Editors' Choice

Science  29 Mar 2013:
Vol. 339, Issue 6127, pp. 1497
  1. Chemistry

    Making Butene in MOFs

    1. Phil Szuromi

    Although homogeneous organometallic catalysts can be very efficient in solution, it can be advantageous for separations and catalyst recovery to “heterogenize” them by using linkers to attach them to a support. However, typical high–surface-area metal oxide materials used as supports for conventional heterogeneous catalysts can deactivate organometallic catalysts through unwanted interactions with the support or between nearby catalyst molecules. One alternative has been to incorporate catalysts into high–surface-area metal organic framework (MOF) materials, and Canivet et al. used this method with an olefin oligomerization catalyst. They started with (Fe)MIL-101-NH2, in which trimeric iron(III) octahedral clusters are linked by 2-aminoterephthalate ligands. This MOF has the high pore volume needed to accommodate a nickel(II) catalyst as well as reactants and products. They achieved different densities of N,N-chelating centers for nickel in the MOF through reaction with 2-pyridine carboxaldehyde, which formed a methanimino bridge between some of the 2-aminoterephthalate linkers and pyridyl groups. These materials were then suspended in heptane and exposed to ∼15 atm of ethylene in the presence of diethylaluminum chloride. One of them, which had a loading of 10 nickel centers per MOF cage, exhibited >95% selectivity for forming 1-butene.

    J. Am. Chem. Soc. 135, 4195 (2013).

  2. Signal Transduction

    Understanding the STIM1-ulous

    1. L. Bryan Ray

    The permeability of the circulatory system is carefully regulated, and disruption of the barrier can contribute to inflammation and sepsis. One important means of regulation is the action of thrombin on vascular endothelial cells. The receptor for thrombin initiates mobilization of calcium from intracellular stores, and Shinde et al. examined the role of such signaling in control of the endothelial barrier formed by human umbilical vein endothelial cells in culture. Signals that cause emptying of calcium stores lead to calcium entry across the plasma membrane by the Orai channel protein and its calcium sensor, stromal interacting molecule 1 (STIM1). STIM1 was required for increased permeability caused by thrombin; however, the role of STIM1 required neither calcium entry nor regulation of the Orai channel. Instead, STIM1 was required to activate the small guanosine triophosphatase RhoA, which coordinates remodeling of the actin cytoskeleton and reduces cell adhesion, which leads to increased permeability.

    Sci. Signal. 6, ra18 (2013).

  3. Climate Science

    Explaining Rapid Climate Fluctuations

    1. H. Jesse Smith

    Dansgaard-Oeschger (DO) cycles—rapid warming events with durations of approximately 1000 years, followed by a more gradual return to cold conditions—are some of the most dramatic examples of rapid climate change that occurred in the North Atlantic region over the last glacial period. Although there has been no lack of suggestions about their possible origins, all of the causal mechanisms proposed thus far have run into difficulty explaining one part of the cycle or another. Petersen et al. step into the fray, suggesting that DO events resulted from a combination of the effects of sea ice and ice shelves—structures that help define the margins of ice sheets—to account for both the rapid and the slower parts of the cycle. Their model relies on the ability of thin sea ice to respond quickly to changing environmental conditions and on the more gradual behavior of thick ice shelves to cause cooling. Although more work needs to be done to support this model, it is consistent with existing proxy records, model results, and modern observations.

    Paleoceanography 10.1029/2012PA002364 (2013).

  4. Neuroscience

    Much-Needed Neurogenesis

    1. Peter Stern

    Destruction of nervous tissue, such as what occurs during stroke, traumatic brain injury, or neurodegeneration, usually causes deficits and malfunctions. However, brain injury can also stimulate plasticity. Perederiy et al. created unilateral lesions of the perforant path in the hippocampus in a mouse model and observed the response of newborn granule cells that were dividing at the time of the lesion. Using transgenic and retroviral labelling techniques, these cells could be followed and traced over the coming days and weeks. Chronic denervation triggered the proliferation of adult-generated neurons. The dendrites of these newborn neurons penetrated into the denervated zone but had a simpler morphology, comparable to the retraction of distal dendrites in mature granule cells. However, they could still produce new dendritic spines and could also be synaptically activated by other nonlesioned pathways. Excitatory axons from these pathways formed new synapses with newborn granule cells. Lesions are thus not only damaging: They can stimulate the production of adult-generated neurons, and these newly produced cells can show enhanced structural plasticity.

