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PNAS Papers on Swine Coronavirus, TP53 Variant, RNA Buildup in Cancer Invasion Model

Researchers from the University of North Carolina-Chapel Hill and the Pacific Northwest National Laboratory characterize a pathogenic coronavirus behind a swine acute diarrhea syndrome (SADS) in pigs. The team came up with a recombinant version of SADS-CoV that had a red fluorescent reporter-coding gene replacing one of the virus' open reading frames, generating complementary DNAs that covered much of the SADS-CoV genome in the process. Along with experiments aimed at teasing out growth patterns, receptor interactions, and other features for the recombinant version of SADS-CoV, the authors demonstrate that the fluorescent protein-expression virus could replicate in several human cell types, including primary human lung cells and intestinal cells, while replicating far less in mouse models. 

A team from the University of Pennsylvania and Wistar Institute report on apparent metabolic differences in a humanized mouse model and human cell lines containing a version of the transcription factor- and tumor suppressor-coding gene TP53 that has serine swapped in for proline in codon 47. This P47S variant of TP53 was previously shown to be overrepresented in individuals with African ancestry, the researchers note. With the help of quantitative RT-PCR, metabolite analyses, protein interaction assays, and other approaches, they saw signs that the serine substitution in question seems to coincide with lower-than-usual levels of catabolic glycolysis and an uptick in pentose phosphate pathway activity and NADPH antioxidant production. Such differences seemed to stem from altered ATF4 expression and related redox state differences, the authors say, suggesting their data "unveil the important functional interplay among pathways regulating thiol-redox status, metabolic adaptation, and cellular responses to oxidative stress."

Finally, investigators at the National Cancer Institute and the Frederick National Laboratory for Cancer Research describe the accumulation of RNA molecules at the invasive front of advancing cancer cells, based on results from experiments done with their inducible three-dimensional invasion model based on breast cancer cells in a matrix of collagen or other material. "To understand the regulation and roles of protrusion-localized RNAs during [three-dimensional] collective invasion," they write, "we developed a system that would allow us to study collective invasion in a controlled manner and simultaneously permit specific RNA imaging." In particular, the team's results highlighted invasive cell enrichment of RNA transcripts coinciding with genes such as RAB13 and NET1, facilitated by microtubules and laminin in the cell.