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This Week in PNAS: Sep 25, 2012

In the early, online edition of the Proceedings of the National Academy of Sciences, French researchers report on the interactions that two Lactobacillus bacteria (believed to have probiotic activity) have with the foodborne pathogen Listeria monocytogenes. In a mouse model of listeriosis infection, their array-based gene and microRNA expression profiling experiments indicate that treatment with Lactobacillus paracasei or L. casei produced seemingly beneficial shifts in the expression of certain host miRNAs and genes — for instance, dialing back the expression of immune genes activated in response to the L. monocytogenes infection. The lactobacilli treatments also altered levels of some pathogen genes and decreased the likelihood that L. monocytogenes infection spread systemically. Those involved in the study say the work "paves the way for a thorough and systematic analysis of the key components mediating the protecting effect of lactobacilli."

Two extremophile archaeal species with nearly identical genomes use dramatically different methods to deal with excess uranium in their environments, according to another study slated to come out online in PNAS this week. A team from North Carolina State University and the University of Nebraska-Lincoln compared thermoacidophilic Metallosphaera sedula archaea from a uranium-rich hot spring in Italy with a closely related extremophile, M. prunae, found at a German uranium mine. Though the archaea shared some 99.99 percent of their genome sequences, the researchers report, the Italian species slurped up excess uranium for energy, while the species sampled in Germany relied on dormancy to avoid uranium toxicity. Together with the team's transcriptomic analyses, the findings "point to uranium extremophily as an adaptive, rather than intrinsic, feature for Metallosphaera species, driven by environmental factors."

Finally, researchers from the US and China explore the role of microRNAs in a set of pre-leukemic conditions known as myeloproliferative neoplasms. Using a gain-of-function screen for miRNAs whose expression could prompt bone marrow-derived cells to take on myeloproliferative neoplasm-like traits, the team narrowed in on a miRNA called miR-125a. A series of follow-up experiments in cell lines, primary bone marrow cells, and mouse models suggested that miR-125a targets several protein phosphatase enzymes in the cell — and that its enhanced expression contributes to an oncogenic environment even before MPNs transition to advance disease states. "Our data demonstrate that miR-125a-induced MPN is addicted to its sustained overexpression," study authors say, "and highlight the complex nature of oncogenic miRNA dependence in an early neoplastic state."

The Scan

Drug Response Variants May Be Distinct in Somatic, Germline Samples

Based on variants from across 21 drug response genes, researchers in The Pharmacogenomics Journal suspect that tumor-only DNA sequences may miss drug response clues found in the germline.

Breast Cancer Risk Gene Candidates Found by Multi-Ancestry Low-Frequency Variant Analysis

Researchers narrowed in on new and known risk gene candidates with variant profiles for almost 83,500 individuals with breast cancer and 59,199 unaffected controls in Genome Medicine.

Health-Related Quality of Life Gets Boost After Microbiome-Based Treatment for Recurrent C. Diff

A secondary analysis of Phase 3 clinical trial data in JAMA Network Open suggests an investigational oral microbiome-based drug may lead to enhanced quality of life measures.

Study Follows Consequences of Early Confirmatory Trials for Accelerated Approval Indications

Time to traditional approval or withdrawal was shorter when confirmatory trials started prior to accelerated approval, though overall regulatory outcomes remained similar, a JAMA study finds.