    J. Neurosci. 33, 4754 (2013).

  5. Biochemistry

    Telomerase Times Two

    1. Valda Vinson

    In eukaryotes, chromosome ends are capped by telomeres: protein-DNA complexes that are essential for genomic stability. Telomere length is maintained by the enzyme telomerase, which comprises an RNA subunit (TER), that contains the template for synthesis of telomeric DNA repeats and a protein subunit, telomerase reverse transcriptase (TERT), that catalyzes nucleotide addition. In contrast to macromolecular machines such as the ribosome and RNA polymerase, structural information on telomerase has been limited to subdomains, and this has hindered understanding of its function. Debate continues over whether telomerase functions as a monomer or a dimer. To resolve this debate, Sauerwald et al. obtained sufficient quantities of purified, active human telomerase for biochemical, structural, and functional studies. Biochemical and functional data showed that telomerase functions as a dimer. It binds two telomeric DNA substrates, and two functional TERT subunits are required for activity. A structure determined by single-particle electron microscopy (EM) at better than 30 Å resolution revealed a bi-lobal architecture with a size consistent with a homodimer. Gold-labeling and fitting of a high-resolution structure of a TERT subunit into the EM density provided further insight into the architecture of telomerase. Future higher-resolution structures will probably give an even more increasingly detailed view of telomerase function.

    Nat. Struct. Mol. Biol. 20, 10.1038/nsmb.2530 (2013).

  6. Plant Science

    Fine-Tuning a Tart Grape

    1. Pamela J. Hines

    A good wine is a complex blend of flavors, at least some of which are based on the acidity of the wine, which is derived from the acidity of the grape. Grape berry acidity depends on potassium concentration, with high potassium content leading to less acidic fruit. As the grape berry ripens and sugars accumulate, potassium also accumulates. Potassium physiology in grape berries, however, is not well understood. Cuéllar et al. have now identified in grapevine (Vitis vinifera) a potassium channel, encoded by the gene VvK1.2, as well as kinase- and calcium-sensing partners that regulate the function of the channel. Accumulation of VvK1.2 transcripts, which are expressed in the berry flesh, accelerated with fruit ripening. Drought stress during the berry-ripening phase brought further increases in VvK1.2 transcript accumulation. Increased capacity for and regulation of potassium transport may be critical for successful ripening of the grape berry as it adjusts to fluctuating conditions that result from changes in internal vascular support and external drought conditions.

    Plant J. 73, 1006 (2013).

  7. Chemistry

    Ubiquitous Alkyne Activity

    1. Jake Yeston

    Over the past decade, the coupling of terminal alkynes with azides—so efficient it's been termed a “click” reaction—has become a prevalent means of linking together larger molecular fragments. One advantage of the scheme was that the alkynes appeared to be otherwise inert in cellular environments, thereby enabling high specificity in the design of various biochemical probes. Two studies now report that terminal alkynes do in fact react with certain enzymes. Ekkebus et al. show that appending the alkyne to the C terminus of ubiquitin leads to inhibition of deubiquitinating enzymes. Crystallography revealed covalent linkage to an active site cysteine, the product of formal Markovnikov addition of the thiol group across the carbon-carbon triple bond (though no reaction was observed with free thiol). Sommer et al. observed the same reaction of C-terminally propargylated small ubiquitin-like modifier (SUMO) with its protease. Scavenger experiments in both studies disfavor a radical mechanism. Both studies leveraged the observation for selective labeling of lysates and suggest that this reaction could have broad application in selective inhibition.

    J. Am. Chem. Soc. 135, 2867; Bioorg. Med. Chem. 21, 10.1016/j.bmc.2013.02.039 (2013).