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Civil society and democracy : the country level interrelations and the individual level impact
No full textThe PhD thesis examines the relationship between civil society and democracy. In doing so, it utilizes a number of new measurements of civil society. It combines the study of the impact civil society has on the polity it operates in, with an examination of the influence civil society has on individual members of the respective society. Thus the research presented in this thesis includes two important levels of interaction between civil society and democracy: the societal level and the individual level. The first part of the analysis establishes the connection between civil society and democracy and addresses the question of a more likely direction of impact between the two variables on the country level. Although no final conclusions can be made due to certain data limitations, the results point towards democracy as having more influence on civil society rather than vice versa. The second part of the analysis adds the individual level to the study of conduciveness of civil society for democracy, by exploring how civil society influences elements of individual democratic political culture. It demonstrates that civil society is an important predictor of support for democracy and political activism. The general conclusion of the work is that on the country level there is no clear evidence of civil society's impact on democracy; civil society however has a positive influence on individual elements of democratic political culture
A geodynamic model of the northern North Atlantic
No full textThe Arctic region plays an important role in the configuration of the present day global climate. In particular the Fram Strait area, presently the only deep-water gateway between the Arctic Ocean and the world ocean, accounts for the Arctic region climate. It is still speculative how and when this deep-water connection opened due to its tectonic and geologic evolution, and how strong this influenced northern ocean circulations. It is assumed that the change of the northern ocean circulations correlate with long-term climate changes. This study provides a compilation of a geodynamic model of the northern North Atlantic, which is continued to the Arctic Ocean, and investigates the tectonic and bathymetric development. Due to the movements of the Eurasia, Greenland, and North American plates, as well as sediment accumulation changes, the width and seafloor depth of the Fram Strait was significantly modified since its initial break-up. Geophysical data in the northern North Atlantic and in the Arctic Ocean, gathered by the Alfred Wegener Institute during the last years, make this study possible. The results present an advanced age model of the oceanic crust. A palaeobathymetric reconstruction results in a timing of the Fram Strait opening of 25 Ma for a shallow-water exchange. From 17 Ma on, a deep-water exchange between the northern North Atlantic and the Arctic Ocean was possible. To link the results of the palaeobathymetric reconstruction to the global climate history, palaeoceanographic model scenarios are calculated for the present day bathymetric configuration and the palaeobathymetry of the Middle Miocene (15 Ma), the Early Miocene (20 Ma) and the Middle Eocene (45 Ma). The study shows the complex relationship between plate tectonics, the crustal development, sediment accumulations, bathymetric changes and changes in ocean circulation in the northern North Atlantic and in the Arctic Ocean and speculates on their link to global past long-term climate changes
Conformational sampling by molecular mechanics and dynamics simulations applied to the flexibility of nucleic acids
No full textThis PhD dissertation deals with the application of atomic-scale computer simulation (Molecular Dynamics) on different aspects of the conformational flexibility of Nucleic Acids (i.e. DNA, RNA). I have used diverse statistical and computational methods such as Umbrella Sampling and Replica Exchange to extract entropic properties, e.g. free energy, characterising (i) the bending of DNA on short length-scale, (ii) the folding of recently discovered RNA ribosomal motifs (the kink-turn motif) and (iii) backbone dihedral conformations accessible to damaged DNA. One achievement is the reproduction of the experimental curve for the probability of very high bend angles observed for short fragment of DNA which demonstrates a non linear (softer) bending flexibility of DNA. Results of my thesis predict that DNA kinks (local defects unstacking neighbour basepairs) occur in vivo and some of them induce a 90⁰-turn in the helix. They are associated with a systematic decrease of the local DNA stiffness constant (half an order of magnitude) which was quite unexpected. DNA bending up to 150⁰ on the 5 nm length scale requires on average 12 kcal/mol. It is slightly less expensive, ̃10 kcal/mol when a run of consecutive adenines is present (Atract sequences which occur frequently in every genome). The same kind of information is provided for a larger kink-turn motif in RNA (̃10 base pairs) for which an almost iso- energetic twist / bend coupled mode has been characterised. A methodological development of Hamiltonian replica exchange sampling techniques enables to characterize several competing DNA backbone conformations accessible to damaged DNA (an abasic site). The method can be used for any combination of backbone dihedral variables which constitute an example of DNA metastable states with very short relaxation time. More generally the PhD thesis presents the development of new methods to tackle the accurate sampling of particular nucleic acid helical propensities
