@phdthesis{Triphan2009,
  author    = {Triphan, Tilman},
  title     = {The Central Control of Gap Climbing Behaviour in Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-43666},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {In this work, a behavioural analysis of different mutants of the fruit fly Drosophila melanogaster has been carried out. Primarily, the gap climbing behaviour (Pick \& Strauss, 2005) has been assayed as it lends itself for the investigation of decision making processes and the neuronal basis of adaptive behaviour. Furthermore it shows how basic motor actions can be combined into a complex motor behaviour. Thanks to the neurogenetic methods, Drosophila melanogaster has become an ideal study object for neurobiological questions. Two different modules of climbing control have been examined in detail. For the decision making, the mutant climbing sisyphus was analysed. While wild-type flies adapt the initiation of climbing behaviour to the width of the gap and the probability for a successful transition. climbing sisyphus flies initiate climbing behaviour even at clearly insurmountable gap widths. The climbing success itself is not improved in comparison to the wild-type siblings. The mutant climbing sisyphus is a rare example of a hyperactive mutant besides many mutants that show a reduced activity. Basic capabilities in vision have been tested in an optomotor and a distance-estimation paradigm. Since they are not affected, a defect in decision making is most probably the cause of this behavioural aberration. A second module of climbing control is keeping up orientation towards the opposite side of the gap during the execution of climbing behaviour. Mutants with a structural defect in the protocerebral bridge show abnormal climbing behaviour. During the climbing attempt, the longitudinal body axis does not necessarily point into the direction of the opposite side. Instead, many climbing events are initiated at the side edge of the walking block into the void and have no chance to ever succeed. The analysed mutants are not blind. In one of the mutants, tay bridge1 (tay1) a partial rescue attempt used to map the function in the brain succeeded such that the state of the bridge was restored. That way, a visual targeting mechanism has been activated, allowing the flies to target the opposite side. When the visibility of the opposing side was reduced, the rescued flies went back to a tay1 level of directional scatter. The results are in accord with the idea that the bridge is a central constituent of the visual targeting mechanism. The tay1 mutant was also analysed in other behavioural paradigms. A reduction in walking speed and walking activity in this mutant could be rescued by the expression of UAS-tay under the control of the 007Y-GAL4 driver line, which concomitantly restores the structure of the protocerebral bridge. The separation of bridge functions from functions of other parts of the brain of tay1 was accomplished by rescuing the reduced optomotor compensation in tay1 by the mb247-GAL4>UAS-tay driver. While still having a tay1-like protocerebral bridge, mb247-GAL4 rescue flies are able to compensate at wild-type levels. An intact compensation is not depended on the tay expression in the mushroom bodies, as mushroom body ablated flies with a tay1 background and expression of UAS-tay under the control of mb247-GAL4 show wild-type behaviour as well. The most likely substrate for the function are currently unidentified neurons in the fan-shaped body, that can be stained with 007Y-GAL4 and mb247-GAL4 as well.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Lapuente2021,
  author    = {Lapuente, Juan M.},
  title     = {The Chimpanzees of the Como{\´e} National Park, Ivory Coast. Status, distribution, ecology and behavior},
  doi       = {10.25972/OPUS-22318},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223180},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Although wild chimpanzees (Pan troglodytes) have been studied intensely for more than 50 years, there are still many aspects of their ecology and behavior that are not well understood. Every time that a new population of chimpanzees has been studied, new behaviors and unknown aspects of their ecology have been discovered. All this accumulated knowledge is helping us to piece together a model of how could last human and chimpanzee common ancestors have lived and behaved between seven and five million years ago. Como{\´e} chimpanzees had never been studied in depth, until we started our research in October 2014, only a few censuses had been realized. The last surveys prior our work, stated that the population was so decimated that was probably functionally extinct. When we started this research, we had to begin with a new intensive survey, using new methods, to ascertain the real status and distribution of the chimpanzees living in Como{\´e} National Park (CNP). During the last five years, we have realized a deep study aiming to know more about their ecology and behavior. We combined transects and reconnaissance marches (recces) with the use of camera traps, for the first time in CNP, obtaining a wealth of data that is not fully comprised in this dissertation. With this research, we determined that there is a sustainable continuous population of Western chimpanzees (Pan troglodytes verus) in CNP and the adjacent area of Mont Tingui, to the West, with a minimum of 127 weaned chimpanzees living in our main 900 km2 study area, SW of CNP. We found that this population is formed by a minimum of eight different chimpanzee communities, of which we studied seven, four of them more in detail. These chimpanzees spent much more time in the forest than in the savanna habitats. We also found that Como{\´e} chimpanzees consumed at least 58 different food items in their dit, which they obtained both from forest and savanna habitats. Another finding was that insectivory had an important role in their diet, with at least four species of ants, three of termites and some beetle larvae. These chimpanzees also hunted at least three species of monkeys and maybe rodents and duikers and occasionally consumed the big land snails of genus Achatina. We found that, during the fruit scarcity period in the late rainy season, they intensely consumed the cambium of Ceiba pentandra, as fallback food, much more than the bark or cambium of any other tree species. Another interesting finding was that all the chimpanzees in the studied area realized this particular bark-peeling behavior and had been repeatedly peeling the trees of this species for years. This did not increase tree mortality and the damage caused to the trees was healed in two years, not reducing the growth, thus being a sustainable use of the trees. We found that Como{\´e} chimpanzees produced and used a great variety of tools, mainly from wooden materials, but also from stone and herbaceous vegetation. Their tool repertory included stick tools to dip for Dorylus burmeisteri ants, to fish for Camponotus and Crematogaster ants, to dip for honey, mainly from Meliponini stingless bees, but sometimes from honey bees (Apis mellifera). It also included the use of stick tools to fish termites of Macrotermes subhyalinus and Odontotermes majus (TFTs), to dip for water from tree holes and investigatory probes for multiple purposes. Additionally, these chimpanzees used leaf-sponges to drink from tree holes and to collect clayish water from salt-licks. They also used stones to hit the buttresses of trees during displays, the so called accumulative stone throwing behavior and probably used stones as hammers, to crack open hard-shelled Strichnos spinosa and Afraegle paniculata fruits and Achatina snails. The chimpanzees also used objects that are not generally accepted as animal tools, for being attached to the substrate, with different purposes: they drummed buttresses of trees with hands and/or feet to produce sound during male displays and they pounded open hard-shelled fruits, Achatina snails and Cubitermes termite mounds on stone or root anvils. We finally measured the stick tools and found significant differences between them suggesting that they were specialized tools made specifically for every purpose. We studied more in detail the differences between apparently similar tools, the honey dipping tools and the water dipping tools, often with brushes made at their tips to collect the fluids. These last tools were exclusive from Como{\´e} and have not been described at any other site. We found that total length, diameter and brush length were significantly different, suggesting that they were specialized tools. We concluded that Como{\´e} chimpanzees had a particular culture, different from those of other populations of Western chimpanzees across Africa. Efficient protection, further research and permanent presence of research teams are required to avoid that this unique population and its culture disappears by the poaching pressure and maybe by the collateral effects of climate change.},
  subject      = {Parc National de la Como{\´e}},
  language  = {en}
}
@phdthesis{Schubert2019,
  author    = {Schubert, Frank Klaus},
  title     = {The circadian clock network of \(Drosophila\) \(melanogaster\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157136},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2019},
  abstract  = {All living organisms need timekeeping mechanisms to track and anticipate cyclic changes in their environment. The ability to prepare for and respond to daily and seasonal changes is endowed by circadian clocks. The systemic features and molecular mechanisms that drive circadian rhythmicity are highly conserved across kingdoms. Therefore, Drosophila melanogaster with its relatively small brain (ca. 135.000 neurons) and the outstanding genetic tools that are available, is a perfect model to investigate the properties and relevance of the circadian system in a complex, but yet comprehensible organism. The last 50 years of chronobiological research in the fruit fly resulted in a deep understanding of the molecular machinery that drives circadian rhythmicity, and various histological studies revealed the neural substrate of the circadian system. However, a detailed neuroanatomical and physiological description on the single-cell level has still to be acquired. Thus, I employed a multicolor labeling approach to characterize the clock network of Drosophila melanogaster with single-cell resolution and additionally investigated the putative in- and output sites of selected neurons. To further study the functional hierarchy within the clock network and to monitor the "ticking clock" over the course of several circadian cycles, I established a method, which allows us to follow the accumulation and degradation of the core clock genes in living brain explants by the means of bioluminescence imaging of single-cells.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Kay2018,
  author    = {Kay, Janina},
  title     = {The circadian clock of the carpenter ant \(Camponotus\) \(floridanus\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158061},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {Due to the earth´s rotation around itself and the sun, rhythmic daily and seasonal changes in illumination, temperature and many other environmental factors occur. Adaptation to these environmental rhythms presents a considerable advantage to survival. Thus, almost all living beings have developed a mechanism to time their behavior in accordance. This mechanism is the endogenous clock. If it fulfills the criteria of (1) entraining to zeitgebers (2) free-running behavior with a period of ~ 24 hours (3) temperature compensation, it is also referred to as "circadian clock". Well-timed behavior is crucial for eusocial insects, which divide their tasks among different behavioral castes and need to respond to changes in the environment quickly and in an orchestrated fashion. Circadian rhythms have thus been studied and observed in many eusocial species, from ants to bees. The underlying mechanism of this clock is a molecular feedback loop that generates rhythmic changes in gene expression and protein levels with a phase length of approximately 24 hours. The properties of this feedback loop are well characterized in many insects, from the fruit fly Drosophila melanogaster, to the honeybee Apis mellifera. Though the basic principles and components of this loop are seem similar at first glance, there are important differences between the Drosophila feedback loop and that of hymenopteran insects, whose loop resembles the mammalian clock loop. The protein PERIOD (PER) is thought to be a part of the negative limb of the hymenopteran clock, partnering with CRYPTOCHROME (CRY). The anatomical location of the clock-related neurons and the PDF-network (a putative in- and output mediator of the clock) is also well characterized in Drosophila, the eusocial honeybee as well as the nocturnal cockroach Leucophea maderae. The circadian behavior, anatomy of the clock and its molecular underpinnings were studied in the carpenter ant Camponotus floridanus, a eusocial insect Locomotor activity recordings in social isolation proved that the majority of ants could entrain to different LD cycles, free-ran in constant darkness and had a temperature-compensated clock with a period slightly shorter than 24 hours. Most individuals proved to be nocturnal, but different types of activity like diurnality, crepuscularity, rhythmic activity during both phases of the LD, or arrhythmicity were also observed. The LD cycle had a slight influence on the distribution of these activities among individuals, with more diurnal ants at shorter light phases. The PDF-network of C. floridanus was revealed with the anti-PDH antibody, and partly resembled that of other eusocial or nocturnal insects. A comparison of minor and major worker brains, only revealed slight differences in the number of somata and fibers crossing the posterior midline. All in all, most PDF-structures that are conserved in other insects where found, with numerous fibers in the optic lobes, a putative accessory medulla, somata located near the proximal medulla and many fibers in the protocerebrum. A putative connection between the mushroom bodies, the optic lobes and the antennal lobes was found, indicating an influence of the clock on olfactory learning. Lastly, the location and intensity of PER-positive cell bodies at different times of a 24 hour day was established with an antibody raised against Apis mellifera PER. Four distinct clusters, which resemble those found in A. mellifera, were detected. The clusters could be grouped in dorsal and lateral neurons, and the PER-levels cycled in all examined clusters with peaks around lights on and lowest levels after lights off. In summary, first data on circadian behavior and the anatomy and workings of the clock of C. floridanus was obtained. Firstly, it´s behavior fulfills all criteria for the presence of a circadian clock. Secondly, the PDF-network is very similar to those of other insects. Lastly, the location of the PER cell bodies seems conserved among hymenoptera. Cycling of PER levels within 24 hours confirms the suspicion of its role in the circadian feedback loop.},
  subject      = {Chronobiologie},
  language  = {en}
}
@phdthesis{Ruf2016,
  author    = {Ruf, Franziska},
  title     = {The circadian regulation of eclosion in \(Drosophila\) \(melanogaster\)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146265},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Eclosion is the emergence of an adult insect from the pupal case at the end of development. In the fruit fly Drosophila melanogaster, eclosion is a circadian clock-gated event and is regulated by various peptides. When studied on the population level, eclosion reveals a clear rhythmicity with a peak at the beginning of the light-phase that persists also under constant conditions. It is a long standing hypothesis that eclosion gating to the morning hours with more humid conditions is an adaption to reduce water loss and increase the survival. Eclosion behavior, including the motor pattern required for the fly to hatch out of the puparium, is orchestrated by a well-characterized cascade of peptides. The main components are ecdysis-triggering hormone (ETH), eclosion hormone (EH) and crustacean cardioactive peptide (CCAP). The molt is initiated by a peak level and pupal ecdysis by a subsequent decline of the ecdysteroid ecdysone. Ecdysteroids are produced by the prothoracic gland (PG), an endocrine tissue that contains a peripheral clock and degenerates shortly after eclosion. Production and release of ecdysteroids are regulated by the prothoracicotropic hormone (PTTH). Although many aspects of the circadian clock and the peptidergic control of the eclosion behavior are known, it still remains unclear how both systems are interconnected. The aim of this dissertation research was to dissect this connection and evaluate the importance of different Zeitgebers on eclosion rhythmicity under natural conditions. Potential interactions between the central clock and the peptides regulating ecdysis motor behavior were evaluated by analyzing the influence of CCAP on eclosion rhythmicity. Ablation and silencing of CCAP neurons, as well as CCAP null-mutation did not affect eclosion rhythmicity under either light or temperature entrainment nor under natural conditions. To dissect the connection between the central and the peripheral clock, PTTH neurons were ablated. Monitoring eclosion under light and temperature entrainment revealed that eclosion became arrhythmic under constant conditions. However, qPCR expression analysis revealed no evidence for cycling of Ptth mRNA in pharate flies. To test for a connection with pigment-dispersing factor (PDF)-expressing neurons, the PDF receptor (PDFR) and short neuropeptide F receptor (sNPFR) were knocked down in the PTTH neurons. Knockdown of sNPFR, but not PDFR, resulted in arrhythmic eclosion under constant darkness conditions. PCR analysis of the PTTH receptor, Torso, revealed its expression in the PG and the gonads, but not in the brain or eyes, of pharate flies. Knockdown of torso in the PG lead to arrhythmicity under constant conditions, which provides strong evidence for the specific effect of PTTH on the PG. These results suggest connections from the PDF positive lateral neurons to the PTTH neurons via sNPF signaling, and to the PG via PTTH and Torso. This interaction presumably couples the period of the peripheral clock in the PG to that of the central clock in the brain. To identify a starting signal for eclosion and possible further candidates in the regulation of eclosion behavior, chemically defined peptidergic and aminergic neurons were optogenetically activated in pharate pupae via ChR2-XXL. This screen approach revealed two candidates for the regulation of eclosion behavior: Dromyosuppressin (DMS) and myo-inhibitory peptides (MIP). However, ablation of DMS neurons did not affect eclosion rhythmicity or success and the exact function of MIP must be evaluated in future studies. To assess the importance of the clock and of possible Zeitgebers in nature, eclosion of the wildtype Canton S and the clock mutant per01 and the PDF signaling mutants pdf01 and han5304 was monitored under natural conditions. For this purpose, the W{\"u}rzburg eclosion monitor (WEclMon) was developed, which is a new open monitoring system that allows direct exposure of pupae to the environment. A general decline of rhythmicity under natural conditions compared to laboratory conditions was observed in all tested strains. While the wildtype and the pdf01 and han5304 mutants stayed weakly rhythmic, the per01 mutant flies eclosed mostly arrhythmic. PDF and its receptor (PDFR encoded by han) are required for the synchronization of the clock network and functional loss can obviously be compensated by a persisting synchronization to external Zeitgebers. The loss of the central clock protein PER, however, lead to a non-functional clock and revealed the absolute importance of the clock for eclosion rhythmicity. To quantitatively analyze the effect of the clock and abiotic factors on eclosion rhythmicity, a statistical model was developed in cooperation with Oliver Mitesser and Thomas Hovestadt. The modelling results confirmed the clock as the most important factor for eclosion rhythmicity. Moreover, temperature was found to have the strongest effect on the actual shape of the daily emergence pattern, while light has only minor effects. Relative humidity could be excluded as Zeitgeber for eclosion and therefore was not further analyzed. Taken together, the present dissertation identified the so far unknown connection between the central and peripheral clock regulating eclosion. Furthermore, a new method for the analysis of eclosion rhythms under natural conditions was established and the necessity of a functional clock for rhythmic eclosion even in the presence of multiple Zeitgebers was shown.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Mishra2011,
  author    = {Mishra, Dushyant},
