This Week in Science

Science  07 Dec 2012:
Vol. 338, Issue 6112, pp. 1259
  1. Platelets Poison Parasites


    Activated platelets bound to malaria parasite–infected red blood cells were once thought to contribute to pathogenesis, but recently the platelets have been found to have a protective effect. McMorran et al. (p. 1348; see the Perspective by Engwerda and Good) extended this discovery to show that platelet activation releases intracellular granules containing a chemokine, PF4, which is internalized by Plasmodium falciparum–infected red cells. Subsequently, mature parasites within the cells die. The Duffy blood-group factor on red blood cells is known to act as a nonspecific receptor for chemokines, such as PF4, as well as a receptor for cell invasion by other species of malaria parasite. When the Duffy antigen was blocked by antibody treatment, platelets and PF4 were less able to kill the P. falciparum parasites within.

  2. Exotic Pulsations

    The launch of the Fermi Gamma-ray Space Telescope in 2008 enabled the detection of large numbers of pulsars. Millisecond pulsars, neutron stars with millisecond periods, are much more difficult to find in gamma-ray data. In a computational tour de force, Pletsch et al. (p. 1314, published online 25 October) detected gamma-ray pulsations from a formerly unidentified gamma-ray source in the Fermi Large Area Telescope Second Source Catalog. The pulsating neutron star orbits a companion star more rapidly than any other such neutron star known, and the system may belong to an exotic class of binary systems where the neutron star is systematically destroying its companion.

  3. Atomic Layers from Solution

    Growth of flat thin films is often plagued by the formation of mounds and pyramids. To avoid this problem, atomic-layer deposition (ALD) can be used whereby alternating self-termination reactions stop the layer growth. Electrochemical approaches to ALD use surface alloys to slow film growth, but often lead to film contamination. Yihua Liu et al. (p. 1327; see the Perspective by Switzer) show that for platinum films, controlling surface potential can lead to adsorbed hydrogen on the surface, which can terminate film growth at one layer, leaving platinum species in solution available for further reduction. Rapid changes in applied potential can oxidize the hydrogen, which allows efficient contamination-free growth of an additional atomic layer.

  4. Robust Reduction

    A major challenge in the design of artificial photosynthesis catalysts has been their instability under the reaction conditions—a problem that plants and other autotrophs address by perpetually reproducing their biochemical machinery. Han et al. (p. 1321, published online 8 November) now demonstrate a system for photoreductive hydrogen generation in water that manifests undiminished activity for weeks at a time. Semiconductor nanoparticles for light absorption were combined with a soluble nickel complex for the catalytic chemistry. The system currently requires a sacrificial electron donor, but its robustness shows promise for future pairing with an integrated oxidation catalyst.

  5. CF3 from Fluoroform

    Fluoroform (CF3H) is a by-product from the manufacture of fluorocarbon-based materials used, for example, in nonstick coatings and refrigerants. Fluoroform's potency as a greenhouse gas is a growing concern as supplies continue to accumulate. In this context, Prakash et al. (p. 1324; see the Perspective by Haufe) show that fluoroform can be used to transfer CF3 to silicon, sulfur, and carbon centers in the development of CF3-bearing pharmaceutical and agrochemical structures.

  6. Planetary Interiors Under Pressure

    The interiors of Earth and other rocky planets generally consist of a few common minerals. Depending largely on the size of the planet, the distribution and relative abundance of these minerals varies; for example, MgO is abundant in the mantles of Earth and large Earth-like planets, but is present in Jupiter's core. The properties of MgO also vary with planetary size as a function of temperature and pressure. McWilliams et al. (p. 1330, published online 22 November) performed laser-shock experiments at pressures over three times higher than Earth's inner core. MgO underwent two phase transformations, first to a solid with a modified crystal structure, and then to a conductive liquid. In terrestrial planets greater than eight Earth masses, MgO in the mantle could generate a magnetic field–generating dynamo such as those that typically found in planetary cores.

  7. Architecture of a CRAC


    The calcium release–activated calcium (CRAC) channel generates intracellular calcium signals in response to depletion of calcium from the endoplasmic reticulum. Hou et al. (p. 1308, published online 22 November) report a high-resolution crystal structure of Orai, the CRAC channel pore from Drosophila melanogaster. Six Orai subunits surround a central pore that extends into the cytosol. The pore is in a closed conformation that is stabilized by anions binding to a basic region near the intracellular side. A ring of glutamates on the extracellular side form a selectivity filter. The channel architecture allows calcium permeation while regulating the flow to prevent overloading the cell with calcium.

  8. Plasmid Partitioning

    Bacterial plasmids need to be able to partition faithfully into daughter cells. Combining structural data and advanced microscopy, Gayathri et al. (p. 1334, published online 25 October; see the cover) describe how actin-like ParM filaments form a bipolar spindle for the faithful segregation of low-copy-number plasmids to the two cell poles of Escherichia coli, despite being polar, with two distinct ends. ParM filaments are elongated by a small adaptor protein ParR that physically links the filament end(s) to a centromere-like region on the plasmid. Antiparallel filament bundling and sliding appear to produce a bipolar spindle made of filaments that elongate unidirectionally so that all the plasmids are segregated together in one large bundle.

