@article{MeinertJessenHufnageletal.2024, author = {Meinert, Madlen and Jessen, Christina and Hufnagel, Anita and Kreß, Julia Katharina Charlotte and Burnworth, Mychal and D{\"a}ubler, Theo and Gallasch, Till and Da Xavier Silva, Thamara Nishida and Dos Santos, Anc{\´e}ly Ferreira and Ade, Carsten Patrick and Schmitz, Werner and Kneitz, Susanne and Friedmann Angeli, Jos{\´e} Pedro and Meierjohann, Svenja}, title = {Thiol starvation triggers melanoma state switching in an ATF4 and NRF2-dependent manner}, series = {Redox Biology}, volume = {70}, journal = {Redox Biology}, doi = {10.1016/j.redox.2023.103011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350328}, year = {2024}, abstract = {The cystine/glutamate antiporter xCT is an important source of cysteine for cancer cells. Once taken up, cystine is reduced to cysteine and serves as a building block for the synthesis of glutathione, which efficiently protects cells from oxidative damage and prevents ferroptosis. As melanomas are particularly exposed to several sources of oxidative stress, we investigated the biological role of cysteine and glutathione supply by xCT in melanoma. xCT activity was abolished by genetic depletion in the Tyr::CreER; Braf\(^{CA}\); Pten\(^{lox/+}\) melanoma model and by acute cystine withdrawal in melanoma cell lines. Both interventions profoundly impacted melanoma glutathione levels, but they were surprisingly well tolerated by murine melanomas in vivo and by most human melanoma cell lines in vitro. RNA sequencing of human melanoma cells revealed a strong adaptive upregulation of NRF2 and ATF4 pathways, which orchestrated the compensatory upregulation of genes involved in antioxidant defence and de novo cysteine biosynthesis. In addition, the joint activation of ATF4 and NRF2 triggered a phenotypic switch characterized by a reduction of differentiation genes and induction of pro-invasive features, which was also observed after erastin treatment or the inhibition of glutathione synthesis. NRF2 alone was capable of inducing the phenotypic switch in a transient manner. Together, our data show that cystine or glutathione levels regulate the phenotypic plasticity of melanoma cells by elevating ATF4 and NRF2.}, language = {en} } @article{KressJessenHufnageletal.2023, author = {Kreß, Julia Katharina Charlotte and Jessen, Christina and Hufnagel, Anita and Schmitz, Werner and Da Xavier Silva, Thamara Nishida and Ferreira Dos Santos, Anc{\´e}ly and Mosteo, Laura and Goding, Colin R. and Friedmann Angeli, Jos{\´e} Pedro and Meierjohann, Svenja}, title = {The integrated stress response effector ATF4 is an obligatory metabolic activator of NRF2}, series = {Cell Reports}, volume = {42}, journal = {Cell Reports}, number = {7}, doi = {10.1016/j.celrep.2023.112724}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350312}, year = {2023}, abstract = {Highlights • The integrated stress response leads to a general ATF4-dependent activation of NRF2 • ATF4 causes a CHAC1-dependent GSH depletion, resulting in NRF2 stabilization • An elevation of NRF2 transcript levels fosters this effect • NRF2 supports the ISR/ATF4 pathway by improving cystine and antioxidant supply Summary The redox regulator NRF2 becomes activated upon oxidative and electrophilic stress and orchestrates a response program associated with redox regulation, metabolism, tumor therapy resistance, and immune suppression. Here, we describe an unrecognized link between the integrated stress response (ISR) and NRF2 mediated by the ISR effector ATF4. The ISR is commonly activated after starvation or ER stress and plays a central role in tissue homeostasis and cancer plasticity. ATF4 increases NRF2 transcription and induces the glutathione-degrading enzyme CHAC1, which we now show to be critically important for maintaining NRF2 activation. In-depth analyses reveal that NRF2 supports ATF4-induced cells by increasing cystine uptake via the glutamate-cystine antiporter xCT. In addition, NRF2 upregulates genes mediating thioredoxin usage and regeneration, thus balancing the glutathione decrease. In conclusion, we demonstrate that the NRF2 response serves as second layer of the ISR, an observation highly relevant for the understanding of cellular resilience in health and disease.}, language = {en} } @article{MaihoffSahlerSchogeretal.2023, author = {Maihoff, Fabienne and Sahler, Simone and Schoger, Simon and Brenzinger, Kristof and Kallnik, Katharina and Sauer, Nikki and Bofinger, Lukas and Schmitt, Thomas and Nooten, Sabine S. and Classen, Alice}, title = {Cuticular hydrocarbons of alpine bumble bees (Hymenoptera: Bombus) are species-specific, but show little evidence of elevation-related climate adaptation}, series = {Frontiers in Ecology and Evolution}, volume = {11}, journal = {Frontiers in Ecology and Evolution}, issn = {2296-701X}, doi = {10.3389/fevo.2023.1082559}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304420}, year = {2023}, abstract = {Alpine bumble bees are the most important pollinators in temperate mountain ecosystems. Although they are used to encounter small-scale successions of very different climates in the mountains, many species respond sensitively to climatic changes, reflected in spatial range shifts and declining populations worldwide. Cuticular hydrocarbons (CHCs) mediate climate adaptation in some insects. However, whether they predict the elevational niche of bumble bees or their responses to climatic changes remains poorly understood. Here, we used three different approaches to study the role of bumble bees' CHCs in the context of climate adaptation: using a 1,300 m elevational gradient, we first investigated whether the overall composition of CHCs, and two potentially climate-associated chemical traits (proportion of saturated components, mean chain length) on the cuticle of six bumble bee species were linked to the species' elevational niches. We then analyzed intraspecific variation in CHCs of Bombus pascuorum along the elevational gradient and tested whether these traits respond to temperature. Finally, we used a field translocation experiment to test whether CHCs of Bombus lucorum workers change, when translocated from the foothill of a cool and wet mountain region to (a) higher elevations, and (b) a warm and dry region. Overall, the six species showed distinctive, species-specific CHC profiles. We found inter- and intraspecific variation in the composition of CHCs and in chemical traits along the elevational gradient, but no link to the elevational distribution of species and individuals. According to our expectations, bumble bees translocated to a warm and dry region tended to express longer CHC chains than bumble bees translocated to cool and wet foothills, which could reflect an acclimatization to regional climate. However, chain lengths did not further decrease systematically along the elevational gradient, suggesting that other factors than temperature also shape chain lengths in CHC profiles. We conclude that in alpine bumble bees, CHC profiles and traits respond at best secondarily to the climate conditions tested in this study. While the functional role of species-specific CHC profiles in bumble bees remains elusive, limited plasticity in this trait could restrict species' ability to adapt to climatic changes.}, language = {en} } @article{LiuFriedrichHemmenetal.2023, author = {Liu, Ruiqi and Friedrich, Mike and Hemmen, Katherina and Jansen, Kerstin and Adolfi, Mateus C. and Schartl, Manfred and Heinze, Katrin G.}, title = {Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism}, series = {Frontiers in Endocrinology}, volume = {14}, journal = {Frontiers in Endocrinology}, issn = {1664-2392}, doi = {10.3389/fendo.2023.1267590}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-354261}, year = {2023}, abstract = {Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by F{\"o}rster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.}, language = {en} } @article{LutherBrandtVylkovaetal.2023, author = {Luther, Christian H. and Brandt, Philipp and Vylkova, Slavena and Dandekar, Thomas and M{\"u}ller, Tobias and Dittrich, Marcus}, title = {Integrated analysis of SR-like protein kinases Sky1 and Sky2 links signaling networks with transcriptional regulation in Candida albicans}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {13}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2023.1108235}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311771}, year = {2023}, abstract = {Fungal infections are a major global health burden where Candida albicans is among the most common fungal pathogen in humans and is a common cause of invasive candidiasis. Fungal phenotypes, such as those related to morphology, proliferation and virulence are mainly driven by gene expression, which is primarily regulated by kinase signaling cascades. Serine-arginine (SR) protein kinases are highly conserved among eukaryotes and are involved in major transcriptional processes in human and S. cerevisiae. Candida albicans harbors two SR protein kinases, while Sky2 is important for metabolic adaptation, Sky1 has similar functions as in S. cerevisiae. To investigate the role of these SR kinases for the regulation of transcriptional responses in C. albicans, we performed RNA sequencing of sky1Δ and sky2Δ and integrated a comprehensive phosphoproteome dataset of these mutants. Using a Systems Biology approach, we study transcriptional regulation in the context of kinase signaling networks. Transcriptomic enrichment analysis indicates that pathways involved in the regulation of gene expression are downregulated and mitochondrial processes are upregulated in sky1Δ. In sky2Δ, primarily metabolic processes are affected, especially for arginine, and we observed that arginine-induced hyphae formation is impaired in sky2Δ. In addition, our analysis identifies several transcription factors as potential drivers of the transcriptional response. Among these, a core set is shared between both kinase knockouts, but it appears to regulate different subsets of target genes. To elucidate these diverse regulatory patterns, we created network modules by integrating the data of site-specific protein phosphorylation and gene expression with kinase-substrate predictions and protein-protein interactions. These integrated signaling modules reveal shared parts but also highlight specific patterns characteristic for each kinase. Interestingly, the modules contain many proteins involved in fungal morphogenesis and stress response. Accordingly, experimental phenotyping shows a higher resistance to Hygromycin B for sky1Δ. Thus, our study demonstrates that a combination of computational approaches with integration of experimental data can offer a new systems biological perspective on the complex network of signaling and transcription. With that, the investigation of the interface between signaling and transcriptional regulation in C. albicans provides a deeper insight into how cellular mechanisms can shape the phenotype.}, language = {en} } @article{WuZhaoHochreinetal.2023, author = {Wu, Hao and Zhao, Xiufeng and Hochrein, Sophia M. and Eckstein, Miriam and Gubert, Gabriela F. and Kn{\"o}pper, Konrad and Mansilla, Ana Maria and {\"O}ner, Arman and Doucet-Ladev{\`e}ze, Remi and Schmitz, Werner and Ghesqui{\`e}re, Bart and Theurich, Sebastian and Dudek, Jan and Gasteiger, Georg and Zernecke, Alma and Kobold, Sebastian and Kastenm{\"u}ller, Wolfgang and Vaeth, Martin}, title = {Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-42634-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358052}, year = {2023}, abstract = {T cell exhaustion is a hallmark of cancer and persistent infections, marked by inhibitory receptor upregulation, diminished cytokine secretion, and impaired cytolytic activity. Terminally exhausted T cells are steadily replenished by a precursor population (Tpex), but the metabolic principles governing Tpex maintenance and the regulatory circuits that control their exhaustion remain incompletely understood. Using a combination of gene-deficient mice, single-cell transcriptomics, and metabolomic analyses, we show that mitochondrial insufficiency is a cell-intrinsic trigger that initiates the functional exhaustion of T cells. At the molecular level, we find that mitochondrial dysfunction causes redox stress, which inhibits the proteasomal degradation of hypoxia-inducible factor 1α (HIF-1α) and promotes the transcriptional and metabolic reprogramming of Tpex cells into terminally exhausted T cells. Our findings also bear clinical significance, as metabolic engineering of chimeric antigen receptor (CAR) T cells is a promising strategy to enhance the stemness and functionality of Tpex cells for cancer immunotherapy.}, language = {en} } @article{MuellerMitesserSchaeferetal.2023, author = {M{\"u}ller, J{\"o}rg and Mitesser, Oliver and Schaefer, H. Martin and Seibold, Sebastian and Busse, Annika and Kriegel, Peter and Rabl, Dominik and Gelis, Rudy and Arteaga, Alejandro and Freile, Juan and Leite, Gabriel Augusto and de Melo, Tomaz Nascimento and LeBien, Jack and Campos-Cerqueira, Marconi and Bl{\"u}thgen, Nico and Tremlett, Constance J. and B{\"o}ttger, Dennis and Feldhaar, Heike and Grella, Nina and Falcon{\´i}-L{\´o}pez, Ana and Donoso, David A. and Moriniere, Jerome and Buřivalov{\´a}, Zuzana}, title = {Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41693-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358130}, year = {2023}, abstract = {Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures - an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data.}, language = {en} } @article{BeetzKrauselJundi2023, author = {Beetz, M. Jerome and Kraus, Christian and el Jundi, Basil}, title = {Neural representation of goal direction in the monarch butterfly brain}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41526-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358073}, year = {2023}, abstract = {Neural processing of a desired moving direction requires the continuous comparison between the current heading and the goal direction. While the neural basis underlying the current heading is well-studied, the coding of the goal direction remains unclear in insects. Here, we used tetrode recordings in tethered flying monarch butterflies to unravel how a goal direction is represented in the insect brain. While recording, the butterflies maintained robust goal directions relative to a virtual sun. By resetting their goal directions, we found neurons whose spatial tuning was tightly linked to the goal directions. Importantly, their tuning was unaffected when the butterflies changed their heading after compass perturbations, showing that these neurons specifically encode the goal direction. Overall, we here discovered invertebrate goal-direction neurons that share functional similarities to goal-direction cells reported in mammals. Our results give insights into the evolutionarily conserved principles of goal-directed spatial orientation in animals.}, language = {en} } @article{DjakovicHennigReinischetal.2023, author = {Djakovic, Lara and Hennig, Thomas and Reinisch, Katharina and Milić, Andrea and Whisnant, Adam W. and Wolf, Katharina and Weiß, Elena and Haas, Tobias and Grothey, Arnhild and J{\"u}rges, Christopher S. and Kluge, Michael and Wolf, Elmar and Erhard, Florian and Friedel, Caroline C. and D{\"o}lken, Lars}, title = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-40217-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358161}, year = {2023}, abstract = {Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.}, language = {en} } @article{HaakeHaackSchaeferetal.2023, author = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg}, title = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39817-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333}, year = {2023}, abstract = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.}, language = {en} } @article{SalehiZarePrezzaetal.2023, author = {Salehi, Saeede and Zare, Abdolhossein and Prezza, Gianluca and Bader, Jakob and Schneider, Cornelius and Fischer, Utz and Meissner, Felix and Mann, Matthias and Briese, Michael and Sendtner, Michael}, title = {Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39787-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357639}, year = {2023}, abstract = {The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3' UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein.}, language = {en} } @article{BachertScheiner2023, author = {Bachert, Antonia and Scheiner, Ricarda}, title = {The ant's weapon improves honey bee learning performance}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-35540-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358064}, year = {2023}, abstract = {Formic acid is the main component of the ant's major weapon against enemies. Being mainly used as a chemical defense, the acid is also exploited for recruitment and trail marking. The repelling effect of the organic acid is used by some mammals and birds which rub themselves in the acid to eliminate ectoparasites. Beekeepers across the world rely on this effect to control the parasitic mite Varroa destructor. Varroa mites are considered the most destructive pest of honey bees worldwide and can lead to the loss of entire colonies. Formic acid is highly effective against Varroa mites but can also kill the honeybee queen and worker brood. Whether formic acid can also affect the behavior of honey bees is unknown. We here study the effect of formic acid on sucrose responsiveness and cognition of honey bees treated at different live stages in field-relevant doses. Both behaviors are essential for survival of the honey bee colony. Rather unexpectedly, formic acid clearly improved the learning performance of the bees in appetitive olfactory conditioning, while not affecting sucrose responsiveness. This exciting side effect of formic acid certainly deserves further detailed investigations.}, language = {en} } @article{KarpatiDeutschKissetal.2023, author = {K{\´a}rp{\´a}ti, Zsolt and Deutsch, Ferenc and Kiss, Bal{\´a}zs and Schmitt, Thomas}, title = {Seasonal changes in photoperiod and temperature lead to changes in cuticular hydrocarbon profiles and affect mating success in Drosophila suzukii}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-32652-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358095}, year = {2023}, abstract = {Seasonal plasticity in insects is often triggered by temperature and photoperiod changes. When climatic conditions become sub-optimal, insects might undergo reproductive diapause, a form of seasonal plasticity delaying the development of reproductive organs and activities. During the reproductive diapause, the cuticular hydrocarbon (CHC) profile, which covers the insect body surface, might also change to protect insects from desiccation and cold temperature. However, CHCs are often important cues and signals for mate recognition and changes in CHC composition might affect mate recognition. In the present study, we investigated the CHC profile composition and the mating success of Drosophila suzukii in 1- and 5-day-old males and females of summer and winter morphs. CHC compositions differed with age and morphs. However, no significant differences were found between the sexes of the same age and morph. The results of the behavioral assays show that summer morph pairs start to mate earlier in their life, have a shorter mating duration, and have more offspring compared to winter morph pairs. We hypothesize that CHC profiles of winter morphs are adapted to survive winter conditions, potentially at the cost of reduced mate recognition cues.}, language = {en} } @article{FrankKesnerLibertietal.2023, author = {Frank, Erik T. and Kesner, Lucie and Liberti, Joanito and Helleu, Quentin and LeBoeuf, Adria C. and Dascalu, Andrei and Sponsler, Douglas B. and Azuma, Fumika and Economo, Evan P. and Waridel, Patrice and Engel, Philipp and Schmitt, Thomas and Keller, Laurent}, title = {Targeted treatment of injured nestmates with antimicrobial compounds in an ant society}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-43885-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358081}, year = {2023}, abstract = {Infected wounds pose a major mortality risk in animals. Injuries are common in the ant Megaponera analis, which raids pugnacious prey. Here we show that M. analis can determine when wounds are infected and treat them accordingly. By applying a variety of antimicrobial compounds and proteins secreted from the metapleural gland to infected wounds, workers reduce the mortality of infected individuals by 90\%. Chemical analyses showed that wound infection is associated with specific changes in the cuticular hydrocarbon profile, thereby likely allowing nestmates to diagnose the infection state of injured individuals and apply the appropriate antimicrobial treatment. This study demonstrates that M. analis ant societies use antimicrobial compounds produced in the metapleural glands to treat infected wounds and reduce nestmate mortality.