  title     = {The content of olfactory memory in larval Drosophila},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66316},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {An animal depends heavily on its sense of smell and its ability to form olfactory associations as this is crucial for its survival. This thesis studies in two parts about such associative olfactory learning in larval Drosophila. The first part deals with different aspects of odour processing while the second part is concerned with aspects related to memory and learning. Chapter I.1 highlights how odour intensities could be integrated into the olfactory percept of larval Drosophila. I first describe the dose-effect curves of learnability across odour intensities for different odours and then choose odour intensities from these curves such that larvae are trained at intermediate odour intensity, but are tested for retention with either that trained intermediate odour intensity, or with respectively HIGHer or LOWer intensities. I observe a specificity of retention for the trained intensity for all the odours used. Further I compare these findings with the case of adult Drosophila and propose a circuit level model of how such intensity coding comes about. Such intensity specificity of learning adds to appreciate the richness in 'content' of olfactory memory traces, and to define the demands on computational models of olfaction and olfactory learning. Chapter I.2 provides a behaviour-based estimate of odour similarity using four different types of experiments to yield a combined, task-independent estimate of perceived difference between odour-pairs. Further comparison of these perceived differences to published measures of physico- chemical difference reveals a weak correlation. Notable exceptions to this correlation are 3-octanol and benzaldehyde. Chapter I.3 shows for two odours (3-octanol and 1-octene-3-ol) that perceptual differences between these odours can either be ignored after non-discriminative training (generalization), or accentuated by odour-specific reinforcement (discrimination). Anosmic Or83b1 mutants have lost these faculties, indicating that this adaptive adjustment is taking place downstream of Or83b expressing sensory neurons. Chapter II.1 of this thesis deals with food supplementation with dried roots of Rhodiola rosea. This dose-dependently improves odour- reward associative function in larval Drosophila. Supplementing fly food with commercially available tablets or extracts, however, does not have a 'cognitive enhancing' effect, potentially enabling us to differentiate between the effective substances in the root versus these preparations. Thus Drosophila as a genetically tractable study case should now allow accelerated analyses of the molecular mechanism(s) that underlie this 'cognitive enhancement' conveyed by Rhodiola rosea. Chapter II.2 describes the role of Synapsin, an evolutionarily conserved presynaptic phosphoprotein using a combined behavioural and genetic approach and asks where and how, this protein affects functions in associative plasticity of larval Drosophila. This study shows that a Synapsin-dependent memory trace can be pinpointed to the mushroom bodies, a 'cortical' brain region of the insects. On the molecular level, data in this study assign Synapsin as a behaviourally- relevant effector of the AC-cAMP-PKA cascade.},
  subject      = {Drosophila},
  language  = {en}
}
@phdthesis{Heisswolf2006,
  author    = {Heisswolf, Annette},
  title     = {The distribution of leaf beetles on multiple spatial scales : causes and consequences},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-18945},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {Herbivorous insects are the major link between primary producers and a multitude of animals at higher trophic levels. Elucidating the causes and consequences of their distribution patterns in the "green world" is thus essential for our understanding of numerous ecological processes on multiple spatial scales. We can ask where and why a certain herbivore can be found in the landscape, within the habitat, on which plant within the habitat and finally, where on that plant. Depending on spatial scale the distribution of herbivores is shaped by different processes (fitness considerations, physiological abilities, population dynamics, dispersal behavior, history of the landscape etc.). Scaling down from fragmented landscapes to individual host plants this thesis analyzes the distribution patterns of the strictly monophagous herbivore Cassida canaliculata Laich. (Coleoptera: Chrysomelidae), which feeds and oviposits exclusively on meadow sage, Salvia pratensis L. (Lamiales: Lamiaceae), and compares it to those of the polyphagous tansy leaf beetle Galeruca tanaceti L. (Coleoptera: Chrysomelidae), which does not oviposit on its host plants, but on dry non-host structures. The specialist Cassida canaliculata depended on all spatial scales (fragmented landscape, microhabitat and host plant individual) mainly on the distribution and quality of its single host plant species Salvia pratensis, whereas enemy-free-space - i.e. avoidance of parasitism and predation of egg clutches, larvae, and pupae - seemed to influence oviposition site choice only on the scale of the host plant individual. On this spatial scale, offspring of Cassida canaliculata had a higher chance of survival on large host plant individuals, which were also preferred for oviposition by the females. In contrast, the distribution patterns of the generalist Galeruca tanaceti was shaped by the interaction with its parasitoid regarding both microhabitat choice and egg distribution within individual host plants. On the microhabitat scale, beetles could escape from their parasitoids by ovipositing into high and dense vegetation. Regarding oviposition site choice within a host plant individual, females oviposited as high as possible in the vegetation and could thus reduce both the risk of parasitism and the probability of winter mortality. The results of my thesis show that the degree of specificity of a herbivore is of central importance for the resulting egg distribution pattern on all spatial scales.},
  subject      = {Blattk{\"a}fer},
  language  = {en}
}
@phdthesis{Hsieh2011,
  author    = {Hsieh, Samuel Yu-Lung},
  title     = {The diversity and ecology of the spider communities of European beech canopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-66966},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2011},
  abstract  = {Ein wesentliches Ziel {\"o}kologischer Forschung ist es, die Frage zu beantworten, wie Arten koexistieren k{\"o}nnen und die biologische Vielfalt erhalten bleibt. Um zu verstehen, wie dabei Gemeinschaften in unterschiedlichen r{\"a}umlich-zeitlichen Dimensionen interagieren, um die biologische Vielfalt zu erhalten, ist ein umfassendes prozessorientiertes Wissen erforderlich. Demzufolge konzentrierte sich meine Studie im Wesentlichen auf die Biodiversit{\"a}t und die sie beeinflussenden raum-zeitlichen {\"o}kologischen Prozesse. Vergleicht man die {\"A}hnlich- bzw. Un{\"a}hnlichkeit der in verschieden alten Best{\"a}nden lebenden Spinnengemeinschaften der Buchen (Fagus sylvatica L.), dann zeigt sich, dass die {\"a}lteste Baumkohorte offensichtlich einzigartige Ressourcen besitzt, welche die Zusammensetzung der Spinnengemeinschaften deutlich pr{\"a}gen. {\"U}ber das Jahr hin zeigten die Spinnengemeinschaften trotz der jahreszeitlich unterschiedlich {\"o}kologischen Randbedingungen eine sich wiederholende, vorhersehbare Dynamik. Der Vergleich {\"u}ber die Jahre ergab, dass das "Neutrale Modell" und das "Nischen-Modell" gleichzeitig funktionieren k{\"o}nnen. Beide sind notwendig, um die Dynamik der in den Buchenkronen der verschiedenen Altersklassen lebenden Spinnengemeinschaften vollst{\"a}ndig erkl{\"a}ren zu k{\"o}nnen.},
  subject      = {Spinnen},
  language  = {en}
}
@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{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{Heidrich2021,
  author    = {Heidrich, Lea},
  title     = {The effect of environmental heterogeneity on communities},
  doi       = {10.25972/OPUS-22178},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221781},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {How diversity of life is generated, maintained, and distributed across space and time is the central question of community ecology. Communities are shaped by three assembly processes: (I) dispersal, (II) environ-mental, and (III) interaction filtering. Heterogeneity in environmental conditions can alter these filtering processes, as it increases the available niche space, spatially partitions the resources, but also reduces the effective area available for individual species. Ultimately, heterogeneity thus shapes diversity. However, it is still unclear under which conditions heterogeneity has positive effects on diversity and under which condi-tions it has negative or no effects at all. In my thesis, I investigate how environmental heterogeneity affects the assembly and diversity of diverse species groups and whether these effects are mediated by species traits. In Chapter II, I first examine how much functional traits might inform about environmental filtering pro-cesses. Specifically, I examine to which extent body size and colour lightness, both of which are thought to reflect the species thermal preference, shape the distribution and abundance of two moth families along elevation. The results show, that assemblages of noctuid moths are more strongly driven by abiotic filters (elevation) and thus form distinct patterns in colour lightness and body size, while geometrid moths are driven by biotic filters (habitat availability), and show no decline in body size nor colour lightness along elevation. Thus, one and the same functional trait can have quite different effects on community assembly even between closely related taxonomic groups. In Chapter III, I elucidate how traits shift the relative importance of dispersal and environmental filtering in determining beta diversity between forests. Environmental filtering via forest heterogeneity had on aver-age higher independent effects than dispersal filtering within and among regions, suggesting that forest heterogeneity determines species turnover even at country-wide extents. However, the relative importance of dispersal filtering increased with decreasing dispersal ability of the species group. From the aspects of forest heterogeneity covered, variations in herb or tree species composition had overall stronger influence on the turnover of species than forest physiognomy. Again, this ratio was influenced by species traits, namely trophic position, and body size, which highlights the importance of ecological properties of a taxo-nomic group in community assembly. In Chapter IV, I assess whether such ecological properties ultimately determine the level of heterogeneity which maximizes species richness. Here, I considered several facets of heterogeneity in forests. Though the single facets of heterogeneity affected diverse species groups both in positive and negative ways, we could not identify any generalizable mechanism based on dispersal nor the trophic position of the species group which would dissolve these complex relationships. In Chapter V, I examine the effect of environmental heterogeneity of the diversity of traits itself to evalu-ate, whether the effects of environmental heterogeneity on species richness are truly based on increases in the number of niches. The results revealed that positive effects of heterogeneity on species richness are not necessarily based on an increased number of niches alone, but proposedly also on a spatially partition of resources or sheltering effects. While ecological diversity increased overall, there were also negative trends which indicate filtering effects via heterogeneity. In Chapter VI, I present novel methods in measuring plot-wise heterogeneity of forests across continental scales via Satellites. The study compares the performance of Sentinel-1 and LiDar-derived measurements in depicting forest structures and heterogeneity and to their predictive power in modelling diversity. Senti-nel-1 could match the performance of Lidar and shows high potential to assess free yet detailed infor-mation about forest structures in temporal resolutions for modelling the diversity of species. Overall, my thesis supports the notion that heterogeneity in environmental conditions is an important driv-er of beta-diversity, species richness, and ecological diversity. However, I could not identify any general-izable mechanism which direction and form this effect will have.},
  subject      = {Heterogenit{\"a}t},
  language  = {en}
}
@phdthesis{Vogel2022,
  author    = {Vogel, Cassandra Ezra},
  title     = {The effects of land-use and agroecological practices on biodiversity and ecosystem services in tropical smallholder farms},
  doi       = {10.25972/OPUS-29066},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290661},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Biodiversity is in rapid decline worldwide. These declines are more pronounced in areas that are currently biodiversity rich, but economically poor - essentially describing many tropical regions in the Global South where landscapes are dominated by smallholder agriculture. Agriculture is an important driver of biodiversity decline, through habitat destruction and unsustainable practices. Ironically, agriculture itself is dependent on a range of ecosystem services, such as pollination and pest control, provided by biodiversity. Biodiversity on fields and the delivery of ecosystem services to crops is often closely tied to the composition of the surrounding landscape - complex landscapes with a higher proportion of (semi-)natural habitats tend to support a high abundances and biodiversity of pollinators and natural enemies that are beneficial to crop production. However, past landscape scale studies have focused primarily on industrialized agricultural landscapes in the Global North, and context dependent differences between regions and agricultural systems are understudied. Smallholder agriculture supports 2 billion people worldwide and contributes to over half the world's food supply. Yet smallholders, particularly in sub-Saharan Africa, are underrepresented in research investigating the consequences of landscape change and agricultural practices. Where research in smallholder agriculture is conducted, the focus is often on commodity crops, such as cacao, and less on crops that are directly consumed by smallholder households, though the loss of services to these crops could potentially impact the most vulnerable farmers the hardest. Agroecology - a holistic and nature-based approach to agriculture, provides an alternative to unsustainable input-intensive agriculture. Agroecology has been found to benefit smallholders through improved agronomical and food-security outcomes. Co-benefits of agroecological practices with biodiversity and ecosystem services are assumed, but not often empirically tested. In addition, the local and landscape effects on biodiversity and ecosystem services are more commonly studied in isolation, but their potentially interactive effects are so far little explored. Our study region in northern Malawi exemplifies many challenges experienced by smallholder farmers throughout sub-Saharan Africa and more generally in the Global South. Malawi is located in a global biodiversity hotspot, but biodiversity is threatened by rapid habitat loss and a push for input-intensive agriculture by government and other stakeholders. In contrast, agroecology has been effectively promoted and implemented in the study region. We investigated how land-use differences and the agroecological practices affects biodiversity and ecosystem services of multiple taxa in a maize-bean intercropping system (Chapter 2), and pollination of pumpkin (Chapter 3) and pigeon pea (Chapter 4). Additionally, the effects of local and landscape scale shrub- to farmland habitat conversion was investigated on butterfly communities, as well as the potential for agroecology to mitigate these effects (Chapter 5).},
  language  = {en}
}
@phdthesis{BergmannBorges2023,
  author    = {Bergmann Borges, Alyssa},
  title     = {The endo-lysosomal system of \(Trypanosoma\) \(brucei\): insights from a protist cell model},
  doi       = {10.25972/OPUS-32924},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-329248},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Most of the studies in cell biology primarily focus on models from the opisthokont group of eukaryotes. However, opisthokonts do not encompass the full diversity of eukaryotes. Thus, it is necessary to broaden the research focus to other organisms to gain a comprehensive understanding of basic cellular processes shared across the tree of life. In this sense, Trypanosoma brucei, a unicellular eukaryote, emerges as a viable alternative. The collaborative efforts in genome sequencing and protein tagging over the past two decades have significantly expanded our knowledge on this organism and have provided valuable tools to facilitate a more detailed analysis of this parasite. Nevertheless, numerous questions still remain. The survival of T. brucei within the mammalian host is intricately linked to the endo-lysosomal system, which plays a critical role in surface glycoprotein recycling, antibody clearance, and plasma membrane homeostasis. However, the dynamics of the duplication of the endo-lysosomal system during T. brucei proliferation and its potential relationship with plasma membrane growth remain poorly understood. Thus, as the primary objective, this thesis explores the endo-lysosomal system of T. brucei in the context of the cell cycle, providing insights on cell surface growth, endosome duplication, and clathrin recruitment. In addition, the study revisits ferritin endocytosis to provide quantitative data on the involvement of TbRab proteins (TbRab5A, TbRab7, and TbRab11) and the different endosomal subpopulations (early, late, and recycling endosomes, respectively) in the transport of this fluid-phase marker. Notably, while these subpopulations function as distinct compartments, different TbRabs can be found within the same region or structure, suggesting a potential physical connection between the endosomal subpopulations. The potential physical connection of endosomes is further explored within the context of the cell cycle and, finally, the duplication and morphological plasticity of the lysosome are also investigated. Overall, these findings provide insights into the dynamics of plasma membrane growth and the coordinated duplication of the endo-lysosomal system during T. brucei proliferation. The early duplication of endosomes suggests their potential involvement in plasma membrane growth, while the late duplication of the lysosome indicates a reduced role in this process. The recruitment of clathrin and TbRab GTPases to the site of endosome formation supports the assumption that the newly formed endosomal system is active during cell division and, consequently, indicates its potential role in plasma membrane homeostasis. Furthermore, considering the vast diversity within the Trypanosoma genus, which includes ~500 described species, the macroevolution of the group was investigated using the combined information of the 18S rRNA gene sequence and structure. The sequence-structure analysis of T. brucei and other 42 trypanosome species was conducted in the context of the diversity of Trypanosomatida, the order in which trypanosomes are placed. An additional analysis focused on Trypanosoma highlighted key aspects of the group's macroevolution. To explore these aspects further, additional trypanosome species were included, and the changes in the Trypanosoma tree topology were analyzed. The sequence-structure phylogeny confirmed the independent evolutionary history of the human pathogens T. brucei and Trypanosoma cruzi, while also providing insights into the evolution of the Aquatic clade, paraphyly of groups, and species classification into subgenera.},
  subject      = {Endocytose},
  language  = {en}
}
@phdthesis{Classen2021,
  author    = {Claßen, Alexandra},
  title     = {The ERK-cascade in the pathophysiology of cardiac hypertrophy},
  doi       = {10.25972/OPUS-22966},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229664},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {ERK1/2 are known key players in the pathophysiology of heart failure, but the members of the ERK cascade, in particular Raf1, can also protect the heart from cell death and ischemic injury. An additional autophosphorylation (ERK1 at Thr208, ERK2 at Thr188) empowers ERK1/2 translocation to the nucleus and phosphorylation of nuclear targets which take part in the development of cardiac hypertrophy. Thereby, targeting this additional phosphorylation is a promising pharmacological approach. In this thesis, an in silico model of ERK cascade in the cardiomyocyte is introduced. The model is a semi-quantitive model and its behavior was tested with different softwares (SQUAD and CellNetAnalyzer). Different phosphorylation states of ERK1/2 as well as different stimuli can be reproduced. The different types of stimuli include hypertrophic as well as non-hypertrophic stimuli. With the introduced in-silico model time courses and synergistic as well as antagonistic receptor stimuli combinations can be predicted. The simulated time courses were experimentally validated. SQUAD was mainly used to make predictions about time courses and thresholds, whereas CNA was used to analyze steady states and feedback loops. Furthermore, new targets of ERK1/2 which partially contribute, also in the formation of cardiac hypertrophy, were identified and the most promising of them were illuminated. Important further targets are Caspase 8, GAB2, Mxi-2, SMAD2, FHL2 and SPIN90. Cardiomyocyte gene expression data sets were analyzed to verify involved components and to find further significantly altered genes after induced hypertrophy with TAC (transverse aortic constriction). Changes in the ultrastructure of the cardiomyocyte are the final result of induced hypertrophy.},
  subject      = {Herzhypertrophie},
  language  = {en}
}
@phdthesis{Mitesser2006,
  author    = {Mitesser, Oliver},
  title     = {The evolution of insect life history strategies in a social context},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22576},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2006},
  abstract  = {This thesis extends the classical theoretical work of Macevicz and Oster (1976, expanded by Oster and Wilson, 1978) on adaptive life history strategies in social insects. It focuses on the evolution of dynamic behavioural patterns (reproduction and activity) as a consequence of optimal allocation of energy and time resources. Mathematical modelling is based on detailed empirical observations in the model species Lasioglossum malachurum (Halictidae; Hymenoptera). The main topics are field observations, optimisation models for eusocial life histories, temporal variation in life history decisions, and annual colony cycles of eusocial insects.},
  subject      = {Schmalbienen},
  language  = {en}
}
@phdthesis{Fraune2014,
  author    = {Fraune, Johanna},
