@article{LichtensteinGruebelSpaethe2018,
  author    = {Lichtenstein, Leonie and Gr{\"u}bel, Kornelia and Spaethe, Johannes},
  title     = {Opsin expression patterns coincide with photoreceptor development during pupal development in the honey bee, Apis mellifera},
  series = {BMC Developmental Biology},
  volume    = {18},
  journal   = {BMC Developmental Biology},
  number    = {1},
  doi       = {10.1186/s12861-018-0162-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175665},
  year      = {2018},
  abstract  = {Background: The compound eyes of insects allow them to catch photons and convert the energy into electric signals. All compound eyes consist of numerous ommatidia, each comprising a fixed number of photoreceptors. Different ommatidial types are characterized by a specific set of photoreceptors differing in spectral sensitivity. In honey bees, males and females possess different ommatidial types forming distinct retinal mosaics. However, data are lacking on retinal ontogeny and the mechanisms by which the eyes are patterned. In this study, we investigated the intrinsic temporal and circadian expression patterns of the opsins that give rise to the ultraviolet, blue and green sensitive photoreceptors, as well as the morphological maturation of the retina during pupal development of honey bees. Results: qPCR and histological labeling revealed that temporal opsin mRNA expression differs between sexes and correlates with rhabdom elongation during photoreceptor development. In the first half of the pupal stage, when the rhabdoms of the photoreceptors are still short, worker and (dorsal) drone retinae exhibit similar expression patterns with relatively high levels of UV (UVop) and only marginal levels of blue (BLop) and green (Lop1) opsin mRNA. In the second half of pupation, when photoreceptors and rhabdoms elongate, opsin expression in workers becomes dominated by Lop1 mRNA. In contrast, the dorsal drone eye shows high expression levels of UVop and BLop mRNA, whereas Lop1 mRNA level decreases. Interestingly, opsin expression levels increase up to 22-fold during early adult life. We also found evidence that opsin expression in adult bees is under the control of the endogenous clock. Conclusions: Our data indicate that the formation of the sex-specific retinal composition of photoreceptors takes place during the second half of the pupal development, and that opsin mRNA expression levels continue to increase in young bees, which stands in contrast to Drosophila, where the highest expression levels are found during the late pupal stage and remain constant in adults. From an evolutionary perspective, we hypothesize that the delayed retinal maturation during the early adult phase is linked to the delayed transition from indoor to outdoor activities in bees, when vision becomes important.},
  language  = {en}
}
@article{BartmannJanakiRamanFloeteretal.2018,
  author    = {Bartmann, Catharina and Janaki Raman, Sudha R. and Fl{\"o}ter, Jessica and Schulze, Almut and Bahlke, Katrin and Willingstorfer, Jana and Strunz, Maria and W{\"o}ckel, Achim and Klement, Rainer J. and Kapp, Michaela and Djuzenova, Cholpon S. and Otto, Christoph and K{\"a}mmerer, Ulrike},
  title     = {Beta-hydroxybutyrate (3-OHB) can influence the energetic phenotype of breast cancer cells, but does not impact their proliferation and the response to chemotherapy or radiation},
  series = {Cancer \& Metabolism},
  volume    = {6},
  journal   = {Cancer \& Metabolism},
  number    = {8},
  doi       = {10.1186/s40170-018-0180-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175607},
  year      = {2018},
  abstract  = {Background: Ketogenic diets (KDs) or short-term fasting are popular trends amongst supportive approaches for cancer patients. Beta-hydroxybutyrate (3-OHB) is the main physiological ketone body, whose concentration can reach plasma levels of 2-6 mM during KDs or fasting. The impact of 3-OHB on the biology of tumor cells described so far is contradictory. Therefore, we investigated the effect of a physiological concentration of 3 mM 3-OHB on metabolism, proliferation, and viability of breast cancer (BC) cells in vitro. Methods: Seven different human BC cell lines (BT20, BT474, HBL100, MCF-7, MDA-MB 231, MDA-MB 468, and T47D) were cultured in medium with 5 mM glucose in the presence of 3 mM 3-OHB at mild hypoxia (5\% oxygen) or normoxia (21\% oxygen). Metabolic profiling was performed by quantification of the turnover of glucose, lactate, and 3-OHB and by Seahorse metabolic flux analysis. Expression of key enzymes of ketolysis as well as the main monocarboxylic acid transporter MCT2 and the glucose-transporter GLUT1 was analyzed by RT-qPCR and Western blotting. The effect of 3-OHB on short- and long-term cell proliferation as well as chemo- and radiosensitivity were also analyzed. Results: 3-OHB significantly changed the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in BT20 cells resulting in a more oxidative energetic phenotype. MCF-7 and MDA-MB 468 cells had increased ECAR only in response to 3-OHB, while the other three cell types remained uninfluenced. All cells expressed MCT2 and GLUT1, thus being able to uptake the metabolites. The consumption of 3-OHB was not strongly linked to mRNA overexpression of key enzymes of ketolysis and did not correlate with lactate production and glucose consumption. Neither 3-OHB nor acetoacetate did interfere with proliferation. Further, 3-OHB incubation did not modify the response of the tested BC cell lines to chemotherapy or radiation. Conclusions: We found that a physiological level of 3-OHB can change the energetic profile of some BC cell lines. However, 3-OHB failed to influence different biologic processes in these cells, e.g., cell proliferation and the response to common breast cancer chemotherapy and radiotherapy. Thus, we have no evidence that 3-OHB generally influences the biology of breast cancer cells in vitro.},
