@article{KohlRutschmannSteffanDewenter2022,
  author    = {Kohl, Patrick L. and Rutschmann, Benjamin and Steffan-Dewenter, Ingolf},
  title     = {Population demography of feral honeybee colonies in central European forests},
  series = {Royal Society Open Science},
  volume    = {9},
  journal   = {Royal Society Open Science},
  number    = {8},
  issn      = {2054-5703},
  doi       = {10.1098/rsos.220565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301335},
  year      = {2022},
  abstract  = {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.},
  language  = {en}
}
@phdthesis{Mayr2021,
  author    = {Mayr, Antonia Veronika},
  title     = {Following Bees and Wasps up Mt. Kilimanjaro: From Diversity and Traits to hidden Interactions of Species},
  doi       = {10.25972/OPUS-18292},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-182922},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Chapter 1 - General Introduction One of the greatest challenges of ecological research is to predict the response of ecosystems to global change; that is to changes in climate and land use. A complex question in this context is how changing environmental conditions affect ecosystem processes at different levels of communities. To shed light on this issue, I investigate drivers of biodiversity on the level of species richness, functional traits and species interactions in cavity-nesting Hymenoptera. For this purpose, I take advantage of the steep elevational gradient of Mt. Kilimanjaro that shows strong environmental changes on a relatively small spatial scale and thus, provides a good environmental scenario for investigating drivers of diversity. In this thesis, I focus on 1) drivers of species richness at different trophic levels (Chapter 2); 2) seasonal patterns in nest-building activity, life-history traits and ecological rates in three different functional groups and at different elevations (Chapter 3) and 3) changes in cuticular hydrocarbons, pollen composition and microbiomes in Lasioglossum bees caused by climatic variables (Chapter 4). Chapter 2 - Climate and food resources shape species richness and trophic interactions of cavity-nesting Hymenoptera Drivers of species richness have been subject to research for centuries. Temperature, resource availability and top-down regulation as well as the impact of land use are considered to be important factors in determining insect diversity. Yet, the relative importance of each of these factors is unknown. Using trap nests along the elevational gradient of Mt. Kilimanjaro, we tried to disentangle drivers of species richness at different trophic levels. Temperature was the major driver of species richness across trophic levels, with increasing importance of food resources at higher trophic levels in natural antagonists. Parasitism rate was both related to temperature and trophic level, indicating that the relative importance of bottom-up and top-down forces might shift with climate change. Chapter 3 - Seasonal variation in the ecology of tropical cavity-nesting Hymenoptera Natural populations fluctuate with the availability of resources, presence of natural enemies and climatic variations. But tropical mountain seasonality is not yet well investigated. We investigated seasonal patterns in nest-building activity, functional traits and ecological rates in three different insect groups at lower and higher elevations separately. Insects were caught with trap nests which were checked monthly during a 17 months period that included three dry and three rainy seasons. Insects were grouped according to their functional guilds. All groups showed strong seasonality in nest-building activity which was higher and more synchronised among groups at lower elevations. Seasonality in nest building activity of caterpillar-hunting and spider-hunting wasps was linked to climate seasonality while in bees it was strongly linked to the availability of flowers, as well as for the survival rate and sex ratio of bees. Finding adaptations to environmental seasonality might imply that further changes in climatic seasonality by climate change could have an influence on life-history traits of tropical mountain species. Chapter 4 - Cryptic species and hidden ecological interactions of halictine bees along an elevational Gradient Strong environmental gradients such as those occurring along mountain slopes are challenging for species. In this context, hidden adaptations or interactions have rarely been considered. We used bees of the genus Lasioglossum as model organisms because Lasioglossum is the only bee genus occurring with a distribution across the entire elevational gradient at Mt. Kilimanjaro. We asked if and how (a) cuticular hydrocarbons (CHC), which act as a desiccation barrier, change in composition and chain length along with changes in temperature and humidity (b), Lasioglossum bees change their pollen diet with changing resource availability, (c) gut microbiota change with pollen diet and climatic conditions, and surface microbiota change with CHC and climatic conditions, respectively, and if changes are rather influenced by turnover in Lasioglossum species along the elevational gradient. We found physiological adaptations with climate in CHC as well as changes in communities with regard to pollen diet and microbiota, which also correlated with each other. These results suggest that complex interactions and feedbacks among abiotic and biotic conditions determine the species composition in a community. Chapter 5 - General Discussion Abiotic and biotic factors drove species diversity, traits and interactions and they worked differently depending on the functional group that has been studied, and whether spatial or temporal units were considered. It is therefore likely, that in the light of global change, different species, traits and interactions will be affected differently. Furthermore, increasing land use intensity could have additional or interacting effects with climate change on biodiversity, even though the potential land-use effects at Mt. Kilimanjaro are still low and not impairing cavity-nesting Hymenoptera so far. Further studies should address species networks which might reveal more sensitive changes. For that purpose, trap nests provide a good model system to investigate effects of global change on multiple trophic levels and may also reveal direct effects of climate change on entire life-history traits when established under different microclimatic conditions. The non-uniform effects of abiotic and biotic conditions on multiple aspects of biodiversity revealed with this study also highlight that evaluating different aspects of biodiversity can give a more comprehensive picture than single observations.},
  subject      = {land use},
  language  = {en}
}
@article{MederKoenigOzretićetal.2016,
  author    = {Meder, Lydia and K{\"o}nig, Katharina and Ozretić, Luka and Schultheis, Anne M. and Ueckeroth, Frank and Ade, Carsten P. and Albus, Kerstin and Boehm, Diana and Rommerscheidt-Fuss, Ursula and Florin, Alexandra and Buhl, Theresa and Hartmann, Wolfgang and Wolf, J{\"u}rgen and Merkelbach-Bruse, Sabine and Eilers, Martin and Perner, Sven and Heukamp, Lukas C. and Buettner, Reinhard},
