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Cell Studies on Protein Structure Dynamics, NeuroPAL, Early Relapsing Liver Cancer

Investigators in Switzerland and Germany explore functional shifts stemming from three-dimensional protein structure changes in bacteria and yeast using a strategy known as "limited proteolysis-mass spectrometry" (LiP-MS). "The structural readout, visualized as structural barcodes, captured enzyme activity changes, phosphorylation, protein aggregation, and complex formation, with the resolution of individual regulated functional sites such as binding and active sites," they report. The team identified new and known interactions and functional changes when it compared information from its "dynamic structural proteomic screens" with existing proteomic datasets, arguing that the "structural readout dramatically increases classical proteomics coverage, generates mechanistic hypotheses, and paves the way for in situ structural systems biology."

A Columbia University-led team outlines a neuronal cell atlas developed for Caenorhabditis elegans worms using a multi-color cell-labeling strategy. The resource — known as "neuronal polychromatic atlas of landmarks," or NeuroPAL — relies on fluorescent reporter tags and semi-automated software for visualizing distinct types of neurons based on their gene expression patterns, the researchers write. Among other proof-of-principle applications, the authors used the NeuroPal approach to document the expression of receptors for several key neurotransmitters, for example, and track the consequences of transcription factor mutations.

Researchers from Fudan University, BGI-Shenzhen, and elsewhere share findings from a single-cell transcriptomic study of hepatocellular carcinoma (HCC) cases marked by early relapse. Using single-cell RNA sequencing profiles from around 17,000 cells from 18 primary or early-relapse HCC cases, the team tracked down distinct immune features that appeared to coincide with early-relapsing HCC, including a dip in regulatory T cells and a rise in dendritic cells and infiltrating CD8+ T cells. The authors highlighted a group of CD8+ T cells with "innate-like, low cytotoxic, and low clonal expansion" features in the recurrent HCC tumors with poorer-than-usual outcomes, for example. "Our comprehensive picture of the HCC ecosystem provides deeper insights into immune evasion mechanisms associated with tumor relapse," they write.