Macrophage TBK1 signaling drives the development and outgrowth of breast cancer brain metastasis.

Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment that promote breast cancer brain metastasis (BCBM). Here, we identify TANK-binding kinase (TBK1) as a critical signaling molecule enriched and activated in TAMs of BCBM tumors, playing an indispensable role in BCBM development and metastatic outgrowth in the brain. Mechanistically, BCBM cell-secreted matrix metalloproteinase 1 binds to protease-activated receptor 1 and integrin αVβ5 on macrophages, leading to TBK1 activation mediated by the nuclear factor-kappa B pathway.

Forest Topsoil Organic Carbon Declines Under Ash Dieback.

Tree diseases are increasingly affecting woodland ecosystems across the world. However, the impact of these diseases upon the soil, and in particular soil carbon, is still poorly understood. Here we present the results of a field survey of ~100 woodlands across Great Britain measured in 1971, 2001 and 2022 and evaluate the fifty-year trend in topsoil (0-15 cm) carbon based upon measurements of soil organic matter (SOM) and the impact of Hymenoscyphus fraxineus (ash dieback).

Enhancing Hydrogen Production from Bioenergy Crops via Photoreforming.

Photoreforming perennial bioenergy crops (willow, , and poplar) has the potential to produce H with reduced environmental impacts. To understand the compositional effects of the biomass on the average rate of H production over the first 30 min of reaction (H), the H values of model biomass component (i.e.

Design of soluble Notch agonists that drive T cell development and boost immunity.

The rational design of receptor agonists to control cell signaling is an emerging strategy for developing disease therapeutics. Creating a soluble cytokine-like agonist for the Notch receptor, which regulates cell fate in embryonic and adult development, is challenging, as receptor activation requires a mechanical force that is usually mediated by cell-associated transmembrane ligands. Here, we exploit computationally designed protein complexes with precise valencies and geometries to generate soluble cytokine-like Notch agonists.