ACAP-A/B Are ArfGAP Homologs in Dictyostelium Involved in Sporulation but Not in Chemotaxis

Arfs and Arf GTPase-activating proteins (ArfGAPs) are regulators of membrane trafficking and actin dynamics in mammalian cells. In this study, we identified a primordial Arf, ArfA, and two ArfGAPs (ACAP-A/B) containing BAR, PH, ArfGAP and Ankyrin repeat domains in the eukaryote Dictyostelium discoideum. In vitro, ArfA has similar nucleotide binding properties as mammalian Arfs and, with GTP bound, is a substrate for ACAP-A and B. We also investigated the physiological functions of ACAP-A/B by characterizing cells lacking both ACAP-A and B. Although ACAP-A/B knockout cells showed no defects in cell growth, migration or chemotaxis, they exhibited abnormal actin protrusions and ∼50% reduction in spore yield. We conclude that while ACAP-A/B have a conserved biochemical mechanism and effect on actin organization, their role in migration is not conserved. The absence of an effect on Dictyostelium migration may be due to a specific requirement for ACAPs in mesenchymal migration, which is observed in epithelial cancer cells where most studies of mammalian ArfGAPs were performed

A precautionary public health protection strategy for the possible risk of childhood leukaemia from exposure to power frequency magnetic fields

<p>Abstract</p> <p>Background</p> <p>Epidemiological evidence showing a consistent association between the risk of childhood leukaemia and exposure to power frequency magnetic fields has been accumulating. This debate considers the additional precautionary intervention needed to manage this risk, when it exceeds the protection afforded by the exposure guidelines as recommended by the International Commission on Non-Ionizing Radiation Protection.</p> <p>Methods</p> <p>The Bradford-Hill Criteria are guidelines for evaluating the scientific evidence that low frequency magnetic fields cause childhood leukaemia. The criteria are used for assessing the strength of scientific evidence and here have been applied to considering the strength of evidence that exposures to extremely low frequency magnetic fields may increase the risk of childhood leukaemia. The applicability of precaution is considered using the risk management framework outlined in a European Commission (EC) communication on the Precautionary Principle. That communication advises that measures should be proportionate, non-discriminatory, consistent with similar measures already taken, based on an examination of the benefits and costs of action and inaction, and subject to review in the light of new scientific findings.</p> <p>Results</p> <p>The main evidence for a risk is an epidemiological association observed in several studies and meta-analyses; however, the number of highly exposed children is small and the association could be due to a combination of selection bias, confounding and chance. Corroborating experimental evidence is limited insofar as there is no clear indication of harm at the field levels implicated; however, the aetiology of childhood leukaemia is poorly understood. Taking a precautionary approach suggests that low-cost intervention to reduce exposure is appropriate. This assumes that if the risk is real, its impact is likely to be small. It also recognises the consequential cost of any major intervention. The recommendation is controversial in that other interpretations of the data are possible, and low-cost intervention may not fully alleviate the risk.</p> <p>Conclusions</p> <p>The debate shows how the EC risk management framework can be used to apply the Precautionary Principle to small and uncertain public health risks. However, despite the need for evidence-based policy making, many of the decisions remain value driven and therefore subjective.</p