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Institute
- Abteilung für Mikrobiologie und Molekularbiologie (8)
- Institut für Biochemie (8)
- Institut für Physik (8)
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- Institut für Pharmazie (4)
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung (MNF) (4)
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- Institut für Geographie und Geologie (2)
- Institut für Mathematik und Informatik (2)
- Institut für Mikrobiologie - Abteilung für Genetik & Biochemie (2)
In this thesis, we elaborate upon Bayesian changepoint analysis, whereby our focus is on three big topics: approximate sampling via MCMC, exact inference and uncertainty quantification. Besides, modeling matters are discussed in an ongoing fashion. Our findings are underpinned through several changepoint examples with a focus on a well-log drilling data.
Background: Sedentary behavior (SB) is a modifiable behavior with increasing prevalence worldwide. There is emerging evidence that time spend in SB and the manner in which SB is accumulated over time is associated with cardiovascular and cardiometabolic health. The requirement for SB data to be accurately measured is minimization, or at least accurate quantification of human-related sources of measurement errors such as accelerometer measurement reactivity (AMR). The present thesis was to examine SB and their associations with cardiovascular and cardiometabolic health, and to focus on challenges related to the assessment of SB. The first aim of the thesis was to identify patterns of SB describing how individuals accumulate their time spend in SB day-by-day over one week, and to examine how these patterns are associated with cardiorespiratory fitness as a marker for cardiovascular health (paper 1). The second aim of the thesis was to examine the multiple types of SB, and how this is associated with a clustered cardiometabolic risk score (CMRS; paper 2). The third aim of the thesis was to examine AMR and the reproducibility in SB and physical activity (PA) in two measurement periods, and to quantify AMR as a confounder for the estimation of the reproducibility of SB and PA data (paper 3).
Methods: The three papers were based on data of two different studies. For study 1, 1165 individuals aged 40 to 75 years were recruited in three different settings. Among these, 582 participated in a cardiovascular risk factor screening program including cardiopulmonary exercise testing. For the analyses of paper 1, 170 participants were eligible, agreed to wear an accelerometer, fulfilled the wearing regime, and completed the study period by wearing the accelerometer for seven consecutive days. Patterns in accelerometer data were classified based on time spent in SB per day applying growth mixture modeling. Model‐implied class‐specific peak oxygen uptake (VO2peak) means were compared using adjusted equality test of means (paper 1). The underlying study of paper 2 and 3 were based on data of a pilot study aiming to investigate the feasibility of a brief tailored letter intervention to increase PA and to reduce SB during leisure time. Among the individuals who agreed to be contacted again in study 1, a random sample of those aged between 40 and 65 years was drawn. Of those, 175 attended in a cardiovascular examination program. Assessment included giving blood sample, standardized measurement of blood pressure, waist circumference, body weight, and height at baseline, and after twelve months. Further, they agreed to complete a paper-pencil questionnaire on SB (Last 7-d Sedentary Behavior Questionnaire, SIT-Q-7d) and PA (International Physical Activity Questionnaire, IPAQ), and to receive seven-day accelerometery at baseline, and after 12 months. In addition, self-administered assessments were conducted at months one, three, four, and six after baseline. Only individuals of a random subsample (= intervention group) received up to three letters tailored to their self-reported SB and PA at months one, three, and four. For paper 2, associations between SBs and a clustered cardiometabolic risk score (CMRS) were analyzed using linear as well as quantile regression. To account for missing values at baseline, multiple imputations using chained equations were performed resulting in a total sample of 173 participants. Paper 3 comprised data of 136 individuals who participated at the baseline and twelve months assessments, and fulfilled the wearing regime. AMR was examined using latent growth modeling in each measurement period. Intraclass correlations (ICC) were calculated to examine the reproducibility of SB and PA data using two-level mixed-effects linear regression analyses.
Results: Results of paper 1 revealed four patterns of SB: 'High, stable', 'Low, increase', 'Low, decrease', and 'High, decrease'. Persons in the class 'High, stable' had significantly lower VO2peak values (M = 25.0 mL/kg/min, SD = 0.6) compared to persons in the class 'Low, increase' (M = 30.5 mL/kg/min, SD = 3.6; p = 0.001), in the class 'Low, decrease' (M = 30.1 mL/kg/min, SD = 5.0; p = 0.009), and in the class High, decrease' (M = 29.6 mL/kg/min, SD = 5.9; p = 0.032), respectively. No differences among the other classes were found. In paper 2, results revealed that the only factor positively associated with a CMRS in all regression models was watching television. Depending on the regression analysis approach used, other leisure-time SBs showed inconsistent (using a computer), or no associations (reading and socializing) with a CMRS. In paper 3, results revealed that time spent in SB increased (baseline: b = 2.3 min/d; after 12 months: b = 3.8 min/d), and time spent in light PA decreased (b = 2.0 min/day; b = 3.3 min/d). However, moderate-to-vigorous PA remained unchanged. Accelerometer wear time was reduced (b = 4.6 min/d) only at baseline. The ICC coefficients ranged from 0.42 (95% CI = 0.29 - 0.57) for accelerometer wear time to 0.70 (95% CI = 0.61 - 0.78) for moderate-to-vigorous PA. None of the regression models identified a reactivity indicator as a confounder for the reproducibility of SB and PA data.
Conclusions: The present thesis highlights SB in the field of cardiovascular and cardiometabolic research that have implications for future research. Individuals sit for different purposes and durations in multiple life domains, and the time spent in SB is accumulated in different patterns over time. Therefore, research should consider the fact that SB is embedded in an individual's daily life routine, hence might have differential effects on cardiovascular and cardiometabolic health. Further, methodological aspects have to be considered when dealing with SB. In order to detect how SB is 'independently' associated to an individual's health, an accurate measurement of SB is fundamental. Therefore, human-related sources of bias such as AMR should be taken into account when either planning studies or when interpreting data drawn from analysis of SB data.
