@phdthesis{Ernst2006,
  author    = {Ernst, Raffael},
  title     = {Anuran communities on the cutting edge : Analysing patterns and processes in anthropogenically altered tropical forests - Studies from the Guiana Shield and West Africa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-18373},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Summary Timber harvesting is currently the most common commercial utilisation activity in tropical forests. Assessing the effects of logging on different aspects of biodiversity and general ecosystem properties is hence of prime importance if the few remaining areas of intact tropical forest are to be protected effectively and efficiently. Tropical amphibian communities are an appropriate model system for studies on the impacts of human-induced environmental changes on the dynamics of complex biological systems. This thesis elaborates on patterns of diversity changes in tropical forest amphibian communities facing habitat alterations associated with selective logging in two globally important eco-regions (C{\^o}te d'Ivoire, Upper Guinea, West Africa and Guyana, the Guiana Shield, northern South America). The thesis is organised along two main themes. After a general introduction, a section on general methodology and an introduction to the model systems studied, the first theme moves from general patterns to underlying processes. A second theme running through both chapters carries from undisturbed systems to disturbed systems. A final section integrates findings and addresses implications for conservation management of anthropogenically altered tropical forests. Several case studies at the species- population and community level are being presented and data on the direct and indirect impacts of anthropogenic habitat alteration on respective organizational levels are provided. A key statement that is stressed on throughout the studies is the fact that common measures of diversity, such as species richness and species-diversity only inadequately reflect processes of diversity change following anthropogenic disturbance. They also fail to describe actual impacts on the dynamics of complex biological systems. It is argued that commonly used measures produce an incoherent and insufficient picture of diversity patterns and the underlying processes that shape these patterns. Thus, an understanding of higher levels of diversity, such as \&\#946;-diversity and functional diversity (and hence compositional patterns) appears to be the key to effectively mitigating the impacts of human-induced disturbance on amphibian communities. It is shown that the predictability of amphibian community composition depends on the respective level of anthropogenic disturbance imposed on a particular habitat. Hence, human activities that lead to changes in the structure of a forest, such as logging, not only alter simple system descriptors, such as the number of species in a given community, but rather alter the dynamics of the entire system. In this context, functional diversity is shown to be an important aspect underlying the actual mechanism that leads to the observed change of predictability patterns. Functional differences between species, rather than number of species per se appear to be the decisive factor in sustaining desirable ecosystem states and thus in maintaining important ecosystem services. Because biological diversity appears to play a substantial role in ecosystem resilience required to safeguard essential ecosystem functions in the face of environmental change, the thesis calls for a critical revision of common diversity assessments approaches. The studies advocate the reconsideration of the uncritical use of widespread measures and descriptors of biodiversity on grounds of inconsistent patterns found throughout numerous studies, including those presented herein.},
  subject      = {Tropischer Regenwald},
  language  = {en}
}
@article{ErbeldingDenkSchroderSchartletal.1994,
  author    = {Erbelding-Denk, Claudia and Schroder, Johannes H. and Schartl, Manfred and Nanda, Indrajit and Schmid, Michael and Epplen, J{\"o}rg T.},
  title     = {Male polymorphism in Limia perugiae (Pisces: Poeciliidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61573},
  year      = {1994},
  abstract  = {The male-polymorphic poeciliid fish, Limia perugiae, a small teleostean endemic to the southeast of the Caribbean island Hispafiola, consists of three male size morphs with uniform females. Large males differentiate at a size va:rying between 25 and 38 mm; intermediate males, between 21 and 25 mm. Under competition, !arge males exhibit an elaborate courtship display, whereas small males show only a sneak-chase behavior. Intermediate males adapt their tactics to the respective competitors. However, all malemorphs can switch from courtship display to sneak-chase behavior. In large mating groups with four males of different size and five or six virgin females, large dominant a-males as weil as small subordinate \(\delta\)-males did not produce any offspring. Unexpectedly, all progeny were sired exclusively by the intemediate subordinate ß- and \(\gamma\)-males. Breeding experiments with the three male morphs can best be explained by a model of Y -linked genes for small and !arge size which are both suspended by the activity of an autosomal recessive repressor responsible for the development of intermediate males. The dominant allele of the recessive repressor, in either its homoorits heterozygous state, activates the Y-chromosomal genes for !arge or small size, respectively. Accordingly, intermediate males may produce male offspring of all size classes, depending on the presence of either the Y-linked gene or the autosomal repressor.},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@incollection{EpplenAmmerEpplenetal.1991,
  author    = {Epplen, J. T. and Ammer, H. and Epplen, C. and Kammerbauer, C. and Mitreiter, R. and Roewer, L. and Schwaiger, W. and Steimle, V. and Zischler, H. and Albert, E. and Andreas, A. and Beyermann, B. and Meyer, W. and Buitkamp, J. and Nanda, I. and N{\"u}rnberg, P. and Pena, S. D. J. and P{\"o}che, H. and Sprecher, W. and Schartl, Manfred and Weising, K. and Yassouridis, A.},
  title     = {Oligonucleotide fingerprinting using simple repeat motifs: a convenient, ubiquitously applicable method to detect hypervariability for multiple purposes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86371},
  publisher      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1991},
  abstract  = {A panel of simple repetitive oligonucleotide probes has been designed and tested for multilocus DNA fingerprinting in some 200 fungal, plant and animal species as well as man. To date at least one of the probes has been found to be informative in each species. The human genome, however, has been the major target of many fingerprintins studies. Using the probe (CAC)5 or (GTG)5, individualization of all humans is possible except for monozygotic twins. Paternity analyses are now perfonned on a routine basis by the use of multilocus fingerprints, inctuding also cases of deficiency, i.e. where one of the parents is not available for analysis. In forensie science stain analysis is feasible in all tissue remains containing nuc)eated cells. Depending on the degree of DNA degradation a variety of oligonucleotides are informative, and they have been proven useful in actual case work. Advantages in comparison to other methods including enzymatic DNA amplification techniques (PCR) are evident. Fingerprint patterns of tumors may be changed due to the gain or loss of chromosomes and/or intrachromosomal deletion and amplification events. Locus-specific probes were isolated from the human (CAC)5/( GTG)5 fingerprint with a varying degree of informativeness (monomorphic versus truly hypervariable markers). The feasibility of three different approaches. for the isolation of hypervariable mono-locus probes was evaluated. Finally, one particular mixed simple (gt)n(ga)m repeat locus in the second intron of the HLA-DRB genes has been scrutinized to allow comparison of the extent of exon-encoded (protein-) polymorphisms versus intronie bypervariability of simple repeats: adjacent to a single gene sequence (e.g. HLA-DRB1*0401) many different length alleles were found. Group-specific structures of basic repeats were identified within the evolutionarily related DRB alleles. As a further application it is suggested here that due to the ubiquitous interspersion of their targets, short probes for simple repeat sequences are especially useful tools for ordering genomic cosmid, yeast artificial chromosome and phage banks.},
  subject      = {DNS},
  language  = {en}
}
@article{EngstlerBeneke2023,
  author    = {Engstler, Markus and Beneke, Tom},
  title     = {Gene editing and scalable functional genomic screening in Leishmania species using the CRISPR/Cas9 cytosine base editor toolbox LeishBASEedit},
  series = {eLife},
  volume    = {12},
  journal   = {eLife},
  doi       = {10.7554/eLife.85605},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350002},
  year      = {2023},
  abstract  = {CRISPR/Cas9 gene editing has revolutionised loss-of-function experiments in Leishmania, the causative agent of leishmaniasis. As Leishmania lack a functional non-homologous DNA end joining pathway however, obtaining null mutants typically requires additional donor DNA, selection of drug resistance-associated edits or time-consuming isolation of clones. Genome-wide loss-of-function screens across different conditions and across multiple Leishmania species are therefore unfeasible at present. Here, we report a CRISPR/Cas9 cytosine base editor (CBE) toolbox that overcomes these limitations. We employed CBEs in Leishmania to introduce STOP codons by converting cytosine into thymine and created http://www.leishbaseedit.net/ for CBE primer design in kinetoplastids. Through reporter assays and by targeting single- and multi-copy genes in L. mexicana, L. major, L. donovani, and L. infantum, we demonstrate how this tool can efficiently generate functional null mutants by expressing just one single-guide RNA, reaching up to 100\% editing rate in non-clonal populations. We then generated a Leishmania-optimised CBE and successfully targeted an essential gene in a plasmid library delivered loss-of-function screen in L. mexicana. Since our method does not require DNA double-strand breaks, homologous recombination, donor DNA, or isolation of clones, we believe that this enables for the first time functional genetic screens in Leishmania via delivery of plasmid libraries.},
  language  = {en}
}
@article{EnglmeiervonHoermannRiekeretal.2022,
  author    = {Englmeier, Jana and von Hoermann, Christian and Rieker, Daniel and Benbow, Marc Eric and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Lackner, Tom{\´a}š and Mitesser, Oliver and Redlich, Sarah and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Salamon, J{\"o}rg-Alfred and Sommer, David and Steffan-Dewenter, Ingolf and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg},
  title     = {Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate},
  series = {Ecology and Evolution},
  volume    = {12},
  journal   = {Ecology and Evolution},
  number    = {10},
  issn      = {2045-7758},
  doi       = {10.1002/ece3.9386},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312846},
  year      = {2022},
  abstract  = {Dung beetles are important actors in the self-regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space-for-time approach to test the effects of land use and climate on α-diversity, local community specialization (H\(_2\)′) on dung resources, and γ-diversity of dung-visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land-use types: forests, grasslands, arable sites, and settlements, embedded in near-natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung-visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ-diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung-visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ-diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung-visiting beetle diversity and alter community networks. A decrease in dung-visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage.},
  language  = {en}
}
@article{EnglmeierMitesserBenbowetal.2023,
  author    = {Englmeier, Jana and Mitesser, Oliver and Benbow, M. Eric and Hothorn, Torsten and von Hoermann, Christian and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Redlich, Sarah and Riebl, Rebekka and Rojas Botero, Sandra and Rummler, Thomas and Steffan-Dewenter, Ingolf and Stengel, Elisa and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg},
  title     = {Diverse effects of climate, land use, and insects on dung and carrion decomposition},
  series = {Ecosystems},
  volume    = {26},
  journal   = {Ecosystems},
  number    = {2},
  issn      = {1432-9840},
  doi       = {10.1007/s10021-022-00764-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325064},
  pages     = {397-411},
  year      = {2023},
  abstract  = {Land-use intensification and climate change threaten ecosystem functions. A fundamental, yet often overlooked, function is decomposition of necromass. The direct and indirect anthropogenic effects on decomposition, however, are poorly understood. We measured decomposition of two contrasting types of necromass, rat carrion and bison dung, on 179 study sites in Central Europe across an elevational climate gradient of 168-1122 m a.s.l. and within both local and regional land uses. Local land-use types included forest, grassland, arable fields, and settlements and were embedded in three regional land-use types (near-natural, agricultural, and urban). The effects of insects on decomposition were quantified by experimental exclusion, while controlling for removal by vertebrates. We used generalized additive mixed models to evaluate dung weight loss and carrion decay rate along elevation and across regional and local land-use types. We observed a unimodal relationship of dung decomposition with elevation, where greatest weight loss occurred between 600 and 700 m, but no effects of local temperature, land use, or insects. In contrast to dung, carrion decomposition was continuously faster with both increasing elevation and local temperature. Carrion reached the final decomposition stage six days earlier when insect access was allowed, and this did not depend on land-use effect. Our experiment identified different major drivers of decomposition on each necromass form. The results show that dung and carrion decomposition are rather robust to local and regional land use, but future climate change and decline of insects could alter decomposition processes and the self-regulation of ecosystems.},
  language  = {en}
}
@phdthesis{Englmeier2024,
  author    = {Englmeier, Jana},
  title     = {Consequences of climate change and land-use intensification for decomposer communities and decomposition processes},
  doi       = {10.25972/OPUS-31399},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313994},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {The increase in intensively used areas and climate change are direct and indirect consequences of anthropogenic actions, caused by a growing population and increasing greenhouse gas emissions. The number of research studies, investigating the effects of land use and climate change on ecosystems, including flora, fauna, and ecosystem services, is steadily growing. This thesis contributes to this research area by investigating land-use and climate effects on decomposer communities (arthropods and microbes) and the ecosystem service 'decomposition of dead material'. Chapter II deals with consequences of intensified land use and climate change for the ecosystem service 'decomposition of dead organic material' (necromass). Considering the severe decline in insects, we experimentally excluded insects from half of the study objects. The decomposition of both dung and carrion was robust to land-use changes. Dung decomposition, moreover, was unaffected by temperature and the presence/ absence of insects. Along the altitudinal gradient, however, highest dung decomposition was observed at medium elevation between 600 and 700 m above sea level (although insignificant). As a consequence, we assume that at this elevation there is an ideal precipitation:temperature ratio for decomposing organisms, such as earthworms or collembolans. Carrion decomposition was accelerated by increasing elevation and by the presence of insects, indicating that increasing variability in climate and an ongoing decline in insects could modify decomposition processes and consequently natural nutrient cycles. Moreover, we show that different types of dead organic material respond differently to environmental factors and should be treated separately in future studies. In Chapter III, we investigated land-use and climate effects on dung-visiting beetles and their resource specialization. Here, all beetles that are preferentially found on dung, carrion or other rotten material were included. Both α- and γ-diversity were strongly reduced in agricultural and urban areas. High precipitation reduced dung-visiting beetle abundance, whereas γ-diversity was lowest in the warmest regions. Resource specialization decreased with increasing temperatures. The results give evidence that land use as well as climate can alter dung-visiting beetle diversity and resource specialization and may hence influence the natural balance of beetle communities and their contribution to the ecosystem service 'decomposition of dead material'. The following chapter, Chapter IV, contributes to the findings in Chapter II. Here, carrion decomposition is not only explained by land-use intensity and climate but also by diversity and community composition of two taxonomic groups found on carrion, beetles and bacteria. The results revealed a strong correlation between bacteria diversity and community composition with temperature. Carrion decomposition was to a great extent directed by bacterial community composition and precipitation. The role of beetles was neglectable in carrion decomposition. With this study, I show that microbes, despite their microscopic size, direct carrion decomposition and may not be neglected in future decomposition studies. In Chapter V a third necromass type is investigated, namely deadwood. The aim was to assess climate and land-use effects on deadwood-inhabiting fungi and bacteria. Main driver for microbial richness (measured as number of OTUs) was climate, including temperature and precipitation. Warmer climates promoted the diversity of bacteria, whereas fungi richness was unaffected by temperature. In turn, fungi richness was lower in urban landscapes compared to near-natural landscapes and bacteria richness was higher on meadows than on forest sites. Fungi were extremely specialized on their host tree, independent of land use and climate. Bacteria specialization, however, was strongly directed by land use and climate. These results underpin previous studies showing that fungi are highly specialized in contrast to bacteria and add new insights into the robustness of fungi specialization to climate and land use. I summarize that climate as well as intensive land use influence biodiversity. Temperature and precipitation, however, had positive and negative effects on decomposer diversity, while anthropogenic land use had mostly negative effects on the diversity of decomposers.},
  subject      = {Mikroorganismus},
  language  = {en}
}
@phdthesis{Englberger2012,
  author    = {Englberger, Eva},
  title     = {Gene regulation in hearts of Hey-mutant mouse embryos and monitoring of sub-cellular Hey1 distribution},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73395},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Hey-mutant mouse hearts at embryonic day E14.5 were shown to react to the knock out of Hey2 with several up-regualted genes. This up-regulation is due to the lack of Hey2 and cannot be explained by the structural changes in heart morphology as shown using control animals. Part of the gene regulation was further validated using in situ hybridization. Hey1 was located to the nucleus in immunofluorescence experiments. However, experiments on protein level showed also amount of Hey1 within the cytoplasm. The nuclear localization of Hey1 was unchanged during all cell cycle phases as well as when CaMKII was co-expressed or other cellular pathways were inhibited or stimulated. Hey1 does not seem to interact with the nuclear transport proteins importin-alpha and -beta, therefore it still needs to be elucidated how Hey1 is transported into the nucleus.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{Engelmann2008,
  author    = {Engelmann, Julia Cath{\´e}rine},
  title     = {DNA microarrays: applications and novel approaches for analysis and interpretation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-29747},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {In der vorliegenden Dissertation wird die Entwicklung eines phylogenetischen DNA Microarrays, die Analyse von mehreren Microarray-Genexpressionsdatens{\"a}tzen und neue Ans{\"a}tze f{\"u}r die Datenanalyse und Interpretation der Ergebnisse vorgestellt. Die Entwicklung und Analyse der Daten eines phylogenetischen DNA Microarrays wird in der ersten Publikation dargestellt. Ich konnte zeigen, dass die Spezies-Detektion mit phylogenetischen Microarrays durch die Datenanalyse mit einem linearen Regressionsansatz signifikant verbessert werden kann. Standard-Methoden haben bislang nur Signalintensit{\"a}ten betrachtet und eine Spezies als an- oder abwesend bezeichnet, wenn die Signalintensit{\"a}t ihres Messpunktes oberhalb eines willk{\"u}rlich gesetzten Schwellenwertes lag. Dieses Verfahren ist allerdings aufgrund von Kreuz-Hybridisierungen nicht auf sehr nah verwandte Spezies mit hoher Sequenzidentit{\"a}t anwendbar. Durch die Modellierung des Hybridisierungs und Kreuz-Hybridisierungsverhaltens mit einem linearen Regressionsmodell konnte ich zeigen, dass Spezies mit einer Sequenz{\"a}hnlichkeit von 97\% im Markergen immer noch unterschieden werden k{\"o}nnen. Ein weiterer Vorteil der Modellierung ist, dass auch Mischungen verschiedener Spezies zuverl{\"a}ssig vorhergesagt werden k{\"o}nnen. Theoretisch sind auch quantitative Vorhersagen mit diesem Modell m{\"o}glich. Um die großen Datenmengen, die in {\"o}ffentlichen Microarray-Datenbanken abgelegt sind besser nutzen zu k{\"o}nnen, bieten sich Meta-Analysen an. In der zweiten Publikation wird eine explorative Meta-Analyse auf Arabidopsis thaliana-Datens{\"a}tzen vorgestellt. Mit der Analyse verschiedener Datens{\"a}tze, die den Einfluss von Pflanzenhormonen, Pathogenen oder verschiedenen Mutationen auf die Genexpression untersucht haben, konnten die Datens{\"a}tze anhand ihrer Genexpressionsprofile in drei große Gruppen eingeordnet werden: Experimente mit Indol-3-Essigs{\"a}ure (IAA), mit Pathogenen und andere Experimente. Gene, die charakteristisch f{\"u}r die Gruppe der IAA-Datens{\"a}tze beziehungsweise f{\"u}r die Gruppe der Pathogen-Datens{\"a}tze sind, wurden n{\"a}her betrachtet. Diese Gene hatten Funktionen, die bereits mit Pathogenbefall bzw. dem Einfluss von IAA in Verbindung gebracht wurden. Außerdem wurden Hypothesen {\"u}ber die Funktionen von bislang nicht annotierten Genen aufgestellt. In dieser Arbeit werden auch Prim{\"a}ranalysen von einzelnen Arabidopsis thaliana Genexpressions-Datens{\"a}tzen vorgestellt. In der dritten Publikation wird ein Experiment beschrieben, das durchgef{\"u}hrt wurde um herauszufinden ob Mikrowellen-Strahlung einen Einfluss auf die Genexpression einer Zellkultur hat. Dazu wurden explorative Analysemethoden angewendet. Es wurden geringe aber signifikante Ver{\"a}nderungen in einer sehr kleinen Anzahl von Genen beobachtet, die experimentell best{\"a}tigt werden konnten. Die Funktionen der regulierten Gene und eine Meta-Analyse mit {\"o}ffentlich zug{\"a}nglichen Datens{\"a}tzen einer Datenbank deuten darauf hin, dass die pflanzliche Zellkultur die Strahlung als eine Art Energiequelle {\"a}hnlich dem Licht wahrnimmt. Des weiteren wird in der vierten Publikation die funktionelle Analyse eines Arabidopsis thaliana Genexpressionsdatensatzes beschrieben. Die Analyse der Genexpressions eines pflanzlichen Tumores zeigte, dass er seinen Stoffwechsel von aerob und auxotroph auf anaerob und heterotroph umstellt. Gene der Photosynthese werden im Tumorgewebe reprimiert, Gene des Aminos{\"a}ure- und Fettstoffwechsels, der Zellwand und Transportkan{\"a}le werden so reguliert, dass Wachstum und Entwicklung des Tumors gef{\"o}rdert werden. In der f{\"u}nften Publikation in dieser Arbeit wird GEPAT (Genome Expression Pathway Analysis Tool) beschrieben. Es besteht aus einer Internet- Anwendung und einer Datenbank, die das einfache Hochladen von Datens{\"a}tzen in die Datenbank und viele M{\"o}glichkeiten der Datenanalyse und die Integration anderer Datentypen erlaubt. In den folgenden zwei Publikationen (Publikation 6 und Publikation 7) wird GEPAT auf humane Microarray-Datens{\"a}tze angewendet um Genexpressionsdaten mit weiteren Datentypen zu verkn{\"u}pfen. Genexpressionsdaten und Daten aus vergleichender Genom-Hybridisierung (CGH) von prim{\"a}ren Tumoren von 71 Mantel-Zell-Lymphom (MCL) Patienten erm{\"o}glichte die Ermittlung eines Pr{\"a}diktors, der die Vorhersage der {\"U}berlebensdauer von Patienten gegen{\"u}ber herk{\"o}mmlichen Methoden verbessert. Die Analyse der CGH Daten zeigte, dass auch diese f{\"u}r die Vorhersage der {\"U}berlebensdauer geeignet sind. F{\"u}r den Datensatz von Patienten mit großzellig diffusem B-Zell-Lymphom DLBCL konnte aus den Genexpressionsdaten ebenfalls ein neuer Pr{\"a}diktor vorgeschlagen werden. Mit den zwischen lang und kurz {\"u}berlebenden Patienten differentiell exprimierten Genen der MCL Patienten und mit den Genen, die zwischen den beiden Untergruppen von DLBCL reguliert sind, wurden Interaktionsnetzwerke gebildet. Diese zeigen, dass bei beiden Krebstypen Gene des Zellzyklus und der Proliferation zwischen Patienten mit kurzer und langer {\"U}berlebensdauer unterschiedlich reguliert sind.},
  subject      = {Microarray},
  language  = {en}
}
@phdthesis{EngelhardtgebChristiansen2013,
  author    = {Engelhardt [geb. Christiansen], Frauke},
  title     = {Synaptic Connectivity in the Mushroom Body Calyx of Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-85058},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Learning and memory is considered to require synaptic plasticity at presynaptic specializations of neurons. Kenyon cells are the intrinsic neurons of the primary olfactory learning center in the brain of arthropods - the mushroom body neuropils. An olfactory mushroom body memory trace is supposed to be located at the presynapses of Kenyon cells. In the calyx, a sub-compartment of the mushroom bodies, Kenyon cell dendrites receive olfactory input provided via projection neurons. Their output synapses, however, were thought to reside exclusively along their axonal projections outside the calyx, in the mushroom body lobes. By means of high-resolution imaging and with novel transgenic tools, we showed that the calyx of the fruit fly Drosophila melanogaster also comprised Kenyon cell presynapses. At these presynapses, synaptic vesicles were present, which were capable of neurotransmitter release upon stimulation. In addition, the newly identified Kenyon cell presynapses shared similarities with most other presynapses: their active zones, the sites of vesicle fusion, contained the proteins Bruchpilot and Syd-1. These proteins are part of the cytomatrix at the active zone, a scaffold controlling synaptic vesicle endo- and exocytosis. Kenyon cell presynapses were present in γ- and α/β-type KCs but not in α/β-type Kenyon cells. The newly identified Kenyon cell derived presynapses in the calyx are candidate sites for an olfactory associative memory trace. We hypothesize that, as in mammals, recurrent neuronal activity might operate for memory retrieval in the fly olfactory system. Moreover, we present evidence for structural synaptic plasticity in the mushroom body calyx. This is the first demonstration of synaptic plasticity in the central nervous system of Drosophila melanogaster. The volume of the mushroom body calyx can change according to changes in the environment. Also size and numbers of microglomeruli - sub-structures of the calyx, at which projection neurons contact Kenyon cells - can change. We investigated the synapses within the microglomeruli in detail by using new transgenic tools for visualizing presynaptic active zones and postsynaptic densities. Here, we could show, by disruption of the projection neuron - Kenyon cell circuit, that synapses of microglomeruli were subject to activity-dependent synaptic plasticity. Projection neurons that could not generate action potentials compensated their functional limitation by increasing the number of active zones per microglomerulus. Moreover, they built more and enlarged microglomeruli. Our data provide clear evidence for an activity-induced, structural synaptic plasticity as well as for the activity-induced reorganization of the olfactory circuitry in the mushroom body calyx.},
  subject      = {Taufliege},
  language  = {en}
}
@article{EndresKneitzOrthetal.2016,
  author    = {Endres, Marcel and Kneitz, Susanne and Orth, Martin F. and Perera, Ruwan K. and Zernecke, Alma and Butt, Elke},
  title     = {Regulation of matrix metalloproteinases (MMPs) expression and secretion in MDA-MB-231 breast cancer cells by LIM and SH3 protein 1 (LASP1)},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {39},
  doi       = {10.18632/oncotarget.11720},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176920},
  pages     = {64244-64259},
  year      = {2016},