  title     = {NOTCH, ASCL1, p53 and RB alterations define an alternative pathway driving neuroendocrine and small cell lung carcinomas},
  series = {International Journal of Cancer},
  volume    = {138},
  journal   = {International Journal of Cancer},
  number    = {4},
  doi       = {10.1002/ijc.29835},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190853},
  pages     = {927-938},
  year      = {2016},
  abstract  = {Small cell lung cancers (SCLCs) and extrapulmonary small cell cancers (SCCs) are very aggressive tumors arising de novo as primary small cell cancer with characteristic genetic lesions in RB1 and TP53. Based on murine models, neuroendocrine stem cells of the terminal bronchioli have been postulated as the cellular origin of primary SCLC. However, both in lung and many other organs, combined small cell/non-small cell tumors and secondary transitions from non-small cell carcinomas upon cancer therapy to neuroendocrine and small cell tumors occur. We define features of "small cell-ness" based on neuroendocrine markers, characteristic RB1 and TP53 mutations and small cell morphology. Furthermore, here we identify a pathway driving the pathogenesis of secondary SCLC involving inactivating NOTCH mutations, activation of the NOTCH target ASCL1 and canonical WNT-signaling in the context of mutual bi-allelic RB1 and TP53 lesions. Additionaly, we explored ASCL1 dependent RB inactivation by phosphorylation, which is reversible by CDK5 inhibition. We experimentally verify the NOTCH-ASCL1-RB-p53 signaling axis in vitro and validate its activation by genetic alterations in vivo. We analyzed clinical tumor samples including SCLC, SCC and pulmonary large cell neuroendocrine carcinomas and adenocarcinomas using amplicon-based Next Generation Sequencing, immunohistochemistry and fluorescence in situ hybridization. In conclusion, we identified a novel pathway underlying rare secondary SCLC which may drive small cell carcinomas in organs other than lung, as well.},
  language  = {en}
}
@article{SinghVermaAkhoonetal.2016,
  author    = {Singh, Krishna P. and Verma, Neeraj and Akhoon, Bashir A . and Bhatt, Vishal and Gupta, Shishir K. and Gupta, Shailendra K. and Smita, Suchi},
  title     = {Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains},
  series = {3 Biotech},
  volume    = {6},
  journal   = {3 Biotech},
  doi       = {10.1007/s13205-015-0352-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191056},
  pages     = {10},
  year      = {2016},
  abstract  = {Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe.},
  language  = {en}
}
@article{DechaudVolffSchartletal.2019,
  author    = {Dechaud, Corentin and Volff, Jean-Nicolas and Schartl, Manfred and Naville, Magali},
  title     = {Sex and the TEs: transposable elements in sexual development and function in animals},
  series = {Mobile DNA},
  volume    = {10},
  journal   = {Mobile DNA},
  doi       = {10.1186/s13100-019-0185-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202510},
  pages     = {42},
  year      = {2019},
  abstract  = {Transposable elements are endogenous DNA sequences able to integrate into and multiply within genomes. They constitute a major source of genetic innovations, as they can not only rearrange genomes but also spread ready-to-use regulatory sequences able to modify host gene expression, and even can give birth to new host genes. As their evolutionary success depends on their vertical transmission, transposable elements are intrinsically linked to reproduction. In organisms with sexual reproduction, this implies that transposable elements have to manifest their transpositional activity in germ cells or their progenitors. The control of sexual development and function can be very versatile, and several studies have demonstrated the implication of transposable elements in the evolution of sex. In this review, we report the functional and evolutionary relationships between transposable elements and sexual reproduction in animals. In particular, we highlight how transposable elements can influence expression of sexual development genes, and how, reciprocally, they are tightly controlled in gonads. We also review how transposable elements contribute to the organization, expression and evolution of sexual development genes and sex chromosomes. This underscores the intricate co-evolution between host functions and transposable elements, which regularly shift from a parasitic to a domesticated status useful to the host.},
  language  = {en}
}
@article{MrestaniPauliKollmannsbergeretal.2021,
  author    = {Mrestani, Achmed and Pauli, Martin and Kollmannsberger, Philip and Repp, Felix and Kittel, Robert J. and Eilers, Jens and Doose, S{\"o}ren and Sauer, Markus and Sir{\´e}n, Anna-Leena and Heckmann, Manfred and Paul, Mila M.},
  title     = {Active zone compaction correlates with presynaptic homeostatic potentiation},
  series = {Cell Reports},
  volume    = {37},
  journal   = {Cell Reports},
  number    = {1},
  doi       = {10.1016/j.celrep.2021.109770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265497},
  pages     = {109770},
  year      = {2021},
  abstract  = {Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic homeostatic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement by incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction microscopy [dSTORM]) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) to study AZ plasticity during PHP at the synaptic mesoscale. We find compaction of individual AZs in acute philanthotoxin-induced and chronic genetically induced PHP but unchanged copy numbers of AZ proteins. Compaction even occurs at the level of Brp subclusters, which move toward AZ centers, and in Rab3 interacting molecule (RIM)-binding protein (RBP) subclusters. Furthermore, correlative confocal and dSTORM imaging reveals how AZ compaction in PHP translates into apparent increases in AZ area and Brp protein content, as implied earlier.},
  language  = {en}
}
@article{SbieraKunzWeigandetal.2019,
  author    = {Sbiera, Silviu and Kunz, Meik and Weigand, Isabel and Deutschbein, Timo and Dandekar, Thomas and Fassnacht, Martin},
  title     = {The new genetic landscape of Cushing's disease: deubiquitinases in the spotlight},
  series = {Cancers},
  volume    = {11},
  journal   = {Cancers},
  number    = {11},
  issn      = {2072-6694},
  doi       = {10.3390/cancers11111761},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193194},
  pages     = {1761},
  year      = {2019},
