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Animal movement is a crucial aspect of life, influencing ecological and evolutionary processes. It plays an important role in shaping biodiversity patterns, connecting habitats and ecosystems. Anthropogenic landscape changes, such as in agricultural environments, can impede the movement of animals by affecting their ability to locate resources during recurring movements within home ranges and, on a larger scale, disrupt migration or dispersal. Inevitably, these changes in movement behavior have far-reaching consequences on the mobile link functions provided by species inhabiting such extensively altered matrix areas. In this thesis, I investigate the movement characteristics and activity patterns of the European hare (Lepus europaeus), aiming to understand their significance as a pivotal species in fragmented agricultural landscapes. I reveal intriguing results that shed light on the importance of hares for seed dispersal, the influence of personality traits on behavior and space use, the sensitivity of hares to extreme weather conditions, and the impacts of GPS collaring on mammals' activity patterns and movement behavior.
In Chapter I, I conducted a controlled feeding experiment to investigate the potential impact of hares on seed dispersal. By additionally utilizing GPS data of hares in two contrasting landscapes, I demonstrated that hares play a vital role, acting as effective mobile linkers for many plant species in small and isolated habitat patches. The analysis of seed intake and germination success revealed that distinct seed traits, such as density, surface area, and shape, profoundly affect hares' ability to disperse seeds through endozoochory. These findings highlight the interplay between hares and plant communities and thus provide valuable insights into seed dispersal mechanisms in fragmented landscapes.
By employing standardized behavioral tests in Chapter II, I revealed consistent behavioral responses among captive hares while simultaneously examining the intricate connection between personality traits and spatial patterns within wild hare populations. This analysis provides insights into the ecological interactions and dynamics within hare populations in agricultural habitats. Examining the concept of animal personality, I established a link between personality traits and hare behavior. I showed that boldness, measured through standardized tests, influences individual exploration styles, with shy and bold hares exhibiting distinct space use patterns. In addition to providing valuable insights into the role of animal personality in heterogeneous environments, my research introduced a novel approach demonstrating the feasibility of remotely assessing personality types using animal-borne sensors without additional disturbance of the focal individual.
While climate conditions severely impact the activity and, consequently, the fitness of wildlife species across the globe, in Chapter III, I uncovered the sensitivity of hares to temperature, humidity, and wind speed during their peak reproduction period. I found a strong response in activity to high temperatures above 25°C, with a particularly pronounced effect during temperature extremes of over 35°C. The non-linear relationship between temperature and activity was characterized by contrasting responses observed for day and night. These findings emphasize the vulnerability of hares to climate change and the potential consequences for their fitness and population dynamics with the ongoing rise of temperature.
Since such insights can only be obtained through capturing and tagging free-ranging animals, I assessed potential impacts and the recovery process post-collar attachment in Chapter IV. For this purpose, I examined the daily distances moved and the temporal-associated activity of 1451 terrestrial mammals out of 42 species during their initial tracking period. The disturbance intensity and the speed of recovery varied across species, with herbivores, females, and individuals captured and collared in relatively secluded study areas experiencing more pronounced disturbances due to limited anthropogenic influences.
Mobile linkers are essential for maintaining biodiversity as they influence the dynamics and resilience of ecosystems. Furthermore, their ability to move through fragmented landscapes makes them a key component for restoring disturbed sites. Individual movement decisions determine the scale of mobile links, and understanding variations in space use among individuals is crucial for interpreting their functions. Climate change poses further challenges, with wildlife species expected to adjust their behavior, especially in response to high-temperature extremes, and comprehending the anthropogenic influence on animal movements will remain paramount to effective land use planning and the development of successful conservation strategies.
This thesis provides a comprehensive ecological understanding of hares in agricultural landscapes. My research findings underscore the importance of hares as mobile linkers, the influence of personality traits on behavior and spatial patterns, the vulnerability of hares to extreme weather conditions, and the immediate consequences of collar attachment on mammalian movements. Thus, I contribute valuable insights to wildlife conservation and management efforts, aiding in developing strategies to mitigate the impact of environmental changes on hare populations. Moreover, these findings enable the development of methodologies aimed at minimizing the impacts of collaring while also identifying potential biases in the data, thereby benefiting both animal welfare and the scientific integrity of localization studies.