  abstract  = {The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane thereby enabling metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cell lines. By analyzing microarray data of in-house generated control and LASP1-depleted MDA-MB-231 breast cancer cells, we observed downregulation of MMP1, -3 and -9 upon LASP1 depletion. This was confirmed by Western blot analysis. Conversely, rescue experiments restored in part MMP expression and secretion. The regulatory effect of LASP1 on MMP expression was also observed in BT-20 breast cancer cells as well as in prostate and bladder cancer cell lines. In line with bioinformatic FunRich analysis of our data, which mapped a high regulation of transcription factors by LASP1, public microarray data analysis detected a correlation between high LASP1 expression and enhanced c-Fos levels, a protein that is part of the transcription factor AP-1 and known to regulate MMP expression. Compatibly, in luciferase reporter assays, AP-1 showed a decreased transcriptional activity after LASP1 knockdown. Zymography assays and Western blot analysis revealed an additional promotion of MMP secretion into the extracellular matrix by LASP1, thus, most likely, altering the microenvironment during cancer progression. The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential of LASP1 overexpressing aggressive tumor cells in earlier studies.},
  language  = {en}
}
@article{EndresJungblutDivyapicigiletal.2022,
  author    = {Endres, Leo M. and Jungblut, Marvin and Divyapicigil, Mustafa and Sauer, Markus and Stigloher, Christian and Christodoulides, Myron and Kim, Brandon J. and Schubert-Unkmeir, Alexandra},
  title     = {Development of a multicellular in vitro model of the meningeal blood-CSF barrier to study Neisseria meningitidis infection},
  series = {Fluids and Barriers of the CNS},
  volume    = {19},
  journal   = {Fluids and Barriers of the CNS},
  number    = {1},
  doi       = {10.1186/s12987-022-00379-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300208},
  year      = {2022},
  abstract  = {Background Bacterial meningitis is a life-threatening disease that occurs when pathogens such as Neisseria meningitidis cross the meningeal blood cerebrospinal fluid barrier (mBCSFB) and infect the meninges. Due to the human-specific nature of N. meningitidis, previous research investigating this complex host-pathogen interaction has mostly been done in vitro using immortalized brain endothelial cells (BECs) alone, which often do not retain relevant barrier properties in culture. Here, we developed physiologically relevant mBCSFB models using BECs in co-culture with leptomeningeal cells (LMCs) to examine N. meningitidis interaction. Methods We used BEC-like cells derived from induced pluripotent stem cells (iBECs) or hCMEC/D3 cells in co-culture with LMCs derived from tumor biopsies. We employed TEM and structured illumination microscopy to characterize the models as well as bacterial interaction. We measured TEER and sodium fluorescein (NaF) permeability to determine barrier tightness and integrity. We then analyzed bacterial adherence and penetration of the cell barrier and examined changes in host gene expression of tight junctions as well as chemokines and cytokines in response to infection. Results Both cell types remained distinct in co-culture and iBECs showed characteristic expression of BEC markers including tight junction proteins and endothelial markers. iBEC barrier function as determined by TEER and NaF permeability was improved by LMC co-culture and remained stable for seven days. BEC response to N. meningitidis infection was not affected by LMC co-culture. We detected considerable amounts of BEC-adherent meningococci and a relatively small number of intracellular bacteria. Interestingly, we discovered bacteria traversing the BEC-LMC barrier within the first 24 h post-infection, when barrier integrity was still high, suggesting a transcellular route for N. meningitidis into the CNS. Finally, we observed deterioration of barrier properties including loss of TEER and reduced expression of cell-junction components at late time points of infection. Conclusions Here, we report, for the first time, on co-culture of human iPSC derived BECs or hCMEC/D3 with meningioma derived LMCs and find that LMC co-culture improves barrier properties of iBECs. These novel models allow for a better understanding of N. meningitidis interaction at the mBCSFB in a physiologically relevant setting.},
  language  = {en}
}
@phdthesis{Endler2006,
  author    = {Endler, Annett},
  title     = {Regulation of reproductive division of labor in the ant Camponotus floridanus : behavioral mechanisms and pheromonal effects},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-18872},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {A hitherto unresolved problem is how workers are prevented from reproducing in large insect societies. The queen informs about her fertility and health which ensures sufficient indirect fitness benefits for workers. In the ant Camponotus floridanus, I found such a signal located on eggs of highly fertile queens. Groups of workers were regularly provided with different sets of brood. Only in groups with queen eggs workers refrain from reproducing. Thus, the eggs seem to inform the workers about queen presence. The signal on queen eggs is presumably the same that enables workers to distinguish between queen and worker-laid eggs, latter are destroyed by workers. Queen and worker-laid eggs differ in their surface hydrocarbons in a similar way as fertile queens differ from workers in the composition of their cuticular hydrocarbons. When I transferred hydrocarbons from the queen cuticle to worker eggs the eggs were no longer destroyed, indicating that they now carry the signal. These hydrocarbons thus represent a queen signal that regulates worker reproduction in this species. But the signal is not present in all fertile queens. Founding queens with low egg-laying rates differ in the composition of cuticular hydrocarbons from queens with high productivity. Similar differences in the composition of surface hydrocarbons were present on their eggs. The queen signal develops along with an increasing fertility and age of the queen, and this is perceived by the workers. Eggs from founding queens were destroyed like worker eggs. This result shows that founding queens lack the appropriate signal. In these little colony foundations chemical communication of queen status may not be necessary to prevent workers from reproducing, since workers may benefit more from investing in colony growth and increased productivity of large colonies rather than from producing male eggs in incipient colonies. If the queen is missing or the productivity of the queen decreases, workers start laying eggs. There is some evidence from correlative studies that, under queenless conditions, worker police each other because of differences in individual odors as a sign of social status. It can be expressed as either aggressive inhibition of ovarian activity, workers with developed ovaries are attacked by nest-mates, or destruction by worker-laid eggs. I found that in C. floridanus workers, in contrast to known studies, police only by egg eating since they are able to discriminate queen- and worker-laid eggs. Workers with developed ovaries will never attacked by nest-mates. This is further supported by qualitative and quantitative differences in the cuticular hydrocarbon profile of queens and workers, whereas profiles of workers with and without developed ovaries show a high similarity. I conclude that workers discriminate worker eggs on the basis of their hydrocarbon profile, but they are not able to recognize egg-laying nest-mates. Improving our knowledge of the proximate mechanisms of the reproductive division of labor in evolutionary derived species like C. floridanus will help to understand the evolution of extreme reproductive altruism involving sterility as a characteristic feature of advanced eusocial systems.},
  subject      = {Camponotus floridanus},
  language  = {en}
}
@article{EndesfelderMalkuschFlottmannetal.2011,
  author    = {Endesfelder, Ulrike and Malkusch, Sebastian and Flottmann, Benjamin and Mondry, Justine and Liguzinski, Piotr and Verveer, Peter J. and Heilemann, Mike},
  title     = {Chemically Induced Photoswitching of Fluorescent Probes - A General Concept for Super-Resolution Microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-74896},
  year      = {2011},
  abstract  = {We review fluorescent probes that can be photoswitched or photoactivated and are suited for single-molecule localization based super-resolution microscopy. We exploit the underlying photochemical mechanisms that allow photoswitching of many synthetic organic fluorophores in the presence of reducing agents, and study the impact of these on the photoswitching properties of various photoactivatable or photoconvertible fluorescent proteins. We have identified mEos2 as a fluorescent protein that exhibits reversible photoswitching under various imaging buffer conditions and present strategies to characterize reversible photoswitching. Finally, we discuss opportunities to combine fluorescent proteins with organic fluorophores for dual-color photoswitching microscopy.},
  subject      = {Super-Resolution Microscopy},
  language  = {en}
}
@article{EndesfelderMalkuschFlottmannetal.2011,
  author    = {Endesfelder, Ulrike and Malkusch, Sebastian and Flottmann, Benjamin and Mondry, Justine and Liguzinski, Piotr and Verveer, Peter J. and Heilemann, Mike},
  title     = {Chemically Induced Photoswitching of Fluorescent Probes - A General Concept for Super-Resolution Microscopy},
  series = {Molecules},
  volume    = {16},
  journal   = {Molecules},
  number    = {4},
  doi       = {10.3390/molecules16043106},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134080},
  pages     = {3106-3118},
  year      = {2011},
  abstract  = {We review fluorescent probes that can be photoswitched or photoactivated and are suited for single-molecule localization based super-resolution microscopy. We exploit the underlying photochemical mechanisms that allow photoswitching of many synthetic organic fluorophores in the presence of reducing agents, and study the impact of these on the photoswitching properties of various photoactivatable or photoconvertible fluorescent proteins. We have identified mEos2 as a fluorescent protein that exhibits reversible photoswitching under various imaging buffer conditions and present strategies to characterize reversible photoswitching. Finally, we discuss opportunities to combine fluorescent proteins with organic fluorophores for dual-color photoswitching microscopy.},
  language  = {en}
}
@phdthesis{Eltz2001,
  author    = {Eltz, Thomas},
  title     = {Ecology of stingless bees (Apidae, Meliponini) in lowland dipterocarp forests in Sabah, Malaysia, and an evaluation of logging impact on populations and communities},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-1130},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {The present thesis reports on four years of field research on stingless bee ecology in Sabah, Malaysia. Hereby, it was the main focus to evaluate the effect of selective logging for timber extraction on communities of bees, and to elucidate causative relationships involved in regulating bee populations. Included were background studies on resource use (3.1, 3.2, 3.3) and nesting biology (3.4) as well as comparative studies on stingless bee diversity and abundance in logged and unlogged lowland rainforest sites (4.1, 4.2). Stingless bees proved to be generalist foragers that used a large range of plant species as pollen sources. Nevertheless, different species of bees had rather distinct pollen diets, a findind that was independent of fluctuations in flowering activity in the habitat. At one particular point in time colonies of one species (Trigona collina)collected mold spores (Rhizopus sp.) as a pollen surrogate. In order to obtain low-effort estimates of meliponine pollen sources a new method was developed: Trapping of bee garbage (with funnel traps) and the quantitative analysis of pollen in garbage samples. Pollen in bee garbage reflected pollen import with a certain time lag and could therefore be used for an assessment of long-term pollen foraging (see below). The majority of stingless bee nests (275 nests of 12 species) were found in cavities in trunks or under the bases of large, living canopy trees. Nest trees mostly belonged to commercial species and were of the correct size and (partly) timber quality to warrant harvesting. It was estimated that roughly one third of stingless bee nests in an given forest area would be killed during a selective logging operation. Besides causing direct mortality, logging may also indirectly affect bee populations by reducing the availability of potential nest sites (trees). However, in a comparison of primary and differentially logged forest sites (10 to 30 years after logging) no effect of the degree of disturbance on meliponine nest density was found. Instead, the variation in nest density (0 to 16.2 nest/ha) was best explained by differences in the available floral resources (assessed by analysis of pollen in bee garbage). Bee populations in forest edge situations were favored: there was a positive correlation between nest density and the proportion of external non-forest pollen (e.g. from crop plants, road edge vegetation, mangroves) in the bees' diet. The highest nest density was found in a site bordering the mangroves in Sandakan Bay. Here, the mangrove tree Rhizophora apiculata represented a extraordinary large fraction of the pollen volume. Presumably, external pollen sources effectively supplement bee diets at times when little flowering occurs inside the forest, thus increasing overall bee carrying-capacity. The idea of differential pollen limitation was strengthened by direct measurements of pollen import and foraging activity over a period of five months. Both were elevated in colonies in a site with high bee density. It is concluded that the abundance of stingless bees in forests in Sabah is chiefly dependent on the local availability of food resources. Hereby, bee populations strongly benefit from edge effects and increased habitat diversity. Although direct negative effects of selective logging are strongly indicated by a close association of bee nests with commercial trees, no clear effects were detected in regenerating forests ten to 30 years after logging.},
  subject      = {Sabah},
  language  = {en}
}
@article{ElkonLoayzaPuchKorkmazetal.2015,
  author    = {Elkon, Ran and Loayza-Puch, Fabricio and Korkmaz, Gozde and Lopes, Rui and van Breugel, Pieter C and Bleijerveld, Onno B and Altelaar, AF Maarten and Wolf, Elmar and Lorenzin, Francesca and Eilers, Martin and Agami, Reuven},
  title     = {Myc coordinates transcription and translation to enhance transformation and suppress invasiveness},
  series = {EMBO reports},
  volume    = {16},
  journal   = {EMBO reports},
  number    = {12},
  doi       = {10.15252/embr.201540717},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150373},
  pages     = {1723-1736},
  year      = {2015},
  abstract  = {c-Myc is one of the major human proto-oncogenes and is often associated with tumor aggression and poor clinical outcome. Paradoxically, Myc was also reported as a suppressor of cell motility, invasiveness, and metastasis. Among the direct targets of Myc are many components of the protein synthesis machinery whose induction results in an overall increase in protein synthesis that empowers tumor cell growth. At present, it is largely unknown whether beyond the global enhancement of protein synthesis, Myc activation results in translation modulation of specific genes. Here, we measured Myc-induced global changes in gene expression at the transcription, translation, and protein levels and uncovered extensive transcript-specific regulation of protein translation. Particularly, we detected a broad coordination between regulation of transcription and translation upon modulation of Myc activity and showed the connection of these responses to mTOR signaling to enhance oncogenic transformation and to the TGFβ pathway to modulate cell migration and invasiveness. Our results elucidate novel facets of Myc-induced cellular responses and provide a more comprehensive view of the consequences of its activation in cancer cells.},
  language  = {en}
}
@phdthesis{ElMasri2005,
  author    = {El-Masri, Harun},
  title     = {A genetic analysis of somitogenesis in the Medaka (Oryzias latipes)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-14515},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {Somites are repeated epithelial segments that are generated in a rhythmic manner from the presomitic mesoderm (PSM) in the embryonic tailbud. Later, they differentiate into skeletal muscle, cartilage and dermis. Somitogenesis is regulated by a complex interplay of different pathways. Notch/Delta signaling is one of the pathways well characterized in zebrafish through mutants affected in its different components. Previous work in mouse, chicken and zebrafish has shown that also additional components are required during somitogenesis, most importantly through an FGF and Retinoic acid (RA) gradient, as well as Wnt signaling. However, no zebrafish mutants with defects in these pathways showing specific somite malformations are described. This was explained by functional redundancies among related genes that have resulted from a whole genome duplication which occurred in a teleost fish ancestor 350 million years ago. As distinct duplicates exist in different teleost species, a large scale mutagenesis screen in the medaka (Oryzias latipes) has been performed successfully in Kyoto, Japan. I analyzed nine of the isolated medaka mutants that show variable aspects of somitic phenotypes. This includes a complete or partial loss of somite boundaries (e.g. bms and sne), somites with irregular sizes and shapes (e.g. krz and fsl) or partially fused and enlarged somites (e.g. dpk). Although some of these medaka mutants share characteristics with previously described zebrafish somite mutants, most of the mutants represent unique phenotypes, not obtained in the zebrafish screens. In-situ hybridization analyses with marker genes implicated in the segmentation clock (e.g. her7), establishment of anterior-posterior (A-P) polarity (e.g. mesp) and differentiation of somites (e.g. myf5, lfng) revealed that the medaka mutants can be separated into two classes. Class I shows defects in tailbud formation and PSM prepatterning, and lateron somite boundary formation was impaired in these mutants. A unique member of this class with a novel phenotype is the doppelkorn (dpk) mutant that has single fused or enlarged somites. This phenotype has not been reported till now in zebrafish somite mutants. In-situ analyses on dpk showed that stabilization of the cyclically expressed somitogenesis clock genes must be affected in this mutant. This is accompanied by a disrupted regulation of A-P polarity genes like mesp. This suggests that dpk is a mutant deficient in the wave front, which is necessary for the down-regulation of oscillating genes in the anterior PSM. Furthermore, as the initiation of oscillation of all three cyclic her genes was unaffected in dpk embryos, I could exclude that this mutant in affected in the Notch/Delta pathway. Another mutant that belongs to this class is the samidare (sam) mutant. Morphologically, sam mutants are similar to zebrafish after eight (aei). In both cases, the first 7-9 somites are formed properly, but after this somite formation ceases. Different to the situation in aei, sam mutant embryos presented an additional defect in the mid-hindbrain boundary (MHB) region. Similar MHB defects were described in the zebrafish fgf8 mutant acerebellar (ace). In ace zebrafish mutant, somites were only slightly defective, although FGF signaling has been shown to be important for somite formation in chicken, mouse and zebrafish. This was explained by functional redundancy between fgf8 and fgf24 ligands in the tailbud of zebrafish. Thus, it is interesting to suggest that the sam mutant, based on the parallel defects in somites and MHB, is a potential member of the FGF signaling pathway muatnts. It was shown that FGF plays a crucial role during MHB formation in medaka. In addition, I showed that fgf8 acts non-redundantly during tailbud formation and somitogenesis in medaka. Furthermore, I showed that FGF signaling regulates somite size also in medaka and that fgfr1 is the only FGF receptor expressed in the tailbud and somites. In class II medaka somite mutants, PSM prepatterning appears normal, whereas A-P polarity, boundary formation, epithelialization or the later differentiation of somites appears to be affected. Such mutants have not been isolated so far in zebrafish, mice or chicken. Therefore, medaka class II somite mutants seem to be a novel group of mutants that opens new perspectives to analyze A-P polarity regulation, determination and boundary formation in the presence of a normally functioning clock in the PSM. Identifying the encoding genes for all analyzed medaka somite mutants will contribute to the understanding of the molecular interactions of different signaling pathways involved during somitogenesis, and is expected to result in the identification of new components.},
  subject      = {Japank{\"a}rpfling},
  language  = {en}
}
@article{ElKeredySchleyerKoenigetal.2012,
  author    = {El-Keredy, Amira and Schleyer, Michael and K{\"o}nig, Christian and Ekim, Aslihan and Gerber, Bertram},
  title     = {Behavioural Analyses of Quinine Processing in Choice, Feeding and Learning of Larval Drosophila},
  series = {PLoS One},
  volume    = {7},
  journal   = {PLoS One},
  number    = {7},
  doi       = {10.1371/journal.pone.0040525},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130811},
  pages     = {e40525},
  year      = {2012},
  abstract  = {Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.},
  language  = {en}
}
@article{ElHajjDittrichBoecketal.2016,
  author    = {El Hajj, Nady and Dittrich, Marcus and B{\"o}ck, Julia and Kraus, Theo F. J. and Nanda, Indrajit and M{\"u}ller, Tobias and Seidmann, Larissa and Tralau, Tim and Galetzka, Danuta and Schneider, Eberhard and Haaf, Thomas},
  title     = {Epigenetic dysregulation in the developing Down syndrome cortex},
  series = {Epigenetics},
  volume    = {11},
  journal   = {Epigenetics},
  number    = {8},
  doi       = {10.1080/15592294.2016.1192736},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-191239},
  pages     = {563-578},
  year      = {2016},
  abstract  = {Using Illumina 450K arrays, 1.85\% of all analyzed CpG sites were significantly hypermethylated and 0.31\% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions.},
  language  = {en}
}
@phdthesis{ElHajj2011,
  author    = {El Hajj, Nady},
  title     = {Epimutations in Germ-Cell and Embryo Development: Possible Consequences for Assisted Reproduction},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-65995},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Assisted reproductive technologies (ART) emerged in the late 1970's as a therapy for human infertility. Up till now more than 3 million babies have been conceived through ART, demonstrating the safety and efficiency of the technique. Published reports showed an increase in the rate of imprinting disorders (Beckwith Wiedemann Syndrome, Angelman Syndrome, etc.) in babies born after ART. What are the effects imposed through ART and should researchers reassess its safety and implications on the future offspring? Throughout this thesis, I analyzed the methylation patterns of germ cells and embryos to determine whether in vitro maturation and in vitro fertilization have a negative impact on the epigenetic patterns. Furthermore, DNA methylation was compared between sperm of infertile and presumably fertile controls in order to understand whether epigenetic disturbances lead to infertility at the first place. The occurrence of methylation aberrations in germ cells of infertile patients could be transmitted to new-borns and then cause epigenetic disorders. In order to elucidate the imprinting status within single cells, I developed a new technique based on limiting dilution where bisulfite treated DNA is distributed across several wells before amplification. This allowed methylation measurement at the single allele level as well parent of origin detection. In a total of 141 sperm samples from couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) including 106 with male factor or combined infertility and 28 with female infertility, I detected a significant correlation between lower quality of semen parameters (sperm count, percentage of abnormal sperm, and percentage of motile sperm) and the rate of imprinting errors. ALU repeats displayed a higher methylation in sperm DNA of patients leading to a pregnancy and live birth, compared to patients in which pregnancy was not achieved or a spontaneous abortion occurred. A discriminant analysis based on ALU methylation allowed correct classification of >70\% of cases. Preliminary data from illumina methylation arrays where more than 27,000 CpGs were analyzed determined that only a single CpG site from the open reading frame C14orf93 was significantly different between the infertile and presumably fertile control group. However, further improvements on data normalization might permit detection of other differentially methylated regions. Comparison of embryos after natural conception, in vitro fertilized embryos from superovulated oocytes, and embryos achieved through fertilization of in vitro cultured oocytes revealed no dramatic effect on the imprinting patterns of Igf2r, H19, and Snrpn. Oocyte cryotop vitrification did not result in a dramatic increase of imprinting mutations in oocytes even though the rate of sporadic methylation errors in single Snrpn CpGs were higher within the in-vitrified group. Collectively, the results I will present within this thesis suggest an increase in the rate of imprinting errors within the germ cells of infertile patients, in addition to a decrease in genome wide methylation of ALU repetitive elements. I did not observe a detrimental effect on the methylation patterns of oocytes and the resulting embryos using in vitro maturation of oocytes and/or standard IVF with in vivo grown superovulated oocytes.},
  subject      = {Reproduktionsmedizin},
  language  = {en}
}
@article{EisenreichRudelHeesemannetal.2021,
  author    = {Eisenreich, Wolfgang and Rudel, Thomas and Heesemann, J{\"u}rgen and Goebel, Werner},
  title     = {Persistence of Intracellular Bacterial Pathogens—With a Focus on the Metabolic Perspective},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {10},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2020.615450},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222348},
  year      = {2021},
  abstract  = {Persistence has evolved as a potent survival strategy to overcome adverse environmental conditions. This capability is common to almost all bacteria, including all human bacterial pathogens and likely connected to chronic infections caused by some of these pathogens. Although the majority of a bacterial cell population will be killed by the particular stressors, like antibiotics, oxygen and nitrogen radicals, nutrient starvation and others, a varying subpopulation (termed persisters) will withstand the stress situation and will be able to revive once the stress is removed. Several factors and pathways have been identified in the past that apparently favor the formation of persistence, such as various toxin/antitoxin modules or stringent response together with the alarmone (p)ppGpp. However, persistence can occur stochastically in few cells even of stress-free bacterial populations. Growth of these cells could then be induced by the stress conditions. In this review, we focus on the persister formation of human intracellular bacterial pathogens, some of which belong to the most successful persister producers but lack some or even all of the assumed persistence-triggering factors and pathways. We propose a mechanism for the persister formation of these bacterial pathogens which is based on their specific intracellular bipartite metabolism. We postulate that this mode of metabolism ultimately leads, under certain starvation conditions, to the stalling of DNA replication initiation which may be causative for the persister state.},
  language  = {en}
}
@article{EisenreichRudelHeesemannetal.2019,
  author    = {Eisenreich, Wolfgang and Rudel, Thomas and Heesemann, J{\"u}rgen and Goebel, Werner},
  title     = {How viral and intracellular bacterial pathogens reprogram the metabolism of host cells to allow their intracellular replication},
  series = {Frontiers in Cellular and Infection Microbiology},
  volume    = {9},
  journal   = {Frontiers in Cellular and Infection Microbiology},
  issn      = {2235-2988},
  doi       = {10.3389/fcimb.2019.00042},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197188},
  year      = {2019},
  abstract  = {Viruses and intracellular bacterial pathogens (IBPs) have in common the need of suitable host cells for efficient replication and proliferation during infection. In human infections, the cell types which both groups of pathogens are using as hosts are indeed quite similar and include phagocytic immune cells, especially monocytes/macrophages (MOs/MPs) and dendritic cells (DCs), as well as nonprofessional phagocytes, like epithelial cells, fibroblasts and endothelial cells. These terminally differentiated cells are normally in a metabolically quiescent state when they are encountered by these pathogens during infection. This metabolic state of the host cells does not meet the extensive need for nutrients required for efficient intracellular replication of viruses and especially IBPs which, in contrast to the viral pathogens, have to perform their own specific intracellular metabolism to survive and efficiently replicate in their host cell niches. For this goal, viruses and IBPs have to reprogram the host cell metabolism in a pathogen-specific manner to increase the supply of nutrients, energy, and metabolites which have to be provided to the pathogen to allow its replication. In viral infections, this appears to be often achieved by the interaction of specific viral factors with central metabolic regulators, including oncogenes and tumor suppressors, or by the introduction of virus-specific oncogenes. Less is so far known on the mechanisms leading to metabolic reprogramming of the host cell by IBPs. However, the still scant data suggest that similar mechanisms may also determine the reprogramming of the host cell metabolism in IBP infections. In this review, we summarize and compare the present knowledge on this important, yet still poorly understood aspect of pathogenesis of human viral and especially IBP infections.},
