Chromium(III) bound to DNA templates promotes increased polymerase processivity and decreased fidelity during replication in vitro

Carcinogenic chromium [Cr(VI)] compounds are reduced intracellularly to DNA- and protein-reactive chromium(III) species. However, the role of Cr(III) ions in chromium-induced genotoxicity remains unclear. We have investigated the effects of chromium(III) binding on DNA replication and polymerase processivity in vitro. Chromium ions bind slowly and in a dose-dependent manner to DNA. Micromolar concentrations of free chromium inhibit DNA replication, but if the unbound chromium is removed by gel filtration, the rate of DNA replication by polymerase I (Klenow fragment) on the chromium-bound template is increased greater than 6-fold relative to the control. This increase is paralleled by as much as a 4-fold increase in processivity and a 2-fold decrease in replication fidelity. These effects are optimum when very low concentrations of chromium ions are bound to the DNA [3-4 Cr(III) ions per 1000 nucleotide phosphates]. Increased concentrations of chromium lead to the production of DNA-DNA cross-links and inhibition of polymerase activity. These results suggest that low levels of DNA-bound chromium(III) ions may contribute to chromium mutagenesis and carcinogenesis by altering the kinetics and fidelity of DNA replication.     

Survey and management of mussel Mytilus species in Scotland

The important ecological role of Mytilus mussels in marine ecosystems, their high abundance in coastal waters and the demand for human consumption has made them a target species for aquaculture. Mussel cultivation is the most important and rapidly growing sector of the Scottish shellfish aquaculture industry and until recently production was considered to be based exclusively on the native species Mytilus edulis. However, the sympatric occurrence of M. edulis, M. trossulus, M. galloprovincialis and their hybrids in cultivation has recently been reported and significant production losses (over 50% at some sites) have been attributed to the presence of fragile-shelled M. trossulus. Given the ecological and economical importance of these species, an urgent need arose for a wider understanding of Mytilus species distribution on Scottish coasts and its implication for the sustainability of the Scottish shellfish industry. Here we present a summary of a 3-year project established within the “ECOsystem approach to SUstainable Management of the Marine Environment and its living Resources” (ECOSUMMER) Marie Curie network to address this need. We developed DNA-based molecular assays for the detection and surveillance of the different Mytilus species in Scotland. Several potential management strategies have been explored, aimed at favouring M. edulis production at mixed-species sites, but these have so far not been found to provide the reliable efficacy necessary for adoption by the industry. Complete eradication of M. trossulus from economically affected areas in Scotland may be unrealistic, especially considering that its introduction and distribution mechanisms in the environment remain uncertain. Area-specific solutions to managing the problem may thus be required, which may or may not involve eradication and fallowing (clearance of mussels from production sites for a given period of time). Nevertheless, the current distribution of M. trossulus is limited and its spread outside its existing range is clearly undesirable. Any management solutions must also be accompanied by an industry wide strategy and awareness, for example, through the development of an industry supported code of good practice.     

A climate-based distribution model of malaria transmission in sub-Saharan Africa.

Malaria remains the single largest threat to child survival in sub-Saharan Africa and warrants long-term investment for control. Previous malaria distribution maps have been vague and arbitrary. Marlies Craig, Bob Snow and David le Sueur here describe a simple numerical approach to defining distribution of malaria transmission, based upon biological constraints of climate on parasite and vector development. The model compared well with contemporary field data and historical 'expert opinion' maps, excepting small-scale ecological anomalies. The model provides a numerical basis for further refinement and prediction of the impact of climate change on transmission. Together with population, morbidity and mortality data, the model provides a fundamental tool for strategic control of malaria.