}, language = {en} } @article{MaichlKirnerBecketal.2023, author = {Maichl, Daniela Simone and Kirner, Julius Arthur and Beck, Susanne and Cheng, Wen-Hui and Krug, Melanie and Kuric, Martin and Ade, Carsten Patrick and Bischler, Thorsten and Jakob, Franz and Hose, Dirk and Seckinger, Anja and Ebert, Regina and Jundt, Franziska}, title = {Identification of NOTCH-driven matrisome-associated genes as prognostic indicators of multiple myeloma patient survival}, series = {Blood Cancer Journal}, volume = {13}, journal = {Blood Cancer Journal}, doi = {10.1038/s41408-023-00907-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357598}, year = {2023}, abstract = {No abstract available.}, language = {en} } @article{KlimmBraeuKoenigetal.2024, author = {Klimm, Fabian S. and Br{\"a}u, Markus and K{\"o}nig, Sebastian and Mandery, Klaus and Sommer, Carolin and Zhang, Jie and Krauss, Jochen}, title = {Importance of habitat area, quality and landscape context for heteropteran diversity in shrub ecotones}, series = {Landscape Ecology}, volume = {39}, journal = {Landscape Ecology}, issn = {0921-2973}, doi = {10.1007/s10980-024-01798-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358106}, year = {2024}, abstract = {Context Habitat loss and degradation impose serious threats on biodiversity. However, not all habitats receive the attention commensurate with their ecological importance. Shrub ecotones (successional stages between grasslands and forests) can be highly species-diverse but are often restricted to small areas as prevalent management practices either promote open grassland or forest habitats, threatening the effective conservation of ecotone species. Objectives In this study, we assessed the importance of habitat and landscape features of shrub ecotones for the rarely studied true bugs (Heteroptera), a functionally diverse taxon that comprises highly specialized species and broad generalists. Methods True bugs were sampled with a beating tray in 118 spatially independent shrub ecotones in a region of 45,000 square kilometers in Germany. In addition to habitat area and landscape context, we used a hedge index to evaluate habitat quality. Results Shrub ecotones in open habitats harbored a greater species richness and abundance compared to shaded ones in later seral stages, and species composition differed. Richness and abundance were positively affected by increasing habitat area and quality, whereas an increase in the proportion of semi-natural habitats within 1 km only enhanced richness. While feeding and habitat specialists were more sensitive to habitat area reduction than generalists, this was not the case for weak dispersers and carnivores. Conclusions Our findings emphasize the importance of large and high-quality ecotones that form a patchy mosaic of shrubs and herbaceous plants. Such ecotones can benefit both grassland species and species depending on woody plants. Conservation authorities should balance between promoting shrubs and keeping such habitats open to maximize species diversity.}, language = {en} } @article{BreyerGruenerKleinetal.2024, author = {Breyer, Maximilian and Gr{\"u}ner, Julia and Klein, Alexandra and Finke, Laura and Klug, Katharina and Sauer, Markus and {\"U}{\c{c}}eyler, Nurcan}, title = {\(In\) \(vitro\) characterization of cells derived from a patient with the GLA variant c.376A>G (p.S126G) highlights a non-pathogenic role in Fabry disease}, series = {Molecular Genetics and Metabolism Reports}, volume = {38}, journal = {Molecular Genetics and Metabolism Reports}, issn = {22144269}, doi = {10.1016/j.ymgmr.2023.101029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350295}, year = {2024}, abstract = {Highlights • The GLA variant S126G is not associated with Fabry symptoms in the presented case • S126G has no effect on α-GAL A activity or Gb3 levels in this patient • S126G sensory neurons show no electrophysiological abnormalities Abstract Fabry disease (FD) is a life-limiting disorder characterized by intracellular globotriaosylceramide (Gb3) accumulations. The underlying α-galactosidase A (α-GAL A) deficiency is caused by variants in the gene GLA. Variants of unknown significance (VUS) are frequently found in GLA and challenge clinical management. Here, we investigated a 49-year old man with cryptogenic lacunar cerebral stroke and the chance finding of the VUS S126G, who was sent to our center for diagnosis and initiation of a costly and life-long FD-specific treatment. We combined clinical examination with in vitro investigations of dermal fibroblasts (HDF), induced pluripotent stem cells (iPSC), and iPSC-derived sensory neurons. We analyzed α-GAL A activity in iPSC, Gb3 accumulation in all three cell types, and action potential firing in sensory neurons. Neurological examination and small nerve fiber assessment was normal except for reduced distal skin innervation. S126G iPSC showed normal α-GAL A activity compared to controls and no Gb3 deposits were found in all three cell types. Baseline electrophysiological characteristics of S126G neurons showed no difference compared to healthy controls as investigated by patch-clamp recordings. We pioneer multi-level cellular characterization of the VUS S126G using three cell types derived from a patient and provide further evidence for the benign nature of S126G in GLA, which is of great importance in the management of such cases in clinical practice.}, language = {en} } @article{LuDreyerDickinsonetal.2023, author = {Lu, Jinping and Dreyer, Ingo and Dickinson, Miles Sasha and Panzer, Sabine and Jaślan, Dawid and Navarro-Retamal, Carlos and Geiger, Dietmar and Terpitz, Ulrich and Becker, Dirk and Stroud, Robert M. and Marten, Irene and Hedrich, Rainer}, title = {Vicia faba SV channel VfTPC1 is a hyperexcitable variant of plant vacuole two pore channels}, series = {eLife}, volume = {12}, journal = {eLife}, doi = {10.7554/eLife.86384}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350264}, year = {2023}, abstract = {To fire action-potential-like electrical signals, the vacuole membrane requires the two-pore channel TPC1, formerly called SV channel. The TPC1/SV channel functions as a depolarization-stimulated, non-selective cation channel that is inhibited by luminal Ca\(^{2+}\). In our search for species-dependent functional TPC1 channel variants with different luminal Ca\(^{2+}\) sensitivity, we found in total three acidic residues present in Ca\(^{2+}\) sensor sites 2 and 3 of the Ca\(^{2+}\)-sensitive AtTPC1 channel from Arabidopsis thaliana that were neutral in its Vicia faba ortholog and also in those of many other Fabaceae. When expressed in the Arabidopsis AtTPC1-loss-of-function background, wild-type VfTPC1 was hypersensitive to vacuole depolarization and only weakly sensitive to blocking luminal Ca\(^{2+}\). When AtTPC1 was mutated for these VfTPC1-homologous polymorphic residues, two neutral substitutions in Ca\(^{2+}\) sensor site 3 alone were already sufficient for the Arabidopsis At-VfTPC1 channel mutant to gain VfTPC1-like voltage and luminal Ca\(^{2+}\) sensitivity that together rendered vacuoles hyperexcitable. Thus, natural TPC1 channel variants exist in plant families which may fine-tune vacuole excitability and adapt it to environmental settings of the particular ecological niche.}, language = {en} } @article{ThomasFiebigKuhnetal.2023, author = {Thomas, Sarah and Fiebig, Juliane E. and Kuhn, Eva-Maria and Mayer, Dominik S. and Filbeck, Sebastian and Schmitz, Werner and Krischke, Markus and Gropp, Roswitha and Mueller, Thomas D.}, title = {Design of glycoengineered IL-4 antagonists employing chemical and biosynthetic glycosylation}, series = {ACS Omega}, volume = {8}, journal = {ACS Omega}, number = {28}, issn = {2470-1343}, doi = {10.1021/acsomega.3c00726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350278}, pages = {24841-24852}, year = {2023}, abstract = {Interleukin-4 (IL-4) plays a key role in atopic diseases. It coordinates T-helper cell differentiation to subtype 2, thereby directing defense toward humoral immunity. Together with Interleukin-13, IL-4 further induces immunoglobulin class switch to IgE. Antibodies of this type activate mast cells and basophilic and eosinophilic granulocytes, which release pro-inflammatory mediators accounting for the typical symptoms of atopic diseases. IL-4 and IL-13 are thus major targets for pharmaceutical intervention strategies to treat atopic diseases. Besides neutralizing antibodies against IL-4, IL-13, or its receptors, IL-4 antagonists can present valuable alternatives. Pitrakinra, an Escherichia coli-derived IL-4 antagonist, has been evaluated in clinical trials for asthma treatment in the past; however, deficits such as short serum lifetime and potential immunogenicity among others stopped further development. To overcome such deficits, PEGylation of therapeutically important proteins has been used to increase the lifetime and proteolytic stability. As an alternative, glycoengineering is an emerging strategy used to improve pharmacokinetics of protein therapeutics. In this study, we have established different strategies to attach glycan moieties to defined positions in IL-4. Different chemical attachment strategies employing thiol chemistry were used to attach a glucose molecule at amino acid position 121, thereby converting IL-4 into a highly effective antagonist. To enhance the proteolytic stability of this IL-4 antagonist, additional glycan structures were introduced by glycoengineering utilizing eucaryotic expression. IL-4 antagonists with a combination of chemical and biosynthetic glycoengineering could be useful as therapeutic alternatives to IL-4 neutralizing antibodies already used to treat atopic diseases.}, language = {en} } @article{OtienoKarpatiPetersetal.2023, author = {Otieno, Mark and Karpati, Zsolt and Peters, Marcell K. and Duque, Laura and Schmitt, Thomas and Steffan-Dewenter, Ingolf}, title = {Elevated ozone and carbon dioxide affects the composition of volatile organic compounds emitted by Vicia faba (L.) and visitation by European orchard bee (Osmia cornuta)}, series = {PLoS One}, volume = {18}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0283480}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350020}, year = {2023}, abstract = {Recent studies link increased ozone (O\(_3\)) and carbon dioxide (CO\(_2\)) levels to alteration of plant performance and plant-herbivore interactions, but their interactive effects on plant-pollinator interactions are little understood. Extra floral nectaries (EFNs) are essential organs used by some plants for stimulating defense against herbivory and for the attraction of insect pollinators, e.g., bees. The factors driving the interactions between bees and plants regarding the visitation of bees to EFNs are poorly understood, especially in the face of global change driven by greenhouse gases. Here, we experimentally tested whether elevated levels of O\(_3\) and CO\(_2\) individually and interactively alter the emission of Volatile Organic Compound (VOC) profiles in the field bean plant (Vicia faba, L., Fabaceae), EFN nectar production and EFN visitation by the European orchard bee (Osmia cornuta, Latreille, Megachilidae). Our results showed that O\(_3\) alone had significant negative effects on the blends of VOCs emitted while the treatment with elevated CO\(_2\) alone did not differ from the control. Furthermore, as with O\(_3\) alone, the mixture of O\(_3\) and CO\(_2\) also had a significant difference in the VOCs' profile. O\(_3\) exposure was also linked to reduced nectar volume and had a negative impact on EFN visitation by bees. Increased CO\(_2\) level, on the other hand, had a positive impact on bee visits. Our results add to the knowledge of the interactive effects of O\(_3\) and CO\(_2\) on plant volatiles emitted by Vicia faba and bee responses. As greenhouse gas levels continue to rise globally, it is important to take these findings into consideration to better prepare for changes in plant-insect interactions.}, language = {en} } @article{BencurovaAkashDobsonetal.2023, author = {Bencurova, Elena and Akash, Aman and Dobson, Renwick C.J. and Dandekar, Thomas}, title = {DNA storage-from natural biology to synthetic biology}, series = {Computational and Structural Biotechnology Journal}, volume = {21}, journal = {Computational and Structural Biotechnology Journal}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.01.045}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349971}, pages = {1227-1235}, year = {2023}, abstract = {Natural DNA storage allows cellular differentiation, evolution, the growth of our children and controls all our ecosystems. Here, we discuss the fundamental aspects of DNA storage and recent advances in this field, with special emphasis on natural processes and solutions that can be exploited. We point out new ways of efficient DNA and nucleotide storage that are inspired by nature. Within a few years DNA-based information storage may become an attractive and natural complementation to current electronic data storage systems. We discuss rapid and directed access (e.g. DNA elements such as promotors, enhancers), regulatory signals and modulation (e.g. lncRNA) as well as integrated high-density storage and processing modules (e.g. chromosomal territories). There is pragmatic DNA storage for use in biotechnology and human genetics. We examine DNA storage as an approach for synthetic biology (e.g. light-controlled nucleotide processing enzymes). The natural polymers of DNA and RNA offer much for direct storage operations (read-in, read-out, access control). The inbuilt parallelism (many molecules at many places working at the same time) is important for fast processing of information. Using biology concepts from chromosomal storage, nucleic acid processing as well as polymer material sciences such as electronical effects in enzymes, graphene, nanocellulose up to DNA macram{\´e} , DNA wires and DNA-based aptamer field effect transistors will open up new applications gradually replacing classical information storage methods in ever more areas over time (decades).}, language = {en} } @article{BrenzingerCostaHoetal.2021, author = {Brenzinger, Kristof and Costa, Ohana Y. A. and Ho, Adrian and Koorneef, Guusje and Robroek, Bjorn and Molenaar, Douwe and Korthals, Gerard and Bodelier, Paul L. E.}, title = {Steering microbiomes by organic amendments towards climate-smart agricultural soils}, series = {Biology and Fertility of Soils}, volume = {57}, journal = {Biology and Fertility of Soils}, number = {8}, doi = {10.1007/s00374-021-01599-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-326930}, pages = {1053-1074}, year = {2021}, abstract = {We steered the soil microbiome via applications of organic residues (mix of cover crop residues, sewage sludge + compost, and digestate + compost) to enhance multiple ecosystem services in line with climate-smart agriculture. Our result highlights the potential to reduce greenhouse gases (GHG) emissions from agricultural soils by the application of specific organic amendments (especially digestate + compost). Unexpectedly, also the addition of mineral fertilizer in our mesocosms led to similar combined GHG emissions than one of the specific organic amendments. However, the application of organic amendments has the potential to increase soil C, which is not the case when using mineral fertilizer. While GHG emissions from cover crop residues were significantly higher compared to mineral fertilizer and the other organic amendments, crop growth was promoted. Furthermore, all organic amendments induced a shift in the diversity and abundances of key microbial groups. We show that organic amendments have the potential to not only lower GHG emissions by modifying the microbial community abundance and composition, but also favour crop growth-promoting microorganisms. This modulation of the microbial community by organic amendments bears the potential to turn soils into more climate-smart soils in comparison to the more conventional use of mineral fertilizers.}, language = {en} } @article{ChumduriTurco2021, author = {Chumduri, Cindrilla and Turco, Margherita Y.}, title = {Organoids of the female reproductive tract}, series = {Journal of Molecular Medicine}, volume = {99}, journal = {Journal of Molecular Medicine}, number = {4}, doi = {10.1007/s00109-020-02028-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-328374}, pages = {531-553}, year = {2021}, abstract = {Healthy functioning of the female reproductive tract (FRT) depends on balanced and dynamic regulation by hormones during the menstrual cycle, pregnancy and childbirth. The mucosal epithelial lining of different regions of the FRT—ovaries, fallopian tubes, uterus, cervix and vagina—facilitates the selective transport of gametes and successful transfer of the zygote to the uterus where it implants and pregnancy takes place. It also prevents pathogen entry. Recent developments in three-dimensional (3D) organoid systems from the FRT now provide crucial experimental models that recapitulate the cellular heterogeneity and physiological, anatomical and functional properties of the organ in vitro. In this review, we summarise the state of the art on organoids generated from different regions of the FRT. We discuss the potential applications of these powerful in vitro models to study normal physiology, fertility, infections, diseases, drug discovery and personalised medicine.}, 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{DaeullaryImdahlDietrichetal.2023, author = {D{\"a}ullary, Thomas and Imdahl, Fabian and Dietrich, Oliver and Hepp, Laura and Krammer, Tobias and Fey, Christina and Neuhaus, Winfried and Metzger, Marco and Vogel, J{\"o}rg and Westermann, Alexander J. and Saliba, Antoine-Emmanuel and Zdzieblo, Daniela}, title = {A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection}, series = {Gut Microbes}, volume = {15}, journal = {Gut Microbes}, number = {1}, doi = {10.1080/19490976.2023.2186109}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350451}, year = {2023}, abstract = {Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.}, language = {en} } @article{CaliskanDangwalDandekar2023, author = {Caliskan, Aylin and Dangwal, Seema and Dandekar, Thomas}, title = {Metadata integrity in bioinformatics: bridging the gap between data and knowledge}, series = {Computational and Structural Biotechnology Journal}, volume = {21}, journal = {Computational and Structural Biotechnology Journal}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.10.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349990}, pages = {4895-4913}, year = {2023}, abstract = {In the fast-evolving landscape of biomedical research, the emergence of big data has presented researchers with extraordinary opportunities to explore biological complexities. In biomedical research, big data imply also a big responsibility. This is not only due to genomics data being sensitive information but also due to genomics data being shared and re-analysed among the scientific community. This saves valuable resources and can even help to find new insights in silico. To fully use these opportunities, detailed and correct metadata are imperative. This includes not only the availability of metadata but also their correctness. Metadata integrity serves as a fundamental determinant of research credibility, supporting the reliability and reproducibility of data-driven findings. Ensuring metadata availability, curation, and accuracy are therefore essential for bioinformatic research. Not only must metadata be readily available, but they must also be meticulously curated and ideally error-free. Motivated by an accidental discovery of a critical metadata error in patient data published in two high-impact journals, we aim to raise awareness for the need of correct, complete, and curated metadata. We describe how the metadata error was found, addressed, and present examples for metadata-related challenges in omics research, along with supporting measures, including tools for checking metadata and software to facilitate various steps from data analysis to published research. Highlights • Data awareness and data integrity underpins the trustworthiness of results and subsequent further analysis. • Big data and bioinformatics enable efficient resource use by repurposing publicly available RNA-Sequencing data. • Manual checks of data quality and integrity are insufficient due to the overwhelming volume and rapidly growing data. • Automation and artificial intelligence provide cost-effective and efficient solutions for data integrity and quality checks. • FAIR data management, various software solutions and analysis tools assist metadata maintenance.