  language  = {en}
}
@phdthesis{Maierhofer2018,
  author    = {Maierhofer, Anna},
  title     = {Altersassoziierte und strahleninduzierte Ver{\"a}nderungen des genomweiten DNA-Methylierungs-Profils},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174134},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Der Prozess des Alterns ist ein komplexer multifaktorieller Vorgang, der durch eine sukzessive Verschlechterung der physiologischen Funktionen charakterisiert ist. Ein hohes Alter ist der Hauptrisikofaktor f{\"u}r die meisten Krankheiten, einschließlich Krebs und Herz-Kreislauf-Erkrankungen. Das Verst{\"a}ndnis der epigenetischen Mechanismen, die in den Prozess des Alterns involviert sind, k{\"o}nnte zur Entwicklung pharmakologischer Interventionen beitragen, die nicht nur die Lebenserwartung erh{\"o}hen, sondern auch den Beginn des altersassoziierten funktionellen Abbaus verz{\"o}gern k{\"o}nnten. Durch die Langzeit-Kultivierung prim{\"a}rer humaner Fibroblasten wurde ein in vitro Modell f{\"u}r das Altern etabliert, das die Identifizierung altersassoziierter DNA-Methylierungs-Ver{\"a}nderungen erm{\"o}glichte. Die in vitro Alterung konnte mit einer globalen Hypomethylierung und einer erh{\"o}hten DNA-Methylierung der ribosomalen DNA assoziiert werden. Dar{\"u}ber hinaus konnten DNA-Methylierungs-Ver{\"a}nderungen in Genen und Signalwegen, die f{\"u}r das Altern relevant sind, und ein erh{\"o}htes epigenetisches Alter nachgewiesen werden. Das in vitro Modell f{\"u}r das Altern wurde verwendet, um neben den direkten Effekten ionisierender Strahlung auf die DNA-Methylierung auch deren Langzeit-Effekte zu untersuchen. Die Strahlentherapie ist ein entscheidendes Element der Krebstherapie, hat aber auch negative Auswirkungen und kann unter anderem das Risiko f{\"u}r die Entwicklung eines Zweittumors erh{\"o}hen. Bei externer Bestrahlung wird neben dem Tumor auch gesundes Gewebe ionisierender Strahlung ausgesetzt. Daher ist es wichtig zu untersuchen, wie Zellen mit intakten DNA-Reparatur-Mechanismen und funktionierenden Zellzyklus-Checkpoints durch diese beeinflusst werden. In der fr{\"u}hen Phase der DNA-Schadensantwort auf Bestrahlung wurden in normalen Zellen keine wesentlichen DNA-Methylierungs-Ver{\"a}nderungen beobachtet. Mehrere Populations-Verdoppelungen nach Strahlenexposition konnten dagegen eine globale Hypomethylierung, eine erh{\"o}hte DNA-Methylierung der ribosomalen DNA und ein erh{\"o}htes epigenetisches Alter detektiert werden. Des Weiteren zeigten Gene und Signalwege, die mit Krebs in Verbindung gebracht wurden, Ver{\"a}nderungen in der DNA-Methylierung. Als Langzeit-Effekte ionisierender Strahlung traten somit die mit der in vitro Alterung assoziierten DNA-Methylierungs-Ver{\"a}nderungen verst{\"a}rkt auf und ein epigenetisches Muster, das stark an das DNA-Methylierungs-Profil von Tumorzellen erinnert, entstand. Man geht davon aus, dass Ver{\"a}nderungen der DNA-Methylierung eine aktive Rolle in der Entwicklung eines Tumors spielen. Die durch ionisierende Strahlung induzierten DNA-Methylierungs-Ver{\"a}nderungen in normalen Zellen k{\"o}nnten demnach in die Krebsentstehung nach Strahlenexposition involviert sein und zu dem sekund{\"a}ren Krebsrisiko nach Strahlentherapie beitragen. Es ist bekannt, dass Patienten unterschiedlich auf therapeutische Bestrahlung reagieren. Die Ergebnisse dieser Arbeit weisen darauf hin, dass die individuelle Sensitivit{\"a}t gegen{\"u}ber ionisierender Strahlung auch auf epigenetischer Ebene beobachtet werden kann. In einem zweiten Projekt wurden Gesamtblutproben von Patienten mit Werner-Syndrom, einer segmental progeroiden Erkrankung, und gesunden Kontrollen analysiert, um mit dem vorzeitigen Altern in Verbindung stehende DNA-Methylierungs-Ver{\"a}nderungen zu identifizieren. Werner-Syndrom konnte nicht mit einer globalen Hypomethylierung, jedoch mit einer erh{\"o}hten DNA-Methylierung der ribosomalen DNA und einem erh{\"o}hten epigenetischen Alter assoziiert werden. Das vorzeitige Altern geht demzufolge mit spezifischen epigenetischen Ver{\"a}nderungen einher, die eine Beschleunigung der mit dem normalen Altern auftretenden DNA-Methylierungs-Ver{\"a}nderungen darstellen. Im Rahmen dieser Arbeit konnte die Bedeutung epigenetischer Mechanismen im Prozess des Alterns hervorgehoben werden und gezeigt werden, dass sowohl exogene Faktoren, wie ionisierende Strahlung, als auch endogene Faktoren, wie das in Werner-Syndrom-Patienten mutiert vorliegende WRN-Gen, altersassoziierte DNA-Methylierungs-Ver{\"a}nderungen beeinflussen k{\"o}nnen.},
  subject      = {Methylierung},
  language  = {de}
}
@phdthesis{Nuernberger2018,
  author    = {N{\"u}rnberger, Fabian},
