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 - TY - JOUR A1 - Vansynghel, Justine A1 - Ocampo-Ariza, Carolina A1 - Maas, Bea A1 - Martin, Emily A. A1 - Thomas, Evert A1 - Hanf-Dressler, Tara A1 - Schumacher, Nils-Christian A1 - Ulloque-Samatelo, Carlos A1 - Tscharntke, Teja A1 - Steffan-Dewenter, Ingolf T1 - Cacao flower visitation: Low pollen deposition, low fruit set and dominance of herbivores JF - Ecological Solutions and Evidence N2 - 1. Pollination services of cacao are crucial for global chocolate production, yet remain critically understudied, particularly in regions of origin of the species. Notably, uncertainties remain concerning the identity of cacao pollinators, the influence of landscape (forest distance) and management (shade cover) on flower visitation and the role of pollen deposition in limiting fruit set. 2. Here, we aimed to improve understanding of cacao pollination by studying limiting factors of fruit set in Peru, part of the centre of origin of cacao. Flower visitors were sampled with sticky insect glue in 20 cacao agroforests in two biogeographically distinct regions of Peru, across gradients of shade cover and forest distance. Further, we assessed pollen quantities and compared fruit set between naturally and manually pollinated flowers. 3. The most abundant flower visitors were aphids, ants and thrips in the north and thrips, midges and parasitoid wasps in the south of Peru. We present some evidence of increasing visitation rates from medium to high shade (40%–95% canopy closure) in the dry north, and opposite patterns in the semi-humid south, during the wet season. 4. Natural pollination resulted in remarkably low fruit set rates (2%), and very low pollen deposition. After hand pollination, fruit set more than tripled (7%), but was still low. 5. The diversity and high relative abundances of herbivore flower visitors limit our ability to draw conclusions on the functional role of different flower visitors. The remarkably low fruit set of naturally and even hand pollinated flowers indicates that other unaddressed factors limit cacao fruit production. Such factors could be, amongst others, a lack of effective pollinators, genetic incompatibility or resource limitation. Revealing efficient pollinator species and other causes of low fruit set rates is therefore key to establish location-specific management strategies and develop high yielding native cacao agroforestry systems in regions of origin of cacao KW - agroforestry KW - cocoa KW - flower visitors KW - forest proximity KW - hand pollination KW - pollen KW - pollination services KW - shade cover Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312722 SN - 2688-8319 VL - 3 IS - 2 ER - TY - JOUR A1 - Peters, Birte A1 - Keller, Alexander A1 - Leonhardt, Sara Diana T1 - Diets maintained in a changing world: Does land-use intensification alter wild bee communities by selecting for flexible generalists? JF - Ecology and evolution N2 - Biodiversity loss, as often found in intensively managed agricultural landscapes, correlates with reduced ecosystem functioning, for example, pollination by insects, and with altered plant composition, diversity, and abundance. But how does this change in floral resource diversity and composition relate to occurrence and resource use patterns of trap-nesting solitary bees? To better understand the impact of land-use intensification on communities of trap-nesting solitary bees in managed grasslands, we investigated their pollen foraging, reproductive fitness, and the nutritional quality of larval food along a land-use intensity gradient in Germany. We found bee species diversity to decrease with increasing land-use intensity irrespective of region-specific community compositions and interaction networks. Land use also strongly affected the diversity and composition of pollen collected by bees. Lack of suitable pollen sources likely explains the absence of several bee species at sites of high land-use intensity. The only species present throughout, Osmia bicornis (red mason bee), foraged on largely different pollen sources across sites. In doing so, it maintained a relatively stable, albeit variable nutritional quality of larval diets (i.e., protein to lipid (P:L) ratio). The observed changes in bee–plant pollen interaction patterns indicate that only the flexible generalists, such as O. bicornis, may be able to compensate the strong alterations in floral resource landscapes and to obtain food of sufficient quality through readily shifting to alternative plant sources. In contrast, other, less flexible, bee species disappear. KW - bee decline KW - biodiversity exploratories KW - foraging KW - metabarcoding KW - pollen nutrients KW - solitary bees Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312786 SN - 2045-7758 VL - 12 IS - 5 ER - TY - JOUR A1 - Kortmann, Mareike A1 - Angelstam, Per A1 - Mayer, Marius A1 - Leibl, Franz A1 - Reichert, Jessica A1 - Thorn, Christine A1 - Thorn, Simon T1 - Disturbance severity and human–nature relationships: A new approach to analyze people’s well-being along a bark beetle infestation gradient JF - Forests N2 - Contact to nature and greenspace is important for emotional well-being and can promote human health. Forest landscapes provide such access to greenspace, especially in protected areas. However, forested protected areas are impacted by natural disturbances such as bark beetle infestations. On the one hand, such disturbances have positive impacts on ecological processes and biodiversity. On the other hand, they have allegedly negative impacts on the recreational value of a landscape. Limited knowledge about the public’s perception of forests subject to natural disturbances still hampers forest management to balance ecological functions and visitors’ recreational experience. Thus, our aim was to determine how attitudes towards nature influence the personal well-being in a naturally disturbed landscape. We investigated self-reported well-being and attitudes towards nature in a standardized questionnaire-based survey of 1008 German inhabitants in an experimentally adapted landscape visualization. Self-reported well-being was generally highest in landscapes with relatively few bark-beetle-killed trees. This was especially the case for people who felt included with nature and preferred an appreciative use or preservation of nature. Conversely, people who had previously visited a national park with visible bark beetle infestations rated their personal well-being highest in landscapes with larger proportions of beetle-killed trees. Our results indicate that it is necessary to analyze people’s knowledge about and relations to forest landscapes as well as concepts of nature conservation, natural landscapes, and biodiversity to gain a better understanding of people’s perceptions of natural disturbances. KW - bark beetle disturbance KW - major environmental values KW - well-being KW - inclusion of nature in one’s self KW - national park Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297429 SN - 1999-4907 VL - 13 IS - 11 ER - TY - JOUR A1 - Değirmenci, Laura A1 - Rogé Ferreira, Fabio Luiz A1 - Vukosavljevic, Adrian A1 - Heindl, Cornelia A1 - Keller, Alexander A1 - Geiger, Dietmar A1 - Scheiner, Ricarda T1 - Sugar perception in honeybees JF - Frontiers in Physiology N2 - Honeybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously in vivo. We show that honeybees rely on two gustatory receptors to sense all relevant sugars. KW - AmGr1 KW - AmGr2 KW - AmGr3 KW - sugar responsiveness KW - proboscis extension response (PER) KW - gustatory receptors (Grs) KW - honeybee taste perception Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-302284 SN - 1664-042X VL - 13 ER - TY - JOUR A1 - Dannhäuser, Sven A1 - Mrestani, Achmed A1 - Gundelach, Florian A1 - Pauli, Martin A1 - Komma, Fabian A1 - Kollmannsberger, Philip A1 - Sauer, Markus A1 - Heckmann, Manfred A1 - Paul, Mila M. T1 - Endogenous tagging of Unc-13 reveals nanoscale reorganization at active zones during presynaptic homeostatic potentiation JF - Frontiers in Cellular Neuroscience N2 - Introduction Neurotransmitter release at presynaptic active zones (AZs) requires concerted protein interactions within a dense 3D nano-hemisphere. Among the complex protein meshwork the (M)unc-13 family member Unc-13 of Drosophila melanogaster is essential for docking of synaptic vesicles and transmitter release. Methods We employ minos-mediated integration cassette (MiMIC)-based gene editing using GFSTF (EGFP-FlAsH-StrepII-TEV-3xFlag) to endogenously tag all annotated Drosophila Unc-13 isoforms enabling visualization of endogenous Unc-13 expression within the central and peripheral nervous system. Results and discussion Electrophysiological characterization using two-electrode voltage clamp (TEVC) reveals that evoked and spontaneous synaptic transmission remain unaffected in unc-13\(^{GFSTF}\) 3rd instar larvae and acute presynaptic homeostatic potentiation (PHP) can be induced at control levels. Furthermore, multi-color structured-illumination shows precise co-localization of Unc-13\(^{GFSTF}\), Bruchpilot, and GluRIIA-receptor subunits within the synaptic mesoscale. Localization microscopy in combination with HDBSCAN algorithms detect Unc-13\(^{GFSTF}\) subclusters that move toward the AZ center during PHP with unaltered Unc-13\(^{GFSTF}\) protein levels. KW - active zone KW - Unc-13 KW - MiMIC KW - presynaptic homeostasis KW - nanoarchitecture KW - localization microscopy KW - STORM KW - HDBSCAN Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299440 SN - 1662-5102 VL - 16 ER - TY - JOUR A1 - Sarukhanyan, Edita A1 - Shanmugam, Tipack Ayothyapattanam A1 - Dandekar, Thomas T1 - In silico studies reveal Peramivir and Zanamivir as an optimal drug treatment even if H7N9 avian type influenza virus acquires further resistance JF - Molecules N2 - An epidemic of avian type H7N9 influenza virus, which took place in China in 2013, was enhanced by a naturally occurring R294K mutation resistant against Oseltamivir at the catalytic site of the neuraminidase. To cope with such drug-resistant neuraminidase mutations, we applied the molecular docking technique to evaluate the fitness of the available drugs such as Oseltamivir, Zanamivir, Peramivir, Laninamivir, L-Arginine and Benserazide hydrochloride concerning the N9 enzyme with single (R294K, R119K, R372K), double (R119_294K, R119_372K, R294_372K) and triple (R119_294_372K) mutations in the pocket. We found that the drugs Peramivir and Zanamivir score best amongst the studied compounds, demonstrating their high binding potential towards the pockets with the considered mutations. Despite the fact that mutations changed the shape of the pocket and reduced the binding strength for all drugs, Peramivir was the only drug that formed interactions with the key residues at positions 119, 294 and 372 in the pocket of the triple N9 mutant, while Zanamivir demonstrated the lowest RMSD value (0.7 Å) with respect to the reference structure. KW - H7N9 influenza virus KW - neuraminidase KW - mutation