This thesis aimed to provide evidence that supports a central role for NGCs in CVD by studying the expression, regulation and function of neuronal guidance cues (NGCs) in endothelial cells and... Show moreThis thesis aimed to provide evidence that supports a central role for NGCs in CVD by studying the expression, regulation and function of neuronal guidance cues (NGCs) in endothelial cells and monocytes, the 2 cells types that play main role in development of atherosclerosis. The findings laid the foundation for future research of NGCs as novel tar- gets for intervention of atherosclerosis. Show less
Nature uses a special class of histone proteins, histone variants, to modulate the properties of chromatin at defined genomic locations. H2A.B is one of the most divergent H2A variants and is... Show moreNature uses a special class of histone proteins, histone variants, to modulate the properties of chromatin at defined genomic locations. H2A.B is one of the most divergent H2A variants and is involved in important cellular functions, such as transcription and mRNA splicing. Incorporation of H2A.B in nucleosomes causes unwrapping of ~15 bp entry/ exit nucleosomal DNA from the histone octamer core. Yet, the molecular basis of such peculiar nucleosome conformation is unclear. The work described in this thesis aimed to determine the impact of H2A.B incorporation on the structural and dynamical properties of the nucleosome, primarily using nuclear magnetic resonance (NMR) spectroscopy. Show less
Plants produce a variety of secondary metabolites. In Catharanthus roseus, several have pharmaceutical applications, including the monomeric alkaloids serpentine and ajmalicine, which are used as a... Show morePlants produce a variety of secondary metabolites. In Catharanthus roseus, several have pharmaceutical applications, including the monomeric alkaloids serpentine and ajmalicine, which are used as a tranquillizer and to reduce hypertension, respectively, and the dimeric alkaloids vincristine and vinblastine, which are potent antitumour drugs. Jasmonic acid (JA) is a key defense hormone, which controls the expression of several alkaloid biosynthesis genes in Catharanthus. The JA-responsive expression is controlled by the AP2-domain transcription factors ORCA2 and ORCA3. The results in this thesis demonstrate that JA-responsive ORCA expression is controlled by an up-stream positive regulator, whose activities are affected by a family of repressors. Understanding the regulation mechanism may help to generate a very valuable tool for engineering the production of valuable secondary metabolites. Show less