  title     = {Timing of colony phenology and foraging activity in honey bees},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-155105},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {I. Timing is a crucial feature in organisms that live within a variable and changing environment. Complex mechanisms to measure time are wide-spread and were shown to exist in many taxa. These mechanisms are expected to provide fitness benefits by enabling organisms to anticipate environmental changes and adapt accordingly. However, very few studies have addressed the adaptive value of proper timing. The objective of this PhD-project was to investigate mechanisms and fitness consequences of timing decisions concerning colony phenology and foraging activity in the honey bee (Apis mellifera), a social insect species with a high degree of social organization and one of the most important pollinators of wild plants and crops. In chapter II, a study is presented that aimed to identify the consequences of disrupted synchrony between colony phenology and the local environment by manipulating the timing of brood onset after hibernation. In a follow-up experiment, the importance of environmental factors for the timing of brood onset was investigated to assess the potential of climate change to disrupt synchronization of colony phenology (Chapter III). Chapter IV aimed to prove for the first time that honey bees can use interval time-place learning to improve foraging activity in a variable environment. Chapter V investigates the fitness benefits of information exchange between nest mates via waggle dance communication about a resource environment that is heterogeneous in space and time. II. In the study presented in chapter II, the importance of the timing of brood onset after hibernation as critical point in honey bee colony phenology in temperate zones was investigated. Honey bee colonies were overwintered at two climatically different sites. By translocating colonies from each site to the other in late winter, timing of brood onset was manipulated and consequently colony phenology was desynchronized with the local environment. Delaying colony phenology in respect to the local environment decreased the capability of colonies to exploit the abundant spring bloom. Early brood onset, on the other hand, increased the loads of the brood parasite Varroa destructor later in the season with negative impact on colony worker population size. This indicates a timing related trade-off and illustrates the importance of investigating effects of climate change on complex multi-trophic systems. It can be concluded that timing of brood onset in honey bees is an important fitness relevant step for colony phenology that is highly sensitive to climatic conditions in late winter. Further, phenology shifts and mismatches driven by climate change can have severe fitness consequences. III. In chapter III, I assess the importance of the environmental factors ambient temperature and photoperiod as well as elapsed time on the timing of brood onset. Twenty-four hibernating honey bee colonies were placed into environmental chambers and allocated to different combinations of two temperature regimes and three different light regimes. Brood onset was identified non-invasively by tracking comb temperature within the winter cluster. The experiment revealed that ambient temperature plays a major role in the timing of brood onset, but the response of honey bee colonies to temperature increases is modified by photoperiod. Further, the data indicate the involvement of an internal clock. I conclude that the timing of brood onset is complex but probably highly susceptible to climate change and especially spells of warm weather in winter. IV. In chapter IV, it was examined if honey bees are capable of interval time-place learning and if this ability improves foraging efficiency in a dynamic resource environment. In a field experiment with artificial feeders, foragers were able to learn time intervals and use this ability to anticipate time periods during which feeders were active. Further, interval time-place learning enabled foragers to increase nectar uptake rates. It was concluded that interval time-place learning can help honey bee foragers to adapt to the complex and variable temporal patterns of floral resource environments. V. The study presented in chapter V identified the importance of the honey bee waggle dance communication for the spatiotemporal coordination of honey bee foraging activity in resource environments that can vary from day to day. Consequences of disrupting the instructional component of honey bee dance communication were investigated in eight temperate zone landscapes with different levels of spatiotemporal complexity. While nectar uptake of colonies was not affected, waggle dance communication significantly benefitted pollen harvest irrespective of landscape complexity. I suggest that this is explained by the fact that honey bees prefer to forage pollen in semi-natural habitats, which provide diverse resource species but are sparse and presumably hard to find in intensively managed agricultural landscapes. I conclude that waggle dance communication helps to ensure a sufficient and diverse pollen diet which is crucial for honey bee colony health. VI. In my PhD-project, I could show that honey bee colonies are able to adapt their activities to a seasonally and daily changing environment, which affects resource uptake, colony development, colony health and ultimately colony fitness. Ongoing global change, however, puts