KW - binding pocket KW - molecular docking Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288240 SN - 1420-3049 VL - 27 IS - 18 ER - TY - JOUR A1 - Widder, Anna A1 - Kelm, Matthias A1 - Reibetanz, Joachim A1 - Wiegering, Armin A1 - Matthes, Niels A1 - Germer, Christoph-Thomas A1 - Seyfried, Florian A1 - Flemming, Sven T1 - Robotic-assisted versus laparoscopic left hemicolectomy — postoperative inflammation status, short-term outcome and cost effectiveness JF - International Journal of Environmental Research and Public Health N2 - Robotic-assisted colon surgery may contain advantages over the laparoscopic approach, but clear evidence is sparse. This study aimed to analyze postoperative inflammation status, short-term outcome and cost-effectiveness of robotic-assisted versus laparoscopic left hemicolectomy. All consecutive patients who received minimal-invasive left hemicolectomy at the Department of Surgery I at the University Hospital of Wuerzburg in 2021 were prospectively included. Importantly, no patient selection for either procedure was carried out. The robotic-assisted versus laparoscopic approaches were compared head to head for postoperative short-term outcomes as well as cost-effectiveness. A total of 61 patients were included, with 26 patients having received a robotic-assisted approach. Baseline characteristics did not differ among the groups. Patients receiving a robotic-assisted approach had a significantly decreased length of hospital stay as well as lower rates of complications in comparison to patients who received laparoscopic surgery (n = 35). In addition, C-reactive protein as a marker of systemic stress response was significantly reduced postoperatively in patients who were operated on in a robotic-assisted manner. Consequently, robotic-assisted surgery could be performed in a cost-effective manner. Thus, robotic-assisted left hemicolectomy represents a safe and cost-effective procedure and might improve patient outcomes in comparison to laparoscopic surgery. KW - robotic surgery KW - colon resection KW - postoperative inflammation KW - cost-effectiveness KW - left hemicolectomy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286203 SN - 1660-4601 VL - 19 IS - 17 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Osmanoglu, Özge A1 - Minocha, Rashmi A1 - Bandi, Sourish Reddy A1 - Bencurova, Elena A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information JF - Frontiers in Medicine N2 - Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design. KW - T-cell epitope KW - epitope prediction KW - positive selection KW - evolution KW - immune-informatics Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-293953 SN - 2296-858X VL - 9 ER - TY - JOUR A1 - Kaya-Zeeb, Sinan A1 - Delac, Saskia A1 - Wolf, Lena A1 - Marante, Ana Luiza A1 - Scherf-Clavel, Oliver A1 - Thamm, Markus T1 - Robustness of the honeybee neuro-muscular octopaminergic system in the face of cold stress JF - Frontiers in Physiology N2 - In recent decades, our planet has undergone dramatic environmental changes resulting in the loss of numerous species. This contrasts with species that can adapt quickly to rapidly changing ambient conditions, which require physiological plasticity and must occur rapidly. The Western honeybee (Apis mellifera) apparently meets this challenge with remarkable success, as this species is adapted to numerous climates, resulting in an almost worldwide distribution. Here, coordinated individual thermoregulatory activities ensure survival at the colony level and thus the transmission of genetic material. Recently, we showed that shivering thermogenesis, which is critical for honeybee thermoregulation, depends on octopamine signaling. In this study, we tested the hypothesis that the thoracic neuro-muscular octopaminergic system strives for a steady-state equilibrium under cold stress to maintain endogenous thermogenesis. We can show that this applies for both, octopamine provision by flight muscle innervating neurons and octopamine receptor expression in the flight muscles. Additionally, we discovered alternative splicing for AmOARβ2. At least the expression of one isoform is needed to survive cold stress conditions. We assume that the thoracic neuro-muscular octopaminergic system is finely tuned in order to contribute decisively to survival in a changing environment. KW - honeybees KW - thermogenesis KW - cold stress KW - octopamine KW - octopamine receptors KW - gene expression Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-288753 SN - 1664-042X VL - 13 ER - TY - JOUR A1 - Volland, Julian Manuel A1 - Kaupp, Johannes A1 - Schmitz, Werner A1 - Wünsch, Anna Chiara A1 - Balint, Julia A1 - Möllmann, Marc A1 - El-Mesery, Mohamed A1 - Frackmann, Kyra A1 - Peter, Leslie A1 - Hartmann, Stefan A1 - Kübler, Alexander Christian A1 - Seher, Axel T1 - Mass spectrometric metabolic fingerprinting of 2-Deoxy-D-Glucose (2-DG)-induced inhibition of glycolysis and comparative analysis of methionine restriction versus glucose restriction under perfusion culture in the murine L929 model system JF - International Journal of Molecular Sciences N2 - All forms of restriction, from caloric to amino acid to glucose restriction, have been established in recent years as therapeutic options for various diseases, including cancer. However, usually there is no direct comparison between the different restriction forms. Additionally, many cell culture experiments take place under static conditions. In this work, we used a closed perfusion culture in murine L929 cells over a period of 7 days to compare methionine restriction (MetR) and glucose restriction (LowCarb) in the same system and analysed the metabolome by liquid chromatography mass spectrometry (LC-MS). In addition, we analysed the inhibition of glycolysis by 2-deoxy-D-glucose (2-DG) over a period of 72 h. 2-DG induced very fast a low-energy situation by a reduced glycolysis metabolite flow rate resulting in pyruvate, lactate, and ATP depletion. Under perfusion culture, both MetR and LowCarb were established on the metabolic level. Interestingly, over the period of 7 days, the metabolome of MetR and LowCarb showed more similarities than differences. This leads to the conclusion that the conditioned medium, in addition to the different restriction forms, substantially reprogramm the cells on the metabolic level. KW - amino acid restriction KW - glucose restriction KW - mass spectrometry KW - low carb KW - 2-deoxy-D-glucose KW - 2-DG KW - methionine KW - perfusion culture KW - energy restriction KW - caloric restriction Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286007 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Minocha, Rashmi A1 - Thapa, Prithivi Jung A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Role of the pangolin in origin of SARS-CoV-2: an evolutionary perspective JF - International Journal of Molecular Sciences N2 - After the recent emergence of SARS-CoV-2 infection, unanswered questions remain related to its evolutionary history, path of transmission or divergence and role of recombination. There is emerging evidence on amino acid substitutions occurring in key residues of the receptor-binding domain of the spike glycoprotein in coronavirus isolates from bat and pangolins. In this article, we summarize our current knowledge on the origin of SARS-CoV-2. We also analyze the host ACE2-interacting residues of the receptor-binding domain of spike glycoprotein in SARS-CoV-2 isolates from bats, and compare it to pangolin SARS-CoV-2 isolates collected from Guangdong province (GD Pangolin-CoV) and Guangxi autonomous regions (GX Pangolin-CoV) of South China. Based on our comparative analysis, we support the view that the Guangdong Pangolins are the intermediate hosts that adapted the SARS-CoV-2 and represented a significant evolutionary link in the path of transmission of SARS-CoV-2 virus. We also discuss the role of intermediate hosts in the origin of Omicron. KW - COVID-19 KW - SARS-CoV-2 KW - origin KW - evolution KW - intermediate host KW - pangolin KW - mutation KW - recombination KW - adaptation KW - transmission KW - comparative sequence analysis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285995 SN - 1422-0067 VL - 23 IS - 16 ER - TY - JOUR A1 - Geiger, Nina A1 - Kersting, Louise A1 - Schlegel, Jan A1 - Stelz, Linda A1 - Fähr, Sofie A1 - Diesendorf, Viktoria A1 - Roll, Valeria A1 - Sostmann, Marie A1 - König, Eva-Maria A1 - Reinhard, Sebastian A1 - Brenner, Daniela A1 - Schneider-Schaulies, Sibylle A1 - Sauer, Markus A1 - Seibel, Jürgen A1 - Bodem, Jochen T1 - The acid ceramidase is a SARS-CoV-2 host factor JF - Cells N2 - SARS-CoV-2 variants such as the delta or omicron variants, with higher transmission rates, accelerated the global COVID-19 pandemic. Thus, novel therapeutic strategies need to be deployed. The inhibition of acid sphingomyelinase (ASM), interfering with viral entry by fluoxetine was reported. Here, we described the acid ceramidase as an additional target of fluoxetine. To discover these effects, we synthesized an ASM-independent fluoxetine derivative, AKS466. High-resolution SARS-CoV-2–RNA FISH and RTqPCR analyses demonstrate that AKS466 down-regulates viral gene expression. It is shown that SARS-CoV-2 deacidifies the lysosomal pH using the ORF3 protein. However, treatment with AKS488 or fluoxetine lowers the lysosomal pH. Our biochemical results show that AKS466 localizes to the endo-lysosomal replication compartments of infected cells, and demonstrate the enrichment of the viral genomic, minus-stranded RNA and mRNAs there. Both fluoxetine and AKS466 inhibit the acid ceramidase activity, cause endo-lysosomal ceramide elevation, and interfere with viral replication. Furthermore, Ceranib-2, a specific acid ceramidase inhibitor, reduces SARS-CoV-2 replication and, most importantly, the exogenous supplementation of C6-ceramide interferes with viral replication. These results support the hypotheses that the acid ceramidase is a SARS-CoV-2 host factor. KW - SARS-CoV-2 KW - ceramides KW - ceramidase KW - fluoxetine KW - acid sphingomyelinase Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286105 SN - 2073-4409 VL - 11 IS - 16 ER - TY - JOUR A1 - Caliskan, Aylin A1 - Crouch, Samantha A. W. A1 - Giddins, Sara A1 - Dandekar, Thomas A1 - Dangwal, Seema T1 - Progeria and aging — Omics based comparative analysis JF - Biomedicines N2 - Since ancient times aging has also been regarded as a disease, and humankind has always strived to extend the natural lifespan. Analyzing the genes involved in aging and disease allows for finding important indicators and biological markers for pathologies and possible therapeutic targets. An example of the use of omics technologies is the research regarding aging and the rare and fatal premature aging syndrome progeria (Hutchinson-Gilford progeria syndrome, HGPS). In our study, we focused on the in silico analysis of differentially expressed genes (DEGs) in progeria and aging, using a publicly available RNA-Seq dataset (GEO dataset GSE113957) and a variety of bioinformatics