The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical insight into in vivo H2O2 and GPx concentrations

Although its concentration is generally not known, glutathione peroxidase-1 (GPx-1) is a key enzyme in the removal of hydrogen peroxide (H2O2) in biological systems. Extrapolating from kinetic results obtained in vitro using dilute, homogenous buffered solutions, it is generally accepted that the rate of elimination of H2O2 in vivo by GPx is independent of glutathione concentration (GSH). To examine this doctrine, a mathematical analysis of a kinetic model for the removal of H2O2 by GPx was undertaken to determine how the reaction species (H2O2, GSH, and GPx-1) influence the rate of removal of H2O2. Using both the traditional kinetic rate law approximation (classical model) and the generalized kinetic expression, the results show that the rate of removal of H2O2 increases with initial GPxr, as expected, but is a function of both GPxr and GSH when the initial GPxr is less than H2O2. This simulation is supported by the biological observations of Li et al.. Using genetically altered human glioma cells in in vitro cell culture and in an in vivo tumour model, they inferred that the rate of removal of H2O2 was a direct function of GPx activity × GSH (effective GPx activity). The predicted cellular average GPxr and H2O2 for their study are approximately GPxr ≤ 1 μm and H2O2 ≈ 5 μm based on available rate constants and an estimation of GSH. It was also found that results from the accepted kinetic rate law approximation significantly deviated from those obtained from the more generalized model in many cases that may be of physiological importance

The ‘Exposed’ Population, Violent Crime in Public Space and the Night-time Economy in Manchester, United Kingdom

The daily rhythms of the city, the ebb and flow of people undertaking routines activities, inform the spatial and temporal patterning of crime. Being able to capture citizen mobility and delineate a crime-specific population denominator is a vital prerequisite of the endeavour to both explain and address crime. This paper introduces the concept of an exposed population-at-risk, defined as the mix of residents and non-residents who may play an active role as an offender, victim or guardian in a specific crime type, present in a spatial unit at a given time. This definition is deployed to determine the exposed population-at-risk for violent crime, associated with the night-time economy, in public spaces. Through integrating census data with mobile phone data and utilising fine-grained temporal and spatial violent crime data, the paper demonstrates the value of deploying an exposed (over an ambient) population-at-risk denominator to determine violent crime in public space hotspots on Saturday nights in Greater Manchester (UK). In doing so, the paper illuminates that as violent crime in public space rises, over the course of a Saturday evening, the exposed population-at-risk falls, implying a shifting propensity of the exposed population-at-risk to perform active roles as offenders, victims and/or guardians. The paper concludes with a discussion of the theoretical and policy relevance of these findings