This Week in Science

Science  25 Jun 2010:
Vol. 328, Issue 5986, pp. 1609
  1. No Dicer for Me


    MicroRNAs (miRNAs) are small noncoding RNAs found in most eukaryotes. Most are processed from primary transcripts in the nucleus by the microprocessor enzyme complex, which includes the nuclease Drosha, with a small number being generated by the messenger RNA splicing machinery. All pre-miRNAs are then exported into the cytoplasm where they are cleaved further by a second nuclease, Dicer, into the mature, functional miRNA. Cifuentes et al. (p. 1694, published online 6 May), now show that in a Dicer mutant fish at least one miRNA, miR-451, is still formed from pre-miR-451. The processing of pre-miR-451 requires the slicing activity of another protein in the miRNA pathway, Argonaute2. The unusual secondary structure of the pre-miR-451 determines its noncanonical processing pathway, which suggests that other miRNAs might also be processed in this way.

  2. Warming Up

    For the past half-million years, our planet has passed through a cycle of glaciation and deglaciation every 100,000 years or so. Each of these cycles consists of a long and irregular period of cooling and ice sheet growth, followed by a termination—a period of rapid warming and ice sheet decay—that precedes a relatively short warm interval. But what causes glacial terminations? Denton et al. (p. 1652) review the field and propose a chain of events that may explain the hows and whys of Earth's emergence from the last glacial period. Pulling together many threads from both hemispheres suggests a unified causal chain involving ice sheet volume, solar radiation energy, atmospheric carbon dioxide concentrations, sea ice, and prevailing wind patterns.

  3. Inhibiting Leukocytosis

    Leukocytosis—an elevated white blood cell count—contributes by unknown mechanisms to the pathogenesis of atherosclerosis and associated coronary heart disease. Now, Yvan-Charvet et al. (p. 1689, published online 20 May; see the Perspective by Hansson and Björkholm) show that the adenosine triphosphate–binding cassette transporters ABCA1 and ABCG1 are critical suppressors of atherosclerosis-associated leukocytosis. Mice deficient in both transporters in blood-producing hematopoietic cells possessed increased levels of hematopoietic stem and multipotential progenitor cells and accelerated atherosclerosis. ABCA1 and ABGA1 protect against atherosclerosis by promoting cholesterol efflux from cholesterol-laden macrophage foam cells to lipid-poor high-density lipoprotein (HDL) and apolipoprotein A-1. The leukocytosis and atherosclerosis in ABCA1- and ABG1-deficient mice were reversed in the presence of high amounts of HDL. Thus, signaling already known to inhibit atherosclerosis by reducing cholesterol in atherosclerotic plaques also reduces atherosclerosis-associated leukocytosis.

  4. Just Breathe


    Design of artificial systems that mimic in vivo organs could provide a better alternative for understanding mechanisms underlying physiological responses than current cell-based models or animal tests. Huh et al. (p. 1662) have created a tissue-tissue interface of human-cultured epithelial cells and endothelial cells together, with extracellular matrix in a device that models the alveolar-capillary interface of the human lung. The device mimicked physiological organ-level functions, including pathogen-induced inflammatory responses and responses to cytokine exposure. Breathing-type movements affected acute pulmonary cell toxicity and proinflammatory activity of widely used nanoparticulates.

  5. Temporal Tomography

    Tomography is a widely used technique for visualizing three-dimensional objects by algorithmic reconstruction from multiple two-dimensional images from distinct vantage points. However, its application has largely been restricted to static imaging. Kwon and Zewail (p. 1668) have now adapted an ultrafast electron microscope to perform tomography with subpicosecond resolution. The method relies on systematically varying the tilt angle of the sample with respect to the incoming electron beam, and enabled assembly of a detailed frame-by-frame record of the response of a curled carbon nanotube to sudden heating.

