Editors' Choice

Science  26 Oct 2007:
Vol. 318, Issue 5850, pp. 535

    Brief Encounter

    The Small and Large Magellanic Clouds are our nearest galactic neighbors, visible in southern skies as thumb-sized smudges on the sky. Recent tracking with the Hubble Space Telescope showed that they are circling the Milky Way faster than was once thought, closely approaching the Milky Way's escape velocity. Besla et al. model the past motions of the Magellanic Clouds using the updated speeds and latest cosmological parameters and find that they are probably interlopers on their first pass of the Milky Way, rather than long-term companions on continuous orbits. This brief encounter scenario resolves some questions but raises others. It may explain why there has been an upsurge in star formation in the Clouds within the past few billion years. However, it also means that the Clouds may have had less of an effect on the diffuse hydrogen envelope of the Milky Way than had been assumed, as they have not been around long enough to warp the edges of the pancake of hydrogen in which the Milky Way sits or to pull out the Magellanic Stream, a band of hydrogen gas that almost circles the Milky Way and seems to follow the Clouds. — JB

    Astrophys. J. 668, 949 (2007).


    A Measured Flow

    Measurement of the flow of thin films is complicated by the coupling of frictional forces and the driving force (pressure) at the molecular level. To this end, Xu et al. designed a set of brush like polymers, with a flexible backbone connected to a dense shell of rigid side chains. When the polymers are driven across a substrate, the reduced interaction of side groups with the substrate causes the backbone to coil, and the extent of this compacting can be used to gauge local variations in film pressure. Conformational changes can also reveal the friction coefficient at the substrate. The authors tracked polymer spreading on mica or graphite using atomic force microscopy (AFM) to probe the local chain conformations. The friction coefficient showed strong humidity dependence on the hydrophilic mica substrate, though not on hydrophobic graphite. The limitations of AFM detection notwithstanding, the authors envision a range of situations where these polymer probes could be useful pressure sensors. — MSL

    Adv. Mater. 19, 2930 (2007).


    Down from the Shelves

    Biological productivity in the ocean—which helps control climate on glacial time scales through its effect on the global carbon cycle—is regulated by the availability of nutrients such as phosphorus. The marine phosphorus cycle has in turn been thought to depend greatly on the variations in sea level caused by the growth and decay of continental ice sheets during the glacial cycle, which alternately expose and submerge continental shelves, but data relating to this hypothesis are scarce. Filippelli et al. combine measurements of the phosphorus concentration in deep sea sediments from the Atlantic and the Pacific with recent advances in the understanding of phosphorus geochemistry to show that the phosphorus inventory of those sediments increased during glacial periods and decreased during interglacials over the past 400,000 years. This finding supports the Shelf-Nutrient Hypothesis, which postulates that phosphorus should be transferred from shallow continental margins to the deep sea when continental shelves become exposed during glacial sea-level lowstands. These results should help to define the role that productivity plays in the regulation of atmospheric carbon dioxide over glacial/interglacial transitions, as well as the respective roles of external processes such as dust deposition, and internal processes such as upwelling, in the regulation and distribution of ocean nutrients. — HJS

    Deep-Sea Res. II 10.1016/j.dsr2.2007.07.021 (2007).


    Hooked on Interference

    Argonaute (Ago) proteins are the effectors that lie at the heart of RNA interference. They bind small interfering (si) or micro (mi) RNAs and use them to target and to repress (in most cases) complementary RNAs, either directly, at the posttranscriptional stage, or indirectly (in the case of some siRNAs) at the transcriptional stage. In fission yeast, transcriptional gene silencing (TGS) is mediated by the RITS complex, which includes the Ago1 and Tas3 proteins. Till et al. have dissected the interaction between Tas3 and Ago1 and find a peptide motif, which they call the Ago hook, in Tas3 that interacts both in vitro and in vivo with the PIWI domain in Ago1. The hook binds in a conserved pocket within the Ago PIWI domain; this same pocket binds the 5′ end of the siRNA/miRNA guide strand. The hook is required for TGS in vivo in fission yeast and can block Drosophila miRNA-mediated repression in vitro. Furthermore, a human Ago-interacting protein harbors a motif that is similar in sequence and in function. The hook is likely to be pivotal in recruiting Ago proteins to specific subcellular locations and in influencing the binding of siRNAs and miRNAs, and thus may determine the functional output of the various Ago complexes. — GR

    Nat. Struct. Mol. Biol. 14, 897 (2007).


