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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.