Skip to main content
Premium Trial:

Request an Annual Quote

PNAS Papers on Ancient Tibetan Animals, HNSCC Drug Response, More

Editor's Note: Some of the articles described below are not yet available at the PNAS site, but they are scheduled to be posted some time this week.

Researchers from the Chinese Academy of Sciences and other centers in China, the UK, and Italy report on findings from an analysis of ancient large animal genomes on the Tibetan Plateau. The team focused on Neolithic animal remains from the northeastern region of the Tibetan Plateau, generating genome sequences and mitochondrial DNA profiles for bovid and rhinoceros representatives going back roughly 5,200 years. The results pointed to the presence of the tropical gaur (Bos gaurus) and Sumatran rhinoceros (Dicerorhinus sumatrensis) at sites that are much farther north than the animals' current range, the authors write, noting that "multidisciplinary exploration indicates that a high summer temperature in the late Neolithic might have facilitated the northward expansion of these tropical animals to the [northern Tibetan Plateau], which enriched the biodiversity of wildlife and contributed to the exploration of the Tibetan Plateau as one of the last habitats for hunting game in East Asia." 

For a paper slated to appear in PNAS this week, a Fred Hutchinson Cancer Research Center and University of Washington team outlines a potential contributor to targeted treatment response in head and neck squamous cell carcinoma (HNSCC) cases marked by high-risk human papilloma virus (HPV) 16 infections. Based on their analyses of available RNA sequence data, cell line experiments, protein interaction data, and more, the researchers suggest that E6 and E7 oncoproteins produced by HPV16 can increase activity by a FOXM1-CDK1 pathway involved in mitosis and DNA damage, apparently boosting response to a WEE1 kinase enzyme inhibitor called AZD1775. "We show that HPV16 E6/E7 render HNSCC sensitive to Wee1 inhibition through a CDK1-FOXM1 circuit that drives premature mitosis and requires E6 activities beyond p53 inactivation," they report, adding that the current results "provide a mechanistic rationale for WEE1 [inhibitor] incorporation into HPV-[positive] HNSCC treatment."

Investigators in Sweden, China, and other international centers present data consistent with a role for the protein kinase enzyme-coding gene MNK2 in anti-inflammation processes in tumor-associated macrophages (TAMs) — a role that appears to be independent from an mTOR signaling pathway that converges on the same eIF4E component of a translation initiation pathway. Based on polysome profiling, RNA sequencing, PCR, and other analyses of mouse cell lines and tumor models, the authors saw signs that MNK2 phosphorylation of eIF4E contributes to anti-inflammation features in macrophages by shifting messenger RNA (mRNA) translation patterns, while dialed down MNK2 activity could curb anti-inflammatory macrophage reprogramming. "[W]e show that, during acquisition of a protumor phenotype, gene expression in TAMs is predominantly modulated via selective changes in mRNA translation rather than changes in mRNA abundance," they write.