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<jats:title>Rolling Snowballs</jats:title> <jats:p> The genetic incompatibilities that separate ongoing speciation events have been hypothesized by the Dobzhansky-Muller model of speciation to snowball—that is, accumulate mutations causing postzygotic isolation at a faster rate than the linear accumulation of mutations. This occurs because of potential deleterious epistatic interactions in hybrids involving two or more interacting genes. Testing QTLs (quantitative trait loci) in seed and pollen sterility between multiple species pairs in the plant group <jats:italic>Solanum</jats:italic> , <jats:bold>Moyle and Nakazato</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1521" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193063">1521</jats:related-article> ) show that hybrid female (seed) sterility accumulates exponentially between increasingly distant species pairs, although not for hybrid male (pollen) sterility. In contrast, loci contributing to differences in other traits show no evidence for nonlinear accumulation over time. <jats:bold> Matute <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1518" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193440">1518</jats:related-article> ) come to similar conclusions through the use of deletion mapping in comparisons between two pairs of species of <jats:italic>Drosophila</jats:italic> . The number of genes causing postzygotic isolation grows as fast as the square of the number of substitutions between two species. Thus, a hybrid snowball effect is found in both plants and animals. </jats:p>

<jats:title>Rolling Snowballs</jats:title> <jats:p> The genetic incompatibilities that separate ongoing speciation events have been hypothesized by the Dobzhansky-Muller model of speciation to snowball—that is, accumulate mutations causing postzygotic isolation at a faster rate than the linear accumulation of mutations. This occurs because of potential deleterious epistatic interactions in hybrids involving two or more interacting genes. Testing QTLs (quantitative trait loci) in seed and pollen sterility between multiple species pairs in the plant group <jats:italic>Solanum</jats:italic> , <jats:bold>Moyle and Nakazato</jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1521" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193063">1521</jats:related-article> ) show that hybrid female (seed) sterility accumulates exponentially between increasingly distant species pairs, although not for hybrid male (pollen) sterility. In contrast, loci contributing to differences in other traits show no evidence for nonlinear accumulation over time. <jats:bold> Matute <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1518" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193440">1518</jats:related-article> ) come to similar conclusions through the use of deletion mapping in comparisons between two pairs of species of <jats:italic>Drosophila</jats:italic> . The number of genes causing postzygotic isolation grows as fast as the square of the number of substitutions between two species. Thus, a hybrid snowball effect is found in both plants and animals. </jats:p>

<jats:title>Clever Crows</jats:title> <jats:p> Understanding the adaptive significance of animal tool use requires reliable information on the foraging behavior in the wild. New Caledonian crows consume a range of foods and use sticks as tools to extract wood-boring beetle larvae from their burrows. These larvae, with their unusual diet, have a distinct isotopic signature that can be traced after consumption by the crows in the crows' feathers and blood. By comparing the stable isotope profiles of crows' tissues with those of their food sources, <jats:bold> Rutz <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1523" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1192053">1523</jats:related-article> ) estimated the proportion of larvae in crow diets, providing a proxy for tool-use dependence in individual crows. Just a few larvae can satisfy a crow's daily energy requirements, highlighting the substantial rewards available to competent tool users and their offspring. Thus, tool use provides New Caledonian crows with access to a very nutritional food source that is not easily exploited by beak alone. </jats:p>

<jats:title>Two Ways to Nucleotide Reduction</jats:title> <jats:p> Ribonucleotide reductases (RNRs) are essential for DNA synthesis and repair in all organisms, initiating nucleotide reduction through a free-radical mechanism. The class Ib RNRs are the primary aerobic RNRs for many human pathogens. NrdF, the class Ib RNR of <jats:italic>Escherichia coli</jats:italic> , can initiate nucleotide reduction through either a Fe <jats:sup>III</jats:sup> <jats:sub arrange="stack">2</jats:sub> -Y• or a Mn <jats:sup>III</jats:sup> <jats:sub arrange="stack">2</jats:sub> -Y• cofactor. Whereas the Fe-based cofactor can self-assemble, assembly of the Mn-based free radical requires a reduced flavoprotein, NrdI. <jats:bold> Boal <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1526" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1190187">1526</jats:related-article> , published online 5 August; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5998" page="1475" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1196347">Sjöberg</jats:related-article> </jats:bold> ) have gained insight into the mechanism of cofactor activation by determining structures of Mn <jats:sup>II</jats:sup> <jats:sub arrange="stack">2</jats:sub> -NrdF, Fe <jats:sup>II</jats:sup> <jats:sub arrange="stack">2</jats:sub> -NrdF, and Mn <jats:sup>II</jats:sup> <jats:sub arrange="stack">2</jats:sub> -NrdF in complex with reduced and oxidized NrdI. The structures show how a single protein, NrdF, can use two different oxidants to activate two different metallocofactors using distinct chemistries. </jats:p>

