最初的梦想

COVER Retinal photoreceptors from a mouse model of retinitis pigmentosa, a degenerative disease that leads to blindness, following gene therapy. Expression of a microbial light-activated ion pump (green) in damaged cone cells restored light sensitivity to the diseased retinas. An activated ganglion cell, which relays visual information to the brain, is shown in magenta (diameter, ~12 µm). See page 413. Image: Volker Busskamp and Botond Roska/Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

科学减肥   减肥心态   减肥经验   减肥误区   心理疗法

This Week in Science
Highlights of Research in This Issue

Volume 329, Number 5990, Issue of 23 July 2010
©2010 by The American Association for the Advancement of Science. 

Ancient Carbonate Minerals on Mars

CREDIT: NASA/JPL/CORNELL

The historical presence of liquid water on Mars together with a CO₂-rich atmosphere should have resulted in the accumulation of large deposits of carbonate minerals. Yet, evidence for the presence of carbonates on the surface of Mars has been scarce. Using data collected by the Mars Exploration Rover, Spirit, Morris et al. (p. 421, published online 3 June; see the Perspective by Harvey) now present evidence for carbonate-rich outcrops in the Comanche outcrops within the Gusev crater. The carbonate is a major outcrop component and may have formed in the Noachian era (4 billion years ago) by precipitation from hydrothermal solutions that passed through buried carbonate deposits. Thus, it is likely that extensive aqueous activity under neutral pH conditions did occur on Mars.

Pulsar Clocks

Pulsars are rotating neutron stars whose rotation rates can be extremely stable, sometimes rivaling the precision atomic clock. Unfortunately, not all pulsars are this precise—most show irregularities in their rotation rates. Using a large data set collected over many years at Jodrell Bank in the United Kingdom, Lyne et al. (p. 408, published online 24 June) show that the rotation of pulsars is not modulated by a single spin-down rate but typically by two, each accompanied by a unique pulse profile. The irregularities are linked to abrupt quasiperiodic changes in the pulsar’s magnetosphere, observed as changes in pulse shape and spin-down rate. Thus, it may be possible to use pulse-shape information to improve the precision of pulsars as stable clocks that can be used as probes of gravitational physics.

Let There Be Light

Retinitis pigmentosa, a disease that can result from a wide variety of genetic defects, causes degeneration of photoreceptor cells in the retina and leads to blindness. In the course of the disease, it is generally the rod photoreceptor cells that degenerate first. Cone photoreceptor cells may persist, but in a damaged and nonfunctional state. Busskamp et al. (p. 413, published online 24 June; see the cover; see the Perspective by Cepko) have now applied a gene therapy approach to mouse models of retinitis pigmentosa. Inducing expression of a bacterial light-activated ion pump, halorhodopsin, in the damaged cone cells improved visual responses in the diseased mouse retinas. Thus, it may be possible to rescue cone photoreceptors therapeutically, even after they have already been damaged.

Quantum Mechanics Born to Be Linear

Two pillars of modern physics, quantum mechanics and gravity, have so far resisted attempts to be reconciled into one grand theory. This has prompted suggestions that theories about either or both need to be modified at a fundamental level. Sinha et al. (p. 418; see the Perspective by Franson) looked at the interference pattern resulting from a number of slits, to test the “Born rule” of quantum mechanics. They verified that Born holds true—that the interference pattern is built up by the interference from two paths, and two paths only, with no higher-order paths interfering. The result rules out any nonlinear theories of quantum mechanics; thus, any modification of theory will need to take into account that quantum mechanics is linear.

Network Approaches to Highly Porous Materials

CREDIT: FURUKAWA ET AL.

Metal-organic frameworks (MOFs), in which inorganic centers are bridged by organic linkers, can achieve very high porosity for gas absorption. However, as the materials develop larger void spaces, there is also more room for growing interpenetrating networks—filling the open spaces not with gas molecules but with more MOFs. Furukawa et al. (p. 424, published online 1 July) describe the synthesis of a MOF in which zinc centers are bridged with long, highly conjugated organic linkers, but in which the overall symmetry of the networks created prevents formation of interpenetrating networks. Extremely high surface areas and storage capacities for hydrogen, carbon dioxide, and methane were observed.

Acidification of the Ancient Oceans

Ocean acidification fueled by rising levels of atmospheric CO₂ is likely to become a major challenge for ocean ecosystems. Understanding how marine biota responded to similar events in Earth’s history may provide clues as to what to expect—and what to prevent—in the future. To this end, Erba et al. (p. 428) present a detailed stratigraphic and geochemical characterization of 120-million-year-old marine sediments from a time when the oceans acidified because of a massive outgassing of volcanic CO₂. Microscopic fossils in the sediments, such as calcareous nannoplankton, show evidence of having responded to this major disruption through species-specific adaptations like deforming and shrinking their cells. These changes allowed these abundant and diverse organisms to avoid extinction, even through a subsequent global depletion of ocean oxygen levels.

