Editors' Choice

Science  18 Jul 2008:
Vol. 321, Issue 5887, pp. 318

    Peering down the Drain

    Recent observations that excreted estrogenic compounds derived from pharmaceuticals can harm fish at concentrations in the ng/liter range have driven researchers with increasing urgency to track the path of these microcontaminants down the drain. Johnson et al. review the various pros and cons of analytical sampling versus modeling approaches toward understanding precisely what flows from the sewer into the wider world. Sampling might seem the most accurate option, but in practice, field conditions vary widely over time and space, necessitating multiple withdrawals; compounds may degrade between acquisition and analysis; and techniques may lack the requisite detection sensitivity. Modeling is a daunting alternative, in light of the numerous factors that must be considered, ranging from human drug consumption and excretion trends, to variations in the effectiveness of sewage treatment protocols, to the range of hydrological features affecting flow dynamics. On the flip side, though, the authors note that models can more easily be scaled to treat diminishingly small concentrations without running into detection thresholds. In cases where physical measurements and model results could be compared, they agreed reassuringly well (often within a factor of 3 or 4), supporting the case for an integrated approach that balances the strengths of each complementary technique. — JSY

    Environ. Sci. Technol. 42, 10.1021/es703091r (2008).


    Trapped in an Eddy Upstream

    Almost all eukaryotic genes initiate the translation of their messenger RNA (mRNA) into protein at an AUG start codon (which codes for the amino acid methionine). Ribosomes, the protein-synthesizing engines of the cell, scan from the 5′ end of an mRNA until they find the first AUG, and then start translation. Some mRNAs contain a supernumerary AUG (and associated short coding region) upstream and independent of the main AUG/coding region, and such upstream open reading frames (uORFs) have the potential to regulate the translation of the downstream gene.

    Ivanov et al. have found a series of conserved short uORFs associated with genes involved in polyamine synthesis, with the curious feature that they often start with a noncanonical AUU codon and hence have been overlooked in bioinformatic scans. The presence of AUU seems to be critical for the uORF to direct polyamine-directed repression of the downstream coding region; polyamines (such as spermidine) reduce the fidelity of the translation initiation complex for AUG, thus allowing increased production of the AUU uORF at the expense of the downstream polyamine biosynthesis gene—creating an autoregulatory feedback loop. The patchy distribution of these AUU uORFs across the eukaryotic phylogenetic tree suggests that they may have arisen independently on several occasions. — GR

    Proc. Natl. Acad. Sci. U.S.A. 105, 10.1073/pnas.0801590105 (2008).


    Fine-Tuning of Spike Timing

    Neurons in layer III of the entorhinal cortex send projections along the perforant pathway that reaches area CA1 of the hippocampus. In addition to well-documented excitatory connections, there is also an important feedforward inhibitory circuit; monosynaptically activated interneurons form inhibitory synapses on CA1 pyramidal cells and thus control the timing of spiking of their target neurons. Feedforward inhibition limits the temporal summation of excitatory potentials and generates a narrow temporal window of excitability during which postsynaptic targets can fire action potentials. One important component of this feedforward inhibitory circuit is the neurogliaform cells, which frequently target the distal dendrites of excitatory neurons. Neurogliaform cells are known to be interconnected extensively through gap junctions, which has led to the hypothesis that feedforward inhibition of CA1 pyramidal cells might be highly synchronized. Price et al. found that stimulation of neurogliaform cells evoked GABAA receptor-mediated inhibitory postsynaptic currents (IPSCs) with a slow decay in pyramidal cells. The IPSCs also had a small but robust GABAB receptor component. Furthermore, these synapses were also subject to presynaptic GABAB receptor-mediated control. It thus makes physiological sense that these inhibitory neurogliaform-to-pyramidal cell synapses are finely tuned to control the integration time for one of the major excitatory pathways into the hippocampus. — PRS

    J. Neurosci. 28, 6974 (2008).


    Adaptive Differentiation in Barley

    Variation in response to local conditions that affect growth and reproduction is a crucial means by which plants optimize their fitness. However, the underlying genetic loci that control differences between populations are generally unknown. Verhoeven et al. have investigated the local adaptation in two wild barley populations by measuring the response to habitat in lines with mapped quantitative trait loci (QTLs) affecting flowering time, relative growth rate, and seed weight. When individuals were transplanted reciprocally between environments, there were differences in the degree of selection on QTLs affecting flowering time, suggesting that it is a target of habitat-specific natural selection and that this adaptation may contribute to population-level divergence. — LMZ

    Mol. Ecol. 17, 3416 (2008).


    A Microfluidic Construction Kit

    The field of microfluidics has blossomed as chemists and engineers have devised clever ways to handle small fluid volumes. Although many approaches exist for making devices, they often include lithographic or printing techniques. To overcome this limitation, Rhee and Burns show the feasibility of a microfluidic construction kit where individual grids are assembled by hand on a substrate. The grids range in size from 4 to 8 mm2 and include units for fluid inlet and outlet, channels for mixing or separation, small or large chambers for sample collection, and valves and culture beds for growing cells. Grids can be placed on bare glass or on a surface coated with a thin polymer layer to improve adhesion. For better bonding, curing agents can be used to fuse the grids to the substrate and each other. Notched or covered grids, though somewhat more complex, can be used to improve grid alignment. The authors envision that these kits can expand the use of microfluidics by non-experts, particularly in the biological sciences. — MSL

    Lab on a Chip 8, 10.1039/b805137b (2008).


    Gilding the Superatom Model

    When metal atoms bind together in the gas phase to form clusters, they tend to gather preferentially in certain discrete numbers. This tendency has been rationalized with a superatom model, in which the addition of atoms to a cluster is analogous to the filling of valence electron shells in atoms themselves, so that when a critical number of atoms donate electrons to the cluster, they effectively form the equivalent of a noble gas configuration. Extending the model to clusters crystallized in solution seemed more complicated, given the requirement in that context of coordinating ligands for steric protection. However, Walter et al. show, using density functional theory, that the superatom model straightforwardly accounts for the particular stability of two crystallographically characterized gold clusters, the thiolate-coordinated Au102 and phosphine/halide-coordinated Au39, as well as several smaller examples. The theory also predicts stability of 44- and 75-membered clusters that are yet to be fully structurally characterized. — JSY

    Proc. Natl. Acad. Sci. U.S.A. 105, 9157 (2008).


    Mobile Intron Meets Magic Spot

    Early on, introns were usually thought of as useless pieces of transcribed RNA that needed to be excised before the product RNA could become fully active. The later identification of intron-encoded species, such as microRNAs, has emphasized the utility of anything and everything that a cell carries around. In Lactococcus lactis, there is a mobile group II intron that consists of the catalytic LtrB RNA and the intron-encoded protein LtrA. The protein serves to stabilize the active conformation of the RNA, which splices itself out of transcripts, and also supplies a reverse transcriptase activity, which enables LtrB to insert itself at vulnerable sites in genomic DNA. One such site is the origin of replication locus (oriC) that in Escherichia coli is located at the ends of each rod-shaped cell.

    Zhao et al. show that LtrA localizes to the poles as well and thus accounts for the preferential integration of LtrB at oriC. They also find, surprisingly, that LtrA binds to polyphosphate, a curious metabolite that increases under conditions of stress and is degraded by the enzyme that synthesizes ppGpp (magic spot); this interaction has the consequence of spreading LtrA and other nucleic acid-binding proteins throughout the cell when nutrients become scarce. Whether this diffusion of polar components is the long-sought function of polyphosphate remains to be determined. — GJC

    PLoS Biol. 6, e150 (2008).