Editors' Choice

Science  19 Aug 2005:
Vol. 309, Issue 5738, pp. 1155

    An Impending Cloud of Death

    1. H. Jesse Smith

    On 12 August 1986, a deadly cloud of CO2 and water mist was released from Lake Nyos, Cameroon, and killed more than 1700 people by asphyxiation as it spilled into adjacent valleys. The dense cloud of gas, which was 50 m thick and traveled farther than 20 km at speeds of 20 to 50 km/hour, was produced by the dissolution of CO2 in the deep part of the lake; a convective overturn displaced the lower layer of the stratified lake, causing the CO2-rich water that had been at the bottom to degas like a bottle of fizzy water being opened. Such events have happened before in this region, and may happen again if steps are not taken to prevent them.

    Schmid et al. report that a similar situation is developing at Lake Kivu, an East African rift lake between Rwanda and the Democratic Republic of Congo. The depths of Lake Kivu are amassing dissolved CO2 and CH4 at a rate fast enough that CH4 concentrations will approach saturation toward the end of this century, making it likely that a magmatic eruption in the volcanically active lake basin, or some other disturbance, could trigger overturn and the release of another lethal CO2 cloud. Without human intervention to reduce the concentration of CH4, the 2 million people along the Lake Kivu shoreline may suffer a catastrophic gas release. — HJS

    Geochem. Geophys. Geosyst. 10.1029/2004GC000892 (2005).


    Designing Carbenes

    1. Jake S. Yeston

    In the past 10 years, N-heterocyclic carbenes (NHCs) have grown from being regarded as chemical curiosities to become versatile ligands for a wide range of homogeneously catalyzed reactions. Most carbenes (molecules bearing a two-coordinate divalent carbon) are unstable at room temperature, but in an NHC, the unsaturated carbon is stabilized by electron-donating nitrogen atoms on either side.

    Lavallo et al. have designed a different type of carbene, termed a cyclic alkyl(amino) carbene (CAAC), in which one of the nitrogens is replaced by a quaternary alkyl center. By appending bulky groups such as cyclohexane to this center, the authors can prepare compounds with stabilities comparable to those of NHCs, but sporting distinct steric and electronic properties. As a ligand, the CAAC is a strong σ-electron donor, and crystallography of a CAAC-coordinated palladium complex reveals steric crowding, particularly close to the metal center. One practical result of these properties is the efficient catalysis by this Pd complex of unactivated aryl chloride couplings to the α-position of aldehydes and ketones. — JSY

    Angew. Chem. Int. Ed. 10.1002/anie.200501841 (2005).


    Minimalist Machinery

    1. Stella M. Hurtley

    The fusion of two biological membranes requires the concerted action of integral membrane proteins (either endogenous ones or those carried by enveloped viruses) that rearrange the lipid bilayers in such a way as to facilitate membrane merger. Top et al. describe a recently characterized family of reovirus proteins that lack a well-defined hydrophobic fusion peptide and hence appear to promote fusion via a somewhat different trigger than that utilized by the archetypal influenza virus hemagglutinin. These fusion-associated small transmembrane (FAST) proteins mediate efficient cell-cell fusion when transfected into a variety of cells. Furthermore, when recon- stituted into proteo-liposomes, a reptilian reovirus FAST protein promoted time- and temperature-dependent liposome-cell and liposome-liposome fusion as assessed by the mixing of lipids and of liposome contents. The precise mechanism by which this simple machine can initiate membrane fusion remains to be elucidated, but may involve the combined action of chaotropic modules in the extramembraneous portions of the FAST protein. — SMH

    EMBO J. 10.1038/sj.emboj.7600767 (2005).


    Insig(ht)s into Metabolic Control

    1. Paula A. Kiberstis

    Cholesterol has received a lot of bad press, but it is essential for human health. When we don't get enough cholesterol from our diet, our bodies—specifically our liver—begin to synthesize it. Conversely, when we eat lots of high- cholesterol foods, this biosynthetic machinery shuts down. How this feedback regulation works has fascinated scientists for over 70 years, and in the past decade, considerable progress has been made toward answering that question at the molecular level.