Staying in Place

The primary cilium is found on nearly all mammalian cells and is a key regulatory organelle for proper signal transduction throughout development and in adults. Extracellular signal transduction, such as that promoted by Sonic hedgehog (Shh), requires the enrichment of receptors and downstream signaling components in the ciliary membrane. Intraflagellar transport is involved in selective trafficking of proteins into the cilium, but it is not known how these proteins are retained in the cilium. It has been speculated that a diffusion barrier exists at the base of the ciliary membrane. Now, Hu et al. (p. 436, published online 17 June) demonstrate directly that a membrane diffusion barrier is indeed present at the base of the ciliary membrane. SEPT2, a member of the septin family that also forms a diffusion barrier in budding yeast and mammalian sperm membranes, localizes to the base of the ciliary membrane and is required for ciliogenesis, ciliary membrane protein localization, and cilium-dependent Shh signaling.

Location, Location, Location

The genome receives epigenetic marks throughout development that regulate the activity of multiple genes. One such mark is methylation, which usually represses gene transcription. Methylation has generally been studied in the promoters of genes, where many regulatory signals coordinate to control the expression of the gene. Studying neural stem cells from mice, Wu et al. (p. 444) now show that DNA methylation can be a double-edged sword. Although methylation of DNA sequences in promoters tends to be repressive, methylation of DNA sequences beyond the promoters can actually promote gene expression. Analysis of the methyltransferase Dnmt3a in mouse neural stem cells revealed that methylations around neurogenic genes—but outside their promoters—maintained the activity of these genes.

Fat’s Mixed Messages

CREDIT: OUCHI ET AL.

Certain metabolic disorders, such as type 2 diabetes, are more prone to arise in obese individuals, a link that has been attributed, in part, to the detrimental activities of adipokines—proteins secreted by fat cells. Most adipokines disrupt glucose homeostasis by promoting inflammation and insulin resistance. Ouchi et al. (p. 454, published online 17 June; see the Perspective by Oh and Olefsky) identify a new adipokine, secreted frizzled-related protein 5 (Sfrp5), which has the opposite effect: It is anti-inflammatory and appears to promote metabolic health. In obese mice, Sfrp5 suppresses the activation of key inflammatory cells (macrophages) residing within adipose tissue by inhibiting the c-Jun N-terminal kinase (JNK) signaling pathway. Further study of this Sfrp5-JNK1 regulatory axis in fat may offer therapeutic opportunities for obesity-linked metabolic disorders.

Complex I Under Scrutiny

Mitochondrial complex I is a large macromolecular membrane complex that couples electron transfer to proton pumping across the mitochondrial membrane and helps to drive adenosine 5′-triphosphate synthesis. Hunte et al. (p. 448, published online 1 July) now describe the structure of complex 1 from the aerobic yeast, Yarrowia lipolytica. The sites involved in redox chemistry are distant from those that pump protons, and the structure suggests that a 60-angstrom-long helix is involved in transducing energy to the proton-pumping elements.

Heme Communication Revealed by Asymmetry

An electronic bus bar is an electrical conductor that connects several circuits. wierczek et al. (p. 451) now find that a similar strategy is used by the protein cytochrome bc₁ that plays a central role in cellular respiration and photosynthesis. Protein engineering was used to break the symmetry of a cytochrome bc₁ homodimer, which revealed that the dimer is bridged by electron transfer between two hemes. This allows electrons to move freely within and between dimers to distribute between four catalytic sites.

Brain Over Muscle

Mutations in the gene encoding the Kir6.2 subunit of the adenosine triphosphate (ATP)–sensitive potassium (K_ATP) channel cause a specific type of neonatal diabetes in humans, known as iDEND, which is often accompanied by muscle weakness of unknown etiology. By studying mice expressing the mutant gene only in muscle or only in nerve, Clark et al. (p. 458, published online 1 July) found that the motor impairments originate from inappropriate activation of the channel in the central nervous system rather than in muscle. Patients with iDEND are often treated with sulphonylurea therapies that block K_ATP channels in both brain and muscle, and these drugs can have adverse effects on heart muscle. Drugs with greater specificity for K_ATP channels in the brain may thus be a safer option.