  language  = {en}
}
@article{EisenhuthVellmerRauhetal.2021,
  author    = {Eisenhuth, Nicole and Vellmer, Tim and Rauh, Elisa T. and Butter, Falk and Janzen, Christian J.},
  title     = {A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei},
  series = {mbio},
  volume    = {12},
  journal   = {mbio},
  number    = {6},
  doi       = {10.1128/mBio.01352-21},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260698},
  pages     = {e01352-21},
  year      = {2021},
  abstract  = {The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.},
  language  = {en}
}
@phdthesis{Eisenhuth2021,
  author    = {Eisenhuth, Nicole Juliana},
  title     = {Novel and conserved roles of the histone methyltransferase DOT1B in trypanosomatid parasites},
  doi       = {10.25972/OPUS-21993},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219936},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {The family of trypanosomatid parasites, including the human pathogens Trypanosoma brucei and Leishmania, has evolved sophisticated strategies to survive in harmful host environments. While Leishmania generate a safe niche inside the host's macrophages, Trypanosoma brucei lives extracellularly in the mammalian bloodstream, where it is constantly exposed to the attack of the immune system. Trypanosoma brucei ensures its survival by periodically changing its protective surface coat in a process known as antigenic variation. The surface coat is composed of one species of 'variant surface glycoprotein' (VSG). Even though the genome possesses a large repertoire of different VSG isoforms, only one is ever expressed at a time from one out of the 15 specialized subtelomeric 'expression sites' (ES). Switching the coat can be accomplished either by a recombination-based exchange of the actively-expressed VSG with a silent VSG, or by a transcriptional switch to a previously silent ES. The conserved histone methyltransferase DOT1B methylates histone H3 on lysine 76 and is involved in ES regulation in T. brucei. DOT1B ensures accurate transcriptional silencing of the inactive ES VSGs and influences the kinetics of a transcriptional switch. The molecular machinery that enables DOT1B to execute these regulatory functions at the ES is still elusive, however. To learn more about DOT1B-mediated regulatory processes, I wanted to identify DOT1B-associated proteins. Using two complementary approaches, specifically affinity purification and proximity-dependent biotin identification (BioID), I identified several novel DOT1B-interacting candidates. To validate these data, I carried out reciprocal co-immunoprecipitations with the most promising candidates. An interaction of DOT1B with the Ribonuclease H2 protein complex, which has never been described before in any other organism, was confirmed. Trypanosomal Ribonuclease H2 maintains genome integrity by resolving RNA-DNA hybrids, structures that if not properly processed might initiate antigenic variation. I then investigated DOT1B's contribution to this novel route to antigenic variation. Remarkably, DOT1B depletion caused an increased RNA-DNA hybrid abundance, accumulation of DNA damage, and increased VSG switching. Deregulation of VSGs from throughout the silent repertoire was observed, indicating that recombination-based switching events occurred. Encouragingly, the pattern of deregulated VSGs was similar to that seen in Ribonuclease H2-depleted cells. Together these data support the hypothesis that both proteins act together in modulating RNA-DNA hybrids to contribute to the tightly-regulated process of antigenic variation. The transmission of trypanosomatid parasites to mammalian hosts is facilitated by insect vectors. Parasites need to adapt to the extremely different environments encountered during transmission. To ensure their survival, they differentiate into various specialized forms adapted to each tissue microenvironment. Besides antigenic variation, DOT1B additionally affects the developmental differentiation from the mammalian-infective to the insect stage of Trypanosoma brucei. However, substantially less is known about the influence of chromatin-associated proteins such as DOT1B on survival and adaptation strategies of related Leishmania parasites. To elucidate whether DOT1B's functions are conserved in Leishmania, phenotypes after gene deletion were analyzed. As in Trypanosoma brucei, generation of a gene deletion mutant demonstrated that DOT1B is not essential for the cell viability in vitro. DOT1B deletion was accompanied with a loss of histone H3 lysine 73 trimethylation (the lysine homologous to trypanosomal H3K76), indicating that Leishmania DOT1B is also solely responsible for catalyzing this post-translational modification. As in T. brucei, dimethylation could only be observed during mitosis/cytokinesis, while trimethylation was detectable throughout the cell cycle in wild-type cells. In contrast to the trypanosome DOT1B, LmxDOT1B was not essential for differentiation in vitro. However, preliminary data indicate that the enzyme is required for effective macrophage infection. In conclusion, this study demonstrated that the identification of protein networks and the characterization of protein functions of orthologous proteins from related parasites are effective tools to improve our understanding of the parasite survival strategies. Such insights are a necessary step on the road to developing better treatments for the devastating diseases they cause.},
  subject      = {Trypanosoma brucei},
  language  = {en}
}
@article{EiringMcLaughlinMatikondaetal.2021,
  author    = {Eiring, Patrick and McLaughlin, Ryan and Matikonda, Siddharth S. and Han, Zhongying and Grabenhorst, Lennart and Helmerich, Dominic A. and Meub, Mara and Beliu, Gerti and Luciano, Michael and Bandi, Venu and Zijlstra, Niels and Shi, Zhen-Dan and Tarasov, Sergey G. and Swenson, Rolf and Tinnefeld, Philip and Glembockyte, Viktorija and Cordes, Thorben and Sauer, Markus and Schnermann, Martin J.},
  title     = {Targetable conformationally restricted cyanines enable photon-count-limited applications},
  series = {Angewandte Chemie Internationale Edition},
  volume    = {60},
  journal   = {Angewandte Chemie Internationale Edition},
  number    = {51},
  doi       = {10.1002/anie.202109749},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256559},
  pages     = {26685-26693},
  year      = {2021},
  abstract  = {Cyanine dyes are exceptionally useful probes for a range of fluorescence-based applications, but their photon output can be limited by trans-to-cis photoisomerization. We recently demonstrated that appending a ring system to the pentamethine cyanine ring system improves the quantum yield and extends the fluorescence lifetime. Here, we report an optimized synthesis of persulfonated variants that enable efficient labeling of nucleic acids and proteins. We demonstrate that a bifunctional sulfonated tertiary amide significantly improves the optical properties of the resulting bioconjugates. These new conformationally restricted cyanines are compared to the parent cyanine derivatives in a range of contexts. These include their use in the plasmonic hotspot of a DNA-nanoantenna, in single-molecule F{\"o}rster-resonance energy transfer (FRET) applications, far-red fluorescence-lifetime imaging microscopy (FLIM), and single-molecule localization microscopy (SMLM). These efforts define contexts in which eliminating cyanine isomerization provides meaningful benefits to imaging performance.},
  language  = {en}
}
@phdthesis{Eiring2021,
  author    = {Eiring, Patrick},
  title     = {Super-resolution microscopy of plasma membrane receptors},
  doi       = {10.25972/OPUS-25004},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250048},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Plasma membrane receptors are the most crucial and most commonly studied components of cells, since they not only ensure communication between the extracellular space and cells, but are also responsible for the regulation of cell cycle and cell division. The composition of the surface receptors, the so-called "Receptome", differs and is characteristic for certain cell types. Due to their significance, receptors have been important target structures for diagnostic and therapy in cancer medicine and often show aberrant expression patterns in various cancers compared to healthy cells. However, these aberrations can also be exploited and targeted by different medical approaches, as in the case of personalized immunotherapy. In addition, advances in modern fluorescence microscopy by so-called single molecule techniques allow for unprecedented sensitive visualization and quantification of molecules with an attainable spatial resolution of 10-20 nm, allowing for the detection of both stoichiometric and expression density differences. In this work, the single molecule sensitive method dSTORM was applied to quantify the receptor composition of various cell lines as well as in primary samples obtained from patients with hematologic malignancies. The focus of this work lies on artefact free quantification, stoichiometric analyses of oligomerization states and co localization analyses of membrane receptors. Basic requirements for the quantification of receptors are dyes with good photoswitching properties and labels that specifically mark the target structure without generating background through non-specific binding. To ensure this, antibodies with a predefined DOL (degree of labeling) were used, which are also standard in flow cytometry. First background reduction protocols were established on cell lines prior analyses in primary patient samples. Quantitative analyses showed clear expression differences between the cell lines and the patient cells, but also between individual patients. An important component of this work is the ability to detect the oligomerization states of receptors, which enables a more accurate quantification of membrane receptor densities compared to standard flow cytometry. It also provides information about the activation of a certain receptor, for example of FLT3, a tyrosine kinase, dimerizing upon activation. For this purpose, different well-known monomers and dimers were compared to distinguish the typical localization statistics of single bound antibodies from two or more antibodies that are in proximity. Further experiments as well as co localization analyses proved that antibodies can bind to closely adjacent epitopes despite their size. These analytical methods were subsequently applied for quantification and visualization of receptors in two clinically relevant examples. Firstly, various therapeutically relevant receptors such as CD38, BCMA and SLAMF7 for multiple myeloma, a malignant disease of plasma cells, were analyzed and quantified on patient cells. Furthermore, the influence of TP53 and KRAS mutations on receptor expression levels was investigated using the multiple myeloma cell lines OPM2 and AMO1, showing clear differences in certain receptor quantities. Secondly, FLT3 which is a therapeutic target receptor for acute myeloid leukemia, was quantified and stoichiometrically analyzed on both cell lines and patient cells. In addition, cells that have developed resistance against midostaurin were compared with cells that still respond to this type I tyrosine-kinase-inhibitor for their FLT3 receptor expression and oligomerization state.},
  subject      = {Fluoreszenzmikroskopie},
  language  = {en}
}
@phdthesis{Eidel2020,
  author    = {Eidel, Matthias T. A. M.},
  title     = {Training Effects of a Tactile Brain-Computer Interface System During Prolonged Use by Healthy And Motor-Impaired People},
  doi       = {10.25972/OPUS-20851},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-208511},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Background - Brain-Computer Interfaces (BCI) enable their users to interact and communicate with the environment without requiring intact muscle control. To this end, brain activity is directly measured, digitized and interpreted by the computer. Thus, BCIs may be a valuable tool to assist severely or even completely paralysed patients. Many BCIs, however, rely on neurophysiological potentials evoked by visual stimulation, which can result in usability issues among patients with impaired vision or gaze control. Because of this, several non-visual BCI paradigms have been developed. Most notably, a recent study revealed promising results from a tactile BCI for wheelchair control. In this multi-session approach, healthy participants used the BCI to navigate a simulated wheelchair through a virtual apartment, which revealed not only that the BCI could be operated highly efficiently, but also that it could be trained over five sessions. The present thesis continues the research on this paradigm in order to - confirm its previously reported high performance levels and trainability - reveal the underlying factors responsible for observed performance increases - establish its feasibility among potential impaired end-users Methods - To approach these goals, three studies were conducted with both healthy participants and patients with amyotrophic lateral sclerosis (ALS). Brain activity during BCI operation was recorded via electroencephalography (EEG) and interpreted using a machine learning-based linear classifier. Wheelchair navigation was executed according to the classification results and visualized on a monitor. For offline statistical analysis, neurophysiological features were extracted from EEG data. Subjective data on usability were collected from all participants. Two specialized experiments were conducted to identify factors for training. Results and Discussion - Healthy participants: Results revealed positive effects of training on BCI performances and their underlying neurophysiological potentials. The paradigm was confirmed to be feasible and (for a non-visual BCI) highly efficient for most participants. However, some had to be excluded from analysis of the training effects because they could not achieve meaningful BCI control. Increased somatosensory sensitivity was identified as a possible mediator for training-related performance improvements. Participants with ALS: Out of seven patients with various stages of ALS, five could operate the BCI with accuracies significantly above chance level. Another ALS patient in a state of near-complete paralysis trained with the BCI for several months. Although no effects of training were observed, he was consistently able to operate the system above chance level. Subjective data regarding workload, satisfaction and other parameters were reported. Significance - The tactile BCI was evaluated on the example of wheelchair control. In the future, it could help impaired patients to regain some lost mobility and self-sufficiency. Further, it has the potential to be adapted to other purposes, including communication. Once visual BCIs and other assistive technologies fail for patients with (progressive) motor impairments, vision-independent paradigms such as the tactile BCI may be among the last remaining alternatives to interact with the environment. The present thesis has strongly confirmed the general feasibility of the tactile paradigm for healthy participants and provides first clues about the underlying factors of training. More importantly, the BCI was established among potential end-users with ALS, providing essential external validity.},
  subject      = {Myatrophische Lateralsklerose},
  language  = {en}
}
@article{EhmannSauerKittel2015,
  author    = {Ehmann, Nadine and Sauer, Markus and Kittel, Robert J.},
  title     = {Super-resolution microscopy of the synaptic active zone},
  series = {Frontiers in Cellular Neuroscience},
  volume    = {9},
  journal   = {Frontiers in Cellular Neuroscience},
  number    = {7},
  doi       = {10.3389/fncel.2015.00007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148997},
  year      = {2015},
  abstract  = {Brain function relies on accurate information transfer at chemical synapses. At the presynaptic active zone (AZ) a variety of specialized proteins are assembled to complex architectures, which set the basis for speed, precision and plasticity of synaptic transmission. Calcium channels are pivotal for the initiation of excitation-secretion coupling and, correspondingly, capture a central position at the AZ. Combining quantitative functional studies with modeling approaches has provided predictions of channel properties, numbers and even positions on the nanometer scale. However, elucidating the nanoscopic organization of the surrounding protein network requires direct ultrastructural access. Without this information, knowledge of molecular synaptic structure-function relationships remains incomplete. Recently, super-resolution microscopy (SRM) techniques have begun to enter the neurosciences. These approaches combine high spatial resolution with the molecular specificity of fluorescence microscopy. Here, we discuss how SRM can be used to obtain information on the organization of AZ proteins},
  language  = {en}
}
@article{EderHollmannMandasarietal.2022,
  author    = {Eder, Sascha and Hollmann, Claudia and Mandasari, Putri and Wittmann, Pia and Schumacher, Fabian and Kleuser, Burkhard and Fink, Julian and Seibel, J{\"u}rgen and Schneider-Schaulies, J{\"u}rgen and Stigloher, Christian and Beyersdorf, Niklas and Dembski, Sofia},
  title     = {Synthesis and characterization of ceramide-containing liposomes as membrane models for different T cell subpopulations},
  series = {Journal of Functional Biomaterials},
  volume    = {13},
  journal   = {Journal of Functional Biomaterials},
  number    = {3},
  issn      = {2079-4983},
  doi       = {10.3390/jfb13030111},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-286130},
  year      = {2022},
  abstract  = {A fine balance of regulatory (T\(_{reg}\)) and conventional CD4\(^+\) T cells (T\(_{conv}\)) is required to prevent harmful immune responses, while at the same time ensuring the development of protective immunity against pathogens. As for many cellular processes, sphingolipid metabolism also crucially modulates the T\(_{reg}\)/T\(_{conv}\) balance. However, our understanding of how sphingolipid metabolism is involved in T cell biology is still evolving and a better characterization of the tools at hand is required to advance the field. Therefore, we established a reductionist liposomal membrane model system to imitate the plasma membrane of mouse T\(_{reg}\) and T\(_{conv}\) with regards to their ceramide content. We found that the capacity of membranes to incorporate externally added azide-functionalized ceramide positively correlated with the ceramide content of the liposomes. Moreover, we studied the impact of the different liposomal preparations on primary mouse splenocytes in vitro. The addition of liposomes to resting, but not activated, splenocytes maintained viability with liposomes containing high amounts of C\(_{16}\)-ceramide being most efficient. Our data thus suggest that differences in ceramide post-incorporation into T\(_{reg}\) and T\(_{conv}\) reflect differences in the ceramide content of cellular membranes.},
  language  = {en}
}
@article{EckhardtAndersMuranyietal.2011,
  author    = {Eckhardt, Manon and Anders, Maria and Muranyi, Walter and Heilemann, Mike and Krijnse-Locker, Jacomine and M{\"u}ller, Barbara},
  title     = {A SNAP-Tagged Derivative of HIV-1-A Versatile Tool to Study Virus-Cell Interactions},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {7},
  doi       = {10.1371/journal.pone.0022007},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133534},
  pages     = {e22007},
  year      = {2011},
  abstract  = {Fluorescently labeled human immunodeficiency virus (HIV) derivatives, combined with the use of advanced fluorescence microscopy techniques, allow the direct visualization of dynamic events and individual steps in the viral life cycle. HIV proteins tagged with fluorescent proteins (FPs) have been successfully used for live-cell imaging analyses of HIV-cell interactions. However, FPs display limitations with respect to their physicochemical properties, and their maturation kinetics. Furthermore, several independent FP-tagged constructs have to be cloned and characterized in order to obtain spectral variations suitable for multi-color imaging setups. In contrast, the so-called SNAP-tag represents a genetically encoded non-fluorescent tag which mediates specific covalent coupling to fluorescent substrate molecules in a self-labeling reaction. Fusion of the SNAP-tag to the protein of interest allows specific labeling of the fusion protein with a variety of synthetic dyes, thereby offering enhanced flexibility for fluorescence imaging approaches. Here we describe the construction and characterization of the HIV derivative HIV(SNAP), which carries the SNAP-tag as an additional domain within the viral structural polyprotein Gag. Introduction of the tag close to the C-terminus of the matrix domain of Gag did not interfere with particle assembly, release or proteolytic virus maturation. The modified virions were infectious and could be propagated in tissue culture, albeit with reduced replication capacity. Insertion of the SNAP domain within Gag allowed specific staining of the viral polyprotein in the context of virus producing cells using a SNAP reactive dye as well as the visualization of individual virions and viral budding sites by stochastic optical reconstruction microscopy. Thus, HIV(SNAP) represents a versatile tool which expands the possibilities for the analysis of HIV-cell interactions using live cell imaging and sub-diffraction fluorescence microscopy.},
  language  = {en}
}
@article{EckertFrankeScheer1975,
  author    = {Eckert, W. A. and Franke, Werner W. and Scheer, Ulrich},
  title     = {Nucleocytoplasmic translocation of RNA in Tetrahymena pyriformis and its inhibition by actinomycin D and cycloheximide},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32399},
  year      = {1975},
  abstract  = {No abstract available},
  language  = {en}
}
@article{EckertFrankeScheer1972,
  author    = {Eckert, W. A. and Franke, Werner W. and Scheer, Ulrich},
  title     = {Actinomycin D and the central granules in the nuclear pore complex: thin sectioning versus negative staining},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40636},
  year      = {1972},
  abstract  = {Thin section electron microscopy of Actinomycin D treated Tetrahymena cells and amphibian oocytes (Xenopus laevis, Triturus aZpestris) reveal no reduction in the central granules in the nuclear pore complexes. Possible reasons for the diversity between these results and earlier observations using negatively stained isolated nuclear envelopes from the same objects are discussed. The results clearly show that the presence of central granules within the nuclear pores does neither depend on nuclear RNA synthesis nor does indicate nucleocytoplasmic RNA transport. This conclusion leads to a reconsideration of the nature of the central granule. The functioning of the central granule of the nuclear pore complexes is further discussed in connection with recent studies on the ultrastructure of various types of cisternal pores.},
  language  = {en}
}
@article{EckertBohnSpaethe2022,
  author    = {Eckert, Johanna and Bohn, Manuel and Spaethe, Johannes},
  title     = {Does quantity matter to a stingless bee?},
  series = {Animal Cognition},
  volume    = {25},
  journal   = {Animal Cognition},
  number    = {3},
  issn      = {1435-9448},
  doi       = {10.1007/s10071-021-01581-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307696},
  pages     = {617-629},
  year      = {2022},
  abstract  = {Quantitative information is omnipresent in the world and a wide range of species has been shown to use quantities to optimize their decisions. While most studies have focused on vertebrates, a growing body of research demonstrates that also insects such as honeybees possess basic quantitative abilities that might aid them in finding profitable flower patches. However, it remains unclear if for insects, quantity is a salient feature relative to other stimulus dimensions, or if it is only used as a "last resort" strategy in case other stimulus dimensions are inconclusive. Here, we tested the stingless bee Trigona fuscipennis, a species representative of a vastly understudied group of tropical pollinators, in a quantity discrimination task. In four experiments, we trained wild, free-flying bees on stimuli that depicted either one or four elements. Subsequently, bees were confronted with a choice between stimuli that matched the training stimulus either in terms of quantity or another stimulus dimension. We found that bees were able to discriminate between the two quantities, but performance differed depending on which quantity was rewarded. Furthermore, quantity was more salient than was shape. However, quantity did not measurably influence the bees' decisions when contrasted with color or surface area. Our results demonstrate that just as honeybees, small-brained stingless bees also possess basic quantitative abilities. Moreover, invertebrate pollinators seem to utilize quantity not only as "last resort" but as a salient stimulus dimension. Our study contributes to the growing body of knowledge on quantitative cognition in invertebrate species and adds to our understanding of the evolution of numerical cognition.},
  language  = {en}
}
@phdthesis{Eck2016,
  author    = {Eck, Saskia},
  title     = {The impact of thermogenetic depolarizations of specific clock neurons on Drosophila melanogaster's circadian clock},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137118},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {The rotation of the earth around its own axis determines periodically changing environmental conditions, like alterations in light and temperature. For the purpose of adapting all organisms' behavior, physiology and metabolism to recurring changes, endogenous clocks have evolved, which allow the organisms to anticipate environmental changes. In chronobiology, the scientific field dealing with the investigation of the underlying mechanisms of the endogenous clock, the fruit fly Drosophila melanogaster serves as a beneficial model organism. The fruit fly's circadian clock exhibits a rather simple anatomical organization, but nevertheless constitutes homologies to the mammalian system. Thus also in this PhD-thesis the fruit fly was used to decipher general features of the circadian clock's interneuronal communication. Drosophila melanogaster's circadian clock consists of about 150 clock neurons, which are located in the central nervous system of the fly. These clock neurons can be subdivided regarding to their anatomical position in the brain into the dorsal neurons (DN1s, DN2s, DN3s), as well as into the lateral neurons (LPNs, LNds, s-LNvs, l-LNvs). Functionally these clock neuron clusters can be classified as Morning- and Evening oscillators (M- and E- oscillators), driving different parts of the fly's locomotor activity in light-dark conditions (LD). The Morning-oscillators are represented by the s-LNvs and are known to be the main pacemakers, driving the pace of the clock in constant conditions (constant darkness; DD). The group of Evening-oscillators consists of the LNds, the DN1s and the 5th s-LNv and is important for the proper timing of the evening activity in LD. All of these clock neurons are not functionally independent, but form complex neuronal connections, which are highly plastic in their response to different environmental stimuli (Zeitgebers), like light or temperature. Even though a lot is known about the function and the importance of some clock neuron clusters, the exact interplay between the neurons is not fully known yet. To investigate the mechanisms, which are involved in communication processes among different clock neurons, we depolarized specific clock cells in a temporally and cell-type restricted manner using dTrpA1, a thermosensitive cation channel, which allows the depolarization of neurons by application of temperature pulses (TP) above 29°C to the intact and freely moving fly. Using different clock specific GAL4-driver lines and applying TPs at different time points within the circadian cycle in DD enabled us with the help of phase shift experiments to draw conclusions on the properties of the endogenous clock. The obtained phase shifts in locomotor behavior elicited by specific clock neuronal activation were plotted as phase response curves (PRCs). The depolarization of all clock neurons shifted the phase of activity the strongest, especially in the delay zone of the PRC. The exclusive depolarization of the M oscillators together with the l-LNvs (PDF+ neurons: s-LNvs \& l-LNvs) caused shifts in the delay and in the advance zone as well, however the advances were severely enhanced in their temporal occurrence ranging into the subjective day. We concluded that light might have inhibitory effects on the PDF+ cells in that particular part of the PRC, as typical light PRCs do not exhibit that kind of distinctive advances. By completely excluding light in the PRC-experiments of this PhD-thesis, this photic inhibitory input to the PDF+ neurons is missing, probably causing the broadened advance zone. These findings suggest the existence of an inhibitory light-input pathway to the PDF+ cells from the photoreceptive organs (Hofbauer-Buchner eyelet, photoreceptor cells of compound eyes, ocelli) or from other clock neurons, which might inhibit phase advances during the subjective day. To get an impression of the molecular state of the clock in the delay and advance zone, staining experiments against Period (PER), one of the most important core clock components, and against the neuropeptide Pigment Dispersing Factor (PDF) were performed. The cycling of PER levels mirrored the behavioral phase shifts in experimental flies, whereas the controls were widely unaffected. As just those neurons, which had been depolarized, exhibited immediate shifted PER oscillations, this effect has to be rapidly regulated in a cell-autonomous manner. However, the molecular link between clock neuron depolarization and shifts in the molecular clock's cycling is still missing. This issue was addressed by CREB (cAMP responsive element binding protein) quantification in the large ventrolateral neurons (l-LNvs), as these neurons responded unexpectedly and strongest to the artificial depolarization exhibiting a huge increase in PER levels. It had been previously suggested that CREB is involved in circadian rhythms by binding to regulatory sequences of the period gene (Belvin et al., 1999), thus activating its transcription. We were able to show, that CREB levels in the l-LNvs are under circadian regulation, as they exhibit higher CREB levels at the end of the subjective night relative to the end of the subjective day. That effect was further reinforced by artificial depolarization, independently of the time point of depolarization. Furthermore the data indicate that rises in CREB levels are coinciding with the time point of increases of PER levels in the l-LNvs, suggesting CREB being the molecular link between the neuronal electrical state and the molecular clock. Taking together, the results indicate that a temporal depolarization using dTrpA1 is able to significantly phase shift the clock on the behavioral and protein level. An artificial depolarization at the beginning of the subjective night caused phase delays, whereas a depolarization at the end of the subjective night resulted in advances. The activation of all clock neurons caused a PRC that roughly resembled a light-PRC. However, the depolarization of the PDF+ neurons led to a PRC exhibiting a shape that did not resemble that of a light-mediated PRC, indicating the complex processing ability of excitatory and inhibitory input by the circadian clock. Even though this experimental approach is highly artificial, just the exclusion of light-inputs enabled us to draw novel conclusions on the network communication and its light input pathways.},
