Editors' Choice

Science  04 Mar 2011:
Vol. 331, Issue 6021, pp. 1114
  1. Chemistry

    Calcium Catalysis

    1. Jake Yeston

    Synthetic asymmetric catalysts have traditionally comprised transition metals bearing chiral ligands, though over the past decade, free amines, phosphate diesters, and urea derivatives have emerged as increasingly effective alternatives. The phosphate class of organocatalysts tends to rely on ion pair formation between a protonated substrate and a residual phosphate anion bearing a chiral, often polycyclic aromatic carbon framework. Zheng et al. were exploring the application of this type of catalyst toward asymmetric chlorination of phenyloxindoles, and they found that a particular phosphate diester afforded high enantioselectivity just after purification by silica gel chromatography, yet minimal selectivity after an acid wash. This result led them to screen phosphate salts with a variety of cations, culminating in the discovery that calcium—a biochemically critical ion that has found comparatively few applications in synthetic catalysis—proved the optimal counterion for conferring selectivity. Though the mechanism remains unclear, the authors posit possible activation of the chlorine source (N-chlorosuccinimide) by calcium coordination, concomitant with oxindole activation by the phosphate. Phenyloxindoles with a range of substitution patterns were chlorinated in nearly quantitative yields within half an hour at room temperature, with enantioselectivities generally exceeding 90%.

    J. Am. Chem. Soc. 133, 10.1021/ja109824x (2011).

  2. Climate Science

    Reservoir Doubts

    1. H. Jesse Smith

    As the last ice age came to an end, the concentration of atmospheric CO2 increased rapidly, and its 14C content declined precipitously between 17.5 and 14.5 thousand years ago. The favored explanation for this drop in the proportion of 14CO2 is that a large amount of old carbon—that is, carbon whose inventory of radioactive 14C had been depleted with age—was outgassed from a deep ocean reservoir where it had been isolated for many thousands of years. That scenario makes good intuitive sense, but conclusive evidence for a reservoir of aged carbon has not yet been found. Hain et al. use an 18-box ocean model to simulate the history of deglacial CO2 and evaluate the likelihood that an old deep-ocean CO2 reservoir was in fact the source of the observed 14C anomaly. They conclude that such a transfer of carbon was unlikely, based on inconsistencies with other records such as those of the 14C history of other depths and regions of the ocean, ocean carbonate and oxygen changes over the interval, and constraints on mixing imposed by ocean circulation.

    Geophys. Res. Lett. 38, L04604 (2011).

  3. Biochemistry

    Minding Their Ps and Ns

    1. Nicholas S. Wigginton

    In the mid-20th century, Alfred Redfield posited that the bulk ratio of nitrogen to phosphorus atoms (N:P) in marine microorganisms should maintain a relatively constant value of ∼16. Work since then has shown that the ratio indeed remains relatively constant across many environments and time scales, including deep oceans and coastal waters, but questions remain about whether innate biochemical or environmental factors are responsible. Loladze and Elser compiled literature values of nutrient ratios in prokaryotic and eukaryotic microorganisms, which, combined with a theoretical model, suggest that the N:P ratio is determined by a balance of maximum macromolecule biosynthesis rates—specifically for nitrogen-rich proteins and phosphorus-rich ribosomal RNA. Although the analysis considered cases in which growth rates were optimal, an N:P ratio of ∼16 isn't necessarily always desirable for efficient growth; communities in environments where the paucity of nitrogen or phosphorus limits growth may have optimal N:P ratios that are shifted away from 16. Because one of these two nutrients is often the main limiting growth factor in aquatic and terrestrial systems, observable deviations in N:P ratios would therefore provide insight into the biogeochemical processes that shape microbial community structure.

    Ecol. Lett. 14, 10.1111/j.1461-0248.2010.01577.x (2011).

