NEWS & VIEWS RESEARCH (in which ensembles of molecules are heated by irradiation with a laser) for very small barriers and, more recently, by single-molecule measurements5,9. What has remained a daunting challenge, however, is quantifying the key ingredients for a Kramers-like description of protein-folding reactions, especially the role of internal friction and how it changes as folding proceeds. Earlier work has shown that internal friction can be a critical factor in folding kinetics10,11; that it can be highly localized to specific regions of the free-energy surface12; and that its contribution tends to increase as unfolded proteins become more compact13. Now, Chung and Eaton have investigated the nature of the barrier for the folding of individual molecules directly. The authors measured the transition-path times for a protein (called α3D) as a function of temperature and solvent viscosity to reveal characteristic signatures of both the solvent and internal friction. The presence of a multitude of simultaneous inter- and intramolecular interactions that slow down barrier crossing might explain why Kramers’ theory applies in this case. By contrast, for some reactions of small molecules, barrier crossing can be so rapid that the solvent cannot keep up, and the simple theory fails3. Chung and Eaton’s results allowed them to estimate the height of the barrier directly — a difficult task in general, because of the large entropic contributions to the folding process, but a fundamental one, because the barrier height is a key determinant of kinetics. To model the shape of the free-energy surface, the authors took advantage of improvements in computational methods that allow simulations of protein folding in atomic detail14 and that agree remarkably well with experimental folding rates and transition-path times. Two goals, however, have yet to be achieved: resolving the sequence of events that occur on the top of the barrier directly from single-molecule experiments, rather than from simulations; and understanding the molecular origin of internal friction. It is still unclear whether internal friction is dominated by steric hindrance (clashes of chemical groups) during rotations about the bonds in the polypeptide chain, by the transient formation of intramolecular hydrogen bonds or of clusters of hydrophobic groups, or by other short-lived interactions that must be broken to allow correct folding to proceed 10,12. However, the convergence of results from sophisticated experiments such as those reported by Chung and Eaton and results from simulations is a promising development, because it will increase our understanding of the detailed mechanisms of biological dynamics at the molecular scale. That will allow us to identify the requirements for applying Kramers’ theory, which is widely used for describing dynamic processes in physics and chemistry3. ■

Benjamin Schuler is in the Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland. Jane Clarke is a Wellcome Trust Senior Research Fellow in the Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK. e-mails: [email protected]; [email protected] 1. Chung, H. S. & Eaton, W. A. Nature 502, 685–688 (2013). 2. Kramers, H. A. Physica 7, 284–304 (1940). 3. Hänggi, P., Talkner, P. & Borkovec, M. Rev. Mod. Phys. 62, 251–341 (1990). 4. Bryngelson, J. D. & Wolynes, P. G. J. Phys. Chem. 93, 6902–6915 (1989). 5. Chung, H. S., McHale, K., Louis, J. M. & Eaton, W. A.

Science 335, 981–984 (2012). 6. Gopich, I. V. & Szabo, A. J. Phys. Chem. B 113, 10965–10973 (2009). 7. Matouschek, A., Kellis, J. T. Jr, Serrano, L. & Fersht, A. R. Nature 340, 122–126 (1989). 8. Yang, W. Y. & Gruebele, M. Nature 423, 193–197 (2003). 9. Yu, H. et al. Proc. Natl Acad. Sci. USA 109, 14452–14457 (2012). 10. Wensley, B. G. et al. Nature 463, 685–688 (2010). 11. Hagen, S. J. Curr. Protein Peptide Sci. 11, 385–395 (2010). 12. Borgia, A. et al. Nature Commun. 3, 1195 (2012). 13. Soranno, A. et al. Proc. Natl Acad. Sci. USA 109, 17800–17806 (2012). 14. Lindorff-Larsen, K., Piana, S., Dror, R. O. & Shaw, D. E. Science 334, 517–520 (2011).

WATER M A N AG E M E NT

The data gap A comprehensive search identifies a global dearth of data on the generation, treatment and use of wastewater. Remedying this situation will help policy-makers to better legislate for the management of this precious resource. BLANCA JIMÉNEZ CISNEROS

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n interesting but worrying analysis of the situation of wastewater assessment around the world is presented by Sato et al.1 in Agricultural Water Management. In a thorough review of different sources of information, including scientific literature and government reports, from a spectrum of countries representing different regions and socio-economic conditions, the authors reveal that data on the generation, treatment and use of wastewater around the world are scarce and poorly reported. Of the 181 countries assessed in the study, Sato and colleagues found that data were available on all three aspects of wastewater for only 55, and that no information at all was available from 57 countries. Only 37% of the available data were reported in the period 2008–12. Although many water-management experts are already well aware of this state of affairs, the authors’ findings demonstrate to a broader audience how policy-makers around the world have, to a large extent, failed to implement policies to gather data on wastewater. This is disappointing, because such information is crucial to making informed decisions on several issues, including pollution management and how the use of wastewater could contribute to addressing water-scarcity issues and the potential threats of climate change in some regions. Water, in contrast to many other natural resources, is renewable, but in an era in which the recycling of solid waste and used materials is strongly promoted in greener societies, the lack of discussion about wastewater generation,