}, language = {en} } @article{CaliskanCaliskanRasbachetal.2023, author = {Caliskan, Aylin and Caliskan, Deniz and Rasbach, Lauritz and Yu, Weimeng and Dandekar, Thomas and Breitenbach, Tim}, title = {Optimized cell type signatures revealed from single-cell data by combining principal feature analysis, mutual information, and machine learning}, series = {Computational and Structural Biotechnology Journal}, volume = {21}, journal = {Computational and Structural Biotechnology Journal}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.06.002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349989}, pages = {3293-3314}, year = {2023}, abstract = {Machine learning techniques are excellent to analyze expression data from single cells. These techniques impact all fields ranging from cell annotation and clustering to signature identification. The presented framework evaluates gene selection sets how far they optimally separate defined phenotypes or cell groups. This innovation overcomes the present limitation to objectively and correctly identify a small gene set of high information content regarding separating phenotypes for which corresponding code scripts are provided. The small but meaningful subset of the original genes (or feature space) facilitates human interpretability of the differences of the phenotypes including those found by machine learning results and may even turn correlations between genes and phenotypes into a causal explanation. For the feature selection task, the principal feature analysis is utilized which reduces redundant information while selecting genes that carry the information for separating the phenotypes. In this context, the presented framework shows explainability of unsupervised learning as it reveals cell-type specific signatures. Apart from a Seurat preprocessing tool and the PFA script, the pipeline uses mutual information to balance accuracy and size of the gene set if desired. A validation part to evaluate the gene selection for their information content regarding the separation of the phenotypes is provided as well, binary and multiclass classification of 3 or 4 groups are studied. Results from different single-cell data are presented. In each, only about ten out of more than 30000 genes are identified as carrying the relevant information. The code is provided in a GitHub repository at https://github.com/AC-PHD/Seurat_PFA_pipeline.}, language = {en} } @article{EngstlerBeneke2023, author = {Engstler, Markus and Beneke, Tom}, title = {Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit}, series = {eLife}, volume = {12}, journal = {eLife}, doi = {10.7554/eLife.85605}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350002}, year = {2023}, abstract = {CRISPR/Cas9 gene editing has revolutionised loss-of-function experiments in Leishmania, the causative agent of leishmaniasis. As Leishmania lack a functional non-homologous DNA end joining pathway however, obtaining null mutants typically requires additional donor DNA, selection of drug resistance-associated edits or time-consuming isolation of clones. Genome-wide loss-of-function screens across different conditions and across multiple Leishmania species are therefore unfeasible at present. Here, we report a CRISPR/Cas9 cytosine base editor (CBE) toolbox that overcomes these limitations. We employed CBEs in Leishmania to introduce STOP codons by converting cytosine into thymine and created http://www.leishbaseedit.net/ for CBE primer design in kinetoplastids. Through reporter assays and by targeting single- and multi-copy genes in L. mexicana, L. major, L. donovani, and L. infantum, we demonstrate how this tool can efficiently generate functional null mutants by expressing just one single-guide RNA, reaching up to 100\% editing rate in non-clonal populations. We then generated a Leishmania-optimised CBE and successfully targeted an essential gene in a plasmid library delivered loss-of-function screen in L. mexicana. Since our method does not require DNA double-strand breaks, homologous recombination, donor DNA, or isolation of clones, we believe that this enables for the first time functional genetic screens in Leishmania via delivery of plasmid libraries.}, language = {en} } @article{SalihogluSrivastavaLiangetal.2023, author = {Salihoglu, Rana and Srivastava, Mugdha and Liang, Chunguang and Schilling, Klaus and Szalay, Aladar and Bencurova, Elena and Dandekar, Thomas}, title = {PRO-Simat: Protein network simulation and design tool}, series = {Computational and Structural Biotechnology Journal}, volume = {21}, journal = {Computational and Structural Biotechnology Journal}, issn = {2001-0370}, doi = {10.1016/j.csbj.2023.04.023}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350034}, pages = {2767-2779}, year = {2023}, abstract = {PRO-Simat is a simulation tool for analysing protein interaction networks, their dynamic change and pathway engineering. It provides GO enrichment, KEGG pathway analyses, and network visualisation from an integrated database of more than 8 million protein-protein interactions across 32 model organisms and the human proteome. We integrated dynamical network simulation using the Jimena framework, which quickly and efficiently simulates Boolean genetic regulatory networks. It enables simulation outputs with in-depth analysis of the type, strength, duration and pathway of the protein interactions on the website. Furthermore, the user can efficiently edit and analyse the effect of network modifications and engineering experiments. In case studies, applications of PRO-Simat are demonstrated: (i) understanding mutually exclusive differentiation pathways in Bacillus subtilis, (ii) making Vaccinia virus oncolytic by switching on its viral replication mainly in cancer cells and triggering cancer cell apoptosis and (iii) optogenetic control of nucleotide processing protein networks to operate DNA storage. Multilevel communication between components is critical for efficient network switching, as demonstrated by a general census on prokaryotic and eukaryotic networks and comparing design with synthetic networks using PRO-Simat. The tool is available at https://prosimat.heinzelab.de/ as a web-based query server.}, language = {en} } @article{ConradKehlMuelleretal.2023, author = {Conrad, David and Kehl, Alexandra and M{\"u}ller, Tobias and Klopfleisch, Robert and Aupperle-Lellbach, Heike}, title = {Immunohistochemical and molecular genetic analysis of canine digital mast cell tumours}, series = {Animals}, volume = {13}, journal = {Animals}, number = {10}, issn = {2076-2615}, doi = {10.3390/ani13101694}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-319199}, year = {2023}, abstract = {Grading, immunohistochemistry and c-kit mutation status are criteria for assessing the prognosis and therapeutic options of canine cutaneous mast cell tumours (MCTs). As a subset, canine digital MCTs have rarely been explored in this context. Therefore, in this retrospective study, 68 paraffin-embedded canine digital MCTs were analysed, and histological grading was assessed according to Patnaik and Kiupel. The immunohistochemical markers KIT and Ki67 were used, as well as polymerase chain reaction (PCR) for mutational screening in c-kit exons 8, 9, 11 and 14. Patnaik grading resulted in 22.1\% grade I, 67.6\% grade II and 10.3\% grade III tumours. Some 86.8\% of the digital MCTs were Kiupel low-grade. Aberrant KIT staining patterns II and III were found in 58.8\%, and a count of more than 23 Ki67-positive cells in 52.3\% of the cases. Both parameters were significantly associated with an internal tandem duplication (ITD) in c-kit exon 11 (12.7\%). French Bulldogs, which tend to form well-differentiated cutaneous MCTs, had a higher proportion of digital high-grade MCTs and ITD in c-kit exon 11 compared with mongrels. Due to its retrospective nature, this study did not allow for an analysis of survival data. Nevertheless, it may contribute to the targeted characterisation of digital MCTs.}, language = {en} } @article{AmatobiOzbekUnalSchaebleretal.2023, author = {Amatobi, Kelechi M. and Ozbek-Unal, Ayten Gizem and Sch{\"a}bler, Stefan and Deppisch, Peter and Helfrich-F{\"o}rster, Charlotte and Mueller, Martin J. and Wegener, Christian and Fekete, Agnes}, title = {The circadian clock is required for rhythmic lipid transport in Drosophila in interaction with diet and photic condition}, series = {Journal of Lipid Research}, volume = {64}, journal = {Journal of Lipid Research}, number = {10}, doi = {10.1016/j.jlr.2023.100417}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-349961}, pages = {100417}, year = {2023}, abstract = {Modern lifestyle is often at odds with endogenously driven rhythmicity, which can lead to circadian disruption and metabolic syndrome. One signature for circadian disruption is a reduced or altered metabolite cycling in the circulating tissue reflecting the current metabolic status. Drosophila is a well-established model in chronobiology, but day-time dependent variations of transport metabolites in the fly circulation are poorly characterized. Here, we sampled fly hemolymph throughout the day and analyzed diacylglycerols (DGs), phosphoethanolamines (PEs) and phosphocholines (PCs) using LC-MS. In wild-type flies kept on sugar-only medium under a light-dark cycle, all transport lipid species showed a synchronized bimodal oscillation pattern with maxima at the beginning and end of the light phase which were impaired in period01 clock mutants. In wild-type flies under constant dark conditions, the oscillation became monophasic with a maximum in the middle of the subjective day. In strong support of clock-driven oscillations, levels of the targeted lipids peaked once in the middle of the light phase under time-restricted feeding independent of the time of food intake. When wild-type flies were reared on full standard medium, the rhythmic alterations of hemolymph lipid levels were greatly attenuated. Our data suggest that the circadian clock aligns daily oscillations of DGs, PEs, and PCs in the hemolymph to the anabolic siesta phase, with a strong influence of light on phase and modality.}, language = {en} } @article{SchuhmannScheiner2023, author = {Schuhmann, Antonia and Scheiner, Ricarda}, title = {A combination of the frequent fungicides boscalid and dimoxystrobin with the neonicotinoid acetamiprid in field-realistic concentrations does not affect sucrose responsiveness and learning behavior of honeybees}, series = {Ecotoxicology and Environmental Safety}, volume = {256}, journal = {Ecotoxicology and Environmental Safety}, doi = {10.1016/j.ecoenv.2023.114850}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350047}, year = {2023}, abstract = {The increasing loss of pollinators over the last decades has become more and more evident. Intensive use of plant protection products is one key factor contributing to this decline. Especially the mixture of different plant protection products can pose an increased risk for pollinators as synergistic effects may occur. In this study we investigated the effect of the fungicide Cantus® Gold (boscalid/dimoxystrobin), the neonicotinoid insecticide Mospilan® (acetamiprid) and their mixture on honeybees. Since both plant protection products are frequently applied sequentially to the same plants (e.g. oilseed rape), their combination is a realistic scenario for honeybees. We investigated the mortality, the sucrose responsiveness and the differential olfactory learning performance of honeybees under controlled conditions in the laboratory to reduce environmental noise. Intact sucrose responsiveness and learning performance are of pivotal importance for the survival of individual honeybees as well as for the functioning of the entire colony. Treatment with two sublethal and field relevant concentrations of each plant protection product did not lead to any significant effects on these behaviors but affected the mortality rate. However, our study cannot exclude possible negative sublethal effects of these substances in higher concentrations. In addition, the honeybee seems to be quite robust when it comes to effects of plant protection products, while wild bees might be more sensitive. Highlights • Mix of SBI fungicides and neonicotinoids can lead to synergistic effects for bees. • Combination of non-SBI fungicide and neonicotinoid in field-realistic doses tested. • Synergistic effect on mortality of honeybees. • No effects on sucrose responsiveness and learning performance of honeybees. • Synergistic effects by other pesticide mixtures or on wild bees cannot be excluded.}, language = {en} } @article{CoelhoAlvesMonteiroetal.2019, author = {Coelho, Luis Pedro and Alves, Renato and Monteiro, Paulo and Huerta-Cepas, Jaime and Freitas, Ana Teresa and Bork, Peer}, title = {NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language}, series = {Microbiome}, volume = {7}, journal = {Microbiome}, number = {84}, doi = {10.1186/s40168-019-0684-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223161}, year = {2019}, abstract = {Background Shotgun metagenomes contain a sample of all the genomic material in an environment, allowing for the characterization of a microbial community. In order to understand these communities, bioinformatics methods are crucial. A common first step in processing metagenomes is to compute abundance estimates of different taxonomic or functional groups from the raw sequencing data. Given the breadth of the field, computational solutions need to be flexible and extensible, enabling the combination of different tools into a larger pipeline. Results We present NGLess and NG-meta-profiler. NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility. It provides built-in support for many common operations on sequencing data and is extensible with external tools with configuration files. Using this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible. Conclusions NG-meta-profiler is a high-performance solution for metagenomics processing built on NGLess. It can be used as-is to execute standard analyses or serve as the starting point for customization in a perfectly reproducible fashion. NGLess and NG-meta-profiler are open source software (under the liberal MIT license) and can be downloaded from https://ngless.embl.de or installed through bioconda.}, language = {en} } @article{CoelhoKultimaCosteaetal.2018, author = {Coelho, Luis Pedro and Kultima, Jens Roat and Costea, Paul Igor and Fournier, Coralie and Pan, Yuanlong and Czarnecki-Maulden, Gail and Hayward, Matthew Robert and Forslund, Sofia K. and Schmidt, Thomas Sebastian Benedikt and Descombes, Patrick and Jackson, Janet R. and Li, Qinghong and Bork, Peer}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet}, series = {Microbiome}, volume = {6}, journal = {Microbiome}, doi = {10.1186/s40168-018-0450-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223177}, year = {2018}, abstract = {Background Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs. Results We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies. Conclusions We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, language = {en} } @article{DedukhDaCruzKneitzetal.2022, author = {Dedukh, Dmitrij and Da Cruz, Irene and Kneitz, Susanne and Marta, Anatolie and Ormanns, Jenny and Tichop{\´a}d, Tom{\´a}š and Lu, Yuan and Alsheimer, Manfred and Janko, Karel and Schartl, Manfred}, title = {Achiasmatic meiosis in the unisexual Amazon molly, Poecilia formosa}, series = {Chromosome Research}, volume = {30}, journal = {Chromosome Research}, number = {4}, doi = {10.1007/s10577-022-09708-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325128}, pages = {443-457}, year = {2022}, abstract = {Unisexual reproduction, which generates clonal offspring, is an alternative strategy to sexual breeding and occurs even in vertebrates. A wide range of non-sexual reproductive modes have been described, and one of the least understood questions is how such pathways emerged and how they mechanistically proceed. The Amazon molly, Poecilia formosa, needs sperm from males of related species to trigger the parthenogenetic development of diploid eggs. However, the mechanism, of how the unreduced female gametes are produced, remains unclear. Cytological analyses revealed that the chromosomes of primary oocytes initiate pachytene but do not proceed to bivalent formation and meiotic crossovers. Comparing ovary transcriptomes of P. formosa and its sexual parental species revealed expression levels of meiosis-specific genes deviating from P. mexicana but not from P. latipinna. Furthermore, several meiosis genes show biased expression towards one of the two alleles from the parental genomes. We infer from our data that in the Amazon molly diploid oocytes are generated by apomixis due to a failure in the synapsis of homologous chromosomes. The fact that this failure is not reflected in the differential expression of known meiosis genes suggests the underlying molecular mechanism may be dysregulation on the protein level or misexpression of a so far unknown meiosis gene, and/or hybrid dysgenesis because of compromised interaction of proteins from diverged genomes.}, language = {en} } @article{RoesslerGrobFleischmann2023, author = {R{\"o}ssler, Wolfgang and Grob, Robin and Fleischmann, Pauline N.}, title = {The role of learning-walk related multisensory experience in rewiring visual circuits in the desert ant brain}, series = {Journal of Comparative Physiology A}, volume = {209}, journal = {Journal of Comparative Physiology A}, number = {4}, doi = {10.1007/s00359-022-01600-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325096}, pages = {605-623}, year = {2023}, abstract = {Efficient spatial orientation in the natural environment is crucial for the survival of most animal species. Cataglyphis desert ants possess excellent navigational skills. After far-ranging foraging excursions, the ants return to their inconspicuous nest entrance using celestial and panoramic cues. This review focuses on the question about how na{\"i}ve ants acquire the necessary spatial information and adjust their visual compass systems. Na{\"i}ve ants perform structured learning walks during their transition from the dark nest interior to foraging under bright sunlight. During initial learning walks, the ants perform rotational movements with nest-directed views using the earth's magnetic field as an earthbound compass reference. Experimental manipulations demonstrate that specific sky compass cues trigger structural neuronal plasticity in visual circuits to integration centers in the central complex and mushroom bodies. During learning walks, rotation of the sky-polarization pattern is required for an increase in volume and synaptic complexes in both integration centers. In contrast, passive light exposure triggers light-spectrum (especially UV light) dependent changes in synaptic complexes upstream of the central complex. We discuss a multisensory circuit model in the ant brain for pathways mediating structural neuroplasticity at different levels following passive light exposure and multisensory experience during the performance of learning walks.}, language = {en} } @article{FrickeRedlichZhangetal.2022, author = {Fricke, Ute and Redlich, Sarah and Zhang, Jie and Tobisch, Cynthia and Rojas-Botero, Sandra and Benjamin, Caryl S. and Englmeier, Jana and Ganuza, Cristina and Riebl, Rebekka and Uhler, Johannes and Uphus, Lars and Ewald, J{\"o}rg and Kollmann, Johannes and Steffan-Dewenter, Ingolf}, title = {Plant richness, land use and temperature differently shape invertebrate leaf-chewing herbivory on plant functional groups}, series = {Oecologia}, volume = {199}, journal = {Oecologia}, number = {2}, doi = {10.1007/s00442-022-05199-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325079}, pages = {407-417}, year = {2022}, abstract = {Higher temperatures can increase metabolic rates and carbon demands of invertebrate herbivores, which may shift leaf-chewing herbivory among plant functional groups differing in C:N (carbon:nitrogen) ratios. Biotic factors influencing herbivore species richness may modulate these temperature effects. Yet, systematic studies comparing leaf-chewing herbivory among plant functional groups in different habitats and landscapes along temperature gradients are lacking. This study was conducted on 80 plots covering large gradients of temperature, plant richness and land use in Bavaria, Germany. We investigated proportional leaf area loss by chewing invertebrates ('herbivory') in three plant functional groups on open herbaceous vegetation. As potential drivers, we considered local mean temperature (range 8.4-18.8 °C), multi-annual mean temperature (range 6.5-10.0 °C), local plant richness (species and family level, ranges 10-51 species, 5-25 families), adjacent habitat type (forest, grassland, arable field, settlement), proportion of grassland and landscape diversity (0.2-3 km scale). We observed differential responses of leaf-chewing herbivory among plant functional groups in response to plant richness (family level only) and habitat type, but not to grassland proportion, landscape diversity and temperature—except for multi-annual mean temperature influencing herbivory on grassland plots. Three-way interactions of plant functional group, temperature and predictors of plant richness or land use did not substantially impact herbivory. We conclude that abiotic and biotic factors can assert different effects on leaf-chewing herbivory among plant functional groups. At present, effects of plant richness and habitat type outweigh effects of temperature and landscape-scale land use on herbivory among legumes, forbs and grasses.