Editors' Choice

Science  15 Jul 2011:
Vol. 333, Issue 6040, pp. 268
  1. Cell Biology

    Orphan No More?

    1. Beverly A. Purnell

    The orphan receptors LGR4, LGR5, and LGR6, members of the G protein—coupled receptor family, function in normal development and tumorigenesis. In the intestine and skin, LGR5 and LGR6 represent stem cell markers. Homozygous mouse knockouts of LGR4 exhibit reduced viability and of LGR5 exhibit neonatal lethality. Although much is known about these orphan receptors, the corresponding receptor ligands have eluded detection. Carmon et al. now report that R-spondin, a Wnt antagonist known to stimulate stem cell proliferation, binds LGRs with high affinity and represents the ligand of LGRs 4 to 6. Furthermore, even though LGRs represent members of the G protein–coupled receptors, G proteins are not activated by R-Spondin bound to LGR. Instead it seems that the mechanism for potentiation of Wnt signaling includes rapid internalization of LGRs in a ligand-dependent manner and enhanced β-catenin activity. These findings suggest that stem cell expression of LGR5 and LGR6 and Wnt signaling contribute to stem cell self-renewal and maintenance.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1106083108 (2011).

  2. Ecology

    Pelagic Predators Face Double Jeopardy, Too

    1. Sacha Vignieri

    Swordfish

    CREDIT: WERNER/ HISTOIRE NATURELLE DES POISSONS

    Human impacts on terrestrial predators have not only decreased their abundance but also resulted in extirpation of populations and subsequent range contraction. Species in these conditions face “double jeopardy” because their populations are both smaller and found in fewer places. Pelagic predators have much greater mobility than terrestrial predators, suggesting, perhaps, that range contractions may not accompany reduced abundance in these species. Worm and Tittensor, however, found this not to be the case. Three large, global fisheries databases were used to quantify the presence or absence of 13 tuna and billfish species at 5° intervals over all the world's oceans, and across three decades. Nine out of 13 of these species have experienced significant range contractions, and those with the greatest decreases in abundance have had the greatest reductions in their range. For example, Atlantic blue fin tuna has experienced a 46% decrease in range size. Such contractions remove apex consumers from many regions where they were previously present—a factor that could have a large impact on the marine ecosystem.

    Proc. Natl. Acad. Sci. U.S.A. 10.1073/pnas.1102353108 (2011).

  3. Microbiology

    Transliterating the Canon

    1. Caroline Ash

    The element chlorine is not a usual constituent of Escherichia coli, but it can be used to replace the methyl group in thymine (i.e., 5-methyluracil) to yield a synthetic nucleic acid precursor, 5-chlorouracil. Marlière et al. exploited metabolic selection in an automated, self-cleaning culture device to evolve strains of E. coli in which the canonical base thymine was nearly fully replaced with the synthetic analog within 150 days of culture. Thymidylate synthase and the trmA gene were excised from the starting strains and nucleoside deoxyribosyltransferase was inserted. After about 1000 generations, the evolved strains became dependent on chlorouracil for growth. Analysis of the chemical composition of the DNA of these isolates showed that thymidine content had dropped to less than 2% of that in the original strain, but DNA sequencing revealed several thousands of base substitutions and chromosomal rearrangements. These mutations may cause base mispairing, but the consequences of this on subsequent evolution of the heterodox bacterium, or indeed the value of the novel organism for the biosynthesis of non-natural fermentation products, remain unclear.

    Angew. Chem. Int. Ed., 10.1002/anie.201100535 (2011).

  4. Medicine

    HDL: Quality Not Quantity?

