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This Week in PLoS: Nov 18, 2008

In PLoS One, researchers used genome-wide miRNA expression profiling on human embryonic stem cells to find several miRNAs that are involved in the differentiation process. Lentiviral induction of several liver-specific miRNAs, including miR-122 and miR-192, caused increased endodermal gene expression.

In another study, Greek scientists used profiling to determine a signature of 16 miRNAs for osteoarthritis. Using reverse-phase protein arrays, they found 76 differentially expressed proteins. They also showed that miR-2 regulates PPARA and BMP7 and its inhibition blocks inflammatory and catabolic changes, suggesting that obesity and inflammation are related to osteoarthritis.

Also in PLoS One, researchers looked at transgenerational alterations in the male and female brain transcriptomes after embryonic exposure to the endocrine disruptor, vinclozolin, which can have epigenetic and phenotypic affects three generations later. In males, they found that expression of 92 genes in the hippocampus and 276 genes in the amygdala was altered across generations, while in females, expression of 1,301 genes in the hippocampus and 172 genes in the amygdala was transgenerationally altered.
A team led by Stanford's David Relman used deep sequencing to map the human gut after exposure to the common antibiotic Ciprofloxacin. Cipro "reduced the diversity of the intestinal microbiota, with significant effects on about one-third of the bacterial taxa," they write. However, most individuals' guts returned to their pre-treatment states within four weeks.

A paper by Scripps' Kevin Morris in PLoS Genetics follows up on previous work describing transcriptional gene silencing. Here, he shows that silencing a p21-specific antisense transcript leads to transcriptional activation of p21 gene expression. His findings, he writes in the summary, support that idea that "bidirectional transcription is an endogenous mechanism whereby RNA-directed gene regulation is operative and that RNA activation is the result of a disruption of this endogenous pathway."

Finally, in PLoS Pathogens, there's a study that used an RNAi screen of the entire kinome in human Huh7 hepatoma cells to find genes potentially involved infection by malaria-causing Plasmodium berghei sporozoites. They found five top hits, including PKCzeta in particular, that caused significant reductions in infection when silenced by RNAi.


The Scan

Study Finds Sorghum Genetic Loci Influencing Composition, Function of Human Gut Microbes

Focusing on microbes found in the human gut microbiome, researchers in Nature Communications identified 10 sorghum loci that appear to influence the microbial taxa or microbial metabolite features.

Treatment Costs May Not Coincide With R&D Investment, Study Suggests

Researchers in JAMA Network Open did not find an association between ultimate treatment costs and investments in a drug when they analyzed available data on 60 approved drugs.

Sleep-Related Variants Show Low Penetrance in Large Population Analysis

A limited number of variants had documented sleep effects in an investigation in PLOS Genetics of 10 genes with reported sleep ties in nearly 192,000 participants in four population studies.

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.