See also Bernardi F. Better or worse than the original. This issue, pp 1350-2.
Essentials• Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis.• A novel missense mutation (Ala512Val -FV Bonn ) was characterized in vitro and in silico.• FV Bonn is a new cause of APC resistance and venous thrombosis.• FV Bonn expresses additionally enhanced procoagulant activity in the absence of APC.Summary. Background: Activated protein C (APC) resistance is a prevalent risk factor for venous thrombosis. This phenotype is most commonly associated with the factor V Arg506Gln mutation (FV Leiden), which impairs the APC-mediated inactivation of both activated FV (FVa) and activated FVIII (FVIIIa Leiden). The APC-mediated inactivation of FVa Bonn was slower than that of WT FVa (mainly because of delayed cleavage at Arg506), but was greatly stimulated by protein S. The APC cofactor activity of FV Bonn in FVIIIa inactivation was~24% lower than that of WT FV. In line with these findings, an in silico analysis showed that the Ala512Val mutation is located in the same loop as the Arg506 APC cleavage site and might hamper its interaction with APC. Moreover, FV Bonn was more procoagulant than WT FV and FV Leiden in the absence of APC, because of an increased activation rate and, possibly, an enhanced interaction with activated FX. Conclusions: FV Bonn induces hypercoagulability via a combination of increased activation/procoagulant activity, decreased susceptibility to APC-mediated inactivation, and slightly reduced APC cofactor activity.
Capillary electrophoresis-based SELEX (CE-SELEX) is an efficient technique for the isolation of aptamers binding to a wide range of target molecules. CE-SELEX has a number of advantages over conventional SELEX procedures such as the selection of aptamers can be performed on non-immobilized targets, usually within a fewer number of selection cycles. Here we describe a complete procedure of CE-SELEX using activated protein C (APC) as the target protein.
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