TY - JOUR A1 - Beetz, M. Jerome A1 - Kraus, Christian A1 - el Jundi, Basil T1 - Neural representation of goal direction in the monarch butterfly brain JF - Nature Communications N2 - 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. KW - animal behaviour KW - navigation KW - neuroscience Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358073 VL - 14 ER - TY - JOUR A1 - Dhillon, Maninder Singh A1 - Dahms, Thorsten A1 - Kübert-Flock, Carina A1 - Liepa, Adomas A1 - Rummler, Thomas A1 - Arnault, Joel A1 - Steffan-Dewenter, Ingolf A1 - Ullmann, Tobias T1 - Impact of STARFM on crop yield predictions: fusing MODIS with Landsat 5, 7, and 8 NDVIs in Bavaria Germany JF - Remote Sensing N2 - 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. KW - MOD13Q1 KW - precision agriculture KW - fusion KW - sustainable agriculture KW - decision making KW - winter wheat KW - oil-seed rape KW - crop models Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311092 SN - 2072-4292 VL - 15 IS - 6 ER - TY - JOUR A1 - Brenner, Daniela A1 - Geiger, Nina A1 - Schlegel, Jan A1 - Diesendorf, Viktoria A1 - Kersting, Louise A1 - Fink, Julian A1 - Stelz, Linda A1 - Schneider-Schaulies, Sibylle A1 - Sauer, Markus A1 - Bodem, Jochen A1 - Seibel, Jürgen T1 - Azido-ceramides, a tool to analyse SARS-CoV-2 replication and inhibition — SARS-CoV-2 is inhibited by ceramides JF - International Journal of Molecular Sciences N2 - 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. KW - ceramides KW - SARS-CoV-2 KW - azido-ceramides KW - sphingolipids Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313581 SN - 1422-0067 VL - 24 IS - 8 ER - TY - JOUR A1 - Frank, Erik T. A1 - Kesner, Lucie A1 - Liberti, Joanito A1 - Helleu, Quentin A1 - LeBoeuf, Adria C. A1 - Dascalu, Andrei A1 - Sponsler, Douglas B. A1 - Azuma, Fumika A1 - Economo, Evan P. A1 - Waridel, Patrice A1 - Engel, Philipp A1 - Schmitt, Thomas A1 - Keller, Laurent T1 - Targeted treatment of injured nestmates with antimicrobial compounds in an ant society JF - Nature Communications N2 - 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. KW - animal behaviour KW - chemical ecology KW - entomology KW - microbial ecology KW - proteomics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358081 VL - 14 ER - TY - JOUR A1 - Kárpáti, Zsolt A1 - Deutsch, Ferenc A1 - Kiss, Balázs A1 - Schmitt, Thomas T1 - Seasonal changes in photoperiod and temperature lead to changes in cuticular hydrocarbon profiles and affect mating success in Drosophila suzukii JF - Scientific Reports N2 - 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. KW - ecology KW - zoology Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358095 VL - 13 ER - TY - JOUR A1 - Wu, Hao A1 - Zhao, Xiufeng A1 - Hochrein, Sophia M. A1 - Eckstein, Miriam A1 - Gubert, Gabriela F. A1 - Knöpper, Konrad A1 - Mansilla, Ana Maria A1 - Öner, Arman A1 - Doucet-Ladevèze, Remi A1 - Schmitz, Werner A1 - Ghesquière, Bart A1 - Theurich, Sebastian A1 - Dudek, Jan A1 - Gasteiger, Georg A1 - Zernecke, Alma A1 - Kobold, Sebastian A1 - Kastenmüller, Wolfgang A1 - Vaeth, Martin T1 - Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming JF - Nature Communications N2 - 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. KW - cytotoxic T cells KW - infection KW - lymphocyte differentiation KW - translational research Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-358052 VL - 14 ER - TY - JOUR A1 - Caliskan, Aylin A1 - Caliskan, Deniz A1 - Rasbach, Lauritz A1 - Yu, Weimeng A1 - Dandekar, Thomas A1 - Breitenbach, Tim T1 - Optimized cell type signatures revealed from single-cell data by combining principal feature analysis, mutual information, and machine learning JF - Computational and Structural Biotechnology Journal N2 - 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. KW - single cell analysis KW - machine learning KW - explainability of machine learning KW - principal KW - feature analysis KW - model reduction KW - feature selection Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349989 SN - 2001-0370 VL - 21 ER - TY - JOUR A1 - Caliskan, Aylin A1 - Dangwal, Seema A1 - Dandekar, Thomas T1 - Metadata integrity in bioinformatics: bridging the gap between data and knowledge JF - Computational and Structural Biotechnology Journal N2 - 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. KW - meta-data KW - error KW - annotation KW - error-transfer KW - wrong labelling KW - patient data KW - control group KW - tools overview Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349990 SN - 2001-0370 VL - 21 ER - TY - JOUR A1 - Däullary, Thomas A1 - Imdahl, Fabian A1 - Dietrich, Oliver A1 - Hepp, Laura A1 - Krammer, Tobias A1 - Fey, Christina A1 - Neuhaus, Winfried A1 - Metzger, Marco A1 - Vogel, Jörg A1 - Westermann, Alexander J. A1 - Saliba, Antoine-Emmanuel A1 - Zdzieblo, Daniela T1 - A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection JF - Gut Microbes N2 - 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. KW - intestinal enteroids KW - biological scaffold KW - Salmonella Typhimurium KW - OLFM4 KW - NOTCH KW - filamentous Salmonella Typhimurium KW - bacterial migration KW - bacterial virulence KW - 3D tissue model KW - olfactomedin 4 KW - infection Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350451 VL - 15 IS - 1 ER - TY - JOUR A1 - Engstler, Markus A1 - Beneke, Tom T1 - Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit JF - eLife N2 - 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. KW - CRISPR/Cas9 KW - Leishmania KW - cytosine base editor (CBE) toolbox KW - gene editing KW - scalable functional genomic screening KW - LeishBASEedit Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-350002 VL - 12 ER -