A New Look at Old Data

Although the full genome of Caenorhabditis elegans has been available for over 10 years, only a portion of the full-length messenger RNAs (mRNAs) and their expression through development has been analyzed. By combining multiple methods, involving a careful reannotation of existing data sets, sequencing of poly-A captured RNAs from multiple developmental stages, as well as cloning and deep sequencing of a subset of genes, Mangone et al. (p. 432, published online 3 June) defined 26,000 distinct mRNA three-prime untranslated regions (3′UTRs) for 85% of the protein-coding genes. Most C. elegans genes have more than one 3′UTR, arising through different mechanisms including trans-splicing–coupled cleavage and polyadenylation. The work highlights the importance of the 3′UTRs in the regulation of mRNA stability and translation.

Making the Final Cut

RNA splicing, which involves selectively cutting and pasting messenger RNA to generate different proteins, is critical in regulating human physiology and diseases. However, our knowledge of the underlying rules governing splicing regulation remains incomplete. The recent emergence of next-generation sequencing and other high-throughput technologies has provided an opportunity to transform our understanding of RNA regulation. Zhang et al. (p. 439, published online 17 June) combined multiple data sets to generate a robust and relatively complete picture of splicing regulation by the mammalian neuronal splicing factor Nova in the brain. About 700 splicing events were identified, including many novel target exons, some likely to be involved in neurological disease. Combining genomic studies with computational biology also yielded insight into the regulation of alternative splicing.

Editors’ Choice

Volume 329, Number 5990, Issue of 23 July 2010
©2010 by The American Association for the Advancement of Science.

Psychology:

Clarity of Writing

Alexandra E. Levitt^{* *} Alexandra E. Levitt is an intern at Science.

CREDIT: M. HICKS/SCIENCE

Teacher evaluations of nonstandardized homework can be vulnerable to various sources of bias. Handwritten work in particular may be susceptible to the valuation that the teacher assigns to good penmanship. Greifeneder et al. describe a systematic bias induced by more pleasing script. When university students were tasked with grading physics essays, work of similar quality was rated more highly (on average, 0.5 grade points higher on a 6-point scale) when legible than when hard to read. The authors suggest that this is due to fluency—that is, information from legible essays can be extracted more easily than from illegible ones. Awareness of the bias was shown to negate its effects, and calling attention to this potential bias would therefore seem particularly important when grading handwritten essays. Those with indecipherable penmanship may be well advised to opt for the keyboard if given the choice.

Soc. Psychol. Pers. Sci. 1, 230 (2010).

Biochemistry:

Inhibiting the Uninhibited

Helen Pickersgill Combining genetic screens with small-compound libraries is an effective way of finding drug candidates, and identifying the chemical target can offer insight into the mechanisms by which these compounds exert their effects. Aghajan et al. have identified a specific inhibitor for an important and functionally diverse class of enzymes and used it to link amino acid biosynthesis to a disease-relevant signaling pathway. The target of rapamycin (TOR) protein kinase plays an important role in nutrient signaling in eukaryotes and regulates cell growth and proliferation; deregulation of the TOR pathway has been linked to human diseases, including cancer. The authors carried out a screen in yeast to identify small molecules that selectively enhanced the effects of rapamycin, which inhibits TOR. One of the compounds inhibited a member of the Skp1–Cullin–F-box (SCF) ubiquitin ligase family, SCF^Met30, which regulates genes involved in methionine biosynthesis and has not previously been linked to the TOR pathway. Thus, this study has identified a potential therapeutic that could be useful in combination with rapamycin in the clinic.

Nat. Biotechnol. 28, 738 (2010).

Ecology:

Hawks Take Out Sparrows

Sherman J. Suter

CREDIT: VARIO IMAGES GMBH & CO. KG/ALAMY

Through its adaptability, deliberate and accidental introductions, and natural dispersal, the house sparrow (Passer domesticus) became the archetypical bird of human-modified habitats around the world. In recent decades, however, populations in many parts of its range have declined markedly. That trend has been attributed to changes in agricultural practices, but in Britain urban populations have suffered the steepest declines. Bell et al. therefore consider the role of predation, specifically by the Eurasian sparrowhawk (Accipiter nisus). Using occurrence data from winter garden feeding stations, the authors compare the eastward and southward recolonization of Britain by the sparrowhawk with spatial and temporal patterns in sparrow populations. A logistic model that incorporates predation successfully simulates the trajectories among sparrow populations in rural and urban sites in different regions. At sites, sparrow numbers were generally stable or increasing before the reestablishment of sparrowhawks; afterward, the numbers declined continuously. In addition, significantly greater declines in sparrow numbers were found where sparrowhawks were present. The authors also suggest that urban sparrows had long been free of pressure from avian predators, which left them especially vulnerable when sparrowhawks colonized urban areas.