  title     = {The evolutionary history of the mammalian synaptonemal complex},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-100043},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Der Synaptonemalkomplex (SC) ist eine hochkonservierte Proteinstruktur. Er weist eine dreiteili-ge, leiter{\"a}hnliche Organisation auf und ist f{\"u}r die stabile Paarung der homologen Chromosomen w{\"a}hrend der Prophase der ersten meiotischen Teilung verantwortlich, die auch als Synpase be-zeichnet wird. Fehler w{\"a}hrend der Synpase f{\"u}hren zu Aneuploidie oder Apoptose der sich entwi-ckelnden Keimzellen. Seit 1956 ist der SC Gegenstand intensiver Forschung. Seine Existenz wurde in zahlreichen Orga-nismen von der Hefe bis zum Menschen beschrieben. Seine Struktur aus zwei parallel verlaufen-den Lateralelementen (LE), die durch eine Vielzahl von sogenannten Transversalfilamenten (TF) verbunden werden und dem Zentralen Element (CE) in der Mitte des SC ist dabei offensichtlich {\"u}ber die Millionen von Jahren der Evolution erhalten geblieben. Einzelne Proteinkomponenten des SC wurden jedoch nur in wenigen Modelorganismen charakterisiert, darunter Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster, Ceanorhabditis elegans und Mus mus-culus. Unerwarteter Weise gelang es bei dieser Charakterisierung nicht, eine evolution{\"a}re Ver-wandtschaft, d.h. eine Homologie zwischen den Proteinsequenzen der verschiedenen SCs nach-zuweisen. Diese Tatsache sprach gegen die grunds{\"a}tzliche Annahme, dass der SC in der Evolution nur einmal entstanden sei. Diese Arbeit hat sich nun der Aufgabe gewidmet, die Diskrepanz zwischen der hochkonservierten Struktur des SC und seiner augenscheinlich nicht-homologen Proteinzusammensetzung zu l{\"o}sen. Dabei beschr{\"a}nkt sie sich auf die Analyse des Tierreichs. Es ist die erste Studie zur Evolution des SC in Metazoa und demonstriert die Monophylie der S{\"a}uger SC Proteinkomponenten im Tierreich. Die Arbeit zeigt, dass mindestens vier von sieben SC Proteinen der Maus sp{\"a}testens im letzten gemeinsamen Vorfahren der Gewebetiere (Eumetazoa) enstanden sind und auch damals Teil ei-nes urspr{\"u}nglichen SC waren, wie er heute in dem Nesseltier Hydra zu finden ist. Dieser SC weist die typische Struktur auf und besitzt bereits alle notwendigen Komponenten, um die drei Dom{\"a}-nen - LE, TF und CE - zu assemblieren. Dar{\"u}ber hinaus ergaben die einzelnen Phylogenien der verschiedenen SC Proteine der Maus, dass der SC eine sehr dynamische Evolutionsgeschichte durchlaufen hat. Zus{\"a}tzliche Proteine wurden w{\"a}hrend der Entstehung der Bilateria und der Wir-beltiere in den SC integriert, w{\"a}hrend andere urspr{\"u}ngliche Komponenten m{\"o}glicherweise Gen-Duplikationen erfuhren bzw. besonders in der Linie der H{\"a}utungstiere verloren gingen oder sich stark ver{\"a}nderten. Es wird die These aufgestellt, dass die auf den ersten Blick nicht-homologen SC Proteine der Fruchtfliege und des Fadenwurms tats{\"a}chlich doch von den urspr{\"u}nglichen Prote-inenkomponenten abstammen, sich aber aufgrund der rasanten Evolution der Arthropoden und der Nematoden bis zu deren Unkenntlichkeit diversifizierten. Zus{\"a}tzlich stellt die Arbeit Hydra als alternatives wirbelloses Modellsystem f{\"u}r die Meiose- und SC-Forschung zu den {\"u}blichen Modellen D. melanogaster und C. elegans vor. Die k{\"u}rzlich gewon-nenen Erkenntnisse {\"u}ber den Hydra SC sowie der Einsatz der Standard-Methoden in diesem Orga-nismus werden in dem abschließenden Kapitel zusammengefasst und diskutiert.},
  subject      = {Synaptinemal-Komplex},
  language  = {en}
}
@phdthesis{Grob2022,
  author    = {Grob, Robin},
  title     = {The Function of Learning Walks of \({Cataglyphis Ants}\): Behavioral and Neuronal Analyses},
  doi       = {10.25972/OPUS-29017},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290173},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Humans and animals alike use the sun, the moon, and the stars to guide their ways. However, the position of celestial cues changes depending on daytime, season, and place on earth. To use these celestial cues for reliable navigation, the rotation of the sky has to be compensated. While humans invented complicated mechanisms like the Antikythera mechanism to keep track of celestial movements, animals can only rely on their brains. The desert ant Cataglyphis is a prime example of an animal using celestial cues for navigation. Using the sun and the related skylight polarization pattern as a compass, and a step integrator for distance measurements, it can determine a vector always pointing homewards. This mechanism is called path integration. Since the sun's position and, therefore, also the polarization pattern changes throughout the day, Cataglyphis have to correct this movement. If they did not compensate for time, the ants' compass would direct them in different directions in the morning and the evening. Thus, the ants have to learn the solar ephemeris before their far-reaching foraging trips. To do so, Cataglyphis ants perform a well-structured learning-walk behavior during the transition phase from indoor worker to outdoor forager. While walking in small loops around the nest entrance, the ants repeatedly stop their forward movements to perform turns. These can be small walked circles (voltes) or tight turns about the ants' body axes (pirouettes). During pirouettes, the ants gaze back to their nest entrance during stopping phases. These look backs provide a behavioral read-out for the state of the path integrator. The ants "tell" the observer where they think their nest is, by looking back to it. Pirouettes are only performed by Cataglyphis ants inhabiting an environment with a prominent visual panorama. This indicates, that pirouettes are performed to learn the visual panorama. Voltes, on the other hand, might be used for calibrating the celestial compass of the ants. In my doctoral thesis, I employed a wide range of state-of-the-art techniques from different disciplines in biology to gain a deeper understanding of how navigational information is acquired, memorized, used, and calibrated during the transition phase from interior worker to outdoor forager. I could show, that celestial orientation cues that provide the main compass during foraging, do not guide the ants during the look-backbehavior of initial learning walks. Instead Cataglyphis nodus relies on the earth's magnetic field as a compass during this early learning phase. While not guiding the ants during their first walks outside of the nest, excluding the ants from perceiving the natural polarization pattern of the skylight has significant consequences on learning-related plasticity in the ants' brain. Only if the ants are able to perform their learning-walk behavior under a skylight polarization pattern that changes throughout the day, plastic neuronal changes in high-order integration centers are induced. Especially the mushroom bogy collar, a center for learning and memory, and the central complex, a center for orientation and motor control, showed an increase in volume after learning walks. This underlines the importance of learning walks for calibrating the celestial compass. The magnetic compass might provide the necessary stable reference system for the ants to calibrate their celestial compass and learn the position of landmark information. In the ant brain, visual information from the polarization-sensitive ocelli converge in tight apposition with neuronal afferents of the mechanosensitive Johnston's organ in the ant's antennae. This makes the ants' antennae an interesting candidate for studying the sensory bases of compass calibration in Cataglyphis ants. The brain of the desert navigators is well adapted to successfully accomplish their navigational needs. Females (gynes and workers) have voluminous mushroom bodies, and the synaptic complexity to store large amount of view-based navigational information, which they acquire during initial learning walks. The male Cataglyphis brain is better suited for innate behaviors that support finding a mate. The results of my thesis show that the well adapted brain of C. nodus ants undergoes massive structural changes during leaning walks, dependent on a changing celestial polarization pattern. This underlies the essential role of learning walks in the calibration of orientation systems in desert ants.},
  subject      = {Cataglyphis},
  language  = {en}
}
@phdthesis{Pietsch2005,
  author    = {Pietsch, Christof},
  title     = {The genetics of species differences within the genus Nasonia ASHMEAD 1904 (Hymenoptera: Pteromalidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-14348},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {The genetics of species differences is an outstanding question in evolutionary biology. How do species evolve to become phenotypically distinct and how is the genetic architecture organized that underlie species differences? Phenotypic diverged traits are supposed to be frequently involved in prezygotic isolation, i.e. they prevent the formation of hybrids, whereas postzygotic isolation occurs when hybrids experience a fitness reduction. The parasitic wasp genus Nasonia represents an appropriate model system to investigate the genetics of species differences as well as the genetics of postzygotic isolation. The genus consists of three species N. vitripennis, N. longicornis and N. giraulti that differ particularly in male traits that are assumed to posses an adaptive significance: courtship behaviour and wing size differences. The courtship behaviour consists of cyclically repeated series of head nods that are separated by pauses. The stereotypic performance allowed to split up the display into distinct courtship components. Males of N. vitripennis bear vestigial forewings and are incapable of flight, whereas N. longicornis wear intermediate sized wings and N. giraulti is fully capable of flying. Nasonia species can produce interspecific hybrids after removing Wolbachia bacteria induced hybrid incompatibilities with antibiotics. Postzygotic isolation occurs to different extent and is asymmetric among reciprocal crosses, e.g. inviability is stronger in the N. vitripennis (\&\#9792;) x N. longicornis (\&\#9794;) cross than in the N. longicornis (\&\#9792;) x N. vitripennis (\&\#9794;) cross. The formation of hybrids allow to study the genetic of species differences in QTL (quantitative trait locus) analyses as well as the genetics of postzygotic isolation causing hybrid inviability. The aim of the study was to investigate the genetic architecture of differences in courtship behaviour and wing size between N. vitripennis and N. longicornis and to assess the genetics of postzygotic isolation to gain clues about the evolutionary processes underlying trait divergence and establishment of reproductive isolation between taxa. In a QTL analysis based on 94 F2-hybrid individuals of an LV cross only few QTL for wing size differences have been found with relatively large effects, although a large proportion of the phenotypic variance remained unexplained. The QTL on courtship behaviour analysis based on 94-F2 hybrid males revealed a complex genetic architecture of courtship behaviour with QTL of large phenotypic effects that explained more than 40 \% of the phenotypic variance in one case. Additionally, an epistatic analysis (non-additive interlocus interaction) of courtship QTL revealed frequent genetic interchromsomal relations leading in some instances to hybrid specific effects, e.g. reversion of phenotypic effects or the transgression of phenotypes. A QTL analysis based on a threefold sample size revealed, however, an overestimation of QTL effects in the analysis based on smaller sample size pointing towards a genetic architecture of many loci with small effects governing the phenotypic differences in courtship behaviour. Furthermore, the the study comprised the analysis of postzygotic isolation in the reciprocal crosses N. vitripennis (\&\#9792;) x N. longicornis (\&\#9794;) versus N. longicornis (\&\#9792;) x N. vitripennis (\&\#9794;) located several loci distributed over different chromosomes that are involved in hybrid incompatibility. The mapping of hybrid incompatibility regions reproduced for the first time the observed asymmetries in the strength of postzygotic isolation in reciprocal crosses of between the more distant related taxa within the genus Nasonia. Stronger postzygotic incompatibilities in the VL cross are supposed to result from the superposition of nuclear-nuclear incompatibilities with nuclear-cytoplasmic incompatibilities, whereas the coincidences of these to types of incompatibilities were found to be much weaker in the reciprocal LV cross.},
  subject      = {Pteromalidae},
  language  = {en}
}
@phdthesis{Pinkert2008,
  author    = {Pinkert, Stefan},
  title     = {The human proteome is shaped by evolution and interactions},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-35566},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {Das menschliche Genom ist seit 2001 komplett sequenziert. Ein Großteil der Proteine wurde mittlerweile beschrieben und t{\"a}glich werden bioinformatische Vorhersagen praktisch best{\"a}tigt. Als weiteres Großprojekt wurde k{\"u}rzlich die Sequenzierung des Genoms von 1000 Menschen gestartet. Trotzdem ist immer noch wenig {\"u}ber die Evolution des gesamten menschlichen Proteoms bekannt. Proteindom{\"a}nen und ihre Kombinationen sind teilweise sehr detailliert erforscht, aber es wurden noch nicht alle Dom{\"a}nenarchitekturen des Menschen in ihrer Gesamtheit miteinander verglichen. Der verwendete große hochqualitative Datensatz von Protein-Protein-Interaktionen und Komplexen stammt aus dem Jahr 2006 und erm{\"o}glicht es erstmals das menschliche Proteom mit einer vorher nicht m{\"o}glichen Genauigkeit analysieren zu k{\"o}nnen. Hochentwickelte Cluster Algorithmen und die Verf{\"u}gbarkeit von großer Rechenkapazit{\"a}t bef{\"a}higen uns neue Information {\"u}ber Proteinnetzwerke ohne weitere Laborarbeit zu gewinnen. Die vorliegende Arbeit analysiert das menschliche Proteom auf drei verschiedenen Ebenen. Zuerst wurde der Ursprung von Proteinen basierend auf ihrer Dom{\"a}nenarchitektur analysiert, danach wurden Protein-Protein-Interaktionen untersucht und schließlich erfolgte Einteilung der Proteine nach ihren vorhandenen und fehlenden Interaktionen. Die meisten bekannten Proteine enthalten mindestens eine Dom{\"a}ne und die Proteinfunktion ergibt sich aus der Summe der Funktionen der einzelnen enthaltenen Dom{\"a}nen. Proteine, die auf der gleichen Dom{\"a}nenarchitektur basieren, das heißt die die gleichen Dom{\"a}nen in derselben Reihenfolge besitzen, sind homolog und daher aus einem gemeinsamen urspr{\"u}nglichen Protein entstanden. Die Dom{\"a}nenarchitekturen der urspr{\"u}nglichen Proteine wurden f{\"u}r 750000 Proteine aus 1313 Spezies bestimmt. Die Gruppierung von Spezies und ihrer Proteine ergibt sich aus taxonomischen Daten von NCBI-Taxonomy, welche mit zus{\"a}tzlichen Informationen basierend auf molekularen Markern erg{\"a}nzt wurden. Der resultierende Datensatz, bestehend aus 5817 Dom{\"a}nen und 32868 Dom{\"a}nenarchitekturen, war die Grundlage f{\"u}r die Bestimmung des Ursprungs der Proteine aufgrund ihrer Dom{\"a}nenarchitekturen. Es wurde festgestellt, dass nur ein kleiner Teil der neu evolvierten Dom{\"a}nenarchitekturen eines Taxons gleichzeitig auch im selben Taxon neu entstandene Proteindom{\"a}nen enth{\"a}lt. Ein weiteres Ergebnis war, dass Dom{\"a}nenarchitekturen im Verlauf der Evolution l{\"a}nger und komplexer werden, und dass so verschiedene Organismen wie der Fadenwurm, die Fruchtfliege und der Mensch die gleiche Menge an unterschiedlichen Proteinen haben, aber deutliche Unterschiede in der Anzahl ihrer Dom{\"a}nenarchitekturen aufweisen. Der zweite Teil besch{\"a}ftigt sich mit der Frage wie neu entstandene Proteine Bindungen mit dem schon bestehenden Proteinnetzwerk eingehen. In fr{\"u}heren Arbeiten wurde gezeigt, dass das Protein-Interaktions-Netzwerk ein skalenfreies Netz ist. Skalenfreie Netze, wie zum Beispiel das Internet, bestehen aus wenigen Knoten mit vielen Interaktionen, genannt Hubs, und andererseits aus vielen Knoten mit wenigen Interaktionen. Man vermutet, dass zwei Mechanismen zur Entstehung solcher Netzwerke f{\"u}hren. Erstens m{\"u}ssen neue Proteine um auch Teil des Proteinnetzwerkes zu werden mit Proteinen interagieren, die bereits Teil des Netzwerkes sind. Zweitens interagieren die neuen Proteine, gem{\"a}ß der Theorie der bevorzugten Bindung, mit h{\"o}herer Wahrscheinlichkeit mit solchen Proteinen im Netzwerk, die schon an zahlreichen weiteren Protein-Interaktionen beteiligt sind. Die Human Protein Reference Database stellt ein auf Informationen aus in-vivo Experimenten beruhendes Proteinnetzwerk f{\"u}r menschliche Proteine zur Verf{\"u}gung. Basierend auf den in Kapitel I gewonnenen Informationen wurden die Proteine mit dem Ursprungstaxon ihrer Dom{\"a}nenarchitekturen versehen. Dadurch wurde gezeigt, dass ein Protein h{\"a}ufiger mit Proteinen, die im selben Taxon entstanden sind, interagiert, als mit Proteinen, die in anderen Taxa neu aufgetreten sind. Es stellte sich heraus, dass diese Interaktionsraten f{\"u}r alle Taxa deutlich h{\"o}her waren, als durch das Zufallsmodel vorhergesagt wurden. Alle Taxa enthalten den gleichen Anteil an Proteinen mit vielen Interaktionen. Diese zwei Ergebnisse sprechen dagegen, dass die bevorzugte Bindung der alleinige Mechanismus ist, der zum heutigen Aufbau des menschlichen Proteininteraktion-Netzwerks beigetragen hat. Im dritten Teil wurden Proteine basierend auf dem Vorhandensein und der Abwesenheit von Interaktionen in Gruppen eingeteilt. Proteinnetzwerke k{\"o}nnen in kleine hoch vernetzte Teile zerlegt werden, die eine spezifische Funktion aus{\"u}ben. Diese Gruppen k{\"o}nnen mit hoher statistischer Signifikanz berechnet werden, haben meistens jedoch keine biologische Relevanz. Mit einem neuen Algorithmus, welcher zus{\"a}tzlich zu Interaktionen auch Nicht-Interaktionen ber{\"u}cksichtigt, wurde ein Datensatz bestehend aus 8,756 Proteinen und 32,331 Interaktionen neu unterteilt. Eine Einteilung in elf Gruppen zeigte hohe auf Gene Ontology basierte Werte und die Gruppen konnten signifikant einzelnen Zellteilen zugeordnet werden. Eine Gruppe besteht aus Proteinen, welche wenige Interaktionen miteinander aber viele Interaktionen zu zwei benachbarten Gruppen besitzen. Diese Gruppe enth{\"a}lt eine signifikant erh{\"o}hte Anzahl an Transportproteinen und die zwei benachbarten Gruppen haben eine erh{\"o}hte Anzahl an einerseits extrazellul{\"a}ren und andererseits im Zytoplasma und an der Membran lokalisierten Proteinen. Der Algorithmus hat damit unter Beweis gestellt das die Ergebnisse nicht bloß statistisch sondern auch biologisch relevant sind. Wenn wir auch noch weit vom Verst{\"a}ndnis des Ursprungs der Spezies entfernt sind, so hat diese Arbeit doch einen Beitrag zum besseren Verst{\"a}ndnis der Evolution auf dem Level der Proteine geleistet. Im Speziellen wurden neue Erkenntnisse {\"u}ber die Beziehung von Proteindom{\"a}nen und Dom{\"a}nenarchitekturen, sowie ihre Pr{\"a}ferenzen f{\"u}r Interaktionspartner im Interaktionsnetzwerk gewonnen.},
  subject      = {Evolution},
  language  = {en}
}
@phdthesis{Jordan2001,
  author    = {Jordan, Bruce},
  title     = {The identification of NRAGE},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1180090},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {The inhibitor of apoptosis proteins (IAPs) have been shown to interact with a growing number of intracellular proteins and signalling pathways in order to fulfil their anti-apoptotic role. In order to investigate in detail how the avian homologue ITA interfered with both TNF induced apoptosis and the NGF mediated differentiation in PC12 cells, a two hybrid screen was performed with a PC12 library using ITA as a bait. The screen resulted in the identification of several overlapping fragments of a previously unknown gene. The complete cDNA for this gene was isolated, the analysis of which revealed a high homology with a large family of tumour antigens known as MAGE (melanoma associated antigens). This newly identified member of the MAGE family, which was later named NRAGE, exhibited some unique characteristics that suggested for the first time a role in normal cellular physiology for this protein family. MAGE proteins are usually restricted in their expression to malignant or tumour cells, however NRAGE was also expressed in terminally differentiated adult tissue. NRAGE also interacted with the human XIAP in direct two-hybrid tests. The interactions observed in yeast cells were confirmed in mammalian cell culture, employing both coimmunoprecipitation and mammalian two-hybrid methods. Moreover, the results of the coimmunoprecipitation experiments indicated that this interaction requires the RING domain. The widely studied 32D cell system was chosen to investigate the effect of NRAGE on apoptosis. NRAGE was stably transduced in 32D cells, and found to augment cell death induced by the withdrawal of Interleukin-3. One reason for this reduced cell viability in NRAGE expressing cells could be the binding of endogenous XIAP, which occurred inducibly after growth factor withdrawal. Interestingly, NRAGE was able to overcome the protection afforded to 32D cells by the exogenous expression of human Bcl-2. Thus NRAGE was identified during this research doctorate as a novel pro-apoptotic, IAP-interacting protein, able to accelerate apoptosis in a pathway independent of Bcl-2 cell protection.},
  subject      = {Apoptosis},
  language  = {en}
}
@phdthesis{Kupper2016,
  author    = {Kupper, Maria},