For decades, evolutionary biologists have sought to understand the evolution of individual behaviour, physiology and ecology allowing organisms to cope to environmental change. One of the main challenges of current climate change is the unprecedent rate of temperature increase, as well as the increased occurence of extreme heat events. Interindividual response variability opens a whole new area of opportunities to understand how individual phenotypic traits are linked to individual response differences. In colour polymorphic species, colour honestly reflects an individual’s life-history strategy, and each morph may, therefore, represent an alternative life-history strategy. As such, colour polymorphic species, such as the Gouldian finch (Erythrura gouldiae), may be good models to assess how different strategies between morphs are linked to their espective responses to environmental variations. However, polymorphic species have mainly been disregarded for that purpose. In this context, the main aim of this thesis was to understand how the two morphs of the Gouldian finch respond through phenotypic plasticity to simulated heatwaves reaching thermocritical temperatures, and whether such differential responses may help to identify a ‘winner’ and a ‘loser’ morph in the light of climate change. To address these issues, we used an integrative approach including measurements of behavioural (Study 1), physiological (Study 2), and reproductive (Study 3) parameters. The novelty of our approach was to assess the immediate behavioural and physiological response variation of individuals of the two morphs longitudinally across different thermal conditions, as well as the postponed effects of this thermocritical heatwave exposure on their reproductive performance. In this study, although the behavioural responses generally did not differ between morphs or according to temperature intensity, the physiological and reproductive parameters differed in response to morph and temperature intensity. Blackheaded females, in particular, seem highly sensitive to thermocritical heatwaves, as they exhibited decreased body mass and increased oxidative damage during the thermocritical heatwaves, and advanced breeding initiation after these conditions, whereas these variables remained mostly unaffected in black-headed males and red-headed individuals. However, despite some response differences between morphs, both invested similarly in reproduction following intense heatwaves, and the offspring of both morphs were similarly affected. Based on these results, no morph therefore seems to appear more disadvantaged than the other following an intense heatwave, and red- and black-headed Gouldian finches may both be considered as climate stress ‘losers’.
Phylogeny of the Koi herpesvirus and development of a vaccine against the Koi herpesvirus disease
(2019)
The aim of this presented dissertation was a stable, live attenuated and protective KHV usable as vaccine. Moreover this vaccine should by cost effective and easy to apply. Differentiation of infected and vaccinated animals was preferred by genetic and / or serological means. After achieving an attenuated virus, whole genome sequencing should be done to examine the genetic of the vaccine as one feature of biosafety. Besides biosafety additional knowledge on the virulence of Alloherpesviruses, especially of KHV was anticipated. Additionally the diagnostics of KHV and KHVD should be improved to increase reliability and to gain more insights into the relationship of different KHVs and hopefully to detect the source of an outbreak.
The present work focusses on the mosquito populations of two zoological gardens in Germany with the aim to better understand mosquito biology of native species and to contribute to a greater awareness of mosquito and mosquito-borne disease agent surveillance in zoos. For this purpose, data on species composition, blood meal patterns and mosquito-borne pathogens were analysed. The investigated zoological gardens differed not only in their sizes and animal stocks, but also in their surrounding environments. The 160 ha Tierpark Berlin is located in a densely populated urban area, while the 15 ha Zoological Garden Eberswalde is surrounded by forest.
To gain an overview about the mosquito fauna of both zoos, adult specimens were caught by aspirating and EVS-trapping during the 2016 season. In addition, larval stages were collected from their breeding sites located in the zoo areas. In total, 2,257 mosquitoes were sampled, belonging to 20 taxa. Seasonal differences between the zoos were documented, both in terms of species composition and the relative abundance of mosquito species collected. As the studied zoos were located in the same climatic region and both locations provided similar breeding sites, differences in species composition were attributed to the entry of mosquitoes from surrounding landscapes. Influencing factors could have been the different sizes of the zoos and variations in the potential host animal populations.
According to the vector potential of most frequently collected taxa in the Zoological Garden Eberswalde (Annulipes Group, Culiseta annulata), TAHV, USUV, WNV, filariae and avian malaria parasites appear to have the highest risk of being transmitted at this location. In the Tierpark Berlin, Aedes vexans was the most frequently collected mosquito species, suggesting a theoretical risk for the transmission of a broader spectrum of pathogens due to covered vector competences. Pathogens such as BATV, SINV, TAHV, USUV and filarial worms could be of major importance regarding transmission risk to zoo animals, as they had previously been found to circulate Germany. In addition, avian malaria parasites represent a considerable risk for susceptible exotic bird species in Berlin.
Since the blood-feeding behaviour of vector-competent mosquito species has a major influence on the transmission of a mosquito-associated pathogen, the analysis of blood meal patterns is crucial to better understand vector-pathogen cycles. Therefore, blood meals of blood-fed mosquitoes caught in 2016 and 2017 by aspirating and EVS-trapping in the Tierpark Berlin and the Zoological Garden Eberswalde were analysed. The aim was to investigate to what extent native mosquito species accept exotic zoo animals, wild native animals and humans as blood hosts. In addition, it was examined whether the collected species are generalists or specialists when selecting vertebrates for blood feeding.
A total of 405 blood-fed mosquitoes from 16 taxa were collected. The genetic analysis of blood meals identified 56 host species, which – in addition to humans – mainly originated from mammals of the zoo animal populations. In agreement with the previous study on the mosquito fauna of the Tierpark Berlin and the Zoological Garden Eberswalde, the analysis of blood meals also showed differences between the two zoos. In the smaller Zoological Garden Eberswalde, a higher number of blood-fed mosquitoes was collected than in the Tierpark Berlin, probably caused by a higher host density in Eberswalde, which may have led to an overall higher mosquito density. However, no differences between both zoos were observed with respect to the blood feeding behaviour of the analysed mosquito species: Mosquitoes of both locations were rather generalistic, although species could be grouped according their blood meals into 'amphibian', 'non-human mammal' and, ‘non-human mammal and human' feeding species. The more random selection of hosts could indicate a low probability of effective pathogen transmission by applying the 'dilution effect'. Notwithstanding, since wild animals have also been accepted as hosts, pathogen transmission by bridge vectors from one vertebrate group to another could be relevant in the sampled zoos.
Adult mosquito specimens collected in 2016 and 2017 were screened for filarial nematodes, avian Haemosporidia and mosquito-borne viruses. Dirofilaria repens was detected in a mosquito from the Zoological Garden Eberswalde. Mosquitoes from Berlin and Eberswalde were tested positive for the nematode species S. tundra. Sindbis virus was found in a mosquito pool collected in the Tierpark Berlin, while no mosquito-associated viruses were detected in specimens collected in the Zoological Garden Eberswalde. Mosquitoes from both zoos were positive for the haemosporidian parasites Haemoproteus sp. and Leucocytozoon sp., and one documentation was made for avian Plasmodium sp. in the Tierpark Berlin.
The identified pathogens have the potential to cause disease in captive and wild animals, and some of them also in humans. Most of the mosquitoes tested positive had been collected in July, suggesting a high infection risk during this month. Since most pathogen detections were made from species belonging to the Cx. pipiens complex, species of this complex seem to be most relevant in the studied zoos when it comes to mosquito-borne pathogen transmission. Although mosquitoes are no proven vectors of most of the avian malaria parasite genera found, evidence for Haemoproteus sp. and Leucozytozoon sp. demonstrated a high prevalence of avian malaria parasites in the zoos.
In summary, the results of the three studies indicate regional differences both in the mosquito species composition and in the occurrence of mosquito-borne pathogens. However, no differences were found between the mosquito communities of both zoos concerning their blood feeding behaviour, suggesting that the general behaviour of the insects is location-independent.
