This Week in Science

Science  11 Jan 2008:
Vol. 319, Issue 5860, pp. 135
  1. EPCs at the Switch


    To ensure a steady supply of oxygen and nutrients, tumors send signals that stimulate the growth of new blood vessels. Bone marrow-derived cells called endothelial progenitor cells (EPCs) are known to be recruited to the tumor-associated growing vessels, but the presence of these cells at only very low levels in the tumor vasculature has made it difficult to assess their functional contribution. Studying mouse models of lung metastasis, Gao et al. (p. 195; see the Perspective by Rafii and Lyden) show that EPCs are critical regulators of the “angiogenic switch” that helps drive the progression of dormant micrometastases to lethal metastases. Genetic manipulations that blocked EPC mobilization in tumor-bearing mice inhibited angiogenesis, impaired formation of lung metastases, and increased survival time.

  2. Exotic Superconductors in Magnetic Field

    When a magnetic field is applied to a superconductor, a regular lattice of vortices usually forms in which each vortex is threaded by a single quantum of magnetic flux. This process is often described by the phenomenological Ginzburg-Landau theory in terms of two length scales for the magnetic field, a coherence length and a penetration depth. Bianchi et al. (p. 177) now report neutron-scattering results on the heavy fermion compound CeCoIn5 that show a complete departure from this model. The authors suggest that the response is caused by spin polarization of the quasiparticles within the normal state vortex core that arises from the superconducting state being near a quantum critical point.

  3. Chemical Ins and Outs

    In bimolecular nucleophilic substitution (the SN2 reaction), an attacking group, usually an anion, binds to a carbon center and simultaneously ejects a leaving group on the opposite side. This reaction has been understood in broad terms for many decades, but many details have been obscured by medium effects and the low-energy discrimination attainable in gas-phase studies. Mikosch et al. (p. 183; see the Perspective by Brauman) have achieved precise control over the gas phase collision energies of Cl and CH3I and mapped out the quantum mechanical dynamics that lead to CH3Cl and I. Analysis in concert with theoretical simulations reveals a progression with increasing energy from a mechanism involving a pre-reaction complex to a more direct displacement.

  4. Cold Cretaceous Pockets

    Although the Cretaceous was a period of exceptionally warm sea surface temperatures and high sea levels, geological and isotopic evidence (such as sea-level changes and Δ18O excursions) suggests that glaciation occurred during that period. Bornemann et al. (p. 189; see the news story by Kerr) now show significant glaciation occurred during the peak of the Creatceous warmth, around 91 million years ago. By combining measurements of the Δ18O of foraminifera, which is a function of ocean temperature and ice volume, and a membrane lipid index that solely reflects temperature changes, the authors show that there was a 200,000-year interval of glaciation, possibly as an ice sheet in Antarctica about half the size of the current ice cap.

  5. Dwarf Galaxy Puzzles


    The stars and dark matter of dwarf galaxies are less concentrated than theories predict. Mashchenko et al. (p. 174, published online 29 November) used computer simulations to model the effects of expelled material from supernovae and stellar winds on the overall properties of dwarf galaxies. Such stellar feedback of material drives large-scale bulk motions of interstellar gas that change the gravitational potential such that the central matter density of the galaxy is reduced. This effect helps explain many puzzling properties of dwarf galaxies, such as their large dark matter cores, globular cluster distributions, and stellar population gradients.

  6. Where the Action Is

    An immune response to infection begins within the secondary lymphoid tissues, where foreign antigen is presented to T cells by dendritic cells. Activated T cells then migrate to the infected peripheral tissues. Wakim et al. (p. 198) present evidence that may revise the view that peripheral sites are simply arenas for the end stages of combat. A pathogen (herpes simplex virus) was experimentally reactivated in transplanted nervous tissue in combination with adoptively transferred T cells. Fresh T cell activation was detected at these sites, and as happens in lymph nodes, this process required dendritic cells and the help of CD4+ T cells.

  7. Expressing Estrogen-Responsive Genes

    Estrogens, upon recruitment of their cognate receptors, govern the expression of target genes. Perillo et al. (p. 202) show that transcription of estrogen-responsive genes is driven by hormone-dependent demethylation of a critical lysine in histone H3 to induce a local oxidative burst that modifies the surrounding DNA by guanine oxidation, which is subsequently removed by specific glycosylases. 8-oxo-guanine-DNA glycosylase 1 and the topoisomerase IIβ enzyme are recruited to these loci and bend the intervening DNA-chromatin region to mark the site where transcription begins and drive expression of estrogen-responsive genes.

  8. Find Your Partner

    The interactions of proteins with each other and of protein subunits within a complex are, as one would expect, primarily dictated by the amino acid side chains located at the contact interfaces. Interfacial residues can be hotspots of evolutionary change, and cross-species comparisons of changes often provide insights into the link between oligomeric structure and catalytic-regulatory functions. Grueningeret al. (p. 206; see the Perspective by Janin) have applied these insights in a project to alter, in a rational fashion, the oligomeric state of five enzymes. The authors conclude that symmetry elements are key to achieving success in the redesign of natural protein-protein interactions.