Auk 127, 411 (2010).

Chemistry:

Gazing Up at a Cone

Jake Yeston Chemical reaction trajectories tend to be largely confined to a single electronic potential energy surface. Occasionally, though, two surfaces intersect when vibrations on the lower surface become vigorous enough to match the energy level of the higher one. Such conical intersections (so termed because the surfaces taper to a cone in their vicinity) are often invoked to explain reaction dynamics but are rarely observed directly. Lim and Kim offer an unusually direct glimpse of a conical intersection in their study of the photolytic cleavage of the PhS-CH₃ bond in thioanisole (Ph is phenyl). Specifically, they find that optically populating the first excited state leads predominantly to the production of an electronically excited PhS radical, yet in the narrow vicinity of a vibrational state 722 cm^–1 above the excitation threshold, there is a sudden burst of ground-state PhS product. The presence in this energy regime of a conical intersection between the first and second excited states, associated with S-C stretching vibrations, appears to account for this behavior.

Nat. Chem. 2, 10.1038/nchem.702 (2010).

Astrophysics:

Flowing Farther

Maria Cruz

CREDIT: ADAPTED FROM DIKPATI ET AL.

The meridional flow of solar plasma, from the sun’s equator to its pole at the surface and then back to the equator at depth, carries magnetic flux in a circulation pattern analogous to a conveyor belt. Recent research has shown that in the last solar cycle (number 23), the meridional flow reached higher latitudes than in previous cycles—a phenomenon speculatively associated with the unexpected length of that cycle (12.5 years), which ended in 2009. Now, a flux-transport dynamo model by Dikpati et al. suggests that the combination of a long meridional flow, extending all the way to the pole, and a reduction in return flow speed may indeed have caused the unusually long duration of the last solar cycle and thereby delayed the onset of the current cycle. Long-term data from the Mount Wilson Observatory indicate that in previous cycles (such as number 22)—all with durations close to 10.5 years—the meridional flow only reached latitudes of 60° or 70°. The model predicts cycle durations consistent with those observed. Thus, it may be possible to determine the length of the solar cycle by measuring the latitudinal extent and speed of the meridional flow.

Geophys. Res. Lett. 37, 10.1029/2010GL044143 (2010).

Climate Science:

Untangling the Threads

H. Jesse Smith During the last deglaciation, between approximately 18,000 and 10,000 years ago, the atmospheric concentration of CO₂ rose from around 180 to more than 260 parts per million. Although several plausible explanations for this increase have been proposed, it has not yet been possible to assign one over the others definitively. Lourantou et al. provide an additional constraint for the competing scenarios: a record of the isotopic composition of the carbon in atmospheric CO₂ over the time interval in question. Because different sources of atmospheric CO₂ have distinct carbon isotopic compositions, the authors could determine where in the carbon system the CO₂ was coming from by comparing their data with proxy records related to carbon cycle processes, and also by conducting simulations using carbon cycle box models. They conclude that most of the increase in atmospheric CO₂ was caused by Southern Ocean ventilation and upwelling, with additional contributions at various times from a decline in marine productivity and a buildup of terrestrial carbon. More sophisticated Earth system models that incorporate carbon cycle–climate feedbacks could help to disentangle the contributions of the processes involved in the rise.

Global Biogeochem. Cycles 24, GB2015 (2010).

Cell Biology:

Where to Mate

L. Bryan Ray When yeast cells detect mating pheromone, they undergo polarized growth or “shmoo” formation at the end of the cell facing the highest concentration of pheromone. Garrenton et al. report that this polarization relies on a localized accumulation of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P₂] and consequent activation of the mitogen-activated protein kinase (MAPK) Fus3. The authors monitored the abundance and localization of PtdIns(4,5)P₂ in pheromone-treated cells with fluorescent probes that contained the pleckstrin homology (PH) domain, which binds with high affinity and specificity to PtdIns(4,5)P₂. The probe accumulated at the shmoo tip and was not seen in cells lacking the kinase that mediates the synthesis of PtdIns(4,5)P₂. The MAPK scaffold protein Ste5 contains a PH domain that binds PtdIns(4,5)P₂, and Ste5 was localized to the shmoo tip as long as PtdIns(4,5)P₂ synthesis was sustained. The Ste5 scaffold brings together the kinase Fus3 and its activating kinases, and activation of Fus3 in response to pheromone was lost when synthesis of PtdIns(4,5)P₂ at the shmoo tip was blocked.

Proc. Natl. Acad. Sci. U.S.A. 107, 11805 (2010).

