Experimental validation of computerised models of clustering of platelet glycoprotein receptors that signal via tandem SH2 domain proteins.

The clustering of platelet glycoprotein receptors with cytosolic YxxL and YxxM motifs, including GPVI, CLEC-2 and PEAR1, triggers activation via phosphorylation of the conserved tyrosine residues and recruitment of the tandem SH2 (Src homology 2) domain effector proteins, Syk and PI 3-kinase. We have modelled the clustering of these receptors with monovalent, divalent and tetravalent soluble ligands and with transmembrane ligands based on the law of mass action using ordinary differential equations and agent-based modelling. The models were experimentally evaluated in platelets and transfected cell lines using monovalent and multivalent ligands, including novel nanobody-based divalent and tetravalent ligands, by fluorescence correlation spectroscopy. Ligand valency, receptor number, receptor dimerisation, receptor phosphorylation and a cytosolic tandem SH2 domain protein act in synergy to drive receptor clustering. Threshold concentrations of a CLEC-2-blocking antibody and Syk inhibitor act in synergy to block platelet aggregation. This offers a strategy for countering the effect of avidity of multivalent ligands and in limiting off-target effects.

The Effect of Ankle Brace Use on a 3-Step Volleyball Spike Jump Height.

PURPOSE: The purpose of this study was to determine whether ankle brace use in university-level varsity volleyball athletes affected their 3-step spike jump height and whether certain types of ankle braces have a greater effect on jump height. METHODS: Nine male university-level varsity volleyball athletes participated in a repeated-measures design study in which each athlete performed three 3-step volleyball spike jumps in 3 ankle brace conditions (soft, rigid, and no brace). Vertical jump height was measured by the Vertec device and video motion analysis at a university biomechanics research laboratory. RESULTS: Vertical jump heights were significantly lower in both brace conditions (soft, 2.3 cm, standard deviation [SD] 1.2 cm, P < .001; rigid, 1.7 cm, SD 0.9 cm, P < .003) compared with the no-brace condition, and no differences in vertical jump height were observed between the brace conditions (0.6 cm, SD 0.3, P = .3). There was a negative correlation between body fat percentage and vertical jump height (r = -0.075, P = .02). The Vertec device reliably measured vertical jump in all 3 conditions. The no-brace vertical ground reaction forces during the loading phase were significantly greater than brace conditions. Ankle range of motion was greatest in the no-brace condition. CONCLUSIONS: Results from this study suggests that high-performance athletes wearing ankle braces experience a significant decrease in vertical jump height independent of the type of ankle brace worn. CLINICAL RELEVANCE: Sports physicians and health care providers caring for high-level athletes should counsel athletes on the trade-offs of wearing protective equipment in sport, as potential decreases in sports performance can lead to increased injury prevention. LEVEL OF EVIDENCE: III.