@article{JanschZieglerForeroetal.2021,
  author    = {Jansch, Charline and Ziegler, Georg C. and Forero, Andrea and Gredy, Sina and W{\"a}ldchen, Sina and Vitale, Maria Rosaria and Svirin, Evgeniy and Z{\"o}ller, Johanna E. M. and Waider, Jonas and G{\"u}nther, Katharina and Edenhofer, Frank and Sauer, Markus and Wischmeyer, Erhard and Lesch, Klaus-Peter},
  title     = {Serotonin-specific neurons differentiated from human iPSCs form distinct subtypes with synaptic protein assembly},
  series = {Journal of Neural Transmission},
  volume    = {128},
  journal   = {Journal of Neural Transmission},
  number    = {2},
  issn      = {1435-1463},
  doi       = {10.1007/s00702-021-02303-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-268519},
  pages     = {225-241},
  year      = {2021},
  abstract  = {Human induced pluripotent stem cells (hiPSCs) have revolutionized the generation of experimental disease models, but the development of protocols for the differentiation of functionally active neuronal subtypes with defined specification is still in its infancy. While dysfunction of the brain serotonin (5-HT) system has been implicated in the etiology of various neuropsychiatric disorders, investigation of functional human 5-HT specific neurons in vitro has been restricted by technical limitations. We describe an efficient generation of functionally active neurons from hiPSCs displaying 5-HT specification by modification of a previously reported protocol. Furthermore, 5-HT specific neurons were characterized using high-end fluorescence imaging including super-resolution microscopy in combination with electrophysiological techniques. Differentiated hiPSCs synthesize 5-HT, express specific markers, such as tryptophan hydroxylase 2 and 5-HT transporter, and exhibit an electrophysiological signature characteristic of serotonergic neurons, with spontaneous rhythmic activities, broad action potentials and large afterhyperpolarization potentials. 5-HT specific neurons form synapses reflected by the expression of pre- and postsynaptic proteins, such as Bassoon and Homer. The distribution pattern of Bassoon, a marker of the active zone along the soma and extensions of neurons, indicates functionality via volume transmission. Among the high percentage of 5-HT specific neurons (~ 42\%), a subpopulation of CDH13 + cells presumably designates dorsal raphe neurons. hiPSC-derived 5-HT specific neuronal cell cultures reflect the heterogeneous nature of dorsal and median raphe nuclei and may facilitate examining the association of serotonergic neuron subpopulations with neuropsychiatric disorders.},
  language  = {en}
}
@phdthesis{Jessen2021,
  author    = {Jessen, Christina},
  title     = {NRF2 links antioxidant and immune-relevant features in melanoma},
  doi       = {10.25972/OPUS-23349},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233495},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {The transcription factor NRF2 is considered as the master regulator of cytoprotective and ROS-detoxifying gene expression. Due to their vulnerability to accumulating reactive oxygen species, melanomas are dependent on an efficient oxidative stress response, but to what extent melanomas rely on NRF2 is only scarcely investigated so far. In tumor entities harboring activating mutations of NRF2, such as lung adenocarcinoma, NRF2 activation is closely connected to therapy resistance. In melanoma, activating mutations are rare and triggers and effectors of NRF2 are less well characterized. This work revealed that NRF2 is activated by oncogenic signaling, cytokines and pro-oxidant triggers, released cell-autonomously or by the tumor microenvironment. Moreover, silencing of NRF2 significantly reduced melanoma cell proliferation and repressed well-known NRF2 target genes, indicating basal transcriptional activity of NRF2 in melanoma. Transcriptomic analysis showed a large set of deregulated gene sets, besides the well-known antioxidant effectors. NRF2 suppressed the activity of MITF, a marker for the melanocyte lineage, and induced expression of epidermal growth factor receptor (EGFR), thereby stabilizing the dedifferentiated melanoma phenotype and limiting pigmentation markers and melanoma-associated antigens. In general, the dedifferentiated melanoma phenotype is associated with a reduced tumor immunogenicity. Furthermore, stress-inducible cyclooxygenase 2 (COX2) expression, a crucial immune-modulating gene, was regulated by NRF2 in an ATF4-dependent manner. Only in presence of both transcription factors was COX2 robustly induced by H2O2 or TNFα. COX2 catalyzes the first step of the prostaglandin E2 (PGE2) synthesis, which was described to be associated with tumor immune evasion and reduction of the innate immune response. In accordance with these potentially immune-suppressive features, immunocompetent mice injected with NRF2 knockout melanoma cells had a strikingly longer tumor-free survival compared to NRF2-proficient cells. In line with the in vitro data, NRF2-deficient tumors showed suppression of COX2 and induction of MITF. Furthermore, transcriptomic analyses of available tumors revealed a strong induction of genes belonging to the innate immune response, such as RSAD2 and IFIH1. The expression of these genes strongly correlated with immune evasion parameters in human melanoma datasets and NRF2 activation or PGE2 supplementation limited the innate immune response in vitro. In summary, the stress dependent NRF2 activation stabilizes the dedifferentiated melanoma phenotype and facilitates the synthesis of PGE2. As a result, NRF2 reduces gene expression of the innate immune response and promotes the generation of an immune-cold tumor microenvironment. Therefore, NRF2 not only elevated the ROS resilience, but also strongly contributed to tumor growth, maintenance, and immune control in cutaneous melanoma.},
  subject      = {Melanom},
  language  = {en}
}
@article{KarimiFreundWageretal.2021,
  author    = {Karimi, Sohail M. and Freund, Matthias and Wager, Brittney M. and Knoblauch, Michael and Fromm, J{\"o}rg and M. Mueller, Heike and Ache, Peter and Krischke, Markus and Mueller, Martin J. and M{\"u}ller, Tobias and Dittrich, Marcus and Geilfus, Christoph-Martin and Alfaran, Ahmed H. and Hedrich, Rainer and Deeken, Rosalia},
  title     = {Under salt stress guard cells rewire ion transport and abscisic acid signaling},
  series = {New Phytologist},
  volume    = {231},
  journal   = {New Phytologist},
  number    = {3},
  doi       = {10.1111/nph.17376},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259635},