标签：科学杂志

    历史上第一次有实验研究证明，阴道凝胶能明确阻止艾滋病毒的传播，相关研究结果今天通过网络发表在最新的Science上。在这次的临床测试中，近900名南非妇女参与其中，收到了包含抗艾滋病病毒药物阴道凝胶的妇女，其爱滋病病毒的感染率比那些接受安慰剂的妇女低39％。

    据网络版Science和在维也纳举行的第18届国际艾滋病大会介绍，444个收到了安慰剂凝胶的妇女中有60个感染了艾滋病病毒，而445个收到了包含抗艾滋病病毒药物阴道凝胶的妇女中仅有38位感染了艾滋病病毒。其阻止艾滋病毒传播的结果是显著的，而且无严重副作用发生。

At Last, Vaginal Gel Scores Victory Against HIV 

Published Online July 19, 2010
Science DOI: 10.1126/science.329.5990.374
by Jon Cohen

For the first time ever, a vaginal gel has unequivocally blocked the transmission of HIV. In a trial that involved nearly 900 South African women, those who received a vaginal gel that contains an anti-HIV drug had a 39% lower chance of becoming infected by the virus than those who received a placebo. As reported today online in Science and in a presentation at the 18th International AIDS Conference in Vienna, of the 444 women who received a placebo gel, 60 became infected with HIV, versus 38 infections in the 445 women who received the microbicide. The result was statistically significant, and no serious side effects occurred.

标签：救援, 生物医药, 科学杂志

COVER A seedling carpet dominated by Dipteryx oleifera (almendro) in the forest understory of Barro Colorado Island, Panama. Seedlings here have a lower probability of surviving when surrounded by neighbors of their own species. However, rare species suffer more from the presence of like neighbors than do common species, suggesting a mechanism that shapes species abundances in diverse tropical forest communities. See page 330. Photo: Christian Ziegler

免费文献下载   生物医药招聘   检索免费文献   免费英文文献

This Week in Science
Highlights of Research in This Issue

Volume 329, Number 5989, Issue of 16 July 2010
©2010 by The American Association for the Advancement of Science.

Snapshot of a Strained Ring

Benzene and cyclobutadiene possess diametrically opposed properties. The former, a hexagonal hydrocarbon with a geometry perfectly suited to its bonding arrangement, exhibits unusual stability. The latter, with its two fewer carbons tightly squeezed into the right angles of a 4-membered ring, rapidly forms a dimer to relieve its considerable geometric and electronic strain. Monomeric cyclobutadiene was first isolated in substantial quantity by confining it within a molecular shell, but it has eluded full structural characterization. Legrand et al. (p. 299) have now found a host lattice that stabilizes a dimethyl-substituted derivative of the molecule sufficiently to allow analysis of its structure and bonding motif by x-ray diffraction.

Golden Regulator

CREDIT: NATHAN A. MARGARVEY

Staphylococcus aureus is a common cause of intractable infections that are exacerbated by an array of toxins and virulence factors. The agr pheromone has been thought to represent the master regulator of virulence in this pathogen, but it is not always expressed and is also found in many nonpathogenic cocci. A strictly conserved, nonribosomal peptide synthetase has now been found by Wyatt et al. (p. 294, published online 3 June) by genome mining. The enzyme assembles valine and tyrosine into cyclic dipeptides called aureusimines that are expressed by all sequenced strains of S. aureus, including the “superbug” MRSA (Methicillin-resistant Staphylococcus aureus). Microarray analysis showed a striking effect of mutation in the synthetase locus on the production of immunomodulators, hemolysins, and other exotoxins by the pathogen. Indeed, mice infected systemically with the mutant strain showed a restricted spread of infection compared with the wild type.

Biocatalytic Boost

Enzymes tend to direct reactions toward specific products much more selectively than synthetic catalysts. Unfortunately, this selectivity has evolved for cellular purposes and may not promote the sorts of reactions chemists are seeking to enhance (see the Perspective by Lutz). Siegel et al. (p. 309) now describe the design of enzymes that catalyze the bimolecular Diels-Alder reaction, a carbon-carbon bond formation reaction that is central to organic synthesis but unknown in natural metabolism. The enzymes display high stereoselectivity and substrate specificity, and an x-ray structure of the most active enzyme confirms that the structure matches the design. Savile et al. (p. 305, published online 17 June) applied a directed evolution approach to modify an existing transaminase enzyme so that it recognized a complex ketone in place of its smaller native substrate, and could tolerate the high temperature and organic cosolvent necessary to dissolve this ketone. This biocatalytic reaction improved the production efficiency of a drug that treats diabetes.

