In the PNAS Early Edition this week, researchers at the Allen Institute for Brain Science in Seattle and their colleagues report "the relationship between genetic background and spatial patterns of gene expression across seven strains of mice," which they deduced via in situ hybridization to 49 mouse-brain genes that encode known drug targets. They found that more than half of those genes "showed inter-strain expression variation" and, further, the "variability was non-uniformly distributed across strain and neuroanatomic region." The Allen Institute-led team suggests that divergence in mouse brain gene expression patterns "could contribute significantly to variations in behavior and responses to neuroactive drugs," in lab animals and "may help to explain individual differences in human responsiveness" to pharmaceutical treatments.
Researchers in India this week provide support for the idea that EGLN1 is involved in high-altitude adaptation under the Ayurvedic concept of Prakriti, "which relates to phenotypic differences in normal individuals — including response to external environment as well as susceptibility to diseases — to explore molecular differences between" individuals. The SNPs rs479200 and rs480902 at EGLN1 are associated with high-altitude adaptation, the authors write, adding that the polymorphisms are "overrepresented in a subgroup of normal lowlanders" and "may confer increased risk for high-altitude pulmonary edema."
Investigators at Stanford and Cornell show that the helix-turn-helix transcription factor SciP is essential for Caulobacter cell cycle regulation. SciP, which is "co-conserved with the global cell cycle regulator CtrA in the α-proteobacteria," is expressed and accumulates in the daughter swarmer cell late in the cell cycle. The team shows that "SciP overexpression disrupts the balance between activation and repression of the CtrA-SciP co-regulated genes yielding filamentous cells and loss of viability," they write.
And researchers at the Broad Institute report in PNAS this week their analysis of the correlation between various small molecules and their protein-binding profiles. By measuring the "protein-binding activities of each individual compound against each of 100 diverse (sequence-unrelated) proteins using small-molecule microarrays," the Broad team found that "increasing the content of sp3-hybridized and stereogenic atoms relative to compounds from commercial sources ... improved binding selectivity and frequency," they write, adding that their study suggests structural elements that ought to be targeted by those who synthesize screening collections for biological discovery.