@article{ChaianunpornHovestadt2022, author = {Chaianunporn, Thotsapol and Hovestadt, Thomas}, title = {Emergence of spatially structured populations by area-concentrated search}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {12}, doi = {10.1002/ece3.9528}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311939}, year = {2022}, abstract = {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.}, language = {en} } @article{EnglmeiervonHoermannRiekeretal.2022, author = {Englmeier, Jana and von Hoermann, Christian and Rieker, Daniel and Benbow, Marc Eric and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Lackner, Tom{\´a}š and Mitesser, Oliver and Redlich, Sarah and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Salamon, J{\"o}rg-Alfred and Sommer, David and Steffan-Dewenter, Ingolf and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {10}, issn = {2045-7758}, doi = {10.1002/ece3.9386}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312846}, year = {2022}, abstract = {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.}, language = {en} } @article{PrietoGarciaHartmannReisslandetal.2022, author = {Prieto-Garcia, Cristian and Hartmann, Oliver and Reissland, Michaela and Braun, Fabian and Bozkurt, S{\"u}leyman and Pahor, Nikolett and Fuss, Carmina and Schirbel, Andreas and Sch{\"u}lein-V{\"o}lk, Christina and Buchberger, Alexander and Calzado Canale, Marco A. and Rosenfeldt, Mathias and Dikic, Ivan and M{\"u}nch, Christian and Diefenbacher, Markus E.}, title = {USP28 enables oncogenic transformation of respiratory cells, and its inhibition potentiates molecular therapy targeting mutant EGFR, BRAF and PI3K}, series = {Molecular Oncology}, volume = {16}, journal = {Molecular Oncology}, number = {17}, doi = {10.1002/1878-0261.13217}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312777}, pages = {3082-3106}, year = {2022}, abstract = {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.}, language = {en} } @article{DiersBaumLehmannetal.2022, author = {Diers, Johannes and Baum, Philip and Lehmann, Kai and Uttinger, Konstatin and Baumann, Nikolas and Pietryga, Sebastian and Hankir, Mohammed and Matthes, Niels and Lock, Johann F. and Germer, Christoph-Thomas and Wiegering, Armin}, title = {Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study}, series = {Cancer Medicine}, volume = {11}, journal = {Cancer Medicine}, number = {22}, doi = {10.1002/cam4.4784}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312858}, pages = {4256-4264}, year = {2022}, abstract = {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.}, language = {en} } @article{DiersAcarWagneretal.2022, author = {Diers, Johannes and Acar, Laura and Wagner, Johanna C. and Baum, Philip and Hankir, Mohammed and Flemming, Sven and Kastner, Carolin and Germer, Christoph-Thomas and L'hoest, Helmut and Marschall, Ursula and Lock, Johan Friso and Wiegering, Armin}, title = {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}, series = {Cancer Communications}, volume = {42}, journal = {Cancer Communications}, number = {7}, doi = {10.1002/cac2.12314}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312862}, pages = {673-676}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{VansynghelOcampoArizaMaasetal.2022, author = {Vansynghel, Justine and Ocampo-Ariza, Carolina and Maas, Bea and Martin, Emily A. and Thomas, Evert and Hanf-Dressler, Tara and Schumacher, Nils-Christian and Ulloque-Samatelo, Carlos and Tscharntke, Teja and Steffan-Dewenter, Ingolf}, title = {Cacao flower visitation: Low pollen deposition, low fruit set and dominance of herbivores}, series = {Ecological Solutions and Evidence}, volume = {3}, journal = {Ecological Solutions and Evidence}, number = {2}, issn = {2688-8319}, doi = {10.1002/2688-8319.12140}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312722}, year = {2022}, abstract = {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}, language = {en} } @phdthesis{Petrov2023, author = {Petrov, Ivan}, title = {Combinational therapy of tumors in syngeneic mouse tumor models with oncolytic Vaccinia virus strains expressing IL-2 and INF-g. Human adipose tissue-derived stem cell mediated delivery of oncolytic Vaccinia virus}, doi = {10.25972/OPUS-27355}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273550}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2023}, abstract = {Cancer is one of the leading causes of death worldwide, with currently assessed chances to develop at least one cancer in a lifetime for about 20\%. High cases rates and mortality require the development of new anticancer therapies and treatment strategies. Another important concern is toxicity normally associated with conventional therapy methods, such as chemo- and radiotherapy. Among many proposed antitumoral agents, oncolytic viruses are still one of the promising and fast-developing fields of research with almost a hundred studies published data on over 3000 patients since the beginning of the new millennia. Among all oncolytic viruses, the Vaccinia virus is arguably one of the safest, with an extremely long and prominent history of use, since it was the one and only vaccine used in the Smallpox Eradication Program in the 1970s. Interestingly enough, it was