    1. Paula A. Kiberstis
    CREDIT: NEPHRON/WIKIMEDIA

    The introduction of drugs that lower serum levels of “bad” (LDL) cholesterol has had a major impact in reducing the prevalence of cardiovascular disease. By contrast, complementary efforts to harness the apparent beneficial effects of “good” (HDL) cholesterol by pharmacologically boosting serum levels of HDL have faltered. To date, such drugs have yielded disappointing results in clinical trials, which has contributed to the growing view that the abundance of HDL in serum may be less important than its biological activity. Supporting the notion that measures of HDL function are clinically relevant, Besler et al. found that HDL from healthy individuals and HDL from patients with coronary artery disease differ in their capacity to induce critical signaling events in the endothelium, the cells lining the interior of blood vessels. HDL normally stimulates nitric oxide synthesis and endothelial repair, but the HDL from the patients inhibited these processes—possibly because of the disease-associated loss of an HDL-associated enzyme, paraoxonase. Further research on the biological functions of HDL will be required to ascertain which are most critical to its protective effects against cardiovascular disease and how best to intervene therapeutically.

    J. Clin. Invest. 10.1172/JCI42946 (2011).

  5. Applied Physics

    Graphene Circuits on Glass

    1. Phil Szuromi

    Although suspended graphene sheets can show extraordinarily high electrical conductivity, in solid-state device applications the choice of supporting substrate can be critical. For high-frequency applications, such as radio-frequency mixers, it is important to avoid parasitic capacitances set up by substrates such as silicon or silicon carbide that limit the extrinsic frequency cutoff in devices. Liao et al. transferred graphene grown on copper foils to a glass substrate, and then fabricated transistors with dielectrophoretically aligned cobalt silicide (Co2Si) nanowires as the top gate. The transistors can operate at a frequency of 30 GHz, and can be used for frequency doubling in the 1 to 10 GHz range. Devices with long nanowires (240 nm) exhibited current saturation, which indicated transistor operatation near the Dirac point of graphene. Such operation avoids the formation of third-order frequency coupling modes.

    Nano Lett. 11, 10.1021/nl201922c (2011).

  6. Microbiology

    Cost of Living

    1. Nicholas S. Wigginton

    For microorganisms in the open ocean, where oligotrophic waters are limited in essential nutrients such as nitrogen, there is a delicate balance between growth and survival. Adapting to maximize the efficiency of biosynthesis may help defray the costs associated with nutrient limitation, but is there also a pressure over time to actually reduce assimilation of such nutrients into biomolecules as a means of minimizing costs? To answer this, Grzymski and Dussaq evaluated several whole-genome sequences and over 20 million protein fragments from databases to look for differences in the use of nitrogen between open-ocean and coastal microbial communities. Indeed, the atomic compositions of amino acids produced by open-ocean microorganisms contain systematically less nitrogen than coastal microbial proteomes to the point that the overall nitrogen requirement is reduced by up to 10% in the open ocean; however, as nitrogen use is minimized, the average mass of amino acids actually increases. Because the effect is pronounced in highly expressed proteins, there must be a fitness trade-off between increased biosynthetic costs of making larger amino acids and minimizing the use of nitrogen. The results show that nutrients are not only important in the life cycle of extant microorganisms, but that their limitation exerts a strong selective pressure on microorganisms over time.

    ISME J. 10.1038/ismej.2011.72 (2011).

  7. Climate Science

    A Peek at Cold Corals

    1. H. Jesse Smith
    CREDIT: NOAA/OER

    The lush, warm-water corals that have become a pervasive example of species threatened by climate change are not the only such organisms so affected: Cold water corals, which live at greater depths and at higher latitudes than their more tropical relatives, are just as susceptible even if they are not as visible. Frank et al. studied the distribution of cold water corals living off the coasts of northwest Africa and Europe over the past 400,000 years, as determined radiometrically, and found that they had markedly different ranges during cold and warm times. At the peaks of glacial periods, these corals grew only as far north as 50°N latitude, whereas during warm interglacials like the present their ranges expanded northward to around 70°N latitude. This climate effect might mean that deep-water corals in the northeastern Atlantic could continue to colonize higher latitudes as global warming continues, although ocean acidification and deep-water trawling may interfere with that migration.

    Geology 39, 743 (2011).

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