From DPSIR the DAPSI(W)R(M) Emerges… a Butterfly – ‘protecting the natural stuff and delivering the human stuff’

The complexity of interactions and feedbacks between human activities and ecosystems can make the analysis of such social-ecological systems intractable. In order to provide a common means to understand and analyse the links between social and ecological process within these systems, a range of analytical frameworks have been developed and adopted. Following decades of practical experience in implementation, the Driver Pressure State Impact Response (DPSIR) conceptual framework has been adapted and re-developed to become the D(A)PSI(W)R(M). This paper describes in detail the D(A)PSI(W)R(M) and its development from the original DPSIR conceptual frame. Despite its diverse application and demonstrated utility, a number of inherent shortcomings are identified. In particular the DPSIR model family tend to be best suited to individual environmental pressures and human activities and their resulting environmental problems, having a limited focus on the supply and demand of benefits from nature. We present a derived framework, the “Butterfly”, a more holistic approach designed to expand the concept. The “Butterfly” model, moves away from the centralised accounting framework approach while more-fully incorporating the complexity of social and ecological systems, and the supply and demand of ecosystem services, which are central to human-environment interactions

The pseudo‐natural product rhonin targets RHOGDI

For the discovery of novel chemical matter generally endowed with bioactivity, strategies may be particularly efficient that combine previous insight about biological relevance, e.g., natural product (NP) structure, with methods that enable efficient coverage of chemical space, such as fragment-based design. We describe the de novo combination of different 5-membered NP-derived N-heteroatom fragments to structurally unprecedented “pseudo-natural products” in an efficient complexity-generating and enantioselective one-pot synthesis sequence. The pseudo-NPs inherit characteristic elements of NP structure but occupy areas of chemical space not covered by NP-derived chemotypes, and may have novel biological targets. Investigation of the pseudo-NPs in unbiased phenotypic assays and target identification led to the discovery of the first small-molecule ligand of the RHO GDP-dissociation inhibitor 1 (RHOGDI1), termed Rhonin. Rhonin inhibits the binding of the RHOGDI1 chaperone to GDP-bound RHO GTPases and alters the subcellular localization of RHO GTPases

The pseudo‐natural product rhonin targets RHOGDI

For the discovery of novel chemical matter generally endowed with bioactivity, strategies may be particularly efficient that combine previous insight about biological relevance, e.g., natural product (NP) structure, with methods that enable efficient coverage of chemical space, such as fragment-based design. We describe the de novo combination of different 5-membered NP-derived N-heteroatom fragments to structurally unprecedented “pseudo-natural products” in an efficient complexity-generating and enantioselective one-pot synthesis sequence. The pseudo-NPs inherit characteristic elements of NP structure but occupy areas of chemical space not covered by NP-derived chemotypes, and may have novel biological targets. Investigation of the pseudo-NPs in unbiased phenotypic assays and target identification led to the discovery of the first small-molecule ligand of the RHO GDP-dissociation inhibitor 1 (RHOGDI1), termed Rhonin. Rhonin inhibits the binding of the RHOGDI1 chaperone to GDP-bound RHO GTPases and alters the subcellular localization of RHO GTPases