Several potential disease agents were found in the collected mosquitoes, although not at high abundances. Whether these pathogens were found by chance in the two zoos or whether the particular zoo environment is a hot spot of arthropod-borne pathogens cannot be determined with the studies conducted. Nonetheless, it seems clear that zoological gardens are attractive to mosquito females not only in their search for breeding sites, but also when looking for blood hosts and places for mating or resting. These advantageous conditions also attract mosquito species that have their larval habitats outside the zoological gardens, which is why elimination of breeding sites on the zoo premises alone will not necessarily keep away all mosquitoes.
A closer collaboration between zoological gardens and entomologists could be beneficial for both. Zoo officials could benefit from being able to identify potential arthropod vectors on the zoo grounds and receiving information on circulating arthropod-borne disease agents, as well as on the animal species susceptible to those. For entomologists, zoological gardens are ideal research locations, as they provide an environment with a high diversity of habitats and potential blood hosts for haematophagous arthropods in a confined space.
Studying mosquito biology will become even more significant in the future, since in a world that is getting smaller, both potential vectors and pathogens are regularly introduced into areas where they did not occur before. Therefore, it would be desirable if more studies targeting ecological as well as infectiological aspects of vector species in zoological gardens in Germany were carried out.
In times of recent climate change, mechanisms to deal with different environments (e.g. via dispersal to other habitats, or via in-situ responses such as genetic adaptation or phenotypic plasticity) are essential. In regions showing seasonality, organisms are already adapted to regular and, thus, often predictable environmental changes. One well-known strategy to survive periods of food shortage, especially during the winter, is hibernation. Although hibernation is already an adaptation to overcome unfavourable conditions, the optimal timing of hibernation to match for example food abundance peaks is likely to be influenced by changing climatic conditions, as expected during human-induced global change. Thus, the ability to respond to changes in optimal timing of hibernation can be crucial for organisms. All hibernators are positioned at the slow end of the slow-fast life history continuum. Longevity combined with a low annual reproductive output can result in slow recovery from population crashes and is expected to be associated with slow genetic adaptation. Therefore, it is assumed that phenotypic plasticity, a rather rapid and sometimes reversible process, is a crucial mechanism in long-lived organisms to adapt to changing environments. However, how differences in individual hibernation behaviour influence mortality and whether individuals are plastic with respect to their hibernation behaviour are largely unknown.
Recent studies suggest that climatic change can influence hibernation behaviour in various species differently, in a positive or negative way. Female Columbian ground squirrels (Urocitellus columbianus) delayed their emergence from hibernation with later snow melt and lower spring temperatures. Next to the environmental impact, emergence date showed a moderate heritability in female Columbian ground squirrels. Yellow-bellied marmots (Marmota flaviventris) emerged earlier from hibernation with warmer spring temperatures which resulted in a longer growing period for their offspring and, therefore, higher survival rates. In contrast, in alpine marmots (Marmota marmota) lower snow cover due to higher temperatures and, thus, less isolation led to lower juvenile survival. Negative effects, such as reduced juvenile survival, would be of high concern, especially for long-lived species with a low reproductive output.
Bats are exceptionally long-lived compared to other mammals of the same size and often show a low reproductive output with one offspring per year. This is especially true in the temperate zone where bats, furthermore, are characterized by seasonality and depend on hibernation during winter period to survive food and water shortage. Because bats are of high conservation concern it is of prime importance to understand their ability to respond to different climatic conditions and associated mortality costs.
The basis of this study was a five-year data set of 1047 RFID-tagged individuals from two bat species, Natterer’s bats (Myotis nattereri) and Daubenton’s bats (Myotis daubentonii), that were automatically tracked when entering or leaving the joint hibernaculum, “Brunnen Meyer”, located in north-western Germany. The two species are similar sized, share demographical traits and often occupy the same areas. Nevertheless, they differ in their foraging strategy and activity pattern during hibernation period. Natterer’s bats are able to glean insects from surfaces, even at low temperatures. Daubenton’s bats depend on flying arthropods and, thus, warmer temperatures. And indeed there is evidence that Natterer’s bats are able to hunt during hibernation period, while in Daubenton’s bats a lack of feeding during the hibernation period is suggested. Furthermore, Natterer’s bats are characterized by a higher activity at the hibernaculum throughout the hibernation period, while Daubenton’s bats on average arrive earlier, stay inactive through the winter and leave later in spring.
In both species, the aim was to investigate the impact of their individual hibernation behaviour, precisely the timing of departure in late winter and early spring, on mortality, their adjustment of departure timing to the North Atlantic Oscillation Index (NAO), as well as differences within and between the two species from 2011 until 2015.
To later on estimate the potential mortality costs of departure timing, gaining knowledge about the seasonal survival pattern (winter vs. summer) in the two species was a first necessity. In birds, particularly small species were described as winter-regulated populations with a higher mortality during winter. In contrast, in hibernating mammal species, such as bats, a relatively lower or similar winter survival compared to summer survival was shown. In this study, the analysed data demonstrated that the winter 2010/2011 was exceptionally catastrophic in Natterer’s bats and did not impact Daubenton’s bats. When excluding this catastrophic winter in Natterer’ bats, our results revealed a stable winter-summer-survival difference (higher winter and lower summer survival) in adult Natterer’s and Daubenton’s bats, with inter-annual variation in the level of survival which indicates a potential environmental impact on survival. This winter-summer survival pattern is in line with the survival pattern shown for other hibernators. Juveniles always had a lower survival rate than adult bats in both species. Nevertheless, the extent to which the species differ between seasons and age classes was stronger in Daubenton’s bats. They always showed a slightly higher winter survival and a lower summer survival than Natterer’s bats. Together with the catastrophic winter 2010/2011 in Natterer’s bats, this indicates a species-specific sensitivity to the timing of specific weather events which is in line with their foraging strategies and activity pattern during hibernation period.
With respect to emergence behaviour from the hibernaculum, the results of this study suggest considerable differences among individuals within as well as between bat species. In comparison to Daubenton’s bats, Natterer’s bats tuned their emergence more closely to weather conditions, specifically the NAO, a large scale weather index related to winter severity, and showed individual variation in behavioural plasticity. In Daubenton’s bats only the females responded to changing conditions and left earlier in individually-experienced warmer and milder winters, comparable to Natterer’s bats females. A potential reason might be reproductive advantages for the females resulting in a longer growing period for their offspring. The shown higher winter survival in adult bats of both species indicated already higher energy expenditure outside the hibernaculum. Thus, leaving early, being active and staying outside longer by itself bore a risk (exposure risk effect). Under consideration of longer exposure times, early departing individuals had on top of that an increased risk to die. This was not given in each year, but a species- and year-specific pattern was revealed. Natterer’s bats were only significantly affected by early departure in 2011, while the remaining years show no significant additional risk of leaving early. In Daubenton’s bats, the years 2014 and 2015 were associated with a significantly higher mortality of leaving early. This is in line with the hypothesis that Daubenton’s bats might not be able to hunt for insects leaving too early and do so as a best out of a bad job. Nevertheless, the year-specific pattern suggests that early bats might profit from advantageous weather conditions during early spring.