  abstract  = {Cushing's disease (CD) is a rare condition caused by adrenocorticotropic hormone (ACTH)-producing adenomas of the pituitary, which lead to hypercortisolism that is associated with high morbidity and mortality. Treatment options in case of persistent or recurrent disease are limited, but new insights into the pathogenesis of CD are raising hope for new therapeutic avenues. Here, we have performed a meta-analysis of the available sequencing data in CD to create a comprehensive picture of CD's genetics. Our analyses clearly indicate that somatic mutations in the deubiquitinases are the key drivers in CD, namely USP8 (36.5\%) and USP48 (13.3\%). While in USP48 only Met415 is affected by mutations, in USP8 there are 26 different mutations described. However, these different mutations are clustering in the same hotspot region (affecting in 94.5\% of cases Ser718 and Pro720). In contrast, pathogenic variants classically associated with tumorigenesis in genes like TP53 and BRAF are also present in CD but with low incidence (12.5\% and 7\%). Importantly, several of these mutations might have therapeutic potential as there are drugs already investigated in preclinical and clinical setting for other diseases. Furthermore, network and pathway analyses of all somatic mutations in CD suggest a rather unified picture hinting towards converging oncogenic pathways.},
  language  = {en}
}
@unpublished{HennigPrustyKauferetal.2021,
  author    = {Hennig, Thomas and Prusty, Archana B. and Kaufer, Benedikt and Whisnant, Adam W. and Lodha, Manivel and Enders, Antje and Thomas, Julius and Kasimir, Francesca and Grothey, Arnhild and Herb, Stefanie and J{\"u}rges, Christopher and Meister, Gunter and Erhard, Florian and D{\"o}lken, Lars and Prusty, Bhupesh K.},
  title     = {Selective inhibition of microRNA processing by a herpesvirus-encoded microRNA triggers virus reactivation from latency},
  edition   = {submitted version},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267858},
  year      = {2021},
  abstract  = {Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation thereof 1,2. A long appreciated, yet elusively defined relationship exists between the lytic-latent switch and viral non-coding RNAs 3,4. Here, we identify miRNA-mediated inhibition of miRNA processing as a novel cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defense and drive the latent-lytic switch. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective pri-miRNA hairpin loops. Subsequent loss of miR-30 and activation of miR-30/p53/Drp1 axis triggers a profound disruption of mitochondrial architecture, which impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 was sufficient to trigger virus reactivation from latency thereby identifying it as a readily drugable master regulator of the herpesvirus latent-lytic switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 provides exciting therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders like myalgic encephalitis/chronic fatigue syndrome (ME/CFS) and Long-COVID.},
  language  = {en}
}
@article{LehenbergerBenkertBiedermann2021,
  author    = {Lehenberger, Maximilian and Benkert, Markus and Biedermann, Peter H. W.},
  title     = {Ethanol-Enriched Substrate Facilitates Ambrosia Beetle Fungi, but Inhibits Their Pathogens and Fungal Symbionts of Bark Beetles},
  series = {Frontiers in Microbiology},
  volume    = {11},
  journal   = {Frontiers in Microbiology},
  issn      = {1664-302X},
  doi       = {10.3389/fmicb.2020.590111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222222},
  year      = {2021},
  abstract  = {Bark beetles (sensu lato) colonize woody tissues like phloem or xylem and are associated with a broad range of micro-organisms. Specific fungi in the ascomycete orders Hypocreales, Microascales and Ophistomatales as well as the basidiomycete Russulales have been found to be of high importance for successful tree colonization and reproduction in many species. While fungal mutualisms are facultative for most phloem-colonizing bark beetles (sensu stricto), xylem-colonizing ambrosia beetles are long known to obligatorily depend on mutualistic fungi for nutrition of adults and larvae. Recently, a defensive role of fungal mutualists for their ambrosia beetle hosts was revealed: Few tested mutualists outcompeted other beetle-antagonistic fungi by their ability to produce, detoxify and metabolize ethanol, which is naturally occurring in stressed and/or dying trees that many ambrosia beetle species preferentially colonize. Here, we aim to test (i) how widespread beneficial effects of ethanol are among the independently evolved lineages of ambrosia beetle fungal mutualists and (ii) whether it is also present in common fungal symbionts of two bark beetle species (Ips typographus, Dendroctonus ponderosae) and some general fungal antagonists of bark and ambrosia beetle species. The majority of mutualistic ambrosia beetle fungi tested benefited (or at least were not harmed) by the presence of ethanol in terms of growth parameters (e.g., biomass), whereas fungal antagonists were inhibited. This confirms the competitive advantage of nutritional mutualists in the beetle's preferred, ethanol-containing host material. Even though most bark beetle fungi are found in the same phylogenetic lineages and ancestral to the ambrosia beetle (sensu stricto) fungi, most of them were highly negatively affected by ethanol and only a nutritional mutualist of Dendroctonus ponderosae benefited, however. This suggests that ethanol tolerance is a derived trait in nutritional fungal mutualists, particularly in ambrosia beetles that show cooperative farming of their fungi.},
  language  = {en}
}
@article{ZielewskaBuettnerHeurichMuelleretal.2018,
  author    = {Zielewska-B{\"u}ttner, Katarzyna and Heurich, Marco and M{\"u}ller, J{\"o}rg and Braunisch, Veronika},
  title     = {Remotely Sensed Single Tree Data Enable the Determination of Habitat Thresholds for the Three-Toed Woodpecker (Picoides tridactylus)},
  series = {Remote Sensing},
  volume    = {10},
  journal   = {Remote Sensing},
  number    = {12},
  issn      = {2072-4292},
  doi       = {10.3390/rs10121972},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197565},
  year      = {2018},
  abstract  = {Forest biodiversity conservation requires precise, area-wide information on the abundance and distribution of key habitat structures at multiple spatial scales. We combined airborne laser scanning (ALS) data with color-infrared (CIR) aerial imagery for identifying individual tree characteristics and quantifying multi-scale habitat requirements using the example of the three-toed woodpecker (Picoides tridactylus) (TTW) in the Bavarian Forest National Park (Germany). This bird, a keystone species of boreal and mountainous forests, is highly reliant on bark beetles dwelling in dead or dying trees. While previous studies showed a positive relationship between the TTW presence and the amount of deadwood as a limiting resource, we hypothesized a unimodal response with a negative effect of very high deadwood amounts and tested for effects of substrate quality. Based on 104 woodpecker presence or absence locations, habitat selection was modelled at four spatial scales reflecting different woodpecker home range sizes. The abundance of standing dead trees was the most important predictor, with an increase in the probability of TTW occurrence up to a threshold of 44-50 dead trees per hectare, followed by a decrease in the probability of occurrence. A positive relationship with the deadwood crown size indicated the importance of fresh deadwood. Remote sensing data allowed both an area-wide prediction of species occurrence and the derivation of ecological threshold values for deadwood quality and quantity for more informed conservation management.},