    It's a Jungle Down Here

    Analyzing DNA sequences in unpurified or partially fractionated samples (such as a drop of water from the Sargasso Sea or from an acid mine drain) has proven to be remarkably informative. A high degree of organismal diversity has been documented, and extending this approach to terrestrial systems has uncovered previously unsuspected and intermingled communities of bacteria, archaea, and fungi. Vandenkoornhuyse et al. have begun to look at the exchange of goods in one such market-place by exposing pieces of turf from UK grassland (Scotland) or from French peatland (Normandy) to 13CO2 and following the transfer of the isotope into ribosomal RNA of microbes associated with the plant roots. Interpreting measurements of a non-stationary process can be somewhat challenging, but a first glance reveals a broader-than-expected population diversity and a marked unevenness in the rate of primary consumption—that is, the uptake of photosynthetic products by the root-dwelling bacteria and fungi. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 104, 16970 (2007).


    Rules of Regulation

    What overarching factors regulate the regulatory T (Treg) cells that guide our immune systems to fight infectious diseases while leaving ourselves unharmed? By scrutinizing molecular events inside Treg cells, Tao et al. implicate the activity of chromatin remodeling proteins. Initial evidence emerged from the observation that a histone deacetylase (HDAC) inhibitor increased the level of the chief transcription factor in Treg cells, Foxp3, as well as the number and activity of Treg cells in mice. Furthermore, in culture-stimulated Treg cells, HDAC9 was the most prominently expressed member of the deacetylase family, and Treg cell function was enhanced in its absence. Acetylation of the Foxp3 protein itself was also observed and corresponded with an increase in Foxp3 binding to its target genes. Finally, HDAC inhibition helped curtail inflammatory T cell responses, both to transplanted grafts and in a model of inflammatory bowel disease. The finding that regulating acetylation/deacetylation has such a measurable influence on Treg function and that it operates at the level of both the Foxp3 locus and the transcription factor suggests that different avenues might be open for testing HDAC inhibition as a form of immunotherapy. — SJS

    Nat. Med. 13, 10.1038/nm1652 (2007).

  7. STKE

    An Endogenous SERM?

    Although estrogens had long been thought to protect against cardiovascular disease, this assumption has been challenged by the results of clinical trials that failed to corroborate protective effects of hormone replacement therapy in postmenopausal women. Umetani et al. found that the cholesterol metabolite 27-hydroxycholesterol (27HC, which is found in atherosclerotic lesions) competed with estradiol for binding to estrogen receptors α and β (ERα and ERβ), inhibited estradiol-dependent activation of transcriptional activity of the receptors, and inhibited the estradiol-dependent association of ERβ with the transcriptional coactivator SRC-1. In mice fed a diet rich in cholesterol and fat, hypercholesterolemia was associated with increased vascular concentrations of 27HC, comparable to those affecting ER function; 27HC also inhibited the estradiol-dependent increase in inducible and endothelial nitric oxide synthase (iNOS and eNOS) expression in mouse aortic cultures. Administration of 27HC decreased aortic expression of iNOS and eNOS in vivo, and dietary hypercholesterolemia was associated with a decrease in iNOS mRNA and protein in male mice. The pro- or anti-estrogenic effects of 27HC depended on tissue type, leading the authors to propose that it may act as an endogenous selective estrogen response modulator (SERM). The anti-estrogenic effects of 27HC in the vasculature led them to suggest that it might contribute to a lack of cardioprotective effects of estrogen in postmenopausal women. — EMA

    Nat. Med. 13, 1185 (2007).