An additional hint for an environmental impact on early bat survival in at least Daubenton’s bats is that the median proportion of night hours above 3 °C within five days after departure was included in the model with the lowest AIC. However, the effect was not strong enough to be selected as the best model and, therefore, further analyses are needed to investigate this first hint.
In conclusion, the reduced winter survival of juveniles compared to adults highlights the importance of considering age class effects in studies that investigate seasonal survival patterns. The stable species-specific winter-summer-survival difference with a higher winter survival compared to summer survival, as well as the one catastrophic winter in Natterer’s bats underline the importance of including seasonal survival patterns in assessing potential fitness costs of changed behaviour. Furthermore, our results suggest that long-lived hibernating bat species have the potential to plastically adjust to changing climatic conditions, but this potential differs between species. Among-individual differences in emergence together with species-specific mortality costs of early emergence suggest the potential for natural selection to shape hibernation phenology. In summary, our findings suggest species-, population- and group-specific differences in the ability to respond to changing environments and, therefore, underline the necessity to further investigate local responses in various organisms to estimate consequences of recent climate change on a wider range.
Climate change threatens marine ecosystems by simultaneous alterations and fluctuations in several abiotic factors like temperature, salinity and pH. Therefore, a strong ability to cope with varying environmental factors is indispensable for marine organisms. Especially, larvae of meroplanktonic species will be affected by predicted alterations in environmental conditions as planktonic larval stages are considered the most sensitive stages during life history (Anger 2001).
The European shore crab Carcinus maenas, as an ecological key species, was chosen as a model species to investigate multiple stressor effects on early life history stages of marine meroplanktonic invertebrates. The life cycle of C. maenas is biphasic consisting of five pelagic larval stages (four zoeal and one megalopal stage), followed by benthic juvenile and adult phases. The metamorphic molt from the last zoeal stage to the semi-benthic Megalopa includes dramatic changes in ecology, habitat, behavior, feeding, morphology, and physiology. During life history, zoeal stages of C. maenas are of particular interest in the course of climate change as these stages are more vulnerable than the following developmental stages to alterations in abiotic factors.
The aim of the present thesis was to develop an integrative view on effects of long-term exposure, from hatching to metamorphosis, to increased temperature and hypo-osmotic conditions on early life history stages of C. maenas. We wanted to gain insights into larval responses to climate driven environmental variables, more specifically, on how tolerance to low salinity is affected by increased temperatures.
Consequently, the present study investigated the effect of long-term exposure to twelve different sub-lethal temperature and salinity combinations in an ecological relevant range on larval development of C. maenas. In a multidisciplinary approach, larval responses in performance (survival and developmental duration) and morphology were measured. Furthermore, analysis on larval ontogeny and organogenesis created the foundation for analysis of larval response to multiple stressors in anatomy.
Results of the present thesis demonstrated that despite their different life-styles and external morphology, brachyuran larvae are smaller versions of their adults when regarding their inner organization: the adult bauplan unfolds from organ anlagen compressed into miniature organisms. In addition, they provide an overall picture of seemingly gradual organogenesis across larval development and the metamorphic molt, an insight that contrasts with the abrupt external morphological changes during metamorphosis. Gradual anatomical changes in e.g. osmoregulatory structures like gills and antennal glands allowed for ontogenetic shifts of tolerance to temperature and salinity during zoeal development and successive increase in osmo- and thermoregulatory capability. On the other hand, osmoregulatory structures as seen for adults were underdeveloped during zoeal development and therefore do not qualify for osmoregulatory function for these stages. This potentially explains the higher sensitivity of zoeae to hypo-osmotic conditions.
Early life history stages of C. maenas were affected on all response levels by the tested multiple stressors. The interaction of temperature and salinity was of antagonistic type, resulting in general reduced stress for larval stages. Nevertheless, low salinity had a strong negative impact on survival, while increased temperature caused ann acceleration of development. Furthermore, the size of zoeae of C. maenas was driven by the interaction of temperature and salinity, with extreme conditions, causing diminished growth, thus resulting in smaller larval size. On the other hand, larval shape was only slightly affected by changes of abiotic factors. Volume of the digestive gland and the heart of larvae from long-term exposure to sub-lethal temperatures and salinities showed high variability.
Larval responses were affected by the stressors intensities: moderately high temperatures lessened the negative effects of low salinities, while extreme high temperatures exceeded the ameliorating effect of temperature on stressful salinity conditions. On the other hand, the tolerance to temperature and salinity increased during larval development indicating an ontogenetic shift in response to multiple stressors with development. In addition, performance, morphology, and multiple stressor interaction showed intrapopulation variability among larvae hatched from different females, and between experimental periods.
In conclusion, this study highlighted direct effects of abiotic factors on all investigated response levels in early life history stages of the meroplanktonic larvae of the invertebrate C. maenas. High mortality rates combined with higher sensitivity confirm that planktonic early life history stages are the bottleneck during life history of this species. Nevertheless, early life history stages of C. maenas had the ability to cope with wide ranges of changing environmental factors. The antagonism between temperature and salinity on larval development offers potential for early life history stages to persist in a changing world. Furthermore, anatomical structures allow for slight eurytolerance and potentially for compensation of abiotic stress. Overall, slight increases in temperature, driven by climate change may enable larvae of C. maenas to tolerate exposure to moderately low salinities and, combinedwith intrapopulation variability, potentially allows for population persistence. Summarized, this study emphasizes the importance of testing a wide range of ecologically relevant traits in developing pelagic larvae in order to properly characterize their response to environmental change.
Changes in abundance and phenology of planktonic larvae like the zoeae of C. maenas have major potential to change a species‘ population structure significantly, and furthermore indirectly affect whole community and ecosystem structures. Therefore, this thesis may serve as a bridge to future studies in evolutionary and ecological developmental biology.
Species persistence in the face of rapidly progressing environmental change requires adaptive responses that allow organisms to either cope with the novel conditions in their habitat or to follow their environmental niche in space. A poleward range shift due to global warming induced habitat loss in the south has been predicted for the lesser horseshoe bat, Rhinolophus hipposideros. Theoretical as well as numerous empirical studies link range expansion success to increased dispersal and reproduction rates due to spatial sorting and r-selection resulting from low population densities at the expansion front. R. hipposideros females however are highly philopatric and the species’ life history reflects a K- rather than an r-strategy, encompassing a long life span and limited individual annual reproductive output. I therefore investigated if adaptations in these traits determining range expansion success (dispersal and reproduction) can be observed in this bat species of high conservation concern. Genetic diversity presents a critical factor for adaptive responses to global change, both for range expansion and for coping with novel environmental conditions. I hence explored the genetic diversity levels of European R. hipposideros leading edge populations and their drivers for an assessment of these populations’ evolutionary potential and the development of conservation recommendations.