timing in honey bee colonies at risk. Climate change has the potential to cause mismatches with the local resource environment. Intensivation of agricultural management with decreased resource diversity and short resource peaks in spring followed by distinctive gaps increases the probability of mismatches. Even the highly efficient foraging system of honey bees might not ensure a sufficiently diverse and healthy diet in such an environment. The global introduction of the parasitic mite V. destructor and the increased exposure to pesticides in intensively managed landscapes further degrades honey bee colony health. This might lead to reduced cognitive capabilities in workers and impact the communication and social organization in colonies, thereby undermining the ability of honey bee colonies to adapt to their environment.},
  subject      = {Biene},
  language  = {en}
}
@phdthesis{Glogger2018,
  author    = {Glogger, Marius},
  title     = {Single-molecule fluorescence microscopy in live \(Trypanosoma\) \(brucei\) and model membranes},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169222},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Der eukaryotische Parasit Trypanosoma brucei hat komplexe Strategien entwickelt um der Immunantwort eines Wirtes zu entkommen und eine persistente Infektion innerhalb dessen aufrechtzuerhalten. Ein zentrales Element seiner Verteidigungsstrategie st{\"u}tzt sich auf die Schutzfunktion seines Proteinmantels auf der Zelloberfl{\"a}che. Dieser Mantel besteht aus einer dichten Schicht aus identischen, Glykosylphosphatidylinositol (GPI)-verankerten variablen Oberfl{\"a}chenglykoproteinen (VSG). Der VSG Mantel verhindert die Erkennung der darunterliegenden, invarianten Epitope durch das Immunsystem. Obwohl es notwendig ist die Funktionsweise des VSG Mantels zu verstehen, vor allem um ihn als m{\"o}gliches Angriffsziel gegen den Parasiten zu verwenden, sind seine biophysikalischen Eigenschaften bisher nur unzureichend verstanden. Dies ist vor allem der Tatsache geschuldet, dass die hohe Motilit{\"a}t der Parasiten mikroskopische Studien in lebenden Zellen bisher weitestgehend verhinderten. In der vorliegenden Arbeit wird nun hochmoderne Einzelmolek{\"u}l-Fluoreszenzmikroskopie (EMFM) als M{\"o}glichkeit f{\"u}r mikroskopische Untersuchungen im Forschungsbereich der Trypanosomen vorgestellt. Die Arbeit umfasst Untersuchungen der VSG Dynamik unter definierten Bedingungen k{\"u}nstlicher Membransysteme. Es wurde zuerst der Einfluss der lateralen Proteindichte auf die VSG Diffusion untersucht. Experimente mittels Fluoreszenz- Wiederkehr nach irreversiblem Photobleichen und komplement{\"a}re Einzelmolek{\"u}l- Verfolgungs Experimente offenbarten, dass ein molekularer Diffusionsschwellenwert existiert. {\"U}ber diesem Schwellenwert wurde eine dichteabh{\"a}nige Reduzierung des Diffusionskoeffizienten gemessen. Eine relative Quantifizierung der rekonstituierten VSGs verdeutlichte, dass der Oberfl{\"a}chenmantel der Trypanosomen sehr nahe an diesem Schwellenwert agiert. Der VSG Mantel ist optimiert um eine hohe Proteindichte bei gleichzeitiger hoher Mobilit{\"a}t der VSGs zu gew{\"a}hrleisten. Des Weiteren wurde der Einfluss der VSG N-Glykosylierung auf die Diffusion des Proteins quantitativ untersucht. Die Messungen ergaben, dass die N-Glykosylierung dazu beitr{\"a}gt eine hohe Mobilit{\"a}t bei hohen Proteindichten aufrechtzuerhalten. Eine detaillierte Analyse von VSG Trajektorien offenbarte, dass zwei unterschiedliche Populationen frei diffundierender VSGs in der k{\"u}nstlichen Membran vorlagen. K{\"u}rzlich wurde entdeckt, dass VSGs zwei strukturell unterschiedliche Konformationen annehmen k{\"o}nnen. Die Messungen in der Arbeit stimmen mit diesen Beschreibungen {\"u}berein. Die Ergebnisse der EMFM in k{\"u}nstlichen Membranen wurden durch VSG Einzelmolek{\"u}l- Verfolgungs Experimente auf lebenden Zellen erg{\"a}nzt. Es wurde eine hohe Mobilit{\"a}t und Dynamik einzelner VSGs gemessen, was die allgemein dynamische Natur des VSG Mantels verdeutlicht. Dies f{\"u}hrte zu der Schlussfolgerung, dass der VSG Mantel auf lebenden Trypanosomen ein dichter und dennoch dynamischer Schutzmantel ist. Die F{\"a}higkeit der VSGs ihre Konformation flexibel anzupassen, unterst{\"u}tzt das Erhalten der Fluidit{\"a}t bei variablen Dichten. Diese Eigenschaften des VSG Mantels sind elementar f{\"u}r die Aufrechterhaltung einer presistenden Infektion eines Wirtes. In dieser Arbeit werden des Weiteren verschiedene, auf Hydrogel basierende Einbettungsmethoden vorgestellt. Diese erm{\"o}glichten die Zellimmobilisierung und erlaubten EMFM in lebenden Trypanosomen. Die Hydrogele wiesen eine hohe Zytokompatibilit{\"a}t auf. Die Zellen {\"u}berlebten in den Gelen f{\"u}r eine Stunde nach Beginn der Immobilisierung. Die Hydrogele erf{\"u}llten die Anforderungen der Superresolution Mikroskopie (SRM) da sie eine geringe Autofluoreszenz im Spektralbereich der verwendeten Fluorophore besaßen. Mittels SRM konnte nachgewiesen werden, dass die Hydrogele die Zellen effizient immobilisierten. Als erstes Anwendungsbeispiel der Methode wurde die Organisation der Plasmamembran in lebenden Trypanosomen untersucht. Die Untersuchung eines fluoreszenten Tracers in der inneren Membranschicht ergab, dass dessen Verteilung nicht homogen war. Es wurden spezifische Membrandom{\"a}nen gefunden, in denen das Molek{\"u}l entweder vermehrt oder vermindert auftrat. Dies f{\"u}hrte zu der Schlussfolgerung, dass diese Verteilung durch eine Interaktion des Tracers mit Proteinen des zellul{\"a}ren Zytoskeletts zustande kam. Die in dieser Arbeit pr{\"a}sentierten Ergebnisse zeigen, dass EMFM erfolgreich f{\"u}r verschiedene biologische Untersuchungen im Forschungsfeld der Trypanosomen angewendet werden kann. Dies gilt zum Beispiel f{\"u}r die Untersuchung von der VSG Dynamik in k{\"u}nstlichen Membransystemen, aber auch f{\"u}r Studien in lebenden Zellen unter Verwendung der auf Hydrogelen basierenden Zelleinbettung.},