  title     = {The immune transcriptome and proteome of the ant Camponotus floridanus and vertical transmission of its bacterial endosymbiont Blochmannia floridanus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142534},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {The evolutionary success of insects is believed to be at least partially facilitated by symbioses between insects and prokaryotes. Bacterial endosymbionts confer various fitness advantages to their hosts, for example by providing nutrients lacking from the insects' diet thereby enabling the inhabitation of new ecological niches. The Florida carpenter ant Camponotus floridanus harbours endosymbiotic bacteria of the genus Blochmannia. These primary endosymbionts mainly reside in the cytoplasm of bacteriocytes, specialised cells interspersed into the midgut tissue, but they were also found in oocytes which allows their vertical transmission. The social lifestyle of C. floridanus may facilitate the rapid spread of infections amongst genetically closely related animals living in huge colonies. Therefore, the ants require an immune system to efficiently combat infections while maintaining a "chronic" infection with their endosymbionts. In order to investigate the immune repertoire of the ants, the Illumina sequencing method was used. The previously published genome sequence of C. floridanus was functionally re-annotated and 0.53\% of C. floridanus proteins were assigned to the gene ontology (GO) term subcategory "immune system process". Based on homology analyses, genes encoding 510 proteins with possible immune function were identified. These genes are involved in microbial recognition and immune signalling pathways but also in cellular defence mechanisms, such as phagocytosis and melanisation. The components of the major signalling pathways appear to be highly conserved and the analysis revealed an overall broad immune repertoire of the ants though the number of identified genes encoding pattern recognition receptors (PRRs) and antimicrobial peptides (AMPs) is comparatively low. Besides three genes coding for homologs of thioester-containing proteins (TEPs), which have been shown to act as opsonins promoting phagocytosis in other insects, six genes encoding the AMPs defesin-1 and defensin-2, hymenoptaecin, two tachystatin-like peptides and one crustin-like peptide are present in the ant genome. Although the low number of known AMPs in comparison to 13 AMPs in the honey bee Apis mellifera and 46 AMPs in the wasp Nasonia vitripennis may indicate a less potent immune system, measures summarised as external or social immunity may enhance the immune repertoire of C. floridanus, as it was discussed for other social insects. Also, the hymenoptaecin multipeptide precursor protein may be processed to yield seven possibly bioactive peptides. In this work, two hymenoptaecin derived peptides were heterologously expressed and purified. The preliminary antimicrobial activity assays indicate varying bacteriostatic effects of different hymenoptaecin derived peptides against Escherichia coli D31 and Staphylococcus aureus which suggests a functional amplification of the immune response further increasing the antimicrobial potency of the ants. Furthermore, 257 genes were differentially expressed upon immune challenge of C. floridanus and most of the immune genes showing differential expression are involved in recognition of microbes or encode immune effectors rather than signalling components. Additionally, genes coding for proteins involved in storage and metabolism were downregulated upon immune challenge suggesting a trade-off between two energy-intensive processes in order to enhance effectiveness of the immune response. The analysis of gene expression via qRT-PCR was used for validation of the transcriptome data and revealed stage-specific immune gene regulation. Though the same tendencies of regulation were observed in larvae and adults, expression of several immune-related genes was generally more strongly induced in larvae. Immune gene expression levels depending on the developmental stage of C. floridanus are in agreement with observations in other insects and might suggest that animals from different stages revert to individual combinations of external and internal immunity upon infection. The haemolymph proteome of immune-challenged ants further established the immune-relevance of several proteins involved in classical immune signalling pathways, e.g. PRRs, extracellularly active proteases of the Toll signalling pathway and effector molecules such as AMPs, lysozymes and TEPs. Additionally, non-canonical proteins with putative immune function were enriched in immune-challenged haemolymph, e.g. Vitellogenins, NPC2-like proteins and Hemocytin. As known from previous studies, septic wounding also leads to the upregulation of genes involved in stress responses. In the haemolymph, proteins implicated in protein stabilisation and in the protection against oxidative stress and insecticides were enriched upon immune challenge. In order to identify additional putative immune effectors, haemolymph peptide samples from immune-challenged larvae and adults were analysed. The analysis in this work focussed on the identification of putative peptides produced via the secretory pathway as previously described for neuropeptides of C. floridanus. 567 regulated peptides derived from 39 proteins were identified in the larval haemolymph, whereas 342 regulated peptides derived from 13 proteins were found in the adult haemolymph. Most of the peptides are derived from hymenoptaecin or from putative uncharacterised proteins. One haemolymph peptide of immune-challenged larvae comprises the complete amino acid sequence of a predicted peptide derived from a Vitellogenin. Though the identified peptide lacks similarities to any known immune-related peptide, it is a suitable candidate for further functional analysis. To establish a stable infection with the endosymbionts, the bacteria have to be transmitted to the next generation of the ants. The vertical transmission of B. floridanus is guaranteed by bacterial infestation of oocytes. This work presents the first comprehensive and detailed description of the localisation of the bacterial endosymbionts in C. floridanus ovaries during oogenesis. Whereas the most apical part of the germarium, which contains the germ-line stem cells, is not infected by the bacteria, small somatic cells in the outer layers of each ovariole were found to be infected in the lower germarium. Only with the beginning of cystocyte differentiation, endosymbionts are exclusively transported from follicle cells into the growing oocytes, while nurse cells were never infected with B. floridanus. This infestation of the oocytes by bacteria very likely involves exocytosis-endocytosis processes between follicle cells and the oocytes. A previous study suggested a down-modulation of the immune response in the midgut tissue which may promote endosymbiont tolerance. Therefore, the expression of several potentially relevant immune genes was analysed in the ovarial tissue by qRT-PCR. The relatively low expression of genes involved in Toll and IMD signalling, and the high expression of genes encoding negative immune regulators, such as PGRP-LB, PGRP-SC2, and tollip, strongly suggest that a down-modulation of the immune response may also facilitate endosymbiont tolerance in the ovaries and thereby contribute to their vertical transmission. Overall, the present thesis improves the knowledge about the immune repertoire of C. floridanus and provides new candidates for further functional analyses. Moreover, the involvement of the host immune system in maintaining a "chronic" infection with symbiotic bacteria was confirmed and extended to the ovaries.},
  subject      = {Camponotus floridanus},
  language  = {en}
}
@phdthesis{Seida2012,
  author    = {Seida, Ahmed Adel},
  title     = {The Immunomodulatory Role of Endogenous Glucocorticoids in Ovarian Cancer},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-73901},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {Ovarian cancer currently causes ~6,000 deaths per year in Germany alone. Since only palliative treatment is available for ovarian carcinomas that have developed resistance against platinum-based chemotherapy and paclitaxel, there is a pressing medical need for the development of new therapeutic approaches. As survival is strongly influenced by immunological parameters, immunotherapeutic strategies appear promising. The research of our group thus aims at overcoming tumour immune escape by counteracting immunosuppressive mechanisms in the tumour microenvironment. In this context, we found that tumour-infiltrating myeloid-derived suppressor cells (MDSC) or tumour associated macrophages (TAM) which are abundant in ovarian cancer express high levels of the enzyme 11β-hydroxysteroid dehydrogenase1 (11-HSD1). This oxido-reductase enzyme is essential for the conversion of biologically inactive cortisone into active cortisol. In line with this observation, high endogenous cortisol levels could be detected in serum, ascitic fluid and tumour exudates from ovarian cancer patients. Considering that cortisol exerts strong anti-inflammatory and immunosuppressive effects on immune cells, it appears likely that high endogenous cortisol levels contribute to immune escape in ovarian cancer. We thus hypothesised that local activation of endogenous glucocorticoids could suppress beneficial immune responses in the tumour microenvironment and thereby prevent a successful immunotherapy. To investigate the in vivo relevance of this postulated immune escape mechanism, irradiated PTENloxP/loxP loxP-Stop-loxP-krasG12D mice were reconstituted with hematopoietic stem cells from either glucocorticoid receptor (GR) expressing mice (GRloxP/loxP) or from mice with a T cell-specific glucocorticoid receptor knock-out (lck-Cre GRloxP/loxP) mice. In the host mice, the combination of a conditional PTEN knock-out with a latent oncogenic kras leads to tumour development when a Cre-encoding adenovirus is injected into the ovarian bursa. Using this model, mice that had been reconstituted with GC-insensitive T cells showed better intratumoural T cell infiltration than control mice that had received functionally unaltered GRloxP/loxP cells via adoptive transfer. However, tumour-infiltrating T cells mostly assumed a Foxp3+ (regulatory) phenotype and survival was even shortened in mice with cortisol-insensitive T cells. Thus, endogenous cortisol seems to inhibit immune cell infiltration in ovarian cancer, but productive anti-tumour immune responses might still be prevented by further factors from the tumour microenvironment. Thus, our data did not provide a sufficiently strong rationale to further pursue the antagonisation of glucocorticoid signalling in ovarian cancer patients, Moreover, glucocorticoids are frequently administered to cancer patients to reduce inflammation and swelling and to prevent chemotherapy-related toxic side effects like nausea or hypersensitivity reactions associated with paclitaxel therapy. Thus, we decided to address the question whether specific signalling pathways in innate immune cells, preferentially in NK cells, could still be activated even in the presence of GC. A careful investigation of the various activating NK cell receptors (i.e. NKp30, NKp44, NKp46), DNAM-1 and NKG2D) was thus performed which revealed that NKp30, NKp44 and NKG2D are all down-regulated by cortisol whereas NKp46 is actually induced by cortisol. Interestingly, NKp46 is the only known receptor that is strictly confined to NK cells. Its activation via crosslinking leads to cytokine release and activation of cytotoxic activity. Stimulation of NK cells via NKp46 may contribute to immune-mediated tumour destruction by triggering the lysis of tumour cells and by altering the cytokine pattern in the tumour microenvironment, thereby generating more favourable conditions for the recruitment of antigen-specific immune cells. Accordingly, our observation that even cortisol-treated NK cells can still be activated via NKp46 and CD2 might become valuable for the design of immunotherapies that can still be applied in the presence of endogenous or therapeutically administered glucocorticoids.},
  subject      = {Cortison},
  language  = {en}
}
@phdthesis{HornneeBunz2020,
  author    = {Horn [n{\´e}e Bunz], Melanie},
  title     = {The impact of Drosophila melanogaster`s endogenous clock on fitness: Influence of day length, humidity and food composition},
  doi       = {10.25972/OPUS-21141},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211415},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {We are living in a system that underlies permanent environmental changes due to the rotation of our planet. These changes are rhythmic with the most prominent one having a period of about 24 hours, but also shorter and longer rhythms characterize our environment. To cope with the ever-changing environmental conditions, it is thought to be beneficial if an organism can track and anticipate these changes. The so called endogenous clocks enable this and might provide a fitness advantage. To investigate and unravel the mechanism of endogenous clocks Chronobiologists have used different model organisms. In this thesis Drosophila melanogaster was used as model organism with its about 150 clock neurons representing the main endogenous clock of the fly in the central brain. The molecular mechanisms and the interlocked feedback loops with the main circadian key players like period, timeless, clock or cycle are under investigation since the 1970s and are characterized quite well so far. But the impact of a functional endogenous clock in combination with diverse factors and the resulting fitness advantages were analysed in only a few studies and remains for the most part unknown. Therefore the aim of this thesis was to unravel the impact of Drosophila melanogaster`s endogenous clock on the fitness of the fly. To achieve this goal different factors - like day length, humidity and food composition - were analyzed in wild type CS and three different period mutants, namely perL, perS and per01, that carry a point mutation altering or abolishing the free-running period of the fruit fly as well as a second arrhythmic strain, clkAR. In competition assay experiments wild type and clock mutant flies competed for up to 63 generations under a normal 24 hour rhythm with 12 hours light/day and 12 hours darkness/night (LD12:12) or T-cycles with 19 or 29 hours, according to the mutants free-running period, or constant light (LL) in case of the arrhythmic mutant as well as under natural-like outdoor conditions in two consecutive years. Overall the wild type CS strain was outcompeting the clock mutant strains independent of the environmental conditions. As the perL fly strain elongated their free-running period, the competition experiments were repeated with naturally cantonized new fly strains. With these experiments it could be shown that the genetic background of the fly strains - which are kept for decades in the lab, with backcrosses every few years - is very important and influences the fitness of flies. But also the day length impacts the fitness of the flies, enabling them to persist in higher percentage in a population under competition. Further factors that might influence the survival in a competing population were investigated, like e.g. mating preferences and locomotor activity of homo- and heterozygous females or sperm number of males transferred per mating. But these factors can still not explain the results in total and play no or only minor roles and show the complexity of the whole system with still unknown characteristics. Furthermore populations of flies were recorded to see if the flies exhibit a common locomotor activity pattern or not and indeed a population activity pattern could be recorded for the first time and social contact as a Zeitgeber could be verified for Drosophila melanogaster. In addition humidity and its impact on the flies´ fitness as well as a potential Zeitgeber was examined in this thesis. The flies experienced different relative humidities for eclosion and wing expansion and humidity cycle phase shifting experiments were performed to address these two different questions of fitness impact and potential Zeitgeber. The fruit fly usually ecloses in the morning hours when the relative humidity is quite high and the general assumption was that they do so to prevent desiccation. The results of this thesis were quite clear and demonstrate that the relative humidity has no great effect on the fitness of the flies according to successful eclosion or wing expansion and that temperature might be the more important factor. In the humidity cycle phase shifting experiments it could be revealed that relative humidity cannot act as a Zeitgeber for Drosophila melanogaster, but it influences and therefore masks the activity of flies by allowing or surpressing activity at specific relative humidity values. As final experiments the lifespan of wild type and clock mutant flies was investigated under different day length and with different food qualities to unravel the impact of these factors on the fitness and therefore survival of the flies on the long run. As expected the flies with nutrient-poor minimum medium died earlier than on the nutrient-rich maximum medium, but a small effect of day length could also be seen with flies living slightly longer when they experience environmental day length conditions resembling their free-running period. The experiments also showed a fitness advantage of the wild type fly strain against the clock mutant strains for long term, but not short term (about the first 2-3 weeks). As a conclusion it can be said that genetic variation is important to be able to adapt to changing environmental conditions and to optimize fitness and therefore survival. Having a functional endogenous clock with a free-running period of about 24 hours provides fitness advantages for the fruit fly, at least under competition. The whole system is very complex and many factors - known and unknown ones - play a role in this system by interacting on different levels, e.g. physiology, metabolism and/or behavior.},
  subject      = {Taufliege},
  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}
}
@phdthesis{Boetzl2022,
  author    = {B{\"o}tzl, Fabian Alexander},
  title     = {The influence of crop management and adjacent agri-environmental scheme type on natural pest control in differently structured landscapes},
  doi       = {10.25972/OPUS-24140},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241400},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Summary Chapters I \& II: General Introduction \& General Methods Agriculture is confronted with a rampant loss of biodiversity potentially eroding ecosystem service potentials and adding up to other stressors like climate change or the consequences of land-use change and intensive management. To counter this 'biodiversity crisis', agri-environment schemes (AES) have been introduced as part of ecological intensification efforts. These AES combine special management regimes with the establishment of tailored habitats to create refuges for biodiversity in agricultural landscapes and thus ensure biodiversity mediated ecosystem services such as pest control. However, little is known about how well different AES habitats fulfil this purpose and whether they benefit ecosystem services in adjacent crop fields. Here I investigated how effective different AES habitats are for restoring biodiversity in different agricultural landscapes (Chapter V) and whether they benefit natural pest control in adjacent oilseed rape (Chapter VI) and winter cereal fields (Chapter VII). I recorded biodiversity and pest control potentials using a variety of different methods (Chapters II, V, VI \& VII). Moreover, I validated the methodology I used to assess predator assemblages and predation rates (Chapters III \& IV). Chapter III: How to record ground dwelling predators? Testing methodology is critical as it ensures scientific standards and trustworthy results. Pitfall traps are widely used to record ground dwelling predators, but little is known about how different trap types affect catches. I compared different types of pitfall traps that had been used in previous studies in respect to resulting carabid beetle assemblages. While barrier traps collected more species and deliver more complete species inventories, conventional simple pitfall traps provide reliable results with comparatively little handling effort. Placing several simple pitfall traps in the field can compensate the difference while still saving handling effort.   Chapter IV: How to record predation rates? A plethora of methods has been proposed and used for recording predation rates, but these have rarely been validated before use. I assessed whether a novel approach to record predation, the use of sentinel prey cards with glued on aphids, delivers realistic results. I compared different sampling efforts and showed that obtained predation rates were similar and could be linked to predator (carabid beetle) densities and body-sizes (a proxy often used for food intake rates). Thus, the method delivers reliable and meaningful predation rates. Chapter V: Do AES habitats benefit multi-taxa biodiversity? The main goal of AES is the conservation of biodiversity in agricultural landscapes. I investigated how effectively AES habitats with different temporal continuity fulfil this goal in differently structured landscapes. The different AES habitats investigated had variable effects on local biodiversity. Temporal continuity of AES habitats was the most important predictor with older, more temporally continuous habitats harbouring higher overall biodiversity and different species assemblages in most taxonomic groups than younger AES habitats. Results however varied among taxonomic groups and natural enemies were equally supported by younger habitats. Semi-natural habitats in the surrounding landscape and AES habitat size were of minor importance for local biodiversity and had limited effects. This stresses that newly established AES habitats alone cannot restore farmland biodiversity. Both AES habitats as well as more continuous semi-natural habitats synergistically increase overall biodiversity in agricultural landscapes. Chapter VI: The effects of AES habitats on predators in adjacent oilseed rape fields Apart from biodiversity conservation, ensuring ecosystem service delivery in agricultural landscapes is a crucial goal of AES. I therefore investigated the effects of adjacent AES habitats on ground dwelling predator assemblages in oilseed rape fields. I found clear distance decay effects from the field edges into the field centres on both richness and densities of ground dwelling predators. Direct effects of adjacent AES habitats on assemblages in oilseed rape fields however were limited and only visible in functional traits of carabid beetle assemblages. Adjacent AES habitats doubled the proportion of predatory carabid beetles indicating a beneficial role for pest control. My results show that pest control potentials are largest close to the field edges and beneficial effects are comparably short ranged. Chapter VII: The effects of AES habitats on pest control in adjacent cereal fields Whether distance functions and potential effects of AES habitats are universal across crops is unknown. Therefore, I assessed distance functions of predators, pests, predation rates and yields after crop rotation in winter cereals using the same study design as in the previous year. Resulting distance functions were not uniform and differed from those found in oilseed rape in the previous year, indicating that the interactions between certain adjacent habitats vary with habitat and crop types. Distance functions of cereal-leaf beetles (important cereal pests) and parasitoid wasps were moreover modulated by semi-natural habitat proportion in the surrounding landscapes. Field edges buffered assemblage changes in carabid beetle assemblages over crop rotation confirming their important function as refuges for natural enemies. My results emphasize the beneficial role of field edges for pest control potentials. These findings back the calls for smaller field sizes and more diverse, more heterogeneously structured agricultural landscapes. Chapter VIII: General Discussion Countering biodiversity loss and ensuring ecosystem service provision in agricultural landscapes is intricate and requires strategic planning and restructuring of these landscapes. I showed that agricultural landscapes could benefit maximally from (i) a mixture of AES habitats and semi-natural habitats to support high levels of overall biodiversity and from (ii) smaller continuously managed agricultural areas (i.e. smaller field sizes or the insertion of AES elements within large fields) to maximize natural pest control potentials in crop fields. I propose a mosaic of younger AES habitats and semi-natural habitats to support ecosystem service providers and increase edge density for ecosystem service spillover into adjacent crops. The optimal extent and density of this network as well as the location in which AES and semi-natural habitats interact most beneficially with adjacent crops need further investigation. My results provide a further step towards more sustainable agricultural landscapes that simultaneously allow biodiversity to persist and maintain agricultural production under the framework of ecological intensification.},