  subject      = {Chronobiologie},
  language  = {en}
}
@article{DuettingGaitsIacovoniStegneretal.2017,
  author    = {D{\"u}tting, Sebastian and Gaits-Iacovoni, Frederique and Stegner, David and Popp, Michael and Antkowiak, Adrien and van Eeuwijk, Judith M.M. and Nurden, Paquita and Stritt, Simon and Heib, Tobias and Aurbach, Katja and Angay, Oguzhan and Cherpokova, Deya and Heinz, Niels and Baig, Ayesha A. and Gorelashvili, Maximilian G. and Gerner, Frank and Heinze, Katrin G. and Ware, Jerry and Krohne, Georg and Ruggeri, Zaverio M. and Nurden, Alan T. and Schulze, Harald and Modlich, Ute and Pleines, Irina and Brakebusch, Cord and Nieswandt, Bernhard},
  title     = {A Cdc42/RhoA regulatory circuit downstream of glycoprotein Ib guides transendothelial platelet biogenesis},
  series = {Nature Communications},
  volume    = {8},
  journal   = {Nature Communications},
  number    = {15838},
  doi       = {10.1038/ncomms15838},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170797},
  year      = {2017},
  abstract  = {Blood platelets are produced by large bone marrow (BM) precursor cells, megakaryocytes (MKs), which extend cytoplasmic protrusions (proplatelets) into BM sinusoids. The molecular cues that control MK polarization towards sinusoids and limit transendothelial crossing to proplatelets remain unknown. Here, we show that the small GTPases Cdc42 and RhoA act as a regulatory circuit downstream of the MK-specific mechanoreceptor GPIb to coordinate polarized transendothelial platelet biogenesis. Functional deficiency of either GPIb or Cdc42 impairs transendothelial proplatelet formation. In the absence of RhoA, increased Cdc42 activity and MK hyperpolarization triggers GPIb-dependent transmigration of entire MKs into BM sinusoids. These findings position Cdc42 (go-signal) and RhoA (stop-signal) at the centre of a molecular checkpoint downstream of GPIb that controls transendothelial platelet biogenesis. Our results may open new avenues for the treatment of platelet production disorders and help to explain the thrombocytopenia in patients with Bernard-Soulier syndrome, a bleeding disorder caused by defects in GPIb-IX-V.},
  language  = {en}
}
@article{DuehringGermerodtSkerkaetal.2015,
  author    = {D{\"u}hring, Sybille and Germerodt, Sebastian and Skerka, Christine and Zipfel, Peter F. and Dandekar, Thomas and Schuster, Stefan},
  title     = {Host-pathogen interactions between the human innate immune system and Candida albicans - understanding and modeling defense and evasion strategies},
  series = {Frontiers in Microbiology},
  volume    = {6},
  journal   = {Frontiers in Microbiology},
  number    = {625},
  doi       = {10.3389/fmicb.2015.00625},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151621},
  year      = {2015},
  abstract  = {The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given.},
  language  = {en}
}
@phdthesis{Duechs2011,
  author    = {D{\"u}chs, Matthias},
  title     = {Effects of Toll-like receptor agonists on the pathogenesis of atopic asthma in mice},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66369},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {In the last decades, both the incidence and the severity of asthma have steadily increased. Furthermore, available therapies only treat the symptoms but do not cure the disease. Immune modulation induced by TLR agonists may be a promising novel approach to effectively treat asthma as it targets the underlying immunopathology directly rather than one mediator alone. The aim of this thesis was to investigate if the immunostimulatory properties of Toll-like receptor (TLR) agonists can be utilized to develop novel therapeutic intervention strategies for the treatment of asthma using murine models of allergic inflammation. For this purpose five different TLR agonists were tested in preclinical mouse models of acute and chronic asthma, both in preventive and therapeutic settings. Firstly, TLR-2, 3, 4, 7/8 and 9 agonists were delivered intratracheally at different doses before pulmonary allergen exposure in the asthma model of acute inflammation. TLR9 agonist CpG-containing oligodeoxynucleotides (CpG) > TLR7 agonist Resiquimod (R848) > TLR3 agonists poly(I:C) strongly reduced allergen induced airway eosinophilia and IL-4 levels in a dose-dependent manner. All TLR agonists increased neutrophil numbers, TLR4 agonist lipopolysaccharide (LPS) > TLR2 agonist lipoteichonic acid (LTA) > poly(I:C) > CpG > R848 and, with the exception of R848, the amount of pro-inflammatory cytokines in the airways. Suppressive effects were not dependent upon IFN-γ and IL-10 or associated with increased numbers of regulatory T cells in the airways. All TLR agonists, except LTA, similarly reduced airway eosinophilia and IL-4 levels when applied therapeutically after allergen challenge. These results show that the TLR agonists have different suppressive effects on TH2 responses in the airways which further depend on the dose and the experimental setup in which they were tested. Interestingly, all agonists induced airway neutrophilia, albeit to different degrees, raising the question if TLR ligands are safe for human use when applied directly into the lung. Different TLR agonists are also being developed for human use as adjuvants combined with allergen in specific immunotherapy. Recent clinical data suggest that this may be achieved by induction of allergen-specific TH1 responses. For this reason, the ability of different TLR agonists to induce allergen-specific TH1 and suppress allergen-specific TH2 responses in a preclinical setting was investigated in this thesis. Different doses of the TLR agonists were applied together with allergen, then mice were exposed to allergen aerosol. CpG > LPS >LTA dose-dependently strongly suppressed the development of airway eosinophilia with poly(I:C) and R848 having no effect. The decrease in eosinophilic numbers was associated withincreased neutrophils present in the airways. IL-4 and IL-5 levels in the bronchoalveolar lavage fluid were also decreased when poly(I:C), LPS, and CpG were used. All TLR agonists increased allergen-specific IgG2a, and with the exception of poly(I:C), reduced allergen-specific IgE levels in the serum. Cutaneous anaphylaxis to allergen was completely prevented when LPS or CpG were given as adjuvant. The strongest TH1 responses were induced by CpG and poly(I:C), characterized by the presence of IFN-γ in the bronchoalveolar lavage and the highest allergen-specific IgG2a levels in the serum. This data supports approaches to use TLR9 or TLR4 agonists for human therapy as adjuvant in combination with allergen in novel specific immunotherapy formulations. In the last part of the thesis, it was investigated if TLR activation can also affect the pathology of severe chronic asthma. Therapeutic administration of R848 or CpG reduced features of inflammation and remodeling. Both agonists showed superior effects to dexamethasone, with CpG being more efficient than R848. This result again supports a TLR9-based therapy as a viable option for the treatment of severe chronic asthma which may present a potential alternative for anti-inflammatory therapy with steroids. Taken together, the results of this thesis support the use of TLR agonists to treat asthma. The most favorable efficacy/safety ratio is to be expected from TLR-based therapies combining TLR4 or TLR9 agonists with allergen in specific immunotherapy. In regard to TLR agonist monotherapy, R848 and CpG showed the most promising profiles, CpG particularly in a model of severe chronic asthma. However, since all TLR agonists used in this study also showed pro-inflammatory potential, the safety aspect of such an approach needs to be taken into account.},
  subject      = {Toll-like Rezeptor},
  language  = {en}
}
@article{DoerkPeterlongoMannermaaetal.2019,
  author    = {D{\"o}rk, Thilo and Peterlongo, Peter and Mannermaa, Arto and Bolla, Manjeet K. and Wang, Qin and Dennis, Joe and Ahearn, Thomas and Andrulis, Irene L. and Anton-Culver, Hoda and Arndt, Volker and Aronson, Kristan J. and Augustinsson, Annelie and Beane Freeman, Laura E. and Beckmann, Matthias W. and Beeghly-Fadiel, Alicia and Behrens, Sabine and Bermisheva, Marina and Blomqvist, Carl and Bogdanova, Natalia V. and Bojesen, Stig E. and Brauch, Hiltrud and Brenner, Hermann and Burwinkel, Barbara and Canzian, Federico and Chan, Tsun L. and Chang-Claude, Jenny and Chanock, Stephen J. and Choi, Ji-Yeob and Christiansen, Hans and Clarke, Christine L. and Couch, Fergus J. and Czene, Kamila and Daly, Mary B. and dos-Santos-Silva, Isabel and Dwek, Miriam and Eccles, Diana M. and Ekici, Arif B. and Eriksson, Mikael and Evans, D. Gareth and Fasching, Peter A. and Figueroa, Jonine and Flyger, Henrik and Fritschi, Lin and Gabrielson, Marike and Gago-Dominguez, Manuela and Gao, Chi and Gapstur, Susan M. and Garc{\´i}a-Closas, Montserrat and Garc{\´i}a-S{\´a}enz, Jos{\´e} A. and Gaudet, Mia M. and Giles, Graham G. and Goldberg, Mark S. and Goldgar, David E. and Guen{\´e}l, Pascal and Haeberle, Lothar and Haimann, Christopher A. and H{\aa}kansson, Niclas and Hall, Per and Hamann, Ute and Hartman, Mikael and Hauke, Jan and Hein, Alexander and Hillemanns, Peter and Hogervorst, Frans B. L. and Hooning, Maartje J. and Hopper, John L. and Howell, Tony and Huo, Dezheng and Ito, Hidemi and Iwasaki, Motoki and Jakubowska, Anna and Janni, Wolfgang and John, Esther M. and Jung, Audrey and Kaaks, Rudolf and Kang, Daehee and Kapoor, Pooja Middha and Khusnutdinova, Elza and Kim, Sung-Won and Kitahara, Cari M. and Koutros, Stella and Kraft, Peter and Kristensen, Vessela N. and Kwong, Ava and Lambrechts, Diether and Le Marchand, Loic and Li, Jingmei and Lindstr{\"o}m, Sara and Linet, Martha and Lo, Wing-Yee and Long, Jirong and Lophatananon, Artitaya and Lubiński, Jan and Manoochehri, Mehdi and Manoukian, Siranoush and Margolin, Sara and Martinez, Elena and Matsuo, Keitaro and Mavroudis, Dimitris and Meindl, Alfons and Menon, Usha and Milne, Roger L. and Mohd Taib, Nur Aishah and Muir, Kenneth and Mulligan, Anna Marie and Neuhausen, Susan L. and Nevanlinna, Heli and Neven, Patrick and Newman, William G. and Offit, Kenneth and Olopade, Olufunmilayo I. and Olshan, Andrew F. and Olson, Janet E. and Olsson, H{\aa}kan and Park, Sue K. and Park-Simon, Tjoung-Won and Peto, Julian and Plaseska-Karanfilska, Dijana and Pohl-Rescigno, Esther and Presneau, Nadege and Rack, Brigitte and Radice, Paolo and Rashid, Muhammad U. and Rennert, Gad and Rennert, Hedy S. and Romero, Atocha and Ruebner, Matthias and Saloustros, Emmanouil and Schmidt, Marjanka K. and Schmutzler, Rita K. and Schneider, Michael O. and Schoemaker, Minouk J. and Scott, Christopher and Shen, Chen-Yang and Shu, Xiao-Ou and Simard, Jaques and Slager, Susan and Smichkoska, Snezhana and Southey, Melissa C. and Spinelli, John J. and Stone, Jennifer and Surowy, Harald and Swerdlow, Anthony J. and Tamimi, Rulla M. and Tapper, William J. and Teo, Soo H. and Terry, Mary Beth and Toland, Amanda E. and Tollenaar, Rob A. E. M. and Torres, Diana and Torres-Mej{\´i}a, Gabriela and Troester, Melissa A. and Truong, Th{\´e}r{\`e}se and Tsugane, Shoichiro and Untch, Michael and Vachon, Celine M. and van den Ouweland, Ans M. W. and van Veen, Elke M. and Vijai, Joseph and Wendt, Camilla and Wolk, Alicja and Yu, Jyh-Cherng and Zheng, Wei and Ziogas, Argyrios and Ziv, Elad and Dunnig, Alison and Pharaoh, Paul D. P. and Schindler, Detlev and Devilee, Peter and Easton, Douglas F.},
  title     = {Two truncating variants in FANCC and breast cancer risk},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  organization    = {ABCTB Investigators, NBCS Collaborators},
  doi       = {10.1038/s41598-019-48804-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222838},
  year      = {2019},
  abstract  = {Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95\%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.},
  language  = {en}
}
@article{DaeullaryImdahlDietrichetal.2023,
  author    = {D{\"a}ullary, Thomas and Imdahl, Fabian and Dietrich, Oliver and Hepp, Laura and Krammer, Tobias and Fey, Christina and Neuhaus, Winfried and Metzger, Marco and Vogel, J{\"o}rg and Westermann, Alexander J. and Saliba, Antoine-Emmanuel and Zdzieblo, Daniela},
  title     = {A primary cell-based in vitro model of the human small intestine reveals host olfactomedin 4 induction in response to Salmonella Typhimurium infection},
  series = {Gut Microbes},
  volume    = {15},
  journal   = {Gut Microbes},
  number    = {1},
  doi       = {10.1080/19490976.2023.2186109},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350451},
  year      = {2023},
  abstract  = {Infection research largely relies on classical cell culture or mouse models. Despite having delivered invaluable insights into host-pathogen interactions, both have limitations in translating mechanistic principles to human pathologies. Alternatives can be derived from modern Tissue Engineering approaches, allowing the reconstruction of functional tissue models in vitro. Here, we combined a biological extracellular matrix with primary tissue-derived enteroids to establish an in vitro model of the human small intestinal epithelium exhibiting in vivo-like characteristics. Using the foodborne pathogen Salmonella enterica serovar Typhimurium, we demonstrated the applicability of our model to enteric infection research in the human context. Infection assays coupled to spatio-temporal readouts recapitulated the established key steps of epithelial infection by this pathogen in our model. Besides, we detected the upregulation of olfactomedin 4 in infected cells, a hitherto unrecognized aspect of the host response to Salmonella infection. Together, this primary human small intestinal tissue model fills the gap between simplistic cell culture and animal models of infection, and shall prove valuable in uncovering human-specific features of host-pathogen interplay.},
  language  = {en}
}
@phdthesis{Dwertmann2012,
  author    = {Dwertmann, Anne},
  title     = {Impact of the Tumor Suppressor Arf on Miz1 and Sumoylation of Myc and Miz1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-71876},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Upon oncogenic stress, the tumor suppressor Arf can induce irreversible cell cycle arrest or apoptosis, depending on the oncogenic insult. In this study, it could be shown that Arf interacts with Myc and the Myc-associated zinc-finger protein Miz1 to facilitate repression of genes involved in cell adhesion. Formation of a DNA-binding Arf/Myc/Miz1 complex disrupts interaction of Miz1 with its coactivator nucleophosmin and induces local heterochromatinisation, causing cells to lose attachment and undergo anoikis. The assembly of the complex relies on Myc, which might explain why high Myc levels trigger apoptosis and not cell cycle arrest in the Arf response. This mechanism could play an important role in eliminating cells harboring an oncogenic mutation. Arf furthermore induces sumoylation of Miz1 at a specific lysine by repressing the desumoylating enzyme Senp3. A sumoylation-deficient mutant of Miz1 however does not show phenotypic differences under the chosen experimental conditions. Myc can also be modified by Sumo by multisumoylation at many different lysines, which is unaffected by Arf. The exact mechanism and effect of this modification however stays unsolved.},
  subject      = {Apoptosis},
  language  = {en}
}
@article{DusikSenthilanMentzeletal.2014,
  author    = {Dusik, Verena and Senthilan, Pingkalai R. and Mentzel, Benjamin and Hartlieb, Heiko and W{\"u}lbeck, Corina and Yoshii, Taishi and Raabe, Thomas and Helfrich-F{\"o}rster, Charlotte},
  title     = {The MAP Kinase p38 Is Part of Drosophila melanogaster's Circadian Clock},
  series = {PLoS Genetics},
  volume    = {10},
  journal   = {PLoS Genetics},
  number    = {8},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1004565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119433},
  pages     = {e1004565},
  year      = {2014},
  abstract  = {All organisms have to adapt to acute as well as to regularly occurring changes in the environment. To deal with these major challenges organisms evolved two fundamental mechanisms: the p38 mitogen-activated protein kinase (MAPK) pathway, a major stress pathway for signaling stressful events, and circadian clocks to prepare for the daily environmental changes. Both systems respond sensitively to light. Recent studies in vertebrates and fungi indicate that p38 is involved in light-signaling to the circadian clock providing an interesting link between stress-induced and regularly rhythmic adaptations of animals to the environment, but the molecular and cellular mechanisms remained largely unknown. Here, we demonstrate by immunocytochemical means that p38 is expressed in Drosophila melanogaster's clock neurons and that it is activated in a clock-dependent manner. Surprisingly, we found that p38 is most active under darkness and, besides its circadian activation, additionally gets inactivated by light. Moreover, locomotor activity recordings revealed that p38 is essential for a wild-type timing of evening activity and for maintaining ∼ 24 h behavioral rhythms under constant darkness: flies with reduced p38 activity in clock neurons, delayed evening activity and lengthened the period of their free-running rhythms. Furthermore, nuclear translocation of the clock protein Period was significantly delayed on the expression of a dominant-negative form of p38b in Drosophila's most important clock neurons. Western Blots revealed that p38 affects the phosphorylation degree of Period, what is likely the reason for its effects on nuclear entry of Period. In vitro kinase assays confirmed our Western Blot results and point to p38 as a potential "clock kinase" phosphorylating Period. Taken together, our findings indicate that the p38 MAP Kinase is an integral component of the core circadian clock of Drosophila in addition to playing a role in stress-input pathways.},
  language  = {en}
}
@article{DuschlJahnBertlingetal.1992,
  author    = {Duschl, Albert and Jahn, Ute and Bertling, Claudia and Sebald, Walter},
  title     = {A comparison of assays for the response of primary human T-cells upon stimulation with interleukin-2, interleukin-4 and interleukin-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86750},
  year      = {1992},
  abstract  = {The most commonly used assay to quantitate the response of peripheral T~cells upon stimulation with growth factors is determination of incorporated (JH]TdR. We compared thls test to three other methods: 1. direct countlog of cells with a Coulter type counter as reference assay, 2. a colorimetric assay using the tetrazolium dye 3-[ 4,S-dimethylthiazol-l-yl]-2,5diphenyl tetrazolium (MTT), which is a cheap and increasingly popular non-radioactive method and 3. incorporation of the thymidine analog 5-bromo-2'-deoxyuridine detection with a monoclonal antibody on cytospins. Primary human PHA-blasts from >30 healthy individuals were stimulated with IL-2, IL-4 aod IL-7 and assayed with up to four different methods. We discuss the advantages and disadvantages of the assays used and tbe effects of differences between cell preparations. We observed no significant variations between individuals for the dose dependence, but the relative emctency of IL4 compared to IL-2 and IL-7 was variable. This was probably due to the slower response observed upon stimulation with this factor.},
  subject      = {T-Lymphozyt},
  language  = {en}
}
@phdthesis{Duraphe2010,
  author    = {Duraphe, Prashant},
  title     = {Identification and characterization of AUM, a novel human tyrosine phosphatase},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44256},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Protein Phosphatasen werden aufgrund der Aminos{\"a}uresequenzen ihrer aktiven Zentren in drei große Familien unterteilt. In einer neu entdeckten Familie von Phosphatasen ist das aktive Zentrum durch die Sequenz DXDX(T/V) charakterisiert. Diese Aspartat-abh{\"a}ngigen Phosphatasen geh{\"o}ren zu der Superfamilie der Hydrolasen vom Haloazid Dehalogenase(HAD)-Typ, einer evolution{\"a}r konservierten und ubiquit{\"a}r verbreiteten Enzymfamilie. Bislang konnten 58 menschliche HAD Enzyme durch Datenbankanalysen identifiziert werden. Ihre Funktionen sind jedoch nach wie vor nur rudiment{\"a}r verstanden. Im Rahmen dieser Arbeit wurde zun{\"a}chst das Komplement aller menschlichen HAD Phosphatasen durch Datenbank-Recherchen erfasst. Zusammen mit phylogenetischen Analysen gelang es, eine zum damaligen Zeitpunkt unbekannte, putative Phosphatase zu identifizieren, die eine vergleichsweise hohe Sequenz-Homologie zu der Zytoskelettregulierenden HAD Phosphatase Chronophin aufweist. Dieses neuartige Enzym wurde kloniert und mit biochemischen und zellbiologischen Methoden charakterisiert. Auf der Basis dieser Befunde bezeichnen wir dieses neuartige Protein als AUM (actin remodeling, ubiquitously expressed, magnesium-dependent HAD phosphatase).Mittels Northern blot, real-time PCR und Western blot Analysen konnte gezeigt werden, dass AUM in allen untersuchten menschlichen und murinen Geweben exprimiert wird. Die h{\"o}chste Expression konnte in Hodengewebe nachgewiesen werden. Durch immunohistochemische Untersuchungen konnte gezeigt werden, dass AUM spezifisch in reifenden Keimzellen mit einem Expressionsmaximum zum Zeitpunkt der Spermiogenese exprimiert wird. Um die Substratpr{\"a}ferenz von AUM zu charakterisieren, wurde zun{\"a}chst ein peptidbasierter in vitro Phosphatase-Substrat-Screen durchgef{\"u}hrt. Hierbei wurden 720 aus menschlichen Phosphoproteinen abgeleitete Phosphopeptide untersucht. Interessanterweise dephosphorylierte AUM ausschließlich Phosphotyrosin (pTyr)-enthaltende Peptide. Nur 17 pTyr-Peptide (~2\% aller untersuchten Peptide) fungierten als AUM-Substrate. Diese Daten legen eine hohe Substratspezifit{\"a}t von AUM nahe. Zu den putativen AUM Substraten geh{\"o}ren Proteine, die in die Dynamik der Zytoskelett-Reorganisation sowie in Tyrosin Kinasevermittelte Signalwege eingebunden sind. In {\"U}bereinstimmung mit den Ergebnissen dieses Phosphopeptid-Screens konnte mittels Phosphatase overlay assays sowie in Zellextrakten aus Pervanadat-behandelten HeLa Zellen demonstriert werden, dass AUM eine begrenzte Anzahl Tyrosin-phosphorylierter Proteinen dephosphorylieren kann.In zellul{\"a}ren Untersuchungen wurde die m{\"o}gliche Rolle von AUM im Rahmen der durch den epidermalen Wachstumsfaktor (EGF) ausgel{\"o}sten Tyrosin-Phosphorylierung in einer Spermatogonien Zelllinie (GC-1 spg-Zellen) analysiert. So konnte nachgewiesen werden, dass die {\"U}berexpression von AUM zu einer moderaten Abnahme Tyrosin phosphorylierter Proteine nach EGF-Stimulation f{\"u}hrte. Im Gegensatz dazu l{\"o}ste jedoch die durch RNAInterferenz vermittelte Depletion von endogenem AUM einen robusten Anstieg Tyrosinphosphorylierter Proteine aus, zu denen auch der EGF-Rezeptor selbst z{\"a}hlt. Zus{\"a}tzlich zu dem EGF-Rezeptor wurde die Src-Kinase im Zuge des Phosphopeptid- Screens als m{\"o}gliches AUM Substrat identifiziert. Daher wurden in vitro Kinase/Phosphatase-Assays mit gereinigtem Src und AUM durchgef{\"u}hrt. Mit diesem Ansatz konnte erstmals gezeigt werden, dass AUM in der Lage ist, die Src-Kinase zu aktivieren, w{\"a}hrend Src AUM phosphoryliert und die AUM Phosphatase-Aktivit{\"a}t blockiert. Diese Ergebnisse deuten auf eine gekoppelte, wechselseitige Regulation von AUM und Src hin. Obwohl die Details dieser Regulation derzeit noch unklar sind, zeigen unsere initialen Ergebnisse, dass AUM die Src-Aktivit{\"a}t unabh{\"a}ngig von seiner Phosphatase Aktivit{\"a}t steigert, w{\"a}hrend Src die AUM Phosphatase-Aktivit{\"a}t Kinase-abh{\"a}ngig vermindert. Auf zellul{\"a}rer Ebene sind AUM-depletierte Zellen durch Ver{\"a}nderungen der Aktin- Zytoskelett-Dynamik und der Zelladh{\"a}sion charakterisiert. So weisen AUM-defiziente Zellen stabilisierte Aktin Streßfasern und vergr{\"o}ßerte fokale Adh{\"a}sionen auf. Weiterhin sind AUMdepletierte Zellen durch ein beschleunigtes spreading auf Fibronektin gekennzeichnet. Wir haben mit AUM ein bisher nicht beschriebenes Mitglied der Familie Aspartat-abh{\"a}ngiger Phosphatasen entdeckt. In dieser Arbeit ist es gelungen, AUM phylogenetisch, biochemisch und zellbiologisch zu charakterisieren. Unsere Ergebnisse legen nahe, dass AUM einen wichtigen, neuartigen Regulator der Src-vermittelten Zytoskelett-Dynamik im Rahmen der Zelladh{\"a}sion und Migration darstellt.},
  subject      = {Tyrosin},
  language  = {en}
}
@article{DuquePoelmanSteffanDewenter2019,
  author    = {Duque, Laura and Poelman, Erik H. and Steffan-Dewenter, Ingolf},
  title     = {Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-56234-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202805},
  pages     = {19891},
  year      = {2019},
  abstract  = {Abiotic stress by elevated tropospheric ozone and temperature can alter plants' metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49\% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common.},
  language  = {en}
}
@article{DuquePoelmanSteffanDewenter2021,
  author    = {Duque, Laura and Poelman, Erik H. and Steffan-Dewenter, Ingolf},
  title     = {Plant age at the time of ozone exposure affects flowering patterns, biotic interactions and reproduction of wild mustard},
  series = {Scientific Reports},
  volume    = {11},
  journal   = {Scientific Reports},
  number    = {1},
  doi       = {10.1038/s41598-021-02878-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265742},
  year      = {2021},
  abstract  = {Exposure of plants to environmental stressors can modify their metabolism, interactions with other organisms and reproductive success. Tropospheric ozone is a source of plant stress. We investigated how an acute exposure to ozone at different times of plant development affects reproductive performance, as well as the flowering patterns and the interactions with pollinators and herbivores, of wild mustard plants. The number of open flowers was higher on plants exposed to ozone at earlier ages than on the respective controls, while plants exposed at later ages showed a tendency for decreased number of open flowers. The changes in the number of flowers provided a good explanation for the ozone-induced effects on reproductive performance and on pollinator visitation. Ozone exposure at earlier ages also led to either earlier or extended flowering periods. Moreover, ozone tended to increase herbivore abundance, with responses depending on herbivore taxa and the plant age at the time of ozone exposure. These results suggest that the effects of ozone exposure depend on the developmental stage of the plant, affecting the flowering patterns in different directions, with consequences for pollination and reproduction of annual crops and wild species.},
  language  = {en}
}
@phdthesis{Duque2022,
  author    = {Duque, Laura Maria Ribeiro},
  title     = {Effects of ozone on plants and plant-insect interactions},