  pages     = {1040-1055},
  year      = {2021},
  abstract  = {Soil salinity is an increasingly global problem which hampers plant growth and crop yield. Plant productivity depends on optimal water-use efficiency and photosynthetic capacity balanced by stomatal conductance. Whether and how stomatal behavior contributes to salt sensitivity or tolerance is currently unknown. This work identifies guard cell-specific signaling networks exerted by a salt-sensitive and salt-tolerant plant under ionic and osmotic stress conditions accompanied by increasing NaCl loads. We challenged soil-grown Arabidopsis thaliana and Thellungiella salsuginea plants with short- and long-term salinity stress and monitored genome-wide gene expression and signals of guard cells that determine their function. Arabidopsis plants suffered from both salt regimes and showed reduced stomatal conductance while Thellungiella displayed no obvious stress symptoms. The salt-dependent gene expression changes of guard cells supported the ability of the halophyte to maintain high potassium to sodium ratios and to attenuate the abscisic acid (ABA) signaling pathway which the glycophyte kept activated despite fading ABA concentrations. Our study shows that salinity stress and even the different tolerances are manifested on a single cell level. Halophytic guard cells are less sensitive than glycophytic guard cells, providing opportunities to manipulate stomatal behavior and improve plant productivity.},
  language  = {en}
}
@article{KastnerHendricksDeinleinetal.2021,
  author    = {Kastner, Carolin and Hendricks, Anne and Deinlein, Hanna and Hankir, Mohammed and Germer, Christoph-Thomas and Schmidt, Stefanie and Wiegering, Armin},
  title     = {Organoid Models for Cancer Research — From Bed to Bench Side and Back},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {19},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13194812},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246307},
  year      = {2021},
  abstract  = {Simple Summary Despite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner). Abstract Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.},
  language  = {en}
}
@phdthesis{Kehrberger2021,
  author    = {Kehrberger, Sandra},
  title     = {Effects of climate warming on the timing of flowering and emergence in a tritrophic relationship: plants - bees - parasitoids},
  doi       = {10.25972/OPUS-21393},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-213932},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {The right timing of phenological events is crucial for species fitness. Species should be highly synchronized with mutualists, but desynchronized with antagonists. With climate warming phenological events advance in many species. However, often species do not respond uniformly to warming temperatures. Species-specific responses to climate warming can lead to asynchrony or even temporal mismatch of interacting species. A temporal mismatch between mutualists, which benefit from each other, can have negative consequences for both interaction partners. For host-parasitoid interactions temporal asynchrony can benefit the host species, if it can temporally escape its parasitoid, with negative consequences for the parasitoid species, but benefit the parasitoid species if it increases synchrony with its host, which can negatively affect the host species. Knowledge about the drivers of phenology and the species-specific responses to these drivers are important to predict future effects of climate change on trophic interactions. In this dissertation I investigated how different drivers act on early flowering phenology and how climate warming affects the tritrophic relationship of two spring bees (Osmia cornuta \& Osmia bicornis), an early spring plant (Pulsatilla vulgaris), which is one of the major food plants of the spring bees, and three main parasitoids of the spring bees (Cacoxenus indagator, Anthrax anthrax, Monodontomerus). In Chapter II I present a study in which I investigated how different drivers and their change over the season affect the reproductive success of an early spring plant. For that I recorded on eight calcareous grasslands around W{\"u}rzburg, Germany the intra-seasonal changes in pollinator availability, number of co-flowering plants and weather conditions and studied how they affect flower visitation rates, floral longevity and seed set of the early spring plant P. vulgaris. I show that bee abundances and the number of hours, which allowed pollinator foraging, were low at the beginning of the season, but increased over time. However, flower visitation rates and estimated total number of bee visits were higher on early flowers of P. vulgaris than later flowers. Flower visitation rates were also positively related to seed set. Over time and with increasing competition for pollinators by increasing numbers of co-flowering plants flower visitation rates decreased. My data shows that a major driver for early flowering dates seems to be low interspecific competition for pollinators, but not low pollinator abundances and unfavourable weather conditions. Chapter III presents a study in which I investigated the effects of temperature on solitary bee emergence and on the flowering of their food plant and of co-flowering plants in the field. Therefore I placed bee cocoons of two spring bees (O. cornuta \& O. bicornis) on eleven calcareous grasslands which differed in mean site temperature. On seven of these grasslands the early spring plant P. vulgaris occurred. I show that warmer temperatures advanced mean emergence in O. cornuta males. However, O. bicornis males and females of both species did not shift their emergence. Compared to the bees P. vulgaris advanced its flowering phenology more strongly with warmer temperatures. Co-flowering plants did not shift flowering onset. I suggest that with climate warming the first flowers of P. vulgaris face an increased risk of pollinator limitation whereas for bees a shift in floral resources may occur. In Chapter IV I present a study in which I investigated the effects of climate warming on host-parasitoid relationships. I studied how temperature and photoperiod affect emergence phenology in two spring bees (O. cornuta \& O. bicornis) and three of their main parasitoids (C. indagator, A. anthrax, Monodontomerus). In a climate chamber experiment with a crossed design I exposed cocoons within nest cavities and cocoons outside of nest cavities to two different temperature regimes (long-term mean