tools. Despite the GSE113957 RNA-Seq dataset being well-known and frequently analyzed, the RNA-Seq data shared by Fleischer et al. is far from exhausted and reusing and repurposing the data still reveals new insights. By analyzing the literature citing the use of the dataset and subsequently conducting a comparative analysis comparing the RNA-Seq data analyses of different subsets of the dataset (healthy children, nonagenarians and progeria patients), we identified several genes involved in both natural aging and progeria (KRT8, KRT18, ACKR4, CCL2, UCP2, ADAMTS15, ACTN4P1, WNT16, IGFBP2). Further analyzing these genes and the pathways involved indicated their possible roles in aging, suggesting the need for further in vitro and in vivo research. In this paper, we (1) compare “normal aging” (nonagenarians vs. healthy children) and progeria (HGPS patients vs. healthy children), (2) enlist genes possibly involved in both the natural aging process and progeria, including the first mention of IGFBP2 in progeria, (3) predict miRNAs and interactomes for WNT16 (hsa-mir-181a-5p), UCP2 (hsa-mir-26a-5p and hsa-mir-124-3p), and IGFBP2 (hsa-mir-124-3p, hsa-mir-126-3p, and hsa-mir-27b-3p), (4) demonstrate the compatibility of well-established R packages for RNA-Seq analysis for researchers interested but not yet familiar with this kind of analysis, and (5) present comparative proteomics analyses to show an association between our RNA-Seq data analyses and corresponding changes in protein expression. KW - progeria KW - aging KW - omics KW - RNA sequencing KW - bioinformatics KW - sun exposure KW - HGPS KW - IGFBP2 KW - ACKR4 KW - WNT Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-289868 SN - 2227-9059 VL - 10 IS - 10 ER - TY - JOUR A1 - Tamihardja, Jörg A1 - Zehner, Leonie A1 - Hartrampf, Philipp A1 - Lisowski, Dominik A1 - Kneitz, Susanne A1 - Cirsi, Sinan A1 - Razinskas, Gary A1 - Flentje, Michael A1 - Polat, Bülent T1 - Salvage nodal radiotherapy as metastasis-directed therapy for oligorecurrent prostate cancer detected by positron emission tomography shows favorable outcome in long-term follow-up JF - Cancers N2 - Simple Summary Patients, who suffer from oligorecurrent prostate cancer with limited nodal involvement, may be offered positron emission tomography (PET)-directed salvage nodal radiotherapy to delay disease progression. This current analysis aimed to access salvage radiotherapy for nodal oligorecurrent prostate cancer with simultaneous integrated boost to PET-involved lymph nodes as metastasis-directed therapy. A long-term oncological outcome was favorable after salvage nodal radiotherapy and severe toxicity rates were low. Androgen deprivation therapy plays a major role in recurrent prostate cancer management and demonstrates a positive influence on the rate of biochemical progression in patients receiving salvage nodal radiotherapy. The present long-term analysis may help clinicians identify patients who would benefit from salvage nodal radiotherapy and androgen deprivation therapy, as a multimodal treatment strategy for oligorecurrent prostate cancer. Abstract Background: The study aimed to access the long-term outcome of salvage nodal radiotherapy (SNRT) in oligorecurrent prostate cancer. Methods: A total of 95 consecutive patients received SNRT for pelvic and/or extrapelvic nodal recurrence after prostate-specific membrane antigen (PSMA) or choline PET from 2010 to 2021. SNRT was applied as external beam radiotherapy with simultaneous integrated boost up to a median total dose of 62.9 Gy (EQD2\(_{1.5Gy}\)) to the recurrent lymph node metastases. The outcome was analyzed by cumulative incidence functions with death as the competing risk. Fine–Gray regression analyses were performed to estimate the relative hazards of the outcome parameters. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (v5.0). The results are as follows: the median follow-up was 47.1 months. The five-year biochemical progression rate (95% CI) was 50.1% (35.7–62.9%). Concomitant androgen deprivation therapy (ADT) was adminstered in 60.0% of the patients. The five-year biochemical progression rate was 75.0% (42.0–90.9%) without ADT versus 35.3% (19.6–51.4%) with ADT (p = 0.003). The cumulative five-year late grade 3 GU toxicity rate was 2.1%. No late grade 3 GI toxicity occured. Conclusions: Metastasis-directed therapy through SNRT for PET-staged oligorecurrent prostate cancer demonstrated a favorable long-term oncologic outcome. Omittance of ADT led to an increased biochemical progression. KW - metastasis-directed therapy KW - long-term outcome KW - oligorecurrence KW - prostate cancer KW - salvage radiotherapy KW - PSMA Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286064 SN - 2072-6694 VL - 14 IS - 15 ER - TY - JOUR A1 - Fathy, Moustafa A1 - Darwish, Mostafa A. A1 - Abdelhamid, Al-Shaimaa M. A1 - Alrashedy, Gehad M. A1 - Othman, Othman Ali A1 - Naseem, Muhammad A1 - Dandekar, Thomas A1 - Othman, Eman M. T1 - Kinetin ameliorates cisplatin-induced hepatotoxicity and lymphotoxicity via attenuating oxidative damage, cell apoptosis and inflammation in rats JF - Biomedicines N2 - Though several previous studies reported the in vitro and in vivo antioxidant effect of kinetin (Kn), details on its action in cisplatin-induced toxicity are still scarce. In this study we evaluated, for the first time, the effects of kinetin in cisplatin (cp)- induced liver and lymphocyte toxicity in rats. Wistar male albino rats were divided into nine groups: (i) the control (C), (ii) groups 2,3 and 4, which received 0.25, 0.5 and 1 mg/kg kinetin for 10 days; (iii) the cisplatin (cp) group, which received a single intraperitoneal injection of CP (7.0 mg/kg); and (iv) groups 6, 7, 8 and 9, which received, for 10 days, 0.25, 0.5 and 1 mg/kg kinetin or 200 mg/kg vitamin C, respectively, and Cp on the fourth day. CP-injected rats showed a significant impairment in biochemical, oxidative stress and inflammatory parameters in hepatic tissue and lymphocytes. PCR showed a profound increase in caspase-3, and a significant decline in AKT gene expression. Intriguingly, Kn treatment restored the biochemical, redox status and inflammatory parameters. Hepatic AKT and caspase-3 expression as well as CD95 levels in lymphocytes were also restored. In conclusion, Kn mitigated oxidative imbalance, inflammation and apoptosis in CP-induced liver and lymphocyte toxicity; therefore, it can be considered as a promising therapy. KW - cisplatin KW - hepatotoxicity KW - lymphotoxicity KW - oxidative stress KW - AKT KW - CD95 KW - caspase-3 Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281686 SN - 2227-9059 VL - 10 IS - 7 ER - TY - JOUR A1 - Schwarz, Jessica Denise A1 - Lukassen, Sören A1 - Bhandare, Pranjali A1 - Eing, Lorenz A1 - Snaebjörnsson, Marteinn Thor A1 - García, Yiliam Cruz A1 - Kisker, Jan Philipp A1 - Schulze, Almut A1 - Wolf, Elmar T1 - The glycolytic enzyme ALDOA and the exon junction complex protein RBM8A are regulators of ribosomal biogenesis JF - Frontiers in Cell and Developmental Biology N2 - Cellular growth is a fundamental process of life and must be precisely controlled in multicellular organisms. Growth is crucially controlled by the number of functional ribosomes available in cells. The production of new ribosomes depends critically on the activity of RNA polymerase (RNAP) II in addition to the activity of RNAP I and III, which produce ribosomal RNAs. Indeed, the expression of both, ribosomal proteins and proteins required for ribosome assembly (ribosomal biogenesis factors), is considered rate-limiting for ribosome synthesis. Here, we used genetic screening to identify novel transcriptional regulators of cell growth genes by fusing promoters from a ribosomal protein gene (Rpl18) and from a ribosomal biogenesis factor (Fbl) with fluorescent protein genes (RFP, GFP) as reporters. Subsequently, both reporters were stably integrated into immortalized mouse fibroblasts, which were then transduced with a genome-wide sgRNA-CRISPR knockout library. Subsequently, cells with altered reporter activity were isolated by FACS and the causative sgRNAs were identified. Interestingly, we identified two novel regulators of growth genes. Firstly, the exon junction complex protein RBM8A controls transcript levels of the intronless reporters used here. By acute depletion of RBM8A protein using the auxin degron system combined with the genome-wide analysis of nascent transcription, we showed that RBM8A is an important global regulator of ribosomal protein transcripts. Secondly, we unexpectedly observed that the glycolytic enzyme aldolase A (ALDOA) regulates the expression of ribosomal biogenesis factors. Consistent with published observations that a fraction of this protein is located in the nucleus, this may be a mechanism linking transcription of growth genes to metabolic processes and possibly to metabolite availability. KW - ribosome biogenesis KW - Ribosomal protein gene KW - genetic screen KW - genome-wide screen KW - RBM8A KW - Y14 KW - AldoA KW - aldolase A Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290875 SN - 2296-634X VL - 10 ER - TY - JOUR A1 - Schilcher, Felix A1 - Hilsmann, Lioba A1 - Ankenbrand, Markus J. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Steffan-Dewenter, Ingolf A1 - Scheiner, Ricarda T1 - Honeybees are buffered against undernourishment during larval stages JF - Frontiers in Insect Science N2 - The negative impact of juvenile undernourishment on adult behavior has been well reported for vertebrates, but relatively little is known about invertebrates. In honeybees, nutrition has long been known to affect task performance and timing of behavioral transitions. Whether and how a dietary restriction during larval development affects the task performance of adult honeybees is largely unknown. We raised honeybees in-vitro, varying the amount of a standardized diet (150 µl, 160 µl, 180 µl in total). Emerging adults were marked and inserted into established colonies. Behavioral performance of nurse bees and foragers was investigated and physiological factors known to be involved in the regulation of social organization were quantified. Surprisingly, adult honeybees raised under different feeding regimes did not differ in any of the behaviors observed. No differences were observed in physiological parameters apart from weight. Honeybees were lighter when undernourished (150 µl), while they were heavier under the overfed treatment (180 µl) compared to the control group raised under a normal diet (160 µl). These data suggest that dietary restrictions during larval development do not affect task performance or physiology in this social insect despite producing clear effects on adult weight. We speculate that possible effects of larval undernourishment might be compensated during the early period of adult life. KW - nutrition KW - juvenile hormone KW - nurse bees KW - foragers KW - triglycerides KW - undernourishment KW - task allocation Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304646 SN - 2673-8600 VL - 2 ER - TY - JOUR A1 - Wegener, Christian A1 - Chen, Jiangtian T1 - Allatostatin A signalling: progress and new challenges from a paradigmatic pleiotropic invertebrate neuropeptide family JF - Frontiers in Physiology N2 - Neuropeptides have gained broad attraction in insect neuroscience and physiology, as new genetic tools are increasingly uncovering their wide-ranging pleiotropic functions with high cellular resolution. Allatostatin A (AstA) peptides constitute one of the best studied insect neuropeptide families. In insects and other panarthropods, AstA peptides qualify as brain-gut peptides and have regained attention with the discovery of their role in regulating feeding, growth, activity/sleep and learning. AstA receptor homologs are found throughout the protostomia and group with vertebrate somatostatin/galanin/kisspeptin receptors. In this review, we summarise the current knowledge on the evolution and the pleiotropic and cell-specific non-allatostatic functions of AstA. We speculate about the core functions of AstA signalling, and derive open questions and challengesfor future research on AstA and invertebrate neuropeptides in general. KW - neuropeptide signalling KW - feeding KW - intestinal control KW - sleep/activity KW - kisspeptin/galanin/spexin signalling KW - metabolism and growth KW - learning KW - cardioactive factor Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-278749 SN - 1664-042X VL - 13 ER - TY - JOUR A1 - Köhler, Franziska A1 - Reese, Lena A1 - Kastner, Carolin A1 - Hendricks, Anne A1 - Müller, Sophie A1 - Lock, Johan F. A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Surgical site infection following single-port appendectomy: a systematic review of the literature and meta-analysis JF - Frontiers in Surgery N2 - Introduction Surgical site infections (SSIs) are one of the most common postoperative complications after appendectomy leading to recurrent surgery, prolonged hospital stay, and the use of antibiotics. Numerous studies and meta-analyses have been published on the effect of open versus conventional laparoscopic appendectomy (CLA) reporting faster postoperative recovery and less postoperative pain for CLA. A development from CLA has been the single-port appendectomy (SPA), associated with a better cosmesis but seemingly having a higher risk of wound infections. The aim of this systematic literature review and meta-analysis is to investigate whether reduced port or SPA alters the ratio of SSIs. Methods Pubmed, Embase, and Cochrane databases were screened for suitable articles. All articles published between January 1, 2002, and March 23, 2022, were included. Articles regarding children below the age of 18 were excluded as well as manuscripts that investigated solemnly open appendectomies. Articles were screened for inclusion criteria by two independent authors. Incidence of SSI was the primary outcome. Duration of operation and length of hospital stay were defined as secondary outcomes. Results A total of 25 studies were found through a database search describing 5484 patients. A total of 2749 patients received SPA and 2735 received CLA. There was no statistical difference in the rate of SSI (P = 0.98). A total of 22 studies including 4699 patients reported the duration of operation (2223 SPA and 2476 CLA). There was a significantly shorter operation time seen in CLA. The length of hospital stay was reported in 23 studies (4735 patients: 2235 SPA and 2500 CLA). A shorter hospital stay was seen in the SPA group (P < 0.00001). Separately performed analysis of randomized controlled trials could not confirm this effect (P = 0.29). Discussion SPA is an equally safe procedure considering SSI compared to CLA and does not lead to an increased risk of SSI. A longer operation time for SPA and a minor difference in the length of stay does lead to the use of SPA in selected patients only. KW - appendicitis KW - appendectomy KW - surgical site infection KW - single-port appendectomy KW - conventional laparoscopic appendectomy KW - wound infection KW - SSI Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276943 SN - 2296-875X VL - 9 ER - TY - JOUR A1 - Trifault, Barbara A1 - Mamontova, Victoria A1 - Burger, Kaspar T1 - In vivo proximity labeling of nuclear and nucleolar proteins by a stably expressed, DNA damage-responsive NONO-APEX2 fusion protein JF - Frontiers in Molecular Biosciences N2 - Cellular stress can induce DNA lesions that threaten the stability of genes. The DNA damage response (DDR) recognises and repairs broken DNA to maintain genome stability. Intriguingly, components of nuclear paraspeckles like the non-POU domain containing octamer-binding protein (NONO) participate in the repair of DNA double-strand breaks (DSBs). NONO is a multifunctional RNA-binding protein (RBP) that facilitates the retention and editing of messenger (m)RNA as well as pre-mRNA processing. However, the role of NONO in the DDR is poorly understood. Here, we establish a novel human U2OS cell line that expresses NONO fused to the engineered ascorbate peroxidase 2 (U2OS:NONO-APEX2-HA). We show that NONO-APEX2-HA accumulates in the nucleolus in response to DNA damage. Combining viability assays, subcellular localisation studies, coimmunoprecipitation experiments and in vivo proximity labeling, we demonstrate that NONO-APEX2-HA is a stably expressed fusion protein that mimics endogenous NONO in terms of expression, localisation and bona fide interactors. We propose that in vivo proximity labeling in U2OS:NONO-APEX2-HA cells is capable for the assessment of NONO interactomes by downstream assays. U2OS:NONO-APEX2-HA cells will likely be a valuable resource for the investigation of NONO interactome dynamics in response to DNA damage and other stimuli. KW - APEX2 KW - proximity labeling KW - NONO KW - paraspeckles KW - nucleolus KW - DNA damage Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-276707 SN - 2296-889X VL - 9 ER - TY - JOUR A1 - Abdel-Latif, Rania A1 - Fathy, Moustafa A1 - Anwar, Hend Ali A1 - Naseem, Muhammad A1 - Dandekar, Thomas A1 - Othman, Eman M. T1 - Cisplatin-induced reproductive toxicity and oxidative stress: ameliorative effect of kinetin JF - Antioxidants N2 - Cisplatin is a commonly used chemotherapeutic agent; however, its potential side effects, including gonadotoxicity and infertility, are a critical problem. Oxidative stress has been implicated in the pathogenesis of cisplatin-induced testicular dysfunction. We investigated whether kinetin use at different concentrations could alleviate gonadal injury associated with cisplatin treatment, with an exploration of the involvement of its antioxidant capacity. Kinetin was administered in different doses of 0.25, 0.5, and 1 mg/kg, alone or along with cisplatin for 10 days. Cisplatin toxicity was induced via a single IP dose of 7 mg/kg on day four. In a dose-dependent manner, concomitant administration of kinetin with cisplatin significantly restored testicular oxidative stress parameters, corrected the distorted sperm quality parameters and histopathological changes, enhanced levels of serum testosterone and testicular StAR protein expression, as well as reduced the up-regulation of testicular TNF-α, IL-1β, Il-6, and caspase-3, caused by cisplatin. It is worth noting that the testicular protective effect of the highest kinetin dose was comparable/more potent and significantly higher than the effects of vitamin C and the lowest kinetin dose, respectively. Overall, these data indicate that kinetin may offer a promising approach for alleviating cisplatin-induced reproductive toxicity and organ damage, via ameliorating oxidative stress and reducing inflammation and apoptosis. KW - cytokinins KW - kinetin KW - cisplatin KW - reproductive toxicity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271223 SN - 2076-3921 VL - 11 IS - 5 ER - TY - JOUR A1 - Uttinger, Konstantin L. A1 - Riedmeier, Maria A1 - Reibetanz, Joachim A1 - Meyer, Thomas A1 - Germer, Christoph Thomas A1 - Fassnacht, Martin A1 - Wiegering, Armin A1 - Wiegering, Verena T1 - Adrenalectomies in children and adolescents in Germany – a diagnose related groups based analysis from 2009-2017 JF - Frontiers in Endocrinology N2 - Background Adrenalectomies are rare procedures especially in childhood. So far, no large cohort study on this topic has been published with data on to age distribution, operative procedures, hospital volume and operative outcome. Methods This is a retrospective analysis of anonymized nationwide hospital billing data (DRG data, 2009-2017). All adrenal surgeries (defined by OPS codes) of patients between the age 0 and 21 years in Germany were included. Results A total of 523 patient records were identified. The mean age was 8.6 ± 7.7 years and 262 patients were female (50.1%). The majority of patients were between 0 and 5 years old (52% overall), while 11.1% were between 6 and 11 and 38.8% older than 12 years. The most common diagnoses were malignant neoplasms of the adrenal gland (56%, mostly neuroblastoma) with the majority being younger than 5 years. Benign neoplasms in the adrenal gland (D350) account for 29% of all cases with the majority of affected patients being 12 years or older. 15% were not defined regarding tumor behavior. Overall complication rate was 27% with a clear higher complication rate in resection for malignant neoplasia of the adrenal gland. Bleeding occurrence and transfusions are the main complications, followed by the necessary of relaparotomy. There was an uneven patient distribution between hospital tertiles (low volume, medium and high volume tertile). While 164 patients received surgery in 85 different “low volume” hospitals (0.2 cases per hospital per year), 205 patients received surgery in 8 different “high volume” hospitals (2.8 cases per hospital per year; p<0.001). Patients in high volume centers were significant younger, had more extended resections and more often malignant neoplasia. In multivariable analysis younger age, extended resections and open procedures were independent predictors for occurrence of postoperative complications. Conclusion Overall complication rate of adrenalectomies in the pediatric population in Germany is low, demonstrating good therapeutic quality. Our analysis revealed a very uneven distribution of patient volume among hospitals. KW - pediatric KW - neuroblastoma – diagnosis KW - therapy KW - adrenocortical adenocarcinoma KW - outcome KW - volume KW - adrenalectomia Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282280 SN - 1664-2392 VL - 13 ER - TY - JOUR A1 - Beetz, M. Jerome A1 - Hechavarría, Julio C. T1 - Neural processing of naturalistic echolocation signals in bats JF - Frontiers in Neural Circuits N2 - Echolocation behavior, a navigation strategy based on acoustic signals, allows scientists to explore neural processing of behaviorally relevant stimuli. For the purpose of orientation, bats broadcast echolocation calls and extract spatial information from the echoes. Because bats control call emission and thus the availability of spatial information, the behavioral relevance of these signals is