  doi       = {10.25972/OPUS-27798},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277983},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Anthropogenic activities are causing air pollution. Amongst air pollutants, tropospheric ozone is a major threat to human health and ecosystem functioning. In this dissertation, I present three studies that aimed at increasing our knowledge on how plant exposure to ozone affects its reproduction and its interactions with insect herbivores and pollinators. For this purpose, a new fumigation system was built and placed in a greenhouse. The annual plant Sinapis arvensis (wild mustard) was used as the model plant. Plants were exposed to either 0 ppb (control) or 120 ppb of ozone, for variable amounts of time and at different points of their life cycle. After fumigation, plants were exposed to herbivores or pollinators in the greenhouse, or to both groups of insects in the field. My research shows that ozone affected reproductive performance differently, depending on the timing of exposure: plants exposed at earlier ages had their reproductive fitness increased, while plants exposed later in their life cycle showed a tendency for reduced reproductive fitness. Plant phenology was a key factor influencing reproductive fitness: ozone accelerated flowering and increased the number of flowers produced by plants exposed at early ages, while plants exposed to ozone at later ages tended to have fewer flowers. On the other hand, the ozone-mediated changes in plant-insect interactions had little impact on plant reproductive success. The strongest effect of ozone on plant-pollinator interactions was the change in the number of flower visits received per plant, which was strongly linked to the number of open flowers. This means that, as a rule, exposure of plants to ozone early in the life cycle resulted in a higher number of pollinator visits, while exposure later in the life cycle resulted in fewer flower visits by potential pollinators. An exception was observed: the higher number of visits performed by large syrphid flies to young ozone-exposed plants than to the respective control plants went beyond the increase in the number of open flowers in those plants. Also, honeybees spent more time per flower in plants exposed to ozone than on control plants, while other pollinators spent similar amounts of time in control and ozone-exposed plants. This guild-dependent preference for ozone-exposed plants may be due to species-specific preferences related to changes in the quality and quantity of floral rewards. In the field, ozone-exposed plants showed only a tendency for increased colonization by sucking herbivores and slightly more damage by chewing herbivores than control plants. On the other hand, in the greenhouse experiment, Pieris brassicae butterflies preferred control plants over ozone-exposed plants as oviposition sites. Eggs laid on ozone-exposed plants took longer to hatch, but the chances of survival were higher. Caterpillars performed better in control plants than in ozone-exposed plants, particularly when the temperature was high. Most of the described effects were dependent on the duration and timing of the ozone exposure and the observed temperature, with the strongest effects being observed for longer exposures and higher temperatures. Furthermore, the timing of exposure altered the direction of the effects. The expected climate change provides ideal conditions for further increases in tropospheric ozone concentrations, therefore for stronger effects on plants and plant-insect interactions. Acceleration of flowering caused by plant exposure to ozone may put plant-pollinator interactions at risk by promoting desynchronization between plant and pollinator activities. Reduced performance of caterpillars feeding on ozone-exposed plants may weaken herbivore populations. On the other hand, the increased plant reproduction that results from exposing young plants to ozone may be a source of good news in the field of horticulture, when similar results would be achieved in high-value crops. However, plant response to ozone is highly species-specific. In fact, Sinapis arvensis is considered a weed and the advantage conferred by ozone exposure may increase its competitiveness, with negative consequences for crops or plant communities in general. Overall, plant exposure to ozone might constitute a threat for the balance of natural and agro-ecosystems.},
  subject      = {Plant},
  language  = {en}
}
@article{DunceMilburnGurusaranetal.2018,
  author    = {Dunce, James M. and Milburn, Amy E. and Gurusaran, Manickam and da Cruz, Irene and Sen, Lee T. and Benavente, Ricardo and Davies, Owen R.},
  title     = {Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1},
  series = {Nature Communications},
  volume    = {9},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-018-07794-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226416},
  year      = {2018},
  abstract  = {Meiotic chromosomes undergo rapid prophase movements, which are thought to facilitate the formation of inter-homologue recombination intermediates that underlie synapsis, crossing over and segregation. The meiotic telomere complex (MAJIN, TERB1, TERB2) tethers telomere ends to the nuclear envelope and transmits cytoskeletal forces via the LINC complex to drive these rapid movements. Here, we report the molecular architecture of the meiotic telomere complex through the crystal structure of MAJIN-TERB2, together with light and X-ray scattering studies of wider complexes. The MAJIN-TERB2 2:2 hetero-tetramer binds strongly to DNA and is tethered through long flexible linkers to the inner nuclear membrane and two TRF1-binding 1:1 TERB2-TERB1 complexes. Our complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate.},
  language  = {en}
}
@article{DummerPosseckertNestleetal.1992,
  author    = {Dummer, R. and Posseckert, G. and Nestle, F. and Witzgall, R. and Burger, M. and Becker, J. C. and Sch{\"a}fer, E. and Wiede, J. and Sebald, Walter and Burg, G.},
  title     = {Soluble interleukin-2 receptors inhibit interleukin 2-dependent proliferation and cytotoxicity: explanation for diminished natural killer cell activity in cutaneous T-cell lymphomas in vivo?},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62473},
  year      = {1992},
  abstract  = {No abstract available},
  subject      = {Biochemie},
  language  = {en}
}
@article{DuWuertzAdolfietal.2019,
  author    = {Du, Kang and Wuertz, Sven and Adolfi, Mateus and Kneitz, Susanne and St{\"o}ck, Matthias and Oliveira, Marcos and N{\´o}brega, Rafael and Ormanns, Jenny and Kloas, Werner and Feron, Romain and Klopp, Christophe and Parrinello, Hugues and Journot, Laurent and He, Shunping and Postlethwait, John and Meyer, Axel and Guiguen, Yann and Schartl, Manfred},
  title     = {The genome of the arapaima (Arapaima gigas) provides insights into gigantism, fast growth and chromosomal sex determination system},
  series = {Scientific Reports},
  volume    = {9},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-019-41457-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201333},
  pages     = {5293},
  year      = {2019},
  abstract  = {We have sequenced the genome of the largest freshwater fish species of the world, the arapaima. Analysis of gene family dynamics and signatures of positive selection identified genes involved in the specific adaptations and unique features of this iconic species, in particular it's large size and fast growth. Genome sequences from both sexes combined with RAD-tag analyses from other males and females led to the isolation of male-specific scaffolds and supports an XY sex determination system in arapaima. Whole transcriptome sequencing showed that the product of the gland-like secretory organ on the head surface of males and females may not only provide nutritional fluid for sex-unbiased parental care, but that the organ itself has a more specific function in males, which engage more in parental care.},
  language  = {en}
}
@article{DuMaYanez‐Serranoetal.2021,
  author    = {Du, Baoguo and Ma, Yuhua and Y{\´a}{\~n}ez-Serrano, Ana Maria and Arab, Leila and Fasbender, Lukas and Alfarraj, Saleh and Albasher, Gadah and Hedrich, Rainer and White, Philip J. and Werner, Christiane and Rennenberg, Heinz},
  title     = {Physiological responses of date palm (Phoenix dactylifera) seedlings to seawater and flooding},
  series = {New Phytologist},
  volume    = {229},
  journal   = {New Phytologist},
  number    = {6},
  doi       = {10.1111/nph.17123},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228226},
  pages     = {3318 -- 3329},
  year      = {2021},
  abstract  = {In their natural environment along coast lines, date palms are exposed to seawater inundation and, hence, combined stress by salinity and flooding. To elucidate the consequences of this combined stress on foliar gas exchange and metabolite abundances in leaves and roots, date palm seedlings were exposed to flooding with seawater and its major constituents under controlled conditions. Seawater flooding significantly reduced CO\(_{2}\) assimilation, transpiration and stomatal conductance, but did not affect isoprene emission. A similar effect was observed upon NaCl exposure. By contrast, flooding with distilled water or MgSO\(_{4}\) did not affect CO\(_{2}\)/H\(_{2}\)O gas exchange or stomatal conductance significantly, indicating that neither flooding itself, nor seawater sulfate, contributed greatly to stomatal closure. Seawater exposure increased Na and Cl contents in leaves and roots, but did not affect sulfate contents significantly. Metabolite analyses revealed reduced abundances of foliar compatible solutes, such as sugars and sugar alcohols, whereas nitrogen compounds accumulated in roots. Reduced transpiration upon seawater exposure may contribute to controlling the movement of toxic ions to leaves and, therefore, can be seen as a mechanism to cope with salinity. The present results indicate that date palm seedlings are tolerant towards seawater exposure to some extent, and highly tolerant to flooding.},
  language  = {en}
}
@article{DreschersSauppHornefetal.2016,
  author    = {Dreschers, Stephan and Saupp, Peter and Hornef, Mathias and Prehn, Andrea and Platen, Christopher and Morschh{\"a}user, Joachim and Orlikowsky, Thorsten W.},
  title     = {Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans},
  series = {PLoS ONE},
  volume    = {11},
  journal   = {PLoS ONE},
  number    = {11},
  doi       = {10.1371/journal.pone.0166648},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166778},
  pages     = {e0166648},
  year      = {2016},
  abstract  = {Background Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). Hypothesis Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses. Methods The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor). Results Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO). Conclusion Our data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO.},
  language  = {en}
}
@article{DrescherKleinSchmittetal.2019,
  author    = {Drescher, Nora and Klein, Alexandra-Maria and Schmitt, Thomas and Leonhardt, Sara Diana},
  title     = {A clue on bee glue: New insight into the sources and factors driving resin intake in honeybees (Apis mellifera)},
  series = {PLoS ONE},
  volume    = {14},
  journal   = {PLoS ONE},
  number    = {2},
  doi       = {10.1371/journal.pone.0210594},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200935},
  pages     = {e0210594},
  year      = {2019},
  abstract  = {Honeybees (Apis mellifera) are threatened by numerous pathogens and parasites. To prevent infections they apply cooperative behavioral defenses, such as allo-grooming and hygiene, or they use antimicrobial plant resin. Resin is a chemically complex and highly variable mixture of many bioactive compounds. Bees collect the sticky material from different plant species and use it for nest construction and protection. Despite its importance for colony health, comparatively little is known about the precise origins and variability in resin spectra collected by honeybees. To identify the botanical resin sources of A. mellifera in Western Europe we chemically compared resin loads of individual foragers and tree resins. We further examined the resin intake of 25 colonies from five different apiaries to assess the effect of location on variation in the spectra of collected resin. Across all colonies and apiaries, seven distinct resin types were categorized according to their color and chemical composition. Matches between bee-collected resin and tree resin indicated that bees used poplar (Populus balsamifera, P. x canadensis), birch (Betula alba), horse chestnut (Aesculus hippocastanum) and coniferous trees (either Picea abies or Pinus sylvestris) as resin sources. Our data reveal that honeybees collect a comparatively broad and variable spectrum of resin sources, thus assuring protection against a variety of antagonists sensitive to different resins and/or compounds. We further unravel distinct preferences for specific resins and resin chemotypes, indicating that honeybees selectively search for bioactive resin compounds.},
  language  = {en}
}
@article{DrescherKleinNeumannetal.2017,
  author    = {Drescher, Nora and Klein, Alexandra-Maria and Neumann, Peter and Ya{\~n}ez, Orlando and Leonhardt, Sara D.},
  title     = {Inside Honeybee Hives: Impact of Natural Propolis on the Ectoparasitic Mite Varroa destructor and Viruses},
  series = {Insects},
  volume    = {8},
  journal   = {Insects},
  number    = {1},
  doi       = {10.3390/insects8010015},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171164},
  pages     = {15},
  year      = {2017},
  abstract  = {Social immunity is a key factor for honeybee health, including behavioral defense strategies such as the collective use of antimicrobial plant resins (propolis). While laboratory data repeatedly show significant propolis effects, field data are scarce, especially at the colony level. Here, we investigated whether propolis, as naturally deposited in the nests, can protect honeybees against ectoparasitic mites Varroa destructor and associated viruses, which are currently considered the most serious biological threat to European honeybee subspecies, Apis mellifera, globally. Propolis intake of 10 field colonies was manipulated by either reducing or adding freshly collected propolis. Mite infestations, titers of deformed wing virus (DWV) and sacbrood virus (SBV), resin intake, as well as colony strength were recorded monthly from July to September 2013. We additionally examined the effect of raw propolis volatiles on mite survival in laboratory assays. Our results showed no significant effects of adding or removing propolis on mite survival and infestation levels. However, in relation to V. destructor, DWV titers increased significantly less in colonies with added propolis than in propolis-removed colonies, whereas SBV titers were similar. Colonies with added propolis were also significantly stronger than propolis-removed colonies. These findings indicate that propolis may interfere with the dynamics of V. destructor-transmitted viruses, thereby further emphasizing the importance of propolis for honeybee health.},
  language  = {en}
}
@article{DrescherBluethgenSchmittetal.2010,
  author    = {Drescher, Jochen and Bluethgen, Nico and Schmitt, Thomas and Buehler, Jana and Feldhaar, Heike},
  title     = {Societies Drifting Apart? Behavioural, Genetic and Chemical Differentiation between Supercolonies in the Yellow Crazy Ant Anoplolepis gracilipes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68573},
  year      = {2010},
  abstract  = {Background: In populations of most social insects, gene flow is maintained through mating between reproductive individuals from different colonies in periodic nuptial flights followed by dispersal of the fertilized foundresses. Some ant species, however, form large polygynous supercolonies, in which mating takes place within the maternal nest (intranidal mating) and fertilized queens disperse within or along the boundary of the supercolony, leading to supercolony growth (colony budding). As a consequence, gene flow is largely confined within supercolonies. Over time, such supercolonies may diverge genetically and, thus, also in recognition cues (cuticular hydrocarbons, CHC's) by a combination of genetic drift and accumulation of colony-specific, neutral mutations. Methodology/Principal Findings: We tested this hypothesis for six supercolonies of the invasive ant Anoplolepis gracilipes in north-east Borneo. Within supercolonies, workers from different nests tolerated each other, were closely related and showed highly similar CHC profiles. Between supercolonies, aggression ranged from tolerance to mortal encounters and was negatively correlated with relatedness and CHC profile similarity. Supercolonies were genetically and chemically distinct, with mutually aggressive supercolony pairs sharing only 33.1\%617.5\% (mean 6 SD) of their alleles across six microsatellite loci and 73.8\%611.6\% of the compounds in their CHC profile. Moreover, the proportion of alleles that differed between supercolony pairs was positively correlated to the proportion of qualitatively different CHC compounds. These qualitatively differing CHC compounds were found across various substance classes including alkanes, alkenes and mono-, di- and trimethyl-branched alkanes. Conclusions: We conclude that positive feedback between genetic, chemical and behavioural traits may further enhance supercolony differentiation through genetic drift and neutral evolution, and may drive colonies towards different evolutionary pathways, possibly including speciation.},
  subject      = {Ameisen},
  language  = {en}
}
@phdthesis{Drescher2011,
  author    = {Drescher, Jochen},
  title     = {The Ecology and Population structure of the invasive Yelllow Crazy Ant Anoplolepis gracilipes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-57332},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {The invasive Yellow Crazy Ant Anoplolepis gracilipes is a widespread tropical ant species which is particularly common in anthropogenically disturbed habitats in South-East Asia and the Indopacific region. Its native range is unknown, and there is little information concerning its social structure as a potential mechanism facilitating invasion as well as its ecology in one of the putative native ranges, South-East Asia. Using mitochondrial DNA sequences, I demonstrated that the majority of the current Indopacific colonies were likely introduced from South-East Asian populations, which in turn may have been introduced much earlier from a yet unidentified native range. By conducting behavioral, genetic and chemical analyses, I found that A. gracilipes supercolonies contain closely related individuals, thus resembling enlarged versions of monogynous, polydomous colonies of other ant species. Furthermore, mutually aggressive A. gracilipes supercolonies were highly differentiated both genetically and chemically, suggesting limited or even absent gene flow between supercolonies. Intranidal mating and colony-budding are most likely the predominant, if not the exclusive mode of reproduction and dispersal strategy of A. gracilipes. Consequently, a positive feedback between genetic, chemical and behavioral traits may further enhance supercolony differentiation though genetic drift and neutral evolution. This potential scenario led to the hypothesis that absent gene flow between different A. gracilipes supercolonies may drive them towards different evolutionary pathways, possibly including speciation. Thus, I examined one potential way by which gene flow between supercolonies of an ant species without nuptial flights may be maintained, i.e. the immigration of sexuals into foreign supercolonies. The results suggest that this option of maintaining gene flow between different supercolonies is likely impaired by severe aggression of workers towards allocolonial sexuals. Moreover, breeding experiments involving males and queens from different supercolonies suggest that A. gracilipes supercolonies may already be on the verge of reproductive isolation, which might lead to the diversification of A. gracilipes into different species. Regarding the ecological consequences of its potential introduction to NE-Borneo, I could show that A. gracilipes supercolonies may affect the local ant fauna. The ant community within supercolonies was less diverse and differed in species composition from areas outside supercolonies. My data suggest that the ecological dominance of A. gracilipes within local ant communities was facilitated by monopolization of food sources within its supercolony territory, achieved by a combination of rapid recruitment, numerical dominance and pronounced interspecific aggression. A. gracilipes' distribution is almost exclusively limited to anthropogenically altered habitat, such as residential and agricultural areas. The rate at which habitat conversion takes place in NE-Borneo will provide A. gracilipes with a rapidly increasing abundance of suitable habitats, thus potentially entailing significant population growth. An potentially increasing population size and ecological dominance, however, are not features that are limited to invasive alien species, but may also occur in native species that become 'pests' in an increasing abundance of anthropogenically altered habitat. Lastly, I detected several ant guests in supercolonies of A. gracilipes. I subsequently describe the relationship between one of them (the cricket Myrmecophilus pallidithorax) and its ant host. By conducting behavioral bioassays and analyses of cuticular hydrocarbon (CHC) profiles, I revealed that although M. pallidithorax is attacked and consumed by A. gracilipes whenever possible, it may evade aggression from its host by a combination of supreme agility and, possibly, chemical deception. This thesis adds to our general understanding of biological invasions by contributing species-specific data on a previously understudied invasive organism, the Yellow Crazy Ant Anoplolepis gracilipes. Introductions which may have occurred a long time ago may make it difficult to determine whether a given species is an introduced invader or a native pest species, as both may have pronounced ecological effects in native species communities. Furthermore, this thesis suggests that supercolonialism in invasive ants may not be an evolutionary dead end, but that it may possibly give rise to new species due to reproductive boundaries between supercolonies evoked by peculiar mating and dispersal strategies.},
  subject      = {Dem{\"o}kologie},
  language  = {en}
}
@phdthesis{Drechsler2008,
  author    = {Drechsler, Patrick Hans},
  title     = {Mechanics of adhesion and friction in stick insects and tree frogs},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-26836},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Many arthropods and vertebrates can cling to surfaces using adhesive pads on their legs. These pads are either smooth and characterised by a specialised, soft cuticle or they are hairy, i.e. densely covered with flexible adhesive setae. Animals climbing with adhesive organs are able to control attachment and detachment dynamically while running. The detailed mechanisms of how tarsal pads generate adhesive and frictional forces and how forces are controlled during locomotion are still largely unclear. The aim of this study was to clarify the attachment mechanism of smooth adhesive pads as present in many insects and tree frogs. To understand the function of these fluid-based adhesive systems, I characterized their performance under standardized conditions. To this end, experiments were conducted by simultaneously measuring adhesion, friction, and contact area in single adhesive pads. The first result of this study showed that friction in stick insect attachment pads is anisotropic: Attachment pads regularly detached when slid away from the body. Further analyses of "immobilized" arolia revealed that this anisotropy is not caused by an increased shear stress in the proximal direction, but by the instability of the tarsus when pushed distally. In the second part of this study, I analysed the role of the pad secretion present in insects and tree frogs. In stick insects, shear stress was largely independent of normal force and increased with velocity, seemingly consistent with the viscosity effect of a continuous fluid film. However, measurements of the remaining force two minutes after a sliding movement showed that adhesive pads could sustain considerable static friction in insects and tree frogs. Repeated sliding movements and multiple consecutive pull-offs of stick insect single legs to deplete adhesive secretion showed that on a smooth surface, friction and adhesion strongly increased with decreasing amount of fluid in insects. In contrast, stick insect pull-off forces significantly decreased on a rough substrate. Thus, the secretion does not generally increase attachment but does so only on rough substrates, where it helps to maximize contact area. When slides with stick insect arolia were repeated at one position so that secretion could accumulate, sliding shear stress decreased but static friction remained clearly present. This suggests that static friction in stick insects, which is biologically important to prevent sliding, is based on non-Newtonian properties of the adhesive emulsion rather than on a direct contact between the cuticle and the substrate. \% Analogous measurements in toe pads of tree frogs showed that they are also able to generate static friction, even though their pads are wetted by mucus. In contrast to the mechanism proposed for insects, static friction in tree frogs apparently results from the very close contact of toe pads to the substrate and boundary lubrication. In the last section of this study, I investigated adhesive forces and the mode of detachment by performing pull-off measurements at different velocities and preloads. These experiments showed that preload has only an increasing effect on adhesion for faster pull-offs. This can be explained by the viscoelastic material properties of the stick insect arolium, which introduce a strong rate-dependence of detachment. During fast pull-offs, forces can spread over the complete area of contact, leading to forces scaling with area. In contrast, the pad material has sufficient time to withdraw elastically and peel during slow detachments. Under these conditions the adhesive force will concentrate on the circumference of the contact area, therefore scaling with a length, supporting models such as the peeling theory. The scaling of single-pad forces supported these conclusions, but large variation between pads of different stick insects did not allow statistically significant conclusions. In contrast, when detachment forces were quantified for whole insects using a centrifuge, forces scaled with pad contact area and not with length.},
  subject      = {Biomechanik},
  language  = {en}
}
@article{DrakulićFeldhaarLisičićetal.2016,
  author    = {Drakulić, Sanja and Feldhaar, Heike and Lisičić, Duje and Mioč, Mia and Cizelj, Ivan and Seiler, Michael and Spatz, Theresa and R{\"o}del, Mark-Oliver},
  title     = {Population-specific effects of developmental temperature on body condition and jumping performance of a widespread European frog},
  series = {Ecology and Evolution},
  volume    = {6},
  journal   = {Ecology and Evolution},
  number    = {10},
  doi       = {10.1002/ece3.2113},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164960},
  pages     = {3115-3128},
  year      = {2016},
  abstract  = {All physiological processes of ectotherms depend on environmental temperature. Thus, adaptation of physiological mechanisms to the thermal environments is important for achieving optimal performance and fitness. The European Common Frog, Rana temporaria, is widely distributed across different thermal habitats. This makes it an exceptional model for studying the adaptations to different thermal conditions. We raised tadpoles from Germany and Croatia at two constant temperature treatments (15°C, 20°C), and under natural temperature fluctuations (in outdoor treatments), and tested how different developmental temperatures affected developmental traits, that is, length of larval development, morphometrics, and body condition, as well as jumping performance of metamorphs. Our results revealed population-specific differences in developmental time, body condition, and jumping performance. Croatian frogs developed faster in all treatments, were heavier, in better body condition, and had longer hind limbs and better jumping abilities than German metamorphs. The populations further differed in thermal sensitivity of jumping performance. While metamorphs from Croatia increased their jumping performance with higher temperatures, German metamorphs reached their performance maximum at lower temperatures. These population-specific differences in common environments indicate local genetic adaptation, with southern populations being better adapted to higher temperatures than those from north of the Alps.},
  language  = {en}
}
@article{DracopoliFeltquateSametal.1990,
  author    = {Dracopoli, Nicholas C. and Feltquate, David M. and Sam, Brigitta and Schartl, Manfred},
  title     = {Taql and Mspl RFLPs are detected by the human 2,3-biphosphoglycerate mutase (BPGM) cDNA},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61763},
  year      = {1990},
  abstract  = {No abstract available},
  subject      = {Physiologische Chemie},
  language  = {en}
}
@article{DotterweichSchlegelmilchKelleretal.2016,
  author    = {Dotterweich, Julia and Schlegelmilch, Katrin and Keller, Alexander and Geyer, Beate and Schneider, Doris and Zeck, Sabine and Tower, Robert J. J. and Ebert, Regina and Jakob, Franz and Sch{\"u}tze, Norbert},
  title     = {Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease},
  series = {Bone},
  volume    = {93},
  journal   = {Bone},
  doi       = {10.1016/j.bone.2016.08.006},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-186688},
  pages     = {155-166},
  year      = {2016},
  abstract  = {Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.},
  language  = {en}
}
@article{DossoYeoKonateetal.2012,
  author    = {Dosso, Kanvaly and Yeo, Kolo and Konate, Souleymane and Linsenmair, Karl Eduard},
  title     = {Importance of protected areas for biodiversity conservation in central Cote d'Ivoire: Comparison of termite assemblages between two neighboring areas under differing levels of disturbance},
  series = {Journal of Insect Science},
  volume    = {12},
  journal   = {Journal of Insect Science},
  number    = {131},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133218},
  year      = {2012},
