TY - JOUR A1 - Uhler, Johannes A1 - Haase, Peter A1 - Hoffmann, Lara A1 - Hothorn, Torsten A1 - Schmidl, Jürgen A1 - Stoll, Stefan A1 - Welti, Ellen A. R. A1 - Buse, Jörn A1 - Müller, Jörg T1 - A comparison of different Malaise trap types JF - Insect Conservation and Diversity N2 - 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. KW - Bartak KW - biodiversity KW - insect communities KW - insect monitoring KW - Malaise trap KW - Townes KW - trap selectivity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293694 VL - 15 IS - 6 SP - 666 EP - 672 ER - TY - JOUR A1 - Fricke, Ute A1 - Redlich, Sarah A1 - Zhang, Jie A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Riebl, Rebekka A1 - Rojas‐Botero, Sandra A1 - Tobisch, Cynthia A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Steffan‐Dewenter, Ingolf T1 - Earlier flowering of winter oilseed rape compensates for higher pest pressure in warmer climates JF - Journal of Applied Ecology N2 - 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. KW - canola KW - climate‐smart pest management KW - crop rotation KW - global warming KW - oilseed rape KW - pollen beetle KW - seed yield KW - stem weevil Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312562 VL - 60 IS - 2 SP - 365 EP - 375 ER - TY - JOUR A1 - Lasway, Julius V. A1 - Peters, Marcell K. A1 - Njovu, Henry K. A1 - Eardley, Connal A1 - Pauly, Alain A1 - Steffan‐Dewenter, Ingolf T1 - Agricultural intensification with seasonal fallow land promotes high bee diversity in Afrotropical drylands JF - Journal of Applied Ecology N2 - 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. KW - bee abundance KW - bee body size KW - bee species richness KW - forage resources KW - inter‐tegular distance KW - mean annual temperature KW - northern Tanzania KW - species community composition Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311877 VL - 59 IS - 12 SP - 3014 EP - 3026 ER - TY - JOUR A1 - Gebert, Friederike A1 - Steffan‐Dewenter, Ingolf A1 - Kronbach, Patrick A1 - Peters, Marcell K. T1 - The role of diversity, body size and climate in dung removal: A correlative and experimental approach JF - Journal of Animal Ecology N2 - 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. KW - altitudinal gradients KW - biodiversity–ecosystem functioning relationship KW - body size KW - diversity gradients KW - ecosystem services KW - land use KW - Scarabaeidae KW - temperature Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293907 VL - 91 IS - 11 SP - 2181 EP - 2191 ER - TY - THES A1 - Schwarz, Jessica Denise T1 - Genome-wide reporter screens identify transcriptional regulators of ribosome biogenesis T1 - Genomweite Reporterscreens identifizieren transkriptionelle Regulatoren ribosomaler Biogenese N2 - Cellular growth and proliferation are among the most important processes for cells and organisms. One of the major determinants of these processes is the amount of proteins and consequently also the amount of ribosomes. Their synthesis involves several hundred proteins and four different ribosomal RNA species, is highly coordinated and very energy-demanding. However, the molecular mechanims of transcriptional regulation of the protein-coding genes involved, is only poorly understood in mammals. In this thesis, unbiased genome-wide knockout reporter screens were performed, aiming to identify previously unknown transcriptional regulators of ribosome biogenesis factors (RiBis), which are important for the assembly and maturation of ribosomes, and ribosomal proteins (RPs), which are ribosomal components themself. With that approach and follow-up (validation) experiments, ALDOA and RBM8A among others, could be identified as regulators of ribosome biogenesis. Depletion of the glycolytic enzyme ALDOA led to a downregulation of RiBi- and RPpromoter driven reporters on protein and transcript level, as well as to a downregulation of ribosome biogenesis gene transcripts and of mRNAs of other genes important for proliferation. Reducing the amount of the exon junction complex protein RBM8A, led to a more prominent downregulation of one of the fluorescent reporters, but this regulation was independent of the promoter driving the expression of the reporter. However, acute protein depletion experiments in combination with nascent RNA sequencing (4sU-Seq) revealed, that mainly cytosolic ribosomal proteins (CRPs) were downregulated upon acute RBM8A withdrawal. ChIP experiments showed RBM8A binding to promoters of RP genes, but also to other chromatin regions. Total POL II or elongating and initiating POL II levels were not altered upon acute RBM8A depletion. These data provide a starting point for further research on the mechanisms of transcriptional regulation of RP and RiBi genes in mammals. N2 - Zelluläres Wachstum und Proliferation zählen zu den wichtigsten Prozessen für Zellen und Organismen. Eine der größten Determinanten dieser Prozesse ist die Menge an Proteinen und in der Konsequenz auch die Menge an Ribosomen. Deren Synthese erfordert mehrere hundert Proteine und vier verschiedene ribosomale RNA-Spezies, ist stark koordiniert und sehr energiefordernd. Dennoch sind die molekularen Mechanismen der transkriptionellen Regulation der beteiligten protein-kodierenden Gene in Säugetieren nur schlecht verstanden. In dieser Arbeit wurden hypothesenfreie genomweite Knockout-Reporterscreens mit dem Ziel durchgeführt, bisher unbekannte transkriptionelle Regulatoren von ribosomalen Biogenesefaktoren (RiBis), welche wichtig für den Zusammenbau und die Reifung der Ribosomen sind, und ribosomalen Proteinen (RPs), welche selbst ribosomale Bestandteile sind, zu identifizieren. Durch diesen Ansatz und nachfolgende (Validierungs- )Experimente, konnten unter anderem ALDOA und RBM8A als Regulatoren ribosomaler Biogenese identifiziert werden. Eine Depletion des glykolytischen Enzyms ALDOA führte sowohl zu einer Herunterregulation von RiBi- und RP-Promotor-gesteuerten Reportern auf Protein- und Transkriptebene, als auch zu einer Herunterregulation von ribosomalen Biogenesegentranskripten und von mRNAs anderer für die Proliferation wichtiger Gene. Eine Reduktion der Menge des Exon-Junction-Komplexproteins RBM8A führte zu einer deutlicheren Herunterregulation eines der beiden fluoreszierenden Reporter, aber diese Regulation war unabhängig vom Promotor, der die Expression des Reporters steuert. Akute Proteinabbauexperimente in Verbindung mit einer Sequenzierung naszenter RNA (4sU-Seq) zeigten allerdings, dass hauptsächlich zytosolische ribosomale Proteine (CRPs) nach akuter RBM8A-Depletion herunterreguliert waren. ChIP-Experimente zeigten RBM8A-Bindung an Promotoren von RP-Genen, aber auch an andere Chromatinregionen. Gesamt-POL II- oder elongierende und initiierende POL II-Mengen waren nach akuter RBM8A-Depletion nicht verändert. Diese Daten stellen einen Ausgangspunkt für weitere Forschung zu den Mechanismen transkriptioneller Regulation von RP- und RiBi-Genen in Säugetieren dar. KW - Ribosom KW - Fructosebisphosphat-Aldolase KW - Transkription KW - Genregulation KW - ribosome biogenesis KW - Rbm8a KW - genetic screen KW - reporter screen Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-279010 ER - TY - JOUR A1 - Kerner, Janika M. A1 - Krauss, Jochen A1 - Maihoff, Fabienne A1 - Bofinger, Lukas A1 - Classen, Alice T1 - Alpine butterflies want to fly high: Species and communities shift upwards faster than their host plants JF - Ecology N2 - 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. KW - Alps KW - altitudinal gradient KW - global warming KW - grazing KW - Lepidoptera KW - mountain biodiversity KW - plant–herbivore interactions KW - species range shifts KW - upslope shift Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312015 VL - 104 IS - 1 ER - TY - JOUR A1 - Sponsler, Douglas B. A1 - Requier, Fabrice A1 - Kallnik, Katharina A1 - Classen, Alice A1 - Maihoff, Fabienne A1 - Sieger, Johanna A1 - Steffan‐Dewenter, Ingolf T1 - Contrasting patterns of richness, abundance, and turnover in mountain bumble bees and their floral hosts JF - Ecology N2 - 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. KW - alpine plants KW - climate KW - elevation gradient KW - mountain ecology KW - pollination network Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287199 VL - 103 IS - 7 ER - TY - JOUR A1 - Kortmann, Mareike A1 - Roth, Nicolas A1 - Buse, Jörn A1 - Hilszczański, Jacek A1 - Jaworski, Tomasz A1 - Morinière, Jérôme A1 - Seidl, Rupert A1 - Thorn, Simon A1 - Müller, Jörg C. T1 - Arthropod dark taxa provide new insights into diversity responses to bark beetle infestations JF - Ecological Applications N2 - 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. KW - arthropods KW - biodiversity KW - conservation KW - metabarcoding KW - national park KW - natural disturbance KW - threshold indicator taxa analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276392 VL - 32 IS - 2 ER - TY - JOUR A1 - Fofanov, Mikhail V. A1 - Prokopov, Dmitry Yu. A1 - Kuhl, Heiner A1 - Schartl, Manfred A1 - Trifonov, Vladimir A. T1 - Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates JF - International Journal of Molecular Sciences N2 - 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. KW - sturgeon KW - whole genome duplication KW - microRNA KW - gene duplications Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285230 SN - 1422-0067 VL - 21 IS - 24 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Osmanoğlu, Özge A1 - Kaltdorf, Martin A1 - Alblooshi, Afnan Ali M. A. A1 - Iqbal, Jibran A1 - Howari, Fares M. A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem JF - International Journal of Molecular Sciences N2 - 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. KW - defense signaling KW - shoot apical meristem KW - CLV3p KW - meta-transcriptome KW - system inference KW - stem-cell-triggered immunity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285730 SN - 1422-0067 VL - 21 IS - 16 ER - TY - JOUR A1 - Ranger, Christopher M. A1 - Biedermann, Peter HW A1 - Phuntumart, Vipaporn A1 - Beligala, Gayathri U. A1 - Ghosh, Satyaki A1 - Palmquist, Debra E. A1 - Mueller, Robert A1 - Barnett, Jenny A1 - Schultz, Peter B. A1 - Reding, Michael E. A1 - Benz, J. Philipp T1 - Symbiont selection via alcohol benefits fungus farming by ambrosia beetles JF - Proceedings of the National Academy of Sciences N2 - 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. KW - fungus-farming insects KW - plant-insect-microbe interactions KW - symbiosis KW - insect-fungus mutualism KW - host screening Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224953 VL - 115 IS - 17 ER - TY - JOUR A1 - Stojanović, Stevan D. A1 - Fuchs, Maximilian A1 - Fiedler, Jan A1 - Xiao, Ke A1 - Meinecke, Anna A1 - Just, Annette A1 - Pich, Andreas A1 - Thum, Thomas A1 - Kunz, Meik T1 - Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts JF - International Journal of Molecular Sciences N2 - 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. KW - bioinformatics KW - miR KW - proteomics KW - functional network analysis KW - senescence KW - lung fibrosis KW - autophagy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285181 SN - 1422-0067 VL - 21 IS - 11 ER - TY - JOUR A1 - Doll, Julia A1 - Kolb, Susanne A1 - Schnapp, Linda A1 - Rad, Aboulfazl A1 - Rüschendorf, Franz A1 - Khan, Imran A1 - Adli, Abolfazl A1 - Hasanzadeh, Atefeh A1 - Liedtke, Daniel A1 - Knaup, Sabine A1 - Hofrichter, Michaela AH A1 - Müller, Tobias A1 - Dittrich, Marcus A1 - Kong, Il-Keun A1 - Kim, Hyung-Goo A1 - Haaf, Thomas A1 - Vona, Barbara T1 - Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients JF - International Journal of Molecular Sciences N2 - 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. KW - CDC14A KW - DFNB32 KW - autosomal recessive hearing loss KW - exome sequencing KW - splicing KW - frameshift KW - non-sense mediated mRNA decay Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285142 SN - 1422-0067 VL - 21 IS - 1 ER - TY - JOUR A1 - Breitenbach, Tim A1 - Lorenz, Kristina A1 - Dandekar, Thomas T1 - How to steer and control ERK and the ERK signaling cascade exemplified by looking at cardiac insufficiency JF - International Journal of Molecular Sciences N2 - 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. KW - optimal pharmacological modulation KW - efficient intervention points KW - ERK signaling KW - optimal treatment strategies KW - optimal drug targeting KW - optimal drug combination Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285164 SN - 1422-0067 VL - 20 IS - 9 ER - TY - JOUR A1 - Batzke, Katharina A1 - Büchel, Gabriele A1 - Hansen, Wiebke A1 - Schramm, Alexander T1 - TrkB-target Galectin-1 impairs immune activation and radiation responses in neuroblastoma: implications for tumour therapy JF - International Journal of Molecular Sciences N2 - 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. KW - Galectin-1 KW - radiation response KW - neuroblastoma Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285097 SN - 1422-0067 VL - 19 IS - 3 ER - TY - THES A1 - Kaya-Zeeb, Sinan David T1 - Octopaminergic Signaling in the Honeybee Flight Muscles : A Requirement for Thermogenesis T1 - Octopaminerge Signalwege in der Flugmuskulatur der Honigbiene : Eine Voraussetzung für die Thermogenese N2 - For all animals the cold represents a dreadful danger. In the event of severe heat loss, animals fall into a chill coma. If this state persists, it is inevitably followed by death. In poikilotherms (e.g. insects), the optimal temperature range is narrow compared to homeotherms (e.g. mammals), resulting in a critical core temperature being reached more quickly. As a consequence, poikilotherms either had to develop survival strategies, migrate or die. Unlike the majority of insects, the Western honeybee (Apis mellifera) is able to organize itself into a superorganism. In this process, worker bees warm and cool the colony by coordinated use of their flight muscles. This enables precise control of the core temperature in the hive, analogous to the core body temperature in homeothermic animals. However, to survive the harsh temperatures in the northern hemisphere, the thermogenic mechanism of honeybees must be in constant readiness. This mechanism is called shivering thermogenesis, in which honeybees generate heat using their flight muscles. My thesis presents the molecular and neurochemical background underlying shivering thermogenesis in worker honeybees. In this context, I investigated biogenic amine signaling. I found that the depletion of vesicular monoamines impairs thermogenesis, resulting in a decrease in thoracic temperature. Subsequent investigations involving various biogenic amines showed that octopamine can reverse this effect. This clearly indicates the involvement of the octopaminergic system. Proceeding from these results, the next step was to elucidate the honeybee thoracic octopaminergic system. This required a multidisciplinary approach to ultimately provide profound insights into the function and action of octopamine at the flight muscles. This led to the identification of octopaminergic flight muscle controlling neurons, which presumably transport octopamine to the flight muscle release sites. These neurons most likely innervate octopamine β receptors and their activation may stimulate intracellular glycolytic pathways, which ensure sufficient energy supply to the muscles. Next, I examined the response of the thoracic octopaminergic system to cold stress conditions. I found that the thoracic octopaminergic system tends towards an equilibrium, even though the initial stress response leads to fluctuations of octopamine signaling. My results indicate the importance of the neuro-muscular octopaminergic system and thus the need for its robustness. Moreover, cold sensitivity was observed for the expression of one transcript of the octopamine receptor gene AmOARβ2. Furthermore, I found that honeybees without colony context show a physiological disruption within the octopaminergic system. This disruption has profound effects on the honeybees protection against the cold. I could show how important the neuro-muscular octopaminergic system is for thermogenesis in honeybees. In this context, the previously unknown neurochemical modulation of the honeybee thorax has now been revealed. I also provide a broad basis to conduct further experiments regarding honeybee thermogenesis and muscle physiology. N2 - Kälte stellt für alle Tiere eine lebensbedrohliche Situation dar. Erleiden sie einen schwerwiegenden Wärmeverlust, stellt sich der Zustand eines Kältekomas ein. Hält dieser Zustand über einen längeren Zeitraum an, folgt unweigerlich der Tod. Poikilotherme (z.B. Insekten) weisen ein schmaleres optimales Temperaturfenster als Homoiotherme (z.B. Säugetiere) auf, wodurch sie ihre kritische Körpertemperatur schneller erreichen. Dadurch waren Poikilotherme gezwungen entweder Überlebenstrategien zu entwickeln, abzuwandern oder zu sterben. Im Gegensatz zu den meisten anderen Insektenarten, ist die Westliche Honigbiene Apis mellifera in der Lage einen Superorganismus zu bilden, in dem Arbeiterbienen durch den koordinierten Einsatz ihrer Flugmuskeln für Erwärmung oder Abkühlung sorgen. In Analogie zur Körpertemperatur von Homoiothermen, ermöglicht dies die exakte Kontrolle der Kerntemperatur des Bienenstocks. Um unter den rauen Bedingungen in der nördlichen Hemisphäre bestehen zu können, muss eine ununterbrochene Einsatzbereitschaft des thermogenen Mechanismus der Honigbiene garantiert werden. Dabei ist die Honigbiene in der Lage durch Zittern der Flugmuskulatur Wärme zu erzeugen. In dieser Dissertation stelle ich die molekularen und neurochemischen Grundlagen des thermogenen Muskelzitterns bei Honigbienenarbeiterinnen vor. In diesem Zusammenhang habe ich die Signalwege von verschiedenen biogenen Aminen untersucht und konnte demonstrieren, dass eine Erschöpfung vesikulärer Monoamine den Prozess der Thermogenese beeinflusst und zu einem Absinken der Thoraxtemperatur führt. Unter Einbeziehung veschiedener biogener Amine, konnten Folgeuntersuchungen zeigen, dass dieser Effekt durch Octopamin rückgängig gemacht werden kann. Dies weist eindeutig auf eine Beteiligung des octopaminergen Systems hin. Auf Basis dieser Erkenntnisse folgte die Erforschung des thorakalen octopaminergen Systems der Honigbiene. Dabei erforderte es einen multidisziplinären Ansatz, um weitere Einblicke in die Funktion und Wirkung von Octopamin in der Flugmuskulatur zu gewinnen. Im Zuge dessen, konnten flugmuskelinnervierende octopaminerge Neuronen identifiziert werden, die mutmaßlich die Flugmuskeln mit Octopamin versorgen. Es sind höchstwahrscheinlich diese Neuronen, die für eine Stimulation von Octopamin-β-Rezeptoren verantwortlich sind und wordurch intrazelluläre glykolytische Prozesse eine ausreichende Muskelversorgung gewährleisten. In den darauffolgenden Experimenten habe ich das Ansprechen des thorakalen octopaminergen Systems auf Kältestress untersucht und konnte zeigen, dass dieses System nach einem Gleichgewichtszustand strebt. Dies trifft selbst nach einer starken initialen Stressantwort zu. Meine Ergebnisse verdeutlichen die Bedeutsamkeit des neuromuskulären octopaminergen Systems und zeigen seine erforderliche Resilienz gegenüber exogenen Faktoren. Es konnte die Kälteempfindlichkeit eines Transkriptes des Octopaminrezeptorgens AmOARβ2 nachgewiesen werden. Zusätzlich konnte ich zeigen, dass Honigbienen ohne den sozialen Kontext der Kolonie eine starke physiologische Störung innerhalb des untersuchten Systems und damit auch in Bezug auf ihre Kälteresilienz aufweisen. Meine Dissertation verdeutlicht die enorme Bedeutung des neuromuskulären octopaminergen Systems im Kontext der Thermogenese im Organismus Honigbiene. In diesem Rahmen konnte die bisher unerforschte neurochemische Modulation des Honigbienenthorax aufgeklärt werden. Darüber hinaus bietet meine Arbeit eine Grundlage für künftige Experimente zur Thermogenese und Muskelphysiologie der Honigbiene. KW - Octopamin KW - Biene KW - Octopamine KW - Thermogenesis KW - Honeybee KW - Octopaminergic signaling KW - Flight muscle Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314089 ER - TY - JOUR A1 - Sbirkov, Yordan A1 - Kwok, Colin A1 - Bhamra, Amandeep A1 - Thompson, Andrew J. A1 - Gil, Veronica A1 - Zelent, Arthur A1 - Petrie, Kevin T1 - Semi-quantitative mass spectrometry in AML cells identifies new non-genomic targets of the EZH2 methyltransferase JF - International Journal of Molecular Sciences N2 - 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. KW - acute myeloid leukaemia KW - EZH2 KW - mass spectrometry KW - methylation KW - eEF1A1 Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285541 SN - 1422-0067 VL - 18 IS - 7 ER - TY - JOUR A1 - Adam, Alexander A1 - Deimel, Stephan A1 - Pardo-Medina, Javier A1 - García-Martínez, Jorge A1 - Konte, Tilen A1 - Limón, M. Carmen A1 - Avalos, Javier A1 - Terpitz, Ulrich T1 - Protein activity of the \(Fusarium\) \(fujikuroi\) rhodopsins CarO and OpsA and their relation to fungus−plant interaction JF - International Journal of Molecular Sciences N2 - 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. KW - fungal rhodopsins KW - CarO KW - OpsA KW - Fusarium fujikuroi KW - Oryza sativa KW - rice–plant infection KW - green light perception KW - indole-3-acetic acid (IAA) KW - bakanae KW - patch-clamp Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285125 SN - 1422-0067 VL - 19 IS - 1 ER - TY - THES A1 - Reinhard, Sebastian T1 - Improving Super-Resolution Microscopy Data Reconstruction and Evaluation by Developing Advanced Processing Algorithms and Artifcial Neuronal Networks T1 - Verbesserung von Datenrekonstruktion und -auswertung in der Super-Resolution Mikroskopie durch die Entwicklung von fortgeschrittenen Verarbeitungsalgorithmen und künstlichen neuronalen Netzen N2 - The fusion of methods from several disciplines is a crucial component of scientific