Green Exercise in the UK Countryside: Effects on Health and Psychological Well-being and Implications for Policy and Planning

There is evidence that contact with the natural environment and green space promotes good health. It is also well known that participation in regular physical activity generates physical and psychological health benefits. The authors have hypothesised that ‘green exercise’ will improve health and psychological well-being, yet few studies have quantified these effects. This study measured the effects of 10 green exercise case studies (including walking, cycling, horse-riding, fishing, canal-boating and conservation activities) in four regions of the UK on 263 participants. Even though these participants were generally an active and healthy group, it was found that green exercise led to a significant improvement in self-esteem and total mood disturbance (with anger-hostility, confusion-bewilderment, depression-dejection and tension-anxiety all improving post-activity). Self-esteem and mood were found not to be affected by the type, intensity or duration of the green exercise, as the results were similar for all 10 case studies. Thus all these activities generated mental health benefits, indicating the potential for a wider health and well-being dividend from green exercise. Green exercise thus has important implications for public and environmental health, and for a wide range of policy sectors.

Mastering the canonical loop of serine protease inhibitors : enhancing potency by optimising the internal hydrogen bond network

Background Canonical serine protease inhibitors commonly bind to their targets through a rigid loop stabilised by an internal hydrogen bond network and disulfide bond(s). The smallest of these is sunflower trypsin inhibitor (SFTI-1), a potent and broad-range protease inhibitor. Recently, we re-engineered the contact β-sheet of SFTI-1 to produce a selective inhibitor of kallikrein-related peptidase 4 (KLK4), a protease associated with prostate cancer progression. However, modifications in the binding loop to achieve specificity may compromise structural rigidity and prevent re-engineered inhibitors from reaching optimal binding affinity. Methodology/Principal Findings In this study, the effect of amino acid substitutions on the internal hydrogen bonding network of SFTI were investigated using an in silico screen of inhibitor variants in complex with KLK4 or trypsin. Substitutions favouring internal hydrogen bond formation directly correlated with increased potency of inhibition in vitro. This produced a second generation inhibitor (SFTI-FCQR Asn14) which displayed both a 125-fold increased capacity to inhibit KLK4 (Ki = 0.0386±0.0060 nM) and enhanced selectivity over off-target serine proteases. Further, SFTI-FCQR Asn14 was stable in cell culture and bioavailable in mice when administered by intraperitoneal perfusion. Conclusion/Significance These findings highlight the importance of conserving structural rigidity of the binding loop in addition to optimising protease/inhibitor contacts when re-engineering canonical serine protease inhibitors.