.7 µg/mL, respectively. The encapsulation of OLE within a (spanlastic) nanocarrier system, using a spraying method and Span 40 and Tween 80 (4:1 molar ratio), was successfully carried out (size 41 ± 2.4 nm, zeta potential 13.6 ± 2.5, and EE 61.43 ± 2.03\%). OLE showed enhanced thermal stability, and an improved in vitro antiproliferative effect against HepG-2, MCF-7, and Caco-2 (IC\(_{50}\) 3.6 ± 0.2, 2.3 ± 0.1, and 1.8 ± 0.1 µg/mL, respectively) in comparison to the unprocessed extract. Both preparations were found to exhibit pro-oxidant potential inside the cancer cells, through the potential inhibitory activity of OLE against glutathione reductase and superoxide dismutase (IC\(_{50}\) 1.18 ± 0.12 and 2.33 ± 0.19 µg/mL, respectively). These inhibitory activities were proposed via a comprehensive in silico study to be linked to the presence of certain compounds in OLE. Consequently, we assume that formulating such a herbal extract within a suitable nanocarrier would be a promising improvement of its therapeutic potential.}, 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{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{ColizziBeerCutietal.2021, author = {Colizzi, Francesca Sara and Beer, Katharina and Cuti, Paolo and Deppisch, Peter and Mart{\´i}nez Torres, David and Yoshii, Taishi and Helfrich-F{\"o}rster, Charlotte}, title = {Antibodies Against the Clock Proteins Period and Cryptochrome Reveal the Neuronal Organization of the Circadian Clock in the Pea Aphid}, series = {Frontiers in Physiology}, volume = {12}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2021.705048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242909}, year = {2021}, abstract = {Circadian clocks prepare the organism to cyclic environmental changes in light, temperature, or food availability. Here, we characterized the master clock in the brain of a strongly photoperiodic insect, the aphid Acyrthosiphon pisum, immunohistochemically with antibodies against A. pisum Period (PER), Drosophila melanogaster Cryptochrome (CRY1), and crab Pigment-Dispersing Hormone (PDH). The latter antibody detects all so far known PDHs and PDFs (Pigment-Dispersing Factors), which play a dominant role in the circadian system of many arthropods. We found that, under long days, PER and CRY are expressed in a rhythmic manner in three regions of the brain: the dorsal and lateral protocerebrum and the lamina. No staining was detected with anti-PDH, suggesting that aphids lack PDF. All the CRY1-positive cells co-expressed PER and showed daily PER/CRY1 oscillations of high amplitude, while the PER oscillations of the CRY1-negative PER neurons were of considerable lower amplitude. The CRY1 oscillations were highly synchronous in all neurons, suggesting that aphid CRY1, similarly to Drosophila CRY1, is light sensitive and its oscillations are synchronized by light-dark cycles. Nevertheless, in contrast to Drosophila CRY1, aphid CRY1 was not degraded by light, but steadily increased during the day and decreased during the night. PER was always located in the nuclei of the clock neurons, while CRY was predominantly cytoplasmic and revealed the projections of the PER/CRY1-positive neurons. We traced the PER/CRY1-positive neurons through the aphid protocerebrum discovering striking similarities with the circadian clock of D. melanogaster: The CRY1 fibers innervate the dorsal and lateral protocerebrum and putatively connect the different PER-positive neurons with each other. They also run toward the pars intercerebralis, which controls hormone release via the neurohemal organ, the corpora cardiaca. In contrast to Drosophila, the CRY1-positive fibers additionally travel directly toward the corpora cardiaca and the close-by endocrine gland, corpora allata. This suggests a direct link between the circadian clock and the photoperiodic control of hormone release that can be studied in the future.}, language = {en} } @article{GuptaSrivastavaOsmanogluetal.2021, author = {Gupta, Shishir K. and Srivastava, Mugdha and Osmanoglu, {\"O}zge and Xu, Zhuofei and Brakhage, Axel A. and Dandekar, Thomas}, title = {Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {10}, issn = {2076-2607}, doi = {10.3390/microorganisms9102014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246318}, year = {2021}, abstract = {Aspergillus is an important fungal genus containing economically important species, as well as pathogenic species of animals and plants. Using eighteen fungal species of the genus Aspergillus, we conducted a comprehensive investigation of conserved genes and their evolution. This also allows us to investigate the selection pressure driving the adaptive evolution in the pathogenic species A. fumigatus. Among single-copy orthologs (SCOs) for A. fumigatus and the closely related species A. fischeri, we identified 122 versus 50 positively selected genes (PSGs), respectively. Moreover, twenty conserved genes of unknown function were established to be positively selected and thus important for adaption. A. fumigatus PSGs interacting with human host proteins show over-representation of adaptive, symbiosis-related, immunomodulatory and virulence-related pathways, such as the TGF-β pathway, insulin receptor signaling, IL1 pathway and interfering with phagosomal GTPase signaling. Additionally, among the virulence factor coding genes, secretory and membrane protein-coding genes in multi-copy gene families, 212 genes underwent positive selection and also suggest increased adaptation, such as fungal immune evasion mechanisms (aspf2), siderophore biosynthesis (sidD), fumarylalanine production (sidE), stress tolerance (atfA) and thermotolerance (sodA). These genes presumably contribute to host adaptation strategies. Genes for the biosynthesis of gliotoxin are shared among all the close relatives of A. fumigatus as an ancient defense mechanism. Positive selection plays a crucial role in the adaptive evolution of A. fumigatus. The genome-wide profile of PSGs provides valuable targets for further research on the mechanisms of immune evasion, antimycotic targeting and understanding fundamental virulence processes.