This Week in Science

Science  24 Feb 2012:
Vol. 335, Issue 6071, pp. 888
  1. Enduring Tolerance

    During an infection, the host organism deploys multiple defense strategies. Disease resistance, the process by which the immune system decreases pathogen burden is perhaps the most well-known, and certainly the mechanism that is best studied and understood. Other defense strategies range from pathogen avoidance, through tolerance of pathogen-induced tissue damage, and endurance of the overall pathogen burden. Medzhitov et al. (p. 936) review the concept of disease tolerance and suggest that particularly in animals, it is an overlooked mechanism of host defense.

  2. Tunnel Barriers for Graphene Transistors


    Transistor operation for integrated circuits not only requires that the gate material has high-charge carrier mobility, but that there is also an effective way of creating a barrier to current flow so that the device can be switched off and not waste power. Graphene offers high carrier mobility, but the shape of its conduction and valence bands enables electron tunneling and makes it difficult to achieve low currents in an “off” state. Britnell et al. (p. 947, published online 2 February) have fabricated field-effect transistors in which a thin tunneling barrier created from a layered material—either hexagonal boron nitride or molybdenum disulfide—is sandwiched between graphene sheets. These devices exhibit on-off switching ratios of ≈50 and ≈10,000, respectively, at room temperature.

  3. Paracrystalline

    Amorphous silicon has traditionally been represented by a continuous random network model in which there is no long-range ordering for the atoms, and some have less than fourfold coordination, which form dangling bonds—a type of defect. Treacy and Borisenko (p. 950; see the Perspective by Gibson) used fluctuation electron microscopy to explain that models including regions of crystalline order are needed to fit the observed local variations in structure. Thus, on the 1- to 2-nanometer-length scale, this material should be thought of as having a paracrystalline structure containing localized crystalline regions.

  4. Warming and Shrinking


    In most mammals, individual body sizes tend to be smaller in warmer regions and larger in cooler regions. Secord et al. (p. 959; see the Perspective by Smith) examined a high-resolution 175,000-year record of equid fossils deposited over a past climate shift—the Paleocene-Eocene Thermal Maximum—for changes in body size. Using oxygen isotopes collected from the teeth of co-occurring mammal species to track prevailing environmental temperature, a clear decrease in equid body size was seen during 130,000 years of warming, followed by a distinct increase as the climate cooled at the end of the period. These results indicate that temperature directly influenced body size in the past and may continue to have an influence as our current climate changes.

  5. How Dry They Were

    How much rainfall failure contributed to the disintegration of classical Maya civilization? Medina-Elizalde and Rohling (p. 956) analyzed records from three lakes and a stalagmite from the Yucatán Peninsula to quantify the change in precipitation that the region experienced between 800 to 1000 years A.D. Precipitation decreased episodically for up to a decade at a time and in total by as much as 40% during the 200 years of the civilization's fall, probably as a result of a reduction in summer tropical storm rainfall. This finding highlights the sensitivity of this region to modest reductions of rainfall that are projected by some climate model.

  6. Cashing Up

    Do small businesses in developing economies benefit from an infusion of cash or of capital, such as inventory or materials, and is the effect a momentary blip or a sustained expansion? De Mel et al. (p. 962) have extended their study of one-time cash or capital transfers to a group of randomized business owners in Sri Lanka to look at the status of the businesses 5 years later and find an increased likelihood of survival and higher profits for male-owned enterprises, but no significant effects on female-owned businesses. The authors suggest that capital transfers are more likely to be used by male-owned firms to grow the business, but more likely to be “cashed-out” from female-owned firms and diverted to household uses.

  7. Distinguishing Ciliopathy

    Cilia were once thought to be evolutionary remnants, but structural defects reveal their importance in signaling pathways and human disease, such as Joubert syndrome. Either of the genes TMEM138 and TMEM216 can be found mutated in phenotypically indistinguishable ciliopathy patients. Interestingly, despite their lack of sequence homology, these genes have always been aligned in head-to-tail configuration during vertebrate evolution. The proteins expressed by these genes mark distinct tethered vesicles, which differentially carry ciliary proteins for assembly. Lee et al. (p. 966, published online 26 January; see the Perspective by Chakravarti and Kapoor) show that the coordinated expression of these adjacent genes depends upon a coevolved regulatory element in the noncoding intergenic region, which thus integrates the roles of both gene products. This discovery explains not only the indistinguishable pathogenesis of the patients' genotypes but also how the evolutionary clustering of genes unrelated in sequence may correlate with coordinated control of expression and function.

  8. Death for Development

    Cell death is critical for animal development and for the promotion of gastrulation, as well as for sculpting tissues. Although cell death by apoptosis is essential in some invertebrates, genes promoting apoptosis in the mouse are not required for viability. This surprising observation prompted investigations by Blum et al. (p. 970; see the Perspective by Link and Saldi), who have discovered a nonapoptotic developmental cell death process mediated by a polyglutamine-repeat protein in the nematode worm Caenorhabditis elegans. This form of cell death is morphologically similar to cell death occurring during vertebrate development, particularly cell death accompanying polyglutamine-dependent neurodegeneration.

