The podoplanin-CLEC-2 axis inhibits inflammation in sepsis.

Platelets play a critical role in vascular inflammation through the podoplanin and collagen/fibrin receptors, C-type-lectin-like-2 (CLEC-2) and glycoprotein VI (GPVI), respectively. Both receptors regulate endothelial permeability and prevent peri-vascular bleeding in inflammation. Here we show that platelet-specific deletion of CLEC-2 but not GPVI leads to enhanced systemic inflammation and accelerated organ injury in two mouse models of sepsis-intra-peritoneal lipopolysaccharide and cecal ligation and puncture.

Mouse podoplanin supports adhesion and aggregation of platelets under arterial shear: A novel mechanism of haemostasis.

The podoplanin-CLEC-2 axis is critical in mice for prevention of hemorrhage in the cerebral vasculature during mid-gestation. This raises the question as to how platelets are captured by podoplanin on neuroepithelial cells in a high shear environment. In this study, we demonstrate that mouse platelets form stable aggregates on mouse podoplanin at arterial shear through a CLEC-2 and Src kinase-dependent pathway.

Raising the curtain on the gray region.

The gray region in EPA Document QA/G-4 is defined as the range of possible parameter values near the action level where the cost of determining that the alternative condition is true outweighs the expected consequences of a decision error. The gray region is also described as a range of true parameter values within the alternative condition near the action level where it is "too close to call." EPA Document QA/G-4HW states that during the planning stage the action level is based on an ideal decision rule, while during the assessment stage an operational decision rule is used.

Lipolytic activity of ricin from Ricinus sanguineus and Ricinus communis on neutral lipids.

The present study was carried out with a view of determining ricin lipolytic activity on neutral lipids in emulsion and in a membrane-like model. Using 2,3-dimercapto-1-propanol tributyrate (BAL-TC(4)) as substrate, the lipolytic activity of ricin was found to be proportional to ricin and substrate concentrations, with an apparent K(m) (K(m,app)) of 2.4 mM, a k(cat) of 200 min(-1) and a specific activity of 1.

Ricin RCA60: evidence of its phospholipase activity.

The present work documents, on a qualitative and quantitative basis, the lipolytic activity of ricin protein RCA60 on glycerophospholipids. RCA60 demonstrates a low level of hydrolysis towards radioactive dipalmitoyl-glycerophosphatidylcholine. This observation was confirmed on a better substrate, palmitoyl-oleoyl-glycerophosphatidylcholine, after analysis of the reaction products by thin-layer and gas chromatography.