With the rapidly growing number of extrasolar planets detected, we have firmly stepped into the era of detailed characterization. Diverse types of exoplanets such as gas giants on close-in orbits ... Show moreWith the rapidly growing number of extrasolar planets detected, we have firmly stepped into the era of detailed characterization. Diverse types of exoplanets such as gas giants on close-in orbits (hot Jupiters) and young massive giants on wide orbits (super Jupiters), with no analogs in the Solar System, pose challenges but also opportunities to our understanding of planet formation and evolution. Exoplanet atmospheres with imprints from their history open an important avenue to retrace the origin and evolution of planets. With high-dispersion spectroscopy, we can resolve atomic and molecular spectral features into unique forests of lines that serve as the fingerprints for identifying different species in planetary atmospheres. In this dissertation, I utilize this technique to explore atmospheric compositions, thermal structures, and dynamics of exoplanet atmospheres. I have discovered minor isotopologues in emission spectra of an exoplanet and a brown dwarf for the first time, pioneering the use of carbon isotopic ratios as potential tracers of planet formation. I have investigated the trend of atomic absorption strengths in a sample of ultra-hot Jupiters, which enables disentangling different dynamic regimes of highly-irradiated exoplanets. These works form the foundation to link spectroscopic observations to planet formation and evolution processes. Show less
Acute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from... Show moreAcute cardiovascular clinical events such as myocardial infarction and cerebral stroke represent the major cause of death in Western societies. These pathologies are primarily resulting from atherosclerosis, a progressive condition characterized by the accumulation of lipids, immune cells, and fibrous elements in large arteries. The pathogenesis of atherosclerosis involves complex interactions between a wide variety of cells, including monocytes, macrophages, neutrophils, and lymphocytes. It is essential to identify novel targets for therapeutic application in order to reduce the residual atherosclerotic cardiovascular disease risk in current and future patients. Recent studies have suggested that members of the protein arginine methyltransferase (PRMT) family can potentially serve as novel therapeutic targets for atherosclerosis because of their regulatory role in inflammation and metabolism. To validate the contribution of PRMTs in the progression of atherosclerosis, in the studies presented in this thesis we have investigated the effect of inhibition of PRMT functionality on atherosclerosis susceptibility in established atherosclerotic mouse models.To address the role of PRMTs in atherosclerosis, we therefore made use of specific PRMT inhibitors, i.e. TC-E 5003 for PRMT1 inhibition, TP-064 for PRMT4 inhibition, and GSK3326595 for PRMT5 inhibition, that thus far have primarily been applied in vivo in the context of cancer treatment. Show less
The work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing... Show moreThe work described in this thesis focuses on the development of linear or cyclized peptide probes against protein N-methyltransferases to characterize their specific binding behavior, providing further binding details for inhibitory activity study. The thesis not only describes the extended application to produce peptide-based transition states mimicking PRMT inhibitors but builds an LC-MS/MS method to evaluate CARM1 inhibition and activity. Show less
The work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide... Show moreThe work described in this Thesis is focused on the assembly of oligosaccharide fragments derived from a fungal polysaccharide, galactosaminogalactan (GAG) and fragments of the exopolysaccharide Pel, generated by Pseudomonas aeruginosa. To assemble the corresponding oligosaccharides, synthetic methodologies, enabling the stereoselective construction of the required cis-glycosidic linkages has been developed. These synthetic fragments will be valuable tools to elucidate the biosynthesis of GAG and Pel, and characterize the enzymes involved therein. Show less
Chapter 1 presents a general introduction to the factors involved in crop domestication and the specific role of transcription factors in this process. Chapter 2 describes the functional analysis... Show moreChapter 1 presents a general introduction to the factors involved in crop domestication and the specific role of transcription factors in this process. Chapter 2 describes the functional analysis of a Dof-type transcription factor, named OsDof24, from rice.chapter 3 describes the role of OsDof25 in the regulation of OsC4PPDK. Interactions between OsDof25 and OsC4PPDK were confirmed in experiments involving EMSA, yeast one-hybrid analysis and transient expression in rice protoplasts. The regulatory role of OsDof25 in OsC4PPDK expression was confirmed using OsDof25 misexpression plants. The results suggested that OsDof25 is a trans-activator of the OsC4PPDK gene in rice. Chapter 4 describes the effects of OsDof24 and OsDof25 on the content of rice seeds storage proteins. First the interaction between both OsDof24 and OsDof25 with the GluB-1 promoter was investigated by a set of in vitro and in vivo experiments. Results showed that both OsDof24 and OsDof25 can affect seed storage protein content probably by activating the transcription of the GluB-1 promoter. Finally, in Chapter 5, a general discussion of the results from Chapters 2, 3 and 4 is presented. Show less
This thesis is the collection of four published papers demonstrating annotation of genes and microRNAs with the aid of bioinformatics, in particular using heterogeneous data integration. Gene... Show moreThis thesis is the collection of four published papers demonstrating annotation of genes and microRNAs with the aid of bioinformatics, in particular using heterogeneous data integration. Gene annotation is the process of detecting the structure and biological function of the raw DNA sequences; while microRNA annotation is mainly about identifying its regulatory targets since microRNA modify gene expression by binding to their targets. In order to ef__ciently and accurately annotate microRNAs and coding region of a novel genome, we developed several complex work__ows which integrate the current most relevant data sources and tools. The essence of integration is not to produce even more data but to increase the sensitivity and/or speci__city of the algorithm and system. Currently, in life sciences high-throughput experiments, multiple platforms, and multiple model or non-model species are very commonly applied in different studies. In line with this trend heterogeneous data integration is no doubt an important strategy for the analysis of biological data. Show less