  9. Networks of Networks

    Quantitative networks, such as those represented by food webs, have become an important way of investigating the structure of ecological communities, but thus far only encompass a small subset of species. Pocock et al. (p. 973) have linked seven different types of ecological networks to form a network of networks. They found that although networks varied in their robustness to species loss, they did not strongly co-vary; that is, what happens to one network is unrelated to what happens to another. The networks studied were identified from an agroecosystem in the southwestern UK, a habitat in which biodiversity has suffered substantially. This study succeeded in revealing which species are potential targets for restoration of ecological function in this and other systems.

  10. Winging It


    Genes that explain phenotypic variation between species have only been identified within a handful of model organisms, which limits the scope and understanding of the genetics of phenotypic diversification. On investigating the phenotypic diversity in wing size among wasps of the genus Nasonia, Loehlin and Werren (p. 943) have identified the genetic basis of a morphological difference between two closely related species and showed how changes in regulatory elements have evolved to change expression of a single gene, unpaired-like (upd-like), a functionally conserved signaling gene. Overall, it appeared that significant morphological change was achieved through a series of relatively rapid, but small-scale changes.

  11. A Fraction of Folding

    An energy barrier has to be crossed as a protein transforms between folded and unfolded states. Molecular dynamic simulations have observed sharp transitions, with barrier crossing times of less than a microsecond, a fraction of the total folding time; however, this time range has been inaccessible to single-molecule experiments. Chung et al. (p. 981) described single-molecule fluorescence experiments that allowed measurement of the transition-path time for a fast-folding protein and to reduce the upper bound for a slow-folding protein. Although the folding rates differed by a factor of 10,000, the transition-path times differ by less than a factor of 5, pointing to energy landscape theory for the explanation.

  12. Sound the Alarm

    When small protein fragments or nucleic acids derived from an invading pathogen are detected by pattern recognition receptors on immune cells, the innate immune response is triggered. This event activates cells of the adaptive immune system, and together, both responses clear the infection. Infections also induce the release of “danger-associated molecular patterns,” or alarmins, from the host as a result of tissue damage. Whether these are also important for the ensuing immune response is less clear. Bonilla et al. (p. 984, published online 2 February) report that the alarmin, interleukin-33, is required for optimal cytotoxic CD8+ T cells responses and antiviral immunity in mice. In virus-infected mice deficient in IL-33 or its receptor, IL-33 is essential for signaling CD8+ T cells to expand, produce multiple cytokines and acquire cytotoxic capabilities. These results showed that endogenous material, independently of pathogen-derived molecules, are also required for antiviral immunity.

  13. When the Rain Comes

    When raindrops fall, frictional forces between the droplet and the surrounding air create a drag that limits the speed at which the raindrop can descend. This drag also dissipates some of the kinetic energy of the falling raindrops within the shear zones surrounding them and is a significant component of the atmospheric energy budget, according to Pauluis and Dias (p. 953; see the Perspective by Frierson). Using data from satellites, they find that precipitation-induced energy dissipation is of the same magnitude as that caused by atmospheric turbulence and therefore that of a strengthened hydrological cycle, which is widely expected to occur as a result of climate warming and could have an impact on the strength of atmospheric circulation.

  14. Piercing Botulinum's Defense

    Botulinum neurotoxins (BoNTs) are poisons that cause muscle paralysis. In the acidic intestine, ingested BoNTs are protected within a progenitor toxin complex. The toxins are released on absorption into the neutral bloodstream. Gu et al. (p. 977; see the Perspective by Adler) present the structure of a minimally functional progenitor toxin complex—BoNT in complex with a nontoxic, nonhemagglutinin protein at 2.7 angstrom resolution. The structure, together with biochemical studies, showed how complex assembly is regulated by pH and may be useful in guiding the development of delivery vehicles for oral administration of biologics and in the design of inhibitors for oral BoNT poisoning.

  15. Curbing the Other Side

    The two hemispheres of the brain are connected via the corpus callosum; however, this pathway and its function are still not fully understood. Palmer et al. (p. 989) used a combination of optogenetic, calcium-imaging, and electrophysiological methods to investigate the cellular mechanism of interhemispheric inhibition of the firing frequency of neocortical layer 5 pyramidal neurons in rats in vivo and in vitro. They discovered that this form of inhibition involved interneurons in the top layers of the cortex that suppressed active dendritic currents synergistically recruited by back-propagating action potentials. This mechanism depended upon a γ-aminobutyric acid type B receptor–mediated mechanism acting on specific ion channels in the dendrites of pyramidal neurons.

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