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This Week in PNAS: Jul 12, 2011

In this week's PNAS Early Edition, investigators at Duke University and elsewhere report results from their genome-wide microarray study of sodium-deficient mice before and after ACTH [adrenocorticotropic hormone] infusion. "Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine)," the authors write, adding that "this finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut." As such, the team says the results of its study may be a starting point for researchers working to "outline a molecular logic for instinctive behavior encoded by the brain."

In another PNAS paper published online in advance this week, a team led by investigators at the National Cancer Institute demonstrates a critical role for the Ras guanine exchange factor Sos1 in early T-cell development. By deleting Sos1 in a targeted manner, the team observed that it was "required for pre-T-cell receptor — but not TCR-stimulated developmental signals." Further, "Sos1 deletion led to a partial block" of the double negative to double positive transition, the NCI-led team adds. As such, the researchers suggest that the Ras guanine exchange factor is "uniquely positioned to affect signal transduction early in thymocyte development."

Researchers at the Dana-Farber Cancer Institute and elsewhere in Boston show that by combining genomic data generated by efforts like The Cancer Genome Atlas with functional information, they've pinpointed "known and previously undescribed lineage-specific dependencies across a wide spectrum of cancers." Using this approach, the researchers initiated a systematic effort called Project Achilles and in its PNAS paper published online this week, the Project Achilles team identifies PAX8 as an ovarian lineage-specific dependency.

Oregon Health and Science University's Dae-Hwan Kim and Jae Lee show in PNAS this week that "p53 lowers bile acid (BA) levels under both normal and stressed conditions primarily through upregulating expression of small heterodimer partner, a critical inhibitor of BA synthesis," which they say represents "a unique metabolic regulatory axis that unexpectedly couples p53 to BA homeostasis."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.