  subject      = {{\"O}kologie},
  language  = {en}
}
@phdthesis{Saverschek2010,
  author    = {Saverschek, Nicole},
  title     = {The influence of the symbiotic fungus on foraging decisions in leaf-cutting ants - Individual behavior and collective patterns},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-52087},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Foraging behavior is a particularly fascinating topic within the studies of social insects. Decisions made by individuals have effects not only on the individual level, but on the colony level as well. Social information available through foraging in a group modulates individual preferences and shapes the foraging pattern of a colony. Identifying parameters influencing foraging behavior in leaf-cutting ants is especially intriguing because they do not harvest for themselves, but for their symbiotic fungus which in turn influences their plant preferences after the incorporation of the substrate. To learn about the substrates' unsuitability for the fungus, ants need to be able to identify the incorporated substrate and associate it with detrimental effects on the fungus. Odor is an important plant characteristic known to be used as recognition key outside the nest in the context of foraging. Chapter 1 shows that foragers are able to recall information about the unsuitability of a substrate through odor alone and consequently reject the substrate, which leads to the conclusion that inside the nest, odor might be enough to indentify incorporated substrate. Identification of plant species is a key factor in the foraging success of leaf-cutting ants as they harvest a multitude of different plant species in a diverse environment and host plant availability and suitability changes throughout the year. Fixed plant preferences of individuals through innate tendencies are therefore only one factor influencing foraging decisions. On the individual as well as the colony level, foraging patterns are flexible and a result of an intricate interplay between the different members involved in the harvesting process: foragers, gardeners and the symbiotic fungus. In chapter 2 I identified several conditions necessary for na{\"i}ve foragers to learn about the unsuitability of substrate inside the nest. In order to exchange of information about the unsuitability of a substrate, the plant in question must be present in the fungus garden. Foragers can learn without own foraging experience and even without experiencing the effects of the substrate on the fungus, solely through the presence of experienced gardeners. The presence of experienced foragers alone on the other hand is not enough to lower the acceptance of substrate by na{\"i}ve foragers in the presence of na{\"i}ve gardeners, even if experienced foragers make up the majority of the workforce inside the nest. Experienced foragers are also able to reverse their previous negative experience and start accepting the substrate again. The individual behavior of foragers and gardeners with different experiential backgrounds in the presence of suitable or unsuitable substrate inside the fungus chamber was investigated in chapter 3 to shed some light on possible mechanisms involved in the flow of information about substrate suitability from the fungus to the ants. Gardeners as well as foragers are involved in the leaf processing and treatment of the applied leaf patches on the fungus. If the plant material is unsuitable, significantly more ants treat the plant patches, but foragers are less active overall. Contacts between workers initiated by either gardeners or foragers occur significantly more frequent and last longer if the substrate is unsuitable. Even though experienced gardeners increase na{\"i}ve foragers' contact rates and duration with other workers in the presence of suitable plant patches, na{\"i}ve foragers show no differences in the handling of the plant patches. This suggests that foragers gain information about plant suitability not only indirectly through the gardening workers, but might also be able to directly evaluate the effects of the substrate on the fungus themselves. Outside the nest, foragers influence each other the trail (chapter 4). Foraging in a group and the presence of social information is a decisive factor in the substrate choice of the individual and leads to a distinct and consentaneous colony response when encountering unfamiliar or unsuitable substrates. As leaf-cutting ants harvest different plant species simultaneously on several trails, foragers gain individual experiences concerning potential host plants. Preferences might vary among individuals of the same colony to the degree that foragers on the same trail perceive a certain substrate as either suitable or unsuitable. If the majority of foragers on the trail perceives one of the currently harvested substrates as unsuitable, na{\"i}ve foragers lower their acceptance within 4 hours. In the absence of a cue in the fungus, na{\"i}ve foragers harvesting by themselves still eventually (within 6 hours) reject the substrate as they encounter experienced gardeners during visits to the nest within foraging bouts. As foraging trails can be up to 100 m long and foragers spend a considerable amount of time away from the nest, learning indirectly from experienced foragers on the trail accelerates the distribution of information about substrate suitability. The level of rejection of a formerly unsuitable substrate after eight hours of foraging by na{\"i}ve foragers correlates with the average percentage of unladen experienced foragers active on the trail. This suggests that unladen experienced foragers might actively contact laden na{\"i}ve workers transmitting information about the unsuitability of the load they carry. Results from experiments were I observed individual laden foragers on their way back to the nest backed up this assumption as individuals were antennated and received bites into the leaf disk they carried. Individuals were contacted significantly more often by nestmates that perceived the carried leaf disk as unsuitable due to previous experience than by nestmates without this experience (chapter 6). Leaf-cutting ants constantly evaluate, learn and re-evaluate the suitability of harvested substrate and adjust their foraging activity accordingly. The importance of the different sources of information within the colony and their effect on the foraging pattern of the colony depend on the presence or absence of each of them as e.g. experienced foragers have a bigger influence on the plant preferences of na{\"i}ve foragers in the absence of a cue in the fungus garden.},
  subject      = {Blattschneiderameisen},
  language  = {en}
}
@phdthesis{Beck2005,
  author    = {Beck, Jan},
  title     = {The macroecology of Southeast-Asian hawkmoths (Lepidoptera: Sphingidae)},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-13001},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {This study investigates the abundance and geographic distribution of the hawkmoth species (Lepidoptera: Sphingidae) of Southeast-Asia and analyses the resulting patterns of biodiversity, biogeography and macroecology. Data on the distribution of species were retrieved from published and unpublished faunal lists and museum collections (in close cooperation with the Natural History Museum, London). Over 34,500 records of the global distribution of the 380 species that occur in Southeast-Asia (including New Guinea and the Solomon Islands) were used for a GIS-supported estimate of distributional ranges, which can be accessed at http://www.sphingidae-sea.biozentrum.uni-wuerzburg.de, an Internet site that also provides pictures of the species and checklists for 114 islands of the Malesian region. The abundance of species in local assemblages was assessed from nightly collections at artificial light sources. Using a compilation of own samples as well as published and unpublished data from other sources, local abundance data on 93 sites were used for analysis, covering 159 species or 17,676 specimens.},
  language  = {en}
}
@phdthesis{Schuecker2018,
  author    = {Sch{\"u}cker, Katharina},
  title     = {The molecular architecture of the meiotic chromosome axis as revealed by super-resolution microscopy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144199},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2018},
  abstract  = {During meiosis proteins of the chromosome axis are important for monitoring chromatin structure and condensation, for pairing and segregation of chromosomes, as well as for accurate recombination. They include HORMA-domain proteins, proteins of the DNA repair system, synaptonemal complex (SC) proteins, condensins and cohesins. To understand more about their function in shaping the meiotic chromosome it is crucial to establish a defined model of their molecular architecture. Up to now their molecular organization was analysed using conventional methods, like confocal scanning microscopy (CLSM) and transmission electron microscopy (TEM). Unfortunately, these techniques are limited either by their resolution power or their localization accuracy. In conclusion, a lot of data on the molecular organization of chromosome axis proteins stays elusive. For this thesis the molecular structure of the murine synaptonemal complex (SC) and the localization of its proteins as well as of three cohesins was analysed with isotropic resolution, providing new insights into their architecture and topography on a nanoscale level. This was done using immunofluorescence labelling in combination with super-resolution microscopy, line profiles and average position determination. The results show that the murine SC has a width of 221.6 nm ± 6.1 nm including a central region (CR) of 148.2 nm ± 2.6 nm. In the CR a multi-layered organization of the central element (CE) proteins was verified by measuring their strand diameters and strand distances and additionally by imaging potential anchoring sites of SYCP1 (synaptonemal complex protein 1) to the lateral elements (LEs). We were able to show that the two LEs proteins SYCP2 and SYCP3 do co-localize alongside their axis and that there is no significant preferential localization towards the inner LE axis of SYCP2. The presented results also predict an orderly organization of murine cohesin complexes (CCs) alongside the chromosome axis in germ cells and support the hypothesis that cohesins in the CR of the SC function independent of CCs. In the end new information on the molecular organization of two main components of the murine chromosome axis were retrieved with nanometer precision and previously unknown details of their molecular architecture and topography were unravelled.},
  subject      = {Meiose},
  language  = {en}
}
@phdthesis{Paul2001,
  author    = {Paul, J{\"u}rgen},
  title     = {The Mouthparts of Ants},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-1179130},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2001},
  abstract  = {Ant mandible movements cover a wide range of forces, velocities and precision. The key to the versatility of mandible functions is the mandible closer muscle. In ants, this muscle is generally composed of distinct muscle fiber types that differ in morphology and contractile properties. Volume proportions of the fiber types are species-specific and correlate with feeding habits. Two biomechanical models explain how the attachment angles are optimized with respect to force and velocity output and how filament-attached fibers help to generate the largest force output from the available head capsule volume. In general, the entire mandible closer muscle is controlled by 10-12 motor neurons, some of which exclusively supply specific muscle fiber groups. Simultaneous recordings of muscle activity and mandible movement reveal that fast movements require rapid contractions of fast muscle fibers. Slow and accurate movements result from the activation of slow muscle fibers. Forceful movements are generated by simultaneous co-activation of all muscle fiber types. For fine control, distinct fiber bundles can be activated independently of each other. Retrograde tracing shows that most dendritic arborizations of the different sets of motor neurons share the same neuropil in the suboesophageal ganglion. In addition, some motor neurons invade specific parts of the neuropil. The labiomaxillary complex of ants is essential for food intake. I investigated the anatomical design of the labiomaxillary complex in various ant species focusing on movement mechanisms. The protraction of the glossa is a non muscular movement. Upon relaxation of the glossa retractor muscles, the glossa protracts elastically. I compared the design of the labiomaxillary complex of ants with that of the honey bee, and suggest an elastic mechanism for glossa protraction in honey bees as well. Ants employ two different techniques for liquid food intake, in which the glossa works either as a passive duct (sucking), or as an up- and downwards moving shovel (licking). For collecting fluids at ad libitum food sources, workers of a given species always use only one of both techniques. The species-specific feeding technique depends on the existence of a well developed crop and on the resulting mode of transporting the fluid food. In order to evaluate the performance of collecting liquids during foraging, I measured fluid intake rates of four ant species adapted to different ecological niches. Fluid intake rate depends on sugar concentration and the associated fluid viscosity, on the species-specific feeding technique, and on the extent of specialization on collecting liquid food. Furthermore, I compared the four ant species in terms of glossa surface characteristics and relative volumes of the muscles that control licking and sucking. Both probably reflect adaptations to the species-specific ecological niche and determine the physiological performance of liquid feeding. Despite species-specific differences, single components of the whole system are closely adjusted to each other according to a general rule.},
  subject      = {Ameisen},
  language  = {en}
}
@phdthesis{Cook2012,
  author    = {Cook, Mandy},
  title     = {The neurodegenerative Drosophila melanogaster AMPK mutant loechrig},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72027},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2012},
  abstract  = {In dieser Doktorarbeit wird die Drosophila Mutante loechrig (loe), die progressive Degeneration des Nervensystems aufweist, weiter beschrieben. In der loe Mutante fehlt eine neuronale Isoform der γ- Untereinheit der Proteinkinase AMPK (AMP-activated protein kinase). Die heterotrimere AMPK (auch als SNF4Aγ bekannt) kontrolliert das Energieniveau der Zelle, was st{\"a}ndiges Beobachten des ATP/AMP- Verh{\"a}ltnis erfordert. AMPK wird durch niedrige Energiekonzentrationen und Beeintr{\"a}chtigungen im Metabolismus, wie zum Beispiel Sauerstoffmangel, aktiviert und reguliert mehrere wichtige Signaltransduktionswege, die den Zellmetabolismus kontrollieren. Jedoch ist die Rolle von AMPK im neuronalen {\"U}berleben noch unklar. Eines der Proteine, dass von AMPK reguliert wird, ist HMGR (hydroxymethylglutaryl-CoA- reductase), ein Schl{\"u}sselenzym in der Cholesterin- und Isoprenoidsynthese. Es wurde gezeigt, dass wenn die Konzentration von HMGR manipuliert wird, auch der Schweregrad des neurodegenerativen Ph{\"a}notyps in loe beeinflusst wird. Obwohl die regulatorische Rolle von AMPK auf HMGR in Drosophila konserviert ist, k{\"o}nnen Insekten Cholesterin nicht de novo synthetisieren. Dennoch ist der Syntheseweg von Isoprenoiden zwischen Vertebraten und Insekten evolution{\"a}r konserviert. Isoprenylierung von Proteinen, wie zum Beispiel von kleinen G-Proteinen, stellt den Proteinen einen hydophobischen Anker bereit, mit denen sie sich an die Zellmembran binden k{\"o}nnen, was in anschließender Aktivierung resultieren kann. In dieser Doktorarbeit wird gezeigt, dass die loe Mutation die Prenylierung von Rho1 und den LIM-Kinasesignalweg beeinflusst, was eine wichtige Rolle im Umsatz von Aktin und axonalem Auswachsen spielt. Die Ergebnisse weisen darauf hin, dass die Mutation in LOE, Hyperaktivit{\"a}t des Isoprenoidsynthesewegs verursacht, was zur erh{\"o}hten Farnesylierung von Rho1 und einer dementsprechend h{\"o}heren Konzentration von Phospho- Cofilin f{\"u}hrt. Eine Mutation in Rho1 verbessert den neurodegenerativen Ph{\"a}notyp und die Lebenserwartung von loe. Der Anstieg vom inaktiven Cofilin in loe f{\"u}hrt zu einer Zunahme von filament{\"o}sen Aktin. Aktin ist am Auswachen von Neuronen beteiligt und Experimente in denen loe Neurone analysiert wurden, gaben wertvolle Einblicke in eine m{\"o}gliche Rolle die AMPK, und dementsprechend Aktin, im Neuronenwachstum spielt. Des Weiteren wurde demonstriert, dass Neurone, die von der loe Mutante stamen, einen verlangsamten axonalen Transport aufweisen, was darauf hinweist dass Ver{\"a}nderungen, die durch den Einfluss von loe auf den Rho1 Signalweg im Zytoskelettnetzwerk hervorgerufen wurden, zur St{\"o}rung des axonalen Transports und anschließenden neuronalen Tod f{\"u}hren. Es zeigte außerdem, dass Aktin nicht nur am neuronalen Auswachsen beteiligt ist, sondern auch wichtig f{\"u}r die Aufrechterhaltung von Neuronen ist. Das bedeutet, dass {\"A}nderungen der Aktindynamik zur progressiven Degeneration von Neuronen f{\"u}hren kann. Zusammenfassend unterstreichen diese Ergebnisse die wichtige Bedeutung von AMPK in den Funktionen und im {\"U}berleben von Neuronen und er{\"o}ffnen einen neuartigen funktionellen Mechanismus in dem {\"A}nderungen in AMPK neuronale Degeneration hervorrufen kann.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Kelber2009,
  author    = {Kelber, Christina},
