This Week in Science

Science  06 Oct 2006:
Vol. 314, Issue 5796, pp. 13
  1. Boron Goes Negative


    The chemistry of boron is generally characterized by electron deficiency. Neutral boron compounds tend to be strong Lewis acids, and in borate anions, the B center is typically electropositive, which is reflected in the utility of borohydride salts as hydride (H) donors. Segawa et al. (p. 113; see the Perspective by Marder) have prepared a molecule that inverts this reactivity pattern. By reductive cleavage of a B-Br bond in a cyclic precursor, they isolate a boryl lithium compound in which the negatively charged B center acts as a base and nucleophile. The compound is stabilized by electron-donating nitrogens that flank the B atom, in analogy with the isoelectronic N-heterocyclic carbenes that have recently been prepared as ligands.

  2. Relativity Tests

    The double-pulsar system PSR J0737-3039A/B, which comprises two radio pulsars that orbit one another quickly and with high acceleration, is the best system that has been identified for tests of general relativity. Kramer et al. (p. 97, published online 14 September; see the 15 September news story by Cho) report precision timing observations for a 3-year period. With mass measurements possible, four independent tests confirm the validity of general relativity at the 0.05% level in the strong-field regime.

  3. From Cradle to Museum

    For most major groups of organisms, diversity decreases from the tropics to the poles, which may either reflect greater rates of speciation or of species persistence in the tropics. A large-scale analysis of the fossil record of marine bivalves by Jablonski et al. (p. 102; see the Perspective by Marshall) shows that the present-day latitudinal gradient in biodiversity reflects both higher originations in the tropics and pole-ward expansions of distributional limits of taxa over time. Thus, the tropics are both a cradle and a museum of biodiversity.

  4. Unraveling Protein Analysis

    Mass spectrometry is a rapid method for proteomic analysis and for identifying posttranslational modifications. Identification is less ambiguous for “top-down” approaches, where the entire protein is introduced into the gas phase (as opposed to bottom-up approaches that analyze proteolytic fragments). However, fragmentation of the protein becomes more difficult for larger proteins, and top-down approaches are usually limited to proteins with masses below 50 kilodaltons (kD). Han et al. (p. 109; see the Perspective by Chait) extend this approach to proteins with masses in excess of 200 kD by adding small molecules to the electrospray solution that inhibits folding and by activating the ions through heating and collisions induced by voltage acceleration. This process creates hundreds of interresidue cleavages at the C- and N-terminal ends of the chain that allow for identification of larger proteins and provides sufficient mass resolution to assign features such as disulfide linkages.

  5. Monsoon Forecasting

    The agricultural output of India depends heavily on the strength of the summer monsoon. Most seasonal forecasts scale the strength of the monsoon to the intensity of the El Niño-Southern Oscillation, a strategy that works well enough predicting heavy rains when equatorial Pacific sea surface temperatures are cold but not nearly as well in predicting drought when temperatures are warm. Krishna Kumar et al. (p. 115, published online 7 September) used Indian rainfall records extending back more than 130 years and an atmospheric general-circulation model to show that drought occurrence in central India depends on whether the warmest sea surface temperatures occur in the central or the eastern parts of the equatorial Pacific Ocean. Incorporating this result into forecasts of the monsoon could have a significant effect on economic planning and risk mitigation.

  6. Magnetic Loops


    The center of the Milky Way Galaxy not only harbors a black hole, but within the inner hundreds of parsecs lie many unusual features, including oddly shaped gas filaments and regions of hot molecular gas with very violent motions. Fukui et al. (p. 106; see the Perspective by Morris) obtained a sequence of CO spectral-line images of the region taken at millimeter wavelengths that reveal vast loops of fast-moving molecular gas. They suggest the loops are expelled by magnetic buoyancy effects similar to those on the Sun's surface. Modeling shows that this magnetic picture can explain the high velocity dispersions of the hot-gas regions.

  7. Gradual Versus Punctuational Evolution

    Punctuational evolution has been a contentious idea, but recently, it has become possible to detect signals of punctuational and gradual evolution on molecular phylogenetic trees. Pagel et al. (p. 119) show that bursts of evolution associated with speciation across a wide range of organisms account for approximately 20% of the nucleotide substitutions in published gene-sequence alignments, the remainder being attributable to more gradual forces of evolution. These “punctuational” effects are more frequent in plants and fungi, compared with animals, presumably because of their higher rates of polyploidy and hybridization.

