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This Week in PNAS: May 21, 2019

Researchers from Icahn School of Medicine, Cedars-Sinai Medical Center, and Johns Hopkins University present findings from a mouse study suggesting fetal-derived caudal-type homeobox-2 (Cdx2) cells can help regenerate heart tissue following the mouse version of a heart attack. The team relied on lineage tracing and green fluorescent protein-labeling to nab Cdx cells stemming from the fetus out of end-gestation placental samples. These fetal cells seemed to differentiate into new cardiomyocyte heart cells and vascular cells in in vitro mouse cells, the authors report. While immune transcriptomic and proteomic analyses hinted that the cells held on to some stem cell-like features in in vivo, they still prompted enhanced heart contractibility in myocardial infarction models and managed to avoid immune surveillance. "Therapeutic use of Cdx2 cells may represent a vital advance," they write, "as these cells are multipotent and immunologically naïve, with a unique proteome, compared with embryonic stem cells."

A National Institutes of Health team profiles PIWI-interacting small RNA (piRNA) levels in human cancers, searching for signs of reactivation that might impact genome stability reining in rogue mobile genetic elements. Based on cancer cell line experiments — combined with gene expression profiles from normal human tissues tested for the Genotype-Tissue Expression project, tumors assessed for the Cancer Genome Atlas project, and data for hundreds of human cell lines — the researchers did see individual piRNA pathway genes with altered expression in some cancers. But their results argued against the formation of functional, reactivated piRNA complexes in cancer. "Our data provide a framework for the investigation of complex aberrant gene expression signatures," the authors report, "and establish the reactivation of piRNA silencing, if at all, is not a prevalent phenomenon in cancer cells." 

Johns Hopkins University researchers describe an evolutionarily informed protein-design strategy based on consensus sequence. In an effort to maintain amino acid residues that were both biologically active and stable, the team considered consensus sequences found with multiple sequence alignments as part of its design process, which aimed to develop and characterize six consensus-informed proteins from half a dozen unrelated, taxonomically diverse protein families. From their results there, the authors suggest that "consensus design shows high success rates in creating well-folded, hyper-stable proteins that retain biological activities."

The Scan

Hormone-Based Gene Therapy to Sterilize Domestic Cat

A new paper in Nature Communication suggests that gene therapy could be a safer alternative to spaying domestic cats.

Active Lifestyle Linked to Type 2 Diabetes Prevention in People at High Genetic Risk

A study in the British Journal of Sports Medicine shows that an active lifestyle goes a long way in type 2 diabetes prevention.

Beneficial, Harmful Effects of Introgression Between Wild and Domesticated European Grapes

A paper in PNAS shows that European wild grapevines were an important resource for improving the flavor of cultivated wine grapes.

Genetic Ancestry of South America's Indigenous Mapuche Traced

Researchers in Current Biology analyzed genome-wide data from more than five dozen Mapuche individuals to better understand their genetic history.