of W{\"u}rzburg, Germany and long-term mean of W{\"u}rzburg + 4 °C) and three photoperiods (W{\"u}rzburg vs. Sn{\aa}sa, Norway vs. constant darkness) and recorded the time of bee and parasitoid emergence. I show that warmer temperatures advanced emergence in all studied species, but bees advanced less strongly than parasitoids. Consequently, the time period between female bee emergence and parasitoid emergence decreased in the warm temperature treatment compared to the cold one. Photoperiod influenced the time of emergence only in cocoons outside of nest cavities (except O. bicornis male emergence). The data also shows that the effect of photoperiod compared to the effect of temperature on emergence phenology was much weaker. I suggest that with climate warming the synchrony of emergence phenologies of bees and their parasitoids will amplify. Therefore, parasitism rates in solitary bees might increase which can negatively affect reproductive success and population size. In this dissertation I show that for early flowering spring plants low interspecific competition for pollinators with co-flowering plants is a major driver of flowering phenology, whereas other drivers, like low pollinator abundances and unfavourable weather conditions are only of minor importance. With climate warming the strength of different drivers, which act on the timing of phenological events, can change, like temperature. I show that warmer temperatures advance early spring plant flowering more strongly than bee emergence and flowering phenology of later co-flowering plants. Furthermore, I show that warmer temperatures advance parasitoid emergence more strongly than bee emergence. Whereas temperature changes can lead to non-uniform temporal shifts, I demonstrate that geographic range shifts and with that altered photoperiods will not change emergence phenology in bees and their parasitoids. In the tritrophic system I investigated in this dissertation climate warming may negatively affect the reproductive success of the early spring plant and the spring bees but not of the parasitoids, which may even benefit from warming temperatures.},
  subject      = {Biene <Gattung>},
  language  = {en}
}
@article{KessieLodesOberwinkleretal.2021,
  author    = {Kessie, David K. and Lodes, Nina and Oberwinkler, Heike and Goldman, William E. and Walles, Thorsten and Steinke, Maria and Gross, Roy},
  title     = {Activity of Tracheal Cytotoxin of Bordetella pertussis in a Human Tracheobronchial 3D Tissue Model},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {10},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2020.614994},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222736},
  year      = {2021},
  abstract  = {Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.},
  language  = {en}
}
@article{KouhestaniGeisAlsourietal.2021,
  author    = {Kouhestani, Dina and Geis, Maria and Alsouri, Saed and Bumm, Thomas G. P. and Einsele, Hermann and Sauer, Markus and Stuhler, Gernot},
  title     = {Variant signaling topology at the cancer cell-T-cell interface induced by a two-component T-cell engager},
  series = {Cellular \& Molecular Immunology},
  volume    = {18},
  journal   = {Cellular \& Molecular Immunology},
  doi       = {10.1038/s41423-020-0507-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241189},
  pages     = {1568-1570},
  year      = {2021},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{KramerMeyerNatusStigloheretal.2021,
  author    = {Kramer, Susanne and Meyer-Natus, Elisabeth and Stigloher, Christian and Thoma, Hanna and Schnaufer, Achim and Engstler, Markus},
  title     = {Parallel monitoring of RNA abundance, localization and compactness with correlative single molecule FISH on LR White embedded samples},
  series = {Nucleic Acids Research},
  volume    = {49},
  journal   = {Nucleic Acids Research},
  number    = {3},
  doi       = {10.1093/nar/gkaa1142},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230647},
  year      = {2021},
  abstract  = {Single mRNA molecules are frequently detected by single molecule fluorescence in situ hybridization (smFISH) using branched DNA technology. While providing strong and background-reduced signals, the method is inefficient in detecting mRNAs within dense structures, in monitoring mRNA compactness and in quantifying abundant mRNAs. To overcome these limitations, we have hybridized slices of high pressure frozen, freeze-substituted and LR White embedded cells (LR White smFISH). mRNA detection is physically restricted to the surface of the resin. This enables single molecule detection of RNAs with accuracy comparable to RNA sequencing, irrespective of their abundance, while at the same time providing spatial information on RNA localization that can be complemented with immunofluorescence and electron microscopy, as well as array tomography. Moreover, LR White embedding restricts the number of available probe pair recognition sites for each mRNA to a small subset. As a consequence, differences in signal intensities between RNA populations reflect differences in RNA structures, and we show that the method can be employed to determine mRNA compactness. We apply the method to answer some outstanding questions related to trans-splicing, RNA granules and mitochondrial RNA editing in single-cellular trypanosomes and we show an example of differential gene expression in the metazoan Caenorhabditis elegans.},
  language  = {en}
}
@article{KriegelFritzeThorn2021,
  author    = {Kriegel, Peter and Fritze, Michael-Andreas and Thorn, Simon},
  title     = {Surface temperature and shrub cover drive ground beetle (Coleoptera: Carabidae) assemblages in short-rotation coppices},
  series = {Agricultural and Forest Entomology},
  volume    = {23},
  journal   = {Agricultural and Forest Entomology},
  number    = {4},
  doi       = {10.1111/afe.12441},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239873},
  pages     = {400 -- 410},
  year      = {2021},