Warming the Deep

The coldest ocean waters are located at the bottoms of the major ocean basins, and, because it takes a long time for water to sink from the surface to these regions, they are relatively isolated from the warming trends that are now occurring at shallower depths. However, warming in these deep waters has recently been observed, sooner than anticipated. Masuda et al. (p. 319, published online 24 June) performed computer simulations of ocean circulation and found that internal waves are able to transport heat rapidly from the surface waters around Antarctica to the bottom of the North Pacific, which can occur within four decades, rather than the centuries that conventional mechanisms have suggested.

Red Sea Coral Decline

Large, rapid sea surface temperature rises of 1°C or greater typically cause bleaching of corals. Cantin et al. (p. 322) show that smaller temperature increases also have detrimental effects on corals, dramatically reducing their rates of calcification and skeletal extension. Corals in the Red Sea, where water temperatures have risen by 0.4 to 1°C since the mid-1970s, have declined in skeletal extension by about 30%, and decreased in calcification rates by around 18% since 1998. This finding suggests that we may see an end to coral growth in the Red Sea this century.

The Greater Good

Zero-sum games (if I win, then you lose) offer an easily grasped heuristic for all sorts of social interactions, especially those that involve money. For instance, companies may offer to contribute some portion of their revenues to charitable causes as an inducement to customers, but it is generally assumed that these pass-throughs directly diminish the corporate bottom line. Gneezy et al. (p. 325; see the Perspective by DellaVigna) have designed a framework that encourages both customers and companies to contribute toward social goods, and, in field tests, this design increased charitable contributions as well as corporate revenues.

Too Close to Home?

Why are some species common while others are exceedingly rare? Attempts to answer this question have met limited success, particularly in hyperdiverse communities, such as tropical forests. Comita et al. (p. 330, published online 24 June; see the cover) reveal a previously overlooked explanation. A large data set on seedling dynamics of 180 tree species on Barro Colorado Island, Panama, combined with Bayesian statistical techniques, revealed that species abundance is shaped by the degree to which species negatively impact their own regeneration. Rare species regenerated far less well than common species in the proximity of conspecific neighbors, suggesting a mechanism determining the relative abundances of tree species in highly diverse tropical forest communities.

Hedgehog and Segmentation

CREDIT: N. DRAY

Segmentation is a key characteristic of body plan organization in some of the largest animal groups, including annelids, arthropods, and vertebrates, but its evolutionary origins remain debated. In arthropod embryos, the Hedgehog signaling pathway plays a crucial role in the axial patterning of developing segments. Dray et al. (p. 339) analyzed the function of this conserved pathway in the annelid worm Platynereis by using specific small molecule inhibitors and found a similar role for Hedgehog signaling in shaping segments in this animal. Thus, Hedgehog was involved in segment formation in the last common ancestor of the protostome animals, earlier in metazoan evolution than previously assumed.

Gobbled by Gobies

A common feature of overfished marine ecosystems is a tendency for biomass to become dominated by jellyfish and microbes, and for the habitat to become anoxic or hypoxic as large fish species are removed. The Benguela ecosystem off the coast of Namibia is a case in point. Utne-Palm et al. (p. 333) describe how the loss of overfished sardines from the Benguela fishery has provided an opportunity for an endemic fish species, the bearded goby, to exploit jellyfish and microbial biomass and to increase in number. These small fish have in turn become the predominant prey species for the larger fish, birds, and mammals in the region. The significance of the goby lies in its ability to forage on resources traditionally regarded as “dead-ends.” The bearded goby has thus become a key stabilizing component to the turnover of energy in the Benguela ecosystem.

Wired

CREDIT: HU AND YU

Just as there are difficulties in making integrated circuits smaller and faster, barriers are also being reached in the fabrication of wires that connect chips to the motherboard. Hu and Yu (p. 313) describe the directed electrodeposition and bonding of copper and platinum wires via a meniscus delivered from a micropipette containing a deposition solution. Wires could be deposited on a range of substrates and were significantly smaller than those obtained using existing techniques. This approach may be useful for device packaging and might offer new approaches for constructing tailored nanoscale structures.

Transcription On and sORF

Eukaryotic transcriptomes include numerous RNAs that are presumed noncoding because they include only short open reading frames (sORFs). However, some sORF RNAs actually produce small peptides with unknown activity. Now Kondo et al. (p. 336; see the Perspective by Rosenberg) report the function of peptides containing 11 to 32 amino acids that are encoded by the gene polished-rice (pri). pri triggers N-terminal truncation of the transcription factor Shavenbaby that controls epidermal differentiation in Drosophila. Following pri expression, Shavenbaby is converted from a transcriptional repressor to an activator. Thus, sORF peptides can control transcriptional programs during embryonic development.

