Skip to main content
Premium Trial:

Request an Annual Quote

This Week in PNAS: Aug 22, 2017

In the early, online version of the Proceedings of the National Academy of Sciences, a Duke University-led team takes a look at host contributors to typhoid fever risk. Using a so-called "high-throughput human in vitro susceptibility testing" (Hi-HOST) approach, the researchers assessed Salmonella enterica serovar Typhi (S. Typhi) invasiveness in relation to genotype in hundreds of human lymphoblastic cell lines, before taking insights from that association analysis forward for a series of molecular and cellular experiments in cell lines, mouse models, and zebrafish. Their results suggest that variants that mute expression of a protein encoded by VAC14 lead to enhanced cholesterol at cell membranes, helping S. Typhi bacteria latch on and make their way into host cells. GenomeWeb has more on this study, here.

A PNAS study by investigators at Ohio State University describes a splicing isoform of NRAS that appears to help BRAF-mutant melanomas develop resistance to BRAF inhibitors such as vemurafenib. The team saw varied NRAS isoform 2 expression across nine melanoma cell lines using real-time RT-PCR to trace transcript expression, prompting a series of experiments to assess NRAS isoform 2 effects on melanoma cell proliferation, tumor growth, and BRAF inhibitor response in cell lines and mouse models of melanoma. While acquired vemurafenib resistance was linked to increased NRAS isoform 2 expression in melanoma cell lines, for example, the authors report that such resistance waned when they dialed down NRAS isoform 2 expression.

Researchers from the UK and Spain explore the effects of obesity-related variants near the TMEM18 gene on chromosome 2 in mouse tissues, cell lines, and models of obesity. The team turned to quantitative PCR, RNA sequencing, and other approaches to follow TMEM18 expression, localization, and interactions in samples from wild type and mutant mice after fasting or feasting. Together, the experiments indicate that enhanced TMEM18 levels in mouse hypothalamus tissues may lead to diminished food intake, while waning TMEM18 expression apparently boosts appetite and reduces energy use, leading to weight gain. "Our data support the hypothesis that TMEM18 itself, acting within the central nervous system, is a plausible mediator of the impact of adjacent genetic variation on human adiposity," they write.