}, language = {en} } @article{SponslerBratman2021, author = {Sponsler, Douglas B. and Bratman, Eve Z.}, title = {Beekeeping in, of or for the city? A socioecological perspective on urban apiculture}, series = {People and Nature}, volume = {3}, journal = {People and Nature}, number = {3}, doi = {10.1002/pan3.10206}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239949}, pages = {550 -- 559}, year = {2021}, abstract = {The term 'urban beekeeping' connotes a host of meanings—sociopolitical, commercial, ecological and personal—beyond the mere description of where bees and beekeepers happen to coincide. Yet, these meanings are seldom articulated explicitly or brought into critical engagement with the relevant fields of urban ecology and political ecology. Beginning with a brief account of the history of urban beekeeping in the United States, we draw upon urban ecological theory to construct a conceptual model of urban beekeeping that distinguishes beekeeping in, of and for the city. In our model, beekeeping in the city describes the mere importation of the traditionally rural practice of beekeeping into urban spaces for the private reasons of the individual beekeeper, whereas beekeeping of the city describes beekeeping that is consciously tailored to the urban context, often accompanied by (semi)professionalization of beekeepers and the formation of local expert communities (i.e. beekeeping associations). Beekeeping for the city describes a shift in mindset in which beekeeping is directed to civic ends beyond the boundaries of the beekeeping community per se. Using this framework, we identify and discuss specific socioecological assets and liabilities of urban beekeeping, and how these relate to beekeeping in, of and for the city. We then formulate actionable guidelines for maturing the practice of urban beekeeping into a beneficent and self-critical form of urban ecological citizenship; these include fostering self-regulation within the beekeeping community, harnessing beekeeping as a 'gateway' experience for a broader rapprochement between urban residents and nature, and recognizing the political-ecological context of beekeeping with respect to matters of socioecological justice.}, language = {en} } @article{BrosterReixFlorimondCayreletal.2021, author = {Broster Reix, Christine E. and Florimond, C{\´e}lia and Cayrel, Anne and Mailh{\´e}, Am{\´e}lie and Agnero-Rigot, Corentin and Landrein, Nicolas and Dacheux, Denis and Havlicek, Katharina and Bonhivers, M{\´e}lanie and Morriswood, Brooke and Robinson, Derrick R.}, title = {Bhalin, an essential cytoskeleton-associated protein of Trypanosoma brucei linking TbBILBO1 of the flagellar pocket collar with the hook complex}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {11}, issn = {2076-2607}, doi = {10.3390/microorganisms9112334}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250301}, year = {2021}, abstract = {Background: In most trypanosomes, endo and exocytosis only occur at a unique organelle called the flagellar pocket (FP) and the flagellum exits the cell via the FP. Investigations of essential cytoskeleton-associated structures located at this site have revealed a number of essential proteins. The protein TbBILBO1 is located at the neck of the FP in a structure called the flagellar pocket collar (FPC) and is essential for biogenesis of the FPC and parasite survival. TbMORN1 is a protein that is present on a closely linked structure called the hook complex (HC) and is located anterior to and overlapping the collar. TbMORN1 is essential in the bloodstream form of T. brucei. We now describe the location and function of BHALIN, an essential, new FPC-HC protein. Methodology/Principal Findings: Here, we show that a newly characterised protein, BHALIN (BILBO1 Hook Associated LINker protein), is localised to both the FPC and HC and has a TbBILBO1 binding domain, which was confirmed in vitro. Knockdown of BHALIN by RNAi in the bloodstream form parasites led to cell death, indicating an essential role in cell viability. Conclusions/Significance: Our results demonstrate the essential role of a newly characterised hook complex protein, BHALIN, that influences flagellar pocket organisation and function in bloodstream form T. brucei parasites.}, language = {en} } @article{MakbulKraftGriessmannetal.2021, author = {Makbul, Cihan and Kraft, Christian and Grießmann, Matthias and Rasmussen, Tim and Katzenberger, Kilian and Lappe, Melina and Pfarr, Paul and Stoffer, Cato and St{\"o}hr, Mara and Wandinger, Anna-Maria and B{\"o}ttcher, Bettina}, title = {Binding of a pocket factor to Hepatitis B virus capsids changes the rotamer conformation of Phenylalanine 97}, series = {Viruses}, volume = {13}, journal = {Viruses}, number = {11}, issn = {1999-4915}, doi = {10.3390/v13112115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248565}, year = {2021}, abstract = {(1) Background: During maturation of the Hepatitis B virus, a viral polymerase inside the capsid transcribes a pre-genomic RNA into a partly double stranded DNA-genome. This is followed by envelopment with surface proteins inserted into a membrane. Envelopment is hypothetically regulated by a structural signal that reports the maturation state of the genome. NMR data suggest that such a signal can be mimicked by the binding of the detergent Triton X 100 to hydrophobic pockets in the capsid spikes. (2) Methods: We have used electron cryo-microscopy and image processing to elucidate the structural changes that are concomitant with the binding of Triton X 100. (3) Results: Our maps show that Triton X 100 binds with its hydrophobic head group inside the pocket. The hydrophilic tail delineates the outside of the spike and is coordinated via Lys-96. The binding of Triton X 100 changes the rotamer conformation of Phe-97 in helix 4, which enables a π-stacking interaction with Trp-62 in helix 3. Similar changes occur in mutants with low secretion phenotypes (P5T and L60V) and in a mutant with a pre-mature secretion phenotype (F97L). (4) Conclusion: Binding of Triton X 100 is unlikely to mimic structural maturation because mutants with different secretion phenotypes show similar structural responses.