    Among the potentially important metabolic regulators identified in studies of cultured cells are the membrane proteins Insigs-1 and -2, so named because they are encoded by insulin-induced genes. The Insigs reside in the endoplasmic reticulum, and they appear to act in part by trapping within this compartment a transcription factor that is required in the nucleus to turn on the expression of genes involved in cholesterol biosynthesis. Engelking et al. show that mice with liver- specific deletions of the Insig genes display a severely blunted feedback response; that is, they continue making cholesterol even when fed a high-cholesterol diet. These results establish the physiological significance of the Insigs in a whole-animal setting and highlight the importance of the liver as the site where the cholesterol feedback system operates. — PAK

    J. Clin. Invest. 10.1172/JCI25614 (2005).


    Beams and Hangers

    1. Pamela J. Hines

    The fully grown oocyte of the frog Xenopus laevis contains considerable internal architecture—in particular, an extensive cytokeratin network—even though it is only a single cell. One of the features of this network is that it compartmentalizes maternally encoded RNA molecules, which are important for development of the embryo after fertilization; disruption of the network results in release of these RNAs.

    Kloc et al. show that the cytokeratin network is also necessary for formation of the germinal granules during oogenesis. A class of maternal RNA molecules forms part of the germinal granules, which accumulate in the oocyte and are passed into a small but important lineage of cells: the primordial germ cells that will eventually give rise to eggs and sperm. The cytokeratin network depends for its own structural integrity on two molecules, VegT and Xlsirts, and both of these function in this setting as RNAs, not as translated proteins. The structural components of this cellular network thus seem to include RNA molecules as well as cytokeratin filaments. — PJH

    Development 132, 3445 (2005).


    Not So Inert

    1. Phillip D. Szuromi

    Sulfur hexafluoride (SF6) is so unreactive that it can be used, among other applications, as a protective blanket for processing highly reactive magnesium metal, yet its long lifetime in the atmosphere (>3000 years) has caused concern because it has the strongest greenhouse effect known for any gas. Despite the reputation of SF6 for inertness, Basta et al. report a reaction in which it proves to be a faster fluorinating agent than normally more reactive compounds such as XeF2 or CoF3. The low-valent Ti compound, Ti[1,3-C5H3(tert-C4H9)2](6,6-dimethylcyclohexadienyl)(P(CH3)3), which can be regarded as a half-open titanocene, reacted readily with SF6 to produce the tetrameric product {Ti[1,3-C5H3(tert-C4H9)2]F2}4 and the byproduct (CH3)3PS. The authors propose that SF6 can coordinate an F atom to the metal center and drive the reaction through an oxidative inner-sphere electron transfer. — PDS

    J. Am. Chem. Soc. 10.1021/ja052214s (2005).

  7. STKE

    The Ligand Is a Gas

    1. L. Bryan Ray

    Nuclear receptors function as ligand-regulated transcription factors, but for many members of this family, the ligands are not known. In fact, before the fine piece of detective work described by Reinking et al., only 1 of the 18 nuclear receptor proteins in Drosophila had an identified ligand. The clue that led to the unexpected partner for the receptor known as E75 was the blood-red color of the purified protein. Electron absorption and mass spectrometry analysis revealed that the receptor has a tightly associated heme group. Further analysis led the authors to propose three possible functions of the receptor complex. First, heme was required for stability of the E75 protein, and thus E75 could serve as a sensor of cellular heme concentration. Second, heme-containing proteins are known to bind diatomic gases, and E75 is no exception. Binding of CO and NO to E75 was detected spectrophotometrically. E75 interacts with another nuclear receptor, HR3, and inhibits activation of target genes by HR3. CO binding inhibited interaction of a peptide from HR3 with E75. Treatment of cells with NO donors relieved the inhibitory effects of E75 on HR3-induced transcription. Thus, E75 may sense CO and NO as intracellular signaling molecules. Finally, E75 might function as a redox sensor because only the reduced form of E75 was stabilized by interaction with the HR3 peptide. — LBR

    Cell 122, 195 (2005).