Loss-of-function fibroblast growth factor receptor-2 mutations in melanoma

We report that 10% of melanoma tumors and cell lines harbor mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. These novel mutations include three truncating mutations and 20 missense mutations occurring at evolutionary conserved residues in FGFR2 as well as among all four FGFRs. The mutation spectrum is characteristic of those induced by UV radiation. Mapping of these mutations onto the known crystal structures of FGFR2 followed by in vitro and in vivo studies show that these mutations result in receptor loss of function through several distinct mechanisms, including loss of ligand binding affinity, impaired receptor dimerization, destabilization of the extracellular domains, and reduced kinase activity. To our knowledge, this is the first demonstration of loss-of-function mutations in a class IV receptor tyrosine kinase in cancer. Taken into account with our recent discovery of activating FGFR2 mutations in endometrial cancer, we suggest that FGFR2 may join the list of genes that play context-dependent opposing roles in cancer.

Dynamics of attacker–defender dyads in Association Football : parameters influencing decision-making

Previous work on pattern-forming dynamics of team sports has investigated sub-phases of basketball and rugby union by focussing on one-versus-one (1v1) attacker-defender dyads. This body of work has identified the role of candidate control parameters, interpersonal distance and relative velocity, in predicting the outcomes of team player interactions. These two control parameters have been described as functioning in a nested relationship where relative velocity between players comes to the fore within a critical range of interpersonal distance. The critical influence of constraints on the intentionality of player behaviour has also been identified through the study of 1v1 attacker-defender dyads. This thesis draws from previous work adopting an ecological dynamics approach, which encompasses both Dynamical Systems Theory and Ecological Psychology concepts, to describe attacker-defender interactions in 1v1 dyads in association football. Twelve male youth association football players (average age 15.3 ± 0.5 yrs) performed as both attackers and defenders in 1v1 dyads in three field positions in an experimental manipulation of the proximity to goal and the role of players. Player and ball motion was tracked using TACTO 8.0 software (Fernandes & Caixinha, 2003) to produce two-dimensional (2D) trajectories of players and the ball on the ground. Significant differences were found for player-to-ball interactions depending on proximity to goal manipulations, indicating how key reference points in the environment such as the location of the goal may act as a constraint that shapes decision-making behaviour. Results also revealed that interpersonal distance and relative velocity alone were insufficient for accurately predicting the outcome of a dyad in association football. Instead, combined values of interpersonal distance, ball-to-defender distance, attacker-to-ball distance, attacker-to-ball relative velocity and relative angles were found to indicate the state of dyad outcomes.