Cosmopolitan sovereignty and the proliferation and stratification of citizenship
No full textIn the past decades a paradigmatic change has been taking place concerning the concept of citizenship with the fading of the former prohibitive attitude towards dual citizenship. With this transformation the former congruity between citizens, the territory of the state, the nation and the sphere of political authority is undermined, which has major ramification on the concept of sovereignty. The thesis contends that sovereignty is the attribute of two entities of the political: the state and the individual and modern political life could be interpreted as the dialectic relationship of these two, with the individual seeking to realize his freedom and the state to create effective means to govern collectives of man. The Westphalian structure provided the framework to divide the world into distinct units of states, on the one hand with the domestic - where democratic politics offered the room for man to realize his freedom - and on the other hand the international - where states interacted in an anarchic environment. It was the corollary of this setup to neatly package individuals into states, creating a hierarchical primacy of states over their citizens. The prevailing of dual citizenship, however, could be conducive to transform this setup and shift it towards a 'more cosmopolitan reality' by entailing changes both for individuals and for the system states. For individuals as the result of dual citizenship membership in states increasingly turns into a choice and the proliferation of citizenships would bring about also the stratification of citizenship statuses, beyond the former rigid dichotomy of citizens and foreigners. On the system level dual citizenship could be conducive to realize cosmopolitan forms of governance, promoting questions of morality and solidarity to trespass borders of states
High resolution DNA methylation analysis of gene promoters in human chromosome 21
No full textDNA methylation is an important epigenetic signal, which has an essential role in gene regulation, development and disease processes. We optimized the work procedure for DNA methylation analysis and set up a sequencing and analysis pipeline for medium to high throughput DNA methylation analysis. In addition, we developed a web interface program for bisulfite sequencing data presentation, compilation and comparison (BDPC). By using the high resolution methods, we analyzed DNA methylation patterns for 190 gene promoter regions on chromosome 21 in five human cell types. Our results show that average DNA methylation levels are distributed bimodally with enrichment of highly methylated and unmethylated sequences. Within CpG-rich sequences, DNA methylation was found to be anti-correlated with CpG dinucleotide density and GC content. We observed over-representation of CpG sites in distances of 9, 18 and 27 bps in highly methylated sequences. DNA methylation in promoter regions is strongly correlated with the absence of gene expression and low levels of activating epigenetic marks. Additionally, we found that amplicons from different parts of a CpG island frequently differ in their DNA methylation level, methylation levels of individual cells in one tissue are very similar and methylation patterns follow a relaxed site specific distribution. We further analyzed DNA methylation pattern of 16 amplicons from chromosome 21 in 38 individuals and identified allele-specific DNA methylation of 6 amplicons. The allele-specific methylation of these amplicons is not connected to imprinting but due to the genetic polymorphisms between the two alleles. Our data indicate that genetic differences strongly influence interindividual variations of DNA methylation. We extrapolate that the allele-specific methylation is likely affecting many genes in the human genome and might contribute to allele specific expression, which is a widespread phenomenon in the human genome
Empathy : Gains and Losses in Adulthood
No full textThe present study investigated age differences in two facets of empathy - empathic accuracy and emotional congruence - in a sample of young (N = 80, M = 32 years) and old (N = 73, M = 59 years) adults. It was hypothesized that age differences in empathic reactions will be moderated by the age relevance of the topic a target person talks about: participants will show more empathic accuracy and emotional congruence if the topic is relevant to their own age group
The application of computational biology to study structure, function, interactions and evolution of DNA and RNA methyltransferases
No full textNowadays there are plenty of Computational Biology programs which are available to study various properties of proteins, like their structure, function, interactions with other proteins or evolution. In this work we have applied these tools to study RNA and DNA methyltransferases. Investigation of the DNA recognition by M.EcoRV aided with a homology model and sequence alignment shed light on the evolutionary pathways leading to change in sequence specificity of this protein, as well as on the mechanism and temporal order of events leading to the DNA recognition and methylation. Dnmt2 is an enzyme which looks like an authentic DNA methyltransferase but methylates tRNA molecules. This enzyme was studied using multiple sequence alignment and phylogenetic analysis as starting point. Our data clearly show that it follows the catalytic mechanism of m5C DNA MTases to methylate RNA. This represents the first example of such