Sustainable Phosphorus Loadings from Effective and Cost-Effective Phosphorus Management Around the Baltic Sea

Nutrient over-enrichment of the Baltic Sea, accompanied by intensified algal blooms and decreasing water clarity, has aroused widespread concern in the surrounding countries during the last four decades. This work has used a well-tested dynamic mass-balance model to investigate which decrease in total phosphorus loading would be required to meet the environmental goal to restore the trophic state in the Baltic Sea to pre-1960s levels. Furthermore, the extent to which various abatement options may decrease the phosphorus loading in a cost-effective manner has been studied. Upgrading urban sewage treatment in the catchment could, alone or in combination with banning phosphates in detergents, be sufficient to meet the set environmental goal, at an estimated annual basin-wide cost of 0.21–0.43 billion euro. Such a plan would potentially decrease the total phosphorus loading to the Baltic Sea with 6,650–10,200 tonnes per year

Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors

Systematic identification of protein-drug interaction networks is crucial to correlate complex modes of drug action to clinical indications. We introduce a novel computational strategy to identify protein-ligand binding profiles on a genome-wide scale and apply it to elucidating the molecular mechanisms associated with the adverse drug effects of Cholesteryl Ester Transfer Protein (CETP) inhibitors. CETP inhibitors are a new class of preventive therapies for the treatment of cardiovascular disease. However, clinical studies indicated that one CETP inhibitor, Torcetrapib, has deadly off-target effects as a result of hypertension, and hence it has been withdrawn from phase III clinical trials. We have identified a panel of off-targets for Torcetrapib and other CETP inhibitors from the human structural genome and map those targets to biological pathways via the literature. The predicted protein-ligand network is consistent with experimental results from multiple sources and reveals that the side-effect of CETP inhibitors is modulated through the combinatorial control of multiple interconnected pathways. Given that combinatorial control is a common phenomenon observed in many biological processes, our findings suggest that adverse drug effects might be minimized by fine-tuning multiple off-target interactions using single or multiple therapies. This work extends the scope of chemogenomics approaches and exemplifies the role that systems biology has in the future of drug discovery