PI3K-δ and PI3K-γ inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models.

Phosphoinositide-3 kinase (PI3K)-δ and PI3K-γ are preferentially expressed in immune cells, and inhibitors targeting these isoforms are hypothesized to have anti-inflammatory activity by affecting the adaptive and innate immune response. We report on a potent oral PI3K-δ and PI3K-γ inhibitor (IPI-145) and characterize this compound in biochemical, cellular, and in vivo assays. These studies demonstrate that IPI-145 exerts profound effects on adaptive and innate immunity by inhibiting B and T cell proliferation, blocking neutrophil migration, and inhibiting basophil activation.

Plants reverse warming effect on ecosystem water balance.

Models predict that global warming may increase aridity in water-limited ecosystems by accelerating evapotranspiration. We show that interactions between warming and the dominant biota in a grassland ecosystem produced the reverse effect. In a 2-year field experiment, simulated warming increased spring soil moisture by 5-10% under both ambient and elevated CO2.

Influence of N-fixing Trifolium on plant species composition and biomass production in alpine tundra.

Alpine Trifolium species have high rates of symbiotic N-fixation which may influence the abundance and growth of plant species growing near them. The potential for facilitative effects on plant abundance and growth in dry meadow alpine tundra of Niwot Ridge, Colo., characterized by low resource availability, was investigated by measuring soil N, aboveground biomass production, and plant species composition in patches of Trifolium dasyphyllum and surrounding tundra.