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00029?aw-units respectively. This underlines the fact that water-activity determinations to one decimal place (equivalent, in this example, to ??29��C) can lack biological meaning, and those made to two decimal INCB018424 clinical trial places (equivalent to an accuracy level of up to 2.9��C) are far less accurate than we would accept for biological studies of temperature or other environmental parameters. Based on our current knowledge, the water-activity and temperature windows for microbes collectively span 0.400?aw-units and 140��C respectively (Fig.?1). In the context of stress biology, and at the scale of the biosphere, the expression of water activity to one decimal place leads to an unacceptable level of accuracy, as 0.100?aw-units equates to a temperature difference of 35��C.17 Even water-activity determinations to three decimal places (equivalent to an accuracy level of ??0.3��C) are imposed by technological limitations rather than being dictated by the sensitivity of the cell. It remains unclear whether microorganisms are capable of subsistence without an extracellular supply of liquid water, and the biological availability of water in aqueous films of varying thickness (and at various temperatures) has also yet to be quantified. Cells may be able to acquire and retain water (de Goffau et?al., 2011) which can be utilized when water activity falls below biologically permissive levels (for instance, see the studies of powdery mildew cited above) but there is no definitive evidence that this does indeed occur (and, if so, what mechanisms are involved) at present (J. D. Rummel, D. W. Beaty, M. A. Jones, C. Bakermans, N. G. Barlow, P. Boston, V. Chevrier, B. Clark, J.-P. de Vera, R. V. Gough, AZ191 PF-02341066 in vitro J. E. Hallsworth, J. W. Head, V. J. Hipkin, T. L. Kieft, A. S. McEwen, M. T. Mellon, J. Mikucki, W. L. Nicholson, C. R. Omelon, R. Peterson, E. Roden, B. Sherwood Lollar, K. L. Tanaka, D. Viola and J. J. Wray, unpublished). Culture-independent studies are needed for high-solute, and other low water-activity, habitats to establish whether metabolic activity remains once water activity is below the threshold for cell division (0.605?aw) and, if so, whether this is commonplace at different locations within the microbial biosphere. In contrast with the increasing understanding of molecular-level adaptations in many other forms of extremophile, there is a paucity of information in relation to physiological, biochemical and genetic mechanisms which facilitate halophile/xerophile function at