development. Artificial Neural Networks, based on the principle of biological neuronal networks, demonstrate how nature provides the best templates for technological advancement. These innovations can then be employed to solve the remaining mysteries of biology, including, in particular, processes that take place on microscopic scales and can only be studied with sophisticated techniques. For instance, direct Stochastic Optical Reconstruction Microscopy combines tools from chemistry, physics, and computer science to visualize biological processes at the molecular level. One of the key components is the computer-aided reconstruction of super-resolved images. Improving the corresponding algorithms increases the quality of the generated data, providing further insights into our biology. It is important, however, to ensure that the heavily processed images are still a reflection of reality and do not originate in random artefacts. Expansion microscopy is expanding the sample by embedding it in a swellable hydrogel. The method can be combined with other super-resolution techniques to gain additional resolution. We tested this approach on microtubules, a well-known filamentous reference structure, to evaluate the performance of different protocols and labelling techniques. We developed LineProfiler an objective tool for data collection. Instead of collecting perpendicular profiles in small areas, the software gathers line profiles from filamentous structures of the entire image. This improves data quantity, quality and prevents a biased choice of the evaluated regions. On the basis of the collected data, we deployed theoretical models of the expected intensity distribution across the filaments. This led to the conclusion that post-expansion labelling significantly reduces the labelling error and thus, improves the data quality. The software was further used to determine the expansion factor and arrangement of synaptonemal complex data. Automated Simple Elastix uses state-of-the-art image alignment to compare pre- and post-expansion images. It corrects linear distortions occurring under isotropic expansion, calculates a structural expansion factor and highlights structural mismatches in a distortion map. We used the software to evaluate expanded fungi and NK cells. We found that the expansion factor differs for the two structures and is lower than the overall expansion of the hydrogel. Assessing the fluorescence lifetime of emitters used for direct Stochastic Optical Reconstruction Microscopy can reveal additional information about the molecular environment or distinguish dyes emitting with a similar wavelength. The corresponding measurements require a confocal scanning of the sample in combination with the fluorescent switching of the underlying emitters. This leads to non-linear, interrupted Point Spread Functions. The software ReCSAI targets this problem by combining the classical algorithm of compressed sensing with modern methods of artificial intelligence. We evaluated several different approaches to combine these components and found, that unrolling compressed sensing into the network architecture yields the best performance in terms of reconstruction speed and accuracy. In addition to a deep insight into the functioning and learning of artificial intelligence in combination with classical algorithms, we were able to reconstruct the described non-linearities with significantly improved resolution, in comparison to other state-of-the-art architectures. N2 - Für die Weiterentwicklung der Wissenschaft wird es immer wichtiger, Methoden aus verschiedenen Gebieten zu kombinieren. Die künstliche Intelligenz beruht beispielsweise auf dem Prinzip biologischer neuronaler Netze. Hier wird die Natur als Vorlage für unsere technische Entwicklung genutzt. Diese Innovationen können dazu eingesetzt werden, die verbliebenen Rätsel der Biologie zu lösen. Dazu gehören insbesondere Prozesse, die sich auf mikroskopischer Ebene abspielen und nur mit hochentwickelten Techniken untersucht werden können. Die direkte Stochastisch Optische Rekonstruktionsmikroskopie kombiniert Methoden der Chemie, Physik und Informatik, um biologische Prozesse auf molekularer Ebene sichtbar zu machen. Eine der Schlüsselkomponenten ist die computergestützte Rekonstruktion von hochaufgelösten Bildern. Die Verbesserung der zugrunde liegenden Algorithmen erhöht die Qualität der erzeugten Daten und ermöglicht weitere Einblicke in unsere Biologie. Es muss jedoch sichergestellt werden, dass die künstlich erstellten Bilder immer noch ein Abbild der Realität sind und nicht auf zufälligen Artefakten beruhen. Expansionsmikroskopie vergrößert die Probe durch Einbettung in ein Hydrogel. Die Methode kann mit anderen hochauflösenden Techniken kombiniert werden, um die Auflösung noch weiter zu verbessern. Dieser Ansatz wurde an Mikrotubuli, einer bekannten flamentösen Referenzstruktur, verwendet, um verschiedene Protokolle und Markierungstechniken zu testen. Mit LineProfiler wurde ein objektives Werkzeug zur Datenerfassung entwickelt. Anstatt Linienprofle in kleinen Bereichen zu erfassen, wertet die Software das gesamte Bild aus. Dies verbessert die Datenmenge und Datenqualität und verhindert eine voreingenommene Auswahl der ausgewerteten Regionen. Auf Grundlage der gesammelten Daten wurden theoretische Modelle für die erwartete Intensitätsverteilung über die Filamente erstellt. Daraus konnte geschlossen werden, dass die Markierung nach der Expansion den Markierungsfehler erheblich reduziert und somit die Qualität der Daten verbessert. Die Software wurde außerdem zur Bestimmung des Expansionsfaktors und der Anordnung der Daten des synaptonemalen Komplexes verwendet. Automated Simple Elastix verwendet modernste Bildregistrierung, um Bilder vor und nach der Expansion zu vergleichen. Lineare Verzerrungen, die bei isotroper Expansion auftreten, werden korrigiert. Der strukturelle Expansionsfaktor wird berechnet und strukturelle Unstimmigkeiten werden in einer Verzerrungskarte hervorgehoben. Die Software wurde zur Bewertung expandierter Pilze und NK-Zellen eingesetzt. Dabei wurde festgestellt, dass der Expansionsfaktor für die beiden Strukturen unterschiedlich ist und unter der Gesamtexpansion des Hydrogels liegt. Die Auswertung der Fluoreszenzlebensdauer von Emittern, die für die direkte Stochastische Optische Rekonstruktionsmikroskopie eingesetzt werden, kann zusätzliche Informationen über die molekulare Umgebung liefern oder Farbstoffe unterscheiden, die VI eine ähnliche Lichtwellenlänge emittieren. Die entsprechenden Messungen erfordern eine konfokale Abtastung der Probe in Kombination mit dem fluoreszenten Schalten der zugrunde liegenden Emitter. Dies führt zu nichtlinearen, unterbrochenen Punktspreizfunktionen. Die Software ReCSAI löst dieses Problem, indem sie den klassischen Algorithmus des Compressed Sensing mit modernen Methoden der künstlichen Intelligenz kombiniert. Es wurden verschiedene Ansätze zur Kombination der Komponenten ausgewertet und festgestellt, dass die Integration von Compressed Sensing in die Netzwerkarchitektur die beste Performance in Bezug auf Rekonstruktionsgeschwindigkeit und -genauigkeit bringt. Neben einem tiefen Einblick in die Funktionsweise und das Lernen von künstlicher Intelligenz in Kombination mit klassischen Algorithmen konnten die beschriebenen Nichtlinearitäten mit einer deutlich verbesserten Auflösung im Vergleich zu anderen modernen Architekturen rekonstruiert werden. KW - Mikroskopie KW - Künstliche Intelligenz KW - Datenanalyse KW - Bildverarbeitung KW - Compressed Sensing KW - Lifetime Imaging KW - dSTORM Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-316959 ER - TY - JOUR A1 - Kaltdorf, Kristin Verena A1 - Schulze, Katja A1 - Helmprobst, Frederik A1 - Kollmannsberger, Philip A1 - Dandekar, Thomas A1 - Stigloher, Christian T1 - Fiji macro 3D ART VeSElecT: 3D automated reconstruction tool for vesicle structures of electron tomograms JF - PLoS Computational Biology N2 - 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. KW - Biology KW - Vesicles KW - Caenorhabditis elegans KW - Zebrafish KW - Septins KW - Synaptic vesicles KW - Neuromuscular junctions KW - Computer software KW - Synapses Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172112 VL - 13 IS - 1 ER - TY - JOUR A1 - Floren, Andreas A1 - Horchler, Peter J. A1 - Müller, Tobias T1 - The impact of the neophyte tree Fraxinus pennsylvanica [Marshall] on beetle diversity under climate change JF - Sustainability N2 - 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. KW - forest conversion KW - neophyte trees KW - ash dieback KW - beetle communities KW - ecosystem function Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262223 SN - 2071-1050 VL - 14 IS - 3 ER - TY - JOUR A1 - Broster Reix, Christine E. A1 - Florimond, Célia A1 - Cayrel, Anne A1 - Mailhé, Amélie A1 - Agnero-Rigot, Corentin A1 - Landrein, Nicolas A1 - Dacheux, Denis A1 - Havlicek, Katharina A1 - Bonhivers, Mélanie A1 - Morriswood, Brooke A1 - Robinson, Derrick R. T1 - Bhalin, an essential cytoskeleton-associated protein of Trypanosoma brucei linking TbBILBO1 of the flagellar pocket collar with the hook complex JF - Microorganisms N2 - 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. KW - trypanosoma KW - flagellar pocket KW - hook complex KW - endocytosis KW - cytoskeleton KW - protozoan KW - flagellar pocket collar Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250301 SN - 2076-2607 VL - 9 IS - 11 ER - TY - JOUR A1 - Welter, Nils A1 - Wagner, Angelo A1 - Furtwängler, Rhoikos A1 - Melchior, Patrick A1 - Kager, Leo A1 - Vokuhl, Christian A1 - Schenk, Jens-Peter A1 - Meier, Clemens Magnus A1 - Siemer, Stefan A1 - Gessler, Manfred A1 - Graf, Norbert T1 - Correction: Welter et al. Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome. Cancers 2021, 13, 5016 JF - Cancers N2 - 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. KW - nephroblastomatosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250135 SN - 2072-6694 VL - 13 IS - 22 ER - TY - JOUR A1 - Riedmeier, Maria A1 - Decarolis, Boris A1 - Haubitz, Imme A1 - Müller, Sophie A1 - Uttinger, Konstantin A1 - Börner, Kevin A1 - Reibetanz, Joachim A1 - Wiegering, Armin A1 - Härtel, Christoph A1 - Schlegel, Paul-Gerhardt A1 - Fassnacht, Martin A1 - Wiegering, Verena T1 - Adrenocortical carcinoma in childhood: a systematic review JF - Cancers N2 - 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. KW - pediatric adrenocortical cancer KW - pediatric adrenocortical adenoma KW - pediatric adrenocortical tumor KW - prognostic factors KW - therapy Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248507 SN - 2072-6694 VL - 13 IS - 21 ER - TY - JOUR A1 - Liang, Chunguang A1 - Rios-Miguel, Ana B. A1 - Jarick, Marcel A1 - Neurgaonkar, Priya A1 - Girard, Myriam A1 - François, Patrice A1 - Schrenzel, Jacques A1 - Ibrahim, Eslam S. A1 - Ohlsen, Knut A1 - Dandekar, Thomas T1 - 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 JF - Microorganisms N2 - 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. KW - metabolism KW - flux balance analysis KW - phosphorylation KW - regulation KW - riboswitch KW - PknB KW - Stp KW - yvcK/glmR operon Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248459 SN - 2076-2607 VL - 9 IS - 10 ER - TY - JOUR A1 - Welter, Nils A1 - Wagner, Angelo A1 - Furtwängler, Rhoikos A1 - Melchior, Patrick A1 - Kager, Leo A1 - Vokuhl, Christian A1 - Schenk, Jens-Peter A1 - Meier, Clemens Magnus A1 - Siemer, Stefan A1 - Gessler, Manfred A1 - Graf, Norbert T1 - Characteristics of nephroblastoma/nephroblastomatosis in children with a clinically reported underlying malformation or cancer predisposition syndrome JF - Cancers N2 - (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. KW - nephroblastoma KW - clinical malformations KW - cancer predisposition syndromes KW - tumor surveillance KW - outcome Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-248434 SN - 2072-6694 VL - 13 IS - 19 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Srivastava, Mugdha A1 - Osmanoglu, Özge A1 - Xu, Zhuofei A1 - Brakhage, Axel A. A1 - Dandekar, Thomas T1 - Aspergillus fumigatus versus genus Aspergillus: conservation, adaptive evolution and specific virulence genes JF - Microorganisms N2 - 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. KW - molecular evolution KW - phylogenetic analysis KW - adaptation KW - recombination KW - positive selection KW - human pathogenic fungi KW - genus Aspergillus KW - Aspergillus fumigatus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246318 SN - 2076-2607 VL - 9 IS - 10 ER - TY - JOUR A1 - Scheiner, Ricarda A1 - Lim, Kayun A1 - Meixner, Marina D. A1 - Gabel, Martin S. T1 - Comparing the appetitive learning performance of six European honeybee subspecies in a common apiary JF - Insects N2 - 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. KW - adaptation KW - Apis mellifera KW - olfactory learning KW - proboscis extension response KW - sucrose responsiveness KW - genetic diversity Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245180 SN - 2075-4450 VL - 12 IS - 9 ER - TY - JOUR A1 - Wagner, Martin A1 - Slaghuis, Jörg A1 - Göbel, Werner A1 - Vázquez-Boland, José Antonio A1 - Rychli, Kathrin A1 - Schmitz-Esser, Stephan T1 - Virulence pattern analysis of three Listeria monocytogenes lineage I epidemic strains with distinct outbreak histories JF - Microorganisms N2 - 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. KW - pathogenicity KW - whole-genome analysis KW - prolonged survival Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-245093 SN - 2076-2607 VL - 9 IS - 8 ER - TY - JOUR A1 - Isaacs, Darren A1 - Mikasi, Sello Given A1 - Obasa, Adetayo Emmanuel A1 - Ikomey, George Mondinde A1 - Shityakov, Sergey A1 - Cloete, Ruben A1 - Jacobs, Graeme Brendon T1 - Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors JF - Viruses N2 - 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-naïve 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. KW - integrase KW - naturally occurring polymorphisms KW - HIV-1 KW - molecular modelling KW - molecular docking KW - diversity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211170 SN - 1999-4915 VL - 12 IS - 9 ER - TY - JOUR A1 - Ditzel, Pia A1 - König, Sebastian A1 - Musembi, Peter A1 - Peters, Marcell K. T1 - Correlation between coral reef condition and the diversity and abundance of fishes and sea urchins on an East African coral reef JF - Oceans N2 - 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. KW - coral reef ecosystem KW - coral reef resilience KW - global warming KW - climate change KW - overfishing KW - indicator species Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284503 SN - 2673-1924 VL - 3 IS - 1 SP - 1 EP - 14 ER - TY - JOUR A1 - Steiner, Thomas A1 - Zachary, Marie A1 - Bauer, Susanne A1 - Müller, Martin J. A1 - Krischke, Markus A1 - Radziej, Sandra A1 - Klepsch, Maximilian A1 - Huettel, Bruno A1 - Eisenreich, Wolfgang A1 - Rudel, Thomas A1 - Beier, Dagmar T1 - Central Role of Sibling Small RNAs NgncR_162 and NgncR_163 in Main Metabolic Pathways of Neisseria gonorrhoeae JF - mBio N2 - Small bacterial regulatory RNAs (sRNAs) have been implicated in the regulation of numerous metabolic pathways. In most of these studies, sRNA-dependent regulation of mRNAs or proteins of enzymes in metabolic pathways has been predicted to affect the metabolism of these bacteria. However, only in a very few cases has the role in metabolism been demonstrated. Here, we performed a combined transcriptome and metabolome analysis to define the regulon of the sibling sRNAs NgncR_162 and NgncR_163 (NgncR_162/163) and their impact on the metabolism of Neisseria gonorrhoeae. These sRNAs have been reported to control genes of the citric acid and methylcitric acid cycles by posttranscriptional negative regulation. By transcriptome analysis, we now expand the NgncR_162/163 regulon by several new members and provide evidence that the sibling sRNAs act as both negative and positive regulators of target gene expression. Newly identified NgncR_162/163 targets are mostly involved in transport processes, especially in the uptake of glycine, phenylalanine, and branched-chain amino acids. NgncR_162/163 also play key roles in the control of serine-glycine metabolism and, hence, probably affect biosyntheses of nucleotides, vitamins, and other amino acids via the supply of one-carbon (C\(_1\)) units. Indeed, these roles were confirmed by metabolomics and metabolic flux analysis, which revealed a bipartite metabolic network with glucose degradation for the supply of anabolic pathways and the usage of amino acids via the citric acid cycle for energy metabolism. Thus, by combined deep RNA sequencing (RNA-seq) and metabolomics, we significantly extended the regulon of NgncR_162/163 and demonstrated the role of NgncR_162/163 in the regulation of central metabolic pathways of the gonococcus. KW - sRNA KW - Neisseria gonorrhoeae KW - posttranscriptional regulation KW - amino acid transporter KW - bipartite metabolism Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313323 VL - 14 ER - TY - JOUR A1 - Kaltdorf, Martin A1 - Breitenbach, Tim A1 - Karl, Stefan A1 - Fuchs, Maximilian A1 - Kessie, David Komla A1 - Psota, Eric A1 - Prelog, Martina A1 - Sarukhanyan, Edita A1 - Ebert, Regina A1 - Jakob, Franz A1 - Dandekar, Gudrun A1 - Naseem, Muhammad A1 - Liang, Chunguang A1 - Dandekar, Thomas T1 - Software JimenaE allows efficient dynamic simulations of Boolean networks, centrality and system state analysis JF - Scientific Reports N2 - The signal modelling framework JimenaE simulates dynamically Boolean networks. In contrast to SQUAD, there is systematic and not just heuristic calculation of all system states. These specific features are not present in CellNetAnalyzer and BoolNet. JimenaE is an expert extension of Jimena, with new optimized code, network conversion into different formats, rapid convergence both for system state calculation as well as for all three network centralities. It allows higher accuracy in determining network states and allows to dissect networks and identification of network control type and amount for each protein with high accuracy. Biological examples demonstrate this: (i) High plasticity of mesenchymal stromal cells for differentiation into chondrocytes, osteoblasts and adipocytes and differentiation-specific network control focusses on wnt-, TGF-beta and PPAR-gamma signaling. JimenaE allows to study individual proteins, removal or adding interactions (or autocrine loops) and accurately quantifies effects as well as number of system states. (ii) Dynamical modelling of cell–cell interactions of plant Arapidopsis thaliana against Pseudomonas syringae DC3000: We analyze for the first time the pathogen perspective and its interaction with the host. We next provide a detailed analysis on how plant hormonal regulation stimulates specific proteins and who and which protein has which type and amount of network control including a detailed heatmap of the A.thaliana response distinguishing between two states of the immune response. (iii) In an immune response network of dendritic cells confronted with Aspergillus fumigatus, JimenaE calculates now accurately the specific values for centralities and protein-specific network control including chemokine and pattern recognition receptors. KW - cellular signalling networks KW - computer modelling Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-313303 VL - 13 ER - TY - THES A1 - Franzke, Myriam T1 - Keep on track : The use of visual cues for orientation in monarch butterflies T1 - Auf Kurs bleiben : Die Nutzung visueller Hinweise zur Orientierung bei Monarchfaltern N2 - The monarch butterfly (Danaus plexippus) performs one of the most astonishing behaviors in the animal kingdom: every fall millions of these butterflies leave their breeding grounds in North Amerika and migrate more than 4.000 km southwards until they reach their overwintering habitat in Central Mexico. To maintain their migratory direction over this enormous distance, the butterflies use a time-compensated sun compass. Beside this, skylight polarization, the Earth’s magnetic field and specific mountain ranges seem to guide the butterflies as well the south. In contrast to this fascinating orientation ability, the behavior of the butterflies in their non-migratory state received less attention. Although they do not travel long distances, they still need to orient themselves to find food, mating partners or get away from competitors. The aim of the present doctoral thesis was to investigate use of visual cues for orientation in migrating as well as non-migrating monarch butterflies. For this, field experiments investigating the migration of the butterflies in Texas (USA) were combined with experiments testing the orientation performance of non-migratory butterflies in Germany. In the first project, I recorded the heading directions of tethered butterflies during their annual fall migration. In an outdoor flight simulator, the butterflies maintained a southwards direction as long as they had a view of the sun’s position. Relocating the position of the sun by 180° using a mirror, revealed that the sun is the animals’ main orientation reference. Furthermore, I demonstrated that when the sun is blocked and a green light stimulus (simulated sun) is introduced, the animals interpreted this stimulus as the ‘real’ sun. However, this cue was not sufficient to set the migratory direction when simulated as the only visual cue in indoor experiments. When I presented the butterflies a linear polarization pattern additionally to the simulated sun, the animals headed in the correct southerly direction showing that multiple skylight cues are required to guide the butterflies during their migration. In the second project, I, furthermore, demonstrated that non-migrating butterflies are able to maintain a constant direction