}, language = {en} } @article{ZupancRoessler2022, author = {Zupanc, G{\"u}nther K. H. and R{\"o}ssler, Wolfgang}, title = {Government funding of research beyond biomedicine: challenges and opportunities for neuroethology}, series = {Journal of Comparative Physiology A}, volume = {208}, journal = {Journal of Comparative Physiology A}, number = {3}, doi = {10.1007/s00359-022-01552-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325113}, pages = {443-456}, year = {2022}, abstract = {Curiosity-driven research is fundamental for neuroethology and depends crucially on governmental funding. Here, we highlight similarities and differences in funding of curiosity-driven research across countries by comparing two major funding agencies—the National Science Foundation (NSF) in the United States and the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG). We interviewed representatives from each of the two agencies, focusing on general funding trends, levels of young investigator support, career-life balance, and international collaborations. While our analysis revealed a negative trend in NSF funding of biological research, including curiosity-driven research, German researchers in these areas have benefited from a robust positive trend in DFG funding. The main reason for the decrease in curiosity-driven research in the US is that the NSF has only partially been able to compensate for the funding gap resulting from the National Institutes of Health restricting their support to biomedical research using select model organisms. Notwithstanding some differences in funding programs, particularly those relevant for scientists in the postdoctoral phase, both the NSF and DFG clearly support curiosity-driven research.}, language = {en} } @article{EnglmeierMitesserBenbowetal.2023, author = {Englmeier, Jana and Mitesser, Oliver and Benbow, M. Eric and Hothorn, Torsten and von Hoermann, Christian and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Redlich, Sarah and Riebl, Rebekka and Rojas Botero, Sandra and Rummler, Thomas and Steffan-Dewenter, Ingolf and Stengel, Elisa and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Diverse effects of climate, land use, and insects on dung and carrion decomposition}, series = {Ecosystems}, volume = {26}, journal = {Ecosystems}, number = {2}, issn = {1432-9840}, doi = {10.1007/s10021-022-00764-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325064}, pages = {397-411}, year = {2023}, abstract = {Land-use intensification and climate change threaten ecosystem functions. A fundamental, yet often overlooked, function is decomposition of necromass. The direct and indirect anthropogenic effects on decomposition, however, are poorly understood. We measured decomposition of two contrasting types of necromass, rat carrion and bison dung, on 179 study sites in Central Europe across an elevational climate gradient of 168-1122 m a.s.l. and within both local and regional land uses. Local land-use types included forest, grassland, arable fields, and settlements and were embedded in three regional land-use types (near-natural, agricultural, and urban). The effects of insects on decomposition were quantified by experimental exclusion, while controlling for removal by vertebrates. We used generalized additive mixed models to evaluate dung weight loss and carrion decay rate along elevation and across regional and local land-use types. We observed a unimodal relationship of dung decomposition with elevation, where greatest weight loss occurred between 600 and 700 m, but no effects of local temperature, land use, or insects. In contrast to dung, carrion decomposition was continuously faster with both increasing elevation and local temperature. Carrion reached the final decomposition stage six days earlier when insect access was allowed, and this did not depend on land-use effect. Our experiment identified different major drivers of decomposition on each necromass form. The results show that dung and carrion decomposition are rather robust to local and regional land use, but future climate change and decline of insects could alter decomposition processes and the self-regulation of ecosystems.}, language = {en} } @article{ShirakashiSisarioTabanetal.2023, author = {Shirakashi, Ryo and Sisario, Dmitri and Taban, Danush and Korsa, Tessa and Wanner, Sophia B. and Neubauer, Julia and Djuzenova, Cholpon S. and Zimmermann, Heiko and Sukhorukov, Vladimir L.}, title = {Contraction of the rigor actomyosin complex drives bulk hemoglobin expulsion from hemolyzing erythrocytes}, series = {Biomechanics and Modeling in Mechanobiology}, volume = {22}, journal = {Biomechanics and Modeling in Mechanobiology}, number = {2}, doi = {10.1007/s10237-022-01654-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325107}, pages = {417-432}, year = {2023}, abstract = {Erythrocyte ghost formation via hemolysis is a key event in the physiological clearance of senescent red blood cells (RBCs) in the spleen. The turnover rate of millions of RBCs per second necessitates a rapid efflux of hemoglobin (Hb) from RBCs by a not yet identified mechanism. Using high-speed video-microscopy of isolated RBCs, we show that electroporation-induced efflux of cytosolic ATP and other small solutes leads to transient cell shrinkage and echinocytosis, followed by osmotic swelling to the critical hemolytic volume. The onset of hemolysis coincided with a sudden self-propelled cell motion, accompanied by cell contraction and Hb-jet ejection. Our biomechanical model, which relates the Hb-jet-driven cell motion to the cytosolic pressure generation via elastic contraction of the RBC membrane, showed that the contributions of the bilayer and the bilayer-anchored spectrin cytoskeleton to the hemolytic cell motion are negligible. Consistent with the biomechanical analysis, our biochemical experiments, involving extracellular ATP and the myosin inhibitor blebbistatin, identify the low abundant non-muscle myosin 2A (NM2A) as the key contributor to the Hb-jet emission and fast hemolytic cell motion. Thus, our data reveal a rapid myosin-based mechanism of hemolysis, as opposed to a much slower diffusive Hb efflux.}, language = {en} } @article{MoustafaFouadIbrahimetal.2023, author = {Moustafa, Moataz A. M. and Fouad, Eman A. and Ibrahim, Emad and Erdei, Anna Laura and K{\´a}rp{\´a}ti, Zsolt and F{\´o}nagy, Adrien}, title = {The comparative toxicity, biochemical and physiological impacts of chlorantraniliprole and indoxacarb on Mamestra brassicae (Lepidoptera: Noctuidae)}, series = {Toxics}, volume = {11}, journal = {Toxics}, number = {3}, issn = {2305-6304}, doi = {10.3390/toxics11030212}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303931}, year = {2023}, abstract = {Background: The cabbage moth, Mamestra brassicae, is a polyphagous pest that attacks several crops. Here, the sublethal and lethal effects of chlorantraniliprole and indoxacarb were investigated on the developmental stages, detoxification enzymes, reproductive activity, calling behavior, peripheral physiology, and pheromone titer of M. brasssicae. Methods: To assess pesticide effects, the second instar larvae were maintained for 24 h on a semi-artificial diet containing insecticides at their LC\(_{10}\), LC\(_{30}\), and LC\(_{50}\) concentrations. Results: M. brassicae was more susceptible to chlorantraniliprole (LC\(_{50}\) = 0.35 mg/L) than indoxacarb (LC\(_{50}\) = 1.71 mg/L). A significantly increased developmental time was observed with both insecticides at all tested concentrations but decreases in pupation rate, pupal weight, and emergence were limited to the LC50 concentration. Reductions in both the total number of eggs laid per female and the egg viability were observed with both insecticides at their LC\(_{30}\) and LC\(_{50}\) concentrations. Both female calling activity and the sex pheromone (Z11-hexadecenyl acetate and hexadecenyl acetate) titer were significantly reduced by chlorantraniliprole in LC\(_{50}\) concentration. Antennal responses of female antennae to benzaldehyde and 3-octanone were significantly weaker than controls after exposure to the indoxocarb LC\(_{50}\) concentration. Significant reductions in the enzymatic activity of glutathione S-transferases, mixed-function oxidases, and carboxylesterases were observed in response to both insecticides.}, language = {en} } @article{RoemerAguilarMeyeretal.2022, author = {R{\"o}mer, Daniela and Aguilar, Gonzalo Pacheco and Meyer, Annika and Roces, Flavio}, title = {Symbiont demand guides resource supply: leaf-cutting ants preferentially deliver their harvested fragments to undernourished fungus gardens}, series = {The Science of Nature}, volume = {109}, journal = {The Science of Nature}, number = {3}, doi = {10.1007/s00114-022-01797-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325080}, year = {2022}, abstract = {Leaf-cutting ants are highly successful herbivores in the Neotropics. They forage large amounts of fresh plant material to nourish a symbiotic fungus that sustains the colony. It is unknown how workers organize the intra-nest distribution of resources, and whether they respond to increasing demands in some fungus gardens by adjusting the amount of delivered resources accordingly. In laboratory experiments, we analyzed the spatial distribution of collected leaf fragments among nest chambers in Acromyrmex ambiguus leaf-cutting ants, and how it changed when one of the fungus gardens experienced undernourishment. Plant fragments were evenly distributed among nest chambers when the fungal symbiont was well nourished. That pattern changed when one of the fungus gardens was undernourished and had a higher leaf demand, resulting in more leaf discs delivered to the undernourished fungus garden over at least 2 days after deprivation. Some ants bypassed nourished gardens to directly deliver their resource to the chamber with higher nutritional demand. We hypothesize that cues arising from that chamber might be used for orientation and/or that informed individuals, presumably stemming from the undernourished chamber, may preferentially orient to them.}, language = {en} } @article{MaloukhNazzalKumarappanetal.2023, author = {Maloukh, Lina and Nazzal, Yousef and Kumarappan, Alagappan and Howari, Fares and Ambika, Lakshmi Kesari and Yahmadi, Rihab and Sharma, Manish and Iqbal, Jibran and Al-Taani, Ahmed A. and Salem, Imen Ben and Xavier, Cijo M. and Naseem, Muhamad}, title = {Metagenomic analysis of the outdoor dust microbiomes: a case study from Abu Dhabi, UAE}, series = {Atmosphere}, volume = {14}, journal = {Atmosphere}, number = {2}, issn = {2073-4433}, doi = {10.3390/atmos14020327}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304391}, year = {2023}, abstract = {Outdoor dust covers a shattered range of microbial agents from land over transportation, human microbial flora, which includes pathogen and commensals, and airborne from the environment. Dust aerosols are rich in bacterial communities that have a major impact on human health and living environments. In this study, outdoor samples from roadside barricades, safety walls, and fences (18 samples) were collected from Abu Dhabi, UAE and bacterial diversity was assessed through a 16S rRNA amplicon next generation sequencing approach. Clean data from HiSeq produced 1,099,892 total reads pairs for 18 samples. For all samples, taxonomic classifications were assigned to the OTUs (operational taxonomic units) representative sequence using the Ribosomal Database Project database. Analysis such as alpha diversity, beta diversity, differential species analysis, and species relative abundance were performed in the clustering of samples and a functional profile heat map was obtained from the OTUs by using bioinformatics tools. A total of 2814 OTUs were identified from those samples with a coverage of more than 99\%. In the phylum, all 18 samples had most of the bacterial groups such as Actinobacteria, Proteobacteria, Firmicutes, and Bacteroidetes. Twelve samples had Propionibacteria acnes and were mainly found in RD16 and RD3. Major bacteria species such as Propionibacteria acnes, Bacillus persicus, and Staphylococcus captis were found in all samples. Most of the samples had Streptococcus mitis, Staphylococcus capitis. and Nafulsella turpanensis and Enhydrobacter aerosaccus was part of the normal microbes of the skin. Salinimicrobium sp., Bacillus alkalisediminis, and Bacillus persicus are halophilic bacteria found in sediments. The heat map clustered the samples and species in vertical and horizontal classification, which represents the relationship between the samples and bacterial diversity. The heat map for the functional profile had high properties of amino acids, carbohydrate, and cofactor and vitamin metabolisms of all bacterial species from all samples. Taken together, our analyses are very relevant from the perspective of out-door air quality, airborne diseases, and epidemics, with broader implications for health safety and monitoring.}, language = {en} } @article{DhillonKuebertFlockDahmsetal.2023, author = {Dhillon, Maninder Singh and K{\"u}bert-Flock, Carina and Dahms, Thorsten and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias}, title = {Evaluation of MODIS, Landsat 8 and Sentinel-2 data for accurate crop yield predictions: a case study using STARFM NDVI in Bavaria, Germany}, series = {Remote Sensing}, volume = {15}, journal = {Remote Sensing}, number = {7}, issn = {2072-4292}, doi = {10.3390/rs15071830}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311132}, year = {2023}, abstract = {The increasing availability and variety of global satellite products and the rapid development of new algorithms has provided great potential to generate a new level of data with different spatial, temporal, and spectral resolutions. However, the ability of these synthetic spatiotemporal datasets to accurately map and monitor our planet on a field or regional scale remains underexplored. This study aimed to support future research efforts in estimating crop yields by identifying the optimal spatial (10 m, 30 m, or 250 m) and temporal (8 or 16 days) resolutions on a regional scale. The current study explored and discussed the suitability of four different synthetic (Landsat (L)-MOD13Q1 (30 m, 8 and 16 days) and Sentinel-2 (S)-MOD13Q1 (10 m, 8 and 16 days)) and two real (MOD13Q1 (250 m, 8 and 16 days)) NDVI products combined separately to two widely used crop growth models (CGMs) (World Food Studies (WOFOST), and the semi-empiric Light Use Efficiency approach (LUE)) for winter wheat (WW) and oil seed rape (OSR) yield forecasts in Bavaria (70,550 km\(^2\)) for the year 2019. For WW and OSR, the synthetic products' high spatial and temporal resolution resulted in higher yield accuracies using LUE and WOFOST. The observations of high temporal resolution (8-day) products of both S-MOD13Q1 and L-MOD13Q1 played a significant role in accurately measuring the yield of WW and OSR. For example, L- and S-MOD13Q1 resulted in an R\(^2\) = 0.82 and 0.85, RMSE = 5.46 and 5.01 dt/ha for WW, R\(^2\) = 0.89 and 0.82, and RMSE = 2.23 and 2.11 dt/ha for OSR using the LUE model, respectively. Similarly, for the 8- and 16-day products, the simple LUE model (R\(^2\) = 0.77 and relative RMSE (RRMSE) = 8.17\%) required fewer input parameters to simulate crop yield and was highly accurate, reliable, and more precise than the complex WOFOST model (R\(^2\) = 0.66 and RRMSE = 11.35\%) with higher input parameters. Conclusively, both S-MOD13Q1 and L-MOD13Q1, in combination with LUE, were more prominent for predicting crop yields on a regional scale than the 16-day products; however, L-MOD13Q1 was advantageous for generating and exploring the long-term yield time series due to the availability of Landsat data since 1982, with a maximum resolution of 30 m. In addition, this study recommended the further use of its findings for implementing and validating the long-term crop yield time series in different regions of the world.}, language = {en} } @article{DhillonDahmsKuebertFlocketal.2023, author = {Dhillon, Maninder Singh and Dahms, Thorsten and K{\"u}bert-Flock, Carina and Liepa, Adomas and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias}, title = {Impact of STARFM on crop yield predictions: fusing MODIS with Landsat 5, 7, and 8 NDVIs in Bavaria Germany}, series = {Remote Sensing}, volume = {15}, journal = {Remote Sensing}, number = {6}, issn = {2072-4292}, doi = {10.3390/rs15061651}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311092}, year = {2023}, abstract = {Rapid and accurate yield estimates at both field and regional levels remain the goal of sustainable agriculture and food security. Hereby, the identification of consistent and reliable methodologies providing accurate yield predictions is one of the hot topics in agricultural research. This study investigated the relationship of spatiotemporal fusion modelling using STRAFM on crop yield prediction for winter wheat (WW) and oil-seed rape (OSR) using a semi-empirical light use efficiency (LUE) model for the Free State of Bavaria (70,550 km\(^2\)), Germany, from 2001 to 2019. A synthetic normalised difference vegetation index (NDVI) time series was generated and validated by fusing the high spatial resolution (30 m, 16 days) Landsat 5 Thematic Mapper (TM) (2001 to 2012), Landsat 7 Enhanced Thematic Mapper Plus (ETM+) (2012), and Landsat 8 Operational Land Imager (OLI) (2013 to 2019) with the coarse resolution of MOD13Q1 (250 m, 16 days) from 2001 to 2019. Except for some temporal periods (i.e., 2001, 2002, and 2012), the study obtained an R\(^2\) of more than 0.65 and a RMSE of less than 0.11, which proves that the Landsat 8 OLI fused products are of higher accuracy than the Landsat 5 TM products. Moreover, the accuracies of the NDVI fusion data have been found to correlate with the total number of available Landsat scenes every year (N), with a correlation coefficient (R) of +0.83 (between R\(^2\) of yearly synthetic NDVIs and N) and -0.84 (between RMSEs and N). For crop yield prediction, the synthetic NDVI time series and climate elements (such as minimum temperature, maximum temperature, relative humidity, evaporation, transpiration, and solar radiation) are inputted to the LUE model, resulting in an average R\(^2\) of 0.75 (WW) and 0.73 (OSR), and RMSEs of 4.33 dt/ha and 2.19 dt/ha. The yield prediction results prove the consistency and stability of the LUE model for yield estimation. Using the LUE model, accurate crop yield predictions were obtained for WW (R\(^2\) = 0.88) and OSR (R\(^2\) = 0.74). Lastly, the study observed a high positive correlation of R = 0.81 and R = 0.77 between the yearly R\(^2\) of synthetic accuracy and modelled yield accuracy for WW and OSR, respectively.}, language = {en} } @article{AupperleLellbachHeidrichKehletal.2023, author = {Aupperle-Lellbach, Heike and Heidrich, Daniela and Kehl, Alexandra and Conrad, David and Brockmann, Maria and T{\"o}rner, Katrin and Beitzinger, Christoph and M{\"u}ller, Tobias}, title = {KITLG copy number germline variations in schnauzer breeds and their relevance in digital squamous cell carcinoma in black giant schnauzers}, series = {Veterinary Sciences}, volume = {10}, journal = {Veterinary Sciences}, number = {2}, issn = {2306-7381}, doi = {10.3390/vetsci10020147}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303913}, year = {2023}, abstract = {Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5-7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7-5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC.}, language = {en} } @article{CerezoEchevarriaKehlBeitzingeretal.2023, author = {Cerezo-Echevarria, Argi{\~n}e and Kehl, Alexandra and Beitzinger, Christoph and M{\"u}ller, Tobias and Klopfleisch, Robert and Aupperle-Lellbach, Heike}, title = {Evaluating the histologic grade of digital squamous cell carcinomas in dogs and copy number variation of KIT Ligand — a correlation study}, series = {Veterinary Sciences}, volume = {10}, journal = {Veterinary Sciences}, number = {2}, issn = {2306-7381}, doi = {10.3390/vetsci10020088}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304824}, year = {2023}, abstract = {Dark-haired dogs are predisposed to the development of digital squamous cell carcinoma (DSCC). This may potentially suggest an underlying genetic predisposition not yet completely elucidated. Some authors have suggested a potential correlation between the number of copies KIT Ligand (KITLG) and the predisposition of dogs to DSCC, containing a higher number of copies in those affected by the neoplasm. In this study, the aim was to evaluate a potential correlation between the number of copies of the KITLG and the histological grade of malignancy in dogs with DSCC. For this, 72 paraffin-embedded DSCCs with paired whole blood samples of 70 different dogs were included and grouped according to their haircoat color as follow: Group 0/unknown haircoat color (n = 11); Group 1.a/black non-Schnauzers (n = 15); group 1.b/black Schnauzers (n = 33); group 1.c/black and tan dogs (n = 7); group 2/tan animals (n = 4). The DSCCs were histologically graded. Additionally, KITLG Copy Number Variation (CNV) was determined by ddPCR. A significant correlation was observed between KITLG copy number and the histological grade and score value. This finding may suggest a possible factor for the development of canine DSCC, thus potentially having an impact on personalized veterinary oncological strategies and breeding programs.}, language = {en} } @article{DongBoeppleThieletal.2023, author = {Dong, Meng and B{\"o}pple, Kathrin and Thiel, Julia and Winkler, Bernd and Liang, Chunguang and Schueler, Julia and Davies, Emma J. and Barry, Simon T. and Metsalu, Tauno and M{\"u}rdter, Thomas E. and Sauer, Georg and Ott, German and Schwab, Matthias and Aulitzky, Walter E.}, title = {Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions}, series = {Cells}, volume = {12}, journal = {Cells}, number = {5}, issn = {2073-4409}, doi = {10.3390/cells12050807}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311030}, year = {2023}, abstract = {Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air-liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.