  6. Dancing in the Light

    Nearly 200 years ago, the botanist Robert Brown noted that pollen particles floating on a liquid displayed a random motion, jittering under the microscope as if the particles were alive. In 1905, Albert Einstein described this Brownian motion in terms of statistical thermodynamics. Now, Li et al. (p. 1673, published online 20 May) use a single, optically trapped silica bead to probe the dynamics of Brownian motion, measuring the predicted instantaneous velocity of the particle and verifying the short-time-scale behavior predicted a century ago. As well as testing fundamental principles of physics, the technique also has practical implications for cooling particles to ultralow temperatures.

  7. Three Fluorines at Once

    The trifluoromethyl (CF3) group is playing an increasingly important role in the design of pharmaceutical and agrochemical compounds. CF3 is a powerful attractor of electron density within a given molecular framework, and recently fluorine-hydrocarbon interactions have emerged as a distinct complement to the more traditional hydrophilic/hydrophobic interplay that governs docking between small molecules and proteins. Cho et al. (p. 1679) now present an efficient method for appending CF3 groups to a broad range of aryl substrates. A carefully optimized palladium catalyst was able to speed up a critical elimination step that has plagued previous efforts to realize a general solution to this synthetic challenge.

  8. Glacial Gas

    A series of sudden and large warming episodes, called Dansgaard-Oeschger events, interrupted the cold conditions of the last glacial period. Large increases in the concentration of atmospheric methane accompanied the events, whose causes have remained the object of much speculation. Bock et al. (p. 1686) report measurements of the hydrogen isotopic composition of methane recovered in the North Greenland Ice Core Project. The excess atmospheric methane accompanying two Dansgaard-Oeschger events did not come from marine clathrates; instead, the methane probably came from increased fluxes from boreal wetlands, another major source of methane.

  9. Bacterial (Interferon)ce

    Intracellular bacterial pathogens, such as Listeria monocytogenes, are detected in the cytosol of host immune cells, where they induce a host response that is often dependent on microbial secretion systems. Woodward et al. (p. 1703, published online 27 May) now show that L. monocytogenes produce and release cyclic diadenosine monophosphate into the host cytosol, which induces the production of host type I interferon. Because a number of intracellular pathogens contain the protein machinery to generate this nucleotide and also activate this same innate immune pathway, a common molecular mechanism may exist for host detection of cytosolic bacterial pathogens.

  10. Hydrated Minerals on Martian Northern Plains


    The presence of hydrated minerals on the surface of Mars implies that the crust of the planet was once altered by the action of liquid water. This conclusion is well established for the ancient southern highlands of Mars, but the situation in the northern lowlands, which are thought to have been resurfaced by lava flows during the Hesperian period about 3 billion years ago, is not so clear. Carter et al. (p. 1682) report the detection of hydrated minerals in nine northern plain craters, which are thought to have exposed the ancient, pre-Hesperian crust. The results suggest that the degree of alteration of the ancient martian crust is more extensive than previously assumed.

  11. Addicts Lose Plasticity

    What are the biological mechanisms associated with the transition from occasional drug use to addiction? In rats, like in humans, even after a prolonged period of drug intake, only a limited number of animals develop addiction-like behavior despite the amount of drug taken by all subjects being the same. Kasanetz et al. (p. 1709) compared the expression of N-methyl-d-aspartate (NMDA)–dependent long-term depression (NMDA-LTD) in the nucleus accumbens of addicted and nonaddicted rats. Initially, once drug self-administration had been learned and consolidated, but before the appearance of addiction-like behavior, LTD was suppressed in all animals independently of their vulnerability to addiction at a later stage. However, after 2 months, when addiction-like behavior appears, LTD was persistently lost in the addicted animals. In contrast, normal NMDA-LTD reappeared in animals that maintained a controlled drug intake without becoming addicted.

  12. Between a Rock and a Hard Judgment

    In general terms, our sensory and motor pathways mature sooner than the so-called higher cognitive centers, which become fully operational later in life. Might these early somatic communication channels with the outside world influence and become buried within the higher levels of processing involved in forming impressions of other people and deciding how to behave toward them? Ackerman et al. (p. 1712) provide evidence for just such a process by focusing on touch. By manipulating the weight, hardness, or roughness of objects that subjects were exposed to, they were able to bias the social judgments and behaviors of the subjects in unrelated realms, such as assessing the rigidness or seriousness of employees and job applicants.