  language  = {en}
}
@phdthesis{Stelzner2020,
  author    = {Stelzner, Kathrin},
  title     = {Identification of factors involved in Staphylococcus aureus- induced host cell death},
  doi       = {10.25972/OPUS-18899},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188991},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Staphylococcus aureus is a Gram-positive commensal bacterium, that asymptomatically colonizes human skin and mucosal surfaces. Upon opportune conditions, such as immunodeficiency or breached barriers of the host, it can cause a plethora of infections ranging from local, superficial infections to life-threatening diseases. Despite being regarded as an extracellular pathogen, S. aureus can invade and survive within non-phagocytic and phagocytic cells. Eventually, the pathogen escapes from the host cell resulting in killing of the host cell, which is associated with tissue destruction and spread of infection. However, the exact molecular mechanisms underlying S. aureus-induced host cell death remain to be elucidated. In the present work, a genome-wide haploid genetic screen was performed to identify host cell genes crucial for S. aureus intracellular cytotoxicity. A mutant library of the haploid cell line HAP1 was infected with the pathogen and cells surviving the infection were selected. Twelve genes were identified, which were significantly enriched when compared to an infection with a non-cytotoxic S. aureus strain. Additionally, characteristics of regulated cell death pathways and the role of Ca2+ signaling in S. aureus-infected cells were investigated. Live cell imaging of Ca2+ reporter cell lines was used to analyze single cells. S. aureus-induced host cell death exhibited morphological features of apoptosis and activation of caspases was detected. Cellular H2O2 levels were elevated during S. aureus intracellular infection. Further, intracellular S. aureus provoked cytosolic Ca2+ overload in epithelial cells. This resulted from Ca2+ release from endoplasmic reticulum and Ca2+ influx via the plasma membrane and led to mitochondrial Ca2+ overload. The final step of S. aureus-induced cell death was plasma membrane permeabilization, a typical feature of necrotic cell death. In order to identify bacterial virulence factors implicated in S. aureus-induced host cell killing, the cytotoxicity of selected mutants was investigated. Intracellular S. aureus employs the bacterial cysteine protease staphopain A to activate an apoptosis-like cell death characterized by cell contraction and membrane bleb formation. Phagosomal escape represents a prerequisite staphopain A-induced cell death, whereas bacterial intracellular replication is dispensable. Moreover, staphopain A contributed to efficient colonization of the lung in a murine pneumonia model. In conclusion, this work identified at least two independent cell death pathways activated by intracellular S. aureus. While initially staphopain A mediates S. aureus-induced host cell killing, cytosolic Ca2+-overload follows later and leads to the final demise of the host cell.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Hartlieb2020,
  author    = {Hartlieb, Heiko},
  title     = {Functional analysis of Mushroom body miniature's RGG-box and its role in neuroblast proliferation in Drosophila melanogaster},
  doi       = {10.25972/OPUS-19967},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199674},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Development of the central nervous system in Drosophila melanogaster relies on neural stem cells called neuroblasts. Neuroblasts divide asymmetrically to give rise to a new neuroblast as well as a small daughter cell which eventually generates neurons or glia cells. Between each division, neuroblasts have to re-grow to be able to divide again. In previous studies, it was shown that neuroblast proliferation, cell size and the number of progeny cells is negatively affected in larvae carrying a P-element induced disruption of the gene mushroom body miniature (mbm). This mbm null mutation called mbmSH1819 is homozygously lethal during pupation. It was furthermore shown that the nucleolar protein Mbm plays a role in the processing of ribosomal RNA (rRNA) as well as the translocation of ribosomal protein S6 (RpS6) in neuroblasts and that it is a transcriptional target of Myc. Therefore, it was suggested that Mbm might regulate neuroblast proliferation through a role in ribosome biogenesis. In the present study, it was attempted to further elucidate these proposed roles of Mbm and to identify the protein domains that are important for those functions. Mbm contains an arginine/glycine rich region in which a di-RG as well as a di-RGG motif could be found. Together, these two motifs were defined as Mbm's RGG-box. RGG-boxes can be found in many proteins of different families and they can either promote or inhibit protein-RNA as well as protein-protein interactions. Therefore, Mbm's RGG-box is a likely candidate for a domain involved in rRNA binding and RpS6 translocation. It could be shown by deletion of the RGG-box, that MbmdRGG is unable to fully rescue survivability and neuroblast cell size defects of the null mutation mbmSH1819. Furthermore, Mbm does indeed rely on its RGG-box for the binding of rRNA in vitro and in mbmdRGG as well as mbmSH1819 mutants RpS6 is partially delocalized. Mbm itself also seems to depend on the RGG-box for correct localization since MbmdRGG is partially delocalized to the nucleus. Interestingly, protein synthesis rates are increased in mbmdRGG mutants, possibly induced by an increase in TOR expression. Therefore, Mbm might possess a promoting function in TOR signaling in certain conditions, which is regulated by its RGG-box. Moreover, RGG-boxes often rely on methylation by protein arginine methyltransferases (in Drosophila: Darts - Drosophila arginine methyltransferases) to fulfill their functions. Mbm might be symmetrically dimethylated within its RGG-box, but the results are very equivocal. In any case, Dart1 and Dart5 do not seem to be capable of Mbm methylation. Additionally, Mbm contains two C2HC type zinc-finger motifs, which could be involved in rRNA binding. In an earlier study, it was shown that the mutation of the zinc-fingers, mbmZnF, does not lead to changes in neuroblast cell size, but that MbmZnF is delocalized to the cytoplasm. In the present study, mbmZnF mutants were included in most experiments. The results, however, are puzzling since mbmZnF mutant larvae exhibit an even lower viability than the mbm null mutants and MbmZnF shows stronger binding to rRNA than wild-type Mbm. This suggests an unspecific interaction of MbmZnF with either another protein, DNA or RNA, possibly leading to a dominant negative effect by disturbing other interaction partners. Therefore, it is difficult to draw conclusions about the zinc-fingers' functions. In summary, this study provides further evidence that Mbm is involved in neuroblast proliferation as well as the regulation of ribosome biogenesis and that Mbm relies on its RGG-box to fulfill its functions.},