}, language = {en} } @article{FerreiraBoffVerzaetal.2021, author = {Ferreira, Eliana Aparecida and Boff, Samuel and Verza, Sandra S. and Mussury, Rosilda Mara}, title = {Bioecological and behavioral interaction between pollinating bees and the pioneer shrub Ludwigia nervosa in degraded area suggests an exotic bee as its major pollinator}, series = {Biology}, volume = {10}, journal = {Biology}, number = {2}, issn = {2079-7737}, doi = {10.3390/biology10020114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228757}, year = {2021}, abstract = {The flowers of plants of the genus Ludwigia are an important source of food for several species of bees. In the current study, we conducted an experiment with the aim to describe the reproductive biology and phenology of L. nervosa; to identify the species of visiting bees; analyze the foraging behavior of bees; and to investigate whether the reproductive success of the species is related to the foraging activity of bees. We found that the flowers received visits from several native bee species (n = 7), in addition of the exotic honey bees which came to be the dominant species. During visits the majority of the bees foraged in both resources, pollen and nectar. The significantly higher production of fruits in open pollinated pollination experiment compared to artificial cross pollination, suggests honey bees as effective pollinator of this plant species in the study site. Pollen deposition occurs efficiently, given the absence of pollen limitation. Despite massive visitation of honey bees, Ludwigianervosa is attractive to native bees, and therefore it may help to sustain population of both native and exotic pollinators in fragmented humid areas.}, 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{WelterWagnerFurtwaengleretal.2021, author = {Welter, Nils and Wagner, Angelo and Furtw{\"a}ngler, Rhoikos and Melchior, Patrick and Kager, Leo and Vokuhl, Christian and Schenk, Jens-Peter and Meier, Clemens Magnus and Siemer, Stefan and Gessler, Manfred and Graf, Norbert}, title = {Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {19}, issn = {2072-6694}, doi = {10.3390/cancers13195016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248434}, year = {2021}, abstract = {(1) Background: about 10\% of Wilms Tumor (WT) patients have a malformation or cancer predisposition syndrome (CPS) with causative germline genetic or epigenetic variants. Knowledge on CPS is essential for genetic counselling. (2) Methods: this retrospective analysis focused on 2927 consecutive patients with WTs registered between 1989 and 2017 in the SIOP/GPOH studies. (3) Results: Genitourinary malformations (GU, N = 66, 2.3\%), Beckwith-Wiedemann spectrum (BWS, N = 32, 1.1\%), isolated hemihypertrophy (IHH, N = 29, 1.0\%), Denys-Drash syndrome (DDS, N = 24, 0.8\%) and WAGR syndrome (N = 20, 0.7\%) were reported most frequently. Compared to others, these patients were younger at WT diagnosis (median age 24.5 months vs. 39.0 months), had smaller tumors (349.4 mL vs. 487.5 mL), less often metastasis (8.2\% vs. 18\%), but more often nephroblastomatosis (12.9\% vs. 1.9\%). WT with IHH was associated with blastemal WT and DDS with stromal subtype. Bilateral WTs were common in WAGR (30\%), DDS (29\%) and BWS (31\%). Chemotherapy induced reduction in tumor volume was poor in DDS (0.4\% increase) and favorable in BWS (86.9\% reduction). The event-free survival (EFS) of patients with BWS was significantly (p = 0.002) worse than in others. (4) Conclusions: CPS should be considered in WTs with specific clinical features resulting in referral to a geneticist. Their outcome was not always favorable.}, language = {en} } @article{PetersKaiserFinketal.2021, author = {Peters, Simon and Kaiser, Lena and Fink, Julian and Schumacher, Fabian and Perschin, Veronika and Schlegel, Jan and Sauer, Markus and Stigloher, Christian and Kleuser, Burkhard and Seibel, Juergen and Schubert-Unkmeir, Alexandra}, title = {Click-correlative light and electron microscopy (click-AT-CLEM) for imaging and tracking azido-functionalized sphingolipids in bacteria}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-83813-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259147}, pages = {4300}, year = {2021}, abstract = {Sphingolipids, including ceramides, are a diverse group of structurally related lipids composed of a sphingoid base backbone coupled to a fatty acid side chain and modified terminal hydroxyl group. Recently, it has been shown that sphingolipids show antimicrobial activity against a broad range of pathogenic microorganisms. The antimicrobial mechanism, however, remains so far elusive. Here, we introduce 'click-AT-CLEM', a labeling technique for correlated light and electron microscopy (CLEM) based on the super-resolution array tomography (srAT) approach and bio-orthogonal click chemistry for imaging of azido-tagged sphingolipids to directly visualize their interaction with the model Gram-negative bacterium Neisseria meningitidis at subcellular level. We observed ultrastructural damage of bacteria and disruption of the bacterial outer membrane induced by two azido-modified sphingolipids by scanning electron microscopy and transmission electron microscopy. Click-AT-CLEM imaging and mass spectrometry clearly revealed efficient incorporation of azido-tagged sphingolipids into the outer membrane of Gram-negative bacteria as underlying cause of their antimicrobial activity.