  abstract  = {To highlight human impact on biodiversity in the Lamto region, termites were studied with regard to their use as bio-indicators of habitat change in the tropics. Using a standardized method, termites were sampled in the three most common habitat types, i.e., in semi-deciduous forest, savanna woodland, and annually burned savanna, all inside Lamto Reserve and its surrounding rural domain. Termite species richness fell from 25 species in the Lamto forest to 13 species in the rural area, involving strong modification in the species composition (species turnover = 59 \%). In contrast, no significant change in diversity was found between the Lamto savannas and the rural ones. In addition, the relative abundance of termites showed a significantly greater decline in the rural domain, even in the species Ancistrotermes cavithorax (Sjostedt) (Isoptera: Termitidae), which is known to be ecologically especially versatile. Overall, the findings of this study suggest further investigation around Lamto Reserve on the impact of human activities on biodiversity, focusing on forest conversion to land uses (e.g. agricultural and silvicultural systems).},
  language  = {en}
}
@phdthesis{Dornhaus2002,
  author    = {Dornhaus, Anna},
  title     = {The role of communication in the foraging process of social bees},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3468},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {In the various groups of social bees, different systems of communication about food sources occur. These communication systems are different solutions to a common problem of social insects: efficiently allocating the necessary number of workers first to the task of foraging and second to the most profitable food sources. The solution chosen by each species depends on the particular ecological circumstances as well as the evolutionary history of that species. For example, the outstanding difference between the bumble bee and the honey bee system is that honey bees can communicate the location of profitable food sources to nestmates, which bumble bees cannot. To identify possible selection pressures that could explain this difference, I have quantified the benefits of communicating location in honey bees. I show that these strongly depend on the habitat, and that communicating location might not benefit bees in temperate habitats. This could be due to the differing spatial distributions of resources in different habitats, in particular between temperate and tropical regions. These distributions may be the reason why the mostly temperate-living bumble bees have never evolved a communication system that allows them to transfer information on location of food sources, whereas most tropical social bees (all honey bees and many stingless bees) are able to recruit nestmates to specific points in their foraging range. Nevertheless, I show that in bumble bees the allocation of workers to foraging is also regulated by communication. Successful foragers distribute in the nest a pheromone which alerts other bees to the presence of food. This pheromone stems from a tergite gland, the function of which had not been identified previously. Usage of a pheromone in the nest to alert other individuals to forage has not been described in other social insects, and might constitute a new mode of communicating about food sources. The signal might be modulated depending on the quality of the food source. Bees in the nest sample the nectar that has been brought into the nest. Their decision whether to go out and forage depends not only on the pheromone signal, but also on the quality of the nectar they have sampled. In this way, foraging activity of a bumble bee colony is adjusted to foraging conditions, which means most bees are allocated to foraging only if high-quality food sources are available. In addition, foraging activity is adjusted to the amount of food already stored. In a colony with full honeypots, no new bees are allocated to foraging. These results help us understand how the allocation of workers to the task of food collection is regulated according to external and internal nest conditions in bumble bees.},
  subject      = {Hummel},
  language  = {en}
}
@article{DopplerSchusterAppeltshauseretal.2019,
  author    = {Doppler, Kathrin and Schuster, Yasmin and Appeltshauser, Luise and Biko, Lydia and Villmann, Carmen and Weishaupt, Andreas and Werner, Christian and Sommer, Claudia},
  title     = {Anti-CNTN1 IgG3 induces acute conduction block and motor deficits in a passive transfer rat model},
  series = {Journal of Neuroinflammation},
  volume    = {16},
  journal   = {Journal of Neuroinflammation},
  number    = {73},
  doi       = {10.1186/s12974-019-1462-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200476},
  year      = {2019},
  abstract  = {Background: Autoantibodies against the paranodal protein contactin-1 have recently been described in patients with severe acute-onset autoimmune neuropathies and mainly belong to the IgG4 subclass that does not activate complement. IgG3 anti-contactin-1 autoantibodies are rare, but have been detected during the acute onset of disease in some cases. There is evidence that anti-contactin-1 prevents adhesive interaction, and chronic exposure to anti-contactin-1 IgG4 leads to structural changes at the nodes accompanied by neuropathic symptoms. However, the pathomechanism of acute onset of disease and the pathogenic role of IgG3 anti-contactin-1 is largely unknown. Methods: In the present study, we aimed to model acute autoantibody exposure by intraneural injection of IgG of patients with anti-contacin-1 autoantibodies to Lewis rats. Patient IgG obtained during acute onset of disease (IgG3 predominant) and IgG from the chronic phase of disease (IgG4 predominant) were studied in comparison. Results: Conduction blocks were measured in rats injected with the "acute" IgG more often than after injection of "chronic" IgG (83.3\% versus 35\%) and proved to be reversible within a week after injection. Impaired nerve conduction was accompanied by motor deficits in rats after injection of the "acute" IgG but only minor structural changes of the nodes. Paranodal complement deposition was detected after injection of the "acute IgG". We did not detect any inflammatory infiltrates, arguing against an inflammatory cascade as cause of damage to the nerve. We also did not observe dispersion of paranodal proteins or sodium channels to the juxtaparanodes as seen in patients after chronic exposure to anti-contactin-1. Conclusions: Our data suggest that anti-contactin-1 IgG3 induces an acute conduction block that is most probably mediated by autoantibody binding and subsequent complement deposition and may account for acute onset of disease in these patients. This supports the notion of anti-contactin-1-associated neuropathy as a paranodopathy with the nodes of Ranvier as the site of pathogenesis.},
  language  = {en}
}
@article{DongBoeppleThieletal.2023,
  author    = {Dong, Meng and B{\"o}pple, Kathrin and Thiel, Julia and Winkler, Bernd and Liang, Chunguang and Schueler, Julia and Davies, Emma J. and Barry, Simon T. and Metsalu, Tauno and M{\"u}rdter, Thomas E. and Sauer, Georg and Ott, German and Schwab, Matthias and Aulitzky, Walter E.},
  title     = {Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions},
  series = {Cells},
  volume    = {12},
  journal   = {Cells},
  number    = {5},
  issn      = {2073-4409},
  doi       = {10.3390/cells12050807},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311030},
  year      = {2023},
  abstract  = {Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air-liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses.},
  language  = {en}
}
@article{DollVonaSchnappetal.2020,
  author    = {Doll, Julia and Vona, Barbara and Schnapp, Linda and R{\"u}schendorf, Franz and Khan, Imran and Khan, Saadullah and Muhammad, Noor and Alam Khan, Sher and Nawaz, Hamed and Khan, Ajmal and Ahmad, Naseer and Kolb, Susanne M. and K{\"u}hlewein, Laura and Labonne, Jonathan D. J. and Layman, Lawrence C. and Hofrichter, Michaela A. H. and R{\"o}der, Tabea and Dittrich, Marcus and M{\"u}ller, Tobias and Graves, Tyler D. and Kong, Il-Keun and Nanda, Indrajit and Kim, Hyung-Goo and Haaf, Thomas},
  title     = {Genetic Spectrum of Syndromic and Non-Syndromic Hearing Loss in Pakistani Families},
  series = {Genes},
  volume    = {11},
  journal   = {Genes},
  number    = {11},
  issn      = {2073-4425},
  doi       = {10.3390/genes11111329},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219293},
  year      = {2020},
  abstract  = {The current molecular genetic diagnostic rates for hereditary hearing loss (HL) vary considerably according to the population background. Pakistan and other countries with high rates of consanguineous marriages have served as a unique resource for studying rare and novel forms of recessive HL. A combined exome sequencing, bioinformatics analysis, and gene mapping approach for 21 consanguineous Pakistani families revealed 13 pathogenic or likely pathogenic variants in the genes GJB2, MYO7A, FGF3, CDC14A, SLITRK6, CDH23, and MYO15A, with an overall resolve rate of 61.9\%. GJB2 and MYO7A were the most frequently involved genes in this cohort. All the identified variants were either homozygous or compound heterozygous, with two of them not previously described in the literature (15.4\%). Overall, seven missense variants (53.8\%), three nonsense variants (23.1\%), two frameshift variants (15.4\%), and one splice-site variant (7.7\%) were observed. Syndromic HL was identified in five (23.8\%) of the 21 families studied. This study reflects the extreme genetic heterogeneity observed in HL and expands the spectrum of variants in deafness-associated genes.},
  language  = {en}
}
@article{DollKolbSchnappetal.2020,
  author    = {Doll, Julia and Kolb, Susanne and Schnapp, Linda and Rad, Aboulfazl and R{\"u}schendorf, Franz and Khan, Imran and Adli, Abolfazl and Hasanzadeh, Atefeh and Liedtke, Daniel and Knaup, Sabine and Hofrichter, Michaela AH and M{\"u}ller, Tobias and Dittrich, Marcus and Kong, Il-Keun and Kim, Hyung-Goo and Haaf, Thomas and Vona, Barbara},
  title     = {Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {1},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21010311},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285142},
  year      = {2020},
  abstract  = {CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.},
  language  = {en}
}
@article{DoerflerCadotteWeisseretal.2020,
  author    = {Doerfler, Inken and Cadotte, Marc W. and Weisser, Wolfgang W. and M{\"u}ller, J{\"o}rg and Gossner, Martin M. and Heibl, Christoph and B{\"a}ssler, Claus and Thorn, Simon and Seibold, Sebastian},
  title     = {Restoration-oriented forest management affects community assembly patterns of deadwood-dependent organisms},
  series = {Journal of Applied Ecology},
  volume    = {57},
  journal   = {Journal of Applied Ecology},
  number    = {12},
  doi       = {10.1111/1365-2664.13741},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217918},
  pages     = {2429 -- 2440},
  year      = {2020},
  abstract  = {Land-use intensification leads to loss and degradation of habitats and is thus a major driver of biodiversity loss. Restoration strategies typically focus on promoting biodiversity but often neglect that land-use intensification could have changed the underlying mechanisms of community assembly. Since assembly mechanisms determine the diversity and composition of communities, we propose that evaluation of restoration strategies should consider effects of restoration on biodiversity and community assembly. Using a multi-taxon approach, we tested whether a strategy that promotes forest biodiversity by restoring deadwood habitats also affects assembly patterns. We assessed saproxylic (i.e. deadwood-dependent) beetles and fungi, as well as non-saproxylic plants and birds in 68 beech forest plots in southern Germany, 8 years after the commencement of a restoration project. To assess changes in community assembly, we analysed the patterns of functional-phylogenetic diversity, community-weighted mean (CWM) traits and their diversity. We hypothesized that restoration increases habitat amount and heterogeneity of deadwood and reduces canopy cover and thereby decreases the strength of environmental filters imposed by past silvicultural intensification, such as a low amount in deadwood. With the restoration of deadwood habitats, saproxylic beetle communities became less functionally-phylogenetically similar, whereas the assembly patterns of saproxylic fungi and non-saproxylic taxa remained unaffected by deadwood restoration. Among the traits analysed, deadwood diameter niche position of species was most strongly affected indicating that the enrichment of large deadwood objects led to lower functional-phylogenetical similarity of saproxylic beetles. Community assembly and traits of plants were mainly influenced by microclimate associated with changes in canopy cover. Synthesis and applications. Our results indicate that the positive effects of deadwood restoration on saproxylic beetle richness are associated with an increase in deadwood amount. This might be linked to an increase in deadwood heterogeneity, and therefore decreasing management-induced environmental filters. Deadwood enrichment can thus be considered an effective restoration strategy which reduces the negative effects of intense forest management on saproxylic taxa by not only promoting biodiversity but also by decreasing the environmental filters shaping saproxylic beetle communities, thus allowing the possibly for more interactions between species and a higher functional diversity.},
  language  = {en}
}
@article{DjuzenovaMemmelSukhorukovetal.2014,
  author    = {Djuzenova, Cholpon S. and Memmel, Simon and Sukhorukov, Vladimir L. and H{\"o}ring, Marcus and Westerling, Katherine and Fiedler, Vanessa and Katzer, Astrid and Krohne, Georg and Flentje, Michael},
  title     = {Cell Surface Area and Membrane Folding in Glioblastoma Cell Lines Differing in PTEN and p53 Status},
  doi       = {10.1371/journal.pone.0087052},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111322},
  year      = {2014},
  abstract  = {Glioblastoma multiforme (GBM) is characterized by rapid growth, invasion and resistance to chemo-/radiotherapy. The complex cell surface morphology with abundant membrane folds, microvilli, filopodia and other membrane extensions is believed to contribute to the highly invasive behavior and therapy resistance of GBM cells. The present study addresses the mechanisms leading to the excessive cell membrane area in five GBM lines differing in mutational status for PTEN and p53. In addition to scanning electron microscopy (SEM), the membrane area and folding were quantified by dielectric measurements of membrane capacitance using the single-cell electrorotation (ROT) technique. The osmotic stability and volume regulation of GBM cells were analyzed by video microscopy. The expression of PTEN, p53, mTOR and several other marker proteins involved in cell growth and membrane synthesis were examined by Western blotting. The combined SEM, ROT and osmotic data provided independent lines of evidence for a large variability in membrane area and folding among tested GBM lines. Thus, DK-MG cells (wild type p53 and wild type PTEN) exhibited the lowest degree of membrane folding, probed by the area-specific capacitance Cm = 1.9 µF/cm2. In contrast, cell lines carrying mutations in both p53 and PTEN (U373-MG and SNB19) showed the highest Cm values of 3.7-4.0 µF/cm2, which corroborate well with their heavily villated cell surface revealed by SEM. Since PTEN and p53 are well-known inhibitors of mTOR, the increased membrane area/folding in mutant GBM lines may be related to the enhanced protein and lipid synthesis due to a deregulation of the mTOR-dependent downstream signaling pathway. Given that membrane folds and extensions are implicated in tumor cell motility and metastasis, the dielectric approach presented here provides a rapid and simple tool for screening the biophysical cell properties in studies on targeting chemo- or radiotherapeutically the migration and invasion of GBM and other tumor types.},
  language  = {en}
}
@article{DjuzenovaFischerKatzeretal.2021,
  author    = {Djuzenova, Cholpon S. and Fischer, Thomas and Katzer, Astrid and Sisario, Dmitri and Korsa, Tessa and Streussloff, Gudrun and Sukhorukov, Vladimir L. and Flentje, Michael},
  title     = {Opposite effects of the triple target (DNA-PK/PI3K/mTOR) inhibitor PI-103 on the radiation sensitivity of glioblastoma cell lines proficient and deficient in DNA-PKcs},
  series = {BMC Cancer},
  volume    = {21},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-021-08930-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265826},
  year      = {2021},
  abstract  = {Background: Radiotherapy is routinely used to combat glioblastoma (GBM). However, the treatment efficacy is often limited by the radioresistance of GBM cells. Methods: Two GBM lines MO59K and MO59J, differing in intrinsic radiosensitivity and mutational status of DNA-PK and ATM, were analyzed regarding their response to DNA-PK/PI3K/mTOR inhibition by PI-103 in combination with radiation. To this end we assessed colony-forming ability, induction and repair of DNA damage by gamma H2AX and 53BP1, expression of marker proteins, including those belonging to NHEJ and HR repair pathways, degree of apoptosis, autophagy, and cell cycle alterations. Results: We found that PI-103 radiosensitized MO59K cells but, surprisingly, it induced radiation resistance in MO59J cells. Treatment of MO59K cells with PI-103 lead to protraction of the DNA damage repair as compared to drug-free irradiated cells. In PI-103-treated and irradiated MO59J cells the foci numbers of both proteins was higher than in the drug-free samples, but a large portion of DNA damage was quickly repaired. Another cell line-specific difference includes diminished expression of p53 in MO59J cells, which was further reduced by PI-103. Additionally, PI-103-treated MO59K cells exhibited an increased expression of the apoptosis marker cleaved PARP and increased subG1 fraction. Moreover, irradiation induced a strong G2 arrest in MO59J cells (similar to 80\% vs. similar to 50\% in MO59K), which was, however, partially reduced in the presence of PI-103. In contrast, treatment with PI-103 increased the G2 fraction in irradiated MO59K cells. Conclusions: The triple-target inhibitor PI-103 exerted radiosensitization on MO59K cells, but, unexpectedly, caused radioresistance in the MO59J line, lacking DNA-PK. The difference is most likely due to low expression of the DNA-PK substrate p53 in MO59J cells, which was further reduced by PI-103. This led to less apoptosis as compared to drug-free MO59J cells and enhanced survival via partially abolished cell-cycle arrest. The findings suggest that the lack of DNA-PK-dependent NHEJ in MO59J line might be compensated by DNA-PK independent DSB repair via a yet unknown mechanism.},
  language  = {en}
}
@article{DjuzenovaFiedlerMemmeletal.2019,
  author    = {Djuzenova, Cholpon S. and Fiedler, Vanessa and Memmel, Simon and Katzer, Astrid and Sisario, Dmitri and Brosch, Philippa K. and G{\"o}hrung, Alexander and Frister, Svenja and Zimmermann, Heiko and Flentje, Michael and Sukhorukov, Vladimir L.},
  title     = {Differential effects of the Akt inhibitor MK-2206 on migration and radiation sensitivity of glioblastoma cells},
  series = {BMC Cancer},
  volume    = {19},
  journal   = {BMC Cancer},
  doi       = {10.1186/s12885-019-5517-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200290},
  pages     = {299},
  year      = {2019},
  abstract  = {Background Most tumor cells show aberrantly activated Akt which leads to increased cell survival and resistance to cancer radiotherapy. Therefore, targeting Akt can be a promising strategy for radiosensitization. Here, we explore the impact of the Akt inhibitor MK-2206 alone and in combination with the dual PI3K and mTOR inhibitor PI-103 on the radiation sensitivity of glioblastoma cells. In addition, we examine migration of drug-treated cells. Methods Using single-cell tracking and wound healing migration tests, colony-forming assay, Western blotting, flow cytometry and electrorotation we examined the effects of MK-2206 and PI-103 and/or irradiation on the migration, radiation sensitivity, expression of several marker proteins, DNA damage, cell cycle progression and the plasma membrane properties in two glioblastoma (DK-MG and SNB19) cell lines, previously shown to differ markedly in their migratory behavior and response to PI3K/mTOR inhibition. Results We found that MK-2206 strongly reduces the migration of DK-MG but only moderately reduces the migration of SNB19 cells. Surprisingly, MK-2206 did not cause radiosensitization, but even increased colony-forming ability after irradiation. Moreover, MK-2206 did not enhance the radiosensitizing effect of PI-103. The results appear to contradict the strong depletion of p-Akt in MK-2206-treated cells. Possible reasons for the radioresistance of MK-2206-treated cells could be unaltered or in case of SNB19 cells even increased levels of p-mTOR and p-S6, as compared to the reduced expression of these proteins in PI-103-treated samples. We also found that MK-2206 did not enhance IR-induced DNA damage, neither did it cause cell cycle distortion, nor apoptosis nor excessive autophagy. Conclusions Our study provides proof that MK-2206 can effectively inhibit the expression of Akt in two glioblastoma cell lines. However, due to an aberrant activation of mTOR in response to Akt inhibition in PTEN mutated cells, the therapeutic window needs to be carefully defined, or a combination of Akt and mTOR inhibitors should be considered.},
  language  = {en}
}
@article{DjuzenovaFiedlerKatzeretal.2016,
  author    = {Djuzenova, Cholpon S. and Fiedler, Vanessa and Katzer, Astrid and Michel, Konstanze and Deckert, Stefanie and Zimmermann, Heiko and Sukhorukov, Vladimir L. and Flentje, Michael},
  title     = {Dual PI3K-and mTOR-inhibitor PI-103 can either enhance or reduce the radiosensitizing effect of the Hsp90 inhibitor NVP-AUY922 in tumor cells: The role of drug-irradiation schedule},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {25},
  doi       = {10.18632/oncotarget.9501},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177770},
  pages     = {38191-38209},
  year      = {2016},
  abstract  = {Inhibition of Hsp90 can increase the radiosensitivity of tumor cells. However, inhibition of Hsp90 alone induces the anti-apoptotic Hsp70 and thereby decreases radiosensitivity. Therefore, preventing Hsp70 induction can be a promising strategy for radiosensitization. PI-103, an inhibitor of PI3K and mTOR, has previously been shown to suppress the up-regulation of Hsp70. Here, we explore the impact of combining PI-103 with the Hsp90 inhibitor NVP-AUY922 in irradiated glioblastoma and colon carcinoma cells. We analyzed the cellular response to drug-irradiation treatments by colony-forming assay, expression of several marker proteins, cell cycle progression and induction/repair of DNA damage. Although PI-103, given 24 h prior to irradiation, slightly suppressed the NVP-AUY922-mediated up-regulation of Hsp70, it did not cause radiosensitization and even diminished the radiosensitizing effect of NVP-AUY922. This result can be explained by the activation of PI3K and ERK pathways along with G1-arrest at the time of irradiation. In sharp contrast, PI-103 not only exerted a radiosensitizing effect but also strongly enhanced the radiosensitization by NVP-AUY922 when both inhibitors were added 3 h before irradiation and kept in culture for 24 h. Possible reasons for the observed radiosensitization under this drug-irradiation schedule may be a down-regulation of PI3K and ERK pathways during or directly after irradiation, increased residual DNA damage and strong G2/M arrest 24 h thereafter. We conclude that duration of drug treatment before irradiation plays a key role in the concomitant targeting of PI3K/mTOR and Hsp90 in tumor cells.},
  language  = {en}
}
@article{DjakovicHennigReinischetal.2023,
  author    = {Djakovic, Lara and Hennig, Thomas and Reinisch, Katharina and Milić, Andrea and Whisnant, Adam W. and Wolf, Katharina and Weiß, Elena and Haas, Tobias and Grothey, Arnhild and J{\"u}rges, Christopher S. and Kluge, Michael and Wolf, Elmar and Erhard, Florian and Friedel, Caroline C. and D{\"o}lken, Lars},
  title     = {The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-40217-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358161},
  year      = {2023},
  abstract  = {Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.},
  language  = {en}
}
@article{DitzelKoenigMusembietal.2022,
  author    = {Ditzel, Pia and K{\"o}nig, Sebastian and Musembi, Peter and Peters, Marcell K.},
  title     = {Correlation between coral reef condition and the diversity and abundance of fishes and sea urchins on an East African coral reef},
  series = {Oceans},
  volume    = {3},
  journal   = {Oceans},
  number    = {1},
  issn      = {2673-1924},
  doi       = {10.3390/oceans3010001},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284503},
  pages     = {1 -- 14},
  year      = {2022},
  abstract  = {Coral reefs are one of the most diverse marine ecosystems, providing numerous ecosystem services. This present study investigated the relationship between coral reef condition and the diversity and abundance of fishes, on a heavily fished East African coral reef at Gazi Bay, Kenya. Underwater visual censuses were conducted on thirty 50 × 5 m belt transects to assess the abundance and diversity of fishes. In parallel, a 25-m length of each of the same transects was recorded with photo-quadrats to assess coral community structure and benthic characteristics. For statistical analyses, multi-model inference based on the Akaike Information Criterion was used to evaluate the support for potential predictor variables of coral reef and fish diversity. We found that coral genus richness was negatively correlated with the abundance of macroalgae, whereas coral cover was positively correlated with both the abundance of herbivorous invertebrates (sea urchins) and with fish family richness. Similarly, fish family richness appeared mainly correlated with coral cover and invertebrate abundance, although no correlates of fish abundance could be identified. Coral and fish diversity were very low, but it appears that, contrary to some locations on the same coast, sea urchin abundance was not high enough to be having a negative influence on coral and fish assemblages. Due to increasing threats to coral reefs, it is important to understand the relationship among the components of the coral reef ecosystem on overfished reefs such as that at Gazi Bay.},
  language  = {en}
}
@phdthesis{Dinev2001,
  author    = {Dinev, Dragomir},
  title     = {Analysis of the role of extracellular signal regulated kinase (ERK5) in the differentiation of muscle cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1180481},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {The MEK5/ ERK5 kinase module is a relatively new discovered mitogen-activated protein kinase (MAPK) signalling pathway with a poorly defined physiological function. Since ERK5 and its upstream activator MEK5 are abundant in skeletal muscle a function of the cascade during muscle differentiation was examined. ERK5 becomes activated upon induction of differentiation in mouse myoblasts. The selective activation of the pathway results in promoter activation of differentiation-specific genes, such as the cdk-inhibitor p21 gene, the myosin light chain (MLC1A) gene, or an E-box containing promoter element, where myogenic basic-helix-loop-helix proteins such as MyoD or myogenin bind. Moreover, myogenic differentiation is completely blocked, when ERK5 expression is inhibited by antisense RNA. The effect can be detected also on the expression level of myogenic determination and differentiation markers such as p21, MyoD and myogenin. Another new finding is that stable expression of ERK5 in C2C12 leads to differentiation like phenotype and to increased p21 expression levels under growth conditions. These results provide first evidence that the MEK5/ERK5 MAP kinase cascade is critical for early steps of muscle cell differentiation.},
  subject      = {Muskelzelle},
  language  = {en}
}
@phdthesis{Dindar2014,
  author    = {Dindar, G{\"u}lcin},
  title     = {Molecular basis for product-specificity of DOT1 methyltransferases in Trypanosoma brucei},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-102524},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Post-translational histone modifications (PTMs) such as methylation of lysine residues influence chromatin structure and function. PTMs are involved in different cellular processes such as DNA replication, transcription and cell differentiation. Deregulations of PTM patterns are responsible for a variety of human diseases including acute leukemia. DOT1 enzymes are highly conserved histone methyltransferases that are responsible for methylation of lysine 79 on histone H3 (H3K79). Most eukaryotes contain one single DOT1 enzyme, whereas African trypanosomes have two homologues, DOT1A and DOT1B, which methylate H3K76 (H3K76 is homologous to H3K79 in other organisms). DOT1A is essential and mediates mono- and di-methylations, whereas DOT1B additionally catalyzes tri-methylation of H3K76. However, a mechanistic understanding how these different enzymatic activities are achieved is lacking. This thesis exploits the fact that trypanosomes possess two DOT1 enzymes with different catalytic properties to understand the molecular basis for the differential product-specificity of DOT1 enzymes. A trypanosomal nucleosome reconstitution system was established to analyze methyltransferase activity under defined in vitro conditions. Homology modeling allowed the identification of critical residues within and outside the catalytic center that modulate product-specificity. Exchange of these residues transferred the product-specificity from one enzyme to the other and revealed regulatory domains adjacent to the catalytic center. This work provides the first evidence that few specific residues in DOT1 enzymes are crucial to catalyze methyl-state-specific reactions. These results have also consequences for the functional understanding of homologous enzymes in other eukaryotes.},