Comparing range expansion traits between an expanding R. hipposideros metapopulation in Germany and a non-expanding one in France revealed that range expansion was associated with an increase in juvenile survival and fecundity, and no decrease in adult survival. These results demonstrate than an increase in reproduction and growth rates is generally possible in R. hipposideros, indicating a potential adaptation (sensu lato) to range expansion. A positive correlation between adult and juvenile survival in the expanding metapopulation suggests higher resource acquisition in the expanding metapopulation, giving rise to the question if the observed demographic changes have a genetic basis or if they are rather induced by differences in environmental conditions between the two metapopulations. Long-term range expansion success requires adaptive evolutionary changes. The relative contribution of the former and that of undirected changes resulting e.g. from differences in resource availability therefore will have to be investigated in more detail in the future to allow predictions about range expansion dynamics in R. hipposideros.
The number of individuals within a radius of approximately 60 to 90 km around a population (as a measure of connectivity) was identified as the main positive driver of the studied populations’ genetic diversity. Overall genetic diversity levels in German R. hipposideros populations were found to be reduced compared to populations in France as a legacy of demographic bottlenecks resulting from severe population declines in the mid-20th century. This finding is alarming as future range expansion can be expected to entail a further decrease in genetic diversity. The resulting loss of genetic diversity can be expected to be particularly strong in R. hipposideros due to the detected dependence of genetic diversity on connectivity, because range expansion often results in small and patchy populations.
Protecting and ideally re-installing genetic diversity in R. hipposideros leading edge populations therefore presents a conservation goal of utmost importance. To achieve this endeavour, conservation efforts should target the protection of extensive networks of well-connected populations. Geographical concentration of individuals should be avoided and populations in key locations that connect clusters must be protected particularly well to prevent populations from becoming isolated. Continuous, regular monitoring of population trends is also important for a quick registration of disturbances or threats, and the subsequent rapid development of countermeasures to preclude further demographic declines.
The reduced levels of genetic diversity in the German metapopulation precluded a reliable quantification of dispersal rates due to the reduced power of discrimination between individuals. While ongoing re-colonization and the establishment of new maternity colonies provide evidence for increased dispersal in the expanding metapopulation, evaluating the expected range expansion velocity of R. hipposideros in relation to the estimated velocity of global warming induced habitat loss will require the confirmation of the existing preliminary dispersal data by employing more genetic markers.
Profiling the activity and hepatotoxicity of flupirtine through medicinal chemistry approaches
(2019)
Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterodimer, voltage‐gated potassium channels 2 and 3 (KV2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug‐like leads. In the present retro metabolic drug design study, a series of 44 compounds were
synthesized and characterized with regards to KV7.2/3 opening activity and efficacy. The most active compounds displays excellent potency (EC50 = 4 nM) and efficacy (154%) as an Kv7.2/3 opener. Limited aqeous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell ilnes (HEP‐G2 and TAMH) in culture.
The southern Baltic Sea embodies an incomparable geological archive of the tectonic evolution of the 450 Ma old Trans‐European Suture Zone (TESZ). This WNW to NW trending suture formed during the collision of Baltica and Avalonia and has accommodated the repeatedly changing stress regimes since then, as evidenced by numerous fault zones and systems. The German offshore part in the vicinity of Rügen Island is strongly block‐faulted, with each block showing a specific geological pattern, enabling the reconstruction of the structural evolution of the area.
The work of this thesis is part of the USO working group of the University of Greifswald and the Geological Survey of Mecklenburg‐Western Pomerania, which aims to build a unified three‐dimensional tectonic model of the southern Baltic Sea area. This thesis presents the results of new structural investigations of the Arkona, Wolin and Gryfice blocks north and east of Rügen. Especially, conflicting structural analyses in the previous work are united into a consistent model.
The integrated interpretation of 144 reprocessed seismic vintage lines (original Petrobaltic data) and 23 high resolution academic seismic sections (from the Universities of Hamburg and Bremen), with additional consideration of on‐ and offshore wells, revealed 19 seismostratigraphic horizons that subdivide the succession between the Proterozoic basement and the Upper Cretaceous. Up to 100 faults of superior fault zones and systems control the tectonic situation. Besides NW trending deep faults formed during the Palaeozoic, for instance the Wiek and Nord Jasmund faults, and NNW trending Mesozoic faults and flexures that belong to the Western Pomeranian Fault System, other major faults such as the Adler‐Kamień Fault Zone document the polyphase evolution of this area.
The restoration of selected seismic sections support the evaluation of separately generated faults and their reactivation, leading to a subdivision of the tectonic evolution of the area into six stages:
(1) The Caledonian Orogeny (Ordovician/Silurian) was accompanied by a NE‐SW compression, resulting in the formation of the TESZ and an accretionary wedge within the upper crust. (2) The following S to SW trending extension of the Variscan Foreland (Devonian/Carboniferous) triggered the
evolution of the Middle Devonian Old Red Rügen Basin south of the Wiek Fault. Further WNW to NW trending faults (e.g. Nord Jasmund Fault) subdivided the basin. (3) The advancing Variscan Orogeny (Late Carboniferous) caused an increasing NE‐SW orientated compression and subsequently reactivated faults and tilted blocks (e.g. Lohme Sub‐block). (4) The North German Basin and Mid Polish Trough formed by thermic subsidence in the S to SE of the research area during the Permo‐Carboniferous. Simultaneously, the evolution of the Gryfice Graben as part of the Teisseyre‐Tornquist Zone commenced. (5) Due to the Arctic‐North Atlantic Rifting an E‐W trending extension increased. Consequently, grabens such as the Gryfice Graben continued their subsidence. As the stress system rotated counter‐clockwise, the shear strength increased along the NE trending faults. The Western Pomeranian Fault System developed due to intense transtension during the Keuper and Jurassic, and is characterised by pull‐apart structures. (6) In the Upper Cretaceous, a NE‐SW compression, forced by the Africa‐Iberia‐Europe convergence, triggered the reactivation of faults and flexures as reverse ones, the inversion of grabens (e.g. Gryfice Graben), and the formation of anticlines, for instance at the Wolin Block.
This thesis combines the calculation of gridded time structure maps and a detailed fault pattern analysis, and represents the base for a velocity‐ and subsequently depth‐based 3D modelling.