  9. Mind the Gap


    Near-field microscopy has benefited from subwavelength near-field plasmonic probes that make use of the field-concentrating properties of gaps. These probes achieve maximum enhancement only in the tip-substrate gap mode, which can yield large near-field signals, but only for a metallic substrate and for very small tip-substrate gap distances. Bao et al. (p. 1317) designed a probe that unites broadband field enhancement and confinement with bidirectional coupling between far-field and near-field electromagnetic energy. Their tips primarily rely on the internal gap modes of the tip itself, thereby enabling it to image nonmetallic samples.

  10. Dissecting Wnt Signaling

    The Wnt signaling pathway plays a key role in regulating a broad range of functions from development to cancer. But a precise understanding of how Wnt proteins act through their receptors (Frizzled proteins) has been elusive. By paring the system down to its core reactions and performing kinetic analysis in cultured cells, Hernández et al. (p. 1337, published online 8 November) were able to deduce the mechanism of Wnt action without invoking any previous assumptions. Such quantitative analysis of mass balance may offer a way to identify essential control points in other complicated signaling systems, and thus help define targets for therapeutic intervention.

  11. The Good Side of Inflammation

    The zebrafish brain is much more adept than the human brain at recovering after traumatic injury. Kyritsis et al. (p. 1353, published online 8 November; see the Perspective by Stella) investigated the cellular events that support regeneration in the zebrafish brain. Although inflammation is part of the response in both settings, the zebrafish brain goes on to initiate proliferation of replacement neurons. By inciting inflammation without neuronal damage, radial glial cells could be pushed into neurogenesis.

  12. Androgen-Driven Sequestration

    Male and female mice differ in the neuronal patterns that serve the mammary glands. Yin Liu et al. (p. 1357) now describe how gonadal hormones drive development of distinct male and female sensory innervations. Although both male and female mammary glands develop their sensory innervation similarly in early embryogenesis, once the androgens take effect, the developmental trajectories diverge. By birth, the rich network of sensory neurons present in the female is absent in the male. Androgens cause a switch from expression of the full-length neurotrophin receptor TrkB to its truncated form, TrkB.T1, both of which are expressed on the neurons. In males, truncated TrkB.T1 sequesters brain-derived neurotrophic factor (BDNF) from further activity, whereas in females, full-length TrkB binds BDNF and supports neuronal development.

  13. From Man to Mouse

    Genome-wide association studies of humans have identified single-nucleotide polymorphisms (SNPs) that increase an individual's risk of developing common diseases like cancer. Most of these SNPs have only a modest effect on risk, and many map to noncoding regions of the genome. Sur et al. (p. 1360, published online 1 November; see the Perspective by Lewis and Tomlinson) used a mouse model to study the functional impact of a particular SNP that resides 300 kilobases upstream of the MYC oncogene on human chromosome 8q24 and has been linked to cancer risk in humans. When a sequence encompassing this SNP was deleted in mice that were predisposed to develop intestinal tumors, the mice displayed fewer tumors than control mice. This SNP may thus play a causal role in human cancer, presumably through altered regulation of MYC.

  14. Seeing the Light

    Rhodopsins respond to a range of electromagnetic radiation—allowing visual perception over a broad wavelength range in animals and facilitating light-driven ion transport and phototaxis in microorganisms. All rhodopsins contain an embedded retinal chromophore in which absorbance is tuned by the protein environment. To gain insight into how the protein tunes absorbance, Wang et al. (p. 1340; see the Perspective by Sakmar) turned to a smaller soluble protein, cellular retinol binding protein II. They engineered the protein to fully encapsulate and covalently bind all-trans-retinal as a Schiff base. From this starting point, they used rational mutagenesis to vary the absorption maximum over a range of more than 200 nanometers by altering the electrostatic environment of the protein-binding pocket.

  15. Sewing Up DNA Repair

    All cells have a battery of DNA-repair pathways to help ensure genome maintenance and stability, including stress-induced DNA break repair in Escherichia coli. Similar pathways—which can be mutagenic—are known in yeast and human cells and have the potential to accelerate evolution. Sixteen proteins are known to be required for the pathway in E. coli. Al Mamun et al. (p. 1344) analyzed the E. coli pathway to determine the full complement of protein contributions to the pathway. Ninety-three genes were found to be required for stress-induced DNA break repair. One-third of the proteins identified in the network were involved in electron transfer, functioning in oxidative phosphorylation, and acting through the σs stress response pathway, which thus represents a critical hub in the network.

  16. Awakening a Life Cycle

    Sleeping sickness continues to afflict populations in sub-Saharan Africa, but for the past 100 years, research on the Trypanosoma brucei protozoan parasite has been hampered by an inaccessibility of the insect vector stages to modern research tools. Kolev et al. (p. 1352) have identified an RNA-binding protein (RBP6) as a master regulator that drives the entire developmental program of the trypanosome through all its life-cycle stages. The ability to perform this transformation in vitro will allow study of the many biochemical and morphological changes as parasites change from dividing noninfectious forms to infectious nondividing antigenically variable forms.

  17. Swapping Recombination Proteins

    Crossing over is a means by which organisms create genetic diversity through the mixing of gene complexes. The primary meiotic crossover pathway in budding yeast, mice, nematodes, and plants requires the Msh4–Msh5 heterodimer, which promotes crossovers by blocking anticrossover activities of the Bloom syndrome helicase. However, some fly species, including members of the genus Drosophila, have lost Msh4–Msh5. Kohl et al. (p. 1363) now show that Drosophila have evolved a minichromosome maintenance (MCM)–like protein, dubbed mei-MCM, that performs the same function as Msh4–Msh5. Furthermore, these genes appear to have evolved under positive selection, possibly as a result of their repurposing to this novel function.

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