an enzyme. A homology model of the Dnmt3a catalytic domain, allowed us to study the function of its conserved residues and to interpret the experimental results. In addition, we have created a novel method to investigate protein-protein interaction sites, called "Absence of Interference" approach. We have employed this method to study the Dnmt3a/Dnmt3L complex. We have also contributed to the repository of bioinformatic programs, by creating new tools which are helpful to interpret and present experimental data. The Prima software is able to calculate conservation scores generated by the "Absence of Interference" method and map them onto protein models. DistriDist can analyze the distribution of pairwise distances between the query occurrences in a provided longer sequence, which can be helpful to identify the regions of the genome that can play a role in epigenetic regulation. BDPC was designed to analyze, present and compare the results from the bisulfite genomic sequencing projects, a laborious task which before had to be done manually
How EU policy in the fight against serious crime affects national regulatory structures in Germany and England : an empirical analysis on the dimensions of liberty and security
No full textCooperation in the fight against crime in the EU has developed significantly over the last decade. This thesis analyzes how the transposition of EU measures affects national policy in Germany and England with regard to security and liberty
Development of experimental and bioinformatics methods for high resolution DNA methylation analysis of gene promoters on human chromosome 21
No full textDNA methylation adds heritable information to the genome without changing the DNA sequence. We developed a medium-throughput pipeline for bisulfite conversion, subcloning, sequencing of individual molecules and new bioinformatics tools (http://biochem.jacobs-university.de/BDPC) for data analysis, compilation and presentation of high resolution DNA methylation patterns. The BISMA software is designed for fast and accurate primary sequencing data analysis from unique and repetitive sequences. The BDPC compilation software is designed to compile the dataset and to prepare databases for the presentation of high resolution methylation patterns. The BDPC clustering software assists visualizing large datasets in form of a clustered heatmap and displays methylation differences in form of a clustered dendrogram. We generated the so far largest DNA methylation dataset at single nucleotide and single allele resolution on CpG-rich gene promoters from human chromosome 21 (http://biochem.jacobs-university.de/name21). We observed a pronounced correlation of DNA methylation with the underlying DNA sequence composition and histone modifications, examples of abrupt methylation changes within the same CpG-island, tissue specific methylation and an inverse correlation of methylation with gene expression. A significant loss of global methylation measured at the Alu repetitive sequences was found in a cancer cell line and to a greater extend in cells treated with the DNA methyltransferase inhibitor 5-azacytidine. No compensatory effect in DNA methylation on chromosome 21 was observed in two samples that had a third copy of this chromosome. We observed inter-individual methylation variability, which was caused by several new cases of allele specific methylation and evoked allele specific gene expression. These strong genotype-epigenotype interactions suggest that the epigenetic drift observed among individuals is mainly determined by the genetic haplotype rather than age or gender
The influence of tapasin on MHC class I-peptide interaction
No full textSince peptide-empty MHC class I molecules at the cell surface would be inefficient and probably dangerous for cells, class I molecules must select peptides with dissociation rates that are sufficiently slow to allow survival of the peptide-class I complex during the transit to the cell surface and for some time thereafter. Elliott and collaborators have shown that class I molecules, however, first bind low-affinity peptides in the ER and later exchange them for high-affinity ones before leaving for the Golgi apparatus (Williams et al., 2002). This process, termed peptide editing, depends on the class I - specific assembly factor, tapasin, which binds directly to class I molecules in the ER. How does tapasin work? Based on our molecular dynamics simulations (Zacharias and Springer, 2004), we hypothesize that it may bind to and deform the peptide binding site of class I molecules by moving one flexible helix away from the peptide. As a consequence, some of the hydrogen bonds between the class I molecule and the peptide backbone may break and reduce the affinity between peptide and class I molecule. This would lead to a rapid dissociation of low-affinity peptides from the class I molecule. As a conclusion, this hypothesis predicts that tapasin universally decreases the affinity of class I molecules for peptide ligands. Since it is difficult to recreate the entire class I loading complex with purified proteins (it contains several other chaperones), we are investigating peptide binding to class I molecules in the lumen of isolated microsomal membranes in the presence and absence of tapasin. Class I molecules are transcribed, translated, and translocated in vitro. Peptide is then added to the microsomes, and peptide-class I complexes are precipitated by conformation-specific antibodies. We have observed that tapasin mediates the binding of high-affinity peptide to MHC class I molecules in the ER by accelerating dissociation of low-affinity peptides