Hepeviruses are small viruses with a RNA-genome of positive polarity that form the family Hepeviridae. The family includes two genera: members of the genus Piscihepevirus were detected in fish species and members of the genus Orthohepevirus were found in different mammal and bird species. The genus Orthohepevirus contains four different species, namely Orthohepevirus A, B, C and D. The species Orthohepevirus A contains five human pathogenic genotypes, with three of them being zoonotic. The species Orthohepevirus C contains mammal-associated pathogens, which were identified in rats and carnivores. The human pathogenic genotypes are responsible for a self-limiting acute hepatitis in humans, which could become chronically in immunocompromised individuals. The main route of transmission is the consumption of undercooked meat and direct contact with HEV-positive excreta or blood. In Germany, hepatitis E is a notifiable disease since 2001 with an increased number of cases per year. Rats are the reservoir of rat-associated HEV (ratHEV), but also the zoonotic HEV-3 genotype was detected in rats. The European rabbit (Oryctolagus cuniculus) was identified as a reservoir host of a subgenotype of human pathogenic HEV-3 (HEV-3ra).
For the development of small mammal animal models, the objective of this study was to evaluate different small mammal populations for novel hepeviruses and to study the presence of HEV and sequence divergence of ratHEV and rabbitHEV in rat and rabbit populations from Europe.
Approximately 3000 rodents from Germany and the Czech Republic were screened by broad spectrum HEV-RT-PCR. As a result, 13 common voles (Microtus arvalis) and one bank vole (Myodes glareolus) were detected to be HEV-RNA positive. Comparison of the obtained sequences, complete genome determination and phylogenetic analysis indicated the finding of a novel common vole-associated HEV (cvHEV), which shows a high sequence divergence towards other members of the species Orthohepevirus C, but shares a high sequence similarity to a HEV-genome derived from a kestrel (Falco tinnunculus). The finding of cvHEV-RNA in a bank vole might be caused by a spillover infection. The cvHEV genome shares the hepevirus-typical open reading frames, but also has unique cvHEV-specific attributes in its genome.
The investigation of 420 Norway rats (Rattus norvegicus) and 88 Black rats (Rattus rattus) identified HEV-RNA in Norway rats from eight of nine and Black rats from two of four European countries. In a single Norway rat from Belgium, a HEV-3-strain with high sequence similarities to rabbitHEV (HEV-3ra), was detected. The investigation of zoo animals revealed a ratHEV spillover infection in a Syrian brown bear (Ursus arctos syriacus). This infection was most likely caused by ratHEV-infected free-living, wild rats from the same zoo.
Investigation of wild rabbit populations trapped in and around Frankfurt am Main, Germany, showed anti-HEV antibodies (34.7%) and rabbitHEV-RNA (25%). A high sequence similarity of rabbitHEV in the animals trapped at the urban site was observed, whereas a high sequence divergence was seen for the animals trapped at the rural trapping sites.
In conclusion, hepeviruses are widespread among different small mammal populations in Europe. The broad geographical distribution of these hepeviruses should be taken into account in further public health risk assessments. Further investigations are needed to characterize the presence of cvHEV in more detail, especially by taking the population dynamics of common voles into account. The detected HEV-strains could be taken as basis for the establishment of novel HEV-animal models, which might replace the so far used swine and non-human primate models.
The advances in high-throughput sequencing technologies have revolutionized the possibilities for pathogen identification in cases of unknown disease origin. Diagnostic metagenomics allows the unbiased and simultaneous detection of almost all nucleic acids in a clinical sample, with the potential to provide pivotal insights into otherwise undeterminable causes of human or animal disease.
In this thesis, possibilities, pitfalls and the suitability of Ion Torrent and Illumina sequencing platforms for comprehensive use in diagnostic metagenomics were assessed and optimized procedures developed. Clinical field samples, undiagnosable by standard diagnostics, were taken as real-life examples for the investigations. The results show that cross-contamination due to index swapping and run-to-run-carryover constitute a major issue on Illumina platforms, severely compromising the correct interpretation of results for clinical specimens. In contrast, Ion Torrent platforms did not display any form of cross-contamination, however, the commercial library preparation method is less efficient. Combining the advantages of both platforms, customized Y adapters, facilitating highly efficient library preparation, were developed for Ion Torrent sequencing and applied in further experiments. The obstacles of strongly degraded RNA in formalin-fixed paraffin-embedded samples were identified and the workflow adapted to meet the requirements of smaller fragments. Additionally, it was shown that adequate sampling is a very important step, if not the most important step, in the workflow, as well as subsequent validation of the obtained results in terms of causation. The achievements in this study allow other researchers the application of a sensitive and optimized diagnostic metagenomics workflow.
Furthermore, the investigations on the clinical samples resulted in the discovery of a novel respirovirus with putative zoonotic potential, the first description of Borna disease virus 1 in human organ transplant recipients, and the discovery of a very distantly related novel ovine picornavirus. These discoveries build a basis for further research and expand the knowledge regarding new and emerging viruses.
The importance of investments by emerging country multinationals to industrialised economies has risen continuously as illustrated by the growing number of Chinese merger and acquisitions (M&A) of German Mittelstand firms. This dissertation aims to analyse the effects of institutional distances on the M&A process. To this end, William Scott’s concept of institutions is newly operationalized to investigate institutional distances on the intra-firm, regional and international level. Through interviews with involved firms, intermediaries and key persons with dual backgrounds, the effects on different dimensions of the subsidiaries’ embeddedness as well as various mechanisms of institutional work during and after the M&A are evaluated.
Escherichia coli has been commonly used as a platform for recombinant protein production and accounts for approximately 30% of current biopharmaceuticals on the market. Nowadays, many recombinant proteins require post-translational modifications which E. coli normally cannot facilitate. Therefore, novel technological advancements are unceasingly being developed to improve the E. coli expression system. In this work, some of the most recently engineered platforms for the production of disulfide bond-containing proteins were used to study the E. coli proteome under heterologous protein production stress. The effects of protein secretion via the Sec and Tat translocation pathways were examined using a comparative LC-MS/MS analysis. The E. coli proteome responds to foreign protein production by activation of several overlapping stress responses with a high degree of interaction. In consequence, a number of important cellular processes such as cellular metabolism, protein transport, redox state of the cytoplasm and membrane structure are altered by the production stress. These changes lead to the reduction of cellular growth and recombinant product yields. Resolving the identified bottlenecks will increase the efficiency of recombinant protein expression processes in E. coli.
Medical doctors sometimes make diagnoses in persons who are not their patients and who did not ask for their medical opinion, e.g., when an off-duty dermatologist diagnoses melanoma in a stranger, outside of the hospital setting. These diagnoses are referred to as unsolicited medical opinions.
The unsolicited medical opinion raises several ethical questions. Most importantly, it poses a moral challenge for the physician: a possible disease, which may lead to a serious loss of health, is recognised in a person who is not the physician’s patient, outside of the formal medical context. The fundamental ethical question addressed in this dissertation is: Does a medical doctor who makes a clinical diagnosis in a stranger, outside of the formal medical context, have an ethical obligation to offer an unsolicited medical opinion?
