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PNAS Papers on Peanut Genetics, Acute Kidney Injury Protection, Colorectal Cancer Carcinogenesis

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

Researchers at the University of Georgia, HudsonAlpha Institute of Biotechnology, and elsewhere present evidence for the widespread presence of Arachis cardenasii GKP 10017 wild peanut accession genetics in A. hypogaea crops in Africa, Asia, the Americas, and Oceania. Using a combination of A. cardenasii GKP 10017 whole-genome sequencing and resequencing — combined with array-based SNP profiling on hundreds of wild or domesticated Arachis accessions — the team detected historical hybridization events involving A. cardenasii and A. hypogaea plants in the 1960s, ultimately leading to peanut crop cultivars with A. cardenasii-related disease or pest resistance at sites around the world. "[W]e uncover the global benefits arising from the introduction of one wild species accession to peanut-breeding programs decades ago," the authors report, noting that "peanut cultivars with genetics from this wild accession provided improved food security and reduced used of fungicidal sprays."

A team from Germany, China, and Switzerland describes acute kidney injury protection in mouse models of kidney toxicity when levels of CD64-expression mononuclear phagocyte cells are selectively dialed down. With the help of an inducible genetic approach for depleting CD64-expression mononuclear phagocyte cells without altering conventional dendritic cell subtypes, the researchers tracked acute kidney effects in mouse models of cisplatin-induced nephrotoxicity. "Our findings in cisplatin-induced injury underscore the value of dissecting the functions of individual [mononuclear phagocyte] subsets in kidney disease, which may enable therapeutic targeting of specific immune components in the absence of general immunosuppression," they report, adding that the work "highlights that individual [mononuclear phagocyte] subsets have unique functions in kidney pathology."

For a paper slated to appear in PNAS this week, investigators in the UK, Egypt, and Hungary outline a role for the nanovesicle production-related tetraspanin pathway protein Tspan6 in colorectal cancer (CRC) development. The team used a combination of mouse gene knockout experiments and immunohistochemistry-based Tspan6 profiling on 184 CRC tumor samples from an EGFR targeting clinical trial to uncover an apparent role for Tspan6 in CRC carcinogenesis. In particular, results from the study suggest lower-than-usual Tspan6 levels can bump up the production a TGF-alpha-related protein that has been linked to extracellular vesicles, leading to enhanced EGF-related signaling. Moreover, the authors note, clinical trial data pointed to enhanced EGFR-targeting drug response in CRC cases with Tspan6 expression compared with CRC cases marked by low tumor levels of Tspan6. "These results identify Tspan6 as a regulator of CRC development and a potential predictive biomarkers for EGFR-targeted therapies," the authors write.