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This Week in PNAS: Feb 15, 2011

In the PNAS Early Edition this week, Sunny Wong and Jeremy Reiter show that wounding recruits stem cells from the hair-follicle bulge and secondary hair germ to the injury site and that the downstream Hedgehog "signal transduction is de-repressed, giving rise to superficial BCC [basal cell carcinoma]-like tumors," which serves to explain, in part, the documented relationship between wounding and tumorigenesis. In another PNAS paper published online in advance this , investigators at Sweden's Karolinska Institutet also report that "wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes."

Researchers at the Beckman Research Institute of the City of Hope report that in advanced, pronuclear stage zygotes, "reprogramming of the paternal genome upon fertilization involves genome-wide oxidation of 5-methylcytosine," such that the "paternal pronucleus contains substantial amounts of 5hmC, but lacks 5mC." The City of Hope team says that bisulfite sequencing data confirms their finding that conversion of modified cytosines to cytosines at several gene loci is limited, as "5hmC persists into mitotic one-cell, two-cell, and later cleavage-stage embryos." Finally, the team suggests that "5mC oxidation is carried out by the Tet3 oxidase."

Investigators at Yale University used neural-specific conditional mutant mouse models to determine the CCM3/programmed cell death 10 gene's cell autonomous role in cerebral cavernous malformations. Overall, the team found that Ccm3 has both neural cell autonomous and non-autonomous functions, and that "Gfap- or Emx1-Cre-mediated Ccm3 neural deletion leads to increased proliferation, increased survival, and activation of astrocytes." Further, loss of neural CCM3 leads to a phenotype similar to that which is associated with human cavernomas, the team says.

Stanford University's Eric Kool and his colleagues show in an advance online publication of PNAS that oligodeoxyfluoroside fluorophores — "short, DNA-like oligomers with fluorophores replacing the DNA bases," or ODFs — can be "used to mark primary antibodies," such that researchers can label molecules in vivo with a wide spectrum of colors. In its paper, the Stanford team reports its labeling of secondary antibodies to "simultaneously mark four antigens in fixed cells" and to image "different surface tumor markers on two live cell lines. Using ODFs, the team writes, "all colors could be visualized simultaneously by eye under the microscope, yielding multicolor images of multiple cellular antigens in real time."

The Scan

Wolf Howl Responses Offer Look at Vocal Behavior-Related Selection in Dogs

In dozens of domestic dogs listening to wolf vocalizations, researchers in Communication Biology see responses varying with age, sex, reproductive status, and a breed's evolutionary distance from wolves.

Facial Imaging-Based Genetic Diagnoses Appears to Get Boost With Three-Dimensional Approach

With data for more than 1,900 individuals affected by a range of genetic conditions, researchers compared facial phenotype-based diagnoses informed by 2D or 3D images in the European Journal of Human Genetics.

Survey Suggests Multigene Cancer Panel VUS Reporting May Vary Across Genetic Counselors

Investigators surveyed dozens of genetic counselors working in clinical or laboratory settings, uncovering attitudes around VUS reporting after multigene cancer panel testing in the Journal of Genetic Counseling.

Study Points to Tuberculosis Protection by Gaucher Disease Mutation

A mutation linked to Gaucher disease in the Ashkenazi Jewish population appears to boost Mycobacterium tuberculosis resistance in a zebrafish model of the lysosomal storage condition, a new PNAS study finds.