  4. Ecology

    Trees Matter, Too

    1. Andrew M. Sugden
    CREDIT: JONATHAN BLAIR/CORBIS

    Although a variety of factors contribute to global wildfire activity, climate is thought to be a major determinant. Ohlson et al. now find that tree species composition has had at least as strong an influence as climate on wildfire activity over time in late Holocene boreal forests. By analyzing humus and peat records in northern Europe, the authors show that the invasion of Norway spruce, Picea abies, southwesterly across the region starting 4500 years ago was accompanied by a reduction in the frequency and severity of fire. The presence of Norway spruce would tend to make the forest more dense and shaded in the drier summer months, which would increase the local humidity of the understory and inhibit the spread of fire. Although the spruce invasion corresponded with a period of cooler and wetter climate, the tight spatial correlation of the arrival of spruce and the reduction in fire in specific locations argues for a key role of species composition in governing the fire regime. In turn, the reduction in fire would have led to other ecological consequences, notably increased sequestration of carbon by the vegetation and the establishment of other species requiring longer-term continuity. Thus, the results show how changes to the dominant forest species can exert a cascading effect on the regional ecology for centuries or millennia to come.

    J. Ecol. 99, 395 (2011).

  5. Biomedicine

    Keep Fit

    1. Stella M. Hurtley
    CREDIT: SAFDAR ET AL., PROC. NATL. ACAD. SCI. U.S.A. 108, 10.1073/PNAS.1019581108 (2011)

    Recent work has implicated mutations in mitochondrial DNA (mtDNA) in aging, and in humans, endurance training has been linked to health benefits, including increased life expectancy. Safdar et al. wanted to see if these processes could be linked in a strain of mice prone to mtDNA damage and who also exhibit a reduced life span. In these mice, a regime of endurance training—running for 45 min three times a week over 5 months—induced mitochondrial biogenesis, increased mitochondrial respiratory capacity, and prevented mtDNA damage. Furthermore, the trained mice no longer exhibited premature mortality or other symptoms associated with accelerated aging including fat loss, muscle loss, anemia, and graying fur (compare 30-week-old endurance-trained mouse, left, to 30-week-old control mouse, right). Future work will be required to see if similar regimes can protect and “rejuvenate” human mitochondria and mitigate the effects of normal or pathological forms of premature aging.

    Proc. Natl. Acad. Sci. U.S.A. 108, 10.1073/pnas.1019581108 (2011).

  6. Biochemistry

    Rethinking Riboswitch Regulation

    1. Valda Vinson

    The enzyme glucosamine-6-phosphate (GlcN6P) synthase (GlmS) is an important point of metabolic control in the synthesis of amino sugars: essential precursors in the biosynthesis of bacterial cell walls. GlmS gene expression is regulated by the glmS riboswitch, a sequence in the 5′ untranslated region of the mRNA that is also a ribozyme. Binding of GlcN6P activates glmS self-cleavage and this negatively regulates expression of GlmS.

    Watson and Fedor now reveal another level of complexity to riboswitch regulation. By growing yeast on various carbon sources and then measuring the ligand concentration dependence of intracellular cleavage kinetics, they found that products of hexose metabolism can competitively inhibit GlcN6P-induced self-cleavage. These results were confirmed in the Gram-positive bacterium Bacillus subtilis, the natural biological context for the riboswitch. These findings suggest that the glmS riboswitch might integrate chemical signals to modulate gene expression in response to the overall metabolic state of the cell.

    Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.1989 (2011).

  7. Molecular Biology

    Export Examined

    1. Guy Riddihough

    Many RNAs made in the cell nucleus function in the cytoplasm and so must be exported from the nucleus. Pre-microRNAs (pre-miRNAs) are exported from the nucleus via the karyopherin exportin-5 and are processed to their mature (miRNA) form in the cytoplasm by the Dicer protein, where they play a critical role in regulating gene expression. Bennasser et al. find that export of the Dicer mRNA from the nucleus of human cells also requires exportin-5 protein. The expression of exportin-5 is limiting, and overexpression of a substrate miRNA is able to saturate the exportin-5 export pathway. This leads to a decreased association between exportin-5 and its other substrates—such as the Dicer mRNA, which results in reduced amounts of Dicer protein in the cell. Thus, there is cross-regulation between pre-miRNAs and their processing enzyme, Dicer, which could help balance the amounts of the enzyme and its substrate.

    Upon infection, adenovirus produces large quantities of two small structured RNAs, which are exported by exportin-5 and can saturate the export pathway and reduce Dicer expression. Knockdown of either exportin-5 or Dicer enhances the growth of a replication-defective adenovirus, hinting that pathogens might also be able to exploit the regulation of Dicer mRNA levels by exportin-5 and, as a result, miRNA and siRNA levels.

    Nat. Struct. Mol. Biol. 18, 10.1038/nsmb.1987 (2011).

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