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PNAS Studies Look at Maternal Blood Extrachromosomal Circular DNAs, Mutation Accumulation, More

A team led by investigators at the Chinese University of Hong Kong takes a look at the extrachromosomal circular DNA (eccDNA) fragments found in blood plasma samples from pregnant women. Using a targeted sequencing strategy that included restriction enzyme of Tn5 transposase enzyme steps to remove background DNA, the researchers assessed eccDNAs in maternal blood plasma from five women in their third trimester of pregnancy. Their results provided a refined look at these circulating eccDNAs, revealing a population of fetal eccDNA fragments that are typically shorter than those originating maternally. "It would be interesting for future studies to explore the potential aberrations of maternal plasma eccDNA profiles in different pregnancy-associated disorders, such as preeclampsia and preterm birth," the authors write, noting that eccDNAs "might add to the toolbox of the rapidly developing field of non-invasive prenatal testing." GenomeWeb has more on this, here.

Somatic mutation accumulation may be limited by tissue compartment size, according to Hungarian researchers. After modeling the consequences of compartment size effects in self-renewing, "hierarchical" tissues undergoing cell differentiation in the presence of fast-proliferating mutant cells, the team argues that compartment size may be an unappreciated mechanism for delaying the build up of risky somatic mutations. "Our results demonstrate that, in sufficiently small compartments, even mutations that confer substantial proliferative advantage cannot persist, but are expelled from the tissue by differentiation along the hierarchy," the authors report, explaining that this produces a selective barrier that "can significantly slow down somatic evolution and reduce the risk of cancer."

A team from the University of Manchester, University of Oxford, and elsewhere describes ties between the circadian clock gene BMAL1 and immune-related processes such as motility in mouse macrophage cells responding to pneumococcal pneumonia-causing bacteria. In mice with macrophages missing the BMAL1 gene, for example, the researchers saw shifts in everything from actin cytoskeletal organization to morphology and motility, leading to enhanced Streptococcus pneumoniae ingestion and defense. With a series of follow-up experiments, including RNA sequencing analyses, the authors placed BMAL1 in a genetic circuit regulating RhoA pathway activation and other processes. "[W]e identify a surprising gain of antibacterial function due to loss of BMAL1 in macrophages, associated with a RhoA-dependent cytoskeletal change, an increase in cell motility, and gain of phagocytic function," they write.

The Scan

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

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