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PNAS Papers on Rheumatoid Arthritis Regulation, Myasthenia Gravis Thymectomy Effects, More

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

For a paper scheduled to appear in PNAS this week, researchers from Brigham and Women's Hospital and other centers in the US and Sweden describe an apparent role for the transcription factor USF2 in refractory rheumatoid arthritis, particularly when it comes to regulating T helper 17 (Th17) cells, known for producing interleukin-17 (IL-17) proinflammatory cytokines. The team relied on high-throughput NanoString nCounter analyses to compare gene expression patterns in T cell samples from individuals with rheumatoid arthritis who did or did not respond to treatments targeting the tumor necrosis factor proinflammatory cytokine. "Proinflammatory signaling was elevated in the CCR6+ T cells of non-responders, and pathogenic Th17 signature genes were up-regulated in these cells," the authors report. "Gene set enrichment analysis on these signature genes identified transcription factor USF2 as their upstream regulator, which was also increased in non-responders." 

A Yale University-led team presents evidence that thymus-associated B cells and plasma cells may still turn up in individuals with myasthenia gravis autoimmune disease who are treated with thymectomy surgery to remove the thymus, a lymphoid organ with immune activity. Using a combination of B cell repertoire sequencing, RNA sequencing, and other approaches, the investigators profiled thymus B cell-related clones before thymectomy and 12 months after surgery in dozens of myasthenia gravis patients participating in a multi-center clinical trial comparing prednisone treatment alone to prednisone with thymectomy. Among other findings, the authors found that "disease-associated B cell clones mature in the thymus before emigrating to the circulation. These B cell clones are present in the circulation after thymectomy and their persistence correlated with less favorable changes in clinical symptoms after thymectomy." 

Investigators at Fudan University delve into the details of interactions between H2A-H2B histone heterodimers and histone chaperone proteins from the nucleosome assembly protein 1 (NAP1) family in Arabidopsis plant models, using a series of crystal structure analyses, in vitro binding assays, transgenic plant model rescue assays done in vivo, and other approaches. Their results made it possible to focus in on a specific NRP1 protein domain that interacts with the H2A-H2B complex, and to get a closer look at the biological processes influenced by these interactions. "Our results provide evidence of multiple interaction modes of a NAP1-family histone chaperone," the authors write, "thereby shedding light on how histone chaperones effectively shield H2A-H2B from non-specific interaction with DNA."

The Scan

Support for Moderna Booster

An FDA advisory committee supports authorizing a booster for Moderna's SARS-CoV-2 vaccine, CNN reports.

Testing at UK Lab Suspended

SARS-CoV-2 testing at a UK lab has been suspended following a number of false negative results.

J&J CSO to Step Down

The Wall Street Journal reports that Paul Stoffels will be stepping down as chief scientific officer at Johnson & Johnson by the end of the year.

Science Papers Present Proteo-Genomic Map of Human Health, Brain Tumor Target, Tool to Infer CNVs

In Science this week: gene-protein-disease map, epigenomic and transcriptomic approach highlights potential therapeutic target for gliomas, and more