  9. Capturing RNA Molecules with DNA Scaffolds

    Analytical detection of nucleic acid molecules usually requires amplification strategies. Ke et al. (p. 180) present a direct capture strategy in which RNAs are imaged with an atomic force microscope (AFM). They modified DNA scaffolding, in which short single-stranded oligonuclides are used to fold a much longer single-stranded DNA into a compact shape. In this case, they fold M13 viral DNA (∼7000 bases) into a rectangular tile with >200 short strands, but a small fraction of the helper strands have 20-nucleotide overhangs that are located in pairs and act as capture sequences for murine messenger RNA targets. After incubation with cellular extracts, the DNA tiles were adsorbed onto mica and then imaged with an AFM. The unpaired nucleotide pairs are flexible and provide little force signal, but binding of the RNA bridges the strands and creates a stiff structure that provides a strong force signal. Registration features tag the tile for its particular gene of interest. This method was used to quantify RNAs at concentrations down to 200 picomolar. P>

  10. Nonvolcanic Tremor Triggers

    Episodes of nonvolcanic tremor and accompanying slow slip occur in the subduction zones of Japan and Cascadia. These events occur over long time scales and have different physical attributes than normal earthquakes (see the Perspective by Richardson and Marone). In Cascadia, Rubinstein et al. (p. 186, published online 22 November) show that this phenomenon cycles with the tides. They recorded three episodes in the Puget Sound-Southern Vancouver Island portion of the Cascadia subduction zone and see clear pulsing of tremor activity with periods of 12.4 and 24 to 25 hours, the same as the principal lunar and lunisolar tides. As tremor is more sensitive to tides than normal earthquakes, it suggests that tremor likely occurs on very low-stress faults. Gomberg et al. (p. 173; published online 22 November) show that surface waves from the 2002 Denali eatherquake triggered nonvolcanic tremor in numerous tectonic environments in California at the North American-Pacific plate boundary.

  11. Amazonia Futures

    The dieback of large areas of the Amazon rainforest is a potential outcome of climate change in this century. Malhi et al. (p. 169; published online 29 November) examine the climatic mechanisms operating in the Amazon basin and their sensitivity to the structure of atmosphere-biosphere models. They also explore the resilience, vulnerability, and feedbacks of both the forest biome and its human populations to such change and the potential consequences for the region and the planet, and show how the reduction of deforestation rates in Amazonia could mitigate regional and global climate change. Finally, they assess conservation and development planning in Amazonia, including economic incentives that would pay rainforest nations for the avoided emissions from protecting their standing forests.

  12. Exploring Extinction Effects

    Tight mutualisms between unrelated species are a common feature of ecosystems, but their interactions with other components of ecosystems are poorly understood. Palmer et al. (p. 192, see the cover) simulated the effects of extinction of large mammalian herbivores on an ant-Acacia tree mutualism in an African savannah ecosystem. Ten years of exclusion of herbivores from 4-hectare plots led to decreases in colony size of mutualistic ants on Acacia trees, in turn leading to increased attack by stem-boring beetles and decreased growth and increased mortality of trees. This experiment shows the strong role played by megaherbivores in the evolution of a classic mutualism, and suggests counter-intuitive repercussions of megafaunal extinctions in East Africa.

  13. Cancer Antigens Uncovered

    The potential of T cells to invade and attack tumors forms the basis for some very promising avenues of cancer immunotherapy. However, progress is often hampered by poor characterization of the antigens that killer T lymphocytes use to target tumor cells. Savage et al. (p. 215; see the Perspective by Schreiber and Rowley) describe a broadly recognized antigen in a mouse model of prostate cancer. Unusually, the antigen was derived from a ubiquitous histone protein that is normally compartmentalized away from detection by the immune system. However, in the context of the tumor, the antigen was revealed to potentially reactive T cells, which suggests that the tumor environment somehow bends the rules of antigen processing and engagement by the immune system. Because features of this model are similar to those seen in human cancers, the system may also be useful in exploring tumor detection and therapeutic immune intervention.

  14. Words for Numbers

    Recent experimental studies of Amazonian languages that contain only a few words describing quantities (such as one, two, and many) suggest that the complement of words in a language can influence thought (such as the inability to enumerate precisely four objects). Beller and Bender (p. 213) present evidence from linguistic and anthropological analyses of cultures in Oceania in support of the argument that thought can influence language. They propose that cultural needs have contributed to the evolution of an ancestrally more abstract and complex system of representing numerosity, which can produce object-specific numbers words or numeral classifiers, such as the use of the word “head” when enumerating cattle.

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