with respect to a simulated sun. Interestingly, they ignored the spectral component of the stimulus and relied on the intensity instead. When a panoramic skyline was presented as the only orientation reference, the butterflies maintained their direction only for short time windows probably trying to stabilize their flight based on optic-flow information. Next, I investigated whether the butterflies combine celestial with local cues by simulating a sun stimulus together with a panoramic skyline. Under this conditions, the animals’ directedness was increased demonstrating that they combine multiple visual cues for spatial orientation. Following up on the observation that a sun stimulus resulted in a different behavior than the panoramic skyline, I investigated in my third project which orientation strategies the butterflies use by presenting different simulated cues to them. While a bright stripe on a dark background elicited a strong attraction of the butterflies steering in the direction of the stimulus, the inverted version of the stimulus was used for flight stabilization. In contrast to this, the butterflies maintained arbitrary directions with a high directedness with respect to a simulated sun. In an ambiguous scenery with two identical stimuli (two bright stripes, two dark stripes, or two sun stimuli) set 180° apart, a constant flight course was only achieved when two sun stimuli were displayed suggesting an involvement of the animals’ internal compass. In contrast, the butterflies used two dark stripes for flight stabilization and were alternatingly attracted by two bright stripes. This shows that monarch butterflies use stimulus-dependent orientation strategies and gives the first evidence for different neuronal pathways controlling the output behavior. N2 - Der Monarchfalter (Danaus plexippus) vollführt eine der atemberaubendsten Verhaltensweisen im Tierreich: Jeden Herbst verlassen Millionen dieser Schmetterlinge ihre Brutgebiete in Nordamerika und migrieren mehr als 4000 km südwärts bis sie ihr Überwinterungsgebiet in Zentralmexico erreichen. Um ihre Migrationsrichtung über diese enorme Distanz einzuhalten, benutzen die Schmetterlinge einen zeitkompensierten Sonnenkompass. Daneben scheinen polarisiertes Licht, das Erdmagnetfeld und bestimmte Gebirgsketten die Schmetterlinge nach Süden zu führen. Im Gegensatz zu dieser faszinierenden Orientierungsfähigkeit wurde dem Verhalten der Schmetterlinge in ihrem nicht-migrierendem Zustand wenig Beachtung geschenkt. Obwohl diese keine großen Distanzen zurücklegen, müssen sie sich dennoch orientieren, um Futter und Paarungspartner zu finden oder Konkurrenten zu entfliehen. Das Ziel der vorliegenden Doktorarbeit war es, die Nutzung visueller Hinweise für die Orientierung von sowohl migrierenden als auch nicht-migrierenden Monarchfaltern zu untersuchen. Dazu wurden Feldexperimente, in denen die Migration der Schmetterlinge in Texas (USA) untersucht wurden, mit Experimenten, in denen das Orientierungsvermögen von nicht-migrierenden Schmetterlingen in Deutschland getestet wurde, verknüpft. Im ersten Projekt habe ich die Flugrichtung von Schmetterlingen während der jährlichen Herbstmigration aufgezeichnet. In einem Flugsimulator im Freien hielten die Schmetterlinge eine südliche Richtung, solange sie eine freie Sicht auf die Sonne hatten. Eine Versetzung der Sonnenposition um 180° mit Hilfe eines Spiegels zeigte auf, dass die Sonne die wichtigste Orientierungsreferenz der Tiere ist. Des Weiteren konnte ich zeigen, dass die Tiere, wenn die Sonne blockiert und ein grüner Lichtstimulus (simulierte Sonne) eingeschaltet wurde, diese simulierte Sonne als "echte" Sonne interpretierten. Dieser Hinweis reichte jedoch nicht aus, um die Migrationsrichtung festzulegen, wenn er als einziger visueller Hinweis im Labor simuliert wurde. Als ich den Schmetterlingen zusätzlich zur simulierten Sonne ein lineares Polarisationsmuster präsentierte, flogen die Tiere in die richtige, südliche Richtung. Das zeigt, dass mehrere Himmelshinweise erforderlich sind, um die Schmetterlinge während ihrer Migration zu steuern. Im zweiten Projekt habe ich weiterhin gezeigt, dass nicht migrierende Schmetterlinge in der Lage sind eine konstante Richtung relativ zu einer simulierten Sonne beizubehalten. Interessanterweise ignorierten sie die spektrale Komponente des Stimulus und verließen sich stattdessen auf die Intensität. Als ein Panorama als einzige Orientierungsreferenz präsentiert wurde, hielten die Schmetterlinge ihre Richtung nur für kurze Zeitfenster und versuchten vermutlich, ihren Flug basierend auf Informationen des optischen Flusses zu stabilisieren. Als Nächstes untersuchte ich, ob die Schmetterlinge Himmelshinweise und lokale Hinweisen kombinieren, indem ich eine Sonne zusammen mit einem Panorama simulierte. Unter diesen Bedingungen war die Gerichtetheit der Flüge erhöht, was zeigt, dass die Tiere mehrere visuelle Hinweise zur räumlichen Orientierung kombinieren. Beruhend auf der Beobachtung, dass ein Sonnenstimulus zu einem anderen Verhaltensmuster führte als das Panorama, untersuchte ich in meinem dritten Projekt, welche Orientierungsstrategien die Schmetterlinge verwenden. Hierfür präsentierte ich den Tieren verschiedene simulierte Hinweise. Während ein heller Streifen auf dunklem Hintergrund eine starke Anziehungskraft auf die Schmetterlinge, die in die Richtung des Reizes flogen, ausübte, wurde die invertierte Version des Stimulus zur Flugstabilisierung verwendet. Im Gegensatz dazu hielten die Schmetterlinge beliebige Richtungen mit einer hohen Gerichtetheit relativ zu einer simulierten Sonne ein. In einer uneindeutigen Szenerie mit zwei identischen Reizen (zwei helle Streifen, zwei dunkle Streifen oder zwei Sonnenstimuli), die um 180° versetzt waren, wurde eine konstante Flugrichtung nur dann erreicht, wenn zwei Sonnenstimuli gezeigt wurden. Das deutet auf eine Beteiligung des inneren Kompasses der Tiere hin. Im Gegensatz dazu nutzten die Schmetterlinge zwei dunkle Streifen zur Flugstabilisierung und wurden abwechselnd von zwei hellen Streifen angezogen. Dies zeigt, dass Monarchfalter stimulus-abhängige Orientierungsstrategien verwenden, und liefert den ersten Nachweis für unterschiedliche neuronale Verschaltungswege, die das Verhalten steuern. KW - Monarchfalter KW - Orientierung KW - Visuelle Orientierung KW - Schmetterlinge KW - Insekten KW - visual cue Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284709 ER - TY - JOUR A1 - Vellmer, Tim A1 - Hartleb, Laura A1 - Fradera Sola, Albert A1 - Kramer, Susanne A1 - Meyer-Natus, Elisabeth A1 - Butter, Falk A1 - Janzen, Christian J. T1 - A novel SNF2 ATPase complex in Trypanosoma brucei with a role in H2A.Z-mediated chromatin remodelling JF - PLoS Pathogens N2 - A cascade of histone acetylation events with subsequent incorporation of a histone H2A variant plays an essential part in transcription regulation in various model organisms. A key player in this cascade is the chromatin remodelling complex SWR1, which replaces the canonical histone H2A with its variant H2A.Z. Transcriptional regulation of polycistronic transcription units in the unicellular parasite Trypanosoma brucei has been shown to be highly dependent on acetylation of H2A.Z, which is mediated by the histone-acetyltransferase HAT2. The chromatin remodelling complex which mediates H2A.Z incorporation is not known and an SWR1 orthologue in trypanosomes has not yet been reported. In this study, we identified and characterised an SWR1-like remodeller complex in T. brucei that is responsible for Pol II-dependent transcriptional regulation. Bioinformatic analysis of potential SNF2 DEAD/Box helicases, the key component of SWR1 complexes, identified a 1211 amino acids-long protein that exhibits key structural characteristics of the SWR1 subfamily. Systematic protein-protein interaction analysis revealed the existence of a novel complex exhibiting key features of an SWR1-like chromatin remodeller. RNAi-mediated depletion of the ATPase subunit of this complex resulted in a significant reduction of H2A.Z incorporation at transcription start sites and a subsequent decrease of steady-state mRNA levels. Furthermore, depletion of SWR1 and RNA-polymerase II (Pol II) caused massive chromatin condensation. The potential function of several proteins associated with the SWR1-like complex and with HAT2, the key factor of H2A.Z incorporation, is discussed. KW - Trypanosoma KW - chromatin KW - histones KW - RNA interference KW - Trypanosoma brucei gambiense KW - luciferase KW - transcriptional control KW - nucleosomes Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301372 VL - 18 IS - 6 ER - TY - THES A1 - Fasemore, Akinyemi Mandela T1 - Genomic and internet based analysis of \(Coxiella\) \(burnetii\) T1 - Genomische und Internet-basierte Analyse von \(Coxiella\) \(burnetii\) N2 - Coxiella burnetii, a Gram negative obligate intracellular bacterium, is the causative agent of Q fever. It has a world wide distribution and has been documented to be capable of causing infections in several domestic animals, livestock species, and human beings. Outbreaks of Q fever are still being observed in livestock across animal farms in Europe, and primary transmission to humans still oc- curs especially in animal handlers. Public health authorities in some countries like Germany are required by law to report human acute cases denoting the significance of the challenge posed by C. burnetii to public health. In this thesis, I have developed a platform alongside methods to address the challenges of genomic analyses of C. burnetii for typing purposes. Identification of C. burnetii isolates is an important task in the laboratory as well as in the clinics and genotyping is a reliable method to identify and characterize known and novel isolates. Therefore, I designed and implemented several methods to facilitate the genotyping analyses of C. burnetii genomes in silico via a web platform. As genotyping is a data intensive process, I also included additional features such as visualization methods and databases for interpretation and storage of obtained results. I also developed a method to profile the resistome of C. burnetii isolates using a machine learning approach. Data about antibiotic resistance in C. burnetii are scarce majorly due to its lifestyle and the difficulty of cultivation in laboratory media. Alternative methods that rely on homology identification of resistance genes are also inefficient in C. burnetii, hence, I opted for a novel approach that has been shown to be promising in other bacteria species. The applied method relied on an artificial neural network as well as amino acid composition of position specific scoring matrix profile for feature extraction. The resulting model achieved an accuracy of ≈ 0.96 on test data and the overall performance was significantly higher in comparison to existing models. Finally, I analyzed two new C. burnetii isolates obtained from an outbreak in