  subject      = {Trypanosoma brucei},
  language  = {en}
}
@phdthesis{Halboth2018,
  author    = {Halboth, Florian},
  title     = {Building behavior and nest climate control in leaf-cutting ants: How environmental cues affect the building responses of workers of \(Atta\) \(vollenweideri\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161701},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The present work investigates the influence of environmental stimuli on the building behavior of workers of the leaf-cutting ant Atta vollenweideri. It focuses on cues related to the airflow-driven ventilation of their giant underground nests, i.e., air movements and their direction, carbon dioxide concentrations and humidity levels of the nest air. First, it is shown that workers are able to use airflow and its direction as learned orientation cue by performing learning experiments with individual foragers using a classical conditioning paradigm. This ability is expected to allow workers to also navigate inside the nest tunnels using the prevailing airflow directions for orientation, for example during tasks related to nest construction and climate control. Furthermore, the influence of carbon dioxide on the digging behavior of workers is investigated. While elevated CO2 levels hardly affect the digging rate of the ants, workers prefer to excavate at locations with lower concentrations and avoid higher CO2 levels when given a choice. Under natural conditions, shifting their digging activity to soil layers containing lower carbon dioxide levels might help colonies to excavate new or to broaden existing nest openings, if the CO2 concentration in the underground rises. It is also shown that workers preferably transport excavated soil along tunnels containing high CO2 concentrations, when carbon dioxide levels in the underground are elevated as well. In addition, workers prefer to carry soil pellets along outflow tunnels instead of inflow tunnels, at least for high humidity levels of the air. The material transported along tunnels providing outflow of CO2-rich air might be used by workers for the construction of ventilation turrets on top of the nest mound, which is expected to promote the wind-induced ventilation and the removal of carbon dioxide from the underground. The climatic conditions inside the nest tunnels also influence the structural features of the turrets constructed by workers on top the nest. While airflow and humidity have no effect on turret structure, outflow of CO2-rich air from the nest causes workers to construct turrets with additional openings and increased aperture, potentially enhancing the airflow-driven gas exchanges within the nest. Finally, the effect of airflow and ventilation turrets on the gas exchanges in Atta vollenweideri nests is tested experimentally on a physical model of a small nest consisting of a single chamber and two nest tunnels. The carbon dioxide clearance rate from the underground was measured depending on both the presence of airflow in the nest and the structural features of the built turrets. Carbon dioxide is removed faster from the physical nest model when air moves through the nest, confirming the contribution of wind-induced flow inside the nest tunnels to the ventilation of Atta vollenweideri nests. In addition, turrets placed on top of one of the tunnel openings of the nest further enhance the CO2 clearance rate and the effect is positively correlated with turret aperture. Taken together, climatic variables like airflow, carbon dioxide and humidity levels strongly affect the building responses of Atta vollenweideri leaf-cutting ants. Workers use these environmental stimuli as orientation cue in the nest during tasks related to excavation, soil transport and turret construction. Although the effects of these building responses on the microclimatic conditions inside the nest remain elusive so far, the described behaviors are expected to allow ant colonies to restore and maintain a proper nest climate in the underground.},
  subject      = {Verhalten},
  language  = {en}
}
@phdthesis{Koenig2018,
  author    = {K{\"o}nig, Julia Maria},
