In this week's Science, investigators at the National Institute of Allergy and Infectious Diseases, the National Human Genome Research Institute, and Columbia University Medical Center report their screening of 61 parasite lines against more than 2,800 compounds in the National Institutes of Health Chemical Genomics Center Pharmaceutical Collection. When that screen was combined with the results of their genome-wide association analyses, the researchers "identified 32 highly active compounds and genetic loci associated with differential chemical phenotypes" between those lines. Further, the NIAID-led team reports its testing of "drugs whose responses mapped to wild-type or mutant pfcrt alleles" both in vitro and in vivo, which it says "yielded promising new leads for antimalarial treatments." Our sister publication GenomeWeb Daily News has more on this study.
In a paper published online in advance this week, a team led by researchers at the Johns Hopkins Kimmel Cancer Center shows that "mutations in CIC and FUBP1 contribute to human oligodendroglioma." By sequencing the exomes of seven tumors, the team found the CIC gene somatically mutated in six cases, and the FUBP1 gene on chromosome 1p somatically mutated in two. When the researchers examined 27 additional oligodendrogliomas, they found 12 had the CIC mutations and three had mutations at FUBP1, suggesting that these genes could play "a critical role … in the biology and pathology of oligodendrocytes," they write.
A team led by investigators at the Chinese Academy of Sciences shows that 5-methylcytosine — or 5mC — and 5-hydroxymethylcytosine — 5hmC — in DNA "are oxidized to 5-carboxylcytosine — 5caC — by Tet dioxygenases in vitro and in cultured cells." Further, in its Science paper published online in advance this week, the team says that "oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation."
Over in Science Signaling, Cornell University's Anand Vaidya and Brian Crane, along with their colleagues at Dartmouth College, present a crystal structure for the fully light-adapted protein VIVID — or VVD — from the filamentous fungus Neurospora crassa, and discuss the "mechanism by which light-driven comformational change" alters its oligomeric state. "The mechanism of dimerization of VVD provides molecular details that explain how members of a large family of photoreceptors convert light responses to alterations in protein-protein interactions," Vaidya, Crane et al. write.