  title     = {The olfactory system of leafcutting ants: neuroanatomy and the correlation to social organization},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47769},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {In leaf-cutting ants (genera Atta and Acromyrmex), the worker caste exhibits a pronounced size-polymorphism, and division of labor is largely dependent on worker size (alloethism). Behavioral studies have shown a rich diversity of olfactory-guided behaviors, and the olfactory system seems to be highly developed and very sensitive. To allow fine-tuned behavioral responses to different tasks, adaptations within the olfactory system of different sized workers are expected. In a recent study, two different phenotypes of the antennal lobe of Atta vollenweideri workers were found: MG- and RG-phenotype (with and without a macroglomerulus, MG). The existence of the macroglomerulus is correlated to the body size of workers, with small workers showing the RG-phenotype and large workers showing the MG-phenotype. In the MG, the information about the releaser component of the trail-pheromone is processed. In the first part of my PhD-project, I focus on quantifying behavioral differences between different sized workers in Atta vollenweideri. The study analyzes the trail following behavior; which can be generally performed by all workers. An artificial trail consisting of the releaser component of the trail-pheromone in decreasing concentration was used to test the trail-following performance of individual workers. The trail-following performance of the polymorphic workers is depended of the existence of the MG in the antennal lobe. Workers possessing the MG-phenotype were significantly better in following a decreasing trail then workers showing the RG-phenotype. In the second part I address the question if there are more structural differences, besides the MG, in the olfactory system of different sized workers. Therefore I analyze whether the glomerular numbers are related to worker size. The antennal lobes of small workers contain ~390 glomeruli (low-number; LN-phenotype), and in large workers I found a substantially higher number of ~440 glomeruli (high-number; HN-phenotype). All LN-phenotype workers and some of the small HN-phenotype workers do not possess an MG (LN-RG-phenotype and HN-RG-phenotype) at all, whereas the remaining majority of HN-phenotype workers do possess an MG (HN-MG-phenotype). Mass-stainings of antennal olfactory receptor neurons revealed that the sensory tracts divide the antennal lobe into six clusters of glomeruli (T1-T6). In the T4-cluster ~50 glomeruli are missing in the LN-phenotype workers. Selective staining of single sensilla and their associated receptor neurons showed that T4-glomeruli are innervated by receptor neurons from the main type of olfactory sensilla, the Sensilla trichodea curvata which are also projecting to glomeruli in all other clusters. The other type of olfactory sensilla, the Sensilla basiconica, exclusively innervates T6-glomeruli. Quantitative analyses revealed a correlation between the number of Sensilla basiconica and the volume of T6 glomeruli in different sized workers. The results of both behavioral and neuroanatomical studies in Atta vollenweideri suggest that developmental plasticity of antennal-lobe phenotypes promotes differences in olfactory-guided behavior which may underlie task specialization within ant colonies. The last part of my project focuses on the evolutionary origin of the macroglomerulus and the number of glomeruli in the antennal lobe. I compared the number, volumes and position of the glomeruli of the antennal lobe of 25 different species from all three major Attini groups (lower, higher and leaf-cutting Attini). The antennal lobes of all investigated Attini comprise a high number of glomeruli (257-630). The highest number was found in Apterostigma cf. mayri. This species is at a basal position within the Attini phylogeny, and a high number of glomeruli might have been advantageous in the evolution of the advanced olfactory systems of this Taxa. The macroglomerulus can be found in all investigated leaf-cutting Attini, but in none of the lower and higher Attini species. It is found only in large workers, and is located close to the entrance of the antennal nerve in all investigated species. The results indicate that the presence of a macroglomerulus in large workers of leaf-cutting Attini is a derived overexpression of a trait in the polymorphic leaf-cutting species. It presumably represents an olfactory adaptation to elaborate foraging and mass recruitment systems, and adds to the complexity of division of labor and social organization known for this group.},
  subject      = {Gehirn},
  language  = {en}
}
@phdthesis{Grue1999,
  author    = {Grue, Pernille},
  title     = {The physiological role of the two isoforms of DNA topoisomerase II in human cells},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-1369},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1999},
  abstract  = {Unique functions of DNA topoisomerase IIalpha and IIbeta have been suggested. A human cell line which carries a homozygeous mutation of the nuclear localization sequence of the topoisomerase IIalpha gene expresses the isoform outside the nucleus at the onset of mitosis. At mitosis topoisomerase IIbeta diffused away from the chromatin despite the nuclear lack of the IIalpha-form. Chromosome condensation and disjunction was performed with the aid of cytosolic topoisomerase IIalpha which bound to the mitotic chromatin with low affinity. Consequently an increased rate of nondisjunction is observed in these cells. It is concluded that high affinity chromatin binding of topoisomerase IIalpha is essential for chromosome condensation/disjunction and that topoisomerase IIbeta does not adopt these functions. A centrosomal protein was recognized by topoisomerase IIalpha. This topoisomerase IIalpha-like protein resembles a modified form of topoisomerase IIalpha with an apparent size of 205 kDa compared to 170 kDa. The expression of the protein is constant in all stages of the cell cycle and it appears in proliferating as well as in resting cells. If there is not sufficient topoisomerase IIalpha present at mitosis the centrosomal proteins might adopt the function and a mitotic catastrophe in the cells could therefore be prevented.},
  subject      = {DNS-Gyrase},
  language  = {en}
}
@phdthesis{Froese2008,
  author    = {Froese, Alexander},
  title     = {The Popeye domain containing gene 2 (Popdc2): Generation and functional characterization of a null mutant in mice and promoter analysis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-26473},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {In the present study a knockout mouse model of the Popeye domain containing gene 2 (Popdc2) was generated and functionally characterized. The Popdc2 null mutants were viable with an apparent normal life span. ß-galactosidase staining to visualize the expression of the Popdc2-LacZ transgene revealed the presence of the Popdc2 in heart, bladder, smooth and skeletal muscles. In the heart LacZ was found to be present in cardiac myocytes with elevated levels in the myocytes of the cardiac conduction system. Holter ECGs records of the heart function of the 8 months (but not in 3 and 6 months) old mutant and WT littermates revealed a pronounced sinus bradycardia in the mutant mice in response to three different stress regimens: isoproterenol infusion, mental stress and a physical exercise. Histological examination of the Popdc2 null mutants SAN revealed structural alterations as was detected by HCN4 staining. Moreover, volume measurements using 3-D reconstructions of serial sections stained with HCN4 antibody revealed a volume reduction of about 30\% in the mutant SAN. Taken together data presented in this study suggest that the Popdc2 KO mouse line may serve as an animal model of human sick sinus syndrome. In the second part of this thesis the Popdc2 gene promoter was analyzed. Three transcription factors binding sites were predicted in the promoter region and characterized.},
  subject      = {Herz},
  language  = {en}
}
@phdthesis{Krones2022,
  author    = {Krones, David},
  title     = {The Role of Acid Sphingomyelinase in \(Staphylococcus\) \(aureus\) Infection of Endothelial Cells},
  doi       = {10.25972/OPUS-29049},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290492},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {Staphylococcus aureus is a human bacterial pathogen responsible for a variety of diseases including bacterial pneumonia and sepsis. Recent studies provided an explanation, how S. aureus and its exotoxins contribute to the degradation of endothelial junction proteins and damage lung tissue [4]. Previous findings were indicating an involvement of acid sphingomyelinase (ASM) activity in cell barrier degradation [5]. In the presented study the impact of singular virulence factors, such as staphylococcal α-toxin, on in vitro cell barrier integrity as well as their ability to elicit an activation of ASM were investigated. Experiments with bacterial supernatants performed on human endothelial cells demonstrated a rapid dissociation after treatment, whereas murine endothelial cells were rather resistant against cell barrier degradation. Furthermore, amongst all tested staphylococcal toxins it was found that only α-toxin had a significant impact on endothelial junction proteins and ASM activity. Ablation of this single toxin was sufficient to protect endothelial cells from cell barrier degradation and activation of ASM was absent. In this process it was verified, that α-toxin induces a recruitment of intracellular ASM, which is accompanied by rapid and oscillating changes in cytoplasmic Ca2+ concentration and an increased exposure of Lysosomal associated membrane protein 1 (LAMP1) on the cell surface. Recruitment of lysosomal ASM is associated, among other aspects, to plasma membrane repair and was previously described to be involved with distinct pathogens as well as other pore forming toxins (PFT). However, with these findings a novel feature for α-toxin has been revealed, indicating that the staphylococcal PFT is able to elicit a similar process to previously described plasma membrane repair mechanisms. Increased exposure and intake of surface membrane markers questioned the involvement of ASM activity in S. aureus internalization by non-professional phagocytes such as endothelial cells. By modifying ASM expression pattern as well as application of inhibitors it was possible to reduce the intracellular bacterial count. Thus, a direct connection between ASM activity and S. aureus infection mechanisms was observed, therefore this study exemplifies how S. aureus is able to exploit the host cell sphingolipid metabolism as well as benefit of it for invasion into non-professional phagocytic cells},
  subject      = {Staphylococcus aureus},
  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}
}
@phdthesis{Iltzsche2017,
  author    = {Iltzsche, Fabian},
  title     = {The Role of DREAM/MMB-mediated mitotic gene expression downstream of mutated K-Ras in lung cancer},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154108},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2017},
  abstract  = {The evolutionary conserved Myb-MuvB (MMB) multiprotein complex has an essential role in transcriptional activation of mitotic genes. MMB target genes as well as the MMB associated transcription factor B-Myb and FoxM1 are highly expressed in a range of different cancer types. The elevated expression of these genes correlates with an advanced tumor state and a poor prognosis. This suggests that MMB could contribute to tumorigenesis by mediating overexpression of mitotic genes. Although MMB has been extensively characterized biochemically, the requirement for MMB to tumorigenesis in vivo remains largely unknown and has not been tested directly so far. In this study, conditional knockout of the MMB core member Lin9 inhibits tumor formation in vivo in a mouse model of lung cancer driven by oncogenic K-Ras and loss of p53. The incomplete recombination observed within tumors points towards an enormous selection pressure against the complete loss of Lin9. RNA interference (RNAi)-mediated depletion of Lin9 or the MMB associated subunit B-Myb provides evidence that MMB is required for the expression of mitotic genes in lung cancer cells. Moreover, it was demonstrated that proliferation of lung cancer cells strongly depends on MMB. Furthermore, in this study, the relationship of MMB to the p53 tumor suppressor was investigated in a primary lung cancer cell line with restorable p53 function. Expression analysis revealed that mitotic genes are downregulated after p53 re-expression. Moreover, activation of p53 induces formation of the repressive DREAM complex and results in enrichment of DREAM at mitotic gene promoters. Conversely, MMB is displaced at these promoters. Based on these findings the following model is proposed: In p53-negative cells, mitogenic stimuli foster the switch from DREAM to MMB. Thus, mitotic genes are overexpressed and may promote chromosomal instability and tumorigenesis. This study provides evidence that MMB contributes to the upregulation of G2/M phase-specific genes in p53-negative cells and suggests that inhibition of MMB (or its target genes) might be a strategy for treatment of lung cancer.},
  subject      = {Nicht-kleinzelliges Bronchialkarzinom (NSCLC)},
  language  = {en}
}
@phdthesis{Herold2003,
  author    = {Herold, Andrea},
  title     = {The role of human and Drosophila NXF proteins in nuclear mRNA export},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5601},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {A distinguishing feature of eukaryotic cells is the spatial separation of the site of mRNA synthesis (nucleus) from the site of mRNA function (cytoplasm) by the nuclear envelope. As a consequence, mRNAs need to be actively exported from the nucleus to the cytoplasm. At the time when this study was initiated, both human TAP and yeast Mex67p had been proposed to play a role in this process. Work presented in this thesis (section 2.1) revealed that TAP and Mex67p belong to an evolutionarily conserved family of proteins which are characterized by a conserved modular domain organization. This family was termed nuclear export factor (NXF) family. While the yeast genome encodes only one NXF protein (Mex67p), the genomes of higher eukaryotes encode several NXF proteins. There are two nxf genes in C. elegans and A. gambiae, four in D. melanogaster, and at least four in H. sapiens and M. musculus. It was unclear whether, apart from TAP and Mex67p, other members of this family would also be involved in mRNA export. In the first part of this thesis (2.1), several human NXF members were tested for a possible function in nuclear mRNA export. They were analyzed for their interaction with RNA, nucleoporins and other known TAP partners in vitro, and tested for their ability to promote nuclear export of a reporter mRNA in vivo. Using these assays, human NXF2, NXF3 and NXF5 were all shown to interact with the known NXF partner p15. NXF2 and NXF5 were also found to bind directly to RNA, but only NXF2 was able to bind directly to nucleoporins and to promote the nuclear export of an (untethered) reporter mRNA. Thus NXF2 possesses many and NXF3 and NXF5 possess some of the features required to serve as an export receptor for cellular mRNAs. As NXF2 and NXF3 transcripts were mainly found in testis, and the closest orthologue of NXF5 in mouse has the highest levels of expression in brain, these NXF members could potentially serve as tissue-specific mRNA export receptors. In the second part of this work (2.2), the role of different Drosophila NXF proteins and other export factors in mRNA export was investigated using double-stranded RNA interference (RNAi) in Drosophila Schneider cells. Three of the four predicted Drosophila NXF members (NXF1-3) were found to be expressed in this cell line and could be targeted by RNAi. Depletion of endogenous NXF1 inhibited growth and resulted in the nuclear accumulation of polyadenylated RNA. Fluorescence in situ hybridization revealed that export of both heat shock and non-heat shock mRNAs, including intron-containing and intronless mRNAs, was inhibited. Depleting endogenous NXF2 or NXF3 had no apparent phenotype. These results suggested that NXF1 (but not NXF2-NXF4) mediates the export of bulk mRNA in Drosophila cells. We and others have shown that human NXF proteins function as heterodimers bound to the small protein p15. Accordingly, silencing of Drosophila p15 resulted in a block of mRNA export which was indistinguishable from the export inhibition seen after targeting NXF1. These observations indicated that neither NXF1 nor p15 can promote export in the absence of the other subunit of the heterodimer. NXF1:p15 heterodimers are implicated in late steps of mRNA export, i.e. in the translocation of mRNP export cargoes across the nuclear pore complex. The mechanism by which NXF1:p15 dimers are recruited to the mRNA is unclear. A protein that is thought to play a role in this process is the putative RNA helicase UAP56. Similar to NXF1 and p15, UAP56 was shown to be essential for mRNA export in Drosophila. UAP56 is recruited cotranscriptionally to nascent transcripts and was suggested to facilitate the interaction of NXF1:p15 with mRNPs. Even though both NXF1:p15 heterodimers and UAP56 had been implicated in general mRNA export, it was unclear whether there are classes of mRNAs that require NXF1:p15, but not UAP56 or vice versa. It was also unclear what fraction of cellular mRNAs is exported by NXF1:p15 dimers and UAP56, and whether mRNAs exist that reach the cytoplasm through alternative routes, i.e. by recruiting other export receptors. To address these issues we performed a genome-wide analysis of nuclear mRNA export pathways using microarray technology (2.2.2). We analyzed the relative abundance of nearly half of the Drosophila transcriptome in the cytoplasm of Drosophila Schneider cells depleted of different export factors by RNAi. We showed that the vast majority of transcripts were underrepresented in the cytoplasm of cells depleted of NXF1, p15 or UAP56 as compared to control cells. Only a small number of mRNAs were apparently not affected by the depletions. These observations, together with the wide and similar effects on mRNA levels caused by the depletion of NXF1, p15 or UAP56, indicate that these proteins define the major mRNA export pathway in these cells. We also identified a small subset of mRNAs which appeared to be exported by NXF1:p15 dimers independently of UAP56. In contrast, no significant changes in mRNA expression profiles were observed in cells depleted of NXF2 or NXF3, suggesting that neither NXF2 nor NXF3 play an essential role in mRNA export in Drosophila Schneider cells. Crm1 is a transport receptor implicated in the export of a variety of non-mRNA and protein cargoes. In addition, human Crm1 has been suggested to be involved in the export of a specific mRNA species, serving as a "specialized" mRNA export receptor. A role of human Crm1 in the export of bulk mRNA is considered unlikely. We analyzed the role of Drosophila Crm1 in mRNA export by inhibiting Crm1 with the drug leptomycin B in Schneider cells. Subsequent microarray analysis demonstrated that the inactivation of Crm1 resulted in decreased cytoplasmic levels of less than 1\% of all mRNAs, indicating that Crm1 is indeed not a major mRNA export receptor. The genome-wide analysis also revealed a feedback loop by which a block to mRNA export triggers the upregulation of genes involved in this process. This thesis also includes two sections describing projects in which I participated during my Ph.D., but which were not the main focus of this thesis. In section 2.3, the role of the different TAP/NXF1 domains in nuclear mRNA export is discussed. Section 2.4 describes results that were obtained as part of a collaboration using the RNAi technique in Schneider cells to study the function of Cdc37.},
  subject      = {Zellkern},
  language  = {en}
}
@phdthesis{Reichert2008,
  author    = {Reichert, Nina},
  title     = {The Role of LIN9 in Mouse Development},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-30889},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2008},
  abstract  = {LINC, the human homologue of an evolutionary conserved complex, regulates the transcription of a set of genes essential during the G2/M transition (Osterloh et al., 2007; Schmit et al., 2007). One component of the LINC core module is LIN-9. LIN-9 is essential for the transcriptional activation of LINC target genes and also promotes differentiation in association with pRB (Gagrica et al., 2004). However, nothing is known about its function in vivo. Histological and molecular analysis revealed that Lin9 is ubiquitously expressed throughout embryonic development and in all examined adult organs. Additionally, Lin9 mRNA is expressed in ES cells and blastocysts. Moreover the analogous distribution of the other LINC components suggested that they all function in the same cells and most likely in the same pathway. To deeper investigate the role of LIN9 in cell cycle and differentiation in vivo, a Lin9 gene trap mouse model (GT) was successfully generated and examined. Heterozygouse Lin9GT/+ mice were inconspicuous and develop normally. However, homozygouse knockout embryos were never obtained. The Lin9GT/GT embryos die at peri-implantation, probably due to a defect in the development of the epiblast, which could be shown with in situ hybridization with specific lineage markers. In vitro, the ICM of Lin9-deficient blastocysts did not develop properly. These data suggest that the loss of Lin9 leads to embryonic lethality at peri-implantation, and indicates that LIN9 is required for proper formation of the epiblast. In parallel, the first conditional Lin9 mouse model based on the Cre-loxP technology was generated. The Lin9fl/fl allele can be deleted by Cre-recombinase, in vivo and in vitro. Therefore an inducible system with Lin9fl/fl mice harboring Cre-ERT2 was established. The MEFs generated from these transgenic mice carried a nearly complete knockout upon induction with tamoxifen. Deletion of LIN9 in MEFs had a major impact upon the cell cycle and growth rates. Specifically, they arrested in G2/M phase and stopped to proliferate. Taken together, I was able to generate a lin9 gene trap and a lin9 conditional knockout mouse model. All results obtained so far demonstrate, that Lin9 is an essential gene for embryonic development and cell cycle control. It will be of great interest to further investigate Lin9-deficiency to gain insights into the mechanism of cell cycle control in early embryonic development and cell differentiation.},
  subject      = {Zellzyklus},
  language  = {en}
}
@phdthesis{Link2013,
  author    = {Link, Jana},
