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The metabolic landscape of cancer greatly influences antitumor immunity, yet it remains unclear how organ-specific metabolites in the tumor microenvironment influence immunosurveillance. We found that accumulation of primary conjugated and secondary bile acids (BAs) are metabolic features of human hepatocellular carcinoma and experimental liver cancer models. Inhibiting conjugated BA synthesis in hepatocytes through deletion of the BA-conjugating enzyme bile acid-CoA:amino acid -acyltransferase (BAAT) enhanced tumor-specific T cell responses, reduced tumor growth, and sensitized tumors to anti-programmed cell death protein 1 (anti-PD-1) immunotherapy.

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Cotton (Gossypium hirsutum L.), a crucial global fibre and oil seed crop faces diverse biotic and abiotic stresses. Among these, temperature stress strongly influences its growth, prompting adaptive physiological, biochemical, and molecular changes.

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Background: In recent years, cancer survival rates have increased exponentially. However, this rise in survival comes with a significant drawback. As the number of treatment lines has grown, so too have the side effects, which can severely impact patients' functionality and quality of life.

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INhibitor of Growth (ING1-5) proteins are epigenetic readers that target histone acetyltransferase (HAT) or histone deacetylase (HDAC) complexes to the H3K4Me3 mark of active transcription. ING5 targets Moz/Morf and HBO1 HAT complexes that alter acetylation of H3 and H4 core histones, affecting gene expression. Previous experiments in vitro indicated that ING5 functions to maintain stem cell character in normal and in cancer stem cells.

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Multiplicity of type 6 secretion system toxins limits the evolution of resistance.

Proc Natl Acad Sci U S A

January 2025

Division of Evolution, Infection and Genomics, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9NT, United Kingdom.

The bacterial type 6 secretion system (T6SS) is a toxin-injecting nanoweapon that mediates competition in plant- and animal-associated microbial communities. Bacteria can evolve de novo resistance against T6SS attacks, but resistance is far from universal in natural communities, suggesting key features of T6SS weaponry may act to limit its evolution. Here, we combine ecoevolutionary modeling and experimental evolution to examine how toxin type and multiplicity in attackers shape resistance evolution in susceptible competitors.

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