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PNAS Studies Look at Bacterial Detection Probes, Cholera Culprit Evolution in Environment, 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 set to appear in PNAS this week, investigators in China, Slovenia, and the UK describe computer simulation-based strategies to design DNA oligonucleotide probes to pick up bacterial genomes. The approach centers on probes capable of multivalent binding to catch sequences along the pathogen's DNA, they say, noting that the computational design focuses on finding probes "that bind weakly but selectively" to high-frequency to sequences in the bacterial genome of interest. "Our results suggest that multivalent targeting of long pieces of genomic DNA can allow highly sensitive and selective binding of the target DNA, even if competing DNA in the samples also contains binding sites for the same probe sequences," the team reports, adding that the current findings "may also be relevant for DNA detection in other fields, such as disease diagnostics more broadly, environmental management, and food safety."

A University of Florida-led team explores the presence, and evolution of, the cholera-causing pathogen Vibrio cholerae in aquatic reservoirs in Haiti. Using surface water samples collected once a month from environmental sites in a coastal region of Haiti between 2012 and 2015, the researchers identified more than two dozen toxigenic V. cholerae O1 strains. Through whole-genome mapping and SNP profiling of the aquatic strains alongside 89 clinical strains, they saw the emergence of new V. cholerae lineages and potential adaptation in the aquatic environments. "Whole-genome sequence Bayesian phylogeography showed robust evidence of V. cholerae O1 evolution in riverine sites, through the establishment of reservoirs, during lull periods of the Haitian epidemic," the authors report. "Novel lineages emerged in the environment from sequential populations bottlenecks, characterized by mutations in genes potentially involved in adaptive responses."

University of Texas researchers report on an apparent role for the small GTPase-coding gene RABL3 in lymphoid development in a mouse model. The team relied on a combination of forward genetic approaches, mouse knockout or gene mutation experiments, crystallization analyses, and other methods to characterize RABL3, an oncogene that also appears to contribute to embryonic development. The results point to a lymphopoiesis role for RABL3, along with interactions with the potential G protein-coupled receptor- or ion channel-coding gene GPR89 and other effectors. In mice carrying a version of RABL3 missing a handful of amino acid-coding sequences in a so-called "interswitch" region, for example, the authors saw lymphopoiesis shifts, including lower-than-usual levels of immune B cells, T cells, and natural killer cells, and high viral titers for mice infected with the mouse cytomegalovirus.