and especially its reuse, is remarkable. It is worth considering some possible ‘invisible’ explanations for the lack of data. One is an inherent rejection of wastewater, owing to its association with water-borne diseases. Another is that, unlike the clean water that users have to pay for, wastewater may be considered to be without value, meaning that there is little interest in measuring what happens to it. But in a world in which the demand for this finite resource is increasing, wastewater — or used water, as I prefer to call it — should also be given a value and be measured. This is starting to happen The use of in parts of the world untreated where water is scarce wastewater for and farmers, for agriculture is a example, must pay public-health for wastewater. concern. Indeed, although many policy-makers have yet to adequately consider the potential of used water, the opposite is true of many farmers (Fig. 1). Both treated and untreated wastewater is already used for irrigation in many regions, and this form of water reuse is increasing, although Sato and colleagues’ study fails to catch this trend because it is based on data not older than 2000. By reusing water instead of relying on rain-fed irrigation, farmers may be able to sow three or four crops per year, rather than only one or two. Used water also contains nutrients, such as nitrogen, phosphorus and organic matter, that enrich the soil and increase crop yields. In fact, the presence of such usable compounds in wastewater may prove to be a motive for

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wastewater for agriculture is a public-health concern: wastewater can function as a vector for diarrhoeal diseases when polluted water is ingested with crops that are consumed raw. Although irrigation is a primary focus of water-reuse issues, wastewater-management considerations should not be confined to agricultural areas. Cities may make up tiny areas of our planet, but they demand large quantities of water and food, and produce a vast amount of used water. Much of this water — and the nutrients it contains — could be reclaimed to help to produce food for urban dwellers. Methods to treat water are becoming available that cost less than conventional methods and also provide the ability to recycle nutrients4. Thus, researchers are developing the means to establish site-specific and cost-effective approaches to water reuse, but the data gap must be closed before such policies can be effectively designed. ■

Figure 1 | Renewable resource.  Wastewater is increasingly being used for irrigation purposes, but a lack of data on wastewater generation, treatment and use1 is hampering the development of policies regarding this resource.

Blanca Jiménez Cisneros is in the Division of Water Sciences, International Hydrological Programme, UNESCO, 75732 Paris Cedex 15, France. e-mail: [email protected]

enhancing water-reuse practices. Natural reserves of phosphorus are rapidly declining, and the phosphorus industry has recently called for action to save and recycle this fertilizer2. Another advantage of the reuse of water for irrigation is that it contributes to the recharging of aquifers, and thereby becomes a new source of usable water. Thus, the attractions of using wastewater,

1. Sato, T., Qadir, M., Yamamoto, S., Endo, T. & Zahoor, A. Agric. Water Mgmt 130, 1–13 (2013). 2. Cordell, D., Drangert, J.-O. & White, S. Glob. Environ. Change 19, 292–305 (2009). 3. Jiménez, B. & Asano, T. (eds) in Water Reuse: An International Survey of Current Practice, Issues and Needs 3–26 (IWA, 2008). 4. Jiménez, B., Mara, D., Carr, R. & Brissaud, F. in Wastewater Irrigation and Health: Assessing and Mitigating Risk in Low-income Countries (eds Dreschel, P. et al.) 149–170 (Earthscan, 2010).

particularly for farmers in low-income regions, are obvious. But in many cases water is being reused without proper policies and practices. Sato et al. find that high-income countries, on average, treat 70% of their wastewater, but this figure drops to 8% in low-income countries, and the reuse of untreated wastewater has been estimated3 to be about 5–8 times greater than that of treated used water. The use of untreated

MARINE B IO LO GY

Coral animals combat stress with sulphur Photosynthetic algal symbionts of corals produce sulphur substances that are involved in the regulation of ocean temperatures. In a twist to the tale, it emerges that coral animals produce the same compounds. See Letter p.677 GRAHAM JONES

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oral reefs owe their success to a symbiosis between the animal host (the coral polyp) and intracellular photosynthetic dinoflagellate algae of the genus Symbiodinium, which supply up to 95% of the host’s energy requirements. Symbiodinium produce abundant amounts of the sulphur compound dimethylsulphoniopropionate (DMSP) and the volatile trace sulphur gas dimethylsulphide (DMS)1–3 — substances that have been proposed4 to be involved in a climate-feedback

cycle. On page 677 of this issue, Raina et al.5 use chemical, genomic and molecular approaches to reveal that coral polyps also produce DMSP, in the absence of their algal symbionts. This biosynthesis may help the corals to survive conditions of thermal stress, and it adds the coral polyp as a possible player in climate regulation in areas rich in reefs*. Reef-building corals, such as Acropora species, are prolific producers of DMSP and DMS. DMS is also formed during the breakdown of *This article and the paper under discussion5 were published online on 23 October 2013.

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DMSP by plankton and other marine microorganisms. Raina et al. studied the larvae of Acropora corals, which lack algal symbionts when first spawned. Keeping the larvae in alga-free conditions, the researchers found that the DMSP content of the corals increased by up to 54% over time as the larvae settled and matured, suggesting that the juvenile corals were producing it themselves. The authors then dug deep into the genomes of Acropora millepora and Acropora digitifera, looking for evolutionary evidence of DMSP synthesis. They found that two genes encoding enzymes known to be involved in DMSP synthesis in diatoms — NADPH reductase and AdoMet-dependent methyltransferase — have clear orthologues in both Acropora and Symbiodinium. This suggests that the function of these enzymes is evolutionarily conserved between diatoms, alveolates (protist organisms that include the dinoflagellates), green plants and corals. Raina and colleagues also analysed genetranscript levels in A. millepora and found that the gene encoding NADPH reductase was highly expressed throughout all the coral’s life stages. Expression of the gene

AUBREY WADE/PANOS

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