Germany, I compared the genome to the RSA 493 reference isolate and found extensive deletions across the genome landscape. This work has provided a new digital infrastructure to analyze and character- ize C. burnetii genomes that was not in existence before and it has also made a significant contribution to the existing information about antibiotic resistance genes in C. burnetii. N2 - Coxiella burnetii, ein Gram-negatives, obligat intrazelluläres Bakterium, ist der Erreger des Q-Fiebers. Er hat eine weltweite Verbreitung und ist nachweis- lich in der Lage, Infektionen bei verschiedenen Haustieren, Nutztieren und Menschen zu verursachen. Ausbrüche von Q-Fieber werden immer noch in Tierbeständen in Europa beobachtet, und die Primärübertragung auf den Men- schen erfolgt nach wie vor allem durch Kontakt mit entsprechenden Tieren und ihren Ausscheidungen. Das öffentliche Gesundheitssystem in einigen Ländern wie Deutschland hat eine Meldepflicht für akute Fälle beim Menschen festge- legt, was die Bedeutung des Erregers bzw. seiner ausgelösten Erkrankung für die öffentliche Gesundheit verdeutlicht. In dieser Doktorarbeit habe ich eine Plattform neben weiteren Methoden entwickelt, um die Herausforderungen der Genomanalyse von C. burnetii für Genotypisierungsverfahren zu adressieren. Die Identifizierung von C. burnetii-Isolaten erfüllt eine wichtige Funktion im La- bor sowie in den Krankenhäusern, und die Genotypisierung ist eine verlässliche Methode, um bekannte und neue Isolate zu identifizieren und zu charakte- risieren. Daher habe ich mehrere Methoden konzipiert und implementiert, um die Analyse zur Genotypisierung von C. burnetii-Genomen in silico über eine Web-Plattform zu erleichtern. Da die Genotypisierung ein datenintensiver Prozess ist, habe ich ebenfalls zusätzliche Features wie Visualisierungsme- thoden und Datenbanken zur Interpretation und Speicherung der erhaltenen Ergebnisse mitaufgenommen. Ferner habe ich eine Methode zur Erstellung des Resistomprofils von C. burnetii-Isolaten unter Verwendung eines Ansat- zes des maschinellen Lernens entwickelt. Daten über Resistenzfaktoren bei C. burnetii sind rar, was hauptsächlich auf die obligat intrazelluläre Lebensweise der Coxiellen und die Schwierigkeiten bei der Kultivierung in Labormedien zurückzuführen ist. Alternative Methoden, die auf der Identifizierung der Ho- mologie von Resistenzgenen basieren, sind bei C. burnetii ebenfalls ineffizient. Aus diesem Grund entschied ich mich für einen neuen Ansatz, der sich bereits bei anderen Bakterienspezies als vielversprechend erwiesen hat. Die verwen- dete Methode basiert auf einem artifiziellen neuronalen Netzwerk sowie auf der Aminosäurezusammensetzung des positionsspezifischen Matrixprofils zur Extraktion von Features. Das daraus resultierende Modell erzielte eine Genauig- keit von ≈ 0,96 bei den Testdaten und die Gesamtleistung war signifikant höher im Vergleich zu den bereits vorhandenen Methoden. Schließlich analysierte ich zwei neue C. burnetii-Isolate, die von einem Q-Fieberausbruch in Deutschland stammten. Ich verglich das Genom mit dem RSA 493 Referenz Isolat und fand extensive Deletionen über das Genom sequenz. Mit dieser Arbeit wird eine neue digitale Infrastruktur zu Analyse von C. burnetii- Genomen bereitgestellt, die es vorher noch nicht gab. Zudem liefert diese Arbeit einen wichtigen Beitrag zu den bereits vorhandenen Informationen über Antibiotikaresistenzgene bei in C. burnetii. KW - Bioinformatics KW - Coxiella burnetii KW - Genotyping KW - Web services KW - Genomics Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-296639 ER - TY - THES A1 - Nguyen, Tu Anh Thi T1 - Neural coding of different visual cues in the monarch butterfly sun compass T1 - Neuronale Kodierung verschiedener visueller Signale im Sonnenkompass des Monarchfalters N2 - Monarch butterflies are famous for their annual long-distance migration. Decreasing temperatures and reduced daylight induce the migratory state in the autumn generation of monarch butterflies. Not only are they in a reproductive diapause, they also produce fat deposits to be prepared for the upcoming journey: Driven by their instinct to migrate, they depart from their eclosion grounds in the northern regions of the North American continent and start their southern journey to their hibernation spots in Central Mexico. The butterflies cover a distance of up to 4000 km across the United States. In the next spring, the same butterflies invert their preferred heading direction due to seasonal changes and start their northward spring migration. The spring migration is continued by three consecutive butterfly generations, until the animals repopulate the northern regions in North America as non-migratory monarch butterflies. The monarch butterflies’ migratory state is genetically and epigenetically regulated, including the directed flight behavior. Therefore, the insect’s internal compass system does not only have to encode the butterflies preferred, but also its current heading direction. However, the butterfly’s internal heading representation has to be matched to external cues, to avoid departing from its initial flight path and increasing its risk of missing its desired destination. During the migratory flight, visual cues provide the butterflies with reliable orientation information. The butterflies refer to the sun as their main orientation cue. In addition to the sun, the butterflies likely use the polarization pattern of the sky for orientation. The sky compass signals are processed within a region in the brain, termed the central complex (CX). Previous research on the CX neural circuitry of the monarch butterflies demonstrated that tangential central complex neurons (TL) carry the visual input information into the CX and respond to a simulated sun and polarized light. However, whether these cells process additional visual cues like the panoramic skyline is still unknown. Furthermore, little is known about how the migratory state affects visual cue processing. In addition to this, most experiments studying the monarch butterfly CX focused on how neurons process single visual cues. However, how combined visual stimuli are processed in the CX is still unknown. This thesis is investigating the following questions: 1) How does the migratory state affect visual cue processing in the TL cells within the monarch butterfly brain? 2) How are multiple visual cues integrated in the TL cells? 3) How is compass information modulated in the CX? To study these questions, TL neurons from both animal groups (migratory and non-migratory) were electrophysiologically characterized using intracellular recordings while presenting different simulated celestial cues and visual sceneries. I showed that the TL neurons of migratory butterflies are more narrowly tuned to the sun, possibly helping them in keeping a directed flight course during migration. Furthermore, I found that TL cells encode a panoramic skyline, suggesting that the CX network combines celestial and terrestrial information. Experiments with combined celestial stimuli revealed that the TL cells combine both cue information linearly. However, if exposing the animals to a simulated visual scenery containing a panoramic skyline and a simulated sun, the single visual cues are weighted differently. These results indicate that the CX’s input region can flexibly adapt to different visual cue conditions. Furthermore, I characterize a previously unknown neuron in the monarch butterfly CX which responds to celestial stimuli and connects the CX with other brain neuropiles. How this cell type affects heading direction encoding has yet to be determined. N2 - Monarchfalter sind berühmt für ihre jährlichen Migrationsflüge. Sinkende Temperaturen und die verkürzte Tageslichtbestrahlung induzieren die Migration in einer Herbstgeneration der Monarchfalter. Sie sind nicht nur in reproduktiver Diapause, sondern produzieren Fettreserven für die bevorstehende Reise: Getrieben von ihrem Migrationsinstinkt verlassen sie ihre Schlüpfstätten in den nördlichen Regionen des Nordamerikanischen Kontinents und starten ihre südliche Wanderung zu ihren Überwinterunsgstätten in Zentralmexiko. Dabei legen die Schmetterlinge Strecken von bis zu 4000 km durch die Vereinigten Staaten zurück. Im nächsten Frühling kehren die gleichen Schmetterlinge ihre Vorzugsrichtung durch die jahreszeitlich bedingten Veränderungen um und die Tiere bewegen sich nordwärts. Die Frühlingsgeneration wird insgesamt über drei Schmetterlingsgeneration durchgeführt, bis die Tiere die nördlichen Regionen in Nordamerika wieder als nicht-migrierende Monarchfalter besiedeln. Der Migrationsstatus der Monarchfalter ist genetisch und epigenetisch reguliert, was auch das gerichtete Flugverhalten einschließt. Demnach muss das interne Kompasssystem der Falter nicht nur die bevorzugte, sondern auch die aktuelle Flugrichtung prozessieren. Die interne Repräsentation der Flugrichtung des Falters muss jedoch mit der Umwelt abgeglichen werden, ansonsten droht das Tier von der ursprünglichen Flugrichtung abzuweichen und erhöht das Risiko den Wunschort nicht zu erreichen. Während des Migrationsfluges bieten visuelle Signale verlässliche Orientierungsinformationen. Dabei ist die Sonne ihre Hauptorientierungsreferenz. Zusätzlich zur Sonne nutzen die Schmetterlinge vermutlich noch das Polarisationsmuster des Himmels zur Orientierung. Diese Himmelskompasssignale werden im Gehirn in einer Gehirnregion, den Zentralkomplex, integriert. Vergangene Forschungsprojekte am Zentralkomplex haben gezeigt, dass tangentiale Zentralkomplex-Neurone (TL) die visuellen Signale in den Zentralkomplex leiten und auf eine simulierte Sonne und polarisiertes Licht sensitiv sind. Ob diese Zellen noch weitere visuelle Signale verarbeiten, wie zum Beispiel den Horizont eines Panoramas, ist nicht bekannt. Auch ist der Einfluss des Migrationsstatus auf die visuelle Signalverarbeitung im Zentralkomplex bisher unerforscht. Des Weiteren haben die meisten Experimente am Zentralkomplex des Monarchfalters den Fokus auf die Verarbeitung einzelner simulierter visueller Reize gelegt. Wie aber Kombinationen aus Stimuli im Zentralkomplex verarbeitet werden, ist nicht bekannt.   Diese Dissertation beschäftigt sich mit folgenden Fragen: 1) Wie beeinflusst der Migrationsstatus die visuelle Reizverarbeitung in TL-Zellen im Monarchfaltergehirn? 2) Wie werden mehrere visuelle Reize in TL-Zellen miteinander kombiniert? 