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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

Team Tracks Down Potential Blood Plasma Markers Linked to Heart Failure in Atrial Fibrillation Patients

Researchers in BMC Genomics found 10 differentially expressed proteins or metabolites that marked atrial fibrillation with heart failure cases.

Study Points to Synonymous Mutation Effects on E. Coli Enzyme Activity

Researchers in Nature Chemistry saw signs of enzyme activity shifts in the presence of synonymous mutations in a multiscale modeling analysis of three Escherichia coli genes.

Team Outlines Paternal Sample-Free Single-Gene Approach for Non-Invasive Prenatal Screening

With data for nearly 9,200 pregnant individuals, researchers in Genetics in Medicine demonstrate the feasibility of their carrier screening and reflex single-gene non-invasive prenatal screening approach.

Germline-Targeting HIV Vaccine Shows Promise in Phase I Trial

A National Institutes of Health-led team reports in Science that a broadly neutralizing antibody HIV vaccine induced bnAb precursors in 97 percent of those given the vaccine.