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PNAS Papers on Mouse Heart Aging, Amphibian Speciation, Default Mode Network Optogenetics

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

For a paper scheduled to appear in PNAS this week, researchers from the Maastricht University and other centers in the Netherlands, Germany, and Spain characterize genomic and transcriptomic features in myocardium heart tissue in mouse models of natural and premature aging, including models of cardiomyocyte-specific DNA repair deficiency, human Hutchinson-Gilford progeria syndrome (HGPS), reduced mitochondria-related antioxidant activity, and telomere-shortening mutations. Based on RNA sequencing and DNA sequencing profiles on heart tissues and samples from other body sites, the authors suggest DNA damage and related genomic instability occur in specific syndromes linked to enhanced aging but may not be a significant driver of normal mouse heart aging. "[O]ur results demonstrate that genomic and transcriptomic instability do not evidently contribute to the natural aging of murine hearts nor in hearts from a mouse model that faithfully mimics the human HGPS genetic disorder," they report. "Only in prematurely aged mouse models with heart-restricted deletion of the DNA repair machinery or severely impaired mitochondrial antioxidant capacity was genomic instability abundant."

An international team looks at speciation contributors in amphibians, focusing on dozens of species pairs from frog and toad lineages falling in a biogeographic region known as the Western Palearctic. Using available reproductive isolation and geographic data, whole-genome sequences, restriction site-associated DNA sequencing, phylogenetics, and other approaches, the researchers saw signs of introgression-resistant genome regions stretching out between more divergent amphibian species, consistent with polygenic reproductive isolation effects that were not necessarily centered on sex-linked loci. "Unlike mammals and birds … the undifferentiated sex chromosomes of amphibians do not always host more genetic incompatibilities than other chromosomes," they write. "These combined results might explain why amphibian speciation is relatively slow, and its clock-like dynamics offer practical perspectives to categorize evolutionary lineages into species or subspecies."

Researchers from the University of Fribourg in Switzerland report on findings from an optogenetic study of the ventral pallidum brain structure's role in default mode network (DMN) activity in a rat model, where they found that activation of the brain structure prompted enhanced DMN activity and reduced performance on auditory discrimination tasks. "Using an optogenetic approach, we show that activation of the ventral pallidum (VP), a subcortical node of the DNM, keeps animals in an inwardly focused state, severely compromising new learning," the team writes. "Conversely, VP inactivation allows escape from automatized behavior, conferring a learning advantage."