This Week in Science

Science  08 Feb 2013:
Vol. 339, Issue 6120, pp. 625
  1. Let There Be Mammals


    The timing of the evolution and radiation of placental mammals and their most recent common ancestor has long been debated, with many questions surrounding the relationships of groups that pre- and postdate the Cretaceous-Paleogene boundary (66 million years ago). While the fossil record suggests that placental mammals radiated after the Cretaceous, molecular clocks have consistently placed the ancestors of mammalian lineages earlier. O'Leary et al. (p. 662; see the Perspective by Yoder) examined the morphology of fossil and extant taxa and conclude that living placentals originated and radiated after the Cretaceous and reconstruct the phenotype of the ancestral placental mammal.

  2. The Holy GRAIL?

    The gravity field of a planet provides a view of its interior and thermal history by revealing areas of different density. GRAIL, a pair of satellites that act as a highly sensitive gravimeter, began mapping the Moon's gravity in early 2012. Three papers highlight some of the results from the primary mission. Zuber et al. (p. 668, published online 6 December) discuss the overall gravity field, which reveals several new tectonic and geologic features of the Moon. Impacts have worked to homogenize the density structure of the Moon's upper crust while fracturing it extensively. Wieczorek et al. (p. 671, published online 6 December) show that the upper crust is 35 to 40 kilometers thick and less dense—and thus more porous—than previously thought. Finally, Andrews-Hanna et al. (p. 675, published online 6 December) show that the crust is cut by widespread magmatic dikes that may reflect a period of expansion early in the Moon's history.

  3. Fixing Broken DNA

    Some physiological processes, such as immunoglobulin class switching and telomere attrition, result in double-stranded DNA breaks. The DNA damage repair protein, 53BP1, prevents nucleolytic processing of these breaks, but the proteins it partners with to do this are unknown (see the Perspective by Lukas and Lukas). Di Virgilio et al. (p. 711, published online 10 January), using mass spectroscopy–based methods, and Zimmermann et al. (p. 700, published online 10 January), using a telomere-based assay, identify Rif1 as a 53BP1 phosphorylation- and DNA damage–dependent interaction partner. Mice with a B cell–specific deletion in Rif1 showed impaired immunoglobulin class switching. Rif1-deficient cells exhibited extensive 5′-3′ resection at DNA ends, with enhanced genetic instability. Thus, Rif1 partners with 53BP1 to promote the proper repair of double-stranded DNA breaks.

  4. E. coli kNOws How to Win

    The harmonious existence among the various microbial inhabitants of the gut is critical for good health. However, inflammation from injury or inflammatory bowel disease, can disrupt this balance and lead to the outgrowth of particular bacteria. The outgrowth of members of the Enterobacteriaceae family, which includes Escherichia coli, is often observed. Because E. coli are facultative rather an obligate anaerobes, Winter et al. (p. 708) postulated that they may be able to use by-products of reactive oxygen and nitrogen species, which are produced during inflammation, for anaerobic respiration, thereby edging out other fermenting bacteria. Indeed, in two mouse models of colitis and in a model of intestinal injury, various E. coli strains were able to use host-derived nitrate as an energy source and outcompete mutant strains unable to do this.

  5. Mimicking Hydrogenase

    Hydrogenase enzymes possess unusual bimetallic active sites that cleave H2. The enzymes make use of abundant metals (iron and sometimes nickel), in contrast to the often expensive synthetic catalysts that rely on rarer elements such as ruthenium or platinum. Ogo et al. (p. 682; see the Perspective by Armstrong) now report a bimetallic coordination compound of iron and nickel that can catalyze electron and hydride transfers from H2 in a manner analogous to the corresponding enzyme and characterize the structure of an intermediate with bound hydride.

  6. Stressed Out


    Large seismic events such as the 2011 magnitude 9.0 Tohoku-Oki earthquake can have profound effects not just on the severity of ground motion and tsunami generation, but also on the overall state of the crust in the surrounding regions. Lin et al. (p. 687) analyzed the stress 1 year after the Tohoku-Oki earthquake and compared it with the estimated stress state before the earthquake. In situ resistivity images were analyzed from three boreholes drilled into the crust across the plate interface where the earthquake occurred. Stress values indicate a nearly complete drop in stress following the earthquake such that the type of faulting above the plate boundary has changed substantially. These findings are consistent with observations that the sea floor moved nearly 50 meters during the earthquake.

