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This Week in PNAS: Jun 5, 2018

A Kyoto University-led team of researchers found an allele that increases a person's risk of age-related macular degeneration is also protective against choroidal thickening, which occurs as part of central serous chorioretinopathy. As the researchers report in the Proceedings of the National Academy of Sciences, they conducted a genome-wide association study of choroidal thickness in 3,418 individuals to identify two susceptibility loci, including CFH rs800292, a known AMD susceptibility polymorphism. In a case-control study, they confirmed the association between the polymorphisms and central serous chorioretinopathy. The researchers further report that the CFH rs800292 G allele is a risk allele for AMD, while the A allele is a risk allele for thicker choroids and CSC development, which they say underscores differences in pathophysiology between the conditions.

Researchers from the Weizmann Institute of Science report in PNAS that the transcriptional program supported by p53 is altered in cancer-associated fibroblasts — which promote tumor progression — as compared to normal fibroblasts. The changes to p53 in the conversion of normal fibroblasts to cancer-associated ones are non-mutational, the researchers add, and they instead rewire its transcriptional program and output, allow it to support rather than restrict tumor growth. This suggests to the researchers that "re-educating" tumor-associated stromal cells could represent a possible therapeutic avenue.

An international team of researchers reports on a link between the gut microbiota and maturation of the adult enteric nervous system. The team used germ-free mice — which have an immature enteric nervous system — and colonized them microbiota of conventionally raised mice to examine how the gut microbiome interacts with the enteric nervous system. Colonization led to increased intestinal transit time and was associated with the release of serotonin (5-HT), the team reports. The researchers then found that the serotonin release and activation of the 5-HT4 receptor enabled communication between the gut microbiota and enteric neurons. This opens up, the researchers say, new avenues to treat inflammatory gut diseases.