  title     = {The role of meiotic nuclear envelope components in chromosome dynamics and meiotic progression},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83540},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {Meiosis is the specialised cell division which produces haploid germ cells, capable of developing into fertile gametes, from diploid progenitor cells. During meiosis, chromosomes undergo strictly regulated and strongly conserved dynamic processes, at the beginning of which the telomeres are actively tethered and intimately attached to the nuclear envelope (NE). The attached telomeres are then moved within the NE through cytoskeletal forces to cluster within a restricted region, forming the highly conserved bouquet stage. Subsequently, the bouquet is released simultaneously to the completion of the synaptonemal complex assembly tightly linking homologous chromosome pairs together. In combination these processes are essential for the successful completion of meiosis. Because the meiotic NE serves as a platform for telomere attachment and movement it can be assumed to be critically involved in these events crucial for fertility. However, the precise roles of many meiotic NE proteins in the attachment and movement of telomeres still remain elusive. Therefore, it was the aim of this thesis to investigate the functions of two mammalian meiotic NE components in telomere attachment and dynamics. The first part of this thesis is concerned with the meiosis-specific lamin C2. Lamin C2 is the only A-type lamin expressed during meiosis and has in previous studies shown to feature altered meiosis-specific properties, clearly distinguishing it from somatic lamins. Because lamin C2 is enriched at sites of telomere attachment, exhibits a high mobility within the nuclear lamina and influences NE integrity, it has been postulated that it may locally increase NE flexibility to allow efficient meiotic telomere movement. Therefore, possible functions of lamin C2 in the movement of attached telomeres were investigated in this thesis by studying the bouquet formation and release of pubertal mice specifically lacking lamin C2. This revealed that lamin C2 deficient mice show a delayed bouquet release, leading to severe defects in the synaptic pairing of homologous chromosomes, which in turn results in infertility of the males. Therefore, the efficient repositioning of attached meiotic telomeres, facilitated by lamin C2, seems essential for completing meiosis. The second part of this thesis focuses on the protein complex responsible for the attachment of meiotic telomeres to the NE and their coupling to the cytoskeleton. The so-called LINC complex is composed of SUN domain proteins in the inner nuclear membrane interacting with KASH domain proteins of the outer nuclear membrane. In previous studies it had been shown that SUN1, SUN2 and KASH5 localise to the attached meiotic telomeres. Regarding the meiotic role of SUN2, however, contradicting results have recently been discussed, showing the need for further investigations. Using an available SUN1 deficient mouse strain, this thesis was able to show that SUN2 is sufficient for telomere attachment per se although telomere attachment is impaired in SUN1 deficient mice leading to infertility. It is also demonstrated that SUN2 forms a functional LINC complex together with KASH5 to mediate this telomere attachment. This LINC complex in the absence of SUN1 is able to move attached telomeres into a bouquet-like cluster formation. Therefore, this demonstrates that SUN2 is involved in the functional attachment and movement of meiotic telomeres. In summary, this thesis has shown SUN2 and the meiotic nuclear lamina to be directly involved in or essential for the highly conserved attachment and movement of telomeres, making them critical for a successful meiosis. The meiotic NE is therefore in this thesis demonstrated to be a determinant of mammalian fertility.},
  subject      = {Meiose},
  language  = {en}
}
@phdthesis{Pei2000,
  author    = {Pei, Geng},
  title     = {The Role of Raf-mediated Signalling Pathways for Motoneuron},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-1846},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2000},
  abstract  = {The transmission of proliferative and developmental signals from activated cell-surface receptors to initiation of cellular responses in the nucleus is synergically controlled by the coordinated action of a diverse set of intracellular signalling proteins. The Ras/Raf/MEK/MAPK signalling pathway has been shown to control the expression of genes which are crucial for the physiological regulation of cell proliferation, differentiation and apoptosis. Within this signalling cascade, the Raf protein family of serine/threonine kinases serves as a central intermediate which connects to many of other signal transduction pathways. To elucidate the signalling functions of the different Raf kinases in motoneurons during development, the expression, distribution and subcellular localization of Rafs in the spinal cord and the facial nucleus in brainstem of mice at various embryonic and postnatal stages were investigated. Moreover, we have investigated the intracellular redistribution of Raf molecules in isolated motoneurons from 13 or 14 day old mouse embryos, after addition or withdrawal of neurotrophic factors to induce Raf kinases activation in vitro. Furthermore, in order to investigate the potential anti-apoptotic function of Raf kinases on motoneurons, we isolated motoneurons from B-raf-/- and c-raf-1-/- mouse embryos and analysed the survival and differentiation effects of neurotrophic factors in motoneurons lacking B-Raf and c-Raf-1. We provide evidence here that all three Raf kinases are expressed in mouse spinal motoneurons. Their expression increases during the period of naturally occurring cell death of motoneurons. In sections of embryonic and postnatal spinal cord, motoneurons express exclusively B-Raf and c-Raf-1, but not A-Raf, and subcellularly Raf kinases are obviously colocalized with mitochondria. In isolated motoneurons, most of the B-Raf or c-Raf-1 immunoreactivity is located in the perinuclear space but also in the nucleus, especially after activation by addition of CNTF and BDNF in vitro. We found that c-Raf-1 translocation from the cytosol into the nucleus of motoneurons after its activation by neurotrophic factors is a distinct event. As a central finding of our study, we observed that the viability of isolated motoneurons from B-raf but not c-raf-1 knockout mice is lost even in the presence of CNTF and other neurotrophic factors. This indicates that B-Raf but not c-Raf-1, which is still present in B-raf deficient motoneurons, plays a crucial role in mediating the survival effect of neurotrophic factors during development. In order to prove that B-Raf is an essential player in this scenario, we have re-expressed B-Raf in mutant sensory and motor neurons by transfection. The motoneurons and the sensory neurons from B-raf knockout mouse which were transfected with exogenous B-raf gene revealed the same viability in the presence of neurotrophic factors as primary neurons from wild-type mice. Our results suggest that Raf kinases have important signalling functions in motoneurons in mouse CNS. In vitro, activation causes redistribution of Raf protein kinases, particularly for c-Raf-1, from motoneuronal cytoplasm into the nucleus. This redistribution of c-Raf-1, however, is not necessary for the survival effect of neurotrophic factors, given that B-raf-/- motor and sensory neurons can not survive despite the presence of c-Raf-1. We hypothesize that c-Raf-1 nuclear translocation may play a direct role in transcriptional regulation as a consequence of neurotrophic factor induced phosphorylation and activation of c-Raf-1 in motoneurons. Moreover, the identification of target genes for nuclear translocated c-Raf-1 and of specific cellular functions initiated by this mechanism awaits its characterization.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{Pasch2016,
  author    = {Pasch, Elisabeth},
  title     = {The role of SUN4 and related proteins in sperm head formation and fertility},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139092},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Spermiogenesis describes the differentiation of haploid germ cells into motile, fertilization-competent spermatozoa. During this fundamental transition the species-specific sperm head is formed, which necessitates profound nuclear restructuring coincident with the assembly of sperm-specific structures and chromatin compaction. In the case of the mouse, it is characterized by reshaping of the early round spermatid nucleus into an elongated sickle-shaped sperm head. This tremendous shape change requires the transduction of cytoskeletal forces onto the nuclear envelope (NE) or even further into the nuclear interior. LINC (linkers of nucleoskeleton and cytoskeleton) complexes might be involved in this process, due to their general function in bridging the NE and thereby physically connecting the nucleus to the peripheral cytoskeleton. LINC complexes consist of inner nuclear membrane integral SUN-domain proteins and outer nuclear membrane KASH-domain counterparts. SUN- and KASH-domain proteins are directly connected to each other within the perinuclear space, and are thus capable of transferring forces across the NE. To date, these protein complexes are known for their essential functions in nuclear migration, anchoring and positioning of the nucleus, and even for chromosome movements and the maintenance of cell polarity and nuclear shape. In this study LINC complexes were investigated with regard to their potential role in sperm head formation, in order to gain further insight into the processes occurring during spermiogenesis. To this end, the behavior and function of the testis-specific SUN4 protein was studied. The SUN-domain protein SUN4, which had received limited characterization prior to this work, was found to be exclusively expressed in haploid stages during germ cell development. In these cell stages, it specifically localized to the posterior NE at regions decorated by the manchette, a spermatid-specific structure which was previously shown to be involved in nuclear shaping. Mice deficient for SUN4 exhibited severely disorganized manchette residues and gravely misshapen sperm heads. These defects resulted in a globozoospermia-like phenotype and male mice infertility. Therefore, SUN4 was not only found to be mandatory for the correct assembly and anchorage of the manchette, but also for the correct localization of SUN3 and Nesprin1, as well as of other NE components. Interaction studies revealed that SUN4 had the potential to interact with SUN3, Nesprin1, and itself, and as such is likely to build functional LINC complexes that anchor the manchette and transfer cytoskeletal forces onto the nucleus. Taken together, the severe impact of SUN4 deficiency on the nucleocytoplasmic junction during sperm development provided direct evidence for a crucial role of SUN4 and other LINC complex components in mammalian sperm head formation and fertility.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{LuiblneeHermann2014,
  author    = {Luibl [n{\´e}e Hermann], Christiane},
  title     = {The role of the neuropeptides NPF, sNPF, ITP and PDF in the circadian clock of Drosophila melanogaster},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-93796},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Organisms have evolved endogenous clocks which allow them to organize their behavior, metabolism and physiology according to the periodically changing environmental conditions on earth. Biological rhythms that are synchronized to daily changes in environment are governed by the so-called circadian clock. Since decades, chronobiologists have been investigating circadian clocks in various model organisms including the fruitfly Drosophila melanogaster, which was used in the present thesis. Anatomically, the circadian clock of the fruitfly consists of about 150 neurons in the lateral and dorsal protocerebrum, which are characterized by their position, morphology and neurochemistry. Some of these neurons had been previously shown to contain either one or several neuropeptides, which are thought to be the main signaling molecules used by the clock. The best investigated of these neuropeptides is the Pigment Dispersing Factor (PDF), which had been shown to constitute a synchronizing signal between clock neurons as well as an output factor of the clock. In collaboration with various coworkers, I investigated the roles of three other clock expressed neuropeptides for the generation of behavioral rhythms and the partly published, partly unpublished data are presented in this thesis. Thereby, I focused on the Neuropeptide F (NPF), short Neuropeptide F (sNPF) and the Ion Transport Peptide (ITP). We show that part of the neuropeptide composition within the clock network seems to be conserved among different Drosophila species. However, the PDF expression pattern in certain neurons varied in species deriving from lower latitudes compared to higher latitudes. Together with findings on the behavioral level provided by other people, these data suggest that different species may have altered certain properties of their clocks - like the neuropeptide expression in certain neurons - in order to adapt their behavior to different habitats. We then investigated locomotor rhythms in Drosophila melanogaster flies, in which neuropeptide circuits were genetically manipulated either by cell ablation or RNA interference (RNAi). We found that none of the investigated neuropeptides seems to be of equal importance for circadian locomotor rhythms as PDF. PDF had been previously shown to be necessary for rhythm maintenance in constant darkness (DD) as well as for the generation of morning (M) activity and for the right phasing of the evening (E) activity in entrained conditions. We now demonstrate that NPF and ITP seem to promote E activity in entrained conditions, but are clearly not the only factors doing so. In addition, ITP seems to reduce nighttime activity. Further, ITP and possibly also sNPF constitute weak period shortening components in DD, thereby opposing the effect of PDF. However, neither NPF or ITP, nor sNPF seem to be necessary in the clock neurons for maintaining rhythmicity in DD. It had been previously suggested that PDF is released rhythmically from the dorsal projection terminals. Now we discovered a rhythm in ITP immunostaining in the dorsal projection terminals of the ITP+ clock neurons in LD, suggesting a rhythm in peptide release also in the case of ITP. Rhythmic release of both ITP and PDF seems to be important to maintain rhythmic behavior in DD, since constantly high levels of PDF and ITP in the dorsal protocerebrum lead to behavioral arrhythmicity. Applying live-imaging techniques we further demonstrate that sNPF acts in an inhibitory way on few clock neurons, including some that are also activated by PDF, suggesting that it acts as signaling molecule within the clock network and has opposing effects to PDF. NPF did only evoke very little inhibitory responses in very few clock neurons, suggesting that it might rather be used as a clock output factor. We were not able to apply the same live-imaging approach for the investigation of the clock neuron responsiveness to ITP, but overexpression of ITP with various driver lines showed that the peptide most likely acts mainly in clock output pathways rather than inter-clock neuron communication. Taking together, I conclude that all investigated peptides contribute to the control of locomotor rhythms in the fruitfly Drosophila melanogaster. However, this control is in most aspects dominated by the actions of PDF and rather only fine-tuned or complemented by the other peptides. I assume that there is a high complexity in spatial and temporal action of the different neuropeptides in order to ensure correct signal processing within the clock network as well as clock output.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Blaettner2016,
  author    = {Bl{\"a}ttner, Sebastian},
  title     = {The role of the non-ribosomal peptide synthetase AusAB and its product phevalin in intracellular virulence of Staphylococcus aureus},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146662},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Staphylococcus aureus is a prevalent commensal bacterium which represents one of the leading causes in health care-associated bacterial infections worldwide and can cause a variety of different diseases ranging from simple abscesses to severe and life threatening infections including pneumonia, osteomyelitis and sepsis. In recent times multi-resistant strains have emerged, causing severe problems in nosocomial as well as community-acquired (CA) infection settings, especially in the United States (USA). Therefore S. aureus has been termed as a superbug by the WHO, underlining the severe health risk originating from it. Today, infections in the USA are dominated by S. aureus genotypes which are classified as USA300 and USA400, respectively. Strains of genotype USA300 are responsible for about 70\% of the CA infections. The molecular mechanisms which render S. aureus such an effective pathogen are still not understood in its entirety. For decades S. aureus was thought to be a strictly extracellular pathogen relying on pore-forming toxins like α-hemolysin to damage human cells and tissue. Only recently it has been shown that S. aureus can enter non-professional phagocytes, using adhesins like the fibronectin-binding proteins which mediate an endocytotic uptake into the host cells. The bacteria are consequently localized to endosomes, where the degradation of enclosed bacterial cells through phagosome maturation would eventually occur. S. aureus can avoid degradation, and translocate to the cellular cytoplasm, where it can replicate. The ability to cause this so-called phagosomal escape has mainly been attributed to a family of amphiphilic peptides called phenol soluble modulins (PSMs), but as studies have shown, they are not sufficient. In this work I used a transposon mutant library in combination with automated fluorescence microscopy to screen for genes involved in the phagosomal escape process and intracellular survival of S. aureus. I thereby identified a number of genes, including a non-ribosomal peptide synthetase (NRPS). The NRPS, encoded by the genes ausA and ausB, produces two types of small peptides, phevalin and tyrvalin. Mutations in the ausAB genes lead to a drastic decrease in phagosomal escape rates in epithelial cells, which were readily restored by genetic complementation in trans as well as by supplementation of synthetic phevalin. In leukocytes, phevalin interferes with calcium fluxes and activation of neutrophils and promotes cytotoxicity of intracellular bacteria in both, macrophages and neutrophils. Further ausAB is involved in survival and virulence of the bacterium during mouse lung pneumoniae. The here presented data demonstrates the contribution of the bacterial cyclic dipeptide phevalin to S. aureus virulence and suggests, that phevalin directly acts on a host cell target to promote cytotoxicity of intracellular bacteria.},
  subject      = {Staphylococcus aureus},
  language  = {en}
}
@phdthesis{Chan2002,
  author    = {Chan, Gordon},
  title     = {The Role of Vav-1, Vav-2 and Lsc in NK T cell development and NK cell cytotoxicity},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3645},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {The hematopoietic-specific Rho-family GTP exchange factor (GEF) Vav-1 is a regulator of lymphocyte antigen receptor signaling and mediates normal maturation and activation of B and T cells. Recent findings suggest that Vav-1 also forms part of signaling pathways required for natural and antibody dependent cellular cytotoxicity (ADCC) of human NK cells. In this study, I show that Vav-1 is also expressed in murine NK cells. Vav-1-/- mice had normal numbers of splenic NK cells, and these displayed a similar expression profile of NK cell receptors as cells from wild type mice. Unexpectedly, IL-2-activated Vav-1-/- NK cells retained normal ADCC. Fc-receptor mediated activation of ERK, JNK, and p38 was also normal. In contrast, Vav-1-/- NK cells exhibited reduced natural cytotoxicity against EL4, C4.4.25, RMA and RMA/S. Together, these results demonstrate that Vav-1 is dispensable for mainstream NK cell development, but is required for NK cell natural cytotoxicity. Vav-2, a protein homologous to Vav-1 has also been implicated in NK cell functions. However, NK cells from Vav-2-/- mice have normal cytotoxic activities and NK cells that lack both Vav-1 and Vav-2 exhibit similar defect as Vav-1-/- cells. Thus Vav-2 has no apparent function in the development and the activation of NK cells. Although NK cell development is normal in Vav-1-/- mice, their numbers of NKT cells were dramatically diminished. Furthermore, NKT cells from Vav-1 mutant mice failed to produce IL-4 and IFNg following in vivo CD3 stimulation. A similar loss of NKT cells was observed in Vav-1-/-Vav-2-/- mice, but not in Vav-2-/- mice, suggesting that only Vav-1, and not Vav-2, is an essential regulator of NKT cell development and NK cell cytotoxicity. Similar to Vav-1, Lsc is a Rho GEF that is expressed specifically in the hematopoietic system. It contains a regulator of G-protein signaling (RGS) domain which negatively regulates the Ga12 and Ga13 subunits of G-protein coupled receptors (GPCRs). This study shows that NK and NKT cell development are normal in Lsc-/- mice. However, NK cells from mutant mice display enhanced cytotoxic responses towards a panel of tumor cells. These data implicate for the first time a RGS-containing Rho GEF in cytotoxic responses and suggest that Lsc down-modulate NK cell activation.},
  subject      = {Maus},
  language  = {en}
}
@phdthesis{Schindelin2005,
  author    = {Schindelin, Johannes},
  title     = {The standard brain of Drosophila melanogaster and its automatic segmentation},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-15518},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2005},
  abstract  = {In this thesis, I introduce the Virtual Brain Protocol, which facilitates applications of the Standard Brain of Drosophila melanogaster. By providing reliable and extensible tools for the handling of neuroanatomical data, this protocol simplifies and organizes the recurring tasks involved in these applications. It is demonstrated that this protocol can also be used to generate average brains, i.e. to combine recordings of several brains with the same features such that the common features are emphasized. One of the most important steps of the Virtual Insect Protocol is the aligning of newly recorded data sets with the Standard Brain. After presenting methods commonly applied in a biological or medical context to align two different recordings, it is evaluated to what extent this alignment can be automated. To that end, existing Image Processing techniques are assessed. I demonstrate that these techniques do not satisfy the requirements needed to guarantee sensible alignments between two brains. Then, I analyze what needs to be taken into account in order to formulate an algorithm which satisfies the needs of the protocol. In the last chapter, I derive such an algorithm using methods from Information Theory, which bases the technique on a solid mathematical foundation. I show how Bayesian Inference can be applied to enhance the results further. It is demonstrated that this approach yields good results on very noisy images, detecting apparent boundaries between structures. The same approach can be extended to take additional knowledge into account, e.g. the relative position of the anatomical structures and their shape. It is shown how this extension can be utilized to segment a newly recorded brain automatically.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Hein2004,
