Biological processes underlying cerebral small vessel disease (cSVD) are largely unknown. We hypothesized that identification of clusters of inter-related bood-based biomarkers that are associated... Show moreBiological processes underlying cerebral small vessel disease (cSVD) are largely unknown. We hypothesized that identification of clusters of inter-related bood-based biomarkers that are associated with the burden of cSVD provides leads on underlying biological processes. In 494 participants (mean age 67.6 +/- 8.7 years; 36% female; 75% cardiovascular diseases; 25% reference participants) we assessed the relation between 92 blood-based biomarkers from the OLINK cardiovascular III panel and cSVD, using cluster-based analyses. We focused particularly on white matter hyperintensities (WMH). Nineteen biomarkers individually correlated with WMH ratio (r range: 0.16-0.27, Bonferroni corrected p-values <0.05), of which sixteen biomarkers formed one biomarker cluster. Pathway analysis showed that this biomarker cluster predominantly reflected coagulation processes. This cluster related also significantly to other cSVD manifestations (lacunar infarcts, microbleeds, and enlarged perivascular spaces), which supports generalizability beyond WMHs. To study possible causal effects of biological processes reflected by the cluster we performed a mediation analysis that showed a mediation effect of the cluster on the relation between age and WMH ratio (proportion mediated 17%), and hypertension and WMH-volume (proportion mediated 21%). In conclusion, we identified a cluster of blood-based biomarkers reflecting coagulation, that is related to manifestations of cSVD, corroborating involvement of coagulation abnormalities in the etiology of cSVD. Show less
The main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy. With the development of paraNMR and DEER experiments,... Show moreThe main subject of this thesis is the design and synthesis of paramagnetic molecules for protein studies with NMR and EPR spectroscopy. With the development of paraNMR and DEER experiments, synthetic paramagnetic centers are becoming popular. About half of the current paramagnetic probes were described in the past five years, reflecting this popularity. Several of them improved the stability and rigidity of the probes, mainly by introducing novel attachment groups forming thioether and triazole linkers.1–3 Such linkages help to extend the application of the probes to in-cell measurements.4,5 Some small probes were designed for 3d-block metal ions as well, but these probes show low metal ion binding affinity.6,7 The research described in this thesis contributed to the development of paramagnetic probes. Hereafter, the properties of these new probes are discussed, and some general conclusions and prospects are given. Show less
Ruhaak, L.R.; Laarse, A. van der; Cobbaert, C.M. 2019