}, language = {en} } @article{dePazAsisHolzschuhetal.2023, author = {de Paz, V{\´i}ctor and As{\´i}s, Josep D. and Holzschuh, Andrea and Ba{\~n}os-Pic{\´o}n, Laura}, title = {Effects of traditional orchard abandonment and landscape context on the beneficial arthropod community in a Mediterranean agroecosystem}, series = {Insects}, volume = {14}, journal = {Insects}, number = {3}, issn = {2075-4450}, doi = {10.3390/insects14030277}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311190}, year = {2023}, abstract = {Agricultural abandonment is one of the main land-use changes in Europe, and its consequences on biodiversity are context- and taxa-dependent. While several studies have worked on this topic, few have focused on traditional orchards, especially in different landscapes and under a Mediterranean climate. In this context, we aimed to determine the effects of almond orchard abandonment on the communities of three groups of beneficial arthropods and the role of the landscape context in modulating these effects. Between February and September 2019, four samplings were carried out in twelve almond orchards (three abandoned and three traditional (active orchards under traditional agricultural management) located in simple landscapes as well as three abandoned and three traditional in complex landscapes). Abandoned and traditional almond orchards harbor different arthropod communities and diversity metrics that are strongly conditioned by seasonality. Abandoned orchards can favor pollinators and natural enemies, providing alternative resources in simple landscapes. However, the role that abandoned orchards play in simple landscapes disappears as the percentage of semi-natural habitats in the landscape increases. Our results show that landscape simplification, through the loss of semi-natural habitats, has negative consequences on arthropod biodiversity, even in traditional farming landscapes with small fields and high crop diversity.}, language = {en} } @article{WersebeckmannBiegerlLeyeretal.2023, author = {Wersebeckmann, Vera and Biegerl, Carolin and Leyer, Ilona and Mody, Karsten}, title = {Orthopteran diversity in steep slope vineyards: the role of vineyard type and vegetation management}, series = {Insects}, volume = {14}, journal = {Insects}, number = {1}, issn = {2075-4450}, doi = {10.3390/insects14010083}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304891}, year = {2023}, abstract = {The abandonment of traditional agricultural practices and subsequent succession are major threats to many open-adapted species and species-rich ecosystems. Viticulture on steep slopes has recently suffered from strong declines due to insufficient profitability, thus increasing the area of fallow land considerably. Changing cultivation systems from vertically oriented to modern vineyard terraces offers an opportunity to maintain management economically viable and thus reduces further abandonment. Hillside parallel terraces favor mechanization, and their embankments offer large undisturbed areas that could provide valuable habitats. We investigated the effects of vineyard abandonment, different vineyard management types (vertically oriented vs. terraced), and local parameters on Orthoptera diversity in 45 study sites along the Upper Middle Rhine Valley in Germany. Our results show that woody structures and vineyard abandonment reduced Orthoptera diversity at the local and landscape scale due to decreased habitat quality, especially for open-adapted species. In contrast, open inter-rows of actively managed vineyard types supported heat-adapted Caelifera species. On terrace embankments, extensive management and taller vegetation benefited Ensifera species, while short and mulched vegetation in vertically oriented vineyards favored the dominance of one single Caelifera species. Our results highlight the significance of maintaining viticultural management on steep slopes for the preservation of both open-adapted Orthoptera species and the cultural landscape.}, language = {en} } @article{ReibetanzKelmUttingeretal.2022, author = {Reibetanz, Joachim and Kelm, Matthias and Uttinger, Konstantin L. and Reuter, Miriam and Schlegel, Nicolas and Hankir, Mohamed and Wiegering, Verena and Germer, Christoph-Thomas and Fassnacht, Martin and Lock, Johan Friso and Wiegering, Armin}, title = {Differences in morbidity and mortality between unilateral adrenalectomy for adrenal Cushing's syndrome and bilateral adrenalectomy for therapy refractory extra-adrenal Cushing's syndrome}, series = {Langenbeck's Archives of Surgery}, volume = {407}, journal = {Langenbeck's Archives of Surgery}, number = {6}, doi = {10.1007/s00423-022-02568-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323947}, pages = {2481-2488}, year = {2022}, abstract = {Purpose In selected cases of severe Cushing's syndrome due to uncontrolled ACTH secretion, bilateral adrenalectomy appears unavoidable. Compared with unilateral adrenalectomy (for adrenal Cushing's syndrome), bilateral adrenalectomy has a perceived higher perioperative morbidity. The aim of the current study was to compare both interventions in endogenous Cushing's syndrome regarding postoperative outcomes. Methods We report a single-center, retrospective cohort study comparing patients with hypercortisolism undergoing bilateral vs. unilateral adrenalectomy during 2008-2021. Patients with adrenal Cushing's syndrome due to adenoma were compared with patients with ACTH-dependent Cushing's syndrome (Cushing's disease and ectopic ACTH production) focusing on postoperative morbidity and mortality as well as long-term survival. Results Of 83 patients with adrenalectomy for hypercortisolism (65.1\% female, median age 53 years), the indication for adrenalectomy was due to adrenal Cushing's syndrome in 60 patients (72.2\%; 59 unilateral and one bilateral), and due to hypercortisolism caused by Cushing's disease (n = 16) or non-pituitary uncontrolled ACTH secretion of unknown origin (n = 7) (27.7\% of all adrenalectomies). Compared with unilateral adrenalectomy (n = 59), patients with bilateral adrenalectomy (n = 24) had a higher rate of severe complications (0\% vs. 33\%; p < 0.001) and delayed recovery (median: 10.2\% vs. 79.2\%; p < 0.001). Using the MTL30 marker, patients with bilateral adrenalectomy fared worse than patients after unilateral surgery (MTL30 positive: 7.2\% vs. 25.0\% p < 0.001). Postoperative mortality was increased in patients with bilateral adrenalectomy (0\% vs. 8.3\%; p = 0.081). Conclusion While unilateral adrenalectomy for adrenal Cushing's syndrome represents a safe and definitive therapeutic option, bilateral adrenalectomy to control ACTH-dependent extra-adrenal Cushing's syndrome or Cushing's disease is a more complicated intervention with a mortality of nearly 10\%.}, language = {en} } @article{KoehlerReeseHendricksetal.2022, author = {K{\"o}hler, Franziska and Reese, Lena and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Lock, Johan F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Low-grade mucinous neoplasms (LAMN) of the appendix in Germany between 2011 and 2018: a nationwide analysis based on data provided by the German Center for Cancer Registry Data (ZfKD) at the Robert Koch Institute (RKI)}, series = {Langenbeck's Archives of Surgery}, volume = {407}, journal = {Langenbeck's Archives of Surgery}, number = {8}, doi = {10.1007/s00423-022-02639-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323919}, pages = {3615-3622}, year = {2022}, abstract = {Introduction Low-grade appendiceal mucinous neoplasms (LAMN) are semi-malignant tumors of the appendix which are incidentally found in up to 1\% of appendectomy specimen. To this day, no valid descriptive analysis on LAMN is available for the German population. Methods Data of LAMN (ICD-10: D37.3) were collected from the population-based cancer registries in Germany, provided by the German Center for Cancer Registry Data (Zentrum f{\"u}r Krebsregisterdaten—ZfKD). Data was anonymized and included gender, age at diagnosis, tumor staging according to the TNM-classification, state of residence, information on the performed therapy, and survival data. Results A total of 612 cases were reported to the ZfKD between 2011 and 2018. A total of 63.07\% were female and 36.93\% were male. Great inhomogeneity in reporting cases was seen in the federal states of Germany including the fact that some federal states did not report any cases at all. Age distribution showed a mean age of 62.03 years (SD 16.15) at diagnosis. However, data on tumor stage was only available in 24.86\% of cases (n = 152). A total of 49.34\% of these patients presented with a T4-stage. Likewise, information regarding performed therapy was available in the minority of patients: 269 patients received surgery, 22 did not and for 312 cases no information was available. Twenty-four patients received chemotherapy, 188 did not, and for 400 cases, no information was available. Overall 5-year survival was estimated at 79.52\%. Patients below the age of 55 years at time of diagnosis had a significantly higher 5-year survival rate compared to patients above the age of 55 years (85.77\% vs. 73.27\%). Discussion In this study, we observed an incidence of LAMN in 0.13\% of all appendectomy specimen in 2018. It seems likely that not all cases were reported to the ZfKD; therefore, case numbers may be considered underestimated. Age and gender distribution goes in line with international studies with females being predominantly affected. Especially regarding tumor stage and therapy in depth information cannot be provided through the ZfKD-database. This data analysis emphasizes the need for further studies and the need for setting up a specialized registry for this unique tumor entity to develop guidelines for the appropriate treatment and follow-up.}, language = {en} } @article{KotlyarKrebsSolimandoetal.2023, author = {Kotlyar, Mischa J. and Krebs, Markus and Solimando, Antonio Giovanni and Marquardt, Andr{\´e} and Burger, Maximilian and K{\"u}bler, Hubert and Bargou, Ralf and Kneitz, Susanne and Otto, Wolfgang and Breyer, Johannes and Vergho, Daniel C. and Kneitz, Burkhard and Kalogirou, Charis}, title = {Critical evaluation of a microRNA-based risk classifier predicting cancer-specific survival in renal cell carcinoma with tumor thrombus of the inferior vena cava}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {7}, issn = {2072-6694}, doi = {10.3390/cancers15071981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311040}, year = {2023}, abstract = {(1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCC\(^{IVC}\)) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier — containing miR-21-5p, miR-126-3p and miR-221-3p expression — which significantly predicted the cancer-specific survival (CSS) of ccRCC\(^{IVC}\) patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCC\(^{IVC}\), we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan-Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan-Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCC\(^{IVC}\) according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCC\(^{IVC}\) cohort.}, language = {en} } @article{BrennerGeigerSchlegeletal.2023, author = {Brenner, Daniela and Geiger, Nina and Schlegel, Jan and Diesendorf, Viktoria and Kersting, Louise and Fink, Julian and Stelz, Linda and Schneider-Schaulies, Sibylle and Sauer, Markus and Bodem, Jochen and Seibel, J{\"u}rgen}, title = {Azido-ceramides, a tool to analyse SARS-CoV-2 replication and inhibition — SARS-CoV-2 is inhibited by ceramides}, series = {International Journal of Molecular Sciences}, volume = {24}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms24087281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313581}, year = {2023}, abstract = {Recently, we have shown that C6-ceramides efficiently suppress viral replication by trapping the virus in lysosomes. Here, we use antiviral assays to evaluate a synthetic ceramide derivative α-NH2-ω-N3-C6-ceramide (AKS461) and to confirm the biological activity of C6-ceramides inhibiting SARS-CoV-2. Click-labeling with a fluorophore demonstrated that AKS461 accumulates in lysosomes. Previously, it has been shown that suppression of SARS-CoV-2 replication can be cell-type specific. Thus, AKS461 inhibited SARS-CoV-2 replication in Huh-7, Vero, and Calu-3 cells up to 2.5 orders of magnitude. The results were confirmed by CoronaFISH, indicating that AKS461 acts comparable to the unmodified C6-ceramide. Thus, AKS461 serves as a tool to study ceramide-associated cellular and viral pathways, such as SARS-CoV-2 infections, and it helped to identify lysosomes as the central organelle of C6-ceramides to inhibit viral replication.}, language = {en} } @article{HenrikssonCalderonMontanoSolvieetal.2022, author = {Henriksson, Sofia and Calder{\´o}n-Monta{\~n}o, Jos{\´e} Manuel and Solvie, Daniel and Warpman Berglund, Ulrika and Helleday, Thomas}, title = {Overexpressed c-Myc sensitizes cells to TH1579, a mitotic arrest and oxidative DNA damage inducer}, series = {Biomolecules}, volume = {12}, journal = {Biomolecules}, number = {12}, issn = {2218-273X}, doi = {10.3390/biom12121777}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297547}, year = {2022}, abstract = {Previously, we reported that MTH1 inhibitors TH588 and TH1579 selectively induce oxidative damage and kill Ras-expressing or -transforming cancer cells, as compared to non-transforming immortalized or primary cells. While this explains the impressive anti-cancer properties of the compounds, the molecular mechanism remains elusive. Several oncogenes induce replication stress, resulting in under replicated DNA and replication continuing into mitosis, where TH588 and TH1579 treatment causes toxicity and incorporation of oxidative damage. Hence, we hypothesized that oncogene-induced replication stress explains the cancer selectivity. To test this, we overexpressed c-Myc in human epithelial kidney cells (HA1EB), resulting in increased proliferation, polyploidy and replication stress. TH588 and TH1579 selectively kill c-Myc overexpressing clones, enforcing the cancer cell selective killing of these compounds. Moreover, the toxicity of TH588 and TH1579 in c-Myc overexpressing cells is rescued by transcription, proteasome or CDK1 inhibitors, but not by nucleoside supplementation. We conclude that the molecular toxicological mechanisms of how TH588 and TH1579 kill c-Myc overexpressing cells have several components and involve MTH1-independent proteasomal degradation of c-Myc itself, c-Myc-driven transcription and CDK activation.}, language = {en} } @article{RohmerDobritzTuncbilekDereetal.2022, author = {Rohmer, Carina and Dobritz, Ronja and Tuncbilek-Dere, Dilek and Lehmann, Esther and Gerlach, David and George, Shilpa Elizabeth and Bae, Taeok and Nieselt, Kay and Wolz, Christiane}, title = {Influence of Staphylococcus aureus strain background on Sa3int phage life cycle switches}, series = {Viruses}, volume = {14}, journal = {Viruses}, number = {11}, issn = {1999-4915}, doi = {10.3390/v14112471}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297209}, year = {2022}, abstract = {Staphylococcus aureus asymptomatically colonizes the nasal cavity of mammals, but it is also a leading cause of life-threatening infections. Most human nasal isolates carry Sa3 phages, which integrate into the bacterial hlb gene encoding a sphingomyelinase. The virulence factor-encoding genes carried by the Sa3-phages are highly human-specific, and most animal strains are Sa3 negative. Thus, both insertion and excision of the prophage could potentially confer a fitness advantage to S. aureus. Here, we analyzed the phage life cycle of two Sa3 phages, Φ13 and ΦN315, in different phage-cured S. aureus strains. Based on phage transfer experiments, strains could be classified into low (8325-4, SH1000, and USA300c) and high (MW2c and Newman-c) transfer strains. High-transfer strains promoted the replication of phages, whereas phage adsorption, integration, excision, or recA transcription was not significantly different between strains. RNASeq analyses of replication-deficient lysogens revealed no strain-specific differences in the CI/Mor regulatory switch. However, lytic genes were significantly upregulated in the high transfer strain MW2c Φ13 compared to strain 8325-4 Φ13. By transcriptional start site prediction, new promoter regions within the lytic modules were identified, which are likely targeted by specific host factors. Such host-phage interaction probably accounts for the strain-specific differences in phage replication and transfer frequency. Thus, the genetic makeup of the host strains may determine the rate of phage mobilization, a feature that might impact the speed at which certain strains can achieve host adaptation.}, language = {en} } @article{RackeveiBorgesEngstleretal.2022, author = {Rackevei, Antonia S. and Borges, Alyssa and Engstler, Markus and Dandekar, Thomas and Wolf, Matthias}, title = {About the analysis of 18S rDNA sequence data from trypanosomes in barcoding and phylogenetics: tracing a continuation error occurring in the literature}, series = {Biology}, volume = {11}, journal = {Biology}, number = {11}, issn = {2079-7737}, doi = {10.3390/biology11111612}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297562}, year = {2022}, abstract = {The variable regions (V1-V9) of the 18S rDNA are routinely used in barcoding and phylogenetics. In handling these data for trypanosomes, we have noticed a misunderstanding that has apparently taken a life of its own in the literature over the years. In particular, in recent years, when studying the phylogenetic relationship of trypanosomes, the use of V7/V8 was systematically established. However, considering the current numbering system for all other organisms (including other Euglenozoa), V7/V8 was never used. In Maia da Silva et al. [Parasitology 2004, 129, 549-561], V7/V8 was promoted for the first time for trypanosome phylogenetics, and since then, more than 70 publications have replicated this nomenclature and even discussed the benefits of the use of this region in comparison to V4. However, the primers used to amplify the variable region of trypanosomes have actually amplified V4 (concerning the current 18S rDNA numbering system).}, language = {en} } @article{BroschKorsaTabanetal.2022, author = {Brosch, Philippa K. and Korsa, Tessa and Taban, Danush and Eiring, Patrick and Hildebrand, Sascha and Neubauer, Julia and Zimmermann, Heiko and Sauer, Markus and Shirakashi, Ryo and Djuzenova, Cholpon S. and Sisario, Dmitri and Sukhorukov, Vladimir L.}, title = {Glucose and inositol transporters, SLC5A1 and SLC5A3, in glioblastoma cell migration}, series = {Cancers}, volume = {14}, journal = {Cancers}, number = {23}, issn = {2072-6694}, doi = {10.3390/cancers14235794}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297498}, year = {2022}, abstract = {(1) Background: The recurrence of glioblastoma multiforme (GBM) is mainly due to invasion of the surrounding brain tissue, where organic solutes, including glucose and inositol, are abundant. Invasive cell migration has been linked to the aberrant expression of transmembrane solute-linked carriers (SLC). Here, we explore the role of glucose (SLC5A1) and inositol transporters (SLC5A3) in GBM cell migration. (2) Methods: Using immunofluorescence microscopy, we visualized the subcellular localization of SLC5A1 and SLC5A3 in two highly motile human GBM cell lines. We also employed wound-healing assays to examine the effect of SLC inhibition on GBM cell migration and examined the chemotactic potential of inositol. (3) Results: While GBM cell migration was significantly increased by extracellular inositol and glucose, it was strongly impaired by SLC transporter inhibition. In the GBM cell monolayers, both SLCs were exclusively detected in the migrating cells at the monolayer edge. In single GBM cells, both transporters were primarily localized at the leading edge of the lamellipodium. Interestingly, in GBM cells migrating via blebbing, SLC5A1 and SLC5A3 were predominantly detected in nascent and mature blebs, respectively. (4) Conclusion: We provide several lines of evidence for the involvement of SLC5A1 and SLC5A3 in GBM cell migration, thereby complementing the migration-associated transportome. Our findings suggest that SLC inhibition is a promising approach to GBM treatment.