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This Week in PNAS: Jun 7, 2011

In the PNAS Early Edition this week, an international team led by investigators at the Max Planck Institute for Developmental Biology report on "whole-genome assemblies of four divergent Arabidopsis thaliana strains that complement the 125 Mb reference genome sequence released a decade ago," which they sequenced as part of the 1,001 Genomes Project. The team says that, in its experience, more than "96 percent of the reference genome was covered by the reference-guided assembly, compared with only 87 percent with a complete de novo assembly." Overall, the team says its assemblies "provide a detailed, genome-wide picture of large-scale differences between A. thaliana individuals, most of which are difficult to access with alignment-consensus methods only."

Researchers at the pharmaceutical firm Gilead Sciences this week report their generation of validated fluorescent protein-labeled hepatitis C virus replicon cell lines, with which they found that viral resistance "emerged from a single cell and pre-existed in a treatment-naïve replicon population." The team then identified, isolated, and characterized the drug-resistant mutants; in their experimental analyses, the researchers found that "antivirals that select low-fitness drug-resistance mutations benefit from both the reduced replication rates of drug-resistant mutants and the reduced frequency of drug-resistance mutations in the treatment-naïve population." Overall, the Gilead team says that insights obtained through its study could "provide guidance for selecting clinical drug concentrations and selecting antiviral drug combinations most likely to suppress resistance."

An international team led by investigators at the University of Louisville in Kentucky show in a paper published online in advance in PNAS this week that "loss of the miR-21 allele elevates the expression of its target genes and reduces tumorigenesis." More specifically, miR-21 allele knockout mice "showed a significant reduction in papilloma formation" as well as elevated cellular apoptosis and decreased cell proliferation when compared with wild-type mice. Further, the team says that when it ablated miR-21, it observed an "up-regulation of Spry1, Pten, and Pdcd4 ... [and] reduced phosphorylation of ERK, AKT, and JNK — three major downstream effectors of Ras activation."

Researchers at Sweden's Lund University show that by over-expressing transcription factors Ascl1, Brn2, and Myt1l, they were able to efficiently convert human fibroblasts into functional neurons. Furthermore, "by combining expression of the three conversion factors with expression of two genes involved in dopamine neuron generation, Lmx1a and FoxA2, we could direct the phenotype of the converted cells toward dopaminergic neurons," the researchers report online in advance in PNAS this week.

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.