}, language = {en} } @article{UphusLuepkeYuanetal.2021, author = {Uphus, Lars and L{\"u}pke, Marvin and Yuan, Ye and Benjamin, Caryl and Englmeier, Jana and Fricke, Ute and Ganuza, Cristina and Schwindl, Michael and Uhler, Johannes and Menzel, Annette}, title = {Climate effects on vertical forest phenology of Fagus sylvatica L., sensed by Sentinel-2, time lapse camera, and visual ground observations}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {19}, issn = {2072-4292}, doi = {10.3390/rs13193982}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248419}, year = {2021}, abstract = {Contemporary climate change leads to earlier spring phenological events in Europe. In forests, in which overstory strongly regulates the microclimate beneath, it is not clear if further change equally shifts the timing of leaf unfolding for the over- and understory of main deciduous forest species, such as Fagus sylvatica L. (European beech). Furthermore, it is not known yet how this vertical phenological (mis)match — the phenological difference between overstory and understory — affects the remotely sensed satellite signal. To investigate this, we disentangled the start of season (SOS) of overstory F.sylvatica foliage from understory F. sylvatica foliage in forests, within nine quadrants of 5.8 × 5.8 km, stratified over a temperature gradient of 2.5 °C in Bavaria, southeast Germany, in the spring seasons of 2019 and 2020 using time lapse cameras and visual ground observations. We explained SOS dates and vertical phenological (mis)match by canopy temperature and compared these to Sentinel-2 derived SOS in response to canopy temperature. We found that overstory SOS advanced with higher mean April canopy temperature (visual ground observations: -2.86 days per °C; cameras: -2.57 days per °C). However, understory SOS was not significantly affected by canopy temperature. This led to an increase of vertical phenological mismatch with increased canopy temperature (visual ground observations: +3.90 days per °C; cameras: +2.52 days per °C). These results matched Sentinel-2-derived SOS responses, as pixels of higher canopy height advanced more by increased canopy temperature than pixels of lower canopy height. The results may indicate that, with further climate change, spring phenology of F. sylvatica overstory will advance more than F. sylvatica understory, leading to increased vertical phenological mismatch in temperate deciduous forests. This may have major ecological effects, but also methodological consequences for the field of remote sensing, as what the signal senses highly depends on the pixel mean canopy height and the vertical (mis)match.}, language = {en} } @article{MamontovaTrifaultBotenetal.2021, author = {Mamontova, Victoria and Trifault, Barbara and Boten, Lea and Burger, Kaspar}, title = {Commuting to work: Nucleolar long non-coding RNA control ribosome biogenesis from near and far}, series = {Non-Coding RNA}, volume = {7}, journal = {Non-Coding RNA}, number = {3}, issn = {2311-553X}, doi = {10.3390/ncrna7030042}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242756}, year = {2021}, abstract = {Gene expression is an essential process for cellular growth, proliferation, and differentiation. The transcription of protein-coding genes and non-coding loci depends on RNA polymerases. Interestingly, numerous loci encode long non-coding (lnc)RNA transcripts that are transcribed by RNA polymerase II (RNAPII) and fine-tune the RNA metabolism. The nucleolus is a prime example of how different lncRNA species concomitantly regulate gene expression by facilitating the production and processing of ribosomal (r)RNA for ribosome biogenesis. Here, we summarise the current findings on how RNAPII influences nucleolar structure and function. We describe how RNAPII-dependent lncRNA can both promote nucleolar integrity and inhibit ribosomal (r)RNA synthesis by modulating the availability of rRNA synthesis factors in trans. Surprisingly, some lncRNA transcripts can directly originate from nucleolar loci and function in cis. The nucleolar intergenic spacer (IGS), for example, encodes nucleolar transcripts that counteract spurious rRNA synthesis in unperturbed cells. In response to DNA damage, RNAPII-dependent lncRNA originates directly at broken ribosomal (r)DNA loci and is processed into small ncRNA, possibly to modulate DNA repair. Thus, lncRNA-mediated regulation of nucleolar biology occurs by several modes of action and is more direct than anticipated, pointing to an intimate crosstalk of RNA metabolic events.}, language = {en} } @article{ScheinerLimMeixneretal.2021, author = {Scheiner, Ricarda and Lim, Kayun and Meixner, Marina D. and Gabel, Martin S.}, title = {Comparing the appetitive learning performance of six European honeybee subspecies in a common apiary}, series = {Insects}, volume = {12}, journal = {Insects}, number = {9}, issn = {2075-4450}, doi = {10.3390/insects12090768}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245180}, year = {2021}, abstract = {The Western honeybee (Apis mellifera L.) is one of the most widespread insects with numerous subspecies in its native range. How far adaptation to local habitats has affected the cognitive skills of the different subspecies is an intriguing question that we investigate in this study. Naturally mated queens of the following five subspecies from different parts of Europe were transferred to Southern Germany: A. m. iberiensis from Portugal, A. m. mellifera from Belgium, A. m. macedonica from Greece, A. m. ligustica from Italy, and A. m. ruttneri from Malta. We also included the local subspecies A. m. carnica in our study. New colonies were built up in a common apiary where the respective queens were introduced. Worker offspring from the different subspecies were compared in classical olfactory learning performance using the proboscis extension response. Prior to conditioning, we measured individual sucrose responsiveness to investigate whether possible differences in learning performances were due to differential responsiveness to the sugar water reward. Most subspecies did not differ in their appetitive learning performance. However, foragers of the Iberian honeybee, A. m. iberiensis, performed significantly more poorly, despite having a similar sucrose responsiveness. We discuss possible causes for the poor performance of the Iberian honeybees, which may have been shaped by adaptation to the local habitat.