3) Wie wird Kompassinformation im Zentralkomplex moduliert? In diesem Zusammenhang wurden TL-Neurone aus beiden Gruppen (migrierende und nichtmigrierende Monarchfalter) elektrophysiologisch mittels intrazellulärer Aufnahmen charakterisiert, während den Tieren unterschiedliche simulierte Himmelkompasssignale und visuelle Szenerien präsentiert wurden. Hierbei konnte ich zeigen dass die TL-Neuronen in migrierenden Tieren ein engeres Tuning zur Sonne aufwiesen, was den Tieren helfen könnte, eine gerichtete Flugrichtung zu halten. Außerdem antworten die TL-Neurone auf ein Panorama, womit der Zentralkomplex in der Lage wäre, Himmelskompasssignale mit terrestrischer Information zu kombinieren. In Experimenten mit zwei kombinierten simulierten Himmelskompasssignalen konnte ich zeigen, dass die TL-Zellen beide Signalinformationen linear miteinander verrechnen. Wenn die TL-Zellen jedoch mit einer visuellen Szenerie stimuliert werden, welche eine simulierte Sonne und ein Panorama beinhaltet, werden die einzelnen visuellen Signale unterschiedlich gewichtet. Die Ergebnisse sind ein Hinweis darauf, dass die Eingangsregion im Zentralkomplex sich flexibel an die visuellen Signalbedingungen anpassen können. Außerdem habe ich ein bis dahin unbekanntes Neuron während meiner Studien charakterisieren können, welches auf simulierte Himmelskompasssignale antwortet und den Zentralkomplex mit anderen Neuropilen im Gehirn verbindet. Wie dieser Neuronentyp Einfluss auf die Kodierung der Flugrichtung nimmt, muss in der Zukunft weiter erforscht werden. KW - Monarchfalter KW - Danaus plexippus KW - Gehirn KW - Orientierung KW - Visuelle Wahrnehmung KW - monarch butterfly KW - brain KW - orientation KW - visual perception KW - central complex Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303807 ER - TY - JOUR A1 - Vollmuth, Nadine A1 - Schlicker, Lisa A1 - Guo, Yongxia A1 - Hovhannisyan, Pargev A1 - Janaki-Raman, Sudha A1 - Kurmasheva, Naziia A1 - Schmitz, Werner A1 - Schulze, Almut A1 - Stelzner, Kathrin A1 - Rajeeve, Karthika A1 - Rudel, Thomas T1 - c-Myc plays a key role in IFN-γ-induced persistence of Chlamydia trachomatis JF - eLife N2 - Chlamydia trachomatis (Ctr) can persist over extended times within their host cell and thereby establish chronic infections. One of the major inducers of chlamydial persistence is interferon-gamma (IFN-γ) released by immune cells as a mechanism of immune defence. IFN-γ activates the catabolic depletion of L-tryptophan (Trp) via indoleamine-2,3-dioxygenase (IDO), resulting in persistent Ctr. Here, we show that IFN-γ induces the downregulation of c-Myc, the key regulator of host cell metabolism, in a STAT1-dependent manner. Expression of c-Myc rescued Ctr from IFN-γ-induced persistence in cell lines and human fallopian tube organoids. Trp concentrations control c-Myc levels most likely via the PI3K-GSK3β axis. Unbiased metabolic analysis revealed that Ctr infection reprograms the host cell tricarboxylic acid (TCA) cycle to support pyrimidine biosynthesis. Addition of TCA cycle intermediates or pyrimidine/purine nucleosides to infected cells rescued Ctr from IFN-γ-induced persistence. Thus, our results challenge the longstanding hypothesis of Trp depletion through IDO as the major mechanism of IFN-γ-induced metabolic immune defence and significantly extends the understanding of the role of IFN-γ as a broad modulator of host cell metabolism. KW - Chlamydia trachomatis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301385 VL - 11 ER - TY - JOUR A1 - Lichter, Katharina A1 - Paul, Mila Marie A1 - Pauli, Martin A1 - Schoch, Susanne A1 - Kollmannsberger, Philip A1 - Stigloher, Christian A1 - Heckmann, Manfred A1 - Sirén, Anna-Leena T1 - Ultrastructural analysis of wild-type and RIM1α knockout active zones in a large cortical synapse JF - Cell Reports N2 - Rab3A-interacting molecule (RIM) is crucial for fast Ca\(^{2+}\)-triggered synaptic vesicle (SV) release in presynaptic active zones (AZs). We investigated hippocampal giant mossy fiber bouton (MFB) AZ architecture in 3D using electron tomography of rapid cryo-immobilized acute brain slices in RIM1α\(^{−/−}\) and wild-type mice. In RIM1α\(^{−/−}\), AZs are larger with increased synaptic cleft widths and a 3-fold reduced number of tightly docked SVs (0–2 nm). The distance of tightly docked SVs to the AZ center is increased from 110 to 195 nm, and the width of their electron-dense material between outer SV membrane and AZ membrane is reduced. Furthermore, the SV pool in RIM1α\(^{−/−}\) is more heterogeneous. Thus, RIM1α, besides its role in tight SV docking, is crucial for synaptic architecture and vesicle pool organization in MFBs. KW - active zone KW - acute brain slices KW - CA3 KW - electron tomography KW - high-pressure freezing KW - hippocampal mossy fiber bouton KW - RIM1α KW - SV pool KW - synaptic ultrastructure KW - presynaptic Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300913 VL - 40 IS - 12 ER - TY - JOUR A1 - Fischer, Thomas A1 - Hartmann, Oliver A1 - Reissland, Michaela A1 - Prieto-Garcia, Cristian A1 - Klann, Kevin A1 - Pahor, Nikolett A1 - Schülein-Völk, Christina A1 - Baluapuri, Apoorva A1 - Polat, Bülent A1 - Abazari, Arya A1 - Gerhard-Hartmann, Elena A1 - Kopp, Hans-Georg A1 - Essmann, Frank A1 - Rosenfeldt, Mathias A1 - Münch, Christian A1 - Flentje, Michael A1 - Diefenbacher, Markus E. T1 - PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy JF - Cell & Bioscience N2 - Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models. KW - PTEN KW - ATM KW - IR KW - NSCLC KW - radiotherapy KW - cancer KW - DNA-PK KW - PI3K Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299865 SN - 2045-3701 VL - 12 ER - TY - JOUR A1 - Storms, Mona A1 - Jakhar, Aryan A1 - Mitesser, Oliver A1 - Jechow, Andreas A1 - Hölker, Franz A1 - Degen, Tobias A1 - Hovestadt, Thomas A1 - Degen, Jacqueline T1 - The rising moon promotes mate finding in moths JF - Communications Biology N2 - To counteract insect decline, it is essential to understand the underlying causes, especially for key pollinators such as nocturnal moths whose ability to orientate can easily be influenced by ambient light conditions. These comprise natural light sources as well as artificial light, but their specific relevance for moth orientation is still unknown. We investigated the influence of moonlight on the reproductive behavior of privet hawkmoths (Sphinx ligustri) at a relatively dark site where the Milky Way was visible while the horizon was illuminated by distant light sources and skyglow. We show that male moths use the moon for orientation and reach females significantly faster with increasing moon elevation. Furthermore, the choice of flight direction depended on the cardinal position of the moon but not on the illumination of the horizon caused by artificial light, indicating that the moon plays a key role in the orientation of male moths. KW - animal behaviour KW - biodiversity KW - conservation biology KW - entomology KW - urban ecology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301365 VL - 5 ER - TY - JOUR A1 - Thiele, Jonas A. A1 - Richter, Aylin A1 - Hilger, Kirsten T1 - Multimodal brain signal complexity predicts human intelligence JF - eNeuro N2 - Spontaneous brain activity builds the foundation for human cognitive processing during external demands. Neuroimaging studies based on functional magnetic resonance imaging (fMRI) identified specific characteristics of spontaneous (intrinsic) brain dynamics to be associated with individual differences in general cognitive ability, i.e., intelligence. However, fMRI research is inherently limited by low temporal resolution, thus, preventing conclusions about neural fluctuations within the range of milliseconds. Here, we used resting-state electroencephalographical (EEG) recordings from 144 healthy adults to test whether individual differences in intelligence (Raven’s Advanced Progressive Matrices scores) can be predicted from the complexity of temporally highly resolved intrinsic brain signals. We compared different operationalizations of brain signal complexity (multiscale entropy, Shannon entropy, Fuzzy entropy, and specific characteristics of microstates) regarding their relation to intelligence. The results indicate that associations between brain signal complexity measures and intelligence are of small effect sizes (r ∼ 0.20) and vary across different spatial and temporal scales. Specifically, higher intelligence scores were associated with lower complexity in local aspects of neural processing, and less activity in task-negative brain regions belonging to the default-mode network. Finally, we combined multiple measures of brain signal complexity to show that individual intelligence scores can be significantly predicted with a multimodal model within the sample (10-fold cross-validation) as well as in an independent sample (external replication, N = 57). In sum, our results highlight the temporal and spatial dependency of associations between intelligence and intrinsic brain dynamics, proposing multimodal approaches as promising means for future neuroscientific research on complex human traits. KW - brain signal complexity KW - cognitive ability KW - EEG KW - intelligence KW - microstates KW - resting-state Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312949 VL - 10 IS - 2 ER - TY - JOUR A1 - Deppisch, Peter A1 - Helfrich-Förster, Charlotte A1 - Senthilan, Pingkalai R. T1 - The gain and loss of cryptochrome/photolyase family members during evolution JF - Genes N2 - The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. In this study, we took advantage of the large number of already sequenced and annotated genes available in databases and systematically searched for the protein sequences of CRY/PL family members in all taxonomic groups primarily focusing on metazoans and limiting the number of species per taxonomic order to five. Using BLASTP searches and subsequent phylogenetic tree and motif analyses, we identified five distinct photolyases (CPDI, CPDII, CPDIII, 6-4 photolyase, and the plant photolyase PPL) and six cryptochrome subfamilies (DASH-CRY, mammalian-type MCRY, Drosophila-type DCRY, cnidarian-specific ACRY, plant-specific PCRY, and the putative magnetoreceptor CRY4. Manually assigning the CRY/PL subfamilies to the species studied, we have noted that over evolutionary history, an initial increase of various CRY/PL subfamilies was followed by a decrease and specialization. Thus, in more primitive organisms (e.g., bacteria, archaea, simple eukaryotes, and in basal metazoans), we find relatively few CRY/PL members. As species become more evolved (e.g., cnidarians, mollusks, echinoderms, etc.), the CRY/PL repertoire also increases, whereas it appears to decrease again in more recent organisms (humans, fruit flies, etc.). Moreover, our study indicates that all cryptochromes, although largely active in the circadian clock, arose independently from different photolyases, explaining their different modes of action. KW - cryptochrome KW - photolyase KW - cryptochrome/photolyase family KW - CPF KW - CRY evolution KW - circadian clock KW - DNA-repair Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312873 VL - 13 IS - 9 ER - TY - JOUR A1 - Otto, Christoph A1 - Kastner, Carolin A1 - Schmidt, Stefanie A1 - Uttinger, Konstantin A1 - Baluapuri, Apoorva A1 - Denk, Sarah A1 - Rosenfeldt, Mathias T. A1 - Rosenwald, Andreas A1 - Roehrig, Florian A1 - Ade, Carsten P. A1 - Schuelein-Voelk, Christina A1 - Diefenbacher, Markus