  abstract  = {Increasing demand for biomass has led to an on-going intensification of fuel wood plantations with possible negative effects on open land biodiversity. Hence, ecologists increasingly call for measures that reduce those negative effects on associated biodiversity. However, our knowledge about the efficiency of such measures remains scarce. We investigated the effects of gap implementation in short rotation coppices (SRCs) on carabid diversity and assemblage composition over 3 years, with pitfall traps in gaps, edges and interiors. In parallel, we quantified soil surface temperature, shrub- and herb cover. Edges had the highest number of species and abundances per trap, whereas rarefied species richness was significantly lower in short rotation coppice interiors than in other habitat types. Carabid community composition differed significantly between habitat types. The main environmental drivers were temperature for number of species and abundance and shrub cover for rarefied species richness. We found significantly higher rarefied species richness in gaps compared with interiors. Hence, we argue that gap implementation benefits overall diversity in short rotation coppices. Furthermore, the differences in species community composition between habitat types through increased species turnover support carabid diversity in short rotation coppices. These positive effects were largely attributed to microclimate conditions. However, to maintain positive effects, continuous management of herb layer might be necessary.},
  language  = {en}
}
@article{KriegelMatevskiSchuldt2021,
  author    = {Kriegel, Peter and Matevski, Dragan and Schuldt, Andreas},
  title     = {Monoculture and mixture-planting of non-native Douglas fir alters species composition, but promotes the diversity of ground beetles in a temperate forest system},
  series = {Biodiversity and Conservation},
  volume    = {30},
  journal   = {Biodiversity and Conservation},
  number    = {5},
  issn      = {1572-9710},
  doi       = {10.1007/s10531-021-02155-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269017},
  pages     = {1479-1499},
  year      = {2021},
  abstract  = {Planting non-native tree species, like Douglas fir in temperate European forest systems, is encouraged to mitigate effects of climate change. However, Douglas fir monocultures often revealed negative effects on forest biota, while effects of mixtures with native tree species on forest ecosystems are less well understood. We investigated effects of three tree species (Douglas fir, Norway spruce, native European beech), on ground beetles in temperate forests of Germany. Beetles were sampled in monocultures of each tree species and broadleaf-conifer mixtures with pitfall traps, and environmental variables were assessed around each trap. We used linear mixed models in a two-step procedure to disentangle effects of environment and tree species identity on ground beetle abundance, species richness, functional diversity and species assemblage structure. Contradictory to our expectations, ground beetle abundance and functional diversity was highest in pure Douglas fir stands, while tree mixtures showed intermediate values between pure coniferous and pure beech stands. The main drivers of these patterns were only partially dependent on tree species identity, which highlights the importance of structural features in forest stands. However, our study revealed distinct shifts in assemblage structure between pure beech and pure Douglas fir stands, which were only partially eased through mixture planting. Our findings suggest that effects of planting non-native trees on associated biodiversity can be actively modified by promoting beneficial forest structures. Nevertheless, integrating non-native tree species, even in mixtures with native trees, will invariably alter assemblage structures of associated biota, which can compromise conservation efforts targeted at typical species composition.},
  language  = {en}
}
@phdthesis{Krimmer2021,
  author    = {Krimmer, Elena},
  title     = {Agri-environment schemes and ecosystem services: The influence of different sown flower field characteristics on pollination, natural pest control and crop yield},
  doi       = {10.25972/OPUS-20657},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206577},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Insects are responsible for the major part of the ecosystem services pollination and natural pest control. If insects decline, these ecosystem services can not longer be reliably delivered. Agricultural intensification and the subsequent loss and fragmentation of habitats has among others been identified to cause insect decline. Ecological intensification aims to promote alternative and sustainable management practices in agricultural farming, for example to decrease the use of external inputs such as pesticides. Agri-environment schemes make amends for farmers if they integrate ecologically beneficial measures into their farming regime and can therefore promote ecological intensification. There is a wide variety of agri-environment schemes, but the implementation of sown flower fields on crop fields is often included. Flower fields offer foraging resources as well as nesting sites for many different insect species and should be able to support insect populations as well as to increase ecosystem services to adjacent fields. However, the potential of flower fields to exhibit these effects is depending on many factors. Among others, the age and size of the flower field can influence if and how different insects profit from the measure. Additionally, the complexity of the surrounding landscape and therefore the existing biodiversity is influencing the potential of flower fields to increase ecosystem services locally. The goal of this study is to disentangle to which degree these factors influence the ecosystem services pollination and natural pest control and if these factors interact with each other. Furthermore, it will be examined if and how flower fields and ecosystem services influence crop yield. Additional factors examined in this study are distance decay and pesticide use. The abundance of beneficial insects can decrease strongly with increasing distance to suitable habitats. Pesticide use in turn could abrogate positive effects of flower fields on beneficial insects. To examine these different aspects and to be able to make recommendations for flower field implementation, field experiments were conducted on differently composed sown flower fields and adjacent oilseed rape fields. Flower fields differed in their age and continuity as well as in their size. Additionally, flower and oilseed rape fields were chosen in landscapes with different amounts of semi-natural habitat. Oilseed rape fields adjacent to calcareous grasslands and conventional crop fields served as controls. Pollinator observations and pollen beetle and parasitism surveys were conducted in the oilseed rape fields. Additionally, different yield parameters of the oilseed rape plants were recorded. Observations were conducted and samples taken in increasing