}, language = {en} } @article{SchererFleishmanJonesetal.2021, author = {Scherer, Marc and Fleishman, Sarel J. and Jones, Patrik R. and Dandekar, Thomas and Bencurova, Elena}, title = {Computational Enzyme Engineering Pipelines for Optimized Production of Renewable Chemicals}, series = {Frontiers in Bioengineering and Biotechnology}, volume = {9}, journal = {Frontiers in Bioengineering and Biotechnology}, issn = {2296-4185}, doi = {10.3389/fbioe.2021.673005}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-240598}, year = {2021}, abstract = {To enable a sustainable supply of chemicals, novel biotechnological solutions are required that replace the reliance on fossil resources. One potential solution is to utilize tailored biosynthetic modules for the metabolic conversion of CO2 or organic waste to chemicals and fuel by microorganisms. Currently, it is challenging to commercialize biotechnological processes for renewable chemical biomanufacturing because of a lack of highly active and specific biocatalysts. As experimental methods to engineer biocatalysts are time- and cost-intensive, it is important to establish efficient and reliable computational tools that can speed up the identification or optimization of selective, highly active, and stable enzyme variants for utilization in the biotechnological industry. Here, we review and suggest combinations of effective state-of-the-art software and online tools available for computational enzyme engineering pipelines to optimize metabolic pathways for the biosynthesis of renewable chemicals. Using examples relevant for biotechnology, we explain the underlying principles of enzyme engineering and design and illuminate future directions for automated optimization of biocatalysts for the assembly of synthetic metabolic pathways.}, language = {en} } @article{MakbulKhayenkoMaricetal.2021, author = {Makbul, Cihan and Khayenko, Vladimir and Maric, Hans Michael and B{\"o}ttcher, Bettina}, title = {Conformational Plasticity of Hepatitis B Core Protein Spikes Promotes Peptide Binding Independent of the Secretion Phenotype}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {5}, issn = {2076-2607}, doi = {10.3390/microorganisms9050956}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236720}, year = {2021}, abstract = {Hepatitis B virus is a major human pathogen, which forms enveloped virus particles. During viral maturation, membrane-bound hepatitis B surface proteins package hepatitis B core protein capsids. This process is intercepted by certain peptides with an "LLGRMKG" motif that binds to the capsids at the tips of dimeric spikes. With microcalorimetry, electron cryo microscopy and peptide microarray-based screens, we have characterized the structural and thermodynamic properties of peptide binding to hepatitis B core protein capsids with different secretion phenotypes. The peptide "GSLLGRMKGA" binds weakly to hepatitis B core protein capsids and mutant capsids with a premature (F97L) or low-secretion phenotype (L60V and P5T). With electron cryo microscopy, we provide novel structures for L60V and P5T and demonstrate that binding occurs at the tips of the spikes at the dimer interface, splaying the helices apart independent of the secretion phenotype. Peptide array screening identifies "SLLGRM" as the core binding motif. This shortened motif binds only to one of the two spikes in the asymmetric unit of the capsid and induces a much smaller conformational change. Altogether, these comprehensive studies suggest that the tips of the spikes act as an autonomous binding platform that is unaffected by mutations that affect secretion phenotypes.}, language = {en} } @article{WelterWagnerFurtwaengleretal.2021, author = {Welter, Nils and Wagner, Angelo and Furtw{\"a}ngler, Rhoikos and Melchior, Patrick and Kager, Leo and Vokuhl, Christian and Schenk, Jens-Peter and Meier, Clemens Magnus and Siemer, Stefan and Gessler, Manfred and Graf, Norbert}, title = {Correction: Welter et al. Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome. Cancers 2021, 13, 5016}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225743}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250135}, year = {2021}, abstract = {In the original article [1] there was a mistake in Table 2 as published. Table 2 contains wrong percentages in lines Bilateral disease and Patients with CPS or GU. For this reason the table should be replaced with the correct one as shown below.}, language = {en} } @article{AdolfiHerpinMartinezBengocheaetal.2021, author = {Adolfi, Mateus C. and Herpin, Amaury and Martinez-Bengochea, Anabel and Kneitz, Susanne and Regensburger, Martina and Grunwald, David J. and Schartl, Manfred}, title = {Crosstalk Between Retinoic Acid and Sex-Related Genes Controls Germ Cell Fate and Gametogenesis in Medaka}, series = {Frontiers in Cell and Developmental Biology}, volume = {8}, journal = {Frontiers in Cell and Developmental Biology}, issn = {2296-634X}, doi = {10.3389/fcell.2020.613497}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222669}, year = {2021}, abstract = {Sex determination (SD) is a highly diverse and complex mechanism. In vertebrates, one of the first morphological differences between the sexes is the timing of initiation of the first meiosis, where its initiation occurs first in female and later in male. Thus, SD is intimately related to the responsiveness of the germ cells to undergo meiosis in a sex-specific manner. In some vertebrates, it has been reported that the timing for meiosis entry would be under control of retinoic acid (RA), through activation of Stra8. In this study, we used a fish model species for sex determination and lacking the stra8 gene, the Japanese medaka (Oryzias latipes), to investigate the connection between RA and the sex determination pathway. Exogenous RA treatments act as a stress factor inhibiting germ cell differentiation probably by activation of dmrt1a and amh. Disruption of the RA degrading enzyme gene cyp26a1 induced precocious meiosis and oogenesis in embryos/hatchlings of female and even some males. Transcriptome analyzes of cyp26a1-/-adult gonads revealed upregulation of genes related to germ cell differentiation and meiosis, in both ovaries and testes. Our findings show that germ cells respond to RA in a stra8 independent model species. The responsiveness to RA is conferred by sex-related genes, restricting its action to the sex differentiation period in both sexes.