  8. Tale of Two Two-Timing Proteins

    Cells put many proteins to more than one use, including the transcription factor TFII-I. Caraveo et al. (p. 122; see the Perspective by Park and Dolmetsch) found that TFII-I may inhibit calcium entry into cells by interacting with another protein that itself has dual roles in regulating cellular calcium concentrations—phospholipase C-γ (PLC-γ). PLC-γ promotes the generation of inositol-1,4,5-trisphosphate, a second messenger that causes calcium release from intracellular stores, and also interacts with the membrane calcium channel TRPC3 and promotes insertion of the channel into the plasma membrane. The interaction of TFII-I with PLC-γ appears to depend on TFII-I's phosphorylation, which may keep PLC-γ from interacting with the TRPC3 channel and thereby limit calcium entry through the plasma membrane.

  9. Immune Gene Therapy for Cancer

    Cancer immunotherapy is based on the premise that the sometimes reluctant immune system can be cajoled into efficiently destroying tumors, either through vaccination or the adoptive transfer of cancer-killing cells. Morgan et al. (p. 126, published online 31 August; see the Perspective by Offringa) genetically modified T cells to express a T cell receptor (TCR) with strong specificity for a selected melanoma tumor antigen. Peripheral blood lymphocytes isolated from patients with advanced metastatic melanoma were transduced with a retroviral vector containing genes of the two chains of the TCR. After re-infusion, the transgenic cells were maintained and, encouragingly, 2 of the original 17 patients carrying the highest numbers of cells also responded with a noticeable regression of their established tumors.

  10. Channeling Local Translation


    Local, activity-dependent changes in excitability are thought to play a role in various aspects of neuromodulation. Translation of dendritically localized messenger RNAs is one way for a neuron to modify its excitability and signal processing machinery at or near active synapses. Raab-Graham et al. (p. 144) used photoconvertible fluorophores to show that potassium channels are locally translated in dendrites. This local translation is regulated by N-methyl-D-aspartate receptor activation via the mammalian target of rapamycin/phosphatidylinositol 3-kinase signaling pathway.

  11. Chronic Wasting Disease Transmission

    Chronic wasting disease (CWD) is a fatal prion disease found in deer and elk. Its transmission between animals seems to be much easier than that of so-called mad cow disease between cattle. Mathiason et al. (p. 133) demonstrate the presence of infectious prions capable of transmitting CWD in body fluids, including the saliva and the blood, of CWD-infected cervids. The results emphasize the need for caution regarding contact with body fluids of infected animals.

  12. Anxious Mice and Men

    The genes that contribute to depression and anxiety disorders are still unknown, but the recently discovered single-nucleotide polymorphism (Val66Met) in the brain-derived neurotrophic factor (BDNF) gene may be related to mood and anxiety disorders common in human populations. Chen et al. (p. 140) report that, in transgenic mice expressing the variant BDNFMet version, there are alterations in brain anatomy and memory as has been described in humans. This allelic variant also reproduces the phenotypic hallmarks of anxiety in humans, but these mutant mice did not respond to a common, widely used antidepressant.

  13. Identifying Culprits

    A variety of neurodegenerative conditions are associated with the accumulation of aberrant protein aggregates in the brain. Neumann et al. (p. 130; see the news story by Marx) identified TDP-43 as the long-sought-after disease protein in the ubiquinated inclusions of frontotemporal dementias characterized by ubiquitin pathologies and amyotrophic lateral sclerosis. TDP-43 represents a previously “missing” misfolded protein found in pathological inclusions of neurodegenerative diseases, and its identification should help in the investigation of dementias and motor neuron disease.

  14. Keep It Moving

    The actin-based molecular motors of the myosin family are encoded by multiple genes. Mammals possess two genes encoding long-tailed “amoeboid” Myo1e and Myo1f forms. Kim et al. (p. 136) now find that Myo1f negatively regulates the activity of neutrophils, the immune cells that engulf and kill bacteria. Myo1f did not directly influence phagocytic activity, or the intracellular oxidative burst in these cells that eventually kills bacteria. However, cells from mice lacking Myo1f had reduced motility and increased adhesion caused by exocytosis of integrin-containing granules upon neutrophil stimulation. Myo1f-deficiency also led to increased susceptibility to bacterial infection. Thus, Myo1f regulates the host response to infection by ensuring mobility of phagocytic cells through the modulation of integrin-dependent adhesion.

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