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This Week in Cell: Dec 6, 2012

An international team led by René Bernards, with The Netherlands Cancer Institute and Agendia, explores the genetics of cancer treatment susceptibility and resistance, focusing first on ALK and EGF receptor tyrosine kinase inhibitor therapies. Using an RNA interference screen in a non-small cell lung cancer line carrying an EML4-ALK translocation, the researchers determined that knocking down a gene called MED12 confers resistance to an ALK-inhibiting drug called crizotinib. Their subsequent experiments indicate that suppression of MED12 bumps up TGF-beta receptor related signaling, which makes other cancers more capable of dodging therapies, too, including treatments based on MEK and BRAF inhibition.

University of Pennsylvania researchers report on factors that help or hinder cellular reprogramming in the presence of the transcription factors Oct4, Sox2, Klf4, and c-Myc in the hopes of learning more about why this process is successful in some cells and not in others. The group used chromatin immunoprecipitation-sequencing, or ChIP-seq, to track the binding profiles for the transcription factors over time — and in relation to histone marks and other genomic features — in human fibroblast cells being reprogrammed to pluripotency. "Our analysis reveals striking differences between initial binding of the factors compared to later stages," the study's authors write, "and unanticipated insights about what needs to be overcome for successful reprogramming."

A team from the Scripps Research Institute takes a look at transcriptional patterns in the mouse brain that are influenced by the histone deacetylase HDAC4, demonstrating that this HDAC4-mediated program is behind both proper synaptic plasticity and memory. The researchers' expression, localization, and other experiments indicate that HDAC4 shifts back and forth between the cell's nucleus and its cytoplasm, mediating the expression of genes that control synapse strength and structure. In contrast, they report, mutant versions of HDAC4 led to transcriptional shifts in the mouse brain, altering the animals' spatial learning, memory, and certain behaviors. "These studies elucidate a mechanism of experience-dependent plasticity," Scripps' cell biologist Anton Maximov and his colleagues write, "and define the biological role of HDAC4 in the brain."

The Scan

Another Resignation

According to the Wall Street Journal, a third advisory panel member has resigned following the US Food and Drug Administration's approval of an Alzheimer's disease drug.

Novavax Finds Its Vaccine Effective

Reuters reports Novavax's SARS-CoV-2 vaccine is more than 90 percent effective in preventing COVID-19.

Can't Be Used

The US Food and Drug Administration says millions of vaccine doses made at an embattled manufacturing facility cannot be used, the New York Times reports.

PLOS Papers on Frozen Shoulder GWAS, Epstein-Barr Effects on Immune Cell Epigenetics, More

In PLOS this week: genome-wide association study of frozen shoulder, epigenetic patterns of Epstein-Barr-infected B lymphocyte cells, and more.