}, language = {en} } @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{MorisChristmannWirtgenetal.2021, author = {Moris, Victoria C. and Christmann, Katharina and Wirtgen, Aline and Belokobylskij, Sergey A. and Berg, Alexander and Liebig, Wolf-Harald and Soon, Villu and Baur, Hannes and Schmitt, Thomas and Niehuis, Oliver}, title = {Cuticular hydrocarbons on old museum specimens of the spiny mason wasp, Odynerus spinipes (Hymenoptera: Vespidae: Eumeninae), shed light on the distribution and on regional frequencies of distinct chemotypes}, series = {Chemoecology}, volume = {31}, journal = {Chemoecology}, number = {5}, issn = {0937-7409}, doi = {10.1007/s00049-021-00350-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-306999}, pages = {311-322}, year = {2021}, abstract = {The mason wasp Odynerus spinipes shows an exceptional case of intrasexual cuticular hydrocarbon (CHC) profile dimorphism. Females of this species display one of two CHC profiles (chemotypes) that differ qualitatively and quantitatively from each other. The ratio of the two chemotypes was previously shown to be close to 1:1 at three sites in Southern Germany, which might not be representative given the Palearctic distribution of the species. To infer the frequency of the two chemotypes across the entire distributional range of the species, we analyzed with GC-MS the CHC profile of 1042 dry-mounted specimens stored in private and museum collections. We complemented our sampling by including 324 samples collected and preserved specifically for studying their CHCs. We were capable of reliably identifying the chemotypes in 91\% of dry-mounted samples, some of which collected almost 200 years ago. We found both chemotypes to occur in the Far East, the presumed glacial refuge of the species, and their frequency to differ considerably between sites and geographic regions. The geographic structure in the chemotype frequencies could be the result of differential selection regimes and/or different dispersal routes during the colonization of the Western Palearctic. The presented data pave the route for disentangling these factors by providing information where to geographically sample O. spinipes for population genetic analyses. They also form the much-needed basis for future studies aiming to understand the evolutionary and geographic origin as well as the genetics of the astounding CHC profile dimorphism that O. spinipes females exhibit.}, 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{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{HelmprobstKneitzKlotzetal.2021, author = {Helmprobst, Frederik and Kneitz, Susanne and Klotz, Barbara and Naville, Magali and Dechaud, Corentin and Volff, Jean-Nicolas and Schartl, Manfred}, title = {Differential expression of transposable elements in the medaka melanoma model}, series = {PLoS One}, volume = {16}, journal = {PLoS One}, number = {10}, doi = {10.1371/journal.pone.0251713}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260615}, year = {2021}, abstract = {Malignant melanoma incidence is rising worldwide. Its treatment in an advanced state is difficult, and the prognosis of this severe disease is still very poor. One major source of these difficulties is the high rate of metastasis and increased genomic instability leading to a high mutation rate and the development of resistance against therapeutic approaches. Here we investigate as one source of genomic instability the contribution of activation of transposable elements (TEs) within the tumor. We used the well-established medaka melanoma model and RNA-sequencing to investigate the differential expression of TEs in wildtype and transgenic fish carrying melanoma. We constructed a medaka-specific TE sequence library and identified TE sequences that were specifically upregulated in tumors. Validation by qRT- PCR confirmed a specific upregulation of a LINE and an LTR element in malignant melanomas of transgenic fish.}, language = {en} } @article{GrassingerFlorenMuelleretal.2021, author = {Grassinger, Julia Maria and Floren, Andreas and M{\"u}ller, Tobias and Cerezo-Echevarria, Argi{\~n}e and Beitzinger, Christoph and Conrad, David and T{\"o}rner, Katrin and Staudacher, Marlies and Aupperle-Lellbach, Heike}, title = {Digital lesions in dogs: a statistical breed analysis of 2912 cases}, series = {Veterinary Sciences}, volume = {8}, journal = {Veterinary Sciences}, number = {7}, issn = {2306-7381}, doi = {10.3390/vetsci8070136}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242690}, year = {2021}, abstract = {Breed predispositions to canine digital neoplasms are well known. However, there is currently no statistical analysis identifying the least affected breeds. To this end, 2912 canine amputated digits submitted from 2014-2019 to the Laboklin GmbH \& Co. KG for routine diagnostics were statistically analyzed. The study population consisted of 155 different breeds (most common: 634 Mongrels, 411 Schnauzers, 197 Labrador Retrievers, 93 Golden Retrievers). Non-neoplastic processes were present in 1246 (43\%), tumor-like lesions in 138 (5\%), and neoplasms in 1528 cases (52\%). Benign tumors (n = 335) were characterized by 217 subungual keratoacanthomas, 36 histiocytomas, 35 plasmacytomas, 16 papillomas, 12 melanocytomas, 9 sebaceous gland tumors, 6 lipomas, and 4 bone tumors. Malignant neoplasms (n = 1193) included 758 squamous cell carcinomas (SCC), 196 malignant melanomas (MM), 76 soft tissue sarcomas, 52 mast cell tumors, 37 non-specified sarcomas, 29 anaplastic neoplasms, 24 carcinomas, 20 bone tumors, and 1 histiocytic sarcoma. Predisposed breeds for SCC included the Schnauzer (log OR = 2.61), Briard (log OR = 1.78), Rottweiler (log OR = 1.54), Poodle (log OR = 1.40), and Dachshund (log OR = 1.30). Jack Russell Terriers (log OR = -2.95) were significantly less affected by SCC than Mongrels. Acral MM were significantly more frequent in Rottweilers (log OR = 1.88) and Labrador Retrievers (log OR = 1.09). In contrast, Dachshunds (log OR = -2.17), Jack Russell Terriers (log OR = -1.88), and Rhodesian Ridgebacks (log OR = -1.88) were rarely affected. This contrasted with the well-known predisposition of Dachshunds and Rhodesian Ridgebacks to oral and cutaneous melanocytic neoplasms. Further studies are needed to explain the underlying reasons for breed predisposition or "resistance" to the development of specific acral tumors and/or other sites.