  7. Targeting HPV

    Papillomaviruses infect mammalian epithelial cells and induce cancers, including cervical cancer in humans. Vaccines against human papillomavirus (HPV) can prevent, but not cure, infection. A key viral oncoprotein, E6, acts by binding and inactivating many host proteins. Zanier et al. (p. 694) determined high-resolution crystal structures of bovine papillomavirus bound to a peptide from the focal adhesion protein, paxillin, and of HPV bound to a peptide from the ubiquitin ligase E6AP. The structures show that the peptide binds in a pocket formed by two zinc domains and a linker helix, which represents a promising target for therapeutics.

  8. Genetic Epigenetics


    Posttranslational modifications of histone proteins have been implicated in the regulation of gene transcription in organisms ranging from yeast to humans. However, epigenetic regulators can modify multiple proteins. By mutating specific histone sites in Drosophila, Pengelly et al. (p. 698) demonstrate that mutation of lysine 27 of histone H3 causes the same transcriptional defects as those observed in mutants lacking the methyltransferase PRC2 that modifies this H3 residue. These results demonstrate the functional importance of H3-K27 methylation in Polycomb repression. Furthermore, this genetic approach may be applied to investigating numerous other metazoan-specific histone modifications.

  9. Acid-Derived Diversity

    Compounds with nitrogen-bearing rings have proven rather promising in pharmaceutical research, spurring the need for improved synthetic methods to access structurally diverse variants of this motif. Duttwyler et al. (p. 678) show that applying acids of different strengths to a dihydropyridine intermediate leads to selective protonation at either of two sites, depending on whether the reaction proceeds under kinetic or thermodynamic (that is, equilibrated) control. The protonations in turn activate the rings for addition of various carbon nucleophiles to the periphery, thereby affording multiple different substitution patterns for use in screening studies.

  10. Impact Dating

    The large mass extinction of terrestrial and marine life—most notably, non-avian dinosaurs—occurred around 66 million years ago, at the boundary between the Cretaceous and Paleogene periods. But attributing the cause to a large asteroid impact depends on precisely dating material from the impact with indicators of ecological stress and environmental change in the rock record. Renne et al. (p. 684; see the Perspective by Pälike) acquired high-precision radiometric dates of stratigraphic layers surrounding the boundary, demonstrating that the impact occurred within 33,000 years of the mass extinction. The data also constrain the length of time in which the atmospheric carbon cycle was severely disrupted to less than 5000 years. Because the climate in the late Cretaceous was becoming unstable, the large-impact event appears to have triggered a state-shift in an already stressed global ecosystem.

  11. Parainfluenza 5 and MDA5

    Our immune system and the viruses that infect us are in a constant arms race, with one side always trying to outwit the other. One example is the inhibition of host protein MDA5, a member of the retinoic acid–inducible gene 1 (RIG-I)–like receptor (RLR) family of innate immune sensors, by the V protein expressed by parainfluenza virus 5 (PIV5). To better understand how this inhibition is accomplished, Motz et al. (p. 690, published online 17 January) solved the crystal structure of PIV5 V protein bound to the adenosine triphosphatase (ATPase) domain of porcine MDA5. This analysis, together with mutational studies using mouse and human versions of MDA5, revealed that the V protein unfolds the ATPase domain of MDA5 and replaces two β strands of this domain's structural core. These changes disrupt the ATPase hydrolysis site and prevent the formation of filaments by MDA5, which are important for transmitting downstream signals that activate antiviral immunity. Mutation of just two amino acids in RLR family member RIG-I also rendered this receptor susceptible to V protein–mediated inhibition.

  12. Sweet Enough to Flower

    In making the developmental switch from vegetative growth to flowering, plants integrate diverse information, including photoperiod, hormone signals, and carbohydrate status. Wahl et al. (p. 704; see the Perspective by Danielson and Frommer) analyzed the physiology of the signaling sugar trehalose-6-phosphate (T6P) in Arabidopsis. Quantities of T6P cycle in daily rhythms that peak toward the end of the day. T6P levels in the shoot apical meristem mirrored sucrose levels. Disruption of T6P production also disrupted expression of the FLOWERING LOCUS T gene, which responds in leaves to day length and generates signals that direct the meristem to initiate flowering programs. T6P production also affected the signaling pathway that links the age of the plant to flowering. By incorporating requirements for T6P signaling in the flowering induction pathways, the plant ensures that adequate carbohydrate reserves have been accumulated. Thus, T6P regulates the shift to flowering by linking carbohydrate status to day length in the leaves and to developmental age in the shoot apical meristem.

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