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A pathway for the production of aromatic amino acid metabolites in Clostridium sporogenes is described; modulation of serum levels of these metabolites in gnotobiotic mice affects intestinal permeability and systemic immunity.
Cancers growing in high-oxygen environments, such as lung adenocarcinomas, select for the iron–sulfur cluster synthesizing enzyme NFS1 to support malignant proliferation and to protect from oxidative damage.
Hepatitis E virus (HEV) is a public health concern in both developing and developed countries. Here, the authors describe advances in understanding HEV biology, clinical infection and the challenges still to be overcome in HEV research, particularly with respect to cell culture and animal models.
Target of rapamycin (TOR) kinase operates within two distinct multiprotein complexes named TORC1 and TORC2. Here the authors report a cryo-EM structure of TORC2, establish its subunit organization, providing a rationale for TORC2’s rapamycin insensitivity and the mutually exclusive inclusion of Avo3/Rictor or Raptor within their respective TOR complex.
Cas9 and Cpf1 have both been adapted for genome engineering, editing and gene expression regulation. Here the authors design a fusion guide RNA that can interact with both proteins for multiple and orthogonal genome manipulation.
The 'off-targets' of a drug are often poorly characterized yet could be harnessed in the treatment of complex diseases. A recent study used a small-molecule screening in non-small-cell lung cancer to repurpose an FDA-approved ALK/IGF1R inhibitor and uncover its mechanism of action.
Phage-assisted evolution can rapidly improve the efficiency and substrate specificity of orthogonal aminoacyl-tRNA synthetases. Furthermore, the crystal structure of the pyrrolysyl-tRNA synthetase N-terminal domain reveals the basis for these improvements and provides a structural rationale for orthogonality.