  subject      = {Taufliege},
  language  = {en}
}
@article{KohlRutschmann2018,
  author    = {Kohl, Patrick Laurenz and Rutschmann, Benjamin},
  title     = {The neglected bee trees: European beech forests as a home for feral honey bee colonies},
  series = {PeerJ},
  volume    = {6},
  journal   = {PeerJ},
  number    = {e4602},
  doi       = {10.7717/peerj.4602},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176512},
  year      = {2018},
  abstract  = {It is a common belief that feral honey bee colonies (Apis mellifera L.) were eradicated in Europe through the loss of habitats, domestication by man and spread of pathogens and parasites. Interestingly, no scientific data are available, neither about the past nor the present status of naturally nesting honeybee colonies. We expected near-natural beech (Fagus sylvatica L.) forests to provide enough suitable nest sites to be a home for feral honey bee colonies in Europe. Here, we made a first assessment of their occurrence and density in two German woodland areas based on two methods, the tracing of nest sites based on forager flight routes (beelining technique), and the direct inspection of potential cavity trees. Further, we established experimental swarms at forest edges and decoded dances for nest sites performed by scout bees in order to study how far swarms from beekeeper-managed hives would potentially move into a forest. We found that feral honey bee colonies regularly inhabit tree cavities in near-natural beech forests at densities of at least 0.11-0.14 colonies/km\(^{2}\). Colonies were not confined to the forest edges; they were also living deep inside the forests. We estimated a median distance of 2,600 m from the bee trees to the next apiaries, while scout bees in experimental swarms communicated nest sites in close distances (median: 470 m). We extrapolate that there are several thousand feral honey bee colonies in German woodlands. These have to be taken in account when assessing the role of forest areas in providing pollination services to the surrounding land, and their occurrence has implications for the species' perception among researchers, beekeepers and conservationists. This study provides a starting point for investigating the life-histories and the ecological interactions of honey bees in temperate European forest environments.},
  language  = {en}
}
@article{SchusterLisackSubotaetal.2021,
  author    = {Schuster, Sarah and Lisack, Jaime and Subota, Ines and Zimmermann, Henriette and Reuter, Christian and Mueller, Tobias and Morriswood, Brooke and Engstler, Markus},
  title     = {Unexpected plasiticty in the life cycle of Trypanosoma brucei},
  series = {eLife},
  volume    = {10},
  journal   = {eLife},
  doi       = {10.7554/eLife.66028.sa2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-261744},
  year      = {2021},
  abstract  = {African trypanosomes cause sleeping sickness in humans and nagana in cattle. These unicellular parasites are transmitted by the bloodsucking tsetse fly. In the mammalian host's circulation, proliferating slender stage cells differentiate into cell cycle-arrested stumpy stage cells when they reach high population densities. This stage transition is thought to fulfil two main functions: first, it auto-regulates the parasite load in the host; second, the stumpy stage is regarded as the only stage capable of successful vector transmission. Here, we show that proliferating slender stage trypanosomes express the mRNA and protein of a known stumpy stage marker, complete the complex life cycle in the fly as successfully as the stumpy stage, and require only a single parasite for productive infection. These findings suggest a reassessment of the traditional view of the trypanosome life cycle. They may also provide a solution to a long-lasting paradox, namely the successful transmission of parasites in chronic infections, despite low parasitemia.},
  language  = {en}
}
@phdthesis{Lehmann2020,
  author    = {Lehmann, Julian},
  title     = {Hochaufl{\"o}sende Fluoreszenzmikroskopie beleuchtet den Oligomerisierungsstatus pflanzlicher Membranproteine},
  doi       = {10.25972/OPUS-21176},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211762},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {SLAC/SLAH Anionenkan{\"a}le, die zur Familie der langsamen Anionenkan{\"a}le geh{\"o}ren, repr{\"a}sentieren Schl{\"u}sselproteine in der pflanzlichen Stressantwort. Neben ihrer Aufgabe in Stresssituationen, ist eine Untergruppe der Kan{\"a}le f{\"u}r die Beladung der Leitgef{\"a}ße mit Nitrat und Chlorid in der Stele der Pflanzenwurzeln verantwortlich. Biophysikalische und pflanzenphysiologische Studien stellten heraus, dass vor Allem der Anionenkanal SLAH3 f{\"u}r die Beladung der Xylem Leitgef{\"a}ße mit Nitrat und Chlorid verantwortlich ist. Ihm zur Seite gestellt werden noch die elektrisch inaktiven Homologe SLAH1 und SLAH4 in der Wurzel exprimiert. Sie steuern die Aktivit{\"a}t von SLAH3 durch die Assemblierung zu SLAH1/SLAH3 oder SLAH3/SLAH4 Heteromeren. Neben der Kontrolle durch Heteromerisierungsereignisse, werden SLAH3 Homomere sehr spezifisch und schnell durch zytosolische Ans{\"a}uerung aktiviert. Obwohl bereits die Kristallstruktur des bakteriellen Homologs HiTehA zu pflanzlichen SLAC/SLAH Anionenkan{\"a}len bekannt ist, welche HiTehA als Trimer charakterisiert, sind die St{\"o}chiometrie und der Polymerisierungsgrad der pflanzlichen SLAC/SLAHs bisher noch unbekannt. Die Fluoreszenzmikroskopie umfasst viele etablierte Anwendungsmethoden, wie die konfokale Laserrastermikroskopie (CLSM), Techniken mit verbesserter Aufl{\"o}sung, wie die Mikroskopie mit strukturierter Beleuchtung (SIM) und hochaufl{\"o}sende Methoden, welche durch die Lokalisationsmikroskopie (z.B. dSTORM und PALM) oder die Expansionsmikroskopie (ExM) vertreten werden. Diese unterschiedlichen Mikroskopie-methoden erm{\"o}glichen neue Einblicke in die Organisation von Proteinen in biologischen Systemen, die bis auf die molekulare Ebene hinunterreichen. Insbesondere im Bereich der hochaufl{\"o}senden Fluoreszenzmikroskopie sind im Gegensatz zu tierischen Frage-stellungen bisher jedoch nur wenige Untersuchungen in pflanzlichen Geweben durchgef{\"u}hrt worden. Die Lokalisationsmikroskopie erm{\"o}glicht die Quantifizierung einzelner Molek{\"u}le in nativen Systemen und l{\"a}sst {\"u}berdies R{\"u}ckschl{\"u}sse auf den Polymerisierungsgrad von Proteinen zu. Da Poly- und Heteromerisierung von Proteinen oftmals mit der Funktionalit{\"a}t eines entsprechenden Proteins einhergeht, wie es bei den SLAC/SLAH Anionenkan{\"a}len der Fall ist, wurden in dieser Arbeit PALM Messungen zur Untersuchung des Polymerisierungsgrades und Interaktionsmuster der Anionenkan{\"a}le angewendet. Ferner wurden Expressionsmuster der SLAC/SLAHs untersucht und zudem Mikroskopieanwendungen im Pflanzengewebe etabliert und