Knowledge of therapeutic targets and early drug candidates is useful for improved drug discovery. In particular, information about target regulators and the patented therapeutic agents facilitates research regarding druggability, systems pharmacology, new trends, molecular landscapes, and the development of drug discovery tools. To complement other databases, we constructed the Therapeutic Target Database (TTD) with expanded information about (i) target-regulating microRNAs and transcription factors, (ii) target-interacting proteins, and (iii) patented agents and their targets (structures and experimental activity values if available), which can be conveniently retrieved and is further enriched with regulatory mechanisms or biochemical classes. We also updated the TTD with the recently released International Classification of Diseases ICD-11 codes and additional sets of successful, clinical trial, and literature-reported targets that emerged since the last update. TTD is accessible at http://bidd.nus.edu.sg/group/ttd/ttd.asp. In case of possible web connectivity issues, two mirror sites of TTD are also constructed (http://db.idrblab.org/ttd/ and http://db.idrblab.net/ttd/).

Biodiversity experiments have shown that species loss reduces ecosystem functioning in grassland. To test whether this result can be extrapolated to forests, the main contributors to terrestrial primary productivity, requires large-scale experiments. We manipulated tree species richness by planting more than 150,000 trees in plots with 1 to 16 species. Simulating multiple extinction scenarios, we found that richness strongly increased stand-level productivity. After 8 years, 16-species mixtures had accumulated over twice the amount of carbon found in average monocultures and similar amounts as those of two commercial monocultures. Species richness effects were strongly associated with functional and phylogenetic diversity. A shrub addition treatment reduced tree productivity, but this reduction was smaller at high shrub species richness. Our results encourage multispecies afforestation strategies to restore biodiversity and mitigate climate change.

. Loss of plant diversity with increased anthropogenic nitrogen (N) deposition in grasslands has occurred globally. In most cases, competitive exclusion driven by preemption of light or space is invoked as a key mechanism. Here, we provide evidence from a 9-yr N-addition experiment for an alternative mechanism: differential sensitivity of forbs and grasses to increased soil manganese (Mn) levels. In Inner Mongolia steppes, increasing the N supply shifted plant community composition from grass-forb codominance (primarily Stipa krylovii and Artemisia frigida , respectively) to exclusive dominance by grass, with associated declines in overall species richness. Reduced abundance of forbs was linked to soil acidifi cation that increased mobilization of soil Mn, with a 10-fold greater accumulation of Mn in forbs than in grasses. The enhanced accumulation of Mn in forbs was correlated with reduced photosynthetic rates and growth, and is consistent with the loss of forb species. Differential accumulation of Mn between forbs and grasses can be linked to fundamental differences between dicots and monocots in the biochemical pathways regulating metal transport. These fi ndings provide a mechanistic explanation for N-induced species loss in temperate grasslands by linking metal mobilization in soil to differential metal acquisition and impacts on key functional groups in these ecosystems.