}, language = {en} } @article{MehmoodAlsalehWantetal.2023, author = {Mehmood, Rashid and Alsaleh, Alanoud and Want, Muzamil Y. and Ahmad, Ijaz and Siraj, Sami and Ishtiaq, Muhammad and Alshehri, Faizah A. and Naseem, Muhammad and Yasuhara, Noriko}, title = {Integrative molecular analysis of DNA methylation dynamics unveils molecules with prognostic potential in breast cancer}, series = {BioMedInformatics}, volume = {3}, journal = {BioMedInformatics}, number = {2}, issn = {2673-7426}, doi = {10.3390/biomedinformatics3020029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321171}, pages = {434 -- 445}, year = {2023}, abstract = {DNA methylation acts as a major epigenetic modification in mammals, characterized by the transfer of a methyl group to a cytosine. DNA methylation plays a pivotal role in regulating normal development, and misregulation in cells leads to an abnormal phenotype as is seen in several cancers. Any mutations or expression anomalies of genes encoding regulators of DNA methylation may lead to abnormal expression of critical molecules. A comprehensive genomic study encompassing all the genes related to DNA methylation regulation in relation to breast cancer is lacking. We used genomic and transcriptomic datasets from the Cancer Genome Atlas (TGCA) Pan-Cancer Atlas, Genotype-Tissue Expression (GTEx) and microarray platforms and conducted in silico analysis of all the genes related to DNA methylation with respect to writing, reading and erasing this epigenetic mark. Analysis of mutations was conducted using cBioportal, while Xena and KMPlot were utilized for expression changes and patient survival, respectively. Our study identified multiple mutations in the genes encoding regulators of DNA methylation. The expression profiling of these showed significant differences between normal and disease tissues. Moreover, deregulated expression of some of the genes, namely DNMT3B, MBD1, MBD6, BAZ2B, ZBTB38, KLF4, TET2 and TDG, was correlated with patient prognosis. The current study, to our best knowledge, is the first to provide a comprehensive molecular and genetic profile of DNA methylation machinery genes in breast cancer and identifies DNA methylation machinery as an important determinant of the disease progression. The findings of this study will advance our understanding of the etiology of the disease and may serve to identify alternative targets for novel therapeutic strategies in cancer.}, language = {en} } @article{HanRenMamtiminetal.2023, author = {Han, Chao and Ren, Pengxuan and Mamtimin, Medina and Kruk, Linus and Sarukhanyan, Edita and Li, Chenyu and Anders, Hans-Joachim and Dandekar, Thomas and Krueger, Irena and Elvers, Margitta and Goebel, Silvia and Adler, Kristin and M{\"u}nch, G{\"o}tz and Gudermann, Thomas and Braun, Attila and Mammadova-Bach, Elmina}, title = {Minimal collagen-binding epitope of glycoprotein VI in human and mouse platelets}, series = {Biomedicines}, volume = {11}, journal = {Biomedicines}, number = {2}, issn = {2227-9059}, doi = {10.3390/biomedicines11020423}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304148}, year = {2023}, abstract = {Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predict a minimal collagen-binding epitope of GPVI dimer and designed an EA-20 antibody that recognizes a linear epitope of this surface. Using platelets and whole blood samples donated from wild-type and humanized GPVI transgenic mice and also humans, our experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin. The EA-20 antibody also prevents thrombus formation in whole blood, on the collagen-coated surface, in arterial flow conditions. We also show that EA-20 does not influence GPVI clustering or receptor shedding. Therefore, we propose that blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach by inhibiting specific interactions between GPVI and the collagen matrix.}, language = {en} } @article{HutinLingTarbouriechetal.2022, author = {Hutin, Stephanie and Ling, Wai Li and Tarbouriech, Nicolas and Schoehn, Guy and Grimm, Clemens and Fischer, Utz and Burmeister, Wim P.}, title = {The vaccinia virus DNA helicase structure from combined single-particle cryo-electron microscopy and AlphaFold2 prediction}, series = {Viruses}, volume = {14}, journal = {Viruses}, number = {10}, issn = {1999-4915}, doi = {10.3390/v14102206}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290523}, year = {2022}, abstract = {Poxviruses are large DNA viruses with a linear double-stranded DNA genome circularized at the extremities. The helicase-primase D5, composed of six identical 90 kDa subunits, is required for DNA replication. D5 consists of a primase fragment flexibly attached to the hexameric C-terminal polypeptide (res. 323-785) with confirmed nucleotide hydrolase and DNA-binding activity but an elusive helicase activity. We determined its structure by single-particle cryo-electron microscopy. It displays an AAA+ helicase core flanked by N- and C-terminal domains. Model building was greatly helped by the predicted structure of D5 using AlphaFold2. The 3.9 {\AA} structure of the N-terminal domain forms a well-defined tight ring while the resolution decreases towards the C-terminus, still allowing the fit of the predicted structure. The N-terminal domain is partially present in papillomavirus E1 and polyomavirus LTA helicases, as well as in a bacteriophage NrS-1 helicase domain, which is also closely related to the AAA+ helicase domain of D5. Using the Pfam domain database, a D5_N domain followed by DUF5906 and Pox_D5 domains could be assigned to the cryo-EM structure, providing the first 3D structures for D5_N and Pox_D5 domains. The same domain organization has been identified in a family of putative helicases from large DNA viruses, bacteriophages, and selfish DNA elements.}, language = {en} } @article{FlorenLinsenmairMueller2022, author = {Floren, Andreas and Linsenmair, Karl Eduard and M{\"u}ller, Tobias}, title = {Diversity and functional relevance of canopy arthropods in Central Europe}, series = {Diversity}, volume = {14}, journal = {Diversity}, number = {8}, issn = {1424-2818}, doi = {10.3390/d14080660}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285924}, year = {2022}, abstract = {Although much is known about the ecology and functional importance of canopy arthropods in temperate forests, few studies have tried to assess the overall diversity and investigate the composition and dynamics of tree-specific communities. This has impeded a deeper understanding of the functioning of forests, and of how to maintain system services. Here, we present the first comprehensive data of whole arthropod communities, collected by insecticidal knockdown (fogging) from 1159 trees in 18 study areas in Central Europe during the last 25 years. The data includes 3,253,591 arthropods from 32 taxa (order, suborder, family) collected on 24 tree species from 18 genera. Fogging collects free-living, ectophytic arthropods in approximately the same number as they occur in the trees. To our knowledge, these are the most comprehensive data available today on the taxonomic composition of arboreal fauna. Assigning all arthropods to their feeding guild provided a proxy of their functional importance. The data showed that the canopy communities were regularly structured, with a clear dominance hierarchy comprised of eight 'major taxa' that represented 87\% of all arthropods. Despite significant differences in the proportions of taxa on deciduous and coniferous trees, the composition of the guilds was very similar. The individual tree genera, on the other hand, showed significant differences in guild composition, especially when different study areas and years were compared, whereas tree-specific traits, such as tree height, girth in breast height or leaf cover, explained little of the overall variance. On the ordinal level, guild composition also differed significantly between managed and primary forests, with a simultaneous low within-group variability, indicating that management is a key factor determining the distribution of biodiversity and guild composition.}, language = {en} } @article{NazzalHowariYaslametal.2022, author = {Nazzal, Yousef and Howari, Fares M. and Yaslam, Aya and Iqbal, Jibran and Maloukh, Lina and Ambika, Lakshmi Kesari and Al-Taani, Ahmed A. and Ali, Ijaz and Othman, Eman M. and Jamal, Arshad and Naseem, Muhammad}, title = {A methodological review of tools that assess dust microbiomes, metatranscriptomes and the particulate chemistry of indoor dust}, series = {Atmosphere}, volume = {13}, journal = {Atmosphere}, number = {8}, issn = {2073-4433}, doi = {10.3390/atmos13081276}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285957}, year = {2022}, abstract = {Indoor house dust is a blend of organic and inorganic materials, upon which diverse microbial communities such as viruses, bacteria and fungi reside. Adequate moisture in the indoor environment helps microbial communities multiply fast. The outdoor air and materials that are brought into the buildings by airflow, sandstorms, animals pets and house occupants endow the indoor dust particles with extra features that impact human health. Assessment of the health effects of indoor dust particles, the type of indoor microbial inoculants and the secreted enzymes by indoor insects as allergens merit detailed investigation. Here, we discuss the applications of next generation sequencing (NGS) technology which is used to assess microbial diversity and abundance of the indoor dust environments. Likewise, the applications of NGS are discussed to monitor the gene expression profiles of indoor human occupants or their surrogate cellular models when exposed to aqueous solution of collected indoor dust samples. We also highlight the detection methods of dust allergens and analytical procedures that quantify the chemical nature of indoor particulate matter with a potential impact on human health. Our review is thus unique in advocating the applications of interdisciplinary approaches that comprehensively assess the health effects due to bad air quality in built environments.}, language = {en} } @article{EderHollmannMandasarietal.2022, author = {Eder, Sascha and Hollmann, Claudia and Mandasari, Putri and Wittmann, Pia and Schumacher, Fabian and Kleuser, Burkhard and Fink, Julian and Seibel, J{\"u}rgen and Schneider-Schaulies, J{\"u}rgen and Stigloher, Christian and Beyersdorf, Niklas and Dembski, Sofia}, title = {Synthesis and characterization of ceramide-containing liposomes as membrane models for different T cell subpopulations}, series = {Journal of Functional Biomaterials}, volume = {13}, journal = {Journal of Functional Biomaterials}, number = {3}, issn = {2079-4983}, doi = {10.3390/jfb13030111}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286130}, year = {2022}, abstract = {A fine balance of regulatory (T\(_{reg}\)) and conventional CD4\(^+\) T cells (T\(_{conv}\)) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the T\(_{reg}\)/T\(_{conv}\) balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse T\(_{reg}\) and T\(_{conv}\) with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C\(_{16}\)-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into T\(_{reg}\) and T\(_{conv}\) reflect differences in the ceramide content of cellular membranes.}, language = {en} } @article{AlWarhiElmaidomyMaheretal.2022, author = {Al-Warhi, Tarfah and Elmaidomy, Abeer H. and Maher, Sherif A. and Abu-Baih, Dalia H. and Selim, Samy and Albqmi, Mha and Al-Sanea, Mohammad M. and Alnusaire, Taghreed S. and Ghoneim, Mohammed M. and Mostafa, Ehab M. and Hussein, Shaimaa and El-Damasy, Ashraf K. and Saber, Entesar Ali and Elrehany, Mahmoud A. and Sayed, Ahmed M. and Othman, Eman M. and El-Sherbiny, Mohamed and Abdelmohsen, Usama Ramadan}, title = {The wound-healing potential of Olea europaea L. Cv. Arbequina leaves extract: an integrated in vitro, in silico, and in vivo investigation}, series = {Metabolites}, volume = {12}, journal = {Metabolites}, number = {9}, issn = {2218-1989}, doi = {10.3390/metabo12090791}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286150}, year = {2022}, abstract = {Olea europaea L. Cv. Arbequina (OEA) (Oleaceae) is an olive variety species that has received little attention. Besides our previous work for the chemical profiling of OEA leaves using LC-HRESIMS, an additional 23 compounds are identified. An excision wound model is used to measure wound healing action. Wounds are provided with OEA (2\% w/v) or MEBO\(^®\) cream (marketed treatment). The wound closure rate related to vehicle-treated wounds is significantly increased by OEA. Comparing to vehicle wound tissues, significant levels of TGF-β in OEA and MEBO\(^®\) (p < 0.05) are displayed by gene expression patterns, with the most significant levels in OEA-treated wounds. Proinflammatory TNF-α and IL-1β levels are substantially reduced in OEA-treated wounds. The capability of several lignan-related compounds to interact with MMP-1 is revealed by extensive in silico investigation of the major OEA compounds (i.e., inverse docking, molecular dynamics simulation, and ΔG calculation), and their role in the wound-healing process is also characterized. The potential of OEA as a potent MMP-1 inhibitor is shown in subsequent in vitro testing (IC\(_{50}\) = 88.0 ± 0.1 nM). In conclusion, OEA is introduced as an interesting therapeutic candidate that can effectively manage wound healing because of its anti-inflammatory and antioxidant properties.}, language = {en} } @article{DieboldSchoenemannEilersetal.2023, author = {Diebold, Mathias and Sch{\"o}nemann, Lars and Eilers, Martin and Sotriffer, Christoph and Schindelin, Hermann}, title = {Crystal structure of a covalently linked Aurora-A-MYCN complex}, series = {Acta Crystallographica}, volume = {D79}, journal = {Acta Crystallographica}, doi = {10.1107/s2059798322011433}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318855}, pages = {1 -- 9}, year = {2023}, abstract = {Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.}, language = {en} } @article{DhillonDahmsKuebertFlocketal.2022, author = {Dhillon, Maninder Singh and Dahms, Thorsten and K{\"u}bert-Flock, Carina and Steffan-Dewenter, Ingolf and Zhang, Jie and Ullmann, Tobias}, title = {Spatiotemporal Fusion Modelling Using STARFM: Examples of Landsat 8 and Sentinel-2 NDVI in Bavaria}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {3}, issn = {2072-4292}, doi = {10.3390/rs14030677}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323471}, year = {2022}, abstract = {The increasing availability and variety of global satellite products provide a new level of data with different spatial, temporal, and spectral resolutions; however, identifying the most suited resolution for a specific application consumes increasingly more time and computation effort. The region's cloud coverage additionally influences the choice of the best trade-off between spatial and temporal resolution, and different pixel sizes of remote sensing (RS) data may hinder the accurate monitoring of different land cover (LC) classes such as agriculture, forest, grassland, water, urban, and natural-seminatural. To investigate the importance of RS data for these LC classes, the present study fuses NDVIs of two high spatial resolution data (high pair) (Landsat (30 m, 16 days; L) and Sentinel-2 (10 m, 5-6 days; S), with four low spatial resolution data (low pair) (MOD13Q1 (250 m, 16 days), MCD43A4 (500 m, one day), MOD09GQ (250 m, one-day), and MOD09Q1 (250 m, eight day)) using the spatial and temporal adaptive reflectance fusion model (STARFM), which fills regions' cloud or shadow gaps without losing spatial information. These eight synthetic NDVI STARFM products (2: high pair multiply 4: low pair) offer a spatial resolution of 10 or 30 m and temporal resolution of 1, 8, or 16 days for the entire state of Bavaria (Germany) in 2019. Due to their higher revisit frequency and more cloud and shadow-free scenes (S = 13, L = 9), Sentinel-2 (overall R\(^2\) = 0.71, and RMSE = 0.11) synthetic NDVI products provide more accurate results than Landsat (overall R\(^2\) = 0.61, and RMSE = 0.13). Likewise, for the agriculture class, synthetic products obtained using Sentinel-2 resulted in higher accuracy than Landsat except for L-MOD13Q1 (R\(^2\) = 0.62, RMSE = 0.11), resulting in similar accuracy preciseness as S-MOD13Q1 (R\(^2\) = 0.68, RMSE = 0.13). Similarly, comparing L-MOD13Q1 (R\(^2\) = 0.60, RMSE = 0.05) and S-MOD13Q1 (R\(^2\) = 0.52, RMSE = 0.09) for the forest class, the former resulted in higher accuracy and precision than the latter. Conclusively, both L-MOD13Q1 and S-MOD13Q1 are suitable for agricultural and forest monitoring; however, the spatial resolution of 30 m and low storage capacity makes L-MOD13Q1 more prominent and faster than that of S-MOD13Q1 with the 10-m spatial resolution.}, 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{BazihizinaBoehmMessereretal.2022, author = {Bazihizina, Nadia and B{\"o}hm, Jennifer and Messerer, Maxim and Stigloher, Christian and M{\"u}ller, Heike M. and Cuin, Tracey Ann and Maierhofer, Tobias and Cabot, Joan and Mayer, Klaus F. X. and Fella, Christian and Huang, Shouguang and Al-Rasheid, Khaled A. S. and Alquraishi, Saleh and Breadmore, Michael and Mancuso, Stefano and Shabala, Sergey and Ache, Peter and Zhang, Heng and Zhu, Jian-Kang and Hedrich, Rainer and Scherzer, S{\"o}nke}, title = {Stalk cell polar ion transport provide for bladder-based salinity tolerance in Chenopodium quinoa}, series = {New Phytologist}, volume = {235}, journal = {New Phytologist}, number = {5}, doi = {10.1111/nph.18205}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287222}, pages = {1822 -- 1835}, year = {2022}, abstract = {Chenopodium quinoa uses epidermal bladder cells (EBCs) to sequester excess salt. Each EBC complex consists of a leaf epidermal cell, a stalk cell, and the bladder. Under salt stress, sodium (Na\(^{+}\)), chloride (Cl\(^{-}\)), potassium (K\(^{+}\)) and various metabolites are shuttled from the leaf lamina to the bladders. Stalk cells operate as both a selectivity filter and a flux controller. In line with the nature of a transfer cell, advanced transmission electron tomography, electrophysiology, and fluorescent tracer flux studies revealed the stalk cell's polar organization and bladder-directed solute flow. RNA sequencing and cluster analysis revealed the gene expression profiles of the stalk cells. Among the stalk cell enriched genes, ion channels and carriers as well as sugar transporters were most pronounced. Based on their electrophysiological fingerprint and thermodynamic considerations, a model for stalk cell transcellular transport was derived.}, language = {en} } @article{GrausLiRathjeetal.2023, author = {Graus, Dorothea and Li, Kunkun and Rathje, Jan M. and Ding, Meiqi and Krischke, Markus and M{\"u}ller, Martin J. and Cuin, Tracey Ann and Al-Rasheid, Khaled A. S. and Scherzer, S{\"o}nke and Marten, Irene and Konrad, Kai R. and Hedrich, Rainer}, title = {Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling}, series = {New Phytologist}, volume = {237}, journal = {New Phytologist}, number = {1}, doi = {10.1111/nph.18501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312152}, pages = {217 -- 231}, year = {2023}, abstract = {Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically-driven leaf movements. Leaf downward movement caused by hydro-passive turgor loss reached a maximum within 2 h. Salt-driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca\(^{2+}\)) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H\(^{+}\)) pumping, a salt uptake-dependent cytosolic alkalization, and a return of the apoplast osmolality to pre-stress levels. Although, transcript numbers of abscisic acid- and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H\(^{+}\)/Na\(^{+}\)-exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na\(^{+}\)) rapidly even under massive salt loads, based on pre-established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca\(^{2+}\) signaling.}, language = {en} } @article{JonesHuangHedrichetal.2022, author = {Jones, Jeffrey J. and Huang, Shouguang and Hedrich, Rainer and Geilfus, Christoph-Martin and Roelfsema, M. Rob G.}, title = {The green light gap: a window of opportunity for optogenetic control of stomatal movement}, series = {New Phytologist}, volume = {236}, journal = {New Phytologist}, number = {4}, doi = {10.1111/nph.18451}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293724}, pages = {1237 -- 1244}, year = {2022}, abstract = {Green plants are equipped with photoreceptors that are capable of sensing radiation in the ultraviolet-to-blue and the red-to-far-red parts of the light spectrum. However, plant cells are not particularly sensitive to green light (GL), and light which lies within this part of the spectrum does not efficiently trigger the opening of stomatal pores. Here, we discuss the current knowledge of stomatal responses to light, which are either provoked via photosynthetically active radiation or by specific blue light (BL) signaling pathways. The limited impact of GL on stomatal movements provides a unique option to use this light quality to control optogenetic tools. Recently, several of these tools have been optimized for use in plant biological research, either to control gene expression, or to provoke ion fluxes. Initial studies with the BL-activated potassium channel BLINK1 showed that this tool can speed up stomatal movements. Moreover, the GL-sensitive anion channel GtACR1 can induce stomatal closure, even at conditions that provoke stomatal opening in wild-type plants. Given that crop plants in controlled-environment agriculture and horticulture are often cultivated with artificial light sources (i.e. a combination of blue and red light from light-emitting diodes), GL signals can be used as a remote-control signal that controls stomatal transpiration and water consumption.