Breast cancer has a high mortality in women worldwide. Tumor cells experience hypoxia, which is accompanied by alterations in cell metabolism and can drive metastasis by triggering an epithelial... Show moreBreast cancer has a high mortality in women worldwide. Tumor cells experience hypoxia, which is accompanied by alterations in cell metabolism and can drive metastasis by triggering an epithelial–mesenchymal transition (EMT) in the tumor cells. Yes-associated protein (YAP) and a transcriptional co-activator with PDZ-binding (TAZ) are two transcriptional co-activators involved in growth, metabolism, and metastasis in cancer. Breast cancer can be divided into different subtypes. One criterium underlying such subtypes is based on the levels of Human Epidermal growth factor Receptor 2 (HER-2), Estrogen Receptor (ER) and Progesterone Receptor (PR). The subtypes include luminal-like (luminal A and luminal B), HER-2 enriched and basal-like (often “triple negative”). Triple negative breast cancer (TNBC) has a lower survival rate due to the lack of therapeutic targets. Fundamental research exploring the molecular mechanisms at work in cancer cells and their response to a hypoxic environment may contribute to insights for future clinical treatment. This thesis focused on profiling breast cancer cells belonging to distinct subtypes under acute and chronic hypoxia, investigating the crosstalk between hypoxia regulated pathways and YAP/TAZ signaling in luminal breast cancer versus TNBC cells, and identification of the potential targets of TAZ in breast cancer cells. Show less
Anthropogenic noise negatively affects wildlife in a wide range of taxonomic groups. Especially for birds, a substantial number of observational studies have now shown negative associations between... Show moreAnthropogenic noise negatively affects wildlife in a wide range of taxonomic groups. Especially for birds, a substantial number of observational studies have now shown negative associations between noise pollution and abundance and diversity along roadsides. Researchers investigating birds’ behavioural responses to high level noise to date have mostly focused on the immediate adjustment of vocal signalling behaviour. However, there is more than one mechanism by which birds might cope with increasing noise levels. They may show immediate behavioural reactions, such as spatial avoidance and/or vocal adjustment, but also more ontogenetic adjustments with long-term consequences like changes in sensory and personality traits. To test these potential effects of traffic noise on birds, I conducted a series of experiments using zebra finches. I have demonstrated that traffic noise per se can contribute to spatial avoidance in birds and cause variation in parental behaviour, and that there can be changes in noise avoidance behaviour in the course of a lifetime. These results provide new insights into the potential impacts of noise on birds. Show less
This Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.The limitations of the contemporary methods of chemical ADP-ribosylation and a... Show moreThis Thesis focuses on the design and synthesis of ADP-ribosylated compounds that can be applied in biological studies.The limitations of the contemporary methods of chemical ADP-ribosylation and a relative scarcity of the well-defined synthetic ADP-ribosylated derivative was an incentive to undertake synthetic studies to further advance the methodologies in the bioorganic chemistry of ADP-ribosylated molecules. This Thesis aims specifically at the developing of new and improved synthetic methodologies and to synthesize advanced mono- or oligo-ADP-ribosylated biomolecules. The target compounds that are described in this Thesis are not only represent a synthetic challenge but also have great value in biology for a better understanding of ADP-ribosylation. Show less