  author    = {Hein, Silke},
  title     = {The survival of grasshoppers and bush crickets in habitats variable in space and time},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-9140},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2004},
  abstract  = {Die zunehmende Nutzung von Landschaften f{\"u}hrt zu einer steigenden Fragmentierung sch{\"u}tzenswerter Fl{\"a}chen. Damit verbunden ist eine Zerschneidung von großen Populationen in Metapopulationen. In solchen F{\"a}llen bestimmt das Gleichgewicht zwischen Aussterben und Besiedlung von Habitaten die regionale {\"U}berlebenswahrscheinlichkeit von Arten. Um diese bestimmen, braucht man ein gutes Verst{\"a}ndnis der Habitatanspr{\"u}che der Arten, sowie Informationen {\"u}ber ihr Ausbreitungsverhalten. Ziel dieser Arbeit war es, geeignete Fl{\"a}chen f{\"u}r Heuschrecken in einer Landschaft identifizieren zu k{\"o}nnen, sowie einen Beitrag zur Quantifizierung der Erreichbarkeit einzelner Fl{\"a}chen durch Individuen zu leisten. Der erste Teil dieser Arbeit besch{\"a}ftigt sich mit der Quantifizierung der Habitateignung von Fl{\"a}chen f{\"u}r Heuschrecken. Dazu habe ich statistische Habitateignungsmodelle mittels logistischer Regression erstellt, evaluiert und validiert. Es zeigte sich, dass die Habitatwahl der Heuschrecken auf einer mittleren r{\"a}umlichen Skalenebene erfolgt. Dies steht mit der beobachteten Ausbreitungsdistanz der Tiere im Einklang. Neben dem nur grob klassifizierten Landschaftsfaktor „Biotoptyp" korrelieren vor allem strukturelle Faktoren sowie abiotische Faktoren mit dem Vorkommen der Heuschreckenarten. Bei der Bestimmung eines gemeinsamen Models f{\"u}r alle drei Heuschreckenarten erwies sich das Model der Art S. lineatus mit den Parametern Biotoptyp und Vegetationsh{\"o}he als am besten geeignet zur Vorhersage der Vorkommen der anderen Heuschreckenarten. Um zu testen, ob auch die Vorkommen von Arten unterschiedlicher Tiergruppen mittels eines gemeinsamen Modells vorhergesagt werden k{\"o}nnen, habe ich sowohl die Heuschreckenmodelle zur Prognose von Faltervorkommen getestet, als auch Modelle f{\"u}r Falter auf Heuschrecken {\"u}bertragen. Dabei erwiesen sich die Heuschreckenmodelle zur Prognose der anderen Arten weniger geeignet als das Modell f{\"u}r das Widderchen Z. carniolica in das der Anteil an geeignetem Habitat sowie die Vorkommen der beiden Saugpflanzen C. jacea und S. columbaria einfließen. Diese Art wird als standorttreu eingestuft und repr{\"a}sentiert damit auch die anderen Arten, die typisch f{\"u}r S{\"a}ume und Halbtrockenrasen sind. Die erh{\"o}hte Mobilit{\"a}t von Z. carniolica im Vergleich zu den Heuschrecken garantiert gleichzeitig auch die Erreichbarkeit aller geeigneten Fl{\"a}chen im Gebiet und damit ein Modell, das nur unwesentlich durch Zufallseffekte bei der Besiedlung beeinflusst wird. Neben der Habitatqualit{\"a}t/-quantit{\"a}t spielt vor allem der Austausch zwischen Fl{\"a}chen eine entscheidende Rolle f{\"u}r das {\"U}berleben der Metapopulation. Im zweiten Teil meiner Arbeit habe ich mich sowohl theoretisch als auch empirisch, mit dem Ausbreitungsverhalten von Heuschrecken besch{\"a}ftigt. In Freilandexperimenten konnte ich zeigen, dass die Annahme eines dichotomen Bewegungsverhaltens f{\"u}r Heuschrecken in einer realen Landschaft nicht zutrifft. Vielmehr wird die Bewegung in einer Fl{\"a}che besser als Kontinuum beschrieben das durch strukturelle Resistenz, Temperatur, Mortalit{\"a}tsrisiko und Ressourcenverf{\"u}gbarkeit bestimmt wird. Die jeweilige Kombination dieser Parameter veranlasst die Tiere dann zu einem entsprechenden Bewegungsmuster, das sich zwischen den beiden Extremen gerichteter und zuf{\"a}lliger Lauf bewegt. In Experimenten zum Grenzverhalten von Heuschrecken best{\"a}tigte sich dieses Ergebnis. F{\"u}r verschiedene Grenzstrukturen konnte ich unterschiedliche {\"U}bertrittswahrscheinlichkeiten nachweisen. Weiterhin konnte ich feststellen, dass Heuschrecken geeignete Habitate aus einer gewissen Entfernung detektieren k{\"o}nnen. Da das Ausbreitungsverhalten von Tieren in theoretischen Modellen eine wichtige Rolle spielt, k{\"o}nnen diese empirischen Daten zur Parametrisierung dieser Modelle verwendet werden. Zus{\"a}tzlich zum Einfluss des Laufmusters der Tiere auf die Erreichbarkeit geeigneter Habitate, zeigte sich in den von mir durchgef{\"u}hrten Simulationsstudien deutlich, dass der landschaftliche Kontext, in dem die Ausbreitung stattfindet, die Erreichbarkeit einzelner Habitate beeinflusst. Dieser Effekt ist zus{\"a}tzlich abh{\"a}ngig von der Mortalit{\"a}tsrate beim Ausbreitungsvorgang. Mit den Ergebnissen aus den Untersuchungen zur Habitateignung lassen sich die f{\"u}r Heuschrecken geeigneten Habitate in einer Landschaft identifizieren. Somit l{\"a}sst sich die potentielle Eignung einer Fl{\"a}che als Habitat, basierend auf Vorhersagen {\"u}ber die {\"A}nderung des Biotoptyps durch ein Managementverfahren, vorhersagen. Diese Information allein reicht aber nicht aus, um die regionale {\"U}berlebenswahrscheinlichkeit einer Art bestimmen zu k{\"o}nnen. Meine Untersuchungen zum Ausbreitungsverhalten zeigen deutlich, dass die Erreichbarkeit geeigneter Fl{\"a}chen von der r{\"a}umlichen Anordnung der Habitate und der Struktur der Fl{\"a}chen, die zwischen Habitaten liegen, abh{\"a}ngt. Zus{\"a}tzlich spielen individuenspezifische Faktoren wie Motivation und physiologische Faktoren eine ausschlaggebende Rolle f{\"u}r die Erreichbarkeit von geeigneten Fl{\"a}chen.},
  subject      = {Naturschutzgebiet Hohe Wann},
  language  = {en}
}
@phdthesis{Pusch2015,
  author    = {Pusch, Tobias},
  title     = {The transcription factor NFATc1 mediates cytotoxic T cell function in vitro and in vivo},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123690},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2015},
  abstract  = {While numerous experiments on NFAT were already performed with CD4+ T cells showing defective cytokine release and a reduced T helper cell development, no detailed studies existed for CD8+ T cells. From this point, we wanted to examine the impact of NFATc1 and c2 on the physiological functions of CD8+ T cells in vitro and in vivo. Therefore, we used a murine infection model with the bacteria Listeria monocytogenes and mice in which NFATc1 was specifically depleted in the T cell compartment. Our first in vitro studies showed a typical NFATc1 and c2 nuclear translocation and changes on mRNA levels upon T cell activation similarly in CD4+ as well as in CD8+ T cells extracted from wild type mice. NFAT nuclear translocation is important for target gene activation and generation of effector functions. Stimulated T cell populations lacking NFATc1 and/or NFATc2 showed a markedly decreased expression of Th1/Tc1 cytokines, as e.g. IL 2 and IFNγ being important for the clearance of intracellular pathogens. From our in vitro model for the generation of allogenically reactive cytotoxic CD8+ T cells, we revealed a decreased killing and lytic granule-release capacity in Nfatc1 inactivated CD8+ T cells whereas NFATc2-/- cytotoxic T cells did not show an altered cytotoxic response compared to wild type cells. Interestingly, we found lytic granules accumulated and mitochondria not getting translocated to the immunological synapse upon re-stimulation in NFATc1-deficient CD8+ T cells. Together with results showing the CsA insensitivity of the CTL killing/degranulation capacities, we assume that some major cellular processes are affected by NFATc1 which are not directly linked to the TCR-induced signal transduction cascade. We also showed the importance of NFATc1 in T cells during intracellular infections with the bacteria Listeria monocytogenes in an in vivo mouse model. After five days, only few bacteria were detected in wt mice whereas high amounts of Listeria particles were extracted from livers of Nfatc1fl/fl x Cd4 cre mice. Although the reactivity towards the pathogen was similar in both groups, a decreased cytokine expression in NFATc1-/- CD8+ T cells was observed together with an altered memory cell generation. Our results show the importance of NFATc1 in CD8+ T cells and give some clue for a possible connection to other basal cellular functions, as e.g. the formation of an immunological synapse.},
  subject      = {Transkriptionsfaktor},
  language  = {en}
}
@phdthesis{Spohn1999,
  author    = {Spohn, Gunther},
  title     = {The transcriptional control of virulence gene expression in Helicobacter pylori},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-2334},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {1999},
  abstract  = {The Gram-negative, spiral-shaped, microaerophilic bacterium Helicobacter pylori is the causative agent of various disorders of the upper gastrointestinal tract, such as chronic superficial gastritis, chronic active gastritis, peptic ulceration and adenocarcinoma. Although many of the bacterial factors associated with disease development have been analysed in some detail in the recent years, very few studies have focused so far on the mechanisms that regulate expression of these factors at the molecular level. In an attempt to obtain an overview of the basic mechanisms of virulence gene expression in H. pylori, three important virulence factors of this pathogen, representative of different pathogenic mechanisms and different phases of the infectious process, are investigated in detail in the present thesis regarding their transcriptional regulation. As an essential factor for the early phase of infection, including the colonisation of the gastric mucosa, the flagella are analysed; the chaperones including the putative adhesion factors GroEL and DnaK are investigated as representatives of the phase of adherence to the gastric epithelium and persistence in the mucus layer; and finally the cytotoxin associated antigen CagA is analysed as representative of the cag pathogenicity island, which is supposed to account for the phenomena of chronic inflammation and tissue damage observed in the later phases of infection. RNA analyses and in vitro transcription demonstrate that a single promoter regulates expression of cagA, while two promoters are responsible for expression of the upstream divergently transcribed cagB gene. All three promoters are shown to be recognised by RNA polymerase containing the vegetative sigma factor sigma 80. Promoter deletion analyses establish that full activation of the cagA promoter requires sequences up to -70 and binding of the C-terminal portion of the alpha subunit of RNA polymerase to an UP-like element located between -40 and -60, while full activation of the major cagB promoter requires sequences upstream of -96 which overlap with the cagA promoter. These data suggest that the promoters of the pathogenicity island represent a class of minimum promoters, that ensure a basic level of transcription, while full activation requires regulatory elements or structural DNA binding proteins that provide a suitable DNA context. Regarding flagellar biosynthesis, a master transcriptional factor is identified that regulates expression of a series of flagellar basal body and hook genes in concert with the alternative sigma factor sigma 54. Evidence is provided that this regulator, designated FlgR (for flagellar regulatory protein), is necessary for motility and transcription of five promoters for seven basal body and hook genes. In addition, FlgR is shown to act as a repressor of transcription of the sigma 28-regulated promoter of the flaA gene, while changes in DNA topology are shown to affect transcription of the sigma 54-regulated flaB promoter. These data indicate that the regulatory network that governs flagellar gene expression in H. pylori shows similarities to the systems of both Salmonella spp. and Caulobacter crescentus. In contrast to the flagellar genes which are regulated by three different sigma factors, the three operons encoding the major chaperones of H. pylori are shown to be transcribed by RNA polymerase containing the vegetative sigma factor sigma 80. Expression of these operons is shown to be regulated negatively by the transcriptional repressor HspR, a homologue of a repressor protein of Streptomyces spp., known to be involved in negative regulation of heat shock genes. In vitro studies with purified recombinant HspR establish that the protein represses transcription by binding to large DNA regions centered around the transcription initiation site in the case of one promoter, and around -85 and -120 in the case of the the other two promoters. In contrast to the situation in Streptomyces, where transcription of HspR-regulated genes is induced in response to heat shock, transcription of the HspR-dependent genes in H. pylori is not inducible with thermal stimuli. Transcription of two of the three chaperone encoding operons is induced by osmotic shock, while transcription of the third operon, although HspR-dependent, is not affected by salt treatment. Taken together, the analyses carried out indicate that H. pylori has reduced its repertoire of specific regulatory proteins to a basic level that may ensure coordinate regulation of those factors that are necessary during the initial phase of infection including the passage through the gastric lumen and the colonisation of the gastric mucosa. The importance of DNA topology and/or context for transcription of many virulence gene promoters may on the other hand indicate, that a sophisticated global regulatory network is present in H. pylori, which influences transcription of specific subsets of virulence genes in response to changes in the microenvironment.},
  subject      = {Helicobacter-pylori-Infektion},
  language  = {en}
}
@phdthesis{Jenett2007,
  author    = {Jenett, Arnim},
  title     = {The Virtual Insect Brain Protocol : development and application of software for the standardization of neuroanatomy},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-22297},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2007},
  abstract  = {Since the fruit fly Drosophila melanogaster entered the laboratories as a model organism, new genetic, physiological, molecular and behavioral techniques for the functional analysis of the brain rapidly accumulated. Nowadays this concerted assault obtains its main thrust form Gal4 expression patterns that can be visualized and provide the means for manipulating -in unrestrained animals- groups of neurons of the brain. To take advantage of these patterns one needs to know their anatomy. This thesis describes the Virtual Insect Brain (VIB) protocol, a software package for the quantitative assessment, comparison, and presentation of neuroanatomical data. It is based on the 3D-reconstruction and visualization software Amira (Mercury Inc.). Its main part is a standardization procedure which aligns individual 3D images (series of virtual sections obtained by confocal microscopy) to a common coordinate system and computes average intensities for each voxel (volume pixel). The VIB protocol facilitates direct comparison of gene expression patterns and describes their interindividual variability. It provides volumetry of brain regions and helps to characterize the phenotypes of brain structure mutants. Using the VIB protocol does not require any programming skills since all operations are carried out at a (near to) self-explanatory graphical user interface. Although the VIB protocol has been developed for the standardization of Drosophila neuroanatomy, the program structure can be used for the standardization of other 3D structures as well. Standardizing brains and gene expression patterns is a new approach to biological shape and its variability. Using the VIB protocol consequently may help to integrate knowledge on the correlation of form and function of the insect brain. The VIB protocol provides a first set of tools supporting this endeavor in Drosophila. The software is freely available at http://www.neurofly.de.},
  subject      = {Taufliege},
  language  = {en}
}
@phdthesis{Willmes2013,
  author    = {Willmes, Christoph},
  title     = {Therapie kutaner Tumoren : Identifizierung molekularer Biomarker der ex vivo Chemosensitivit{\"a}t des malignen Melanoms und Evaluierung der Wirkungsweise von Interferonen und Artemisininen auf das Merkelzellkarzinom},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-83470},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {F{\"u}r Patienten mit malignem Melanom im Stadium der Fernmetastasierung gibt es bis heute lediglich Therapieoptionen mit sehr eingeschr{\"a}nkten Erfolgsaussichten. Diese Tatsache best{\"a}tigt die Notwendigkeit von Biomarkern zur Vorhersage des Erfolgs verschiedener Therapien. Der ATP-basierende ex vivo Chemosensitivit{\"a}tsassay hat sich als erfolgreiche Methode zur individuellen Vorhersage eines Chemotherapieerfolgs herausgestellt. Tats{\"a}chlich zeigte der Assay ein heterogenes Sensitivit{\"a}tsprofil gegen verschiedene Chemotherapeutika und ließ in getesteten Patienten ein ex vivo wirksames Chemotherapieregime identifizieren, das anschließend auch klinische Therapieerfolge bei Verwendung der Therapie mit dem besten individuellen Chemosensitivit{\"a}tsindex(BICSI) zeigte. Um diesen sehr aufwendigen Assay zuk{\"u}nftig zu umgehen, sollten in der vorliegenden Arbeit pr{\"a}diktive molekulare Biomarker der Chemosensitivit{\"a}t identifiziert werden. Hierf{\"u}r wurden im Voraus durch einen Microarray die Kandidaten Secernin 1 (SCRN1), Lysyl oxidaselike 1 (LOXL1), Thymosin beta 4 X-linked (TMSB4X), Vesicle-associated membrane protein 5 (VAMP5) und Serine protease inhibitor B1 (SERPINB1) als differentiell exprimierte Gene in chemosensitivem gegen{\"u}ber chemoresistentem Gewebe identifiziert. Die relative Expression dieser Kandidatengene wurde daraufhin in bis zu 128 verschiedenen Melanomgeweben mit dem Chemosensitivit{\"a}tsindex verschiedener Chemotherapeutika korreliert. Hierbei konnte eine signifikante Korrelation zwischen SerpinB1 mit der Chemosensitivit{\"a}t gegen{\"u}ber der Therapiekombination mit Paclitaxel und Cisplatin auf Gen- aber nicht auf Proteinebene identifiziert werden. Weiterhin konnte eine differentielle Expression ebenfalls in chemosensitiven und -resistenten Melanomzelllinien nachgewiesen werden, die allerdings im Vergleich mit dem analysierten Gewebe in gegens{\"a}tzlicher Richtung verlief. Zusammenfassend l{\"a}sst sich sagen, dass SerpinB1 ein vielversprechender Marker f{\"u}r die Chemosensitivit{\"a}t gegen{\"u}ber Paclitaxel und Cisplatin ist, dessen funktionelle Bedeutung aber unklar bleibt. Das Merkelzellkarzinom (MCC) ist ein seltener und hoch aggressiver Tumor der mit dem Merkelzellpolyomavirus (MCV) in Zusammenhang steht. Da MCC Zelllinien zur Aufrechterhaltung ihrer Viabilit{\"a}t die MCV T-Antigene ben{\"o}tigen, k{\"o}nnte der Einsatz von Interferonen (IFN) ein m{\"o}glicher therapeutischer Ansatz zur Behandlung dieser Krebserkrankung sein. In der vorliegenden Arbeit haben wir daher die Effekte von IFNs auf MCC Zelllinien, mit besonderer Ber{\"u}cksichtigung der MCV+ Linien, untersucht. IFNs vom Typ I (hier Multiferon, ein Mix verschiedener IFN α Subtypen, und IFN β) wirkten stark inhibierend auf die zellul{\"a}re Viabilit{\"a}t. Die Zellzyklusanalyse zeigte eine Erh{\"o}hung des sub-G Anteils der Zellen nach Behandlung mit IFN, was auf Apoptose als ausschlagebenden Grund schließen ließ. Diese Effekte waren f{\"u}r die Behandlung mit IFN β weniger stark ausgepr{\"a}gt. Der inhibitorische Effekt von Typ I IFNs auf MCV+ MCC Zelllinien war assoziiert mit einer verringerten Expression des viralen großen T-Antigens (LTA) und einer Erh{\"o}hung in der Expression von promyelocytic leukemia protein (PML), das daf{\"u}r bekannt ist, die Funktion des LTA st{\"o}rend zu beeinflussen. Zus{\"a}tzlich f{\"u}hrte die intratumorale Anwendung von Multiferon in vivo zu einer Regression im Wachstum von MCV+, aber nicht MCV- MCC Xenotransplantaten. Die Ergebnisse zeigen das Typ I IFNs einen starken antitumoralen Effekt haben, der zum Teil durch die Regulierung des LTA herbeigef{\"u}hrt wird. Neben diesen direkten Effekten der IFNs auf die Zellproliferation induzieren diese auch die Expression von MHC Klasse I Molek{\"u}len in MCC Zelllinien. Die Durchflusszytometrie zeigte eine Induktion der MHC Klasse I Expression in drei MHC I negativen MCC Zelllinien und eine Erh{\"o}hung der Expression, die vor der Behandlung eine geringe Menge an MHC I aufwiesen. Diese Effekte konnten auch in den in vivo Xenotransplantaten beobachtet werden. Die Ergebnisse zeigen, dass die Behandlung mit IFN sowohl direkte als auch indirekte Effekte auf das MCC hat und eine breite Anwendung in Patienten mit MCV+ und MCV- Tumoren finden kann. Neben IFNs sind auch Artemisinin und seine Derivate bekannt f{\"u}r ihre antitumoralen und antiviralen Eigenschaften. Daher haben wir den Effekt des Artemisininderivats Artesunate auf MCV+ und MCV- MCC Zelllinien getestet. Tats{\"a}chlich konnten wir auch hier einen antiproliferativen Effekt des Stoffes nachweisen, der st{\"a}rker auf MCV+ als auf MCV- Zelllinien wirkte und bei ersteren wiederum mit einer reduzierten LTA Expression einherging. Im Vergleich dazu blieben Fibroblasten von der Behandlung unbeeinflusst. Das verringerte Tumorwachstum konnte ebenfalls f{\"u}r in vivo Xenotransplantationsmodelle gezeigt werden. Auf Grundlage dieser Erkenntnis sollte eine genauere Untersuchung dieses alten Naturheilstoffes f{\"u}r die Behandlung von MCC Patienten in Betracht gezogen werden.},
  subject      = {Interferon},
  language  = {de}
}