Functional variation in the arginine vasopressin 2 receptor as a modifier of human plasma von Willebrand factor levels\ud

Objectives: Stimulation of arginine vasopressin 2 receptor (V2R) with arginine vasopressin (AVP) results in a rise in von Willebrand factor (VWF) and factor VIII plasma levels. We hypothesized that gain-of-function variations in the V2R gene (AVPR2) would lead to higher plasma levels of VWF and FVIII. Methods and Results: We genotyped the control populations of two population-based studies for four AVPR2 variations: a-245c, G12E, L309L, and S331S. Rare alleles of a-245c, G12E, and S331S, which were in linkage disequilibrium, were associated with higher VWF propeptide, VWF and FVIII levels. The functionality of the G12E variant was studied in stably transfected MDCKII cells, expressing constructs of either 12G-V2R or 12E-V2R. Both V2R variants were fully glycosylated and expressed on the basolateral membrane. The binding affinity of V2R for AVP was increased three-fold in 12E-V2R–green fluorescent protein (GFP) cells, which is in accordance with increased levels of VWF propeptide associated with the 12E variant. The dissociation constant (KD) was 4.5 nm [95% confidence interval (CI) 3.6–5.4] for 12E-V2R–GFP and 16.5 nm (95% CI 10.1–22.9) for 12G-V2R–GFP. AVP-induced cAMP generation was enhanced in 12E-V2R–GFP cells. Conclusions: The 12E-V2R variant has increased binding affinity for AVP, resulting in increased signal transduction, and is associated with increased levels of VWF propeptide, VWF, and FVII

De rol van Collimonas sp. 343 in de onderdrukking van Rhizotonia solani AG2 onder nutriëntenlimitering in de bodem

Onder bepaalde omstandigheden, zoals behandelingen met verschillende soorten organische stof, zijn bodems weerbaarder tegen Rhizoctonia solani. De vraag is wat het mechanisme achter deze verhoogde weerbaarheid is en de hypothese van de onderzoekers is dat de levende fractie van de bodem hier voor verantwoordelijk is