Editors' Choice

Science  30 Apr 2010:
Vol. 328, Issue 5978, pp. 548
  1. Economics

    The Invisible College of Ideas

    1. Gilbert Chin

    Leena Peltonen-Palotie, 1952–2010.

    CREDIT: PASI HYTTI

    It is no longer uncommon to see multi-authored original research papers, and in many instances, these studies represent the fruits of collaborations between multiple laboratories, especially in the biomedical sciences. How important are the lead researchers in these social and scientific networks?

    Answering this question empirically appears at first glance to be intractable, but Azoulay et al. have compiled a data set that enables them to take advantage of natural events—when still-active superstar researchers are subtracted from collaborations via death. Of the roughly 230,000 U.S. medical school faculty members, 10,000 were classified as elite according to seven objective professional criteria; during the last two decades of the 20th century, 112 of these scientists died suddenly. The effect on the productivity of the surviving faculty-level collaborators in these superstar-coauthor dyads was unambiguous and persistent: They suffered decrements of almost 10% in publications and funding. The authors' analyses of these consequences favor a causal explanation in which the critical factor in these downward trends was being deprived of the intellectual input from these superstars, as opposed to a loss of collective experimental expertise or of privileged channels of communication to funding panels and journal editors.

    Q. J. Econ. 125, 549 (2010).

  2. Chemistry

    A Better Sort of Beads

    1. Julia Fahrenkamp-Uppenbrink

    Combinatorial libraries are widely used to find new active compounds—for example, in drug discovery. Traditionally, the library compounds are attached to a solid support, but this approach has several drawbacks. An alternative is the use of beads that are uniquely encoded, such that an active compound can easily be identified with optical methods. Meldal and Christensen have now developed a bead-encoding approach, termed MPM (microparticle matrix) encoding, that allows very large numbers of beads to be encoded rapidly and reliably, with automated screening and detection of active compounds. In a test scenario involving 3000 beads, the technique enabled identification of avidin ligands from a focused compound library.

    Rasmussen et al. combined this methodology with virtual screening (in which the compound library itself is designed through computational screening of chemical building blocks) to identify small molecules for use in protein purification. They showed that the ligands thus discovered could efficiently isolate the targeted protein from a complex fermentation mixture.

    Angew. Chem. Int. Ed. 49, 10.1002/anie.200906563; 10.1002/anie.200906602 (2010).

  3. Immunology

    Intestinal Goings-On

    1. Kristen L. Mueller

    Allelic variants in the human interleukin-23 (IL-23) receptor are associated with susceptibility to several inflammatory diseases, such as psoriasis and inflammatory bowel disease. In mice, both T cell–dependent and T cell–independent “innate” models of colitis are driven by IL-23–mediated inflammation. In T cell–dependent models, IL-23–dependent inflammation is primarily the result of pro-inflammatory cytokine production by CD4+ T helper type 17 (TH17) cells. The mechanistic basis for IL-23–driven innate colitis has not been determined.

    Buonocore et al. show that, in a manner similar to that of T cell–dependent colitis, innate colitis is also driven by TH17-associated pro-inflammatory cytokines. Rather than being produced by T cells, however, these cytokines are produced by a population of IL-23–responsive colonic lamina propria cells. These cells are similar in phenotype to lymphoid tissue inducer–like cells, which have previously been shown to produce TH17-associated cytokines. Depletion of these cells led to abrogation of colitis, and the authors were able to confirm their results in another mouse model of innate colitis. These results suggest that the TH17 gene expression profile is an important driver of intestinal inflammation in both the innate and adaptive immune systems.

    Nature 10.1038/nature08949 (2010).

