The Mekong River Basin, site of the biggest inland fishery in the world, is undergoing massive hydropower development. Planned dams will block critical fish migration routes between the river's downstream floodplains and upstream tributaries. Here we estimate fish biomass and biodiversity losses in numerous damming scenarios using a simple ecological model of fish migration. Our framework allows detailing trade-offs between dam locations, power production, and impacts on fish resources. We find that the completion of 78 dams on tributaries, which have not previously been subject to strategic analysis, would have catastrophic impacts on fish productivity and biodiversity. Our results argue for reassessment of several dams planned, and call for a new regional agreement on tributary development of the Mekong River Basin.sustainable development | hydropower planning | fish species richness

Interactions between denaturants and proteins are commonly used to probe the structures of the denatured state ensemble and their stabilities. Osmolytes, a class of small intracellular organic molecules found in all taxa, also profoundly affect the equilibrium properties of proteins. We introduce the molecular transfer model, which combines simulations in the absence of denaturants or osmolytes, and Tanford T o function proteins fold (1), whereas misfolding is linked to a number of conformational diseases (2, 3), thus making it important to determine the factors that control stability of proteins (1) and their assembly mechanisms (4-6). A molecular understanding of protein folding requires quantitative estimates of the energetic changes (7,8) in the folding reaction and characterization of the populated structures along the folding pathways. A large number of studies have dissected the interactions that contribute to the stability of proteins (1,(7)(8)(9)(10)(11)(12)(13)(14)(15).In contrast, only relatively recently has there been a concerted effort to determine the structures of the denatured state ensemble (DSE) (16) whose experimental resolution is difficult because of fluctuations in the unfolded structures. In particular, it is difficult to determine the properties of the DSE under conditions in which the native state is stable because the population of the unfolded structures is low (17). Single-molecule FRET experiments have begun to investigate the variations in the global properties of the DSE under native conditions (18)(19)(20). Despite these intense efforts, structural characterization of the DSE and its link to global thermodynamic properties and the folding process is lacking.Denaturants, such as urea and guanidinium chloride (GdmCl), destabilize proteins. In contrast, osmolytes that protect cells against environmental stresses such as high temperature, desiccation, and pressure can stabilize proteins (21). Thus, a complete understanding of the stability of proteins and a description of the structures in the diverse DSEs requires experimental and theoretical studies that provide a quantitative description of the effects of both osmolytes and denaturants.From a theoretical perspective, significant advances in our understanding of how proteins fold have come from molecular simulations by using coarse-grained (CG) off-lattice models (22)(23)(24)(25)(26)(27). However, the CG models only probe the folding of proteins by changing temperature, making it difficult to compare the predictions directly with many experiments that use denaturants. In principle, all-atom simulations of proteins in aqueous denaturant solutions can be used to calculate the conformational properties of proteins. However, the difficulty in adequately sampling the protein conformational space makes most of these simulations inherently nonergodic (28). Here, we overcome these problems by combining Tanford's transfer model (TM) (29, 30) with simulations using an off-lattice side chain representation of polypeptide chains (26) to predi...

Proteins attain their function only after folding into a highly organized three-dimensional structure. Much remains to be learned about the mechanisms of folding of large multidomain proteins, which may populate metastable intermediate states on their energy landscapes. Here we introduce a novel method, based on high-throughput single-molecule fluorescence experiments, which is specifically geared towards tracing the dynamics of folding in the presence of a plethora of intermediates. We employ this method to characterize the folding reaction of a three-domain protein, adenylate kinase. Using thousands of single-molecule trajectories and hidden Markov modelling, we identify six metastable states on adenylate kinase’s folding landscape. Remarkably, the connectivity of the intermediates depends on denaturant concentration; at low concentration, multiple intersecting folding pathways co-exist. We anticipate that the methodology introduced here will find broad applicability in the study of folding of large proteins, and will provide a more realistic scenario of their conformational dynamics.

21There is a growing pressure of human activities on natural habitats, which leads to 22 biodiversity losses. To mitigate the impact of human activities, environmental policies are 23 developed and implemented, but their effects are commonly not well understood because 24 of the lack of tools to predict the effects of conservation policies on habitat quality and/or 25 diversity. We present a straightforward model for the simultaneous assessment of terrestrial 26and aquatic habitat quality in river basins as a function of land use and anthropogenic 27 threats to habitat that could be applied under different management scenarios to help 28 understand the trade-offs of conservation actions. We modify the InVEST model for the 29 assessment of terrestrial habitat quality and extend it to freshwater habitats. We assess the 30 model reliability in a severely impaired basin by comparing modeled results to observed 31 terrestrial and aquatic biodiversity data. We believe that the developed model can be useful to assess potential levels of 37 biodiversity, and to support conservation planning given its capacity to forecast the effects 38 of management actions in river basins. 39 40 Keywords: anthropogenic threats; biodiversity; environmental management; habitat quality; 41 scenario analysis; river basin. 42 43 3