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This Week in PNAS: Apr 5, 2011

In the PNAS Early Edition this week, investigators at the Laboratory of Experimental Hemato-Oncology in Luxembourg, along with their collaborators at the Institute for Systems Biology in Seattle and elsewhere, show that some circulating microRNAs "can be sensitive biomarkers" for chronic lymphocytic leukemia, as they've found that "certain extracellular miRNAs are present in CLL patient plasma at levels significantly different from healthy controls and from patients affected by other hematologic malignancies."

The University of Washington's Mary-Claire King and her colleagues report online in advance in PNAS this week that "mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome," a genetically heterogeneous recessive disorder. By sequencing members of a non-consanguineous family with five affected siblings, King's team found "compound heterozygosity for mutations in ... HARS2 at two highly conserved amino acids, L200V and V368L," which, when taken with results from its functional analyses in yeast and nematode, the team says is responsible for the reduction of HARS2 activity that may have caused Perrault syndrome in the affected family members.

A team led by researchers at the Morgridge Institute for Research and the University of Wisconsin, both in Madison, shows that gene-correlated, patient-specific induced pluripotent stem cells "may carry a significant mutational load at initial isolation," although it adds that "clonal events and prolonged cultured required for correction of a genetic defect can be accomplished without a substantial increase in mutational burden."

Investigators at the National Institute on Alcohol Abuse and Alcoholism and the University of Miami School of Medicine describe "substance-specific and shared transcription and epigenetic changes in the human hippocampus chronically exposed to cocaine and alcohol." In particular, the researchers found "functional changes ... related only to long-term cocaine exposure" as well as neuronal adaptations common to addictions to both substances. Using both RNA- and ChIP-seq, the team also found that "cocaine- and alcohol-related histone H3K4me3 changes [are] highly overlapped," though it detected greater aberrations under exposure to cocaine. Overall, though, "there was no direct correlation ... between either cocaine- or alcohol- related histone H3k4me3 and gene expression changes at an individual gene level, indicating that transcriptional regulation as well as drug-related gene expression changes are outcomes of a complex gene-regulatory process that includes multifaceted histone modifications," the authors write in PNAS this week.

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.