  subject      = {Histon-Methyltransferase},
  language  = {en}
}
@article{DietzHasseFerrarisetal.2013,
  author    = {Dietz, Mariana S. and Hasse, Daniel and Ferraris, Davide M. and G{\"o}hler, Antonia and Niemann, Hartmut H. and Heilemann, Mike},
  title     = {Single-molecule photobleaching reveals increased MET receptor dimerization upon ligand binding in intact cells},
  series = {BMC Biophysics},
  volume    = {6},
  journal   = {BMC Biophysics},
  number    = {6},
  issn      = {2046-1682},
  doi       = {10.1186/2046-1682-6-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121835},
  year      = {2013},
  abstract  = {Background: The human receptor tyrosine kinase MET and its ligand hepatocyte growth factor/scatter factor are essential during embryonic development and play an important role during cancer metastasis and tissue regeneration. In addition, it was found that MET is also relevant for infectious diseases and is the target of different bacteria, amongst them Listeria monocytogenes that induces bacterial uptake through the surface protein internalin B. Binding of ligand to the MET receptor is proposed to lead to receptor dimerization. However, it is also discussed whether preformed MET dimers exist on the cell membrane. Results: To address these issues we used single-molecule fluorescence microscopy techniques. Our photobleaching experiments show that MET exists in dimers on the membrane of cells in the absence of ligand and that the proportion of MET dimers increases significantly upon ligand binding. Conclusions: Our results indicate that partially preformed MET dimers may play a role in ligand binding or MET signaling. The addition of the bacterial ligand internalin B leads to an increase of MET dimers which is in agreement with the model of ligand-induced dimerization of receptor tyrosine kinases.},
  language  = {en}
}
@phdthesis{Dietemann2002,
  author    = {Dietemann, Vincent},
  title     = {Differentiation in reproductive potential and chemical communication of reproductive status in workers and queens of the ant Myrmecia gulosa},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-2202},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Division of reproductive labour in societies represents a topic of interest in evolutionary biology at least since Darwin. The puzzle of how helpers can be selected for, in spite of their reduced fertility has found an explanation in the kin selection theory: workers can overcome the cost of helping and of forgiving direct reproduction by rearing sufficiently related individuals. However, in the Hymenoptera, little is known on the proximate mechanisms that regulate the division of labour in colonies. Our knowledge is based on several "primitive" ants from the subfamily Ponerinae and two highly eusocial Hymenoptera species. In the former, the dominance hierarchies allowing for the establishment of individuals as reproductives are well understood. In contrast, the pheromonal mechanisms that help maintain their reproductive status are not understood. Similarly in "higher" ants, pheromonal regulation mechanisms of worker reproduction by queens remain largely unknown. The aim of this study is to determine the modalities of production, distribution and action, as well as the identity of the queen pheromones affecting worker reproduction in the ant Myrmecia gulosa. This species belongs to the poorly studied subfamily Myrmeciinae, which is endemic to the Australian region. The subfamily represents, together with the Ponerinae, the most "primitive" ants: their morphology is close to that of the hypothetical ancestor of ants, and the specialisation of queens is weaker than that of "higher" ants. Simple regulation mechanisms were therefore expected to facilitate the investigation. The first step in this study was to characterise the morphological specialisation of queens and workers, and to determine the differences in reproductive potential associated with this specialisation. This study contributes to our understanding of the link between regulation of division of reproductive labour and social complexity. Furthermore, it will help shed light on the reproductive biology in the poorly known subfamily Myrmeciinae. Queens were recognised by workers on the basis of cuticular as well as gland extracts or products. What is the exact function of the multiple pheromones identified and how they interact remains to be determined. This could help understand why queen "signal" in a "primitive" ant with weakly specialised queens such as M. gulosa appears to be as complex as in highly eusocial species. Primer pheromones act on workers? physiology and have long-term effect. Whether workers of M. gulosa reproduce or not is determined by the detection of a queen pheromone of this type. Direct physical contact with the queen is necessary for workers to detect this pheromone. Thus, the colony size of M. gulosa is compatible with a simple system of pheromone perception by workers based on direct physical contact with the queen. When prevented from establishing physical contact with their queen, some workers start to reproduce and are policed by nestmates. The low volatility of the cuticular hydrocarbons (CHCs), their repartition over the entire cuticle and the existence of queen and worker specific CHC profiles suggest that these chemicals constitute a queen pheromone. Importance of HC versus non-HC compounds was confirmed by bioassaying purified fraction of both classes of chemicals. This study demonstrates for the first time that purified HCs indeed are at the basis of the recognition of reproductive status. This supports the idea that they are also at the basis of the recognition of queens by their workers. As CHCs profiles of workers and queens become similar with acquisition of reproductive status, they represent honest fertility markers. These markers could be used as signals of the presence of reproductives in the colonies, and represent the basis of the regulation of division of reproductive labour.},
  subject      = {Myrmecia gulosa},
  language  = {en}
}
@article{DiersBaumLehmannetal.2022,
  author    = {Diers, Johannes and Baum, Philip and Lehmann, Kai and Uttinger, Konstatin and Baumann, Nikolas and Pietryga, Sebastian and Hankir, Mohammed and Matthes, Niels and Lock, Johann F. and Germer, Christoph-Thomas and Wiegering, Armin},
  title     = {Disproportionately high failure to rescue rates after resection for colorectal cancer in the geriatric patient population - A nationwide study},
  series = {Cancer Medicine},
  volume    = {11},
  journal   = {Cancer Medicine},
  number    = {22},
  doi       = {10.1002/cam4.4784},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312858},
  pages     = {4256-4264},
  year      = {2022},
  abstract  = {Background Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in-hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. Methods All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in-hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Results Three lakh twenty-eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In-hospital mortality following colorectal cancer surgery was 4.9\% but geriatric patients displayed a significantly higher postoperative in-hospital mortality of 10.6\%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3\% for SSI and 29.9\% mortality for patients with AI, both p < 0.001). Logistic regression analysis adjusting for confounders showed that geriatric patients had almost five-times higher odds for death after surgery than the baseline age group below 60 (OR 4.86; 95\%CI [4.45-5.53], p < 0.001). Conclusion Geriatric patients have higher mortality after colorectal cancer surgery. This may be partly due to higher frailty and disproportionately higher rates of failure to rescue arising from postoperative complications.},
  language  = {en}
}
@article{DiersAcarWagneretal.2022,
  author    = {Diers, Johannes and Acar, Laura and Wagner, Johanna C. and Baum, Philip and Hankir, Mohammed and Flemming, Sven and Kastner, Carolin and Germer, Christoph-Thomas and L'hoest, Helmut and Marschall, Ursula and Lock, Johan Friso and Wiegering, Armin},
  title     = {Cancer diagnosis is one quarter lower than the expected cancer incidence in the first year of COVID-19 pandemic in Germany: A retrospective register-based cohort study},
  series = {Cancer Communications},
  volume    = {42},
  journal   = {Cancer Communications},
  number    = {7},
  doi       = {10.1002/cac2.12314},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312862},
  pages     = {673-676},
  year      = {2022},
  abstract  = {No abstract available.},
  language  = {en}
}
@article{DiersWagnerBaumetal.2020,
  author    = {Diers, J. and Wagner, J. and Baum, P. and Lichthardt, S. and Kastner, C. and Matthes, N. and Matthes, H. and Germer, C.-T. and L{\"o}b, S. and Wiegering, A.},
  title     = {Nationwide in-hospital mortality rate following rectal resection for rectal cancer according to annual hospital volume in Germany},
  series = {BJS Open},
  volume    = {4},
  journal   = {BJS Open},
  number    = {2},
  doi       = {10.1002/bjs5.50254},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-212878},
  pages     = {310 -- 319},
  year      = {2020},
  abstract  = {Background The impact of hospital volume after rectal cancer surgery is seldom investigated. This study aimed to analyse the impact of annual rectal cancer surgery cases per hospital on postoperative mortality and failure to rescue. Methods All patients diagnosed with rectal cancer and who had a rectal resection procedure code from 2012 to 2015 were identified from nationwide administrative hospital data. Hospitals were grouped into five quintiles according to caseload. The absolute number of patients, postoperative deaths and failure to rescue (defined as in-hospital mortality after a documented postoperative complication) for severe postoperative complications were determined. Results Some 64 349 patients were identified. The overall in-house mortality rate was 3·9 per cent. The crude in-hospital mortality rate ranged from 5·3 per cent in very low-volume hospitals to 2·6 per cent in very high-volume centres, with a distinct trend between volume categories (P < 0·001). In multivariable logistic regression analysis using hospital volume as random effect, very high-volume hospitals (53 interventions/year) had a risk-adjusted odds ratio of 0·58 (95 per cent c.i. 0·47 to 0·73), compared with the baseline in-house mortality rate in very low-volume hospitals (6 interventions per year) (P < 0·001). The overall postoperative complication rate was comparable between different volume quintiles, but failure to rescue decreased significantly with increasing caseload (15·6 per cent after pulmonary embolism in the highest volume quintile versus 38 per cent in the lowest quintile; P = 0·010). Conclusion Patients who had rectal cancer surgery in high-volume hospitals showed better outcomes and reduced failure to rescue rates for severe complications than those treated in low-volume hospitals.},
  language  = {en}
}
@article{DiersWagnerBaumetal.2019,
  author    = {Diers, J. and Wagner, J. and Baum, P. and Lichthardt, S. and Kastner, C. and Matthes, N. and L{\"o}b, S. and Matthes, H. and Germer, C.-T. and Wiegering, A.},
  title     = {Nationwide in-hospital mortality following colonic cancer resection according to hospital volume in Germany},
  series = {BJS Open},
  volume    = {3},
  journal   = {BJS Open},
  number    = {5},
  doi       = {10.1002/bjs5.50173},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204385},
  pages     = {672-677},
  year      = {2019},
  abstract  = {Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identifed from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5⋅8 per cent, ranging from 6⋅9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4⋅8 per cent (1239 of 25 825) in very high-volume centres (P < 0⋅001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0⋅75 (95 per cent c.i. 0⋅66 to 0⋅84) in very high-volume hospitals performing a mean of 85⋅0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12⋅7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals},
  language  = {en}
}
@article{DieboldSchoenemannEilersetal.2023,
  author    = {Diebold, Mathias and Sch{\"o}nemann, Lars and Eilers, Martin and Sotriffer, Christoph and Schindelin, Hermann},
  title     = {Crystal structure of a covalently linked Aurora-A-MYCN complex},
  series = {Acta Crystallographica},
  volume    = {D79},
  journal   = {Acta Crystallographica},
  doi       = {10.1107/s2059798322011433},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318855},
  pages     = {1 -- 9},
  year      = {2023},
  abstract  = {Formation of the Aurora-A-MYCN complex increases levels of the oncogenic transcription factor MYCN in neuroblastoma cells by abrogating its degradation through the ubiquitin proteasome system. While some small-molecule inhibitors of Aurora-A were shown to destabilize MYCN, clinical trials have not been satisfactory to date. MYCN itself is considered to be `undruggable' due to its large intrinsically disordered regions. Targeting the Aurora-A-MYCN complex rather than Aurora-A or MYCN alone will open new possibilities for drug development and screening campaigns. To overcome the challenges that a ternary system composed of Aurora-A, MYCN and a small molecule entails, a covalently cross-linked construct of the Aurora-A-MYCN complex was designed, expressed and characterized, thus enabling screening and design campaigns to identify selective binders.},
  language  = {en}
}
@article{DiaoMoussetHorsburghetal.2016,
  author    = {Diao, Wenwen and Mousset, Mathilde and Horsburgh, Gavin J. and Vermeulen, Cornelis J. and Johannes, Frank and van de Zande, Louis and Ritchie, Michael G. and Schmitt, Thomas and Beukeboom, Leo W.},
  title     = {Quantitative Trait Locus Analysis of Mating Behavior and Male Sex Pheromones in Nasonia Wasps},
  series = {G3: Genes Genomes Genetics},
  volume    = {6},
  journal   = {G3: Genes Genomes Genetics},
  number    = {6},
  doi       = {10.1534/g3.116.029074},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165412},
  pages     = {1549-1562},
  year      = {2016},
  abstract  = {A major focus in speciation genetics is to identify the chromosomal regions and genes that reduce hybridization and gene flow. We investigated the genetic architecture of mating behavior in the parasitoid wasp species pair Nasonia giraulti and Nasonia oneida that exhibit strong prezygotic isolation. Behavioral analysis showed that N. oneida females had consistently higher latency times, and broke off the mating sequence more often in the mounting stage when confronted with N. giraulti males compared with males of their own species. N. oneida males produce a lower quantity of the long-range male sex pheromone (4R,5S)-5-hydroxy-4-decanolide (RS-HDL). Crosses between the two species yielded hybrid males with various pheromone quantities, and these males were used in mating trials with females of either species to measure female mate discrimination rates. A quantitative trait locus (QTL) analysis involving 475 recombinant hybrid males (F2), 2148 reciprocally backcrossed females (F3), and a linkage map of 52 equally spaced neutral single nucleotide polymorphism (SNP) markers plus SNPs in 40 candidate mating behavior genes revealed four QTL for male pheromone amount, depending on partner species. Our results demonstrate that the RS-HDL pheromone plays a role in the mating system of N. giraulti and N. oneida, but also that additional communication cues are involved in mate choice. No QTL were found for female mate discrimination, which points at a polygenic architecture of female choice with strong environmental influences.},
  language  = {en}
}
@article{DhillonKuebertFlockDahmsetal.2023,
  author    = {Dhillon, Maninder Singh and K{\"u}bert-Flock, Carina and Dahms, Thorsten and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias},
  title     = {Evaluation of MODIS, Landsat 8 and Sentinel-2 data for accurate crop yield predictions: a case study using STARFM NDVI in Bavaria, Germany},
  series = {Remote Sensing},
  volume    = {15},
  journal   = {Remote Sensing},
  number    = {7},
  issn      = {2072-4292},
  doi       = {10.3390/rs15071830},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311132},
  year      = {2023},
  abstract  = {The increasing availability and variety of global satellite products and the rapid development of new algorithms has provided great potential to generate a new level of data with different spatial, temporal, and spectral resolutions. However, the ability of these synthetic spatiotemporal datasets to accurately map and monitor our planet on a field or regional scale remains underexplored. This study aimed to support future research efforts in estimating crop yields by identifying the optimal spatial (10 m, 30 m, or 250 m) and temporal (8 or 16 days) resolutions on a regional scale. The current study explored and discussed the suitability of four different synthetic (Landsat (L)-MOD13Q1 (30 m, 8 and 16 days) and Sentinel-2 (S)-MOD13Q1 (10 m, 8 and 16 days)) and two real (MOD13Q1 (250 m, 8 and 16 days)) NDVI products combined separately to two widely used crop growth models (CGMs) (World Food Studies (WOFOST), and the semi-empiric Light Use Efficiency approach (LUE)) for winter wheat (WW) and oil seed rape (OSR) yield forecasts in Bavaria (70,550 km\(^2\)) for the year 2019. For WW and OSR, the synthetic products' high spatial and temporal resolution resulted in higher yield accuracies using LUE and WOFOST. The observations of high temporal resolution (8-day) products of both S-MOD13Q1 and L-MOD13Q1 played a significant role in accurately measuring the yield of WW and OSR. For example, L- and S-MOD13Q1 resulted in an R\(^2\) = 0.82 and 0.85, RMSE = 5.46 and 5.01 dt/ha for WW, R\(^2\) = 0.89 and 0.82, and RMSE = 2.23 and 2.11 dt/ha for OSR using the LUE model, respectively. Similarly, for the 8- and 16-day products, the simple LUE model (R\(^2\) = 0.77 and relative RMSE (RRMSE) = 8.17\%) required fewer input parameters to simulate crop yield and was highly accurate, reliable, and more precise than the complex WOFOST model (R\(^2\) = 0.66 and RRMSE = 11.35\%) with higher input parameters. Conclusively, both S-MOD13Q1 and L-MOD13Q1, in combination with LUE, were more prominent for predicting crop yields on a regional scale than the 16-day products; however, L-MOD13Q1 was advantageous for generating and exploring the long-term yield time series due to the availability of Landsat data since 1982, with a maximum resolution of 30 m. In addition, this study recommended the further use of its findings for implementing and validating the long-term crop yield time series in different regions of the world.},
  language  = {en}
}
@article{DhillonDahmsKuebertFlocketal.2022,
  author    = {Dhillon, Maninder Singh and Dahms, Thorsten and K{\"u}bert-Flock, Carina and Steffan-Dewenter, Ingolf and Zhang, Jie and Ullmann, Tobias},
  title     = {Spatiotemporal Fusion Modelling Using STARFM: Examples of Landsat 8 and Sentinel-2 NDVI in Bavaria},
  series = {Remote Sensing},
  volume    = {14},
  journal   = {Remote Sensing},
  number    = {3},
  issn      = {2072-4292},
  doi       = {10.3390/rs14030677},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323471},
  year      = {2022},
  abstract  = {The increasing availability and variety of global satellite products provide a new level of data with different spatial, temporal, and spectral resolutions; however, identifying the most suited resolution for a specific application consumes increasingly more time and computation effort. The region's cloud coverage additionally influences the choice of the best trade-off between spatial and temporal resolution, and different pixel sizes of remote sensing (RS) data may hinder the accurate monitoring of different land cover (LC) classes such as agriculture, forest, grassland, water, urban, and natural-seminatural. To investigate the importance of RS data for these LC classes, the present study fuses NDVIs of two high spatial resolution data (high pair) (Landsat (30 m, 16 days; L) and Sentinel-2 (10 m, 5-6 days; S), with four low spatial resolution data (low pair) (MOD13Q1 (250 m, 16 days), MCD43A4 (500 m, one day), MOD09GQ (250 m, one-day), and MOD09Q1 (250 m, eight day)) using the spatial and temporal adaptive reflectance fusion model (STARFM), which fills regions' cloud or shadow gaps without losing spatial information. These eight synthetic NDVI STARFM products (2: high pair multiply 4: low pair) offer a spatial resolution of 10 or 30 m and temporal resolution of 1, 8, or 16 days for the entire state of Bavaria (Germany) in 2019. Due to their higher revisit frequency and more cloud and shadow-free scenes (S = 13, L = 9), Sentinel-2 (overall R\(^2\) = 0.71, and RMSE = 0.11) synthetic NDVI products provide more accurate results than Landsat (overall R\(^2\) = 0.61, and RMSE = 0.13). Likewise, for the agriculture class, synthetic products obtained using Sentinel-2 resulted in higher accuracy than Landsat except for L-MOD13Q1 (R\(^2\) = 0.62, RMSE = 0.11), resulting in similar accuracy preciseness as S-MOD13Q1 (R\(^2\) = 0.68, RMSE = 0.13). Similarly, comparing L-MOD13Q1 (R\(^2\) = 0.60, RMSE = 0.05) and S-MOD13Q1 (R\(^2\) = 0.52, RMSE = 0.09) for the forest class, the former resulted in higher accuracy and precision than the latter. Conclusively, both L-MOD13Q1 and S-MOD13Q1 are suitable for agricultural and forest monitoring; however, the spatial resolution of 30 m and low storage capacity makes L-MOD13Q1 more prominent and faster than that of S-MOD13Q1 with the 10-m spatial resolution.},
  language  = {en}
}
@article{DhillonDahmsKuebertFlocketal.2023,
  author    = {Dhillon, Maninder Singh and Dahms, Thorsten and K{\"u}bert-Flock, Carina and Liepa, Adomas and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias},
  title     = {Impact of STARFM on crop yield predictions: fusing MODIS with Landsat 5, 7, and 8 NDVIs in Bavaria Germany},
  series = {Remote Sensing},
  volume    = {15},
  journal   = {Remote Sensing},
  number    = {6},
  issn      = {2072-4292},
  doi       = {10.3390/rs15061651},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311092},
  year      = {2023},
  abstract  = {Rapid and accurate yield estimates at both field and regional levels remain the goal of sustainable agriculture and food security. Hereby, the identification of consistent and reliable methodologies providing accurate yield predictions is one of the hot topics in agricultural research. This study investigated the relationship of spatiotemporal fusion modelling using STRAFM on crop yield prediction for winter wheat (WW) and oil-seed rape (OSR) using a semi-empirical light use efficiency (LUE) model for the Free State of Bavaria (70,550 km\(^2\)), Germany, from 2001 to 2019. A synthetic normalised difference vegetation index (NDVI) time series was generated and validated by fusing the high spatial resolution (30 m, 16 days) Landsat 5 Thematic Mapper (TM) (2001 to 2012), Landsat 7 Enhanced Thematic Mapper Plus (ETM+) (2012), and Landsat 8 Operational Land Imager (OLI) (2013 to 2019) with the coarse resolution of MOD13Q1 (250 m, 16 days) from 2001 to 2019. Except for some temporal periods (i.e., 2001, 2002, and 2012), the study obtained an R\(^2\) of more than 0.65 and a RMSE of less than 0.11, which proves that the Landsat 8 OLI fused products are of higher accuracy than the Landsat 5 TM products. Moreover, the accuracies of the NDVI fusion data have been found to correlate with the total number of available Landsat scenes every year (N), with a correlation coefficient (R) of +0.83 (between R\(^2\) of yearly synthetic NDVIs and N) and -0.84 (between RMSEs and N). For crop yield prediction, the synthetic NDVI time series and climate elements (such as minimum temperature, maximum temperature, relative humidity, evaporation, transpiration, and solar radiation) are inputted to the LUE model, resulting in an average R\(^2\) of 0.75 (WW) and 0.73 (OSR), and RMSEs of 4.33 dt/ha and 2.19 dt/ha. The yield prediction results prove the consistency and stability of the LUE model for yield estimation. Using the LUE model, accurate crop yield predictions were obtained for WW (R\(^2\) = 0.88) and OSR (R\(^2\) = 0.74). Lastly, the study observed a high positive correlation of R = 0.81 and R = 0.77 between the yearly R\(^2\) of synthetic accuracy and modelled yield accuracy for WW and OSR, respectively.},
  language  = {en}
}
@article{DhillonDahmsKuebertFlocketal.2023,
  author    = {Dhillon, Maninder Singh and Dahms, Thorsten and Kuebert-Flock, Carina and Rummler, Thomas and Arnault, Joel and Steffan-Dewenter, Ingolf and Ullmann, Tobias},
  title     = {Integrating random forest and crop modeling improves the crop yield prediction of winter wheat and oil seed rape},
  series = {Frontiers in Remote Sensing},
  volume    = {3},
  journal   = {Frontiers in Remote Sensing},
  issn      = {2673-6187},
  doi       = {10.3389/frsen.2022.1010978},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301462},
  year      = {2023},
  abstract  = {The fast and accurate yield estimates with the increasing availability and variety of global satellite products and the rapid development of new algorithms remain a goal for precision agriculture and food security. However, the consistency and reliability of suitable methodologies that provide accurate crop yield outcomes still need to be explored. The study investigates the coupling of crop modeling and machine learning (ML) to improve the yield prediction of winter wheat (WW) and oil seed rape (OSR) and provides examples for the Free State of Bavaria (70,550 km2), Germany, in 2019. The main objectives are to find whether a coupling approach [Light Use Efficiency (LUE) + Random Forest (RF)] would result in better and more accurate yield predictions compared to results provided with other models not using the LUE. Four different RF models [RF1 (input: Normalized Difference Vegetation Index (NDVI)), RF2 (input: climate variables), RF3 (input: NDVI + climate variables), RF4 (input: LUE generated biomass + climate variables)], and one semi-empiric LUE model were designed with different input requirements to find the best predictors of crop monitoring. The results indicate that the individual use of the NDVI (in RF1) and the climate variables (in RF2) could not be the most accurate, reliable, and precise solution for crop monitoring; however, their combined use (in RF3) resulted in higher accuracies. Notably, the study suggested the coupling of the LUE model variables to the RF4 model can reduce the relative root mean square error (RRMSE) from -8\% (WW) and -1.6\% (OSR) and increase the R 2 by 14.3\% (for both WW and OSR), compared to results just relying on LUE. Moreover, the research compares models yield outputs by inputting three different spatial inputs: Sentinel-2(S)-MOD13Q1 (10 m), Landsat (L)-MOD13Q1 (30 m), and MOD13Q1 (MODIS) (250 m). The S-MOD13Q1 data has relatively improved the performance of models with higher mean R 2 [0.80 (WW), 0.69 (OSR)], and lower RRMSE (\%) (9.18, 10.21) compared to L-MOD13Q1 (30 m) and MOD13Q1 (250 m). Satellite-based crop biomass, solar radiation, and temperature are found to be the most influential variables in the yield prediction of both crops.},
  language  = {en}
}
@article{DeğirmenciRogeFerreiraVukosavljevicetal.2023,
  author    = {Değirmenci, Laura and Rog{\´e} Ferreira, Fabio Luiz and Vukosavljevic, Adrian and Heindl, Cornelia and Keller, Alexander and Geiger, Dietmar and Scheiner, Ricarda},
  title     = {Sugar perception in honeybees},
  series = {Frontiers in Physiology},
  volume    = {13},
  journal   = {Frontiers in Physiology},
  issn      = {1664-042X},
  doi       = {10.3389/fphys.2022.1089669},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-302284},
  year      = {2023},
  abstract  = {Honeybees (Apis mellifera) need their fine sense of taste to evaluate nectar and pollen sources. Gustatory receptors (Grs) translate taste signals into electrical responses. In vivo experiments have demonstrated collective responses of the whole Gr-set. We here disentangle the contributions of all three honeybee sugar receptors (AmGr1-3), combining CRISPR/Cas9 mediated genetic knock-out, electrophysiology and behaviour. We show an expanded sugar spectrum of the AmGr1 receptor. Mutants lacking AmGr1 have a reduced response to sucrose and glucose but not to fructose. AmGr2 solely acts as co-receptor of AmGr1 but not of AmGr3, as we show by electrophysiology and using bimolecular fluorescence complementation. Our results show for the first time that AmGr2 is indeed a functional receptor on its own. Intriguingly, AmGr2 mutants still display a wildtype-like sugar taste. AmGr3 is a specific fructose receptor and is not modulated by a co-receptor. Eliminating AmGr3 while preserving AmGr1 and AmGr2 abolishes the perception of fructose but not of sucrose. Our comprehensive study on the functions of AmGr1, AmGr2 and AmGr3 in honeybees is the first to combine investigations on sugar perception at the receptor level and simultaneously in vivo. We show that honeybees rely on two gustatory receptors to sense all relevant sugars.},
  language  = {en}
}
@phdthesis{DeğirmencineePoelloth2023,
  author    = {Değirmenci [n{\´e}e P{\"o}lloth], Laura},
  title     = {Sugar perception and sugar receptor function in the honeybee (\(Apis\) \(mellifera\))},
