In this thesis, I study 1) metabolic alterations in tuberculosis related to wasting syndrome in human patients as well as in rodent and fish animal models. 2) effects of the mutation of the leptin... Show moreIn this thesis, I study 1) metabolic alterations in tuberculosis related to wasting syndrome in human patients as well as in rodent and fish animal models. 2) effects of the mutation of the leptin gene on cachexia and diabetes in rodent and zebrafish animal models. 3) how tuberculosis infection and resulting metabolic reprogramming are dependent on leptin signaling in mice and zebrafish larvae. Show less
In this thesis, the systemic host metabolic response to experimental Opistorchis felineus infection using Nuclear Magnetic Resonance spectroscopy has been investigated. Overall, the studies... Show moreIn this thesis, the systemic host metabolic response to experimental Opistorchis felineus infection using Nuclear Magnetic Resonance spectroscopy has been investigated. Overall, the studies examined the experimental model of opisthorchiasis, which included male and female animals, mild and severe infections, acute and chronic as well as biofluids and organs. Multi-block data analysis was applied to the model of chronic opisthorchiasis to delineate how infection affects the metabolic profile of infected versus uninfected animals at a detailed level, enhancing our understanding of this neglected disease affecting 56 million worldwide. Show less
Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and... Show moreNeurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms, has led to a greater demand for improved disease understanding, therapies and diagnostic procedures. In this thesis, we use systems biology approaches to construct disease-specific models intended for biomarker discovery, therapeutic treatment strategy identification and drug repurposing in PD. Systems biology is a mathematical field of research that analyses biological systems via construction of a computational model using experimental data. This is achieved by integration of omics data, including genomics, proteomics, transcriptomics and metabolomics. A specific approach used to identify the physico- and biochemical bounds within a biological system is constraint-based modelling, which requires the input of absolute quantitative metabolomics data. To improve our absolute quantitative coverage of the metabolome, we developed and improved new quantitative metabolomics methods using a targeted mass spectrometry workflow to obtain data intended to be integrated into constraint-based metabolic models for the study of PD. Show less
This thesis aimed to provide insight in the etiology, predictors, and outcomes of aggression and antisocial behavior in children and adolescents. The first part of this thesis focused on more... Show moreThis thesis aimed to provide insight in the etiology, predictors, and outcomes of aggression and antisocial behavior in children and adolescents. The first part of this thesis focused on more conventional prediction of outcomes and continuation of aggression and antisocial behavior on the basis of the following constructs: parental psychopathology (Chapter 2), anxiety and depression (Chapter 3), and Oppositional Defiant Disorder symptoms (Chapter 4). Next, the second part of this thesis focused on novel biological markers of aggression, consisting of a review on the genetics of aggression (Chapter 5) and an empirical study on the metabolomics of aggression (Chapter 6). Chapter 7 provides a summary and general discussion of the thesis' contents. Show less
Marine sponges are important members of reef ecosystems, as they play ecological roles that are essential for the health of the reef. From a chemical perspective, sponges have been widely studied,... Show moreMarine sponges are important members of reef ecosystems, as they play ecological roles that are essential for the health of the reef. From a chemical perspective, sponges have been widely studied, showing great chemical diversity with biological activity, although this chemical diversity can often not be linked to for instance variation in environmental conditions experienced by sponges. Metabolomics, with its holistic overview of the metabolites present in samples, has provided new tools to gain insight into the function of metabolites in the intricate relationship between sponges and their environment. Among sponges, giant barrel sponges have stood out for their predominance in many reefs, their longevity and the fact that they are widely spread across oceans. this thesis showed how environmental, genetic and biological factors individually or as a result of their interaction can influence the metabolome of giant barrel sponges. This is only the first step towards a better understanding of the role that chemical compounds play in interactions between sponges and the surrounding environment. The advances in this field will rely, among others, on the development of technologies that would allow real time measurement of the metabolome and the study of the interaction between the metabolome and other omics. Show less