distance to the flower fields to examine distance decay functions. Spray windows were established to inspect the influence of pesticides on ecosystem services and crop yields. Linear mixed models were used for statistical analysis. The results show, that newly established flower fields with high amounts of flower cover are very attractive for pollinators. If the flower fields reached a certain size (> 1.5ha), the pollinators tended to stay in these fields and did not distribute into the surroundings. High amounts of semi-natural habitat in the surrounding landscape increased the value of small flower fields as starting points for pollinators and their subsequent spillover into crop fields. Additionally, high amounts of semi-natural habitat decreased the decay of pollinators with increasing distance to the flower fields. Based on these results, it can be recommended to establish many small flower fields in landscapes with high amounts of semi-natural habitat and large flower fields in landscapes with low amounts of semi-natural habitat. However, it is mentionable that flower fields are no substitute for perennial semi-natural habitats. These still must be actively conserved to increase pollination to crop fields. Furthermore, the lowest amount of pollen beetle infestation was found on oilseed rape fields adjacent to continuous flower fields aged older than 6 years. Flower fields and calcareous grasslands in general increased pollen beetle parasitism in adjacent oilseed rape fields compared to conventional crop fields. The threshold for effective natural pest control could only be reached in the pesticide free areas in the oilseed rape fields adjacent to continuous flower fields and calcareous grasslands. Parasitism and superparasitism declined with increasing distance to the adjacent fields in pesticide treated areas of the oilseed rape fields. However, they remained on a similar level in spray windows without pesticides. Large flower fields increased parasitism and superparasitism more than small flower fields. Flower fields generally have the potential to increase pollen beetle parasitism rates, but pesticides can abrogate these positive effects of flower fields on natural pest control. Last but not least, effects of flower fields and ecosystem services on oilseed rape yield were examined. No positive effects of pollination on oilseed rape yield could be found. Old and continuous flower fields increased natural pest control in oilseed rape fields, which in turn increased seed set and total seed weight of oilseed rape plants. The pesticide treatment had negative effects on natural pest control, but positive effects on crop yield. Pollination and natural pest control decreased with increasing distance to the field edge, but fruit set slightly increased. The quality of the field in terms of soil and climatic conditions did not influence the yield parameters examined in this study. Yield formation in oilseed rape plants is a complex process with many factors involved, and it is difficult to disentangle indirect effects of flower fields on yield. However, perennial flower fields can promote ecological intensification by increasing crop yield via natural pest control. This study contributes to a better understanding of the effects of differently composed flower fields on pollination, natural pest control and oilseed rape yield.},
  subject      = {{\"O}kologie},
  language  = {en}
}
@article{KronesRuehlingBeckeretal.2021,
  author    = {Krones, David and R{\"u}hling, Marcel and Becker, Katrin Anne and Kunz, Tobias C. and Sehl, Carolin and Paprotka, Kerstin and Gulbins, Erich and Fraunholz, Martin},
  title     = {Staphylococcus aureus α-Toxin Induces Acid Sphingomyelinase Release From a Human Endothelial Cell Line},
  series = {Frontiers in Microbiology},
  volume    = {12},
  journal   = {Frontiers in Microbiology},
  issn      = {1664-302X},
  doi       = {10.3389/fmicb.2021.694489},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244843},
  year      = {2021},
  abstract  = {Staphylococcus aureus (S. aureus) is well known to express a plethora of toxins of which the pore-forming hemolysin A (α-toxin) is the best-studied cytolysin. Pore-forming toxins (PFT) permeabilize host membranes during infection thereby causing concentration-dependent effects in host cell membranes ranging from disordered ion fluxes to cytolysis. Host cells possess defense mechanisms against PFT attack, resulting in endocytosis of the breached membrane area and delivery of repair vesicles to the insulted plasma membrane as well as a concurrent release of membrane repair enzymes. Since PFTs from several pathogens have been shown to recruit membrane repair components, we here investigated whether staphylococcal α-toxin is able to induce these mechanisms in endothelial cells. We show that S. aureus α-toxin induced increase in cytosolic Ca2+ in endothelial cells, which was accompanied by p38 MAPK phosphorylation. Toxin challenge led to increased endocytosis of an extracellular fluid phase marker as well as increased externalization of LAMP1-positive membranes suggesting that peripheral lysosomes are recruited to the insulted plasma membrane. We further observed that thereby the lysosomal protein acid sphingomyelinase (ASM) was released into the cell culture medium. Thus, our results show that staphylococcal α-toxin triggers mechanisms in endothelial cells, which have been implicated in membrane repair after damage of other cell types by different toxins.},
  language  = {en}
}
@article{KruegerMausKressetal.2021,
  author    = {Kr{\"u}ger, Timothy and Maus, Katharina and Kreß, Verena and Meyer-Natus, Elisabeth and Engstler, Markus},
  title     = {Single-cell motile behaviour of Trypanosoma brucei in thin-layered fluid collectives},
  series = {The European Physical Journal E},
  volume    = {44},
  journal   = {The European Physical Journal E},
  number    = {3},
  issn      = {1292-895X},
  doi       = {10.1140/epje/s10189-021-00052-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-273022},
  year      = {2021},