This ethical question involves some related questions: If physicians do have an ethical obligation to offer an unsolicited medical opinion, are there any limiting factors to this obligation, which would justify not acting? A more practical question is also raised: How should a physician approach the person in whom an unsolicited diagnosis is made?
The cumulative dissertation is based on three publications addressing the unsolicited medical opinion. Firstly, the unsolicited medical opinion is explored from the perspective of utilitarianism, and a utilitarian argument is made in favour of offering an unsolicited medical opinion. Secondly, the topic is placed in the context of the existing scientific literature and analysed from the perspective of several ethical theories: virtue ethics, care ethics, principlism and contract theory. Lastly, the unsolicited medical opinion is discussed in the context of “medically unknown symptoms”. As in the central argument of this thesis, a utilitarian principle is applied and an argument made in favour of an unsolicited mental health diagnosis.
The first part of my work comprises empirical findings and theoretical foundations on stress in its historical development and socio-emotional and behavioural factors.
The first study of my dissertation focuses on the relationship between perceived stress in adolescence, the context variables of perceived helpfulness and competition and socio-emotional and behavioural strengths and difficulties (i.e., emotional problems, symptoms of hyperactivity, problems with peers, prosocial behaviour and conduct problems) from early to middle adolescence. I postulated a moderation or mediation of the effect of perceived stress on socio-emotional and behavioural strengths and difficulties through the two context variables. My hypotheses were tested using a latent moderating structural equation model (moderation analysis) and a multi-group structural equation model taking into account the gender and age of the students (mediation analysis). The theoretical basis of my first study is the transactional stress model by Lazarus and Folkman (1984).
The second study of my dissertation is dedicated to the question whether perceived stress is a moderator in the relationship between depressive symptoms in early adolescence and socio-emotional and behavioural strengths and difficulties in middle adolescence. Based on the cognitive vulnerability-transactional stress theory of Hankin and Abramson (2001), which assumes reciprocal and dynamic relationships between the individual and the environment, I investigated this question and tested the relationships using a latent moderating structural equation model.
The third study of my dissertation is based on Bronfenbrenner’s socio-ecological model (1975). Using a cross-lagged panel design, I investigate the within time and longitudinal relationships between variables of emotional (in-)stability (i.e., depressive symptoms, perceived stress and loneliness) and socio-environmental factors (i.e., sense of belonging, student-student and teacher-student-relationship) from early to middle adolescence.
At the end of my work there is a summary of all results, a discussion and an outlook for future research.
The goal of this thesis was to characterize the properties of tetramyristoyl cardiolipin (TMCL) and several environmental influences on it. This included investigating the pH and temperature dependency of TMCL as well as the influences of ROS on TMCL and exam-ining the lipid-protein interactions between TMCL and cytc. Furthermore, I extended the research to the analysis of binary mixtures composed of TMCL and dimyristoyl phosphati-dylcholine (DMPC). To this end, I investigated the samples with the aid of the Langmuir monolayer technique. This method allowed me to mimic interactions occurring at the membrane surface as it represents one membrane layer. The recording of π-A isotherms was also coupled with further other techniques like Brewster angle microscopy (BAM), Infrared Reflection-Absorption Spectroscopy (IRRAS), Grazing Incidence X-Ray Diffraction (GIXD) and Total Reflection X-Ray Fluorescence (TRXF) to enable a more comprehensive monolayer study. In addition, some systems were analyzed using Thin-layer Chromatography (TLC) and/or Differential Scanning Calorimetry (DSC) to be able to draw conclusions about sample composition or characteristic temperatures, respectively.
In the present work high density helicon plasma discharges are created and characterized as a promising concept towards the realization of plasma wakefield accelerators to build up electric fields in the order of GV/m to accelerate electrons to energies in the TeV range with proton driving bunches. For such a concept plasma sources are needed that are able to maintain discharges with plasma densities of n_e = 7E20 m^-3 over long distances with a low variation in plasma density. Measurements at the PROMETHEUS-A device are performed for variable parameters, like magnetic induction, RF heating power and filling gas pressure. A CO2 laser interferometer, a laser induced fluorescence (LIF) diagnostic and a reaction rate model are combined to give a full picture. It is shown that in most cases the plasma density is centrally peaked with a high density region +- 5 mm from the center. The peak plasma density increases with increasing filling gas pressure, RF heating power and magnetic induction, limited by the number of neutral particles in low pressure discharges, by the transferred heating power and the increasing recombination and electron quenching rates of argon ions in high filling pressure cases. The increase in plasma density with increasing magnetic induction correlates to the direct proportionality in the helicon dispersion relation. For all investigated operational parameters the time evolution of the helicon discharge shows the same characteristics and is reliably reproducable inside the error bars. The electron temperature is determined by combining the collisional radiative model with line ratio measurements of two spontaneously emitted LIF lines. The low electron temperature regime of 1.2 eV < T_e < 1.4 eV and the electron temperature profiles are consistent with helicon wave heating via collisional power dissipation. The maximum plasma density of n_e = (6 +- 1)E20 m^-3 is measured at high RF power of P_RF = 24 kW, p_0 = 9 Pa filling gas pressure and a magnetic induction of B = 105 mT with a maximum electron temperature at 1.4 eV. At these operational parameters the plasma density peaking time and width are determined to be 270E-6 s and 50E-6 s, respectively. This shows that specific plasma density requirements for the use of a wakefield accelerator are reachable and the duration of the peak plasma density is more than sufficient for a relativistic particle to pass a 1 km long plasma cell. Additionally time-resolved LIF profile measurements for neutral and singly ionized argon were conducted to complement the previously evaluated measurements. The time resolution of the LIF diagnostic was chosen in a way to adequately represent the evolution of densities and to allow full profile measurements over one day. A resolution of 200E-6 s was chosen. The time-resolved neutral and ion metastable densities show hollow profiles with high densities at the edges over the first ms indicating higher ionization levels and increasing electron quenching rates. The metastable densities are highly determined by electron temperature, RF heating power and filling neutral gas pressure and do not reflect the neutral argon evolution. To investigate the influence of neutral depletion on the density evolution and maximum plasma density, the argon neutral and ion ground state densities are determined. Both time-resolved density profiles show a hollow profile with highest densities at the edges over a longer time interval of 3-4 ms. The penetration depths (ionization mean-free paths) indicate increased ionization of neutral argon while dissipating inwards, corresponding well to the theoretical value of lambda = 20 mm. This results in a depletion of neutrals in the center of the discharge, leading to a limitation and a fast decrease of plasma density after the neutrals are partially ionized. The shown refilling effect of neutral argon is too slow to have an important impact. At operation parameters for highest plasma density, the calculated ground states also show a fast increase in density at the end of the discharge after the RF-heating is switched off. This indicates recombination effects to these atomic states and higher ionization levels than ArII in the helicon discharge.