  13. Defining Time-Zero

    When a high-energy photon hits an atom and is absorbed, the result can be the excitation and emission of an electron. This photoemission, or photoelectric effect, is generally assumed to occur instantaneously, and represents the definition of “time-zero” in clocking such ultrafast events. Schultze et al. (p. 1658, see the cover; see the Perspective by van der Hart) use ultrafast spectroscopy, with light pulses on the time scale of several tens of attoseconds, to test this assumption directly. They excite neon atoms with 100 eV photons and find that there is a small (20-attosecond) time delay between the emission of electrons from the 2s and 2p orbitals of the atoms. These results should have implications in modeling electron dynamics occurring on ultrafast time scales.

  14. Tangle-Free Polymer Dynamics

    The dynamics of polymer chains at interfaces will differ from the dynamics in the bulk. While hard interfaces generally cause chain motions to slow down, at free surfaces the dynamics should generally speed up. A consequence is that for thin polymer films, there should be a reduction in the glass transition temperature (Tg), but a wide range of effects have been seen in different polymeric materials. Now, Yang et al. (p. 1676) show that for short, unentangled polystyrene polymers, there is a direct correlation between the viscosity and the glass transition temperature, and that the reduction in Tg is due to a surface mobile layer that dominates the behavior as the films decrease in thickness.

  15. In, Out, Positive Charge About

    The mechanism by which multispanning, helix-bundle membrane proteins are inserted into their target membrane is not completely understood. EmrE is an Escherichia coli inner-membrane protein with four transmembrane helices that can take up two distinct topologies—with its amino terminus toward the cytosol, or away from the cytosol. Seppälä et al. (p. 1698, published online 27 May; see the Perspective by Tate) exploited the dual-topology property of EmrE to study the mechanism of membrane protein assembly in Escherichia coli. Systematically exploring the effects of positively charged residues on the topology of EmrE revealed that the membrane orientation of EmrE constructs with four or five transmembrane helices could be controlled by a single positively charged residue placed in different locations throughout the protein, including the very carboxyl terminus. Such global control of membrane protein topology raises important questions concerning how multispanning membrane proteins are handled by the membrane protein insertion machinery.

  16. Breaking Hamilton's Rule

    Hamilton's rule states that the evolution of cooperation is correlated with the kin relationship between the actor and the recipient and the degree of the benefit. However, this approximation relies on several steps of simplification that are often violated in natural systems. Smith et al. (p. 1700) derived a non-additive model for the evolution of cooperation by kin selection that could be applied to all domains of life—not just animals. Experimental data examining the bacteria Myxococcus xanthus showed that nonlinear interactions among cells make bacterial cooperation surprisingly resistant to cheating.

  17. A Gut Feeling

    The mammalian gut is colonized by many nonpathogenic, commensal microbes. In order to prevent the body from mounting inappropriate immune responses to these microbes, plasma cells in the gut produce large amounts of immunoglobulin A (IgA) specific for commensal bacteria. Because of the difficulties of uncoupling IgA production from microbial colonization, how commensal bacteria shape the gut IgA response is not well understood. Hapfelmeier et al. (p. 1705; see the Perspective by Cerutti) have now devised a way to get around this problem by developing a reversible system of gut bacterial colonization in mice. Commensal-specific IgA responses were able to persist for long periods of time in the absence of microbial colonization and required the presence of high microbial loads in the gut for their induction. IgA responses upon bacterial reexposure did not resemble the synergistic prime-boost effect seen in classical immunological memory responses but rather exhibited an additive effect that matched the current bacterial content present in the gut. The body thus constantly adapts the commensal-specific immune response to the microbial species present in the gut, which contrasts with the systemic immune response, which persists in the absence of pathogenic microbes.

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