  abstract  = {We describe a system for the analysis of an important unicellular eukaryotic flagellate in a confining and crowded environment. The parasite Trypanosoma brucei is arguably one of the most versatile microswimmers known. It has unique properties as a single microswimmer and shows remarkable adaptations (not only in motility, but prominently so), to its environment during a complex developmental cycle involving two different hosts. Specific life cycle stages show fascinating collective behaviour, as millions of cells can be forced to move together in extreme confinement. Our goal is to examine such motile behaviour directly in the context of the relevant environments. Therefore, for the first time, we analyse the motility behaviour of trypanosomes directly in a widely used assay, which aims to evaluate the parasites behaviour in collectives, in response to as yet unknown parameters. In a step towards understanding whether, or what type of, swarming behaviour of trypanosomes exists, we customised the assay for quantitative tracking analysis of motile behaviour on the single-cell level. We show that the migration speed of cell groups does not directly depend on single-cell velocity and that the system remains to be simplified further, before hypotheses about collective motility can be advanced.},
  language  = {en}
}
@article{KuhlGuiguenHoehneetal.2021,
  author    = {Kuhl, Heiner and Guiguen, Yann and H{\"o}hne, Christin and Kreuz, Eva and Du, Kang and Klopp, Christophe and Lopez-Roques,, C{\´e}line and Yebra-Pimentel, Elena Santidrian and Ciorpac, Mitica and Gessner, J{\"o}rn and Holostenco, Daniela and Kleiner, Wibke and Kohlmann, Klaus and Lamatsch, Dunja K. and Prokopov, Dmitry and Bestin, Anastasia and Bonpunt, Emmanuel and Debeuf, Bastien and Haffray, Pierrick and Morvezen, Romain and Patrice, Pierre and Suciu, Radu and Dirks, Ron and Wuertz, Sven and Kloas, Werner and Schartl, Manfred and St{\"o}ck, Matthias},
  title     = {A 180 Myr-old female-specific genome region in sturgeon reveals the oldest known vertebrate sex determining system with undifferentiated sex chromosomes},
  series = {Philosophical Transactions of the Royal Society B},
  volume    = {376},
  journal   = {Philosophical Transactions of the Royal Society B},
  doi       = {10.1098/rstb.2020.0089},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363050},
  year      = {2021},
  abstract  = {Several hypotheses explain the prevalence of undifferentiated sex chromosomes in poikilothermic vertebrates. Turnovers change the master sex determination gene, the sex chromosome or the sex determination system (e.g. XY to WZ). Jumping master genes stay main triggers but translocate to other chromosomes. Occasional recombination (e.g. in sex-reversed females) prevents sex chromosome degeneration. Recent research has uncovered conserved heteromorphic or even homomorphic sex chromosomes in several clades of non-avian and non-mammalian vertebrates. Sex determination in sturgeons (Acipenseridae) has been a long-standing basic biological question, linked to economical demands by the caviar-producing aquaculture. Here, we report the discovery of a sex-specific sequence from sterlet (Acipenser ruthenus). Using chromosome-scale assemblies and pool-sequencing, we first identified an approximately 16 kb female-specific region. We developed a PCR-genotyping test, yielding female-specific products in six species, spanning the entire phylogeny with the most divergent extant lineages (A. sturio, A. oxyrinchus versus A. ruthenus, Huso huso), stemming from an ancient tetraploidization. Similar results were obtained in two octoploid species (A. gueldenstaedtii, A. baerii). Conservation of a female-specific sequence for a long period, representing 180 Myr of sturgeon evolution, and across at least one polyploidization event, raises many interesting biological questions. We discuss a conserved undifferentiated sex chromosome system with a ZZ/ZW-mode of sex determination and potential alternatives. This article is part of the theme issue 'Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)'.},
  language  = {en}
}
@article{KuhlemannBeliuJanzenetal.2021,
  author    = {Kuhlemann, Alexander and Beliu, Gerti and Janzen, Dieter and Petrini, Enrica Maria and Taban, Danush and Helmerich, Dominic A. and Doose, S{\"o}ren and Bruno, Martina and Barberis, Andrea and Villmann, Carmen and Sauer, Markus and Werner, Christian},
  title     = {Genetic Code Expansion and Click-Chemistry Labeling to Visualize GABA-A Receptors by Super-Resolution Microscopy},
  series = {Frontiers in Synaptic Neuroscience},
  volume    = {13},
  journal   = {Frontiers in Synaptic Neuroscience},
  issn      = {1663-3563},
  doi       = {10.3389/fnsyn.2021.727406},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251035},
  year      = {2021},
  abstract  = {Fluorescence labeling of difficult to access protein sites, e.g., in confined compartments, requires small fluorescent labels that can be covalently tethered at well-defined positions with high efficiency. Here, we report site-specific labeling of the extracellular domain of γ-aminobutyric acid type A (GABA-A) receptor subunits by genetic code expansion (GCE) with unnatural amino acids (ncAA) combined with bioorthogonal click-chemistry labeling with tetrazine dyes in HEK-293-T cells and primary cultured neurons. After optimization of GABA-A receptor expression and labeling efficiency, most effective variants were selected for super-resolution microscopy and functionality testing by whole-cell patch clamp. Our results show that GCE with ncAA and bioorthogonal click labeling with small tetrazine dyes represents a versatile method for highly efficient site-specific fluorescence labeling of proteins in a crowded environment, e.g., extracellular protein domains in confined compartments such as the synaptic cleft.},
  language  = {en}
}
@article{KunzRuehlingMoldovanetal.2021,
  author    = {Kunz, Tobias C. and R{\"u}hling, Marcel and Moldovan, Adriana and Paprotka, Kerstin and Kozjak-Pavlovic, Vera and Rudel, Thomas and Fraunholz, Martin},
  title     = {The Expandables: Cracking the Staphylococcal Cell Wall for Expansion Microscopy},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {11},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2021.644750},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232292},
  year      = {2021},
  abstract  = {Expansion Microscopy (ExM) is a novel tool improving the resolution of fluorescence microscopy by linking the sample into a hydrogel that gets physically expanded in water. Previously, we have used ExM to visualize the intracellular Gram-negative pathogens Chlamydia trachomatis, Simkania negevensis, and Neisseria gonorrhoeae. Gram-positive bacteria have a rigid and thick cell wall that impedes classic expansion strategies. Here we developed an approach, which included a series of enzymatic treatments resulting in isotropic 4× expansion of the Gram-positive pathogen Staphylococcus aureus. We further demonstrate the suitability of the technique for imaging of planktonic bacteria as well as endocytosed, intracellular bacteria at a spatial resolution of approximately 60 nm with conventional confocal laser scanning microscopy.},
