Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.

Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).

Exploring the Effect of Sampling Frequency on Real-World Mobility, Sedentary Behaviour, Physical Activity and Sleep Outcomes Measured with Wearable Devices in Rheumatoid Arthritis: Feasibility, Usability and Practical Considerations.

Modern treat-to-target management of rheumatoid arthritis (RA) involves titration of drug therapy to achieve remission, requiring close monitoring of disease activity through frequent clinical assessments. Accelerometry offers a novel method for continuous remote monitoring of RA activity by capturing fluctuations in mobility, sedentary behaviours, physical activity and sleep patterns over prolonged periods without the expense, inconvenience and environmental impact of extra hospital visits. We aimed to (a) assess the feasibility, usability and acceptability of wearable devices in patients with active RA; (b) investigate the multivariate relationships within the dataset; and (c) explore the robustness of accelerometry outcomes to downsampling to facilitate future prolonged monitoring.

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks.

Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein-solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein-ligand and -solvent molecule interactions.