}, language = {en} } @article{RackeveiKarnkowskaWolf2023, author = {Rackevei, Antonia S. and Karnkowska, Anna and Wolf, Matthias}, title = {18S rDNA sequence-structure phylogeny of the Euglenophyceae (Euglenozoa, Euglenida)}, series = {Journal of Eukaryotic Microbiology}, volume = {70}, journal = {Journal of Eukaryotic Microbiology}, number = {2}, doi = {10.1111/jeu.12959}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311896}, year = {2023}, abstract = {The phylogeny of Euglenophyceae (Euglenozoa, Euglenida) has been discussed for decades with new genera being described in the last few years. In this study, we reconstruct a phylogeny using 18S rDNA sequence and structural data simultaneously. Using homology modeling, individual secondary structures were predicted. Sequence-structure data are encoded and automatically aligned. Here, we present a sequence-structure neighbor-joining tree of more than 300 taxa classified as Euglenophyceae. Profile neighbor-joining was used to resolve the basal branching pattern. Neighbor-joining, maximum parsimony, and maximum likelihood analyses were performed using sequence-structure information for manually chosen subsets. All analyses supported the monophyly of Eutreptiella, Discoplastis, Lepocinclis, Strombomonas, Cryptoglena, Monomorphina, Euglenaria, and Colacium. Well-supported topologies were generally consistent with previous studies using a combined dataset of genetic markers. Our study supports the simultaneous use of sequence and structural data to reconstruct more accurate and robust trees. The average bootstrap value is significantly higher than the average bootstrap value obtained from sequence-only analyses, which is promising for resolving relationships between more closely related taxa.}, language = {en} } @article{UhlerHaaseHoffmannetal.2022, author = {Uhler, Johannes and Haase, Peter and Hoffmann, Lara and Hothorn, Torsten and Schmidl, J{\"u}rgen and Stoll, Stefan and Welti, Ellen A. R. and Buse, J{\"o}rn and M{\"u}ller, J{\"o}rg}, title = {A comparison of different Malaise trap types}, series = {Insect Conservation and Diversity}, volume = {15}, journal = {Insect Conservation and Diversity}, number = {6}, doi = {10.1111/icad.12604}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293694}, pages = {666 -- 672}, year = {2022}, abstract = {Recent reports on insect decline have highlighted the need for long-term data on insect communities towards identifying their trends and drivers. With the launch of many new insect monitoring schemes to investigate insect communities over large spatial and temporal scales, Malaise traps have become one of the most important tools due to the broad spectrum of species collected and reduced capture bias through passive sampling of insects day and night. However, Malaise traps can vary in size, shape, and colour, and it is unknown how these differences affect biomass, species richness, and composition of trap catch, making it difficult to compare results between studies. We compared five Malaise trap types (three variations of the Townes and two variations of the Bartak Malaise trap) to determine their effects on biomass and species richness as identified by metabarcoding. Insect biomass varied by 20\%-55\%, not strictly following trap size but varying with trap type. Total species richness was 20\%-38\% higher in the three Townes trap models compared to the Bartak traps. Bartak traps captured lower richness of highly mobile taxa but increased richness of ground-dwelling taxa. The white roofed Townes trap captured a higher richness of pollinators. We find that biomass, total richness, and taxa group specific richness are all sensitive to Malaise trap type. Trap type should be carefully considered and aligned to match monitoring and research questions. Additionally, our estimates of trap type effects can be used to adjust results to facilitate comparisons across studies.}, language = {en} } @article{FrickeRedlichZhangetal.2023, author = {Fricke, Ute and Redlich, Sarah and Zhang, Jie and Benjamin, Caryl S. and Englmeier, Jana and Ganuza, Cristina and Haensel, Maria and Riebl, Rebekka and Rojas-Botero, Sandra and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Steffan-Dewenter, Ingolf}, title = {Earlier flowering of winter oilseed rape compensates for higher pest pressure in warmer climates}, series = {Journal of Applied Ecology}, volume = {60}, journal = {Journal of Applied Ecology}, number = {2}, doi = {10.1111/1365-2664.14335}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312562}, pages = {365 -- 375}, year = {2023}, abstract = {Global warming can increase insect pest pressure by enhancing reproductive rates. Whether this translates into yield losses depends on phenological synchronisation of pests with their host plants and natural enemies. Simultaneously, landscape composition may mitigate climate effects by shaping the resource availability for pests and their antagonists. Here, we study the combined effects of temperature and landscape composition on pest abundances, larval parasitism, crop damage and yield, while also considering crop phenology, to identify strategies for sustainable management of oilseed rape (OSR) pests under warming climates. In all, 29 winter OSR crop fields were investigated in different climates (defined by multi-annual mean temperature, MAT) and landscape contexts in Bavaria, Germany. We measured abundances of adult pollen beetles and stem weevil larvae, pollen beetle larval parasitism, bud loss, stem damage and seed yield, and calculated the flowering date from growth stage observations. Landscape parameters (proportion of non-crop and OSR area, change in OSR area relative to the previous year) were calculated at six spatial scales (0.6-5 km). Pollen beetle abundance increased with MAT but to different degrees depending on the landscape context, that is, increased less strongly when OSR proportions were high (1-km scale), interannually constant (5-km scale) or both. In contrast, stem weevil abundance and stem damage did not respond to landscape composition nor MAT. Pollen beetle larval parasitism was overall low, but occasionally exceeded 30\% under both low and high MAT and with reduced OSR area (0.6-km scale). Despite high pollen beetle abundance in warm climates, yields were high when OSR flowered early. Thereby, higher temperatures favoured early flowering. Only among late-flowering OSR crop fields yield was higher in cooler than warmer climates. Bud loss responded analogously. Landscape composition did not substantially affect bud loss and yield. Synthesis and applications: Earlier flowering of winter OSR compensates for higher pollen beetle abundance in warmer climates, while interannual continuity of OSR area prevents high pollen beetle abundance in the first place. Thus, regional coordination of crop rotation and crop management promoting early flowering may contribute to sustainable pest management in OSR under current and future climatic conditions.}, language = {en} } @article{LaswayPetersNjovuetal.2022, author = {Lasway, Julius V. and Peters, Marcell K. and Njovu, Henry K. and Eardley, Connal and Pauly, Alain and Steffan-Dewenter, Ingolf}, title = {Agricultural intensification with seasonal fallow land promotes high bee diversity in Afrotropical drylands}, series = {Journal of Applied Ecology}, volume = {59}, journal = {Journal of Applied Ecology}, number = {12}, doi = {10.1111/1365-2664.14296}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311877}, pages = {3014 -- 3026}, year = {2022}, abstract = {The exponential increase in the human population in tandem with increased food demand has caused agriculture to be the global-dominant form of land use. Afrotropical drylands are currently facing the loss of natural savannah habitats and agricultural intensification with largely unknown consequences for bees. Here we investigate the effects of agricultural intensification on bee assemblages in the Afrotropical drylands of northern Tanzania. We disentangled the direct effects of agricultural intensification and temperature on bee richness from indirect effects mediated by changes in floral resources. We collected data from 24 study sites representing three levels of management intensity (natural savannah, moderate intensive and highly intensive agriculture) spanning an extensive gradient of mean annual temperature (MAT) in northern Tanzania. We used ordinary linear models and path analysis to test the effects of agricultural intensity and MAT on bee species richness, bee species composition and body-size variation of bee communities. We found that bee species richness increased with agricultural intensity and with increasing temperature. The effects of agricultural intensity and temperature on bee species richness were mediated by the positive effects of agriculture and temperature on the richness of floral resources used by bees. During the off-growing season, agricultural land was characterized by an extensive period of fallow land holding a very high density of flowering plants with unique bee species composition. The increase in bee diversity in agricultural habitats paralleled an increasing variation of bee body sizes with agricultural intensification that, however, diminished in environments with higher temperatures. Synthesis and applications. Our study reveals that bee assemblages in Afrotropical drylands benefit from agricultural intensification in the way it is currently practiced. However, further land-use intensification, including year-round irrigated crop monocultures and excessive use of agrochemicals, is likely to exert a negative impact on bee diversity and pollination services, as reported in temperate regions. Moreover, several bee species were restricted to natural savannah habitats. To conserve bee communities and guarantee pollination services in the region, a mixture of savannah and agriculture, with long periods of fallow land should be maintained.}, language = {en} } @article{GebertSteffan‐DewenterKronbachetal.2022, author = {Gebert, Friederike and Steffan-Dewenter, Ingolf and Kronbach, Patrick and Peters, Marcell K.}, title = {The role of diversity, body size and climate in dung removal: A correlative and experimental approach}, series = {Journal of Animal Ecology}, volume = {91}, journal = {Journal of Animal Ecology}, number = {11}, doi = {10.1111/1365-2656.13798}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293907}, pages = {2181 -- 2191}, year = {2022}, abstract = {The mechanisms by which climatic changes influence ecosystem functions, that is, by a direct climatic control of ecosystem processes or by modifying richness and trait compositions of species communities, remain unresolved. This study is a contribution to this discourse by elucidating the linkages between climate, land use, biodiversity, body size and ecosystem functions. We disentangled direct climatic from biodiversity-mediated effects by using dung removal by dung beetles as a model system and by combining correlative field data and exclosure experiments along an extensive elevational gradient on Mt. Kilimanjaro, Tanzania. Dung removal declined with increasing elevation, being associated with a strong reduction in the richness and body size traits of dung beetle communities. Climate influenced dung removal rates by modifying biodiversity rather than by direct effects. The biodiversity-ecosystem effect was driven by a change in the mean body size of dung beetles. Dung removal rates were strongly reduced when large dung beetles were experimentally excluded. This study underscores that climate influences ecosystem functions mainly by modifying biodiversity and underpins the important role of body size for dung removal.}, language = {en} } @article{KernerKraussMaihoffetal.2023, author = {Kerner, Janika M. and Krauss, Jochen and Maihoff, Fabienne and Bofinger, Lukas and Classen, Alice}, title = {Alpine butterflies want to fly high: Species and communities shift upwards faster than their host plants}, series = {Ecology}, volume = {104}, journal = {Ecology}, number = {1}, doi = {10.1002/ecy.3848}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312015}, year = {2023}, abstract = {Despite sometimes strong codependencies of insect herbivores and plants, the responses of individual taxa to accelerating climate change are typically studied in isolation. For this reason, biotic interactions that potentially limit species in tracking their preferred climatic niches are ignored. Here, we chose butterflies as a prominent representative of herbivorous insects to investigate the impacts of temperature changes and their larval host plant distributions along a 1.4-km elevational gradient in the German Alps. Following a sampling protocol of 2009, we revisited 33 grassland plots in 2019 over an entire growing season. We quantified changes in butterfly abundance and richness by repeated transect walks on each plot and disentangled the direct and indirect effects of locally assessed temperature, site management, and larval and adult food resource availability on these patterns. Additionally, we determined elevational range shifts of butterflies and host plants at both the community and species level. Comparing the two sampled years (2009 and 2019), we found a severe decline in butterfly abundance and a clear upward shift of butterflies along the elevational gradient. We detected shifts in the peak of species richness, community composition, and at the species level, whereby mountainous species shifted particularly strongly. In contrast, host plants showed barely any change, neither in connection with species richness nor individual species shifts. Further, temperature and host plant richness were the main drivers of butterfly richness, with change in temperature best explaining the change in richness over time. We concluded that host plants were not yet hindering butterfly species and communities from shifting upwards. However, the mismatch between butterfly and host plant shifts might become a problem for this very close plant-herbivore relationship, especially toward higher elevations, if butterflies fail to adapt to new host plants. Further, our results support the value of conserving traditional extensive pasture use as a promoter of host plant and, hence, butterfly richness.}, language = {en} } @article{SponslerRequierKallniketal.2022, author = {Sponsler, Douglas B. and Requier, Fabrice and Kallnik, Katharina and Classen, Alice and Maihoff, Fabienne and Sieger, Johanna and Steffan-Dewenter, Ingolf}, title = {Contrasting patterns of richness, abundance, and turnover in mountain bumble bees and their floral hosts}, series = {Ecology}, volume = {103}, journal = {Ecology}, number = {7}, doi = {10.1002/ecy.3712}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287199}, year = {2022}, abstract = {Environmental gradients generate and maintain biodiversity on Earth. Mountain slopes are among the most pronounced terrestrial environmental gradients, and the elevational structure of species and their interactions can provide unique insight into the processes that govern community assembly and function in mountain ecosystems. We recorded bumble bee-flower interactions over 3 years along a 1400-m elevational gradient in the German Alps. Using nonlinear modeling techniques, we analyzed elevational patterns at the levels of abundance, species richness, species β-diversity, and interaction β-diversity. Though floral richness exhibited a midelevation peak, bumble bee richness increased with elevation before leveling off at the highest sites, demonstrating the exceptional adaptation of these bees to cold temperatures and short growing seasons. In terms of abundance, though, bumble bees exhibited divergent species-level responses to elevation, with a clear separation between species preferring low versus high elevations. Overall interaction β-diversity was mainly caused by strong turnover in the floral community, which exhibited a well-defined threshold of β-diversity rate at the tree line ecotone. Interaction β-diversity increased sharply at the upper extreme of the elevation gradient (1800-2000 m), an interval over which we also saw steep decline in floral richness and abundance. Turnover of bumble bees along the elevation gradient was modest, with the highest rate of β-diversity occurring over the interval from low- to mid-elevation sites. The contrast between the relative robustness bumble bee communities and sensitivity of plant communities to the elevational gradient in our study suggests that the strongest effects of climate change on mountain bumble bees may be indirect effects mediated by the responses of their floral hosts, though bumble bee species that specialize in high-elevation habitats may also experience significant direct effects of warming.}, language = {en} } @article{KortmannRothBuseetal.2022, author = {Kortmann, Mareike and Roth, Nicolas and Buse, J{\"o}rn and Hilszczański, Jacek and Jaworski, Tomasz and Morini{\`e}re, J{\´e}r{\^o}me and Seidl, Rupert and Thorn, Simon and M{\"u}ller, J{\"o}rg C.}, title = {Arthropod dark taxa provide new insights into diversity responses to bark beetle infestations}, series = {Ecological Applications}, volume = {32}, journal = {Ecological Applications}, number = {2}, doi = {10.1002/eap.2516}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-276392}, year = {2022}, abstract = {Natural disturbances are increasing around the globe, also impacting protected areas. Although previous studies have indicated that natural disturbances result in mainly positive effects on biodiversity, these analyses mostly focused on a few well established taxonomic groups, and thus uncertainty remains regarding the comprehensive impact of natural disturbances on biodiversity. Using Malaise traps and meta-barcoding, we studied a broad range of arthropod taxa, including dark and cryptic taxa, along a gradient of bark beetle disturbance severities in five European national parks. We identified order-level community thresholds of disturbance severity and classified barcode index numbers (BINs; a cluster system for DNA sequences, where each cluster corresponds to a species) as negative or positive disturbance indicators. Negative indicator BINs decreased above thresholds of low to medium disturbance severity (20\%-30\% of trees killed), whereas positive indicator BINs benefited from high disturbance severity (76\%-98\%). BINs allocated to a species name contained nearly as many positive as negative disturbance indicators, but dark and cryptic taxa, particularly Diptera and Hymenoptera in our data, contained higher numbers of negative disturbance indicator BINs. Analyses of changes in the richness of BINs showed variable responses of arthropods to disturbance severity at lower taxonomic levels, whereas no significant signal was detected at the order level due to the compensatory responses of the underlying taxa. We conclude that the analyses of dark taxa can offer new insights into biodiversity responses to disturbances. Our results suggest considerable potential for forest management to foster arthropod diversity, for example by maintaining both closed-canopy forests (>70\% cover) and open forests (<30\% cover) on the landscape.}, language = {en} } @article{FofanovProkopovKuhletal.2020, author = {Fofanov, Mikhail V. and Prokopov, Dmitry Yu. and Kuhl, Heiner and Schartl, Manfred and Trifonov, Vladimir A.}, title = {Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {24}, issn = {1422-0067}, doi = {10.3390/ijms21249562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285230}, year = {2020}, abstract = {MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments.}, language = {en} } @article{NaseemOsmanoğluKaltdorfetal.2020, author = {Naseem, Muhammad and Osmanoğlu, {\"O}zge and Kaltdorf, Martin and Alblooshi, Afnan Ali M. A. and Iqbal, Jibran and Howari, Fares M. and Srivastava, Mugdha and Dandekar, Thomas}, title = {Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms21165745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285730}, year = {2020}, abstract = {The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions.}, language = {en} } @article{RangerBiedermannPhuntumartetal.2018, author = {Ranger, Christopher M. and Biedermann, Peter HW and Phuntumart, Vipaporn and Beligala, Gayathri U. and Ghosh, Satyaki and Palmquist, Debra E. and Mueller, Robert and Barnett, Jenny and Schultz, Peter B. and Reding, Michael E. and Benz, J. Philipp}, title = {Symbiont selection via alcohol benefits fungus farming by ambrosia beetles}, series = {Proceedings of the National Academy of Sciences}, volume = {115}, journal = {Proceedings of the National Academy of Sciences}, number = {17}, doi = {10.1073/pnas.1716852115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224953}, pages = {4447-4452}, year = {2018}, abstract = {Animal-microbe mutualisms are typically maintained by vertical symbiont transmission or partner choice. A third mechanism, screening of high-quality symbionts, has been predicted in theory, but empirical examples are rare. Here we demonstrate that ambrosia beetles rely on ethanol within host trees for promoting gardens of their fungal symbiont and producing offspring. Ethanol has long been known as the main attractant for many of these fungus-farming beetles as they select host trees in which they excavate tunnels and cultivate fungal gardens. More than 300 attacks by Xylosandrus germanus and other species were triggered by baiting trees with ethanol lures, but none of the foundresses established fungal gardens or produced broods unless tree tissues contained in vivo ethanol resulting from irrigation with ethanol solutions. More X. germanus brood were also produced in a rearing substrate containing ethanol. These benefits are a result of increased food supply via the positive effects of ethanol on food-fungus biomass. Selected Ambrosiella and Raffaelea fungal isolates from ethanol-responsive ambrosia beetles profited directly and indirectly by (i) a higher biomass on medium containing ethanol, (ii) strong alcohol dehydrogenase enzymatic activity, and (iii) a competitive advantage over weedy fungal garden competitors (Aspergillus, Penicillium) that are inhibited by ethanol. As ambrosia fungi both detoxify and produce ethanol, they may maintain the selectivity of their alcohol-rich habitat for their own purpose and that of other ethanol-resistant/producing microbes. This resembles biological screening of beneficial symbionts and a potentially widespread, unstudied benefit of alcohol-producing symbionts (e.g., yeasts) in other microbial symbioses.