Editors' Choice

Science  31 Mar 2006:
Vol. 311, Issue 5769, pp. 1836

    Three into One Makes Three

    1. Gilbert J. Chin

    Molecular explorations into the origins of the three major cellular domains—Archaea, Bacteria, and Eukarya—have generated warring interpretations of their differences and similarities. For instance, the components of the translational machinery (ribosomal RNAs and proteins) serve as a distinctive identifier for each domain, whereas some of the enzymes involved in DNA replication (as well as recombination and repair) are shared (in the sense of being homologs) between two domains, though not consistently the same two.

    Forterre discusses a scenario in which the initiating events for converting a primordial common ancestor (a cell containing an RNA genome) into the modern-day triumvirate were infection and transformation (via a plasmid-like intermediate stage) by three DNA viruses. The substitution of DNA for RNA as the cellular genetic repository is postulated to have reduced the rate of evolution of proteins and to have established a barrier to subsequent takeovers. It is not clear whether the long-standing problems that this proposal addresses will simply be replaced by new ones, but the reminder that viral lineages are also a part of the early landscape is welcome. Indeed, structural analyses have placed viruses with an enormous range of host specificity (bacteriophage PRD1, Paramecium bursaria Chlorella algal virus, and mammalian adenovirus) in the same family on the basis of their major capsid protein (MCP) architectures, as revealed most recently by Khayat et al. for the Sulfolobus turreted icosahedral virus (STIV) and by Laurinmäki et al. for bacteriophage Bam35. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 103, 3669 (2006); 102, 18944 (2005); Structure 13, 1819 (2005).


    A Conserved Complement Collector

    1. Stella Hurtley

    The complement system is important in the clearance of circulating pathogens; component C3 reacts with bacterial surfaces and promotes their binding to phagocytic cells that then internalize and destroy the bacteria. Some of the key players in clearing complement-coated pathogens are the Kupffer cells, a class of macrophages that reside in the liver.

    Helmy et al. have identified a receptor present in Kupffer cells, the complement receptor of the immunoglobulin family (CRIg), which is required for the efficient binding and phagocytosis of complement-coated pathogens. Mice lacking CRIg were unable to clear complement-coated pathogens from the circulation and were more likely to succumb to infection. Thus, CRIg, which is conserved in mice and humans, represents a critical component of the innate immune system allowing the liver to act as a sentinel to invasion by pathogens. — SMH

    Cell 124, 915 (2006).


    A Colorectal Catalog

    1. Gilbert J. Chin

    Global surveys, inaugurated by almost complete compendiums of the genes of various organisms, have been expanded to cover proteins and, more recently, microRNAs (miRNAs), which are roughly 25-nucleotide-long RNA molecules that function to block the production of proteins from mRNAs. Cummins et al. describe a protocol—the miRNA serial analysis of gene expression (miRAGE)—and its application to assessing the miRNA composition of human colorectal cancer cells. Their approach meets the technical challenge of recovering short RNA pieces, present in vanishingly small quantities; analyzing an enormous number of parallel amplification reactions resulted in the identification of 200 miRNAs known within these cells (with one-quarter differentially expressed in comparison to normal colonic epithelial cells) and of 168 candidate miRNAs, of which one-fifth were independently identified and deposited by other groups during the course of their study. — GJC

    Proc. Natl. Acad. Sci. U.S.A. 103, 3687 (2006).


    Crystal Tuning

    1. Jake Yeston

    Chemists can rationally tune the extended structure of thin films by choosing the substrate on which the films are grown. However, the growth conditions that yield specific morphologies of three-dimensional crystals are still largely determined by trial and error, without a clear understanding of the factors that promote specific structural outcomes.

