The PID-directed shift in PIN polarity has been broadly accepted as one of the essential mechanisms for the regulation of auxin transport polarity. We verified that both PID functionality and its... Show moreThe PID-directed shift in PIN polarity has been broadly accepted as one of the essential mechanisms for the regulation of auxin transport polarity. We verified that both PID functionality and its subcellular localization do not depend on PDK1 function. However, by detailed analysis on these phenotypes and the expression of the auxin response reporter, we found the pdk1 pdk2 double mutant to be impaired in auxin transport in vascular tissues. Together with other mutant phenotypes, we suspect that PDK1 may be the master regulator of AGC1 kinases. The pdk1 pdk2 short root phenotype caused by phloem differentiation defects phenocopied the pax mutant. Complementation results of wild type and phosphomimic PAX in the pdk1 pdk2 background suggest that PDK1-dependent PAX phosphorylation and activation are essential for its full biological function. We also explain the molecular basis of PDK1 basal localization and the unnecessity of this polarity for vascular development. In addition, we investigated downstream action after PID phosphorylation. Several conserved tyrosine residues close to serine phosphorylation sites in the PIN1 and PIN2 HLs are mutated. Two of these tyrosines redundantly affected PIN polarity. However, PID mediated phosphorylation and tyrosine-based PIN trafficking are independent processes. Show less
This thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature. By using... Show moreThis thesis systematically analyzes the physical-chemistry of lipid-graphene interactions with the major objective of reconciliating the variety of results reported in the literature. By using five major characterization techniques typically used to study lipids, namely IR spectroscopy, ellipsometry, AFM, neutron reflectivity and QCM-D, this thesis characterizes – in details – layered structures of graphene and lipids (so called superstructures) and separately studies the dynamics of the interaction between lipids and graphene. The most remarkable result is that through the systematic construction of i) a lipid monolayer on a silicon substrate; ii) the subsequent coating with graphene and iii) the deposition of a last lipid monolayer on top of the two layers stack; graphene could be encapsulated in the hydrophobic core of a lipid bilayer for the first time, promising a range of applications to sense biological processes occurring near or inside a lipid bilayer. Show less
This thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis... Show moreThis thesis examines how both genetic and more conventional epidemiological endeavors may complement research into effects of statin therapy. These include a pharmacogenetic GWAS meta-analysis on statin-induced HDL-C response by the Genomic Investigation of consortium, which identified CETP as a loci of interest, and two-sample Mendelian randomization studies utilizing summary level data from the GIST and other GWAS consortia on fasted blood lipids and type 2 diabetes. We additionally examine the issue of survival bias in Mendelian randomization studies. Finally, we show that intra-individual lipid variability associates with worse neurocognitive outcomes in older individuals at high risk for vascular disease, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. Show less