Due to a variety of plasma sources in terms of type of discharge, energy yield, working gas or geometric factors, it is recommended to standardize the study protocol by choosing a plasma source and easy access to rugged tumor surfaces as demonstrated by the CAP-plasma-jet. The intention of the trial shall be to optimize the plasma jet for tumor site capability and operating room implementation.
It makes sense to start clinical trials in plasma medicine with the treatment of head and neck squamous cell carcinoma patients of infected wounds and ulcerations.
CAP is able to reduce contamination of cancer ulcerations and the typical fetid odor that often accompanies head and neck cancer patients. The intention of the trial shall be to evaluate the efficiency of decontamination in head and neck cancer ulcerations in terms of pathogenic species, amount of reduction and reliability.
Standardize study protocol:
Phase I, clinical explorative single-arm, randomized, open, multicenter
Primary objective
Reduction of microbial burden of cancer ulcerations by application of CAP
Secondary objective:
Reduction of tumor following local CAP application
Inclusion:
20 Patients suffering from locally advanced oral cavity carcinoma with open tumor surfaces, treated with palliative intention and no more curative treatment options
Exclusion:
No wish for treatment, no compliance and understanding the protocol of the clinical study
Efficacy:
reduction of microbial burden; Documentation of visible changes by photography; Pathohistological and biochemical examination of specimen, taken from the tumor area and control areas
Procedure:
Plasma is applied for 1 minute per cm², spot area of 3 mm diameter distance between nozzle and tumor surface of 14 mm. 3 times/week with a break of 1 week followed by a repeated cycle for another week.
Conclusion:
The most important intention of the trial from the clinician’s point of view shall be to make CAP-treatment an effective and well-accepted addition to standard cancer therapy based upon EBM at least in palliative medicine.
Global climate change is occurring all over the world, but in the Arctic the climate is changing more rapidly and drastically than in many other parts of our planet. Many species that are already at their climatic limit need to adapt to recent climate conditions or migrate in order to not go extinct. The possibilities of adaption include phenotypic plasticity and adaptation to various extents. This is also the case for white spruce P. glauca, which belongs to the conifers and thus in the largest group of gymnosperms still living today. Among the approx. 600 extant conifer species white spruce is one of the most widespread trees in North American boreal forests. Its range extends from 69° N in the Canadian Northwest Territories to the Great Lakes at about 44° N, where it occurs from sea level to an altitude of about 1520 m (Burns and Honkala, 1990). Site related, climate-dependent differences in white spruce reproduction can be seen as a strategy to survive under the harsh climatic conditions at Alaska's treelines: Besides sexual reproduction, the vegetative propagation occurs in the white spruce as an additional reproductive mechanism. This can be realized by "layering" when the lower branches of the tree crown touch the ground and develop roots to later grow as a separate individual with or without a connection to the mother tree. Known as other mechanisms of vegetative propagation are also the rooting of fallen trees which were not completely uprooted, and the "root suckering", in which new shoots sprout from the roots of the tree. However, the latter was not yet observed in the genus Picea. With the help of short, repetitive, non-coding sequences in the genome, which are therefore not subject to selection and are called microsatellites, these clones can be determined by genotyping.
For this purpose, using different polymorphic microsatellites, an individual multilocus genotype is created for each tree, by means of which it can be compared with all other trees of the same species.
In the first part of this work (article I), the occurrence of clones in three study areas at Alaskan treelines are examined and the reasons for their appearance in variable numbers are discussed. For this purpose, 2571 white spruces (P. glauca) were genotyped and their position was determined via differential GPS in the field. The percentage of clonal trees is higher in areas with harsh climatic conditions and correlates with the height of the lowest branches of the tree crown. This suggests that the vegetative propagation of white spruce is a backup strategy for times when climatic conditions hamper sexual reproduction. The correlation between clone numbers and tree crown height suggests "layering" as the main mechanism for cloning whereas selection for vegetative reproduction seems to be very unlikely shown by the results for genetic differentiation between the clonal and the singleton trees in this study.
In the second part of this work (articles II and III), the influence of environmental factors and phenotypic traits on the mycobiome of the needles (including all fungi living on (epiphytic) and in (endophytic) the needles) in our study areas in Alaska was investigated. The mycobiome of the white spruce needles was chosen as a proxy for the parasite infection rate by fungi and thus serves as a fitness parameter. For this purpose, all epiphytic and endophytic fungal species were analyzed by a metabarcoding analysis.
In article II, 48 trees of one study area at Alaska’s northern treeline (Brooks Range) were examined for differences in mycobiome due to genetic differentiation, phenotypic characteristics and / or habitat characteristics. The trees used for this study were sampled from two adjacent plots on a south-facing mountain slope with an elevation gradient from 875 to 950 meters above sea level. It could be shown that, in contrast to the trees genotype, the height above sea level, the mountain slope, as well as the height and age of the trees have a significant impact on the mycobiome. The genetic differentiation between the tree individuals, however, showed no significant effect.
Based on article II we examined the mycobiome composition of a total of 96 trees in 2 plots (16 trees each) at three sites in Alaska over a distance of 500 kilometers. Additionally, we sampled needles of two different ages for each tree (current year and three years old needles) summing up to 192 samples in total. The incentive of this study (article III) was to investigate the influence of origin and age of spruce needles on their mycobiome and if there is a genetic predisposition that is related to the fungal species community. In addition, the sampling design was improved by collecting needles from all four orientations (North, South, East and West) and sampling trees at a standardized distance to each other to avoid systematic errors. Comparable to article II the influence of the trees genetics on the species community of the epiphytic and endophytic fungi of the white spruce needles seems to be very unlikely. In contrast, a significant influence of the geographic origin and the needle age on the species structure of the needle inhabiting fungal species was found. The phenotypic tree traits height and dbh (diameter at breast height) had only minor influence and did in fact explain less than 2% of the mycobiome variance. Using Illumina sequencing, 10.2 million reads from the nucleotide sequence between the internal transcribed spacer (ITS) genes could be obtained, which yielded in 1575 ribotypes (called operational taxonomic unit, OTU) for the fungi. These were compared with a reference database to compare and assign them to known fungal species. For example, 942 OTUs with >95% similarity could be identified as known species, with 1975 samples identified on genus level and 2683 when determined to family level. The most pronounced difference between the two studies (article II and III) were due to the fungal species of the class of Pucciniomycetes, more specifically the genus Chrysomyxa which belongs to the rust fungi and is plant pathogenic. In the study of article II (sampling in 2012), Pucciniomycetes accounted for only a minor portion of the assigned DNA sequences. In the second study (article III, sampling in 2015) they accounted for more than half of all basidiomycetes found, which in turn contain 20.0% of all DNA sequences, the second largest phylum found beside Ascomycetes (51.4%).