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This Week in Science: Feb 26, 2010

Tsz-Leung To and Narendra Maheshri at MIT describe positive-feedback loops in gene regulatory networks which may exhibit bimodal responses in Science this week. Using a synthetic system in budding yeast, To and Maheshri show that “a promoter with multiple transcription factor binding sites can induce a steady-state bimodal response without cooperative binding of the TF.” The researcher’s deterministic models did not predict bistability, however, which is a finding contrary to common thought.

A trio of researchers report their finding that inhibition of the NF-κB signaling by A20, a zinc finger protein, occurs through the disruption of ubiquitin conjugating enzyme complexes. They show that A20 inhibits the E3 ligase activities of three genes ― TRAF6, TRAF2, and cIAP1 ― by antagonizing interactions with the enzymes Ubc13 and UbcH5c. “A20, together with the regulatory molecule TAX1BP1, interacted with Ubc13 and UbcH5c and triggered their ubiquitination and proteasome-dependent degradation,” the team writes. They suggest that their findings suggest the role of A20 in the inhibition of inflammatory signaling pathways.

Also in Science this week, German researchers report that two insecticidal toxins in the bacterium Photorhabdus luminescens force actin polymerization. They found that the concerted action of both toxins inhibited phagocytosis of target cells and induced extensive intracellular clustering of actin.

In a perspectives article in Science Translational Medicine this week, Ludmila Prokunina-Olsson and Stephen Chanock at the National Cancer Institute report their review of the Leary et al. PARE method for massive, parallel, and near-complete sequencing of individual tumor genomes. In “Cancer gets a little more personal,” the authors write that the researchers findings support that notion that cancer genomes contain myriad genetic alterations, many of which are unique to individual tumors. Prokunina-Olsson and Chanock also write that further validation, and a reduction of cost, in the PARE method is required.

The Scan

Researchers Compare WGS, Exome Sequencing-Based Mendelian Disease Diagnosis

Investigators find a diagnostic edge for whole-genome sequencing, while highlighting the cost advantages and improving diagnostic rate of exome sequencing in EJHG.

Researchers Retrace Key Mutations in Reassorted H1N1 Swine Flu Virus With Avian-Like Features

Mutations in the acidic polymerase-coding gene boost the pathogenicity and transmissibility of Eurasian avian-like H1N1 swine influenza viruses, a PNAS paper finds.

Genome Sequences Reveal Evolutionary History of South America's Canids

An analysis in PNAS of South American canid species' genomes offers a look at their evolutionary history, as well as their relationships and adaptations.

Lung Cancer Response to Checkpoint Inhibitors Reflected in Circulating Tumor DNA

In non-small cell lung cancer patients, researchers find in JCO Precision Oncology that survival benefits after immune checkpoint blockade coincide with a dip in ctDNA levels.