  doi       = {10.25972/OPUS-32187},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-321873},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {In the eusocial insect honeybee (Apis mellifera), many sterile worker bees live together with a reproductive queen in a colony. All tasks of the colony are performed by the workers, undergoing age-dependent division of labor. Beginning as hive bees, they take on tasks inside the hive such as cleaning or the producing of larval food, later developing into foragers. With that, the perception of sweetness plays a crucial role for all honeybees whether they are sitting on the honey stores in the hive or foraging for food. Their ability to sense sweetness is undoubtedly necessary to develop and evaluate food sources. Many of the behavioral decisions in honeybees are based on sugar perception, either on an individual level for ingestion, or for social behavior such as the impulse to collect or process nectar. In this context, honeybees show a complex spectrum of abilities to perceive sweetness on many levels. They are able to perceive at least seven types of sugars and decide to collect them for the colony. Further, they seem to distinguish between these sugars or at least show clear preferences when collecting them. Additionally, the perception of sugar is not rigid in honeybees. For instance, their responsiveness towards sugar changes during the transition from in-hive bees (e.g. nurses) to foraging and is linked to the division of labor. Other direct or immediate factors changing responsiveness to sugars are stress, starvation or underlying factors, such as genotype. Interestingly, the complexity in their sugar perception is in stark contrast to the fact that honeybees seem to have only three predicted sugar receptors. In this work, we were able to characterize the three known sugar receptors (AmGr1, AmGr2 and AmGr3) of the honeybee fully and comprehensively in oocytes (Manuscript II, Chapter 3 and Manuscript III, Chapter 4). We could show that AmGr1 is a broad sugar receptor reacting to sucrose, glucose, maltose, melezitose and trehalose (which is the honeybees' main blood sugar), but not fructose. AmGr2 acts as its co-receptor altering AmGr1's specificity, AmGr3 is a specific fructose receptor and we proved the heterodimerization of all receptors. With my studies, I was able to reproduce and compare the ligand specificity of the sugar receptors in vivo by generating receptor mutants with CRISPR/Cas9. With this thesis, I was able to define AmGr1 and AmGr3 as the honeybees' basis receptors already capable to detect all sugars of its known taste spectrum. In the expression analysis of my doctoral thesis (Manuscript I, Chapter 2) I demonstrated that both basis receptors are expressed in the antennae and the brain of nurse bees and foragers. This thesis assumes that AmGr3 (like the Drosophila homologue) functions as a sensor for fructose, which might be the satiety signal, while AmGr1 can sense trehalose as the main blood sugar in the brain. Both receptors show a reduced expression in the brain of foragers when compared with nurse bees. These results may reflect the higher concentrated diet of nurse bees in the hive. The higher number of receptors in the brain may allow nurse bees to perceive hunger earlier and to consume the food their sitting on. Forager bees have to be more persistent to hunger, when they are foraging, and food is not so accessible. The findings of reduced expression of the fructose receptor AmGr3 in the antennae of nurse bees are congruent with my other result that nurse bees are also less responsive to fructose at the antennae when compared to foragers (Manuscript I, Chapter 2). This is possible, since nurse bees sit more likely on ripe honey which contains not only higher levels of sugars but also monosaccharides (such as fructose), while foragers have to evaluate less-concentrated nectar. My investigations of the expression of AmGr1 in the antennae of honeybees found no differences between nurse bees and foragers, although foragers are more responsive to the respective sugar sucrose (Manuscript I, Chapter 2). Considering my finding that AmGr2 is the co-receptor of AmGr1, it can be assumed that AmGr1 and the mediated sucrose taste might not be directly controlled by its expression, but indirectly by its co-receptor. My thesis therefore clearly shows that sugar perception is associated with division of labor in honeybees and appears to be directly or indirectly regulated via expression. The comparison with a characterization study using other bee breeds and thus an alternative protein sequence of AmGr1 shows that co-expression of different AmGr1 versions with AmGr2 alters the sugar response differently. Therefore, this thesis provides first important indications that alternative splicing could also represent an important regulatory mechanism for sugar perception in honeybees. Further, I found out that the bitter compound quinine lowers the reward quality in learning experiments for honeybees (Manuscript IV, Chapter 5). So far, no bitter receptor has been found in the genome of honeybees and this thesis strongly assumes that bitter substances such as quinine inhibit sugar receptors in honeybees. With this finding, my work includes other molecules as possible regulatory mechanism in the honeybee sugar perception as well. We showed that the inhibitory effect is lower for fructose compared to sucrose. Considering that sugar signals might be processed as differently attractive in honeybees, this thesis concludes that the sugar receptor inhibition via quinine in honeybees might depend on the receptor (or its co-receptor), is concentration-dependent and based on the salience or attractiveness and concentration of the sugar present. With my thesis, I was able to expand the knowledge on honeybee's sugar perception and formulate a complex, comprehensive overview. Thereby, I demonstrated the multidimensional mechanism that regulates the sugar receptors and thus the sugar perception of honeybees. With this work, I defined AmGr1 and AmGr3 as the basis of sugar perception and enlarged these components to the co-receptor AmGr2 and the possible splice variants of AmGr1. I further demonstrated how those sugar receptor components function, interact and that they are clearly involved in the division of labor in honeybees. In summary, my thesis describes the mechanisms that enable honeybees to perceive sugar in a complex way, even though they inhere a limited number of sugar receptors. My data strongly suggest that honeybees overall might not only differentiate sugars and their diet by their general sweetness (as expected with only one main sugar receptor). The found sugar receptor mechanisms and their interplay further suggest that honeybees might be able to discriminate directly between monosaccharides and disaccharides or sugar molecules and with that their diet (honey and nectar).},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Devine2013,
  author    = {Devine, Eric},
  title     = {Increased removal of protein bound uremic toxins through reversible modification of the ionic strength during hemodiafiltration},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83583},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {A large number of metabolic waste products accumulate in the blood of patients with renal failure. Since these solutes have deleterious effects on the biological functions, they are called uremic toxins and have been classified in three groups: 1) small water soluble solutes (MW < 500 Da), 2) small solutes with known protein binding (MW < 500 Da), and 3) middle molecules (500 Da < MW < 60 kDa). Protein bound uremic toxins are poorly removed by conventional hemodialysis treatments because of their high protein binding and high distribution volume. The prototypical protein bound uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) are associated with the progression of chronic kidney disease, cardiovascular outcomes, and mortality of patients on maintenance hemodialysis. Furthermore, these two compounds are bound to albumin, the main plasma protein, via electrostatic and/or Van-der-Waals forces. The aim of the present thesis was to develop a dialysis strategy, based on the reversible modification of the ionic strength in the blood stream by increasing the sodium chloride (NaCl) concentration, in order to enhance the removal of protein bound substances, such as IS and pCS, with the ultimate goal to improve clinical patient outcomes. Enhancing the NaCl concentration ([NaCl]) in both human normal and uremic plasma was efficient to reduce the protein bound fraction of both IS and pCS by reducing their binding affinity to albumin. Increasing the ionic strength was feasible during modified pre-dilution hemodiafiltration (HDF) by increasing the [NaCl] in the substitution fluid. The NaCl excess was adequately removed within the hemodialyzer. This method was effective to increase the removal rate of both protein bound uremic toxins. Its ex vivo hemocompatibility, however, was limited by the osmotic shock induced by the high [NaCl] in the substituate. Therefore, modified pre-dilution HDF was further iterated by introducing a second serial cartridge, named the serial dialyzers (SDial) setup. This setting was validated for feasibility, hemocompatibility, and toxin removal efficiency. A better hemocompatibility at similar efficacy was obtained with the SDial setup compared with the modified pre-dilution HDF. Both methods were finally tested in an animal sheep model of dialysis to verify biocompatibility. Low hemolysis and no activation of both the complement and the coagulation systems were observed when increasing the [NaCl] in blood up to 0.45 and 0.60 M with the modified pre-dilution HDF and the SDial setup, respectively. In conclusion, the two dialysis methods developed to transitory enhance the ionic strength in blood demonstrated adequate biocompatibility and improved the removal of protein bound uremic toxins by decreasing their protein bound fraction. The concepts require follow-on clinical trials to assess their in vivo efficacy and their impact on long-term clinical outcomes.},
  subject      = {H{\"a}modiafiltration},
  language  = {en}
}
@article{DerksenTrendelenburgScheeretal.1973,
  author    = {Derksen, J. and Trendelenburg, Michael F. and Scheer, Ulrich and Franke, Werner W.},
  title     = {Spread chromosomal nucleoli of Chironomus salivary glands},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-32209},
  year      = {1973},
  abstract  = {No abstract available},
  language  = {en}
}
@article{DerakhshaniKurzJaptoketal.2019,
  author    = {Derakhshani, Shaghayegh and Kurz, Andreas and Japtok, Lukasz and Schumacher, Fabian and Pilgram, Lisa and Steinke, Maria and Kleuser, Burkhard and Sauer, Markus and Schneider-Schaulies, Sibylle and Avota, Elita},
  title     = {Measles virus infection fosters dendritic cell motility in a 3D environment to enhance transmission to target cells in the respiratory epithelium},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  number    = {1294},
  doi       = {10.3389/fimmu.2019.01294},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201818},
  year      = {2019},
  abstract  = {Transmission of measles virus (MV) from dendritic to airway epithelial cells is considered as crucial to viral spread late in infection. Therefore, pathways and effectors governing this process are promising targets for intervention. To identify these, we established a 3D respiratory tract model where MV transmission by infected dendritic cells (DCs) relied on the presence of nectin-4 on H358 lung epithelial cells. Access to recipient cells is an important prerequisite for transmission, and we therefore analyzed migration of MV-exposed DC cultures within the model. Surprisingly, enhanced motility toward the epithelial layer was observed for MV-infected DCs as compared to their uninfected siblings. This occurred independently of factors released from H358 cells indicating that MV infection triggered cytoskeletal remodeling associated with DC polarization enforced velocity. Accordingly, the latter was also observed for MV-infected DCs in collagen matrices and was particularly sensitive to ROCK inhibition indicating infected DCs preferentially employed the amoeboid migration mode. This was also implicated by loss of podosomes and reduced filopodial activity both of which were retained in MV-exposed uninfected DCs. Evidently, sphingosine kinase (SphK) and sphingosine-1-phosphate (S1P) as produced in response to virus-infection in DCs contributed to enhanced velocity because this was abrogated upon inhibition of sphingosine kinase activity. These findings indicate that MV infection promotes a push-and-squeeze fast amoeboid migration mode via the SphK/S1P system characterized by loss of filopodia and podosome dissolution. Consequently, this enables rapid trafficking of virus toward epithelial cells during viral exit.},
  language  = {en}
}
@article{DeppischHelfrichFoersterSenthilan2022,
  author    = {Deppisch, Peter and Helfrich-F{\"o}rster, Charlotte and Senthilan, Pingkalai R.},
  title     = {The gain and loss of cryptochrome/photolyase family members during evolution},
  series = {Genes},
  volume    = {13},
  journal   = {Genes},
  number    = {9},
  doi       = {10.3390/genes13091613},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312873},
  year      = {2022},
  abstract  = {The cryptochrome/photolyase (CRY/PL) family represents an ancient group of proteins fulfilling two fundamental functions. While photolyases repair UV-induced DNA damages, cryptochromes mainly influence the circadian clock. In this study, we took advantage of the large number of already sequenced and annotated genes available in databases and systematically searched for the protein sequences of CRY/PL family members in all taxonomic groups primarily focusing on metazoans and limiting the number of species per taxonomic order to five. Using BLASTP searches and subsequent phylogenetic tree and motif analyses, we identified five distinct photolyases (CPDI, CPDII, CPDIII, 6-4 photolyase, and the plant photolyase PPL) and six cryptochrome subfamilies (DASH-CRY, mammalian-type MCRY, Drosophila-type DCRY, cnidarian-specific ACRY, plant-specific PCRY, and the putative magnetoreceptor CRY4. Manually assigning the CRY/PL subfamilies to the species studied, we have noted that over evolutionary history, an initial increase of various CRY/PL subfamilies was followed by a decrease and specialization. Thus, in more primitive organisms (e.g., bacteria, archaea, simple eukaryotes, and in basal metazoans), we find relatively few CRY/PL members. As species become more evolved (e.g., cnidarians, mollusks, echinoderms, etc.), the CRY/PL repertoire also increases, whereas it appears to decrease again in more recent organisms (humans, fruit flies, etc.). Moreover, our study indicates that all cryptochromes, although largely active in the circadian clock, arose independently from different photolyases, explaining their different modes of action.},
  language  = {en}
}
@phdthesis{Denker2006,
  author    = {Denker, Katrin},
  title     = {Isolation and characterization of channel-forming proteins in the outer membrane of E. coli and Borrelia species},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-16955},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {In this study pore forming proteins of the gram-negative bacteria B. burgdorferi, B. duttonii and E.coli were investigated. Therefore the study is subdivided into three parts. In the first part outer membrane preparation of three relapsing fever Borrelia were investigated. In the second part the putative TolC homologue BB0124 of B. burgdorferi, the Lyme borreliosis agent, was studied. In the last part the influence of point mutants within the greasy slide of the maltose specific porin (LamB) of E. coli were shown. In the first part of this study outer membrane preparations of three Borrelia relapsing fever strains have been studied for pore-forming activity in the black lipid bilayer assay. Histograms of conductance fluctuations were obtained from single-channel experiments with outer membrane preparations of B. hermsii, B. recurentis and B. duttonii. All strains had a different conductance fluctuation pattern with a broad range of single-channel conductance values varying from 0.5 nS - 11 nS. Common for all three strains was a high pore-forming activity at around 0.5 nS. Furthermore the proteins of the outer membrane of B. duttonii were separated by chromatographic methods. Some eluate fractions contained a channel-forming protein, which was forming stable channels with a single-channel conductance of 80 pS in 1 M KCl. Characterization of this channel showed that it is slightly anionic selective and voltage independent. The small single-channel conductance suggests that it is a specific pore. However, a substrate specificity could not be determined. In the second part, for the B. burgdorferi HB19 and p66 knock out strain HB19/K02, their outer membrane preparations were characterized in the black lipid bilayer assay. Comparing the histograms of single-channel conductions fluctuations of both strains showed no single-channel activity at 11.5 nS for the p66 knock out strain. This verifies earlier studies that P66 is a pore-forming protein in B. burgdorferi. Furthermore, one fraction obtained by anion exchange chromatography of the p66 knock out outer membrane protein preparation showed a uniform channel-forming activity with a single channel conductance of 300 pS. The electrophysically characterization of the 300 pS channel showed that it is not ionselective or voltage dependent. By mass spectrometry using peptide mass finger prints, BB0142 could be identified as the sole channel forming candidate in the active fraction. A BLAST search and a conserved domain search showed that BB0142 is a putative TolC homologue in B. burgdorferi. Furthermore the location of the bb0142 gene within the chromosome is in an operon encoding a multidrug efflux pump. In this study the expression of an outer membrane component of a putative drug efflux system of B. burgdorferi was shown for the first time. In the third part functional studies of the maltooligosaccharide-specific LamB channel were performed. The 3D-structure of LamB suggests that a number of aromatic residues (Y6, Y41, W74, F229, W358 and W420) within the channel lumen is involved in carbohydrate and ion transport. All aromatic residues were replaced by alanine (A) scanning mutagenesis. Furthermore, LamB mutants were created in which one, two, three, four and five aromatic residues were replaced to study their effects on ion and maltopentaose transport through LamB. The purified mutant proteins were reconstituted into lipid bilayer membranes and the single-channel conductance was studied. The results suggest that all aromatic residues provide some steric hindrance for ion transport through LamB. Highest impact is provided by Y6 and Y41, which are localized opposite to Y118, which forms the central constriction of the LamB channel. Stability constants for binding of maltopentaose to the mutant channels were measured using titration experiments with the carbohydrate. The mutation of one or several aromatic amino acids led to a substantial decrease of the stability constant of binding. The highest effect was observed when all aromatic amino acids were replaced by alanine because no binding of maltopentaose could be detected in this case. However, binding was again possible when Y118 was replaced by tryptophane (W). The carbohydrate-induced block of the channel function could also be used for the study of current noise through the different mutant LamB-channels. The analysis of the power density spectra of some of the mutants allowed the evaluation of the on- and off-rate constants (k1 and k-1) of carbohydrate binding to the binding-site inside the channels. The results suggest that both on- and off-rate constants were affected by the mutations. For most mutants k1 decreased and k-1 increased.},
  subject      = {Escherichia coli},
  language  = {en}
}
@article{DemchukMuellerOschkinatetal.1994,
  author    = {Demchuk, E. and Mueller, T. and Oschkinat, H. and Sebald, Walter and Wade, R. C.},
  title     = {Receptor binding properties of four-helix-bundle growth factors deduced from electrostatic analysis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62424},
  year      = {1994},
  abstract  = {Hormones of the hematopoietin class mediate signal transduction by binding to specific transmembrane receptors. Structural data show that the human growth hormone (hGH) forms a complex with a homodimeric receptor and that hGH is a member of a class of hematopoietins possessing an antiparallel 4-a-helix bundle fold. Mutagenesis experiments suggest that electrostatic interactions may have an important influence on hormonereceptor recognition. In order to examine the specificity of hormone-receptor complexation, an analysis was made of the electrostatic potentials of hGH, interleukin-2 (IL-2), interleukin-4 (IL-4), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the hGH and IL-4 receptors. The binding surfaces of hGH and its receptor, and of IL-4 and its receptor, show complementary electrostatic potentials. The potentials of the hGH and its receptor display approximately 2-fold rotational symmetry because the receptor subunits are identical. In contrast, the potentials of GM-CSF and IL-2 Iack such symmetry, consistent with their known high affinity for hetero-oligomeric receptors. Analysis of the electrostatic potentials supports a recently proposed hetero-oligomeric model for a high-affinity IL-4 receptor and suggests a possible new receptor binding mode for G-CSF; it also provides valuable information for guiding structural and mutagenesis studies of signal-transducing proteins and their receptors.},
  subject      = {Biochemie},
  language  = {en}
}
@phdthesis{Dejure2018,
  author    = {Dejure, Francesca Romana},
  title     = {Investigation of the role of MYC as a stress responsive protein},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158587},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The transcription factor MYC is deregulated in over 70\% of all human tumors and, in its oncogenic form, plays a major role in the cancer metabolic reprogramming, promoting the uptake of nutrients in order to sustain the biosynthetic needs of cancer cells. The research presented in this work aimed to understand if MYC itself is regulated by nutrient availability, focusing on the two major fuels of cancer cells: glucose and glutamine. Initial observations showed that endogenous MYC protein levels strongly depend on the availability of glutamine, but not of glucose. Subsequent analysis highlighted that the mechanism which accounts for the glutamine-mediated regulation of MYC is dependent on the 3´-untranslated region (3´-UTR) of MYC. Enhanced glutamine utilization by tumors has been shown to be directly linked to MYC oncogenic activity and MYC-dependent apoptosis has been observed under glutamine starvation. Such effect has been described in experimental systems which are mainly based on the use of MYC transgenes that do not contain the 3´-UTR. It was observed in the present study that cells are able to survive under glutamine starvation, which leads to cell cycle arrest and not apoptosis, as previously reported. However, enforced expression of a MYC transgene, which lacks the 3´-UTR, strongly increases the percentage of apoptotic cells upon starvation. Evaluation of glutamine-derived metabolites allowed to identify adenosine nucleotides as the specific stimulus responsible for the glutamine-mediated regulation of MYC, in a 3´-UTR-dependent way. Finally, glutamine-dependent MYC-mediated effects on RNA Polymerase II (RNAPII) function were evaluated, since MYC is involved in different steps of global transcriptional regulation. A global loss of RNAPII recruitment at the transcriptional start site results upon glutamine withdrawal. Such effect is overcome by enforced MYC expression under the same condition. This study shows that the 3´UTR of MYC acts as metabolic sensor and that MYC globally regulates the RNAPII function according to the availability of glutamine. The observations presented in this work underline the importance of considering stress-induced mechanisms impinging on the 3´UTR of MYC.},
  subject      = {Myc},
  language  = {en}
}
@article{DejungSubotaBuceriusetal.2016,
  author    = {Dejung, Mario and Subota, Ines and Bucerius, Ferdinand and Dindar, G{\"u}lcin and Freiwald, Anja and Engstler, Markus and Boshart, Michael and Butter, Falk and Janzen, Chistian J.},
  title     = {Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosoma brucei},
  series = {PLoS Pathogens},
  volume    = {12},
  journal   = {PLoS Pathogens},
  number    = {2},
  doi       = {10.1371/journal.ppat.1005439},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146362},
  pages     = {e1005439},
  year      = {2016},
  abstract  = {Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes.},
  language  = {en}
}
@phdthesis{Dehmer2024,
  author    = {Dehmer, Markus},
  title     = {A novel USP11-TCEAL1-mediated mechanism protects transcriptional elongation by RNA Polymerase II},
  doi       = {10.25972/OPUS-36054},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-360544},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2024},
  abstract  = {Deregulated expression of MYC oncoproteins is a driving event in many human cancers. Therefore, understanding and targeting MYC protein-driven mechanisms in tumor biology remain a major challenge. Oncogenic transcription in MYCN-amplified neuroblastoma leads to the formation of the MYCN-BRCA1-USP11 complex that terminates transcription by evicting stalling RNAPII from chromatin. This reduces cellular stress and allows reinitiation of new rounds of transcription. Basically, tumors with amplified MYC genes have a high demand on well orchestration of transcriptional processes-dependent and independent from MYC proteins functions in gene regulation. To date, the cooperation between promoter-proximal termination and transcriptional elongation in cancer cells remains still incomplete in its understanding. In this study the putative role of the dubiquitinase Ubiquitin Specific Protease 11 (USP11) in transcription regulation was further investigated. First, several USP11 interaction partners involved in transcriptional regulation in neuroblastoma cancer cells were identified. In particular, the transcription elongation factor A like 1 (TCEAL1) protein, which assists USP11 to engage protein-protein interactions in a MYCN-dependent manner, was characterized. The data clearly show that TCEAL1 acts as a pro-transcriptional factor for RNA polymerase II (RNAPII)-medi- ated transcription. In detail, TCEAL1 controls the transcription factor S-II (TFIIS), a factor that assists RNAPII to escape from paused sites. The findings claim that TCEAL1 outcompetes the transcription elongation factor TFIIS in a non-catalytic manner on chromatin of highly expressed genes. This is reasoned by the need regulating TFIIS function in transcription. TCEAL1 equili- brates excessive backtracking and premature termination of transcription caused by TFIIS. Collectively, the work shed light on the stoichiometric control of TFIIS demand in transcriptional regulation via the USP11-TCEAL1-USP7 complex. This complex protects RNAPII from TFIIS-mediated termination helping to regulate productive transcription of highly active genes in neuroblastoma.},
  subject      = {Transkription},
  language  = {en}
}
@article{DegenkolbeKoenigZimmeretal.2013,
  author    = {Degenkolbe, Elisa and K{\"o}nig, Jana and Zimmer, Julia and Walther, Maria and Reißner, Carsten and Nickel, Joachim and Pl{\"o}ger, Frank and Raspopovic, Jelena and Sharpe, James and Dathe, Katharina and Hecht, Jacqueline T. and Mundlos, Stefan and Doelken, Sandra C. and Seemann, Petra},
  title     = {A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2},
  series = {PLOS Genetics},
  volume    = {9},
  journal   = {PLOS Genetics},
  number    = {10},
  issn      = {1553-7404},
  doi       = {10.1371/journal.pgen.1003846},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127556},
  pages     = {e1003846},
  year      = {2013},
  abstract  = {Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5 W-414R variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain-and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA.},
  language  = {en}
}
@article{DegenHovestadtMitesseretal.2017,
  author    = {Degen, Tobias and Hovestadt, Thomas and Mitesser, Oliver and H{\"o}lker, Franz},
  title     = {Altered sex-specific mortality and female mating success: ecological effects and evolutionary responses},
  series = {Ecosphere},
  volume    = {8},
  journal   = {Ecosphere},
  number    = {5},
  doi       = {10.1002/ecs2.1820},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170953},
  pages     = {e01820},
  year      = {2017},
  abstract  = {Theory predicts that males and females should often join the mating pool at different times (sexual dimorphism in timing of emergence [SDT]) as the degree of SDT affects female mating success. We utilize an analytical model to explore (1) how important SDT is for female mating success, (2) how mating success might change if either sex's mortality (abruptly) increases, and (3) to what degree evolutionary responses in SDT may be able to mitigate the consequences of such mortality increase. Increasing male pre-mating mortality has a non-linear effect on the fraction of females mated: The effect is initially weak, but at some critical level a further increase in male mortality has a stronger effect than a similar increase in female mortality. Such a change is expected to impose selection for reduced SDT. Increasing mortality during the mating season has always a stronger effect on female mating success if the mortality affects the sex that emerges first. This bias results from the fact that enhancing mortality of the earlier emerging sex reduces female-male encounter rates. However, an evolutionary response in SDT may effectively mitigate such consequences. Further, if considered independently for females and males, the predicted evolutionary response in SDT could be quite dissimilar. The difference between female and male evolutionary response in SDT leads to marked differences in the fraction of fertilized females under certain conditions. Our model may provide general guidelines for improving harvesting of populations, conservation management of rare species under altered environmental conditions, or maintaining long-term efficiency of pest-control measures.},
  language  = {en}
}