E. A1 - Germer, Christoph-Thomas A1 - Wolf, Elmar A1 - Eilers, Martin A1 - Wiegering, Armin T1 - RNA polymerase I inhibition induces terminal differentiation, growth arrest, and vulnerability to senolytics in colorectal cancer cells JF - Molecular Oncology N2 - Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461-induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC-interacting zinc-finger protein 1 (MIZ1)- and retinoblastoma protein (Rb)-dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine- and patient-derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside. KW - CRC KW - CX5461 KW - MIZ1 KW - MYC KW - ribosome KW - RNAPOL1 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312806 VL - 16 IS - 15 ER - TY - JOUR A1 - Maihoff, Fabienne A1 - Friess, Nicolas A1 - Hoiss, Bernhard A1 - Schmid‐Egger, Christian A1 - Kerner, Janika A1 - Neumayer, Johann A1 - Hopfenmüller, Sebastian A1 - Bässler, Claus A1 - Müller, Jörg A1 - Classen, Alice T1 - Smaller, more diverse and on the way to the top: Rapid community shifts of montane wild bees within an extraordinary hot decade JF - Diversity and Distributions N2 - Aim Global warming is assumed to restructure mountain insect communities in space and time. Theory and observations along climate gradients predict that insect abundance and richness, especially of small‐bodied species, will increase with increasing temperature. However, the specific responses of single species to rising temperatures, such as spatial range shifts, also alter communities, calling for intensive monitoring of real‐world communities over time. Location German Alps and pre‐alpine forests in south‐east Germany. Methods We empirically examined the temporal and spatial change in wild bee communities and its drivers along two largely well‐protected elevational gradients (alpine grassland vs. pre‐alpine forest), each sampled twice within the last decade. Results We detected clear abundance‐based upward shifts in bee communities, particularly in cold‐adapted bumble bee species, demonstrating the speed with which mobile organisms can respond to climatic changes. Mean annual temperature was identified as the main driver of species richness in both regions. Accordingly, and in large overlap with expectations under climate warming, we detected an increase in bee richness and abundance, and an increase in small‐bodied species in low‐ and mid‐elevations along the grassland gradient. Community responses in the pre‐alpine forest gradient were only partly consistent with community responses in alpine grasslands. Main Conclusion In well‐protected temperate mountain regions, small‐bodied bees may initially profit from warming temperatures, by getting more abundant and diverse. Less severe warming, and differences in habitat openness along the forested gradient, however, might moderate species responses. Our study further highlights the utility of standardized abundance data for revealing rapid changes in bee communities over only one decade. KW - Alps KW - altitudinal gradient KW - body size KW - climate change KW - global warming KW - hymenoptera KW - pollinator KW - range shifts Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312126 VL - 29 IS - 2 ER - TY - JOUR A1 - Chaianunporn, Thotsapol A1 - Hovestadt, Thomas T1 - Emergence of spatially structured populations by area‐concentrated search JF - Ecology and Evolution N2 - The idea that populations are spatially structured has become a very powerful concept in ecology, raising interest in many research areas. However, despite dispersal being a core component of the concept, it typically does not consider the movement behavior underlying any dispersal. Using individual‐based simulations in continuous space, we explored the emergence of a spatially structured population in landscapes with spatially heterogeneous resource distribution and with organisms following simple area‐concentrated search (ACS); individuals do not, however, perceive or respond to any habitat attributes per se but only to their foraging success. We investigated the effects of different resource clustering pattern in landscapes (single large cluster vs. many small clusters) and different resource density on the spatial structure of populations and movement between resource clusters of individuals. As results, we found that foraging success increased with increasing resource density and decreasing number of resource clusters. In a wide parameter space, the system exhibited attributes of a spatially structured populations with individuals concentrated in areas of high resource density, searching within areas of resources, and “dispersing” in straight line between resource patches. “Emigration” was more likely from patches that were small or of low quality (low resource density), but we observed an interaction effect between these two parameters. With the ACS implemented, individuals tended to move deeper into a resource cluster in scenarios with moderate resource density than in scenarios with high resource density. “Looping” from patches was more likely if patches were large and of high quality. Our simulations demonstrate that spatial structure in populations may emerge if critical resources are heterogeneously distributed and if individuals follow simple movement rules (such as ACS). Neither the perception of habitat nor an explicit decision to emigrate from a patch on the side of acting individuals is necessary for the emergence of such spatial structure. KW - area‐concentrated search KW - individual‐based model KW - metapopulation KW - spatially structured population Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311939 VL - 12 IS - 12 ER - TY - JOUR A1 - Englmeier, Jana A1 - von Hoermann, Christian A1 - Rieker, Daniel A1 - Benbow, Marc Eric A1 - Benjamin, Caryl A1 - Fricke, Ute A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Lackner, Tomáš A1 - Mitesser, Oliver A1 - Redlich, Sarah A1 - Riebl, Rebekka A1 - Rojas-Botero, Sandra A1 - Rummler, Thomas A1 - Salamon, Jörg-Alfred A1 - Sommer, David A1 - Steffan-Dewenter, Ingolf A1 - Tobisch, Cynthia A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Zhang, Jie A1 - Müller, Jörg T1 - Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate JF - Ecology and Evolution N2 - Dung beetles are important actors in the self-regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space-for-time approach to test the effects of land use and climate on α-diversity, local community specialization (H\(_2\)′) on dung resources, and γ-diversity of dung-visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land-use types: forests, grasslands, arable sites, and settlements, embedded in near-natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung-visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ-diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung-visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ-diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung-visiting beetle diversity and alter community networks. A decrease in dung-visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage. KW - coleoptera KW - coprophagous beetles KW - decomposition KW - global change KW - hill numbers KW - network analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312846 SN - 2045-7758 VL - 12 IS - 10 ER - TY - JOUR A1 - Prieto-Garcia, Cristian A1 - Hartmann, Oliver A1 - Reissland, Michaela A1 - Braun, Fabian A1 - Bozkurt, Süleyman A1 - Pahor, Nikolett A1 - Fuss, Carmina A1 - Schirbel, Andreas A1 - Schülein-Völk, Christina A1 - Buchberger, Alexander A1 - Calzado Canale, Marco A. A1 - Rosenfeldt, Mathias A1 - Dikic, Ivan A1 - Münch, Christian A1 - Diefenbacher, Markus E. T1 - USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K JF - Molecular Oncology N2 - Oncogenic transformation of lung epithelial cells is a multistep process, frequently starting with the inactivation of tumour suppressors and subsequent development of activating mutations in proto-oncogenes, such as members of the PI3K or MAPK families. Cells undergoing transformation have to adjust to changes, including altered metabolic requirements. This is achieved, in part, by modulating the protein abundance of transcription factors. Here, we report that the ubiquitin carboxyl-terminal hydrolase 28 (USP28) enables oncogenic reprogramming by regulating the protein abundance of proto-oncogenes such as c-JUN, c-MYC, NOTCH and ∆NP63 at early stages of malignant transformation. USP28 levels are increased in cancer compared with in normal cells due to a feed-forward loop, driven by increased amounts of oncogenic transcription factors such as c-MYC and c-JUN. Irrespective of oncogenic driver, interference with USP28 abundance or activity suppresses growth and survival of transformed lung cells. Furthermore, inhibition of USP28 via a small-molecule inhibitor resets the proteome of transformed cells towards a ‘premalignant’ state, and its inhibition synergizes with clinically established compounds used to target EGFR\(^{L858R}\)-, BRAF\(^{V600E}\)- or PI3K\(^{H1047R}\)-driven tumour cells. Targeting USP28 protein abundance at an early stage via inhibition of its activity is therefore a feasible strategy for the treatment of early-stage lung tumours, and the observed synergism with current standard-of-care inhibitors holds the potential for improved targeting of established tumours. KW - buparlisib KW - c-MYC KW - gefitinib KW - lung cancer KW - USP28 KW - vemurafenib Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312777 VL - 16 IS - 17 ER - TY - JOUR A1 - Diers, Johannes A1 - Baum, Philip A1 - Lehmann, Kai A1 - Uttinger, Konstatin A1 - Baumann, Nikolas A1 - Pietryga, Sebastian A1 - Hankir, Mohammed A1 - Matthes, Niels A1 - Lock, Johann F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study JF - Cancer Medicine N2 - Background Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. Methods All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Results Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3% for SSI and 29.9% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95%CI [4.45–5.53], p < 0.001). Conclusion Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications. KW - colorectal cancer KW - geriatric KW - octogenerians KW - surgery Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312858 VL - 11 IS - 22 ER - TY - JOUR A1 - Diers, Johannes A1 - Acar, Laura A1 - Wagner, Johanna C. A1 - Baum, Philip A1 - Hankir, Mohammed A1 - Flemming, Sven A1 - Kastner, Carolin A1 - Germer, Christoph-Thomas A1 - L’hoest, Helmut A1 - Marschall, Ursula A1 - Lock, Johan Friso A1 - Wiegering, Armin T1 - Cancer diagnosis is one quarter lower than the expected cancer incidence in the first year of COVID-19 pandemic in Germany: A retrospective register-based cohort study JF - Cancer Communications N2 - No abstract available. KW - cancer diagnosis KW - COVID-19 pandemic KW - Germany Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312862 VL - 42 IS - 7 ER -