  language  = {en}
}
@article{KoehlerHendricksKastneretal.2021,
  author    = {K{\"o}hler, Franziska and Hendricks, Anne and Kastner, Carolin and M{\"u}ller, Sophie and Boerner, Kevin and Wagner, Johanna C. and Lock, Johan F. and Wiegering, Armin},
  title     = {Laparoscopic appendectomy versus antibiotic treatment for acute appendicitis-a systematic review},
  series = {International Journal of Colorectal Disease},
  volume    = {36},
  journal   = {International Journal of Colorectal Disease},
  number    = {10},
  issn      = {1432-1262},
  doi       = {10.1007/s00384-021-03927-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266616},
  pages     = {2283-2286},
  year      = {2021},
  abstract  = {Background Over the last years, laparoscopic appendectomy has progressively replaced open appendectomy and become the current gold standard treatment for suspected, uncomplicated appendicitis. At the same time, though, it is an ongoing discussion that antibiotic therapy can be an equivalent treatment for patients with uncomplicated appendicitis. The aim of this systematic review was to determine the safety and efficacy of antibiotic therapy and compare it to the laparoscopic appendectomy for acute, uncomplicated appendicitis. Methods The PubMed database, Embase database, and Cochrane library were scanned for studies comparing laparoscopic appendectomy with antibiotic treatment. Two independent reviewers performed the study selection and data extraction. The primary endpoint was defined as successful treatment of appendicitis. Secondary endpoints were pain intensity, duration of hospitalization, absence from work, and incidence of complications. Results No studies were found that exclusively compared laparoscopic appendectomy with antibiotic treatment for acute, uncomplicated appendicitis. Conclusions To date, there are no studies comparing antibiotic treatment to laparoscopic appendectomy for patients with acute uncomplicated appendicitis, thus emphasizing the lack of evidence and need for further investigation.},
  language  = {en}
}
@article{KuehnemundtLeifeldSchergetal.2021,
  author    = {K{\"u}hnemundt, Johanna and Leifeld, Heidi and Scherg, Florian and Schmitt, Matthias and Nelke, Lena C. and Schmitt, Tina and Bauer, Florentin and G{\"o}ttlich, Claudia and Fuchs, Maximilian and Kunz, Meik and Peindl, Matthias and Br{\"a}hler, Caroline and Kronenthaler, Corinna and Wischhusen, J{\"o}rg and Prelog, Martina and Walles, Heike and Dandekar, Thomas and Dandekar, Gudrun and Nietzer, Sarah L.},
  title     = {Modular micro-physiological human tumor/tissue models based on decellularized tissue for improved preclinical testing},
  series = {ALTEX},
  volume    = {38},
  journal   = {ALTEX},
  doi       = {10.14573/altex.2008141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231465},
  pages     = {289-306},
  year      = {2021},
  abstract  = {High attrition-rates entailed by drug testing in 2D cell culture and animal models stress the need for improved modeling of human tumor tissues. In previous studies our 3D models on a decellularized tissue matrix have shown better predictivity and higher chemoresistance. A single porcine intestine yields material for 150 3D models of breast, lung, colorectal cancer (CRC) or leukemia. The uniquely preserved structure of the basement membrane enables physiological anchorage of endothelial cells and epithelial-derived carcinoma cells. The matrix provides different niches for cell growth: on top as monolayer, in crypts as aggregates and within deeper layers. Dynamic culture in bioreactors enhances cell growth. Comparing gene expression between 2D and 3D cultures, we observed changes related to proliferation, apoptosis and stemness. For drug target predictions, we utilize tumor-specific sequencing data in our in silico model finding an additive effect of metformin and gefitinib treatment for lung cancer in silico, validated in vitro. To analyze mode-of-action, immune therapies such as trispecific T-cell engagers in leukemia, as well as toxicity on non-cancer cells, the model can be modularly enriched with human endothelial cells (hECs), immune cells and fibroblasts. Upon addition of hECs, transmigration of immune cells through the endothelial barrier can be investigated. In an allogenic CRC model we observe a lower basic apoptosis rate after applying PBMCs in 3D compared to 2D, which offers new options to mirror antigen-specific immunotherapies in vitro. In conclusion, we present modular human 3D tumor models with tissue-like features for preclinical testing to reduce animal experiments.},
  language  = {en}
}
@phdthesis{Lapuente2021,
  author    = {Lapuente, Juan M.},
  title     = {The Chimpanzees of the Como{\´e} National Park, Ivory Coast. Status, distribution, ecology and behavior},
  doi       = {10.25972/OPUS-22318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223180},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Although wild chimpanzees (Pan troglodytes) have been studied intensely for more than 50 years, there are still many aspects of their ecology and behavior that are not well understood. Every time that a new population of chimpanzees has been studied, new behaviors and unknown aspects of their ecology have been discovered. All this accumulated knowledge is helping us to piece together a model of how could last human and chimpanzee common ancestors have lived and behaved between seven and five million years ago. Como{\´e} chimpanzees had never been studied in depth, until we started our research in October 2014, only a few censuses had been realized. The last surveys prior our work, stated that the population was so decimated that was probably functionally extinct. When we started this research, we had to begin with a new intensive survey, using new methods, to ascertain the real status and distribution of the chimpanzees living in Como{\´e} National Park (CNP). During the last five years, we have realized a deep study aiming to know more about their ecology and behavior. We combined transects and reconnaissance marches (recces) with the use of camera traps, for the first time in CNP, obtaining a wealth of data that is not fully comprised in this dissertation. With this research, we determined that there is a sustainable continuous population of Western chimpanzees (Pan troglodytes verus) in CNP and