verbessert. In Bezug auf die Mikroskopieanwendungen konnten wir in Arabidopsis thaliana (At) Wurzeln die polare Verteilung von PIN Proteinen mittels SIM best{\"a}tigen und die gruppierte Verteilung in der Plasmamembran am Zellpol aufl{\"o}sen. In Wurzel-querschnitten war es m{\"o}glich, Zellw{\"a}nde zu vermessen, den Aufbau der Pflanzenwurzel mit den verschiedenen Zelltypen zu rekonstruieren und diesen in Zusammenhang mit Zellwanddicken zu bringen. Anhand dieser Aufnahmen ließ sich die Aufl{\"o}sungsgrenze eines SIM-Mikroskops bestimmen, weshalb diese Probe als Modellstruktur f{\"u}r Aufl{\"o}sungsanalysen, zur Kontrolle f{\"u}r die korrekte Bildverarbeitung bei hochaufl{\"o}sender Bildgebung und andere Fragestellungen empfohlen werden kann. F{\"u}r die Expansionsmikroskopie in pflanzlichen Proben konnten ein enzym- und ein denaturierungsbasiertes Pr{\"a}parationsprotokoll etabliert werden. Dabei wurden ganze At Setzlinge, Wurzelabschnitte und Blattst{\"u}cke gef{\"a}rbt, expandiert und mit zwei bis drei Mal verbesserter Aufl{\"o}sung bildlich dargestellt. In diesem Zusammenhang waren Aufnahmen ganzer Wurzel- und Blattproben mit beeindruckender Eindringtiefe und extrem geringem Hintergrundsignal m{\"o}glich. Zudem wurden die Daten kritisch betrachtet, Probleme aufgezeigt, gewebespezifische Ver{\"a}nderungen dargestellt und limitierende Faktoren f{\"u}r die ExM in Pflanzenproben thematisiert. Im Fokus dieser Arbeit stand die Untersuchung der SLAC/SLAH Proteine. SLAH2 wird in den Wurzeln vornehmlich in Endodermis- und Perizykelzellen exprimiert, was anhand verschiedener At SLAH2 YFP Mutanten untersucht werden konnte. Dies unterst{\"u}tzt die Annahme, dass SLAH2 bei der Beladung der Leitgef{\"a}ße mit Nitrat maßgeblich beteiligt ist. Es ist denkbar, dass SLAH2 ebenfalls eine wachstumsbeeinflussende Funktion {\"u}ber die Regulation von Nitratkonzentrationen zugeschrieben werden kann. Darauf deuten vor allem die verst{\"a}rkte Expression von SLAH2 im Bereich der Seitenwurzeln und die heterogene Expression in der Elongations-, Differenzierungs- und meristematischen Zone hin. Die Membranst{\"a}ndigkeit von SLAH4 konnte nachgewiesen werden und FRET FLIM Untersuchungen zeigten eine hohe Affinit{\"a}t von SLAH4 zu SLAH3, was die beiden Homologe als Interaktionspartner identifiziert. F{\"u}r die Bestimmung des Oligomerisierungsgrades mittels PALM wurden die pflanzlichen Anionenkan{\"a}le in tierischen COS7-Zellen exprimiert. Die elektrophysiologische Funktionalit{\"a}t der mEOS2-SLAC/SLAH-Konstrukte wurde mit Hilfe von Patch-Clamp-Versuchen in COS7-Zellen {\"u}berpr{\"u}ft. Um Expressionslevel, Membranst{\"a}ndigkeit und die Verteilung {\"u}ber die Membran der SLAC/SLAHs zu verifizieren, wurden dSTORM-Aufnahmen herangezogen Schließlich erm{\"o}glichten PALM-Aufnahmen die Bestimmung des Polymerisierungs-grades der SLAC/SLAH Anionenkan{\"a}le, die st{\"o}chiometrischen Ver{\"a}nderungen bei Heteromerisierung von SLAH3 mit SLAH1 oder SLAH4 und auch der Einfluss einer zytosolischer Ans{\"a}uerung auf den Polymerisierungsgrad von SLAH3 Homomeren. Zudem weisen die Oligomerisierungsanalysen von SLAH3 Mutanten darauf hin, dass die Aminos{\"a}uren Histidin His330 und His454 entscheidend an der pH sensitiven Regulierung von SLAH3 beteiligt sind. Durch die erhobenen Daten konnten also entscheidende, neue Erkenntnisse {\"u}ber die Regulationsmechanismen von pflanzlichen Anionenkan{\"a}len auf molekularer Ebene gewonnen werden: Unter Standardbedingungen liegen SLAC1, SLAH2 und SLAH3 haupts{\"a}chlich als Dimer vor. Auf eine zytosolische Ans{\"a}uerung reagiert ausschließlich SLAH3 mit einer signifikanten st{\"o}chiometrischen Ver{\"a}nderung und liegt im aktiven Zustand vor Allem als Monomer vor. Der Oligomerisierungsgrad von SLAC1 und SLAH2 bleibt hingegen bei einer zytosolischen Ans{\"a}uerung unver{\"a}ndert. Ferner kommt es bei der Interaktion von SLAH3 mit SLAH1 oder SLAH4 zur Formierung eines Heterodimers, welches unbeeinflusst durch den zytosolischen pH bleibt. Im Gegensatz dazu bleiben die elektrisch inaktiven Untereinheiten SLAH1 und SLAH4 monomerisch und assemblieren ganz spezifisch nur mit SLAH3. Die hochaufl{\"o}sende Fluoreszenz-mikroskopie, insbesondere PALM erlaubt es also Heteromerisierungsereignisse und {\"A}nderungen im Poylmerisierungsgrad von Membranproteinen wie den SLAC/SLAHs auf molekularer Ebene zu untersuchen und l{\"a}sst so R{\"u}ckschl{\"u}sse auf physiologische Ereignisse zu.},
  subject      = {Fluoreszenzmikroskopie},
  language  = {de}
}
@phdthesis{Zachary2021,
  author    = {Zachary, Marie},
  title     = {Functional characterization of small non-coding RNAs of \(Neisseria\) \(gonorrhoeae\)},
  doi       = {10.25972/OPUS-24582},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-245826},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {During infection, bacteria need to adapt to a changing environment and have to endure various stress conditions. Small non-coding RNAs are considered as important regulators of bacterial gene expression and so allow quick adaptations by altering expression of specific target genes. Regulation of gene expression in the human-restricted pathogen Neisseria gonorrhoeae, the causative agent of the sexually transmitted disease gonorrhoea, is only poorly understood. The present study aims a better understanding of gene regulation in N. gonorrhoeae by studying small non-coding RNAs. The discovery of antisense RNAs for all opa genes led to the hypothesis of asRNA-mediated degradation of out-of-frame opa transcripts. Analysis of asRNA expression revealed a very low abundance of the transcripts and inclusion of another phase-variable gene in the study indicates that the asRNAs are not involved in degradation of out-of-frame transcripts. This doctoral thesis focuses on the analysis of trans-acting sRNAs. The sibling sRNAs NgncR_162 and NgncR_163 were discovered as post-transcriptional regulators altering expression of genes involved in metabolic processes, amino acid uptake and transcriptional regulation. A more detailed analysis by in silico and transcriptomic approaches showed that the sRNAs regulate a broad variety of genes coding for proteins of central metabolism, amino acid biosynthesis and degradation and several transport processes. Expression levels of the sibling sRNAs depend on the growth phase of the bacteria and on the growth medium. This indicates that NgncR_162 and NgncR_163 are involved in the adaptation of the gonococcal metabolism to specific growth conditions. This work further initiates characterisation of the sRNA NgncR_237. An in silico analysis showed details on sequence conservation and a possible secondary structure. A combination of in silico target prediction and differential RNA sequencing resulted in the identification of several target genes involved in type IV pilus biogenesis and DNA recombination. However, it was not successful to find induction conditions for sRNA expression. Interestingly, a possible sibling sRNA could be identified that shares the target interaction sequence with NgncR_237 and could therefore target the same mRNAs. In conclusion, this thesis provides further insights in gene regulation by non-coding RNAs in N. gonorrhoeae by analysing two pairs of sibling sRNAs modulating bacterial metabolism or possibly type IV pilus biogenesis.},
