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<jats:title>Adding to the Antiviral Arsenal</jats:title> <jats:p> The envelope of influenza virus contains two immunodominant glycoproteins: hemagglutinin and neuraminidase (NA). Existing antivirals like zanamivir (Relenza) and oseltamivir (Tamiflu) target NA; however, the development of drug resistance is a problem. <jats:bold> Kim <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="71" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1232552">71</jats:related-article> , published online 21 February) now report a different class of NA inhibitors. NA catalyzes the removal of sialic acids from the surface of host cells to initiate entry. Discovery of a NA–sialic acid intermediate led to the production of sialic acid analogs that bound covalently to NA and inhibited its enzymatic activity. These compounds showed activity against a wide variety of influenza strains, inhibited viral replication in cell culture, and were able to protect mice against influenza infection. Protection of mice was equivalent to protection seen from zanamivir. Moreover, the compounds showed activity against drug-resistant strains in vitro. These compounds represent a potentially useful addition to the arsenal of antivirals used to treat influenza infection. </jats:p>

<jats:title>Putting Selenium in Proteins</jats:title> <jats:p> The 21st amino acid, selenocysteine (Sec), occurs in the active site of many redox enzymes. Its cognate transfer RNA (tRNA) is first loaded with Ser by seryl-tRNA synthetase and the Ser-tRNA <jats:sup>Sec</jats:sup> is then converted to Sec-tRNA <jats:sup>Sec</jats:sup> . <jats:bold> Itoh <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="75" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1229521">75</jats:related-article> ) determined the crystal structures of the selenocysteine synthase, SelA, that is responsible for this conversion in bacteria, alone and in complex with tRNA. The decameric SelA complex binds to 10 tRNA <jats:sup>Sec</jats:sup> molecules. The structures, together with biochemistry, show how SelA discriminates tRNA <jats:sup>Sec</jats:sup> from tRNA <jats:sup>Ser</jats:sup> , give insight into the mechanism of catalysis, and show that decamerization is essential for function. </jats:p>

<jats:title>Silencing Transposons</jats:title> <jats:p> Eukaryotic DNA is packaged onto nucleosomes, which are composed of four core histones (H2A, H2B, H3, and H4). Chromatin also contains a fifth histone, H1, which binds to both the core particles and the “linker” DNA that joins adjacent nucleosomes, where it helps chromatin to fold into higher-order structures and generally silences gene expression. In <jats:italic>Drosophila</jats:italic> germline and somatic cells and tissues, <jats:bold> Lu <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="78" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1234654">78</jats:related-article> ) found that the repressive function of H1 in vivo was directed toward transposable elements and independent of small RNA silencing pathways. Instead, H1 acted through direct recruitment of the histone methyltransferase Su(var)3–9, which methylates histone H3 lysine 9, a repressive histone mark. </jats:p>

<jats:title>MicroRNA Mechanism</jats:title> <jats:p> MicroRNAs are small noncoding RNAs that regulate gene expression by binding complementary target messenger RNAs (mRNAs) and repressing their expression through repression of protein translation and mRNA degradation. <jats:bold> Meijer <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="82" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1231197">82</jats:related-article> ) show that in a HeLa cell system mRNA degradation is a consequence of translational inhibition via the initiation factor eIF4A2. </jats:p>

<jats:title>Archaea Powered by Rocket Fuel</jats:title> <jats:p> Perchlorate is a ubiquitous chlorine-based compound that forms naturally in the atmosphere. It is only present in large deposits in a few locations, such as the Atacama Desert in Chile, which has been assumed to be because perchlorate-reducing bacteria normally degrade it into chloride and oxygen. <jats:bold> Liebensteiner <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="85" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1233957">85</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="6128" page="38" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1236336">Nerenberg</jats:related-article> </jats:bold> ), however, found that an archeon, <jats:italic>Archaeoglobus fulgidus</jats:italic> , can also reduce perchlorate. The archaeal perchlorate reduction pathway shares limited similarity with bacterial perchlorate reduction: Instead of producing chloride and oxygen, enzymatically produced chlorite reacts with sulfide to produce oxidized sulfur compounds. Because hyperthermophilic anaerobic archaea similar to <jats:italic>A. fulgidus</jats:italic> are thought to have been among the first complex organisms to evolve on Earth, they may have started creating oxidized conditions in some habitats before the emergence of oxygen-generating photosynthesis. </jats:p>

<jats:title>Thwarting HIV</jats:title> <jats:p> Multiple genome-wide association studies have revealed that human leukocyte antigen (HLA) genes of the major histocompatibility complex locus have the strongest impact on HIV. In particular, a single-nucleotide polymorphism 35 base pairs upstream of HLA-C shows significant association with viral load and protection against HIV. How HLA-C mediates these effects is unknown. <jats:bold> Apps <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="87" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1232685">87</jats:related-article> ) now demonstrate that increasing surface expression of HLA-C is associated with reduced viral load and reduced rate of progression to low CD4 <jats:sup>+</jats:sup> T cell counts in African and European Americans. High HLA-C expression likely promoted improved HIV control through a more effective cytotoxic CD8 <jats:sup>+</jats:sup> T cell response. In contrast to HIV infection, high HLA-C expression was associated with a higher risk of the inflammatory bowel disease, Crohn's disease. </jats:p>

<jats:title>Neuronal Transposons</jats:title> <jats:p> Transposons comprise a hefty chunk of the <jats:italic>Drosophila</jats:italic> genome and, unregulated, can generate mutations; thus, mechanisms exist to suppress transposon activity, particularly in the germline. <jats:bold> Perrat <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="91" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1231965">91</jats:related-article> ) investigated transposon motility in neurons of the <jats:italic>Drosophila</jats:italic> brain. The mushroom body of the brain, responsible for olfactory memory, contains several different types of neurons. One class of neurons, the αβ neurons, exhibited increased transposon mobility, which generated increased neuronal diversity. </jats:p>

<jats:title>How to Make Decisions</jats:title> <jats:p> Recently, a number of methods to probe internal properties of nonlinear neural systems have been developed. In these methods, highly variable stimuli are used to explore the input space of the system. Neural responses are then studied using models that take advantage of the known trial-by-trial stimulus information. <jats:bold> Brunton <jats:italic>et al.</jats:italic> </jats:bold> (p. <jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6128" page="95" related-article-type="in-this-issue" vol="340" xlink:href="10.1126/science.1233912">95</jats:related-article> ) adapted this combined approach to decision-making. Both in rats and humans, the diffusion constant of the drift-diffusion model of decision-making was zero, implying that the noise is all in the processing of sensory input and not in the evidence accumulator. In addition, rats gradually accumulated evidence for decision-making, with strong effects of sensory adaptation on gradual accumulation of evidence. </jats:p>

<jats:p>Listen to stories on the ethics of de-extinction, decoding dreams, more evidence for mantle plumes, 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>