Sulfur Signal Dinner

Phytoplankton produces large amounts of the compound dimethylsulfoniopropionate (DMSP), which can be transformed into the gas dimethylsulfide and emitted into the atmosphere in sufficient quantities to affect cloud formation. The functional role of DMSP is somewhat unclear, but it is degraded by marine bacteria as a source of reduced carbon and sulfur. It also acts as a foraging cue for a variety of aquatic animals ranging from copepods to marine mammals. Now, Seymour et al. (p. 342) have developed a microfluidic device to observe the behavior of motile microorganisms in response to pulses of DMSP. Contrary to accepted thought, these compounds appear primarily to play a defensive role—for most motile organisms, they are strongly attractive and act as an important infochemical throughout the marine food web.

Observing the Magnon Hall Effect

The anomalous thermal Hall effect occurs when transverse heat transport is generated in the absence of an external magnetic field. The transport may be mediated by free carriers, phonons, or spin waves (magnons). Onose et al. (p. 297) observed this effect in an insulating ferromagnet and were able to rule out free carriers and phonons as the mediators of the thermal transport. Instead, the observations are consistent with a theory ascribing its origin to magnon propagation. This thermal magnon Hall effect is caused by the spin-orbit interaction, which acts in a fashion similar to the magnetic field in the conventional Hall effect. Its observation in an insulator may enable the elimination of losses in spintronic applications.

Coolly Disordered

Generally speaking, at higher temperature phases materials are more disordered—for example, when solids melt to form liquids. In some cases, however—for example, under high pressure—a more disordered phase can emerge upon cooling. Schöll et al. (p. 303) now show that an organic molecule, a naphthalene derivative, adsorbed on a silver surface disorders upon cooling below room temperature. This process is driven by the surface bond becoming stronger upon cooling and preventing weaker interactions that allow ordering between molecules in the plane.

C-Family Oxidase Structure

The heme-copper oxidases (HCOs) play a key role in aerobic respiration by coupling oxygen reduction to transmembrane proton pumping to generate electrochemical ion gradients across biological membranes that provide energy for many cellular processes. Based on subunit composition, electron donor, and heme type, the HCOs are divided into three families, of which families A and B have been structurally characterized. Buschmann et al. (p. 327, published online 24 June) now report the crystal structure of the C-family cbb3 oxidase from Pseudomonas stutzeri. The structure suggests a different redox-driven pumping mechanism from A and B HCOs, and gives insight into why C HCOs are catalytically active at low oxygen concentrations.

Cenozoic Tectonics

The Basin and Range Province of western North America—exemplified by the alternating mountain ridge and valley landscapes across nearly the entire U.S. state of Nevada—started to form 50 million years ago through a series of extensions of the continental crust. Prior to that, massive mountain-building collisions at the boundary between North America and the Pacific Ocean formed a subduction zone and compressed the continent. By combining observations of global subduction zone velocities with numerical modeling, Schellart et al. (p. 316) demonstrate that the thinning of the subducting portion of the oceanic plate controlled how and when the transition from compression to extension occurred. Even today, where the much smaller remnant oceanic plate continues to slowly subduct below North America in the Pacific Northwest, the width of the slab and not its age controls the velocity of subduction. Indeed, this relation may explain the dynamics of other modern subduction zones, from South America to Japan.

Editors’ Choice

Volume 329, Number 5989, Issue of 16 July 2010
©2010 by The American Association for the Advancement of Science.

Biotechnology:

Harnessing Commensals

Barbara R. Jasny Our gastrointestinal tracts contain a variety of commensal bacteria that digest our food, kill harmful microorganisms, and help us function. Investigators are beginning to engineer such bacteria to make them even more beneficial. Duan and March have augmented a signaling pathway that enables a model probiotic bacterium, Escherichia coli Nissle 1917 (Nissle), to ward off cholera. The pathogenic bacterium Vibrio cholerae contains a signaling pathway that is sensitive to secreted autoinducers whose environmental concentration increases as the population density increases. At high cell densities, these autoinducers inhibit the expression of virulence genes (for cholera toxin and the intestinal attachment pilus). The authors transformed Nissle with a construct containing the gene cqsA, which is required for synthesis of the autoinducer. When infant mice were fed with transformed Nissle 8 hours before challenge with V. cholerae, 92% survived. Protection was less at shorter pretreatment times and at lower doses of transformed bacteria and was associated with a decrease in the numbers of V. cholerae in the intestines of infected mice. Although much further work needs to be done, the authors speculate that this might be an important preventive approach in regions where natural disaster increases the probability of an outbreak or even as part of the diet in impoverished areas.