  subject      = {Neisseria gonorrhoeae},
  language  = {en}
}
@phdthesis{Schubert2021,
  author    = {Schubert, Jonathan},
  title     = {Bildgebende Zweifarben-Einzelmolek{\"u}l-PET-Fluoreszenzspektroskopie am molekularen Chaperon Hsp90},
  doi       = {10.25972/OPUS-24493},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244938},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Im Forschungsfeld der Proteindynamik h{\"a}ufen sich in den letzten Jahren Untersuchungen an einzelnen Molek{\"u}len. Damit k{\"o}nnen molekulare Ereignisse, die in konventioneller Spektroskopie durch stochastische Prozesse unentdeckt bleiben, durch direkte Beobachtung identifiziert und analysiert werden, was zu tieferem mechanistischem Verst{\"a}ndnis des untersuchten Systems beitragen kann. Die Implikation des molekularen Chaperons Hsp90 in die korrekte Faltung und Aktivierung einer Vielzahl davon abh{\"a}ngiger Klientenproteine machen es zu einem zentralen Knotenpunkt der zellul{\"a}ren Proteinhom{\"o}ostase, allerdings ist der Mechanismus seiner breiten Klientenerkennung und -prozessierung bisher nur l{\"u}ckenhaft untersucht. Mit der Erkenntnis, dass Hsp90 ATP abh{\"a}ngig große, ratenlimitierende Umstrukturierungen erf{\"a}hrt, wurden Reportersysteme entwickelt, die auf dem F{\"o}rster-Resonanzenergietransfer mit einer r{\"a}umlichen Aufl{\"o}sung von ca. 2-10 nm basieren. Diese dokumentieren einen Klammerschluss des Chaperons und prognostizieren einen intermediatbbasierten Konformations-Zyklus. Details {\"u}ber den Mechanismus der Umstrukturierungen wurden mit der Entwicklung von Reportersystemen ermittelt, die auf dem photoinduzierten Elektronentransfer zwischen der Aminos{\"a}ure Tryptophan und einem organischen Farbstoff basieren. Die Technik beruht auf kontaktinduzierter Fluoreszenzl{\"o}schung und damit verbundenen digitalen Intensit{\"a}ts{\"u}berg{\"a}ngen, dabei erm{\"o}glicht die r{\"a}umliche Sensitivit{\"a}t von < 1 nm die Beobachtung von lokalen Umstrukturierungen. In Hsp90 wurden damit mittels konventioneller Spektroskopie drei kritische lokale Umlagerungen untersucht und daraus ein Modell mit heterogenen apo-Konformationen sowie ein kooperativer Konformationszyklus abgeleitet, der dem intermediatbasierten Modell gegen{\"u}bersteht. Im Rahmen dieser Dissertation wurde anhand des Hsp90-Chaperons eine Methode entwickelt, die eine bildgebende PET Fluoreszenzspektroskopie von mehreren Umstrukturierungen gleichzeitig an einzelnen Molek{\"u}len erlaubt. Ein umfangreiches Farbstoffscreening f{\"u}hrte zur Identifizierung eines Farbstoffpaars, das die PET-basierte simultane Aufzeichnung zweier Konformations-Koordinaten erm{\"o}glicht. {\"U}ber verschiedene Modifikationen des Chaperons konnten einzelmolek{\"u}ltaugliche Oberfl{\"a}chen hergestellt werden, auf denen zweifach markierte Hsp90-Proteine immobilisiert sind. Fluoreszenzintensit{\"a}tszeitspuren einzelner Chaperone und entsprechende Kontrollkonstrukte best{\"a}tigen qualitativ den Erfolg der Methode, f{\"u}r die quantitative Analyse wurde eine Routine in der Programmiersprache Python entwickelt, mit welcher kinetische Informationen ermittelt werden konnten. Diese legen eine enge wechselseitige Abh{\"a}ngigkeit der drei lokalen Elemente nahe, wobei der Großteil der Konformations{\"u}berg{\"a}nge zweier simultan aufgezeichneter Umstrukturierungen Synchronit{\"a}t innerhalb von zwei Sekunden zeigt. Im Vergleich zur Hydrolyse von einem ATP in mehreren Minuten deutet das auf eine enge Kopplung hin. Weiter konnte eine Beschleunigung der Dynamiken durch aromatische Modifikation des N-Terminus von Hsp90 beobachtet werden, zudem erlaubt der Einzelmolek{\"u}lansatz die Verwendung des nativen Nukleotids ATP, wodurch auch die lokalen {\"O}ffnungsdynamiken zug{\"a}nglich werden. Die zur Bestimmung der Zeitkonstanten durchgef{\"u}hrte Analyse unterst{\"u}tzt die Ansicht heterogener apo-Zust{\"a}nde und einer einheitlich geschlossenen Konformation. Die bildgebende Zweifarben-Einzelmolek{\"u}l-PET-Spektroskopie konnte insgesamt zu einem Komplement der Einzelmolek{\"u}l-FRET-Spektroskopie entwickelt werden, um damit lokale Konformationsdynamiken zu untersuchen. Der bildgebende Ansatz erlaubt eine einfache Implementierung in einen experimentellen Einzelmolek{\"u}l-FRET Aufbau bei gleichzeitiger Erweiterung der beobachteten Koordinaten und wird so zu einem breit anwendbaren Werkzeug multidimensionaler Dynamikuntersuchungen einzelner Proteine.},
  subject      = {Fluoreszenzspektroskopie},
  language  = {de}
}
@phdthesis{Rajab2021,
  author    = {Rajab, Suhaila},
  title     = {Untersuchung von Sub-Millisekunden Dynamiken und allosterischer Kommunikation in Ligandenbindedom{\"a}nen ionotroper Glutamatrezeptoren},
  doi       = {10.25972/OPUS-24494},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244946},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Ionotrope Glutamatrezeptoren (iGluRs) sind ligandengesteuerte Ionenkan{\"a}le und vermitteln den Großteil der exzitatorischen Signalweiterleitung im gesamten zentralen Nervensystem. Dar{\"u}ber hinaus spielen iGluRs eine entscheidende Rolle bei der neuronalen Entwicklung und Funktion, einschließlich Lernprozessen und Ged{\"a}chtnisbildung. Da eine Fehlfunktion dieser Rezeptoren mit zahlreichen neurodegenerativen Erkrankungen verbunden ist, stellen iGluRs zudem wichtige Zielproteine f{\"u}r die pharmakologische Wirkstoffentwicklung dar. Im Allgemeinen wird zwischen drei Untergruppen ionotroper Glutamatrezeptoren unterschieden, welche aufgrund ihrer Selektivit{\"a}t f{\"u}r einen bestimmten Liganden benannt sind: AMPA-, Kainate-, und NMDA-Rezeptoren. Die iGluRs jeder dieser Untergruppen bestehen in der Regel aus vier Untereinheiten, welche wiederum aus vier semiautonomen Dom{\"a}nen aufgebaut sind: (i) die aminoterminale Dom{\"a}ne (ATD), (ii) die Ligandenbindedom{\"a}ne (LBD), (iii) die Transmembrandom{\"a}ne (TMD) und (iv) die carboxyterminale Dom{\"a}ne (CTD). Die Ligandenbindedom{\"a}ne, welche wiederum aus zwei Lobes (D1 und D2) besteht und in ihrer Struktur einer Muschelschale {\"a}hnelt, vollzieht bei Bindung eines Neurotransmitters eine Konformations{\"a}nderung, wobei sie sich um den gebundenen Agonisten herumschließt. Diese Konformations{\"a}nderung der LBD wird auf die Transmembrandom{\"a}ne, welche den membran{\"u}berspannenden Ionenkanal ausbildet, {\"u}bertragen, was in einer Umlagerung der Transmembranhelices und infolgedessen der {\"O}ffnung des Ionenkanals resultiert. Die Konformations{\"a}nderung der LBD ist demnach die treibende Kraft, welche dem {\"O}ffnen und Schließen des Ionenkanals zugrunde liegt. Aus diesem Grund stellt die isolierte Ligandenbindedom{\"a}ne, welche als l{\"o}sliches Protein hergestellt werden kann, ein etabliertes Modellsystem zur Untersuchung der strukturellen und funktionellen Zusammenh{\"a}nge innerhalb des Funktionsmechanismus ionotroper Glutamatrezeptoren