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This Week in PNAS: Oct 5, 2010

In PNAS this week, researchers in New York, Massachusetts, and California collaborated to show how the polyamine pathway contributes to the pathogenesis of Parkinson's disease. The team started by using fMRI to identify regions of the brain stem resistant to the disease and then profiled gene expression levels from postmortem brain regions and identified a decrease in the catabolic polyamine enzyme spermidine/spermine N1-acetyltransferase 1, related to the disease. "Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport," the researchers write. "Taken together, the findings from human patients, yeast, and a mouse model implicate the polyamine pathway in PD pathogenesis."

Also in PNAS this week, researchers in California suggest that selective cell death is mediated by small conditional RNAs. The RNAs interact and change conformation to mechanically transduce detection of a cancer mutation and activation of a therapeutic pathway, the researchers say. The RNAs undergo hybridization chain reactions to induce cell death by an immune response that is triggered only if a cognate mRNA cancer marker is present in a cell. "Our results indicate that programmable mechanical transduction with small conditional RNAs represents a fundamental principle for exploring therapeutic conditional regulation in living cells," the authors write.

An international team of researchers present their allele-specific copy number analysis of the in vivo breast cancer genome in PNAS this week. The team took this unique bioinformatics approach to accurately dissect the allele-specific copy number of solid tumors. "This allows calculation of 'ASCAT profiles' (genome-wide allele-specific copy-number profiles) from which gains, losses, copy number-neutral events, and loss of heterozygosity can accurately be determined," the authors write. Using this method, the researchers were able to find alternative alleles that have a different influence on the development of breast carcinoma.

Finally, in PNAS this week, researchers in Michigan and North Carolina suggest that a spontaneous Irs1 passenger mutation is linked to a gene-targeted SerpinB2 allele. The team characterized mice with targeted disruption of the SerpinB2 gene and observed that the mice were smaller at birth, had delayed growth, and had decreased life expectancy. Upon examination of additional progeny from the SerpinB2-deficient mice, the team found recombination between the small phenotype and the SerpinB2 locus. "Although the smla phenotype is similar to previously reported Irs1 alleles, mice exhibited decreased survival, in contrast to the enhanced longevity reported for IRS1 deficiency generated by gene targeting," the team writes. "When linked to a targeted allele, such mutations could lead to incorrect assignment of phenotype and may account for a subset of markedly discordant results from experiments independently targeting the same gene."

The Scan

Tens of Millions Saved

The Associated Press writes that vaccines against COVID-19 saved an estimated 20 million lives in their first year.

Supersized Bacterium

NPR reports that researchers have found and characterized a bacterium that is visible to the naked eye.

Also Subvariants

Moderna says its bivalent SARS-CoV-2 vaccine leads to a strong immune response against Omicron subvariants, the Wall Street Journal reports.

Science Papers Present Gene-Edited Mouse Models of Liver Cancer, Hürthle Cell Carcinoma Analysis

In Science this week: a collection of mouse models of primary liver cancer, and more.