    Grzesiak et al. sought to influence the structure of a metal organic framework solid by adding insoluble polymers to the crystallization solutions, for the purpose of guiding the nucleation process and thereby producing unusual bulk morphologies. The suspended polymers contained either acidic (methacrylic acid) or basic (4-vinylpyridine) components in varied proportion to a hydrophobic cross-linker (divinylbenzene). In the absence of polymer, two crystal phases were known to form from the Zn2+ and benzenedicarboxylate building blocks. A distinct third phase emerged when predominantly nonpolar polymers were added (>70 % divinylbenzene), and the authors characterized its plate-like structure by powder and single-crystal x-ray diffraction, as well as Raman spectroscopy. This heterogeneous nucleation strategy produced additional phases when the benzenedicarboxylate bridges were functionalized with either Br or NH2 groups. — JSY

    Angew. Chem. Int. Ed. 45, 10.1002/anie.200504312 (2006).


    On the Face of It

    1. Phil Szuromi

    Varying the size of a nanometer-scale metal cluster can alter its catalytic activity. This phenomenon is usually attributed either to geometrical effects (such as the distribution of defect atoms or step sites) or to electronic effects (such as the scaling of metallic character with particle size) but has rarely been quantified for very small catalyst particles. Wilson et al. have systematically measured the size-dependent activity of cuboctahedral Pd clusters toward the catalysis of allyl alcohol hydrogenation. Clusters of precise size were synthesized using dendrimer templates and ranged in diameter from 1.3 to 1.9 nm (or ∼50 to ∼250 atoms). For clusters larger than 1.5 nm, the observed increase in reaction rate with increasing diameter was best fit by positing preferential reaction on facial sites, thus suggesting a geometrical origin for the activity change. For smaller clusters, reactivity did not correlate with physical properties such as the number of defect atoms or surface area, and activity changes were therefore attributed to electronic effects. — PDS

    J. Am. Chem. Soc. 128, 10.1021/ja058217m (2006).


    Biologically Inspired Networking

    1. David Voss

    Biological systems are typically better at adapting to new situations than computers because their design emphasizes robustness and sustainability even though the proximal response may not be the optimal one. In an information network such as the Internet, data are broken up into packets before being transmitted, and each packet can take a different path across the nodes of the network. How might a method for data transmission over multiple paths be redesigned whereby the network can itself adapt to an unpredictable and fluctuating environment?

    Leibnitz et al. based their biologically inspired network routing scheme on a model developed to account for the response of Escherichia coli bacteria to variations in nutrient availability. The model uses stable attractors: equilibrium states into which the system settles until disrupted by a change in the environment, at which point the system converges to a new attractor. For network switching, information about the data paths (available bandwidth or transit time) is collected to find a stable attractor. When conditions change (for example, if a link breaks), a new attractor is selected, and the packets are switched to a new path. Because randomness is an intrinsic feature of the optimization method, the system is highly stable in noisy environments. — DV

    Commun. Assoc. Comput. Mach. 49, 63 (2006).


    Strength in Numbers

    1. Stephen Simpson

    The autoimmune condition myasthenia gravis results from the production of self-reactive antibodies to the nicotinic acetylcholine receptor (AChR). Because this receptor is required for the transmission of signals at the neuromuscular junction, the aberrant nerve-muscle communication that results from an antibody-mediated inhibition of AChR clustering leads to muscular weakness at a range of anatomic locations.

    A small proportion of myasthenic patients do not carry detectable levels of AChR antibodies, and most of these present instead with antibodies directed against muscle-specific kinase (MuSK). Using an experimental model for myasthenia, Shigemoto et al. show that such self-reactive antibodies may mediate pathogenesis, too. After the induction of antibodies to MuSK by vaccination with a chimeric protein, rabbits developed progressive muscular weakness. Reduced AChR clustering was detected at neuromuscular junctions in tissue sections taken from these animals; and in cell culture, antibodies to MuSK diminished experimentally induced AChR clustering. It will be important to establish whether antibodies to MuSK or other neuromuscular targets have an equivalent influence on myasthenia gravis in humans; if this is the case, then improved mechanistic understanding of the disease and new therapeutic options may follow. — SJS

    J. Clin. Invest. 116, 10.1172/JCI21545 (2006).

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