dar. Im Rahmen dieser Arbeit wurden die Konformationsdynamiken der in Escherichia coli-Bakterien exprimierten isolierten Ligandenbindedom{\"a}nen der drei homologen Untergruppen - AMPA-, Kainate- und NMDA-Rezeptoren - sowohl als Monomer als auch als Dimer untersucht. Hierbei wurden im ungebundenen Apo-Zustand der Proteine signifikante Kinetiken im Bereich von Nanosekunden bis Mikrosekunden festgestellt, welche bei Bindung eines Agonisten sowie bei Dimerisierung erheblichen Ver{\"a}nderungen zeigen. Dar{\"u}ber hinaus wurde allosterische Kommunikation zwischen den LBDs der NMDA-Untergruppe untersucht, wobei in der Tat ein deutlicher allosterischer Effekt in Bezug auf die Konformationsdynamiken der Proteine gemessen werden konnte. Weiterhin wurde ein PET-FCS-basiertes Verfahren zur Messung der Dissoziationskonstante der Bindung eines Liganden an die LBD eines AMPA-Rezeptors entwickelt. Zuletzt wurde außerdem ermittelt, ob ein Unterschied zwischen vollen und partiellen Agonisten hinsichtlich ihres Einflusses auf die Konformationsdynamiken einer AMPA-Rezeptor LBD besteht, was nachgewiesenermaßen nicht der Fall ist. Alle Messungen wurden auf Einzelmolek{\"u}lebene auf Zeitskalen von Nanosekunden bis Millisekunden basierend auf Fluoreszenzfluktuationen unter Verwendung des photoinduzierten Elektronentransfers (PET) in Kombination mit Korrelationsspektroskopie (PET-FCS) durchgef{\"u}hrt. Zu diesem Zweck wurden PET-basierte Fluoreszenzsonden entwickelt, um Konformations{\"a}nderungen auf einer r{\"a}umlichen Skala von einem Nanometer zu detektieren. Durch die Experimente innerhalb dieser Arbeit konnte gezeigt werden, dass die PET-FCS-Methode eine vielversprechende Erg{\"a}nzung zu allen bisher bestehenden Methoden zur Untersuchung der Konformationsdynamiken der Ligandenbindedom{\"a}ne ionotroper Glutamatrezeptoren darstellt und daher eine aussichtsreiche M{\"o}glichkeit zur Erweiterung des zuk{\"u}nftigen Verst{\"a}ndnisses der Funktionsweise von iGluRs bietet.},
  subject      = {Fluoreszenzkorrelationsspektroskopie},
  language  = {de}
}
@article{LetunicBork2016,
  author    = {Letunic, Ivica and Bork, Peer},
  title     = {Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees},
  series = {Nucleic Acids Research},
  volume    = {44},
  journal   = {Nucleic Acids Research},
  number    = {W1},
  doi       = {10.1093/nar/gkw290},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166181},
  pages     = {W242-W245},
  year      = {2016},
  abstract  = {Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. The current version was completely redesigned and rewritten, utilizing current web technologies for speedy and streamlined processing. Numerous new features were introduced and several new data types are now supported. Trees with up to 100,000 leaves can now be efficiently displayed. Full interactive control over precise positioning of various annotation features and an unlimited number of datasets allow the easy creation of complex tree visualizations. iTOL 3 is the first tool which supports direct visualization of the recently proposed phylogenetic placements format. Finally, iTOL's account system has been redesigned to simplify the management of trees in user-defined workspaces and projects, as it is heavily used and currently handles already more than 500,000 trees from more than 10,000 individual users.},
  language  = {en}
}
@phdthesis{Georgiev2021,
  author    = {Georgiev, Kostadin},
  title     = {Sustainable management of naturally disturbed forests},
  doi       = {10.25972/OPUS-24285},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242854},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Owing to climate change, natural forest disturbances and consecutive salvage logging are drastically increasing worldwide, consequently increasing the importance of understanding how these disturbances would affect biodiversity conservation and provision of ecosystem services. In chapter II, I used long-term water monitoring data and mid-term data on α-diversity of twelve species groups to quantify the effects of natural disturbances (windthrow and bark beetle) and salvage logging on concentrations of nitrate and dissolved organic carbon (DOC) in streamwater and α-diversity. I found that natural disturbances led to a temporal increase of nitrate concentrations in streamwater, but these concentrations remained within the health limits recommended by the World Health Organization for drinking water. Salvage logging did not exert any additional impact on nitrate and DOC concentrations, and hence did not affect streamwater quality. Thus, neither natural forest disturbances in watersheds nor associated salvage logging have a harmful effect on the quality of the streamwater used for drinking water. Natural disturbances increased the α-diversity in eight out of twelve species groups. Salvage logging additionally increased the α-diversity of five species groups related to open habitats, but decreased the biodiversity of three deadwood-dependent species groups. In chapter III, I investigated whether salvage logging following natural disturbances (wildfire and windthrow) altered the natural successional trajectories of bird communities. I compiled data on breeding bird assemblages from nine study areas in North America, Europe and Asia, over a period of 17 years and tested whether bird community dissimilarities changed over time for taxonomic, functional and phylogenetic diversity when rare, common and dominant species were weighted differently. I found that salvage logging led to significantly larger dissimilarities than expected by chance and that these dissimilarities persisted over time for rare, common and dominant species, evolutionary lineages, and for rare functional groups. Dissimilarities were highest for rare, followed by common and dominant species. In chapter IV, I investigated how β-diversity of 13 taxonomic groups would differ in intact, undisturbed forests, disturbed, unlogged forests and salvage-logged forests 11 years after a windthrow and salvage logging. The study suggests that both windthrow and salvage logging drive changes in between-treatment β-diversity, whereas windthrow alone seems to drive changes in within-treatment β-diversity. Over a decade after the windthrow at the studied site, the effect of subsequent salvage logging on within-treatment β-diversity was no longer detectable but the effect on between-treatment β-diversity persisted, with more prominent changes in saproxylic groups and rare species than in non-saproxylic groups or common and dominant species. Based on these results, I suggest that salvage logging needs to be carefully weighed against its long-lasting impact on communities of rare species. Also, setting aside patches of naturally disturbed areas is a valuable management alternative as these patches would enable post-disturbance succession of bird communities in unmanaged patches and would promote the conservation of deadwood-dependent species, without posing health risks to drinking water sources.},
  subject      = {species richness},
  language  = {en}
}