undiscussable. While most neurophysiological studies, conducted in the past, used synthesized acoustic stimuli that mimic portions of the echolocation signals, recent progress has been made to understand how naturalistic echolocation signals are encoded in the bat brain. Here, we review how does stimulus history affect neural processing, how spatial information from multiple objects and how echolocation signals embedded in a naturalistic, noisy environment are processed in the bat brain. We end our review by discussing the huge potential that state-of-the-art recording techniques provide to gain a more complete picture on the neuroethology of echolocation behavior. KW - biosonar KW - neural coding KW - naturalistic stimuli KW - bats KW - acoustic stream KW - neuroethology Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-274605 SN - 1662-5110 VL - 16 ER - TY - JOUR A1 - Mamontova, Victoria A1 - Trifault, Barbara A1 - Burger, Kaspar T1 - Compartment-specific proximity ligation expands the toolbox to assess the interactome of the long non-coding RNA NEAT1 JF - International Journal of Molecular Sciences N2 - The nuclear paraspeckle assembly transcript 1 (NEAT1) locus encodes two long non-coding (lnc)RNA isoforms that are upregulated in many tumours and dynamically expressed in response to stress. NEAT1 transcripts form ribonucleoprotein complexes with numerous RNA-binding proteins (RBPs) to assemble paraspeckles and modulate the localisation and activity of gene regulatory enzymes as well as a subset of messenger (m)RNA transcripts. The investigation of the dynamic composition of NEAT1-associated proteins and mRNAs is critical to understand the function of NEAT1. Interestingly, a growing number of biochemical and genetic tools to assess NEAT1 interactomes has been reported. Here, we discuss the Hybridisation Proximity (HyPro) labeling technique in the context of NEAT1. HyPro labeling is a recently developed method to detect spatially ordered interactions of RNA-containing nuclear compartments in cultured human cells. After introducing NEAT1 and paraspeckles, we describe the advantages of the HyPro technology in the context of other methods to study RNA interactomes, and review the key findings in mapping NEAT1-associated RNA transcripts and protein binding partners. We further discuss the limitations and potential improvements of HyPro labeling, and conclude by delineating its applicability in paraspeckles-related cancer research. KW - proximity ligation KW - paraspeckles KW - NEAT1 KW - long non-coding RNA KW - cancer Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284185 SN - 1422-0067 VL - 23 IS - 8 ER - TY - JOUR A1 - Herbert, Saskia-Laureen A1 - Fick, Andrea A1 - Heydarian, Motaharehsadat A1 - Metzger, Marco A1 - Wöckel, Achim A1 - Rudel, Thomas A1 - Kozjak-Pavlovic, Vera A1 - Wulff, Christine T1 - Establishment of the SIS scaffold-based 3D model of human peritoneum for studying the dissemination of ovarian cancer JF - Journal of Tissue Engineering N2 - Ovarian cancer is the second most common gynecological malignancy in women. More than 70% of the cases are diagnosed at the advanced stage, presenting as primary peritoneal metastasis, which results in a poor 5-year survival rate of around 40%. Mechanisms of peritoneal metastasis, including adhesion, migration, and invasion, are still not completely understood and therapeutic options are extremely limited. Therefore, there is a strong requirement for a 3D model mimicking the in vivo situation. In this study, we describe the establishment of a 3D tissue model of the human peritoneum based on decellularized porcine small intestinal submucosa (SIS) scaffold. The SIS scaffold was populated with human dermal fibroblasts, with LP-9 cells on the apical side representing the peritoneal mesothelium, while HUVEC cells on the basal side of the scaffold served to mimic the endothelial cell layer. Functional analyses of the transepithelial electrical resistance (TEER) and the FITC-dextran assay indicated the high barrier integrity of our model. The histological, immunohistochemical, and ultrastructural analyses showed the main characteristics of the site of adhesion. Initial experiments using the SKOV-3 cell line as representative for ovarian carcinoma demonstrated the usefulness of our models for studying tumor cell adhesion, as well as the effect of tumor cells on endothelial cell-to-cell contacts. Taken together, our data show that the novel peritoneal 3D tissue model is a promising tool for studying the peritoneal dissemination of ovarian cancer. KW - ovarian cancer KW - 3D tissue model KW - co-culture KW - peritoneal metastasis KW - cancer dissemination Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301311 SN - 2041-7314 VL - 13 ER - TY - JOUR A1 - Reinhard, Nils A1 - Schubert, Frank K. A1 - Bertolini, Enrico A1 - Hagedorn, Nicolas A1 - Manoli, Giulia A1 - Sekiguchi, Manabu A1 - Yoshii, Taishi A1 - Rieger, Dirk A1 - Helfrich-Förster, Charlotte T1 - The neuronal circuit of the dorsal circadian clock neurons in Drosophila melanogaster JF - Frontiers in Physiology N2 - Drosophila’s dorsal clock neurons (DNs) consist of four clusters (DN1as, DN1ps, DN2s, and DN3s) that largely differ in size. While the DN1as and the DN2s encompass only two neurons, the DN1ps consist of ∼15 neurons, and the DN3s comprise ∼40 neurons per brain hemisphere. In comparison to the well-characterized lateral clock neurons (LNs), the neuroanatomy and function of the DNs are still not clear. Over the past decade, numerous studies have addressed their role in the fly’s circadian system, leading to several sometimes divergent results. Nonetheless, these studies agreed that the DNs are important to fine-tune activity under light and temperature cycles and play essential roles in linking the output from the LNs to downstream neurons that control sleep and metabolism. Here, we used the Flybow system, specific split-GAL4 lines, trans-Tango, and the recently published fly connectome (called hemibrain) to describe the morphology of the DNs in greater detail, including their synaptic connections to other clock and non-clock neurons. We show that some DN groups are largely heterogenous. While certain DNs are strongly connected with the LNs, others are mainly output neurons that signal to circuits downstream of the clock. Among the latter are mushroom body neurons, central complex neurons, tubercle bulb neurons, neurosecretory cells in the pars intercerebralis, and other still unidentified partners. This heterogeneity of the DNs may explain some of the conflicting results previously found about their functionality. Most importantly, we identify two putative novel communication centers of the clock network: one fiber bundle in the superior lateral protocerebrum running toward the anterior optic tubercle and one fiber hub in the posterior lateral protocerebrum. Both are invaded by several DNs and LNs and might play an instrumental role in the clock network. KW - circadian clock KW - dorsal clock neurons KW - trans-tango KW - flybow KW - neuroanatomy KW - hemibrain KW - clock network Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-272527 SN - 1664-042X VL - 13 ER - TY - JOUR A1 - Fathy, Moustafa A1 - Saad Eldin, Sahar M. A1 - Naseem, Muhammad A1 - Dandekar, Thomas A1 - Othman, Eman M. T1 - Cytokinins: wide-spread signaling hormones from plants to humans with high medical potential JF - Nutrients N2 - Nature is a rich source of biologically active novel compounds. Sixty years ago, the plant hormones cytokinins were first discovered. These play a major role in cell division and cell differentiation. They affect organogenesis in plant tissue cultures and contribute to many other physiological and developmental processes in plants. Consequently, the effect of cytokinins on mammalian cells has caught the attention of researchers. Many reports on the contribution and potential of cytokinins in the therapy of different human diseases and pathophysiological conditions have been published and are reviewed here. We compare cytokinin effects and pathways in plants and mammalian systems and highlight the most important biological activities. We present the strong profile of the biological actions of cytokinins and their possible therapeutic applications. KW - cytokinins KW - phytohormones KW - biological activities KW - plant system KW - mammalian system Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-271017 SN - 2072-6643 VL - 14 IS - 7 ER - TY - JOUR A1 - Bencurova, Elena A1 - Shityakov, Sergey A1 - Schaack, Dominik A1 - Kaltdorf, Martin A1 - Sarukhanyan, Edita A1 - Hilgarth, Alexander A1 - Rath, Christin A1 - Montenegro, Sergio A1 - Roth, Günter A1 - Lopez, Daniel A1 - Dandekar, Thomas T1 - Nanocellulose composites as smart devices with chassis, light-directed DNA Storage, engineered electronic properties, and chip integration JF - Frontiers in Bioengineering and Biotechnology N2 - The rapid development of green and sustainable materials opens up new possibilities in the field of applied research. Such materials include nanocellulose composites that can integrate many components into composites and provide a good chassis for smart devices. In our study, we evaluate four approaches for turning a nanocellulose composite into an information storage or processing device: 1) nanocellulose can be a suitable carrier material and protect information stored in DNA. 2) Nucleotide-processing enzymes (polymerase and exonuclease) can be controlled by light after fusing them with light-gating domains; nucleotide substrate specificity can be changed by mutation or pH change (read-in and read-out of the information). 3) Semiconductors and electronic capabilities can be achieved: we show that nanocellulose is rendered electronic by iodine treatment replacing silicon including microstructures. Nanocellulose semiconductor properties are measured, and the resulting potential including single-electron transistors (SET) and their properties are modeled. Electric current can also be transported by DNA through G-quadruplex DNA molecules; these as well as classical silicon semiconductors can easily be integrated into the nanocellulose composite. 