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PNAS Papers on Historic Helicobacter Spread, Brain Development, C. difficile RNAs

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

Researchers from the University of Venda, the University of Warwick, and elsewhere explore Helicobacter pylori diversity in Siberia to understand the gut bug's historical spread to the Americas via migrating human populations. With multi-locus sequence typing data on more than 550 H. pylori strains cultivated from individuals in 16 populations in Siberia and Mongolia, along with draft genome sequencing on 54 isolates, the team profiled the genetic diversity of H. pylori strains in the region, compared to available sequences isolates found in individuals from Native American and other populations. Along with H. pylori clusters found in the Americas and Eurasia, the authors saw five ancient and more recently admixed H. pylori sub-populations in Siberia, providing clues to past populations movements into the Americas and beyond. "We inferred a single migration across the Bering land bridge, accompanied by a dramatic reduction in effective population size," they write, "followed by bidirectional Holocene gene flow between Asia and the Americas." GenomeWeb has more on the study, here.

Using single-cell RNA sequencing and other approaches, a team from Boston Children's Hospital and other centers look at the gene expression patterns behind human neocortex brain development, highlighting a role for the sodium-potassium ATPase enzyme-coding gene ATP1A3 in typical brain development and in a cerebral cortex malformation condition called polymicrogyria. Based on transcriptomic patterns detected in single cells from human fetal cortex samples — as well as exome sequence and other data fromfour children carrying ATP1A3 variants who were affected by cortical malformations — the investigators tracked ATP1A3 expression during brain development and the apparent consequences of variants affecting different subunit isoforms encoded by the gene. "Together, the developmental malformation phenotype of affected individuals and single-cell ATP1A3 expression patterns point to a key role for [the ATP1A3 alpha-3 subunit] in human cortex development," they write, "as well as a cell-type basis for pre- and post-natal ATP1A3-associated diseases."

Investigators in Germany and the UK dig into the role for a gene called Hfq in post-transcriptional regulation and small RNA features in the pathogenic, spore-forming bacteria Clostridioides difficile. "Clostridioides difficile is the leading cause of healthcare-associated diarrhea worldwide following antibiotic treatment," they write. "Consequently, there is a medical need for novel antibacterial agents acting against C. difficile that leave the resident microbiota unharmed." With that in mind, the team relied on two RNA sequencing strategies, Hfq immunoprecipitation with RIP-seq, and other approaches to assess transcriptomic, post-transcriptional, and regulatory features in C. difficile during three different growth stages.  "Overall," the authors say, "our study lays the foundation for understanding clostridial riboregulation with implications for the infection process and provides evidence for a global role of Hfq in post-transcriptional regulation in a gram-positive bacterium."