42 research outputs found
The “social” aspect of social-ecological systems : a critique of analytical frameworks and findings from a multisite study of coastal sustainability
The work described here was partly funded by the European Commission’s FP6 contract 036992.We evaluate whether society can adequately be conceptualized as a component of social-ecological systems, given social theory and the current outputs of systems-based research. A mounting critique from the social sciences posits that resilience theory has undertheorized social entities with the concept of social-ecological systems. We trace the way that use of the term has evolved, relating to social science theory. Scientometic and network analysis provide a wide range of empirical data about the origin, growth, and use of this term in academic literature. A content analysis of papers in Ecology and Society demonstrates a marked emphasis in research on institutions, economic incentives, land use, population, social networks, and social learning. These findings are supported by a review of systems science in 18 coastal assessments. This reveals that a systems-based conceptualization tends to limit the kinds of social science research favoring quantitative couplings of social and ecological components and downplaying interpretive traditions of social research. However, the concept of social-ecological systems remains relevant because of the central insights concerning the dynamic coupling between humans and the environment, and its salient critique about the need for multidisciplinary approaches to solve real world problems, drawing on heuristic devices. The findings of this study should lead to more circumspection about whether a systems approach warrants such claims to comprehensiveness. Further methodological advances are required for interdisciplinarity. Yet there is evidence that systems approaches remain highly productive and useful for considering certain social components such as land use and hybrid ecological networks. We clarify advantages and restrictions of utilizing such a concept, and propose a reformulation that supports engagement with wider traditions of research in the social sciences.Publisher PDFPeer reviewe
Structures of pyruvate kinases display evolutionarily divergent allosteric strategies
The transition between the inactive T-state (apoenzyme) and active R-state (effector bound enzyme) of Trypanosoma cruzi pyruvate kinase (PYK) is accompanied by a symmetrical 8° rigid body rocking motion of the A- and C-domain cores in each of the four subunits, coupled with the formation of additional salt bridges across two of the four subunit interfaces. These salt bridges provide increased tetramer stability correlated with an enhanced specificity constant (k(cat)/S(0.5)). A detailed kinetic and structural comparison between the potential drug target PYKs from the pathogenic protists T. cruzi, T. brucei and Leishmania mexicana shows that their allosteric mechanism is conserved. By contrast, a structural comparison of trypanosomatid PYKs with the evolutionarily divergent PYKs of humans and of bacteria shows that they have adopted different allosteric strategies. The underlying principle in each case is to maximize (k(cat)/S(0.5)) by stabilizing and rigidifying the tetramer in an active R-state conformation. However, bacterial and mammalian PYKs have evolved alternative ways of locking the tetramers together. In contrast to the divergent allosteric mechanisms, the PYK active sites are highly conserved across species. Selective disruption of the varied allosteric mechanisms may therefore provide a useful approach for the design of species-specific inhibitors
Structures of Leishmania Fructose-1,6-Bisphosphatase Reveal Species-Specific Differences in the Mechanism of Allosteric Inhibition
A new family of covalent inhibitors block nucleotide binding to the active site of pyruvate kinase
PYK (pyruvate kinase) plays a central role in the metabolism of many organisms and cell types, but the elucidation of the details of its function in a systems biology context has been hampered by the lack of specific high-affinity small-molecule inhibitors. High-throughput screening has been used to identify a family of saccharin derivatives which inhibit LmPYK (Leishmania mexicana PYK) activity in a time- (and dose-) dependent manner, a characteristic of irreversible inhibition. The crystal structure of DBS {4-[(1,1-dioxo-1,2-benzothiazol-3-yl)sulfanyl]benzoic acid} complexed with LmPYK shows that the saccharin moiety reacts with an active-site lysine residue (Lys335), forming a covalent bond and sterically hindering the binding of ADP/ATP. Mutation of the lysine residue to an arginine residue eliminated the effect of the inhibitor molecule, providing confirmation of the proposed inhibitor mechanism. This lysine residue is conserved in the active sites of the four human PYK isoenzymes, which were also found to be irreversibly inhibited by DBS. X-ray structures of PYK isoforms show structural differences at the DBS-binding pocket, and this covalent inhibitor of PYK provides a chemical scaffold for the design of new families of potentially isoform-specific irreversible inhibitors
Firefly distribution and abundance on mangrove vegetation assemblages in Sepetang estuary, Peninsular Malaysia
Pteroptyx fireflies are commonly reported to congregate in large numbers in mangroves. Not much is known about the relationships between firefly distribution and abundance with specific mangrove vegetation assemblages. We conducted a study to investigate the vegetation assemblages that structure the distribution and abundance of Pteroptyx tener in Peninsular Malaysia. The distribution and abundance of fireflies were assessed along an 8 km stretch of mangroves in Sepetang estuary using visual assessment. Statistical analysis was carried out to test the correlation between length of display section and percentage cover of P. tener colonies and the relationship between percentage cover of fireflies with different vegetation assemblages. Five distinct vegetation assemblages were identified comprising different combination of four mangrove species. It was found that shorter display sections had higher percentage cover of P. tener colonies. In addition, vegetation assemblage which consisting of mainly Sonneratia caseolaris and Nypa fruticans was the most preferred type. The results of this study point to the necessity to consider not only a single mangrove species but the entire vegetation assemblage for firefly conservation
MeCP2 binding to DNA depends upon hydration at methyl-CpG
MeCP2 is an essential transcriptional repressor that mediates gene silencing through binding to methylated DNA. Binding specificity has been thought to depend on hydrophobic interactions between cytosine methyl groups and a hydrophobic patch within the methyl-CpG-binding domain (MBD). X-ray analysis of a methylated DNA-MBD cocrystal reveals, however, that the methyl groups make contact with a predominantly hydrophilic surface that includes tightly bound water molecules. This suggests that MeCP2 recognizes hydration of the major groove of methylated DNA rather than cytosine methylation per se. The MeCP2-DNA complex also identifies a unique structural role for T158, the residue most commonly mutated in Rett syndrome
Pyruvate kinases have an intrinsic and conserved decarboxylase activity
The phosphotransfer mechanism of pyruvate kinases (PYKs) has been studied in detail, but the mechanism of the intrinsic decarboxylase reaction catalysed by PYKs is still unknown. 1H NMR was used in this work to follow oxaloacetate (OAA) decarboxylation by trypanosomatid and human PYKs confirming that the decarboxylase activity is conserved across distantly related species. Crystal structures of Trypanosoma brucei PYK (TbPYK) complexed with the product of the decarboxylase reaction (pyruvate), and a series of substrate analogues (D-malate, α-ketoglutarate and oxalate) show that the OAA analogues bind to the kinase active site with similar binding modes, confirming that both decarboxylase and kinase activities share a common site for substrate binding and catalysis. Decarboxylation of OAA as monitored by NMR for TbPYK is relatively slow with turn-over values of 0.86 s-1 and 1.47 s-1 in the absence and presence of fructose 2,6-bisphosphate (F26BP), respectively. Human M1PYK has a measured turn-over value of 0.50 s-1. The X-ray structures explain why the decarboxylation activity is specific for OAA and is not general for α-keto acid analogues. Conservation of the decarboxylase reaction across divergent species is a consequence of piggybacking on the conserved kinase mechanism which requires a stabilised enol intermediate