<jats:title>Location Matters</jats:title> <jats:p> Plasmacytoid dendritic cells (pDCs), an immune cell specialized to respond to viral infections, use Toll-like receptors (TLRs) 7 and 9 expressed in endosomes to sense viral nucleic acids. Triggering of TLR7 or 9 results in the induction of two distinct signaling pathways, one that leads to the production of proinflammatory cytokines and another that induces the expression of antiviral type I interferons. How one receptor can trigger two distinct signaling pathways, however, is not clear. <jats:bold> Sasai <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1530" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1187029">1530</jats:related-article> ) now show that subcellular localization is key. Cells from mice deficient in the Adapter Protein 3 (AP-3) complex, which regulates protein sorting to intracellular vesicles, did not produce type I interferons in response to TLR9 ligand, but proinflammatory cytokine production remained intact. AP-3 was required for trafficking of TLR9 from early endosomes, where proinflammatory signaling can occur, to lysosome-related organelles, where the signaling machinery required for type I interferon induction is located. Such spatial segregation may represent a common mechanism whereby activation of one receptor can result in the induction of multiple independent signaling cascades. </jats:p>

<jats:title>Making Modifications</jats:title> <jats:p> Arginylation of β-actin regulates cell motility and the actin cytoskeleton, but how differential arginylation of the two highly similar actin isoforms—β and γ—is achieved in vivo is unclear. <jats:bold> Zhang <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1534" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1191701">1534</jats:related-article> ; see the Perspective by <jats:bold> <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5998" page="1473" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1195567">Weygand-Durasevic and Ibba</jats:related-article> </jats:bold> ) describe a cotranslational mechanism that selectively regulates the arginylation of proteins through degradation and is dependent on the nucleotide coding sequence coupled to the translation speed. The work provides an explanation for the different N-terminal arginylation states of β- and γ-actin in vivo and suggests translation rate affected by nucleotide coding sequence confers different posttranslational states to proteins and selectively regulates protein degradation. </jats:p>

<jats:title>MicroRNA-16 and Depression</jats:title> <jats:p> Signal transmission between neurons is effected by neurotransmitters such as serotonin. Membrane-bound transporters remove excess neurotransmitters. Disruption of the delicate balance between neurotransmitter release and removal can lead to larger disruptions in neuronal circuitry. Depression and anxiety may be linked to dysfunction of some of these circuits. Uptake inhibitors can be used to treat depression, but the molecular pathways affected have been unclear. <jats:bold> Baudry <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1537" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1193692">1537</jats:related-article> ) now show that microRNA-16 controls synthesis of the serotonin transporter and that the amount of microRNA-16 can be controlled by the same uptake inhibitors used to treat depression. </jats:p>

<jats:title>Naval Gazing</jats:title> <jats:p> Simple perceptual tasks, such as detecting the contrast between light and dark bars in a grating, have been a mainstay of psychophysical research for decades. This kind of task makes it possible to obtain both an objective measure of how accurate subjects are and a subjective measure of how confident they are in their judgments. <jats:bold> Fleming <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" page="1541" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1191883">1541</jats:related-article> ; see the Perspective by <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="5998" page="1478" related-article-type="in-this-issue" vol="329" xlink:href="10.1126/science.1195983"> <jats:bold>Lau and Maniscalco</jats:bold> </jats:related-article> ) have taken this approach one step further by constructing a measure of how accurate subjects are in their confidence judgments. This capacity for introspection, which can be regarded as one facet of metacognition (thinking about thinking), is shown to vary across individuals and to correlate positively with the gray matter volume of the frontopolar cortex (the frontmost region of the brain) and also with white matter in the tracts of the corpus callosum that connect these regions in the left and right hemispheres. </jats:p>

<jats:p>The show includes 30 years of China's one-child policy, hydrocarbon-degrading bacteria in the Gulf of Mexico, tool-making crows, and more.</jats:p>

<jats:p>A weekly roundup of information on newly offered instrumentation, apparatus, and laboratory materials of potential interest to researchers.</jats:p>