Highlights d A pan-tissue AHR signature identifies IL4I1 as a major AHRactivating enzyme d IL4I1-mediated Trp catabolism yields indoles and kynurenic acid that activate the AHR d IL4I1 promotes AHR-driven cancer cell motility and suppresses adaptive immunity d IL4I1 enhances CLL progression and is induced by immune checkpoint blockade

Amino acids (aa) are not only building blocks for proteins, but also signalling molecules, with the mammalian target of rapamycin complex 1 (mTORC1) acting as a key mediator. However, little is known about whether aa, independently of mTORC1, activate other kinases of the mTOR signalling network. To delineate aa-stimulated mTOR network dynamics, we here combine a computational–experimental approach with text mining-enhanced quantitative proteomics. We report that AMP-activated protein kinase (AMPK), phosphatidylinositide 3-kinase (PI3K) and mTOR complex 2 (mTORC2) are acutely activated by aa-readdition in an mTORC1-independent manner. AMPK activation by aa is mediated by Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). In response, AMPK impinges on the autophagy regulators Unc-51-like kinase-1 (ULK1) and c-Jun. AMPK is widely recognized as an mTORC1 antagonist that is activated by starvation. We find that aa acutely activate AMPK concurrently with mTOR. We show that AMPK under aa sufficiency acts to sustain autophagy. This may be required to maintain protein homoeostasis and deliver metabolite intermediates for biosynthetic processes.

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We describe EMOBANK, a corpus of 10k English sentences balancing multiple genres, which we annotated with dimensional emotion metadata in the Valence-ArousalDominance (VAD) representation format. EMOBANK excels with a bi-perspectival and bi-representational design. On the one hand, we distinguish between writer's and reader's emotions, on the other hand, a subset of the corpus complements dimensional VAD annotations with categorical ones based on Basic Emotions. We find evidence for the supremacy of the reader's perspective in terms of IAA and rating intensity, and achieve close-to-human performance when mapping between dimensional and categorical formats.

GeNo, including its underlying resources, will be available from www.julielab.de. It is also currently deployed in the Semedico search engine at www.semedico.org.