}, language = {en} } @article{StojanovićFuchsFiedleretal.2020, author = {Stojanović, Stevan D. and Fuchs, Maximilian and Fiedler, Jan and Xiao, Ke and Meinecke, Anna and Just, Annette and Pich, Andreas and Thum, Thomas and Kunz, Meik}, title = {Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {11}, issn = {1422-0067}, doi = {10.3390/ijms21114126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285181}, year = {2020}, abstract = {Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.}, language = {en} } @article{DollKolbSchnappetal.2020, author = {Doll, Julia and Kolb, Susanne and Schnapp, Linda and Rad, Aboulfazl and R{\"u}schendorf, Franz and Khan, Imran and Adli, Abolfazl and Hasanzadeh, Atefeh and Liedtke, Daniel and Knaup, Sabine and Hofrichter, Michaela AH and M{\"u}ller, Tobias and Dittrich, Marcus and Kong, Il-Keun and Kim, Hyung-Goo and Haaf, Thomas and Vona, Barbara}, title = {Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms21010311}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285142}, year = {2020}, abstract = {CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.}, language = {en} } @article{BreitenbachLorenzDandekar2019, author = {Breitenbach, Tim and Lorenz, Kristina and Dandekar, Thomas}, title = {How to steer and control ERK and the ERK signaling cascade exemplified by looking at cardiac insufficiency}, series = {International Journal of Molecular Sciences}, volume = {20}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms20092179}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285164}, year = {2019}, abstract = {Mathematical optimization framework allows the identification of certain nodes within a signaling network. In this work, we analyzed the complex extracellular-signal-regulated kinase 1 and 2 (ERK1/2) cascade in cardiomyocytes using the framework to find efficient adjustment screws for this cascade that is important for cardiomyocyte survival and maladaptive heart muscle growth. We modeled optimal pharmacological intervention points that are beneficial for the heart, but avoid the occurrence of a maladaptive ERK1/2 modification, the autophosphorylation of ERK at threonine 188 (ERK\(^{Thr188}\) phosphorylation), which causes cardiac hypertrophy. For this purpose, a network of a cardiomyocyte that was fitted to experimental data was equipped with external stimuli that model the pharmacological intervention points. Specifically, two situations were considered. In the first one, the cardiomyocyte was driven to a desired expression level with different treatment strategies. These strategies were quantified with respect to beneficial effects and maleficent side effects and then which one is the best treatment strategy was evaluated. In the second situation, it was shown how to model constitutively activated pathways and how to identify drug targets to obtain a desired activity level that is associated with a healthy state and in contrast to the maleficent expression pattern caused by the constitutively activated pathway. An implementation of the algorithms used for the calculations is also presented in this paper, which simplifies the application of the presented framework for drug targeting, optimal drug combinations and the systematic and automatic search for pharmacological intervention points. The codes were designed such that they can be combined with any mathematical model given by ordinary differential equations.}, language = {en} } @article{BatzkeBuechelHansenetal.2018, author = {Batzke, Katharina and B{\"u}chel, Gabriele and Hansen, Wiebke and Schramm, Alexander}, title = {TrkB-target Galectin-1 impairs immune activation and radiation responses in neuroblastoma: implications for tumour therapy}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {3}, issn = {1422-0067}, doi = {10.3390/ijms19030718}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285097}, year = {2018}, abstract = {Galectin-1 (Gal-1) has been described to promote tumour growth by inducing angiogenesis and to contribute to the tumour immune escape. We had previously identified up-regulation of Gal-1 in preclinical models of aggressive neuroblastoma (NB), the most common extracranial tumour of childhood. While Gal-1 did not confer a survival advantage in the absence of exogenous stressors, Gal-1 contributed to enhanced cell migratory and invasive properties. Here, we review these findings and extend them by analyzing Gal-1 mediated effects on immune cell regulation and radiation resistance. In line with previous results, cell autonomous effects as well as paracrine functions contribute to Gal-1 mediated pro-tumourigenic functions. Interfering with Gal-1 functions in vivo will add to a better understanding of the role of the Gal-1 axis in the complex tumour-host interaction during immune-, chemo- and radiotherapy of neuroblastoma.}, language = {en} } @article{SbirkovKwokBhamraetal.2017, author = {Sbirkov, Yordan and Kwok, Colin and Bhamra, Amandeep and Thompson, Andrew J. and Gil, Veronica and Zelent, Arthur and Petrie, Kevin}, title = {Semi-quantitative mass spectrometry in AML cells identifies new non-genomic targets of the EZH2 methyltransferase}, series = {International Journal of Molecular Sciences}, volume = {18}, journal = {International Journal of Molecular Sciences}, number = {7}, issn = {1422-0067}, doi = {10.3390/ijms18071440}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285541}, year = {2017}, abstract = {Alterations to the gene encoding the EZH2 (KMT6A) methyltransferase, including both gain-of-function and loss-of-function, have been linked to a variety of haematological malignancies and solid tumours, suggesting a complex, context-dependent role of this methyltransferase. The successful implementation of molecularly targeted therapies against EZH2 requires a greater understanding of the potential mechanisms by which EZH2 contributes to cancer. One aspect of this effort is the mapping of EZH2 partner proteins and cellular targets. To this end we performed affinity-purification mass spectrometry in the FAB-M2 HL-60 acute myeloid leukaemia (AML) cell line before and after all-trans retinoic acid-induced differentiation. These studies identified new EZH2 interaction partners and potential non-histone substrates for EZH2-mediated methylation. Our results suggest that EZH2 is involved in the regulation of translation through interactions with a number of RNA binding proteins and by methylating key components of protein synthesis such as eEF1A1. Given that deregulated mRNA translation is a frequent feature of cancer and that eEF1A1 is highly expressed in many human tumours, these findings present new possibilities for the therapeutic targeting of EZH2 in AML.}, language = {en} } @article{AdamDeimelPardoMedinaetal.2018, author = {Adam, Alexander and Deimel, Stephan and Pardo-Medina, Javier and Garc{\´i}a-Mart{\´i}nez, Jorge and Konte, Tilen and Lim{\´o}n, M. Carmen and Avalos, Javier and Terpitz, Ulrich}, title = {Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus-plant interaction}, series = {International Journal of Molecular Sciences}, volume = {19}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms19010215}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285125}, year = {2018}, abstract = {Fungi possess diverse photosensory proteins that allow them to perceive different light wavelengths and to adapt to changing light conditions in their environment. The biological and physiological roles of the green light-sensing rhodopsins in fungi are not yet resolved. The rice plant pathogen Fusarium fujikuroi exhibits two different rhodopsins, CarO and OpsA. CarO was previously characterized as a light-driven proton pump. We further analyzed the pumping behavior of CarO by patch-clamp experiments. Our data show that CarO pumping activity is strongly augmented in the presence of the plant hormone indole-3-acetic acid and in sodium acetate, in a dose-dependent manner under slightly acidic conditions. By contrast, under these and other tested conditions, the Neurospora rhodopsin (NR)-like rhodopsin OpsA did not exhibit any pump activity. Basic local alignment search tool (BLAST) searches in the genomes of ascomycetes revealed the occurrence of rhodopsin-encoding genes mainly in phyto-associated or phytopathogenic fungi, suggesting a possible correlation of the presence of rhodopsins with fungal ecology. In accordance, rice plants infected with a CarO-deficient F. fujikuroi strain showed more severe bakanae symptoms than the reference strain, indicating a potential role of the CarO rhodopsin in the regulation of plant infection by this fungus.}, language = {en} } @article{KaltdorfSchulzeHelmprobstetal.2017, author = {Kaltdorf, Kristin Verena and Schulze, Katja and Helmprobst, Frederik and Kollmannsberger, Philip and Dandekar, Thomas and Stigloher, Christian}, title = {Fiji macro 3D ART VeSElecT: 3D automated reconstruction tool for vesicle structures of electron tomograms}, series = {PLoS Computational Biology}, volume = {13}, journal = {PLoS Computational Biology}, number = {1}, doi = {10.1371/journal.pcbi.1005317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172112}, year = {2017}, abstract = {Automatic image reconstruction is critical to cope with steadily increasing data from advanced microscopy. We describe here the Fiji macro 3D ART VeSElecT which we developed to study synaptic vesicles in electron tomograms. We apply this tool to quantify vesicle properties (i) in embryonic Danio rerio 4 and 8 days past fertilization (dpf) and (ii) to compare Caenorhabditis elegans N2 neuromuscular junctions (NMJ) wild-type and its septin mutant (unc-59(e261)). We demonstrate development-specific and mutant-specific changes in synaptic vesicle pools in both models. We confirm the functionality of our macro by applying our 3D ART VeSElecT on zebrafish NMJ showing smaller vesicles in 8 dpf embryos then 4 dpf, which was validated by manual reconstruction of the vesicle pool. Furthermore, we analyze the impact of C. elegans septin mutant unc-59(e261) on vesicle pool formation and vesicle size. Automated vesicle registration and characterization was implemented in Fiji as two macros (registration and measurement). This flexible arrangement allows in particular reducing false positives by an optional manual revision step. Preprocessing and contrast enhancement work on image-stacks of 1nm/pixel in x and y direction. Semi-automated cell selection was integrated. 3D ART VeSElecT removes interfering components, detects vesicles by 3D segmentation and calculates vesicle volume and diameter (spherical approximation, inner/outer diameter). Results are collected in color using the RoiManager plugin including the possibility of manual removal of non-matching confounder vesicles. Detailed evaluation considered performance (detected vesicles) and specificity (true vesicles) as well as precision and recall. We furthermore show gain in segmentation and morphological filtering compared to learning based methods and a large time gain compared to manual segmentation. 3D ART VeSElecT shows small error rates and its speed gain can be up to 68 times faster in comparison to manual annotation. Both automatic and semi-automatic modes are explained including a tutorial.}, language = {en} } @article{FlorenHorchlerMueller2022, author = {Floren, Andreas and Horchler, Peter J. and M{\"u}ller, Tobias}, title = {The impact of the neophyte tree Fraxinus pennsylvanica [Marshall] on beetle diversity under climate change}, series = {Sustainability}, volume = {14}, journal = {Sustainability}, number = {3}, issn = {2071-1050}, doi = {10.3390/su14031914}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262223}, year = {2022}, abstract = {We studied the impact of the neophyte tree Fraxinus pennsylvanica on the diversity of beetles in floodplain forests along the river Elbe in Germany in 2016, 2017 and in 2020, where 80\% of all Fraxinus excelsior trees had died following severe droughts. Beetles were collected by insecticidal knock-down from 121 trees (64 F. excelsior and 57 F. pennsylvanica) and identified to 547 species in 15,214 specimens. The trees sampled in 2016 and 2017 showed no signs of drought stress or ash dieback and serve as a reference for the comparison with the 2020 fauna. The data proved that F. excelsior harbours the most diverse beetle community, which differed also significantly in guild composition from F. pennsylvanica. Triggered by extremely dry and long summer seasons, the 2020 ash dieback had profound and forest-wide impacts. Several endangered, red-listed beetle species of Saxonia Anhalt had increased in numbers and became secondary pests on F. excelsior. Diversity decreased whilst numbers of xylobionts increased on all trees, reaching 78\% on F. excelsior. Proportions of xylobionts remained constant on F. pennsylvanica. Phytophages were almost absent from all trees, but mycetophages increased on F. pennsylvanica. Our data suggest that as a result of the dieback of F. excelsior the neophyte F. pennsylvanica might become a rescue species for the European Ash fauna, as it provides the second-best habitat. We show how difficult it is to assess the dynamics and the ecological impact of neophytes, especially under conditions similar to those projected by climate change models. The diversity and abundance of canopy arthropods demonstrates their importance in understanding forest functions and maintenance of ecosystem services, illustrating that their consideration is essential for forest adaptation to climate change.}, 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{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{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{LiangRiosMiguelJaricketal.2021, author = {Liang, Chunguang and Rios-Miguel, Ana B. and Jarick, Marcel and Neurgaonkar, Priya and Girard, Myriam and Fran{\c{c}}ois, Patrice and Schrenzel, Jacques and Ibrahim, Eslam S. and Ohlsen, Knut and Dandekar, Thomas}, title = {Staphylococcus aureus transcriptome data and metabolic modelling investigate the interplay of Ser/Thr kinase PknB, its phosphatase Stp, the glmR/yvcK regulon and the cdaA operon for metabolic adaptation}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {10}, issn = {2076-2607}, doi = {10.3390/microorganisms9102148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248459}, year = {2021}, abstract = {Serine/threonine kinase PknB and its corresponding phosphatase Stp are important regulators of many cell functions in the pathogen S. aureus. Genome-scale gene expression data of S. aureus strain NewHG (sigB\(^+\)) elucidated their effect on physiological functions. Moreover, metabolic modelling from these data inferred metabolic adaptations. We compared wild-type to deletion strains lacking pknB, stp or both. Ser/Thr phosphorylation of target proteins by PknB switched amino acid catabolism off and gluconeogenesis on to provide the cell with sufficient components. We revealed a significant impact of PknB and Stp on peptidoglycan, nucleotide and aromatic amino acid synthesis, as well as catabolism involving aspartate transaminase. Moreover, pyrimidine synthesis was dramatically impaired by stp deletion but only slightly by functional loss of PknB. In double knockouts, higher activity concerned genes involved in peptidoglycan, purine and aromatic amino acid synthesis from glucose but lower activity of pyrimidine synthesis from glucose compared to the wild type. A second transcriptome dataset from S. aureus NCTC 8325 (sigB\(^-\)) validated the predictions. For this metabolic adaptation, PknB was found to interact with CdaA and the yvcK/glmR regulon. The involved GlmR structure and the GlmS riboswitch were modelled. Furthermore, PknB phosphorylation lowered the expression of many virulence factors, and the study shed light on S. aureus infection processes.}, 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{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{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{WagnerSlaghuisGoebeletal.2021, author = {Wagner, Martin and Slaghuis, J{\"o}rg and G{\"o}bel, Werner and V{\´a}zquez-Boland, Jos{\´e} Antonio and Rychli, Kathrin and Schmitz-Esser, Stephan}, title = {Virulence pattern analysis of three Listeria monocytogenes lineage I epidemic strains with distinct outbreak histories}, series = {Microorganisms}, volume = {9}, journal = {Microorganisms}, number = {8}, issn = {2076-2607}, doi = {10.3390/microorganisms9081745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245093}, year = {2021}, abstract = {Strains of the food-borne pathogen Listeria (L.) monocytogenes have diverse virulence potential. This study focused on the virulence of three outbreak strains: the CC1 strain PF49 (serovar 4b) from a cheese-associated outbreak in Switzerland, the clinical CC2 strain F80594 (serovar 4b), and strain G6006 (CC3, serovar 1/2a), responsible for a large gastroenteritis outbreak in the USA due to chocolate milk. We analysed the genomes and characterized the virulence in vitro and in vivo. Whole-genome sequencing revealed a high conservation of the major virulence genes. Minor deviations of the gene contents were found in the autolysins Ami, Auto, and IspC. Moreover, different ActA variants were present. Strain PF49 and F80594 showed prolonged survival in the liver of infected mice. Invasion and intracellular proliferation were similar for all strains, but the CC1 and CC2 strains showed increased spreading in intestinal epithelial Caco2 cells compared to strain G6006. Overall, this study revealed long-term survival of serovar 4b strains F80594 and PF49 in the liver of mice. Future work will be needed to determine the genes and molecular mechanism behind the long-term survival of L. monocytogenes strains in organs.}, language = {en} } @article{IsaacsMikasiObasaetal.2020, author = {Isaacs, Darren and Mikasi, Sello Given and Obasa, Adetayo Emmanuel and Ikomey, George Mondinde and Shityakov, Sergey and Cloete, Ruben and Jacobs, Graeme Brendon}, title = {Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors}, series = {Viruses}, volume = {12}, journal = {Viruses}, number = {9}, issn = {1999-4915}, doi = {10.3390/v12090936}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211170}, year = {2020}, abstract = {The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-na{\"i}ve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.}, language = {en} } @article{DitzelKoenigMusembietal.2022, author = {Ditzel, Pia and K{\"o}nig, Sebastian and Musembi, Peter and Peters, Marcell K.}, title = {Correlation between coral reef condition and the diversity and abundance of fishes and sea urchins on an East African coral reef}, series = {Oceans}, volume = {3}, journal = {Oceans}, number = {1}, issn = {2673-1924}, doi = {10.3390/oceans3010001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284503}, pages = {1 -- 14}, year = {2022}, abstract = {Coral reefs are one of the most diverse marine ecosystems, providing numerous ecosystem services. This present study investigated the relationship between coral reef condition and the diversity and abundance of fishes, on a heavily fished East African coral reef at Gazi Bay, Kenya. Underwater visual censuses were conducted on thirty 50 × 5 m belt transects to assess the abundance and diversity of fishes. In parallel, a 25-m length of each of the same transects was recorded with photo-quadrats to assess coral community structure and benthic characteristics. For statistical analyses, multi-model inference based on the Akaike Information Criterion was used to evaluate the support for potential predictor variables of coral reef and fish diversity. We found that coral genus richness was negatively correlated with the abundance of macroalgae, whereas coral cover was positively correlated with both the abundance of herbivorous invertebrates (sea urchins) and with fish family richness. Similarly, fish family richness appeared mainly correlated with coral cover and invertebrate abundance, although no correlates of fish abundance could be identified. Coral and fish diversity were very low, but it appears that, contrary to some locations on the same coast, sea urchin abundance was not high enough to be having a negative influence on coral and fish assemblages. Due to increasing threats to coral reefs, it is important to understand the relationship among the components of the coral reef ecosystem on overfished reefs such as that at Gazi Bay.}, language = {en} }