Today, analytical chemistry does not longer consist of only the big measuring devices and methods which are time consuming and expensive, which can furthermore only be handled by the qualified staff and in addition the results can also only be evaluated by this qualified staff. Usually, this technique, which shall be described in the following as 'classic analytic measuring technique', requires also rooms equipped especially and often a relative big quantity of the test compounds which should be prepared especially. Beside this classic analytic measuring technique, limited on definite substance groups and requests, a new measuring technique has gained acceptance particularly within the last years, which one can often be used by a layman, too. Often the new measuring technique has very little pieces of equipment. The needed sample volumes are also small and a special sample preparation isn't required. In addition, the new measuring instruments are simple to handle. They are cheap both in their production and in the use and they permit even a continuous measurement recording usually. Numerous of this new measuring instruments base on the research in the field of Biosensorik during the last 40 years. Since Clark and Lyon in the year 1962 were able to measure glucose with a simple oxygen electrode, completed by an enzyme the development of the new measuring technique did not have to be held back any longer. Biosensors, special pickups which consists of a combination from a biological component (permits a specific recognition of the analyte also without purification of the sample previously) and a physical pickup (convert the primary physicochemical effect into an electronically measurable signal), conquered the market. In the context of this thesis different tyrosinasesensors were developed which fulfilling the various requests, depending on origin and features of the used tyrosinase. One of the tyrosinasesensors for example was used for quantification of phenolic compounds in river and sea water and the results could correlated very well with the corresponding DIN-test for the determination of phenolic compounds. An other developed tyrosinasesensor showed a very high sensitiveness for catecholamines, substances which are of special importance in the medical diagnostics. In addition, the investigations of two different tyrosinases, which were carried out also in the context of this thesis, have shown, that a special tyrosinase (tyrosinase from Streptomyces antibioticus) will be the better choice as tyrosinase from Agaricus bisporus, which is used in the area of biosensor research till now, if one wants to develop in future even more sensitive tyrosinasesensors. Furthermore, first successes became reached on a molecular biological field, the production of tyrosinasemutants with special, before well-considered features. These successes can be used to develop a new generation of tyrosinasesensors, tyrosinasesensors in which tyrosinase can be bound directionally both to the corresponding physical pickup or also to another enzyme. From this one expects to achieve ways minimized which the substance to be determined (or whose product) otherwise must cover. Finally, this should result in an clearly visible increase of sensitivity of the Biosensor.
Neuroinflammatory and neurodegenerative diseases such as Parkinson's (PD) and multiple sclerosis (MS) often result in a severe impairment of the patient´s quality of life. Effective therapies for the treatment are currently not available, which results in a high socio-economic burden. Due to the heterogeneity of the disease subtypes, stratification is particularly difficult in the early phase of the disease and is mainly based on clinical parameters such as neurophysiological tests and central nervous imaging. Due to good accessibility and stability, blood and cerebrospinal fluid metabolite markers could serve as surrogates for neurodegenerative processes. This can lead to an improved mechanistic understanding of these diseases and further be used as "treatment response" biomarkers in preclinical and clinical development programs. Therefore, plasma and CSF metabolite profiles will be identified that allow differentiation of PD from healthy controls, association of PD with dementia (PDD) and differentiation of PD subtypes such as akinetic rigid and tremor dominant PD patients. In addition, plasma metabolites for the diagnosis of primary progressive MS (PPMS) should be investigated and tested for their specificity to relapsing-remitting MS (RRMS) and their development during PPMS progression.