  title     = {Fungal grass endophytes and their dependence on land-use intensity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-163890},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Plant-associated fungi can affect the plants' interaction with herbivores and other microorganisms. For example, many common forage grasses are infected with Epichlo{\"e} endophytes. The endophytes systemically colonize the aerial parts of the plants. They produce bioprotective alkaloids that can negatively affect insects and livestock feeding on the grasses, and interact with other fungal species which living from the plants' nutrients. Environmental conditions strongly influence Epichlo{\"e} endophytes. Endophyte-mediated effects on herbivores are more pronounced under increased temperatures and the endophytes may benefit from land use in managed grasslands. Under the framework of the large-scale German project "Biodiversity Exploratories", I investigated whether infection rates and alkaloid concentrations of Epichlo{\"e} festucae var. lolii in Lolium perenne (Chapter I) and Epichlo{\"e} endophytes (E. uncinata, E. siegelii) in Festuca pratensis (Chapter II) depend on land use and season. Further I analysed, whether foliar fungal assemblages of L. perenne are affected by the presence of Epichlo{\"e} endophytes (Chapter IV).},
  subject      = {Endophytische Pilze},
  language  = {en}
}
@phdthesis{Boeck2018,
  author    = {B{\"o}ck, Julia},
  title     = {Differenzielle Methylierungsanalysen mittels verschiedener Next-Generation Sequencing-basierter Techniken: Die Bedeutung von differenziell methylierten Regionen in der menschlichen Hirnevolution und bei der Krebsentstehung},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164220},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Die Evolution der Primaten zeigt eine Verbindung zwischen der zunehmenden Komplexit{\"a}t des sozialen Verhaltens und der Vergr{\"o}ßerung des humanen Gehirns, insbesondere des pr{\"a}frontalen Cortex. Deshalb stellt der pr{\"a}frontale Cortex bez{\"u}glich der Evolution des Menschen eine der interessantesten Strukturen im humanen Gehirn dar. Es wird angenommen, dass nicht allein die Gr{\"o}ße, sondern auch die Funktion, vor allem das Zusammenspiel von Neuronen und nicht-neuronalen Zellen, wie z.B. Gliazellen, zur Differenzierung des menschlichen Gehirns von dem rezenter Primaten gef{\"u}hrt hat. Daraus l{\"a}sst sich schließen, dass die Gehirnfunktionen {\"u}ber eine ausgeglichene und gut aufeinander abgestimmte transkriptionelle Landschaft kontrolliert werden, die durch ein zugrundeliegendes genetisches und epigentisches R{\"u}ckgrat organisiert ist. In dieser Studie wurden das Methylierungsprofil neuronaler und nicht-neuronaler Zellen des pr{\"a}frontalen Cortex (Brodmann-Areal 10) von drei Menschen und drei Schimpansen miteinander verglichen. Die intra- und interspezifischen differenziell methylierten Regionen (DMRs) waren in bestimmten genomischen Regionen angereichert. Intraspezifische Methylierungsunterschiede zwischen neuronalen und nicht-neuronalen Zellen konnten dreimal h{\"a}ufiger beobachtet werden als interspezifische Unterschiede in den einzelnen Zelltypen. Rund 90\% der humanen intraspezifischen DMRs wiesen eine Hypomethylierung in den neuronalen Zellen im Vergleich zu den nicht-neuronalen Zellen auf. In den intraspezifischen DMRs (Mensch und Schimpanse) waren Gene angereichert, die mit verschiedenen neuropsychiatrischen Erkrankungen assoziiert sind. Der Vergleich zwischen Menschen und Schimpanse in den neuronalen und nicht-neuronalen Zelltypen zeigte eine Anreicherung von Genen mit human-spezifischer Histonsignatur. In den nicht-neuronalen Zellen konnten mehr interspezifische DMRs (n=666) detektiert werden als in den neuronalen Zellen (n=96). Ungef{\"a}hr 95\% der nicht-neuronalen interspezifischen DMRs waren im Menschen, im Vergleich zum Schimpansen, hypermethyliert. Daraus ergibt sich der Eindruck, dass mehrere hundert der nicht-neuronalen Gene w{\"a}hrend der humanen Gehirnevolution einer Methylierungswelle unterlagen. Dies f{\"u}hrt zu der Annahme, dass der Einfluss dieser Ver{\"a}nderungen in den nicht-neuronalen Zellen auf die Verg{\"o}ßerung des menschlichen Gehirns bisher stark untersch{\"a}tzt wurde. Die bekannteste genetische Ursache f{\"u}r erblichen Brust- und Eierstockkrebs sind Mutationen in den Tumorsuppressorgenen (TSG) BRCA1 und BRCA2. Dennoch k{\"o}nnen nur rund 20-25\% der famili{\"a}ren Brustkrebserkrankungen {\"u}ber Keimbahnmutationen in BRCA1/BRCA2 erkl{\"a}rt werden, besonders bei Frauen, deren Erkrankung vor dem vierzigsten Lebensjahr auftritt. Epigenetische Ver{\"a}nderungen, die zu einer aberranten Genexpression f{\"u}hren, spielen ebenfalls eine wichtige Rolle bei der Karzinogenese und der Entwicklung einer Brustkrebserkrankung. Es ist bekannt, dass TSG nicht nur durch den Verlust der Heterozygotie (engl. loss of heterozygosity, LOH) oder homozygote Deletionen, sondern auch durch transkriptionelle Stilllegung via DNA-Methylierung inaktiviert werden k{\"o}nnen. Im Rahmen dieser Arbeit wurde {\"u}berpr{\"u}ft, welchen Einfluss aberrante Methylierungsmuster im Promotorbereich von TSG auf die Brustkrebskarzinogenese und die Expression der Gene haben. F{\"u}r die Quantifizierung der Epimutationen wurden die Promotorbereiche von acht TSG (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) und des estrogene receptor (ESR1) Gens, welches eine Rolle in der Tumorprogression spielt, mittels Deep Bisulfite Amplicon Sequencing (DBAS) analysiert. Es wurden Blutproben von zwei unabh{\"a}ngigen BRCA1/BRCA2-mutationsnegativen Brustkrebs (BC)-Patientenkohorten, sowie von zwei unabh{\"a}ngigen alters-gematchten, gesunden Kontrollkohorten untersucht. BC-Kohorte 1 beinhaltet early-onset (EO) BC-Patientinnen. Kohorte 2 enth{\"a}lt BC-Patientinnen mit einem Risiko von >95\% eine heterozygote Mutation in BRCA1/BRCA2 (high-risk, HR) zu tragen. Allele mit >50\% methylierten CpGs werden als funktionell relevante Epimutationen erachtet, da bekannt ist, dass TSG {\"u}ber eine