}, 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{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{VogelBusslerFinnbergetal.2021, author = {Vogel, Sebastian and Bussler, Heinz and Finnberg, Sven and M{\"u}ller, J{\"o}rg and Stengel, Elisa and Thorn, Simon}, title = {Diversity and conservation of saproxylic beetles in 42 European tree species: an experimental approach using early successional stages of branches}, series = {Insect Conservation and Diversity}, volume = {14}, journal = {Insect Conservation and Diversity}, number = {1}, doi = {10.1111/icad.12442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218401}, pages = {132 -- 143}, year = {2021}, abstract = {Tree species diversity is important to maintain saproxylic beetle diversity in managed forests. Yet, knowledge about the conservational importance of single tree species and implications for forest management and conservation practices are lacking. We exposed freshly cut branch-bundles of 42 tree species, representing tree species native and non-native to Europe, under sun-exposed and shaded conditions for 1 year. Afterwards, communities of saproxylic beetles were reared ex situ for 2 years. We tested for the impact of tree species and sun exposure on alpha-, beta-, and gamma-diversity as well as composition of saproxylic beetle communities. Furthermore, the number of colonised tree species by each saproxylic beetle species was determined. Tree species had a lower impact on saproxylic beetle communities compared to sun exposure. The diversity of saproxylic beetles varied strongly among tree species, with highest alpha- and gamma-diversity found in Quercus petraea. Red-listed saproxylic beetle species occurred ubiquitously among tree species. We found distinct differences in the community composition of broadleaved and coniferous tree species, native and non-native tree species as well as sun-exposed and shaded deadwood. Our study enhances the understanding of the importance of previously understudied and non-native tree species for the diversity of saproxylic beetles. To improve conservation practices for saproxylic beetles and especially red-listed species, we suggest a stronger incorporation of tree species diversity and sun exposure of into forest management strategies, including the enrichment of deadwood from native and with a specific focus on locally rare or silviculturally less important tree species.}, 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{VillagomezNuernbergerRequieretal.2021, author = {Villagomez, Gemma N. and N{\"u}rnberger, Fabian and Requier, Fabrice and Schiele, Susanne and Steffan-Dewenter, Ingo}, title = {Effects of temperature and photoperiod on the seasonal timing of Western honey bee colonies and an early spring flowering plant}, series = {Ecology and Evolution}, volume = {11}, journal = {Ecology and Evolution}, number = {12}, doi = {10.1002/ece3.7616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258770}, pages = {7834-7849}, year = {2021}, abstract = {Temperature and photoperiod are important Zeitgebers for plants and pollinators to synchronize growth and reproduction with suitable environmental conditions and their mutualistic interaction partners. Global warming can disturb this temporal synchronization since interacting species may respond differently to new combinations of photoperiod and temperature under future climates, but experimental studies on the potential phenological responses of plants and pollinators are lacking. We simulated current and future combinations of temperature and photoperiod to assess effects on the overwintering and spring phenology of an early flowering plant species (Crocus sieberi) and the Western honey bee (Apis mellifera). We could show that increased mean temperatures in winter and early spring advanced the flowering phenology of C. sieberi and intensified brood rearing activity of A. mellifera but did not advance their brood rearing activity. Flowering phenology of C. sieberi also relied on photoperiod, while brood rearing activity of A. mellifera did not. The results confirm that increases in temperature can induce changes in phenological responses and suggest that photoperiod can also play a critical role in these responses, with currently unknown consequences for real-world ecosystems in a warming climate.}, 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{LeverkusThornGustafssonetal.2021, author = {Leverkus, Alexandro B. and Thorn, Simon and Gustafsson, Lena and Noss, Reed and M{\"u}ller, J{\"o}rg and Pausas, Juli G. and Lindenmayer, David B.}, title = {Environmental policies to cope with novel disturbance regimes-steps to address a world scientists' warning to humanity}, series = {Environmental Research Letters}, volume = {16}, journal = {Environmental Research Letters}, number = {2}, issn = {1748-9326}, doi = {10.1088/1748-9326/abdc5a}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254180}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{LehenbergerBenkertBiedermann2021, author = {Lehenberger, Maximilian and Benkert, Markus and Biedermann, Peter H. W.