By applying untargeted high-resolution metabolomics of PD patient samples and in using random forest and partial least square machine learning algorithms, this study identified 20 plasma metabolites and 14 CSF metabolite biomarkers. These differentiate against healthy individuals with an AUC of 0.8 and 0.9 in PD, respectively. We also identify ten PDD specific serum metabolites, which differentiate against healthy individuals and PD patients without dementia with an AUC of 1.0, respectively. Furthermore, 23 akinetic-rigid specific plasma markers were identified, which differentiate against tremor-dominant PD patients with an AUC of 0.94 and against healthy individuals with an AUC of 0.98. These findings also suggest more severe disease pathology in the akinetic-rigid PD than in tremor dominant PD. In the analysis of MS patient samples a partial least square analysis yielded predictive models for the classification of PPMS and resulted in 20 PPMS specific metabolites. In another MS study unknown changes in human metabolism were identified after administration of the multiple sclerosis drug dimethylfumarate, which is used for the treatment of RRMS. These results allow to describe and understand the hitherto completely unknown mechanism of action of this new drug and to use these findings for the further development of new drugs and targets against RRMS.
In conclusion, these results have the potential for improved diagnosis of these diseases and improvement of mechanistic understandings, as multiple deregulated pathways were identified. Moreover, novel Dimethylfumarate targets can be used to aid drug development and treatment efficiency. Overall, metabolite profiling in combination with machine learning identified as a promising approach for biomarker discovery and mode of action elucidation.
Inflammatory bowel diseases (IBD), characterised by a chronic inflammation of the gut wall, develop as consequence of an overreacting immune response to commensal bacteria, caused by a combination of genetic and environmental conditions. Large inter-individual differences in the outcome of currently available therapies complicate the decision for the best option for an individual patient. Predicting the prospects of therapeutic success for an individual patient is currently only possible to a limited extent; for this, a better understanding of possible differences between responders and non-responders is needed.
In this thesis, we have developed a mathematical model describing the most important processes of the gut mucosal immune system on the cellular level. The model is based on literature data, which were on the one hand used (qualitatively) to choose which cell types and processes to incorporate and to derive the model structure, and on the other hand (quantitatively) to derive the parameter values. Using ordinary differential equations, it describes the concentration-time course of neutrophils, macrophages, dendritic cells, T cells and bacteria, each subdivided into different cell types and activation states, in the lamina propria and mesenteric lymph nodes. We evaluate the model by means of simulations of the healthy immune response to salmonella infection and mucosal injury.
A virtual population includes IBD patients, which we define through their initially asymptomatic, but after a trigger chronically inflamed gut wall. We demonstrate the model's usefulness in different analyses: (i) The comparison of virtual IBD patients with virtual healthy individuals shows that the disease is elicited by many small or fewer large changes, and allows to make hypotheses about dispositions relevant for development of the disease. (ii) We simulate the effects of different therapeutic targets and make predictions about the therapeutic outcome based on the pre-treatment state. (iii) From the analysis of differences between virtual responders and non-responders, we derive hypotheses about reasons for the inter-individual variability in treatment outcome. (iv) For the example of anti-TNF-alpha therapy, we analyse, which alternative therapies are most promising in case of therapeutic failure, and which therapies are most suited for combination therapies: For drugs also directly targeting the cytokine levels or inhibiting the recruitment of innate immune cells, we predict a low probability of success when used as alternative treatment, but a large gain when used in a combination treatment. For drugs with direct effects on T cells, via modulation of the sphingosine-1-phosphate receptor or inhibition of T cell proliferation, we predict a considerably larger probability of success when used as alternative treatment, but only a small additional gain when used in a combination therapy.
Chloroplast membranes have a unique composition characterized by very high contents of the galactolipids, MGDG and DGDG. Many studies on constitutive, galactolipid-deficient mutants revealed conflicting results about potential functions of galactolipids in photosynthetic membranes. Likely, this was caused by pleiotropic effects such as starvation artefacts because of impaired photosynthesis from early developmental stages of the plants onward. Therefore, an ethanol inducible RNAi-approach has been taken to suppress two key enzymes of galactolipid biosynthesis in the chloroplast, MGD1 and DGD1. Plants were allowed to develop fully functional source leaves prior to induction, which then could support plant growth. Then, after the ethanol induction, both young and mature leaves were investigated over time.