Methylierung im Promotorbereich transkriptionell stillgelegt werden. Im Vergleich zu ESR1 ({\O} Methylierung, 3\%), welches die Methylierungslevel eines durchschnittlichen Promotors wiederspiegelt, zeigten die TSG sehr geringe durchschnittliche Methylierungswerte von weniger als 1\%. Zudem waren die durchschnittlichen Epimutationsraten (EMR; <0,0001-0,1\%) der TSG sehr gering. Mit der Ausnahme von BRCA1, welches eine erh{\"o}hte EMR in der BC-Kohorte verglichen zu den Kontrollen (0,31\% gegen 0,06\%) zeigte, gab es keine signifikanten Gruppenunterschiede zwischen BC-Patientinnen und Kontrollen. Eine von 36 HR BC-Patientinnen zeigte im Vergleich zu den restlichen Proben eine stark erh{\"o}hte EMR von 14,7\% in BRCA1. Rund ein Drittel (15/44) der EO BC-Patientinnen wiesen eine erh{\"o}hte Rate an Einzel-CpG Fehlern in mehreren TSG auf. Die nachfolgenden Expressionsanalysen ergaben eine erniedrigte Expression vieler TSG je analysierter Patientin. Diese Ergebnisse f{\"u}hren zu der Annahme, dass epigenetische Ver{\"a}nderungen in normalen K{\"o}rperzellen als ein m{\"o}glicher Indikator f{\"u}r einen gest{\"o}rten Mechanismus, der f{\"u}r die Aufrechterhaltung des unmethylierten Status und der daraus resultierenden normalen Genexpression zust{\"a}ndig ist, angesehen werden k{\"o}nnen. Dies kann mit einem erh{\"o}hten BC-Risiko assoziiert werden.},
  subject      = {Epigenetik},
  language  = {de}
}
@phdthesis{Kropf2018,
  author    = {Kropf, Jan},
  title     = {The Dual Olfactory Pathway in the Honeybee Brain: Sensory Supply and Electrophysiological Properties},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-108369},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {The olfactory sense is of utmost importance for honeybees, Apis mellifera. Honeybees use olfaction for communication within the hive, for the identification of nest mates and non-nest mates, the localization of food sources, and in case of drones (males), for the detection of the queen and mating. Honeybees, therefore, can serve as excellent model systems for an integrative analysis of an elaborated olfactory system. To efficiently filter odorants out of the air with their antennae, honeybees possess a multitude of sensilla that contain the olfactory sensory neurons (OSN). Three types of olfactory sensilla are known from honeybee worker antennae: Sensilla trichoidea, Sensilla basiconica and Sensilla placodea. In the sensilla, odorant receptors that are located in the dendritic arborizations of the OSNs transduce the odorant information into electrical information. Approximately 60.000 OSN axons project in two parallel bundles along the antenna into the brain. Before they enter the primary olfactory brain center, the antennal lobe (AL), they diverge into four distinct tracts (T1-T4). OSNs relay onto ~3.000-4.000 local interneurons (LN) and ~900 projection neurons (PN), the output neurons of the AL. The axons of the OSNs together with neurites from LNs and PNs form spheroidal neuropil units, the so-called glomeruli. OSN axons from the four AL input tracts (T1-T4) project into four glomerular clusters. LNs interconnect the AL glomeruli, whereas PNs relay the information to the next brain centers, the mushroom body (MB) - associated with sensory integration, learning and memory - and the lateral horn (LH). In honeybees, PNs project to the MBs and the LH via two separate tracts, the medial and the lateral antennal-lobe tract (m/lALT) which run in parallel in opposing directions. The mALT runs first to the MB and then to the LH, the lALT runs first to the LH and then to the MB. This dual olfactory pathway represents a feature unique to Hymenoptera. Interestingly, both tracts were shown to process information about similar sets of odorants by extracting different features. Individual mALT PNs are more odor specific than lALT PNs. On the other hand, lALT PNs have higher spontaneous and higher odor response action potential (AP) frequencies than mALT PNs. In the MBs, PNs form synapses with ~184.000 Kenyon cells (KC), which are the MB intrinsic neurons. KCs, in contrast to PNs, show almost no spontaneous activity and employ a spatially and temporally sparse code for odor coding. In manuscript I of my thesis, I investigated whether the differences in specificity of odor responses between m- and lALT are due to differences in the synaptic input. Therefore, I investigated the axonal projection patterns of OSNs housed in S. basiconica in honeybee workers and compared them with S. trichoidea and S. placodea using selective anterograde labeling with fluorescent tracers and confocal- microscopy analyses of axonal projections in AL glomeruli. Axons of S. basiconica-associated OSNs preferentially projected into the T3 input-tract cluster in the AL, whereas the two other types of sensilla did not show a preference for a specific glomerular cluster. T3- associated glomeruli had previously been shown to be innervated by mALT PNs. Interestingly, S. basiconica as well as a number of T3 glomeruli lack in drones. Therefore I set out to determine whether this was associated with the reduction of glomeruli innervated by mALT PNs. Retrograde tracing of mALT PNs in drones and counting of innervated glomeruli showed that the number of mALT-associated glomeruli was strongly reduced in drones compared to workers. The preferential projections of S. basiconica-associated OSNs into T3 