}, title = {Ethanol-Enriched Substrate Facilitates Ambrosia Beetle Fungi, but Inhibits Their Pathogens and Fungal Symbionts of Bark Beetles}, series = {Frontiers in Microbiology}, volume = {11}, journal = {Frontiers in Microbiology}, issn = {1664-302X}, doi = {10.3389/fmicb.2020.590111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222222}, year = {2021}, abstract = {Bark beetles (sensu lato) colonize woody tissues like phloem or xylem and are associated with a broad range of micro-organisms. Specific fungi in the ascomycete orders Hypocreales, Microascales and Ophistomatales as well as the basidiomycete Russulales have been found to be of high importance for successful tree colonization and reproduction in many species. While fungal mutualisms are facultative for most phloem-colonizing bark beetles (sensu stricto), xylem-colonizing ambrosia beetles are long known to obligatorily depend on mutualistic fungi for nutrition of adults and larvae. Recently, a defensive role of fungal mutualists for their ambrosia beetle hosts was revealed: Few tested mutualists outcompeted other beetle-antagonistic fungi by their ability to produce, detoxify and metabolize ethanol, which is naturally occurring in stressed and/or dying trees that many ambrosia beetle species preferentially colonize. Here, we aim to test (i) how widespread beneficial effects of ethanol are among the independently evolved lineages of ambrosia beetle fungal mutualists and (ii) whether it is also present in common fungal symbionts of two bark beetle species (Ips typographus, Dendroctonus ponderosae) and some general fungal antagonists of bark and ambrosia beetle species. The majority of mutualistic ambrosia beetle fungi tested benefited (or at least were not harmed) by the presence of ethanol in terms of growth parameters (e.g., biomass), whereas fungal antagonists were inhibited. This confirms the competitive advantage of nutritional mutualists in the beetle's preferred, ethanol-containing host material. Even though most bark beetle fungi are found in the same phylogenetic lineages and ancestral to the ambrosia beetle (sensu stricto) fungi, most of them were highly negatively affected by ethanol and only a nutritional mutualist of Dendroctonus ponderosae benefited, however. This suggests that ethanol tolerance is a derived trait in nutritional fungal mutualists, particularly in ambrosia beetles that show cooperative farming of their fungi.}, language = {en} } @article{FussOtherHeinzeetal.2021, author = {Fuss, Carmina Teresa and Other, Katharina and Heinze, Britta and Landwehr, Laura-Sophie and Wiegering, Armin and Kalogirou, Charis and Hahner, Stefanie and Fassnacht, Martin}, title = {Expression of the chemokine receptor CCR7 in the normal adrenal gland and adrenal tumors and its correlation with clinical outcome in adrenocortical carcinoma}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {22}, issn = {2072-6694}, doi = {10.3390/cancers13225693}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250112}, year = {2021}, abstract = {Background: The chemokine receptor CCR7 is crucial for an intact immune function, but its expression is also associated with clinical outcome in several malignancies. No data exist on the expression of CCR7 in adrenocortical tumors. Methods: CCR7 expression was investigated by qRT-PCR and immunohistochemistry in 4 normal adrenal glands, 59 adrenocortical adenomas, and 181 adrenocortical carcinoma (ACC) samples. Results: CCR7 is highly expressed in the outer adrenocortical zones and medulla. Aldosterone-producing adenomas showed lower CCR7 protein levels (H-score 1.3 ± 1.0) compared to non-functioning (2.4 ± 0.5) and cortisol-producing adenomas (2.3 ± 0.6), whereas protein expression was variable in ACC (1.8 ± 0.8). In ACC, CCR7 protein expression was significantly higher in lymph node metastases (2.5 ± 0.5) compared to primary tumors (1.8±0.8) or distant metastases (2.0 ± 0.4; p < 0.01). mRNA levels of CCR7 were not significantly different between ACCs, normal adrenals, and adrenocortical adenomas. In contrast to other tumor entities, neither CCR7 protein nor mRNA expression significantly impacted patients' survival. Conclusion: We show that CCR7 is expressed on mRNA and protein level across normal adrenals, benign adrenocortical tumors, as well as ACCs. Given that CCR7 did not influence survival in ACC, it is probably not involved in tumor progression, but it could play a role in adrenocortical homeostasis.}, language = {en} } @article{BerberichKurzReinhardetal.2021, author = {Berberich, Andreas and Kurz, Andreas and Reinhard, Sebastian and Paul, Torsten Johann and Burd, Paul Ray and Sauer, Markus and Kollmannsberger, Philip}, title = {Fourier Ring Correlation and anisotropic kernel density estimation improve deep learning based SMLM reconstruction of microtubules}, series = {Frontiers in Bioinformatics}, volume = {1}, journal = {Frontiers in Bioinformatics}, doi = {10.3389/fbinf.2021.752788}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261686}, year = {2021}, abstract = {Single-molecule super-resolution microscopy (SMLM) techniques like dSTORM can reveal biological structures down to the nanometer scale. The achievable resolution is not only defined by the localization precision of individual fluorescent molecules, but also by their density, which becomes a limiting factor e.g., in expansion microscopy. Artificial deep neural networks can learn to reconstruct dense super-resolved structures such as microtubules from a sparse, noisy set of data points. This approach requires a robust method to assess the quality of a predicted density image and to quantitatively compare it to a ground truth image. Such a quality measure needs to be differentiable to be applied as loss function in deep learning. We developed a new trainable quality measure based on Fourier Ring Correlation (FRC) and used it to train deep neural networks to map a small number of sampling points to an underlying density. Smooth ground truth images of microtubules were generated from localization coordinates using an anisotropic Gaussian kernel density estimator. We show that the FRC criterion ideally complements the existing state-of-the-art multiscale structural similarity index, since both are interpretable and there is no trade-off between them during optimization. The TensorFlow implementation of our FRC metric can easily be integrated into existing deep learning workflows.}, language = {en} }