4) To elaborate upon miniaturization and integration for a smart nanocellulose chip device, we demonstrate pH-sensitive dyes in nanocellulose, nanopore creation, and kinase micropatterning on bacterial membranes as well as digital PCR micro-wells. Future application potential includes nano-3D printing and fast molecular processors (e.g., SETs) integrated with DNA storage and conventional electronics. This would also lead to environment-friendly nanocellulose chips for information processing as well as smart nanocellulose composites for biomedical applications and nano-factories. KW - nanocellulose KW - DNA storage KW - light-gated proteins KW - single-electron transistors KW - protein chip Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283033 SN - 2296-4185 VL - 10 ER - TY - JOUR A1 - Nguyen, Tu Anh Thi A1 - Beetz, M. Jerome A1 - Merlin, Christine A1 - Pfeiffer, Keram A1 - el Jundi, Basil T1 - Weighting of celestial and terrestrial cues in the monarch butterfly central complex JF - Frontiers in Neural Circuits N2 - Monarch butterflies rely on external cues for orientation during their annual long-distance migration from Northern US and Canada to Central Mexico. These external cues can be celestial cues, such as the sun or polarized light, which are processed in a brain region termed the central complex (CX). Previous research typically focused on how individual simulated celestial cues are encoded in the butterfly's CX. However, in nature, the butterflies perceive several celestial cues at the same time and need to integrate them to effectively use the compound of all cues for orientation. In addition, a recent behavioral study revealed that monarch butterflies can rely on terrestrial cues, such as the panoramic skyline, for orientation and use them in combination with the sun to maintain a directed flight course. How the CX encodes a combination of celestial and terrestrial cues and how they are weighted in the butterfly's CX is still unknown. Here, we examined how input neurons of the CX, termed TL neurons, combine celestial and terrestrial information. While recording intracellularly from the neurons, we presented a sun stimulus and polarized light to the butterflies as well as a simulated sun and a panoramic scene simultaneously. Our results show that celestial cues are integrated linearly in these cells, while the combination of the sun and a panoramic skyline did not always follow a linear integration of action potential rates. Interestingly, while the sun and polarized light were invariantly weighted between individual neurons, the sun stimulus and panoramic skyline were dynamically weighted when both stimuli were simultaneously presented. Taken together, this dynamic weighting between celestial and terrestrial cues may allow the butterflies to flexibly set their cue preference during navigation. KW - insect KW - central complex KW - navigation KW - orientation KW - landmark KW - migration KW - panorama KW - lepidoptera Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-279445 SN - 1662-5110 VL - 16 ER - TY - JOUR A1 - Nanda, Indrajit A1 - Schories, Susanne A1 - Simeonov, Ivan A1 - Adolfi, Mateus Contar A1 - Du, Kang A1 - Steinlein, Claus A1 - Alsheimer, Manfred A1 - Haaf, Thomas A1 - Schartl, Manfred T1 - Evolution of the degenerated Y-chromosome of the swamp guppy, Micropoecilia picta JF - Cells N2 - The conspicuous colour sexual dimorphism of guppies has made them paradigmatic study objects for sex-linked traits and sex chromosome evolution. Both the X- and Y-chromosomes of the common guppy (Poecilia reticulata) are genetically active and homomorphic, with a large homologous part and a small sex specific region. This feature is considered to emulate the initial stage of sex chromosome evolution. A similar situation has been documented in the related Endler’s and Oropuche guppies (P. wingei, P. obscura) indicating a common origin of the Y in this group. A recent molecular study in the swamp guppy (Micropoecilia. picta) reported a low SNP density on the Y, indicating Y-chromosome deterioration. We performed a series of cytological studies on M. picta to show that the Y-chromosome is quite small compared to the X and has accumulated a high content of heterochromatin. Furthermore, the Y-chromosome stands out in displaying CpG clusters around the centromeric region. These cytological findings evidently illustrate that the Y-chromosome in M. picta is indeed highly degenerated. Immunostaining for SYCP3 and MLH1 in pachytene meiocytes revealed that a substantial part of the Y remains associated with the X. A specific MLH1 hotspot site was persistently marked at the distal end of the associated XY structure. These results unveil a landmark of a recombining pseudoautosomal region on the otherwise strongly degenerated Y chromosome of M. picta. Hormone treatments of females revealed that, unexpectedly, no sexually antagonistic color gene is Y-linked in M. picta. All these differences to the Poecilia group of guppies indicate that the trajectories associated with the evolution of sex chromosomes are not in parallel. KW - sex chromosomes KW - heterochromatin KW - Y chromosome degeneration KW - meiosis KW - synaptonemal complex KW - recombination KW - 5-methylcytosine KW - testosterone KW - sexual antagonistic genes KW - sex linked pigmentation pattern Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-267242 SN - 2073-4409 VL - 11 IS - 7 ER - TY - JOUR A1 - Reinhard, Sebastian A1 - Helmerich, Dominic A. A1 - Boras, Dominik A1 - Sauer, Markus A1 - Kollmannsberger, Philip T1 - ReCSAI: recursive compressed sensing artificial intelligence for confocal lifetime localization microscopy JF - BMC Bioinformatics N2 - Background Localization-based super-resolution microscopy resolves macromolecular structures down to a few nanometers by computationally reconstructing fluorescent emitter coordinates from diffraction-limited spots. The most commonly used algorithms are based on fitting parametric models of the point spread function (PSF) to a measured photon distribution. These algorithms make assumptions about the symmetry of the PSF and thus, do not work well with irregular, non-linear PSFs that occur for example in confocal lifetime imaging, where a laser is scanned across the sample. An alternative method for reconstructing sparse emitter sets from noisy, diffraction-limited images is compressed sensing, but due to its high computational cost it has not yet been widely adopted. Deep neural network fitters have recently emerged as a new competitive method for localization microscopy. They can learn to fit arbitrary PSFs, but require extensive simulated training data and do not generalize well. A method to efficiently fit the irregular PSFs from confocal lifetime localization microscopy combining the advantages of deep learning and compressed sensing would greatly improve the acquisition speed and throughput of this method. Results Here we introduce ReCSAI, a compressed sensing neural network to reconstruct localizations for confocal dSTORM, together with a simulation tool to generate training data. We implemented and compared different artificial network architectures, aiming to combine the advantages of compressed sensing and deep learning. We found that a U-Net with a recursive structure inspired by iterative compressed sensing showed the best results on realistic simulated datasets with noise, as well as on real experimentally measured confocal lifetime scanning data. Adding a trainable wavelet denoising layer as prior step further improved the reconstruction quality. Conclusions Our deep learning approach can reach a similar reconstruction accuracy for confocal dSTORM as frame binning with traditional fitting without requiring the acquisition of multiple frames. In addition, our work offers generic insights on the reconstruction of sparse measurements from noisy experimental data by combining compressed sensing and deep learning. We provide the trained networks, the code for network training and inference as well as the simulation tool as python code and Jupyter notebooks for easy reproducibility. KW - compressed sensing KW - AI KW - SMLM KW - FLIMbee KW - dSTORM Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-299768 VL - 23 IS - 1 ER - TY - JOUR A1 - Prada, Juan Pablo A1 - Maag, Luca Estelle A1 - Siegmund, Laura A1 - Bencurova, Elena A1 - Liang, Chunguang A1 - Koutsilieri, Eleni A1 - Dandekar, Thomas A1 - Scheller, Carsten T1 - Estimation of R0 for the spread of SARS-CoV-2 in Germany from excess mortality JF - Scientific Reports N2 - For SARS-CoV-2, R0 calculations in the range of 2–3 dominate the literature, but much higher estimates have also been published. Because capacity for RT-PCR testing increased greatly in the early phase of the Covid-19 pandemic, R0 determinations based on these incidence values are subject to strong bias. We propose to use Covid-19-induced excess mortality to determine R0 regardless of RT-PCR testing capacity. We used data from the Robert Koch Institute (RKI) on the incidence of Covid cases, Covid-related deaths, number of RT-PCR tests performed, and excess mortality calculated from data from the Federal Statistical Office in Germany. We determined R0 using exponential growth estimates with a serial interval of 4.7 days. We used only datasets that were not yet under the influence of policy measures (e.g., lockdowns or school closures). The uncorrected R0 value for the spread of SARS-CoV-2 based on RT-PCR incidence data was 2.56 (95% CI 2.52–2.60) for Covid-19 cases and 2.03 (95% CI 1.96–2.10) for Covid-19-related deaths. However, because the number of RT-PCR tests increased by a growth factor of 1.381 during the same period, these R0 values must be corrected accordingly (R0corrected = R0uncorrected/1.381), yielding 1.86 for Covid-19 cases and 1.47 for Covid-19 deaths. The R0 value based on excess deaths was calculated to be 1.34 (95% CI 1.32–1.37). A sine-function-based adjustment for seasonal effects of 40% corresponds to a maximum value of R0January = 1.68 and a minimum value of R0July = 1.01. Our calculations show an R0 that is much lower than previously thought. This relatively low range of R0 fits very well with the observed seasonal pattern of infection across Europe in 2020 and 2021, including the emergence of more contagious escape variants such as delta or omicron. In general, our study shows that excess mortality can be used as a reliable surrogate to determine the R0 in pandemic situations. KW - SARS-CoV-2 KW - R0 KW - mortality Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301415 VL - 12 IS - 1 ER - TY - JOUR A1 - Martinez-Bengochea, A. L. A1 - Kneitz, S. A1 - Herpin, A. A1 - Nobrega, R. H. A1 - Adolfi, M. C. A1 - Schartl, M. T1 - Sexual development dysgenesis in interspecific hybrids of Medaka fish JF - Scientific Reports N2 - Fish are amongst vertebrates the group with the highest diversity of known sex-determining genes. Particularly, the genus Oryzias is a suitable taxon to understand how different sex determination genetic networks evolved in closely related species. Two closely related species, O. latipes and O. curvinotus, do not only share the same XX/XY sex chromosome system, but also the same male sex-determining gene, dmrt1bY. We performed whole mRNA transcriptomes and morphology analyses of the gonads of hybrids resulting from reciprocal crosses between O. latipes and O. curvinotus. XY male hybrids, presenting meiotic arrest and no production of sperm were sterile, and about 30% of the XY hybrids underwent male-to-female sex reversal. Both XX and XY hybrid females exhibited reduced fertility and developed ovotestis while aging. Transcriptome data showed that male-related genes are upregulated in the XX and XY female hybrids. The transcriptomes of both types of female and of the male gonads are characterized by upregulation of meiosis and germ cell differentiation genes. Differences in the parental species in the downstream pathways of sexual development could explain sex reversal, sterility, and the development of intersex gonads in the hybrids. We hypothesize that male-to-female sex reversal may be connected to a different development time between species at which dmrt1bY expression starts. Our results provide molecular clues for the proximate mechanisms of hybrid incompatibility and Haldane’s rule. KW - sexual development dysgenesis KW - Medaka fish KW - sex-determining genes. Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300295 VL - 12 IS - 1 ER - TY - JOUR A1 - Maihoff, Fabienne A1 - Bohlke, Kyte A1 - Brockmann, Axel A1 - Schmitt, Thomas T1 - Increased complexity of worker CHC profiles in Apis dorsata correlates with nesting ecology JF - PLoS ONE N2 - Cuticular hydrocarbons (CHC) are known to serve as discrimination cues and will trigger defence behaviour in a plethora of eusocial insects. However, little is known how about nestmate recognition ability selects for CHC diversification. In this study we investigate differences in CHC composition of four major honey bee species with respect to the differences in their nesting behavior. In contrast to A. mellifera, A. cerana and A. florea, the giant honey bee A. dorsata prefers to build their nests in aggregations with very small spatial distances between nests, which increases the probability of intrusions. Thus, A. dorsata exhibits a particularly challenging nesting behavior which we hypothesize should be accompanied with an improved nestmate recognition system. Comparative analyses of the worker CHC profiles indicate that A. dorsata workers exhibit a unique and more complex CHC profile than the other three honey bee species. This increased complexity is likely based on a developmental process that retains the capability to synthesize methyl-branched hydrocarbons as adults. Furthermore, two sets of behavioral experiments provide evidence that A. dorsata shows an improved nestmate discrimination ability compared to the phylogenetically ancestral A. florea, which is also open-nesting but does not form nest aggregations. The results of our study suggest that ecological traits like nesting in aggregation might be able to drive CHC profile diversification even in closely related insect species. KW - Apis dorsata KW - cuticular hydrocarbons KW - nesting Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301353 VL - 17 IS - 7 ER - TY - JOUR A1 - Kohl, Patrick L. A1 - Steffan‐Dewenter, Ingolf T1 - Nectar robbing rather than pollinator availability constrains reproduction of a bee‐flowered plant at high elevations JF - Ecosphere N2 - Abiotic factors are generally assumed to determine whether species can exist at the extreme ends of environmental gradients, for example, at high elevations, whereas the role of biotic interactions is less clear. On temperate mountains, insect‐pollinated plant species with bilaterally symmetrical flowers exhibit a parallel elevational decline in species richness and abundance with bees. This suggests that the lack of mutualistic interaction partners sets the elevational range limits of plants via a reduction in reproductive success. We used the bee‐pollinated mountain plant Clinopodium alpinum (Lamiaceae), which blooms along a continuous 1000‐m elevational gradient and has bilaterally symmetrical flowers, as a model to test the predicted parallel elevational decline in flower visitation and seed production. Although the community of flower visitors changed with elevation, the flower visitation rate by the most frequent visitors, bumble bees (33.8% of legitimate visits), and the overall rate of flower visitation by potential pollinators did not vary significantly with elevation. However, we discovered that nectar robbing by bumble bees and nectar theft by ants, two interactions with potentially negative effects on flowers, sharply increased with elevation. Seed set depended on pollinators across elevations and followed a weak hump‐shaped pattern, peaking at mid‐elevations and decreasing by about 20% toward both elevational range edges. Considering the mid‐ and high elevations, elevational variation in seed production could not be explained by legitimate bee visitation rates but was inversely correlated with the frequency of nectar robbing. Our observations challenge the hypothesis that a decrease in the availability of pollinators limits seed production of bee‐flowered plants at high elevations but suggest that an increase in negative interactions (nectar robbing and larceny) constrains reproductive success. KW - altitudinal gradients KW - bee pollination KW - chalcidoid wasps KW - climatic gradients KW - elevational diversity patterns KW - floral larceny KW - fly pollination KW - mountain ecosystems KW - plant–pollinator interactions KW - range limits KW - zygomorphy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287141 VL - 13 IS - 6 ER - TY - JOUR A1 - Koster, Stefanie A1 - Gurumurthy, Rajendra Kumar A1 - Kumar, Naveen A1 - Prakash, Pon Ganish A1 - Dhanraj, Jayabhuvaneshwari A1 - Bayer, Sofia A1 - Berger, Hilmar A1 - Kurian, Shilpa Mary A1 - Drabkina, Marina A1 - Mollenkopf, Hans-Joachim A1 - Goosmann, Christian A1 - Brinkmann, Volker A1 - Nagel, Zachary A1 - Mangler, Mandy A1 - Meyer, Thomas F. A1 - Chumduri, Cindrilla T1 - Modelling Chlamydia and HPV co-infection in patient-derived ectocervix organoids reveals distinct cellular reprogramming JF - Nature Communications N2 - Coinfections with pathogenic microbes continually confront cervical mucosa, yet their implications in pathogenesis remain unclear. Lack of in-vitro models recapitulating cervical epithelium has been a bottleneck to study coinfections. Using patient-derived ectocervical organoids, we systematically modeled individual and coinfection dynamics of Human papillomavirus (HPV)16 E6E7 and Chlamydia, associated with carcinogenesis. The ectocervical stem cells were genetically manipulated to introduce E6E7 oncogenes to mimic HPV16 integration. Organoids from these stem cells develop the characteristics of precancerous lesions while retaining the self-renewal capacity and organize into mature stratified epithelium similar to healthy organoids. HPV16 E6E7 interferes with Chlamydia development and induces persistence. Unique transcriptional and post-translational responses induced by Chlamydia and HPV lead to distinct reprogramming of host cell processes. Strikingly, Chlamydia impedes HPV-induced mechanisms that maintain cellular and genome integrity, including mismatch repair in the stem cells. Together, our study employing organoids demonstrates the hazard of multiple infections and the unique cellular microenvironment they create, potentially contributing to neoplastic progression. KW - Chlamydia KW - HPV KW - cellular reprogramming Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301349 VL - 13 IS - 1 ER - TY - JOUR A1 - Kohl, Patrick L. A1 - Rutschmann, Benjamin A1 - Steffan-Dewenter, Ingolf T1 - Population demography of feral honeybee colonies in central European forests JF - Royal Society Open Science N2 - European honeybee populations are considered to consist only of managed colonies, but recent censuses have revealed that wild/feral colonies still occur in various countries. To gauge the ecological and evolutionary relevance of wild-living honeybees, information is needed on their population demography. We monitored feral honeybee colonies in German forests for up to 4 years through regular inspections of woodpecker cavity trees and microsatellite genotyping. Each summer, about 10% of the trees were occupied, corresponding to average densities of 0.23 feral colonies km\(^{−2}\) (an estimated 5% of the regional honeybee populations). Populations decreased moderately until autumn but dropped massively during winter, so that their densities were only about 0.02 colonies km\(^{−2}\) in early spring. During the reproductive (swarming) season, in May and June, populations recovered, with new swarms preferring nest sites that had been occupied in the previous year. The annual survival rate and the estimated lifespan of feral colonies (n = 112) were 10.6% and 0.6 years, respectively. We conclude that managed forests in Germany do not harbour self-sustaining feral honeybee populations, but they are recolonized every year by swarms escaping from apiaries. KW - pollinator decline KW - nest site selection KW - life-history traits KW - wild honeybees KW - beech forests KW - swarming Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301335 SN - 2054-5703 VL - 9 IS - 8 ER - TY - JOUR A1 - Kaya-Zeeb, Sinan A1 - Engelmayer, Lorenz A1 - Straßburger, Mara A1 - Bayer, Jasmin A1 - Bähre, Heike A1 - Seifert, Roland A1 - Scherf-Clavel, Oliver A1 - Thamm, Markus T1 - Octopamine drives honeybee thermogenesis JF - eLife N2 - In times of environmental change species have two options to survive: they either relocate to a new habitat or they adapt to the altered environment. Adaptation requires physiological plasticity and provides a selection benefit. In this regard, the Western honeybee (Apis mellifera) protrudes with its thermoregulatory capabilities, which enables a nearly worldwide distribution. Especially in the cold, shivering thermogenesis enables foraging as well as proper brood development and thus survival. In this study, we present octopamine signaling as a neurochemical prerequisite for honeybee thermogenesis: we were able to induce hypothermia by depleting octopamine in the flight muscles. Additionally, we could restore the ability to increase body temperature by administering octopamine. Thus, we conclude that octopamine signaling in the flight muscles is necessary for thermogenesis. Moreover, we show that these effects are mediated by β octopamine receptors. The significance of our results is highlighted by the fact the respective receptor genes underlie enormous selective pressure due to adaptation to cold climates. Finally, octopamine signaling in the service of thermogenesis might be a key strategy to survive in a changing environment. KW - honeybee KW - octopamine KW - thermogenesis Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301327 VL - 11 ER - TY - JOUR A1 - Buellesbach, Jan A1 - Vetter, Sebastian G. A1 - Schmitt, Thomas T1 - Differences in the reliance on cuticular hydrocarbons as sexual signaling and species discrimination cues in parasitoid wasps JF - Frontiers in Zoology N2 - Background Cuticular hydrocarbons (CHC) have been documented to play crucial roles as species- and sex-specific cues in the chemical communication systems of a wide variety of insects. However, whether they are sufficient by themselves as the sole cue triggering sexual behavior as well as preference of con- over heterospecific mating partners is rarely assessed. We conducted behavioral assays in three representative species of parasitoid wasps (Hymenoptera: Pteromalidae) to determine their reliance on CHC as species-specific sexual signaling cues. Results We found a surprising degree of either unspecific or insufficient sexual signaling when CHC are singled out as recognition cues. Most strikingly, the