Correction to: Rewiring of glucose metabolism defines trained immunity induced by oxidized low-density lipoprotein

The correct name of the 17th Author is presented in this paper. In the paragraph “Metabolic analysis” of the Method section “an XFp Analyzer” should be changed to “an XFe96 Analyzer”.</p

Chiral α-substituted α-hydroxy acids : (stereoselective) synthesis using transition metal and enzyme catalysis

Dit proefschrift handelt over nieuwe syntheseroutes voor enantiomeer zuivere α-gesubstitueerde α-hydroxyzuren. Deze verbindingen zijn belangrijke synthetische intermediairen in de stereoselektieve synthese. Tot dusver zijn optisch aktieve α-gesubstitueerde α-hydroxyzuren gesynthetiseerd gebruik makend van tamelijk bewerkelijke syntheses. De toegang tot deze verbindingen in enantiomeer zuivere vorm is beperkt aangezien een algemene stereoselektieve route niet beschikbaar is. Het doel van het in dit proefschrift beschreven onderzoek is om een algemene katalytische stereoselektieve synthese van α-gesubstitueerde α-hydroxymren te ontwikkelen. Dit kan verder onderzoek naar de synthetische mogelijkheden van deze chirale bouwstenen mogelijk maken.

Inhibition of proinflammatory genes in anti-GBM glomerulonephritis by targeted dexamethasone-loaded Ab(Esel) liposomes

E-selectin-directed targeted drug delivery was analyzed in anti-glomerular basement membrane glomerulonephritis. Liposomes conjugated with anti-E-selectin antibodies (Ab(Esel) liposomes) were internalized by activated endothelial cells in vitro through E-selectin-mediated endocytosis. At the onset of glomerulonephritis in mice, E-selectin was expressed on glomerular endothelial cells, which resulted in homing of Ab(Esel) liposomes to glomeruli after intravenous administration. Accumulation of Ab(Esel) liposomes in the kidney was 3.6 times higher than nontargeted IgG liposomes, whereas the accumulation of both liposomes in the clearance organs liver and spleen and in heart and lungs was comparable. In glomeruli, the Ab(Esel) liposomes colocalized with the endothelial cell marker CD31. Quantitative RT-PCR analysis of laser-microdissected arterioles, glomeruli, and postcapillary venules demonstrated that targeted delivery of dexamethasone by Ab(Esel) liposomes reduced glomerular endothelial expression of P-selectin, E-selectin, and vascular cell adhesion molecule-1 by 60-70%. The expression of these genes was not modulated in endothelial cells in nontargeted renal microvasculatures. Decrease of glomerular endothelial activation at disease onset was followed by reduced albuminuria at day 7. This study demonstrates the potential of vascular bed-specific drug delivery aimed at disease-induced epitopes on the microvascular endothelial cells as a therapeutic strategy for glomerulonephritis

BCG Vaccination Protects against Experimental Viral Infection in Humans through the Induction of Cytokines Associated with Trained Immunity

The tuberculosis vaccine bacillus Calmette-Gue 'rin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, wefound that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional changes indicative of trained immunity. Reduction of viremia was highly correlated with the upregulation of IL-1b, a heterologous cytokine associated with the induction of trained immunity, but not with the specific IFNg response. The importance of IL-1b for the induction of trained immunity was validated through genetic, epigenetic, and immunological studies. In conclusion, BCG induces epigenetic reprogramming in human monocytes in vivo, followed by functional reprogramming and protection against non-related viral infections, with a key role for IL-1b as a mediator of trained immunity responses