glomeruli in female workers together with the reduction of mALT-associated glomeruli in drones support the presence of a female-specific olfactory subsystem that is partly innervated by OSNs from S. basiconica and is associated with mALT projection neurons. As mALT PNs were shown to be more odor specific, I suppose that already the OSNs in this subsystem are more odor specific than lALT associated OSNs. I conclude that this female-specific subsystem allows the worker honeybees to respond adequately to the enormous variety of odorants they experience during their lifetime. In manuscript II, I investigated the ion channel composition of mALT and lALT PNs and KCs in situ. This approach represents the first study dealing with the honeybee PN and KC ion channel composition under standard conditions in an intact brain preparation. With these recordings I set out to investigate the potential impact of intrinsic neuronal properties on the differences between m- and lALT PNs and on the sparse odor coding properties of KCs. In PNs, I identified a set of Na+ currents and diverse K+ currents depending on voltage and Na+ or Ca2+ that support relatively high spontaneous and odor response AP frequencies. This set of currents did not significantly differ between mALT and lALT PNs, but targets for potential modulation of currents leading to differences in AP frequencies were found between both types of PNs. In contrast to PNs, KCs have very prominent K+ currents, which are likely to contribute to the sparse response fashion observed in KCs. Furthermore, Ca2+ dependent K+ currents were found, which may be of importance for coincidence detection, learning and memory formation. Finally, I conclude that the differences in odor specificity between m- and lALT PNs are due to their synaptic input from different sets of OSNs and potential processing by LNs. The differences in spontaneous activity between the two tracts may be caused by different neuronal modulation or, in addition, also by interaction with LNs. The temporally sparse representation of odors in KCs is very likely based on the intrinsic KC properties, whereas general excitability and spatial sparseness are likely to be regulated through GABAergic feedback neurons.},
  subject      = {Voltage-Clamp-Methode},
  language  = {en}
}
@phdthesis{Jung2018,
  author    = {Jung, Jamin},
  title     = {Precise timing of the trypanosome cell division cycle},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114932},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {African trypanosomes are the causative agents of fatal diseases in humans and livestock. Trypanosomes show a complex lifecycle and shuttle between the transmitting vector, the tsetse (Glossina spec.), and the mammalian host. As a result of this the parasite undergoes tremendous changes in morphology and metabolism to adapt to the different living environments. The two best-studied lifecycle stages are the procyclic forms (PCF) that live in the tsetse fly and the proliferative bloodstream form (BSF) that resides in the mammalian blood. The most conspicuous weapon that trypanosomes use to evade the host immune attack is a dense layer of a single protein type, the variant surface glycoprotein (VSG), which shields the entire cell surface. Immune evasion required high rates of surface membrane turnover and surface coat recycling. Trypanosomes show highly polarised cell architecture with all major eukaryotic organelles (endoplasmic reticulum, Golgi apparatus, endosomal apparatus, lysosome, mitochondrion and peroxisome-like glycosomes) generally present in single copy. Furthermore, trypanosomes possess a single flagellum, which is important not only for cellular motility but also for cell division. How the duplication of all these cellular components is coordinated in order to progresss through the cell division cycle is poorly understood. We used trypanosomes as a model organism due to the relative simplicity and the polarised nature of their cell architecture and determined the duplication of all their compartments. This was only possible due to a new synchronisation approach developed during this project. In the first part of the thesis a precise temporal map of the cell division cycle of the BSF T. brucei cell division cycle was generated. By the use of well-described morphological markers (K/N status, new flagellum outgrowth and DNA synthesis) the position of individual cells was determined with high temporal resolution; this allowed us for the first time to synchronise a cell population in silico without affecting the naturally asynchronous growth. In the second part of the thesis we used this tool to follow duplication events of the Major organelles during progression through the cell division cycle. We precisely determined the time points of organelle duplication and found that it is ordered in trypanosomes. Furthermore we found that BSF T. brucei cells do not grow continuously, cell size start to increase rapidly, during a short period of time, late in the cell division cycle. We speculate that the initiation of cell volume increase is temporally separated from the formation of all secretory organelles in order to ensure maintenance of the protective coat, which must remain intact at all times in order for BSF trypanosomes to be able to evade the host immune response.},
  subject      = {Zellteilung},
  language  = {en}
}