the first oncolytic virus proven to have tumor tropism in vitro and in vivo in laboratory settings, and this year we can celebrate an unofficial 100th anniversary since the publication of the fact. While being highly immunogenic, Vaccinia virus DNA replication takes place in the cytoplasm of the infected cell, and virus genes never integrate into the host genome. Another advantage of using Vaccinia as an oncolytic agent is its high genome capacity, which allows inserting up to 25 kbps of exogenous genes, thus allowing to additionally arm the virus against the tumor. Oncolytic virus action consists of two major parts: direct oncolysis and immune activation against the tumor, with the latter being the key to successful treatment. To this moment, preclinical research data are mostly generated in immunocompromised xenograft models, which have hurdles to be properly translated for clinical use. In the first part of the current study, fourteen different recombinant Vaccinia virus strains were tested in two different murine tumor cell lines and corresponding immunocompetent animal models. We found, that Copenhagen backbone Vaccinia viruses while being extremely effective in cell culture, do not show significant oncolytic efficacy in animals. In contrast, several of the LIVP backbone viruses tested (specifically, IL-2 expressing ones) have little replication ability when compared to the Copenhagen strain, but are able to significantly delay tumor growth and prolong survival of the treated animals. We have also noted cytokine related toxicity of the animals to be mouse strain specific. We have also tested the virus with the highest therapeutic benefit in combination with romidepsin and cyclophosphamide. While the combination with histone deacetylase inhibitor romidepsin did not result in therapeutic benefit in our settings, the addition of cyclophosphamide significantly improved the efficacy of the treatment, at the same time reducing cytokine-associated toxicity of the IL-2 expressing virus. In the second part of the work, we analyzed the ability of adipose-derived mesenchymal stem cells to serve as a carrier for the oncolytic Vaccinia virus. We showed for the first time that the cells can be infected with the virus and can generate virus progeny. They are also able to survive for a substantially long time and, when injected into the bloodstream of tumor-bearing animals, produce the virus that is colonizing the tumor. Analysis of the systemic distribution of the cells after injection revealed that infected and uninfected cells are not distributed in the same manner, possibly suggesting that infected cells are getting recognized and cleared by an impaired immune system of athymic mice faster than non-infected cells. Despite this, injection of virus-loaded adipose-derived mesenchymal stem cells to human A549 tumor-bearing xenograft mice resulted in rapid tumor regression and reduced virus-related side effects of the treatment when compared to injection of the naked virus. In conclusion, we have tested two different approaches to augmenting oncolytic Vaccinia virus therapy. First, the combination of recombinant Vaccinia virus expressing IL-2 and cyclophosphamide showed promising results in a syngeneic mouse model, despite the low permissivity of murine cells to the virus. Second, we loaded the oncolytic Vaccinia virus into mesenchymal stem cells and have proven that they can potentially serve as a vehicle for the virus.}, subject = {Vaccinia-virus}, language = {en} } @article{PetersKellerLeonhardt2022, author = {Peters, Birte and Keller, Alexander and Leonhardt, Sara Diana}, title = {Diets maintained in a changing world: Does land-use intensification alter wild bee communities by selecting for flexible generalists?}, series = {Ecology and evolution}, volume = {12}, journal = {Ecology and evolution}, number = {5}, issn = {2045-7758}, doi = {10.1002/ece3.8919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312786}, year = {2022}, abstract = {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.}, language = {en} } @article{KortmannAngelstamMayeretal.2022, author = {Kortmann, Mareike and Angelstam, Per and Mayer, Marius and Leibl, Franz and Reichert, Jessica and Thorn, Christine and Thorn, Simon}, title = {Disturbance severity and human-nature relationships: A new approach to analyze people's well-being along a bark beetle infestation gradient}, series = {Forests}, volume = {13}, journal = {Forests}, number = {11}, issn = {1999-4907}, doi = {10.3390/f13111954}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297429}, year = {2022}, abstract = {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.}, language = {en} } @article{DeğirmenciRogeFerreiraVukosavljevicetal.2023, author = {Değirmenci, Laura and Rog{\´e} Ferreira, Fabio Luiz and Vukosavljevic, Adrian and Heindl, Cornelia and Keller, Alexander and Geiger, Dietmar and Scheiner, Ricarda}, title = {Sugar perception in honeybees}, series = {Frontiers in Physiology}, volume = {13}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2022.1089669}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302284}, year = {2023}, abstract = {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.}, language = {en} }