  4. Paleontology

    A Wet Route South

    1. Brooks Hanson
    CREDIT: JAN GOTTWALD/ISTOCKPHOTO.COM

    For tens of millions of years, North and South America were mutually isolated and evolved their own flora and fauna. Plate motions gradually consolidated a series of volcanic islands and crustal fragments into a land bridge, the Isthmus of Panama, that finally closed approximately 3.5 million years ago. This closure changed ocean circulation, separated Pacific and Atlantic marine species, and accelerated the exchange of land animals between the formerly isolated continents. Documenting the earlier migrations, before final closure, can enhance understanding of the paleogeography of the region and biotic impacts of the invasions. Campbell et al. resolved the paleomagnetic record of Amazonian sediments containing some of the earliest North American fauna. This record implies that the sediments were deposited about 9 million years ago, consistent with some earlier notions. Thus, some early gomphotheres (similar to elephants), peccaries, and tapirs managed to make it to South America long before the final closure, presumably by swimming between distant islands.

    J. South Am. Earth Sci. 29, 619 (2010).

  5. Cell Biology

    The More the Merrier

    1. Helen Pickersgill

    Cajal bodies in the zebrafish embryo.

    CREDIT: MAGDALENA STRZELECKA

    Many biological processes are compartmentalized within the cell by restricting the localization of proteins and other molecules. The spatial organization of these compartments, often bounded by internal membranes, can facilitate the delicate control of complex processes—for instance, the transcription of DNA into RNA, which occurs within the nucleus of eukaryotic cells. However, many non—membrane-bound intracellular compartments have known molecular compositions yet largely unknown functions. Studies attempting to identify their function by mutating or removing protein components to disrupt the compartment physically have been hard to interpret because of the apparent lack of phenotypic changes. This has led to speculation that this kind of compartmentalization may serve to increase the efficiency of an otherwise ongoing process, which may only become rate-limiting under rare physiological conditions. Strzelecka et al. have uncovered just such a critical role for coilin, which is a conserved component of Cajal bodies, during embryogenesis in zebrafish. Cajal bodies are 0.5- to 1-µm structures first described by Ramón y Cajal in 1903. They are found in the nuclei of plant and animal cells, most noticeably in those cells engaging intensely in transcription, and are composed of proteins and RNAs, such as the small nuclear ribonucleoprotein (snRNP) complexes that are important for pre-mRNA splicing. The snRNPs are complicated assemblies that undergo a multistep maturation process, which, it has been proposed, takes place in Cajal bodies. The authors depleted coilin in zebrafish embryos, which caused a disruption of Cajal bodies and the dispersal of snRNPs, before leading subsequently to cell death. These coilin morphants exhibited defective snRNP biogenesis and pre-mRNA splicing, which could be rescued by adding purified mature human snRNPs, revealing a role for coilin in snRNP biogenesis in the zebrafish embryo. The authors suggest that the formation of Cajal bodies concentrates snRNP components and promotes their faithful interaction, which is critical during early embryogenesis when transcriptional activity, and thus the need for snRNPs, is particularly high. These principles may be generally applicable to other non–membrane-bound subcellular compartments with currently unknown functions.

    Nat. Struct. Mol. Biol. 17, 403 (2010).

  6. Chemistry

    Location, Location, Location

    1. Jake Yeston

    Reductively coupling aldehydes with alkynes is a versatile means of preparing allylic alcohols. However, it has proven challenging to reliably select which of the two triply bonded carbon centers in the alkyne attacks the carbonyl. Modestly differing substituents at the two sites tend to induce a mixture of products, whereas substituents that favor one product have largely precluded access to the other by this route. Malik et al. show that careful ligand selection for a nickel catalyst can override such substrate preferences (or lack of preference) and thereby afford tunable control over the reaction's regiochemistry. They specifically screened a ligand set comprising three N-heterocyclic carbene scaffolds functionalized with a variety of bulky groups, and a fourth, less hindered cyclopropenyl derivative. The resulting catalysts permit selection of either alkynyl reaction site across a series of substitution patterns, with ratios in both directions ranging from 81:19 to >98:2. Yields for the room-temperature procedure ranged from 71 to 99%.

    J. Am. Chem. Soc. 132, 10.1021/ja102262v (2010).

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