the adjacent area of Mont Tingui, to the West, with a minimum of 127 weaned chimpanzees living in our main 900 km2 study area, SW of CNP. We found that this population is formed by a minimum of eight different chimpanzee communities, of which we studied seven, four of them more in detail. These chimpanzees spent much more time in the forest than in the savanna habitats. We also found that Como{\´e} chimpanzees consumed at least 58 different food items in their dit, which they obtained both from forest and savanna habitats. Another finding was that insectivory had an important role in their diet, with at least four species of ants, three of termites and some beetle larvae. These chimpanzees also hunted at least three species of monkeys and maybe rodents and duikers and occasionally consumed the big land snails of genus Achatina. We found that, during the fruit scarcity period in the late rainy season, they intensely consumed the cambium of Ceiba pentandra, as fallback food, much more than the bark or cambium of any other tree species. Another interesting finding was that all the chimpanzees in the studied area realized this particular bark-peeling behavior and had been repeatedly peeling the trees of this species for years. This did not increase tree mortality and the damage caused to the trees was healed in two years, not reducing the growth, thus being a sustainable use of the trees. We found that Como{\´e} chimpanzees produced and used a great variety of tools, mainly from wooden materials, but also from stone and herbaceous vegetation. Their tool repertory included stick tools to dip for Dorylus burmeisteri ants, to fish for Camponotus and Crematogaster ants, to dip for honey, mainly from Meliponini stingless bees, but sometimes from honey bees (Apis mellifera). It also included the use of stick tools to fish termites of Macrotermes subhyalinus and Odontotermes majus (TFTs), to dip for water from tree holes and investigatory probes for multiple purposes. Additionally, these chimpanzees used leaf-sponges to drink from tree holes and to collect clayish water from salt-licks. They also used stones to hit the buttresses of trees during displays, the so called accumulative stone throwing behavior and probably used stones as hammers, to crack open hard-shelled Strichnos spinosa and Afraegle paniculata fruits and Achatina snails. The chimpanzees also used objects that are not generally accepted as animal tools, for being attached to the substrate, with different purposes: they drummed buttresses of trees with hands and/or feet to produce sound during male displays and they pounded open hard-shelled fruits, Achatina snails and Cubitermes termite mounds on stone or root anvils. We finally measured the stick tools and found significant differences between them suggesting that they were specialized tools made specifically for every purpose. We studied more in detail the differences between apparently similar tools, the honey dipping tools and the water dipping tools, often with brushes made at their tips to collect the fluids. These last tools were exclusive from Como{\´e} and have not been described at any other site. We found that total length, diameter and brush length were significantly different, suggesting that they were specialized tools. We concluded that Como{\´e} chimpanzees had a particular culture, different from those of other populations of Western chimpanzees across Africa. Efficient protection, further research and permanent presence of research teams are required to avoid that this unique population and its culture disappears by the poaching pressure and maybe by the collateral effects of climate change.},
  subject      = {Parc National de la Como{\´e}},
  language  = {en}
}
@article{LarrieuCabanettesCourbaudetal.2021,
  author    = {Larrieu, Laurent and Cabanettes, Alain and Courbaud, Benoit and Goulard, Michel and Heintz, Wilfried and Koz{\´a}k, Daniel and Kraus, Daniel and Lachat, Thibault and Ladet, Sylvie and M{\"u}ller, J{\"o}rg and Paillet, Yoan and Schuck, Andreas and Stillhard, Jonas and Svoboda, Miroslav},
  title     = {Co-occurrence patterns of tree-related microhabitats: A method to simplify routine monitoring},
  series = {Ecological Indicators},
  volume    = {127},
  journal   = {Ecological Indicators},
  doi       = {10.1016/j.ecolind.2021.107757},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-363158},
  year      = {2021},
  abstract  = {A Tree-related Microhabitat (TreM) is a distinct, well-delineated morphological singularity occurring on living or standing dead trees, which constitutes a crucial substrate or life site for various species. TreMs are widely recognized as key features for biodiversity. Current TreM typology identifies 47 TreM types according to their morphology and their associated taxa. In order to provide a range of resolutions and make the typology more user-friendly, these 47 TreM types have been pooled into 15 groups and seven forms. Depending on the accuracy required and the time available, a user can now choose to describe TreMs at resolution levels corresponding to type, group or form. Another way to more easily record TreMs during routine management work would be to use co-occurrence patterns to reduce the number of observed TreMs required. Based on a large international TreM database (2052 plots; 70,958 individual trees; 78 tree species), we evaluated both the significance and the magnitude of TreM co-occurrence on living trees for 11 TreM groups. We highlighted 33 significant co-occurrences for broadleaves and nine for conifers. Bark loss, rot hole, crack and polypore had the highest number of positive co-occurrences (N = 8) with other TreMs on broadleaves; bark loss (N = 4) had the highest number for conifers. We found mutually exclusive occurrences only for conifers: Exposed Heartwood excluded both dendrotelm and sap run. Among the four variables we tested for their positive contribution to significant co-occurrences, tree diameter at breast height was the most consistent. Based on our results and practical considerations, we selected three TreM groups for broadleaves, and nine for conifers, and formed useful short lists to reduce the number of TreM groups to assess during routine forest management work in the field. In addition, detecting potential similarities or associations between TreMs has potential theoretical value, e.g. it may help researchers identify common factors favouring TreM formation or help managers select trees with multiple TreMs as candidates for retention.},
  language  = {en}
}