cosmopolitan species Nasonia vitripennis, expected to experience enhanced selection pressure to discriminate against other co-occurring parasitoids, did not discriminate against CHC of a partially sympatric species from another genus, Trichomalopsis sarcophagae. Focusing on the latter species, in turn, it became apparent that CHC are even insufficient as the sole cue triggering conspecific sexual behavior, hinting at the requirement of additional, synergistic sexual cues particularly important in this species. Finally, in the phylogenetically and chemically most divergent species Muscidifurax uniraptor, we intriguingly found both CHC-based sexual signaling as well as species discrimination behavior intact although this species is naturally parthenogenetic with sexual reproduction only occurring under laboratory conditions. Conclusions Our findings implicate a discrepancy in the reliance on and specificity of CHC as sexual cues in our tested parasitioid wasps. CHC profiles were not sufficient for unambiguous discrimination and preference behavior, as demonstrated by clear cross-attraction between some of our tested wasp genera. Moreover, we could show that only in T. sarcophagae, additional behavioral cues need to be present for triggering natural mating behavior, hinting at an interesting shift in signaling hierarchy in this particular species. This demonstrates the importance of integrating multiple, potentially complementary signaling modalities in future studies for a better understanding of their individual contributions to natural sexual communication behavior. KW - chemical communication KW - assortative mating KW - mate recognition KW - prezygotic reproductive isolation KW - speciation KW - Nasonia KW - Trichomalopsis KW - Muscidifurax KW - Pteromalidae KW - Hymenoptera Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221702 VL - 15 ER - TY - JOUR A1 - Bartel, Karin A1 - Pein, Helmut A1 - Popper, Bastian A1 - Schmitt, Sabine A1 - Janaki-Raman, Sudha A1 - Schulze, Almut A1 - Lengauer, Florian A1 - Koeberle, Andreas A1 - Werz, Oliver A1 - Zischka, Hans A1 - Müller, Rolf A1 - Vollmar, Angelika M. A1 - Schwarzenberg, Karin von T1 - Connecting lysosomes and mitochondria – a novel role for lipid metabolism in cancer cell death JF - Cell Communication and Signaling N2 - Background The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood. Methods LC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements. Results Our data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells. Conclusion This study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors. KW - lysosome KW - V-ATPase KW - mitochondria KW - fission KW - apoptosis KW - lipid metabolism KW - cardiolipin Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221524 VL - 17 ER - TY - JOUR A1 - Jeanclos, Elisabeth A1 - Schlötzer, Jan A1 - Hadamek, Kerstin A1 - Yuan-Chen, Natalia A1 - Alwahsh, Mohammad A1 - Hollmann, Robert A1 - Fratz, Stefanie A1 - Yesilyurt-Gerhards, Dilan A1 - Frankenbach, Tina A1 - Engelmann, Daria A1 - Keller, Angelika A1 - Kaestner, Alexandra A1 - Schmitz, Werner A1 - Neuenschwander, Martin A1 - Hergenröder, Roland A1 - Sotriffer, Christoph A1 - von Kries, Jens Peter A1 - Schindelin, Hermann A1 - Gohla, Antje T1 - Glycolytic flux control by drugging phosphoglycolate phosphatase JF - Nature Communications N2 - Targeting the intrinsic metabolism of immune or tumor cells is a therapeutic strategy in autoimmunity, chronic inflammation or cancer. Metabolite repair enzymes may represent an alternative target class for selective metabolic inhibition, but pharmacological tools to test this concept are needed. Here, we demonstrate that phosphoglycolate phosphatase (PGP), a prototypical metabolite repair enzyme in glycolysis, is a pharmacologically actionable target. Using a combination of small molecule screening, protein crystallography, molecular dynamics simulations and NMR metabolomics, we discover and analyze a compound (CP1) that inhibits PGP with high selectivity and submicromolar potency. CP1 locks the phosphatase in a catalytically inactive conformation, dampens glycolytic flux, and phenocopies effects of cellular PGP-deficiency. This study provides key insights into effective and precise PGP targeting, at the same time validating an allosteric approach to control glycolysis that could advance discoveries of innovative therapeutic candidates. KW - phosphoglycolate phosphatase KW - glycolytic flux control KW - intrinsic metabolism Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300928 VL - 13 IS - 1 ER - TY - JOUR A1 - Rat, Charlotte A1 - Heiby, Julia C. A1 - Bunz, Jessica P. A1 - Neuweiler, Hannes T1 - Two-step self-assembly of a spider silk molecular clamp JF - Nature Communications N2 - Web spiders synthesize silk fibers of unique strength and extensibility through the controlled self-assembly of protein building blocks, so-called spidroins. The spidroin C-terminal domain is highly conserved and connects two polypeptide chains through formation of an all-helical, intertwined dimer. Here we use contact-induced fluorescence self-quenching and resonance energy transfer in combination with far-UV circular dichroism spectroscopy as three orthogonal structural probes to dissect the mechanism of folding and dimerization of a spidroin C-terminal domain from the major ampullate gland of the nursery web spider Euprosthenops australis. We show that helices forming the dimer core assemble very rapidly and fold on association. Subsequently, peripheral helices fold and dock slowly onto the preformed core. Lability of outer helices facilitates formation of a highly expanded, partially folded dimer. The high end-to-end distance of chain termini in the partially folded dimer suggests an extensibility module that contributes to elasticity of spider silk. KW - Circular dichroism KW - Fluorescence spectroscopy KW - Biokinetics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225016 VL - 9 ER - TY - JOUR A1 - Rubio-Cosials, Anna A1 - Schulz, Eike C. A1 - Lambertsen, Lotte A1 - Smyshlyaev, Georgy A1 - Rojas-Cordova, Carlos A1 - Forslund, Kristoffer A1 - Karaca, Ezgi A1 - Bebel, Aleksandra A1 - Bork, Peer A1 - Barabas, Orsolya T1 - Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance JF - Cell N2 - Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes. KW - DNA complex KW - crystallography KW - Tn1549 transposon KW - Tn916-like transposon family KW - conjugative transposition KW - tyrosine recombinase KW - antibiotic resistance KW - gene transfer KW - vancomycin KW - multidrug-resistant bacteria Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-227085 VL - 173 IS - 1 ER - TY - JOUR A1 - Ganuza, Cristina A1 - Redlich, Sarah A1 - Uhler, Johannes A1 - Tobisch, Cynthia A1 - Rojas-Botero, Sandra A1 - Peters, Marcell K. A1 - Zhang, Jie A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Ewald, Jörg A1 - Fricke, Ute A1 - Haensel, Maria A1 - Kollmann, Johannes A1 - Riebl, Rebekka A1 - Uphus, Lars A1 - Müller, Jörg A1 - Steffan-Dewenter, Ingolf T1 - Interactive effects of climate and land use on pollinator diversity differ among taxa and scales JF - Science Advances N2 - Changes in climate and land use are major threats to pollinating insects, an essential functional group. Here, we unravel the largely unknown interactive effects of both threats on seven pollinator taxa using a multiscale space-for-time approach across large climate and land-use gradients in a temperate region. Pollinator community composition, regional gamma diversity, and community dissimilarity (beta diversity) of pollinator taxa were shaped by climate-land-use interactions, while local alpha diversity was solely explained by their additive effects. Pollinator diversity increased with reduced land-use intensity (forest < grassland < arable land < urban) and high flowering-plant diversity at different spatial scales, and higher temperatures homogenized pollinator communities across regions. Our study reveals declines in pollinator diversity with land-use intensity at multiple spatial scales and regional community homogenization in warmer and drier climates. Management options at several scales are highlighted to mitigate impacts of climate change on pollinators and their ecosystem services. KW - climate KW - land use KW - pollinator diversity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301303 VL - 8 IS - 18 ER - TY - JOUR A1 - Fricke, Ute A1 - Steffan-Dewenter, Ingolf A1 - Zhang, Jie A1 - Tobisch, Cynthia A1 - Rojas-Botero, Sandra A1 - Benjamin, Caryl S. A1 - Englmeier, Jana A1 - Ganuza, Cristina A1 - Haensel, Maria A1 - Riebl, Rebekka A1 - Uhler, Johannes A1 - Uphus, Lars A1 - Ewald, Jörg A1 - Kollmann, Johannes A1 - Redlich, Sarah T1 - Landscape diversity and local temperature, but not climate, affect arthropod predation among habitat types JF - PLoS ONE N2 - Arthropod predators are important for ecosystem functioning by providing top-down regulation of insect herbivores. As predator communities and activity are influenced by biotic and abiotic factors on different spatial scales, the strength of top-down regulation (‘arthropod predation’) is also likely to vary. Understanding the combined effects of potential drivers on arthropod predation is urgently needed with regard to anthropogenic climate and land-use change. In a large-scale study, we recorded arthropod predation rates using artificial caterpillars on 113 plots of open herbaceous vegetation embedded in contrasting habitat types (forest, grassland, arable field, settlement) along climate and land-use gradients in Bavaria, Germany. As potential drivers we included habitat characteristics (habitat type, plant species richness, local mean temperature and mean relative humidity during artificial caterpillar exposure), landscape diversity (0.5–3.0-km, six scales), climate (multi-annual mean temperature, ‘MAT’) and interactive effects of habitat type with other drivers. We observed no substantial differences in arthropod predation rates between the studied habitat types, related to plant species richness and across the Bavarian-wide climatic gradient, but predation was limited when local mean temperatures were low and tended to decrease towards higher relative humidity. Arthropod predation rates increased towards more diverse landscapes at a 2-km scale. Interactive effects of habitat type with local weather conditions, plant species richness, landscape diversity and MAT were not observed. We conclude that landscape diversity favours high arthropod predation rates in open herbaceous vegetation independent of the dominant habitat in the vicinity. This finding may be harnessed to improve top-down control of herbivores, e.g. agricultural pests, but further research is needed for more specific recommendations on landscape management. The absence of MAT effects suggests that high predation rates may occur independent of moderate increases of MAT in the near future. KW - arthropod predators KW - habitat types KW - landscape diversity Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-301292 VL - 17 IS - 4 ER -