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This Week in Science: Jan 7, 2011

As an expansion of a CGG repeat in the 5'-UTR of the fragile X mental retardation 1 gene leads to the up-regulation of metabotropic glutamate receptor 5-mediated signaling, an international research team sought to determine "whether a receptor subtype-selective inhibitor of mGluR5, AFQ056, improves the behavioral symptoms of FXS in a randomized, double-blind, two-treatment, two-period, crossover study of 30 male FXS patients aged 18 to 35 years." In Science Translational Medicine this week, the team reports that "seven patients with full FMR1 promoter methylation and no detectable FMR1 messenger RNA improved" post-treatment, 18 individuals with partial promoter methylation showed no response, and 24 experienced mild adverse events overall. While confirmation in a larger study is needed, the team writes that "these results suggest that the blockade of the mGluR5 receptor in patients with full methylation at the FMR1 promoter may show improvement in the behavioral attributes of FXS."

In another Science Translational Medicine paper published this week, Harvard's Anna Mandinova and Sam Lee examine the promise of p53 activators in anti-cancer strategies and express their concerns over current clinical trials in this arena. Though the "restoration or reactivation of wild-type p53 function prompts rapid elimination of tumors," Mandinova and Lee write, "some of these agents appear to elicit undesirable toxic effects on normal cells and tissues," and must be dutifully monitored.

Harvard's Shu Kondo and Norbert Perrimon show in Science Signaling this week that "the DNA replication pre-initiation complex, which includes MUS101, and the MUS312-containing nuclease complexes ... function in the G2-M checkpoint." More specifically, in their in vivo analyses, Kondo and Perrimon identified roles for the DNA damage response genes mus101 and mus312, which "link DNA damage and the checkpoint signaling pathway," they report.

And in this week's issue of Science, researchers at the University of California, Los Angeles, report their use of "Pavlovian fear conditioning, activity-dependent immediate early gene expression, and in vivo electrophysiology" in rats, with which they "discovered that blocking neuronal gap junctions within the dorsal hippocampus impaired context-dependent fear learning, memory, and extinction." Specifically, blocking the expression of c-fos — the protein that the CFOS gene encodes — at pre-training gap junctions, the team found, affects c-fos expression within the amygdalohippocampal network.

The Scan

Could Cost Billions

NBC News reports that the new Alzheimer's disease drug from Biogen could cost Medicare in the US billions of dollars.

Not Quite Sent

The Biden Administration likely won't meet its goal of sending 80 million SARS-CoV-2 vaccine doses abroad by the end of the month, according to the Washington Post.

DTC Regulation Proposals

A new report calls on UK policymakers to review direct-to-consumer genetic testing regulations, the Independent reports.

PNAS Papers on Mosquito MicroRNAs, Acute Kidney Injury, Trichothiodystrophy

In PNAS this week: microRNAs involved in Aedes aegypti reproduction, proximal tubule cell response to kidney injury, and more.