Our studies revealed similar changes in both MGDG- and DGDG-deficient lines, however young and mature leaves of transgenic lines showed a different response to galactolipid deficiency. While no changes of photosynthetic parameters and minor changes in lipid content were observed in mature leaves of transgenic lines, strong reductions in total chlorophyll content and in the accumulation of all photosynthetic complexes and significant changes in contents of various lipid groups occurred in young leaves. Microscopy studies revealed an appearance of lipid droplets in the cytosol of young leaves in all transgenic lines which correlates with significantly higher levels of TAGs. Since in young leaves the production of membrane lipids is lowered, the excess of fatty acids is used for storage lipids production, resulting in the accumulation of TAGs.
Our data indicate that both investigated galactolipids serve as structural lipids since changes in photosynthetic parameters were mainly the result of reduced amounts of all photosynthetic constituents. In response to restricted galactolipid synthesis, thylakoid biogenesis is precisely readjusted to keep the proper stoichiometry and functionality of the photosynthetic apparatus. Ultimately, the data revealed that downregulation of one galactolipid triggers changes not only in chloroplasts but also in the nucleus as shown by downregulation of nuclear encoded subunits of the photosynthetic complexes.
Objective: The behaviors of endothelial cells or mesenchymal stem cells are remarkably influenced by the mechanical properties of their surrounding microenvironments. Here, electrospun fiber meshes containing various mechanical characteristics were developed from polyetheresterurethane (PEEU) copolymers. The goal of this study was to explore how fiber mesh stiffness affected endothelial cell shape, growth, migration, and angiogenic potential of endothelial cells. Furthermore, the effects of the E-modulus of fiber meshes on human adipose-derived stem cells (hADSCs) osteogenic potential was investigated.
Methods: Polyesteretherurethane (PEEU) polymers with various poly(p-dioxanone) (PPDO) to poly (ε-caprolactone) (PCL) weight percentages (40 wt.%, 50 wt.%, 60 wt.%, and 70 wt.%) were synthesized, termed PEEU40, PEEU50, PEEU60, and PEEU70, accordingly. The electrospinning method was used for the preparation of PEEU fiber meshes. The effects of PEEU fiber meshes with varying elasticities on the human umbilical vein endothelial cells (HUVECs) shape, growth, migration and angiogenic potential were characterized. To determine how the E-modulus of fiber meshes affects the osteogenic potential of hADSCs, the cellular and nuclear morphologies and osteogenic differentiation abilities were evaluated.
Results: With the increasing stiffness of PEEU fiber meshes, the aspect ratios of HUVECs cultivated on PEEU materials increased. HUVECs cultivated on high stiffness fiber meshes (4.5 ± 0.8 MPa) displayed a considerably greater proliferation rate and migratory velocity, in addition demonstrating increased tube formation capability, compared with those of the cells cultivated on lower stiffness fiber meshes (2.6 ± 0.8 MPa). Furthermore, in comparison to those cultivated on lower stiffness fiber meshes, hADSCs adhered to the highest stiffness fiber meshes PEEU70 had an elongated shape. The hADSCs grown on the softer PEEU40 fiber meshes showed a reduced nuclear aspect ratio (width to height) than those cultivated on the stiffer fiber meshes. Culturing hADSCs on stiffer fibers improved their osteogenic differentiation potential. Compared with cells cultured on PEEU40, osteocalcin expression and alkaline phosphatase (ALP) activity increased by 73 ± 10% and 43 ± 16%, respectively, in cells cultured on PEEU70.
Conclusion: The mechanical characteristics of the substrate are crucial in the modulation of cell behaviors. These findings indicate that adjusting the elasticity of fiber meshes might be a useful method for controlling the blood vessels development and regeneration. Furthermore, the mechanical characteristics of PEEU fiber meshes might be modified to control the osteogenic potential of hADSCs.