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This Week in PNAS: Apr 26, 2011

In this week's PNAS Early Edition, researchers at the University of California, Los Angeles, and their collaborators, show that in the absence of GPIHBP1 — a protein found in capillary endothelial cells that "shuttles lipoprotein lipase [LPL] from subendothelial spaces to the capillary lumen" — LPL-mediated triglyceride hydrolysis is blocked, and plasma triglyceride levels are elevated. In its investigations, the team found two LPL missense mutations in patients with elevated plasma triglyceride levels that it says "could elicit disease." Further investigations, the researchers add, could also "provide insights into LPL sequences required for binding to GPIHBP1."

Another group led by investigators at UCLA shows that the "role of autonomous androgen receptor signaling in prostate cancer initiation is dichotomous and depends on the oncogenic signal." More specifically, using a prostate regeneration model system, the team assessed the response of androgen receptor-null epithelia to paracrine and cell autonomous oncogenic signals. "Epithelial-specific loss of AR blocked paracrine FGF10-induced PIN [prostate intraepithelial neoplasia], whereas the add back of exogenous AR restored this response. In contrast, PIN initiated by cell-autonomous, chronic-activated AKT developed independent of epithelial AR signaling," the authors report. The team suggests that its work opens avenues for further research as to the "role of hormone receptor signaling in the initiation of epithelial tumors."

The University of Colorado's Jeremy Bono and his colleagues describe the post-mating transcriptional responses of the lower reproductive tract in female Drosophila mojavensis at three time points after copulation with either conspecific or Drosophila arizonae males. While 15 genes showed differential regulation in the D. mojavensis female lower reproductive tract following conspecific copulation, "heterospecifically mated females exhibited significant perturbations in the expression of the majority of these genes, and also down-regulated transcription of a number of others, including several involved in mitochondrial function," Bono et al. write. The team also shows that male accessory-gland protein transcripts are transferred from males to females during copulation, a finding which it says has "potentially broad implications for understanding … molecular interactions between the sexes."

The University of Georgia's Yao-Wu Yuan and Susan Wessler discuss "the catalytic domain of all eukaryotic cut-and-paste transposase superfamilies" this week in PNAS. Using a "diverse collection of previously identified and recently annotated elements from a wide range of organisms," Yan and Wessler performed multiple-alignment on transposase sequences, through which they identified "the putative DDE/D triad for all superfamilies" as well as "highly conserved amino acid residues or motifs within the DDE/D domain that together form a 'signature string' that is specific to each superfamily." Overall, the pair says the study suggests that "all eukaryotic cut-and-paste transposable element superfamilies have a common evolutionary origin."

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.