Proc. Natl. Acad. Sci. U.S.A. 107, 11260 (2010).

Geochemistry:

Ore Origins

Nicholas S. Wigginton

CREDIT: NEWSCOM

Major mining operations of porphyry-type ore deposits—emplaced by hot magma that melted and mixed with continental crust—provide a major source of the world’s supply of copper. One of the largest copper mines in operation is the 100-year-old open-pit Bingham Canyon Mine in the western United States. By measuring the lead isotope signature of tiny fluid bubbles trapped within minerals adjacent to the copper ore, Pettke et al. suggest that the Bingham Canyon deposits originate from some of the first crust formed on the primitive Earth. In this model, metal-rich fluid emerged and concentrated 1.8 billion years ago in the mantle after the ancient crust subducted below what is now North America. The deposits further evolved 37 million years ago when partial melting of the mantle underneath North America occurred during the formation of the Basin and Range province. Because this model does not require metal enrichment to occur contemporaneously with subduction processes (the generally accepted formation mechanism), additional quantities of ore-grade metals may exist in locations not typically considered favorable for metal exploration or mining.

Earth Planet. Sci. Lett. 10.1016/j.epsl.2010.05.007 (2010).

Applied Physics:

Optical Wireless

Ian S. Osborne Numerous homes and offices are kitted out with wireless communication systems, with many components now capable of sharing a single or coupled set of routers and access points to the internet. Radio-based wireless is affected by interference, tight regulation over which bands of the frequency spectrum can be used, and technological limitations on the bandwidth and information transfer rates that be attained. As the number of added components increases, however, the first thing to give is download speed. Van Acoleyen et al. show that optical wireless communication, in which very high bandwidth and rates of transmission are available, may provide a solution. They have designed a two-dimensional optical phased array antenna that is based on the silicon-on-insulator platform used extensively in the optoelectronics industry. The incoming optical information, which can be fed in by an optic fiber, is split and directed across an array of focusing gratings by a series of patterned on-chip waveguides. The light from the gratings can be beamed off-chip at an adjustable angle by tuning the input wavelength, and can then be captured and read out some distance away, providing the basis for an optical wireless communication technology.

Opt. Express 18, 13655 (2010).

Ecology:

Driving Diversity Underground

Andrew M. Sugden

CREDIT: CLAUDIA STEIN

An experimental study of hay meadows in central Germany shows that the species richness of the plant community affects the impact that invertebrate herbivores exert on the vegetation. Using insecticide and molluscicide to exclude herbivores in plots of widely differing plant species diversity and productivity in a 5-year program, Stein et al. were able to confirm theoretical predictions about the relationship between diversity and herbivore effects. The exclusion of herbivores led to alterations in the composition of the plant community and also to reduced diversity; belowground herbivores had a greater impact on the community composition than their aboveground counterparts. Biomass and productivity, on the other hand, showed no clear patterns of change, suggesting that the effects of herbivore removal and diversity were not artefacts caused by increased soil fertility. These findings add to the growing body of evidence showing intricate relationships between biodiversity and ecosystem function.

Ecology 91, 1639 (2010).

Biomedicine:

Multiple Causes

Kristen L. Mueller

CREDIT: CADWELL ET AL., CELL 141, 1135 (2010)

Complex diseases, like the inflammatory bowel condition Crohn’s disease, are thought to arise from a combination of genetic and environmental factors. This two-hit pathway to disease development would explain why a genetic susceptibility allele for Crohn’s disease, the autophagy gene ATG16L1, is present at approximately 50% frequency in populations of European descent, yet the incidence of Crohn’s disease in these populations is quite rare. Cadwell et al. provide evidence that in mice, virus infection can interact with susceptibility genes to promote a Crohn’s disease-like pathology. Mice hypomorphic for Atg16L1 and housed in an enhanced-barrier facility exhibited intestinal pathology only when infected with a persistent strain of mouse norovirus, an RNA virus that causes gastroenteritis. When mice were treated with a compound that induces intestinal injury, Atg16L1-hypomorphic virus-infected mice developed pathology (thickening of the muscularis propria and submucosal fibrosis) that resembled what is seen in Crohn’s disease patients, whereas uninfected mice that expressed the hypomorphic allele did not develop Crohn’s disease-like pathology, nor did virus-infected wild-type mice. Thus, an interaction between a virus and a susceptibility gene, in the presence of additional environmental factors, can determine host response phenotypes in inflammatory disease.

Cell 141, 1135 (2010).

Education:

Learning Pays Off

Melissa McCartney The current trend in education is to focus on testing. Are potentially gifted scientists being weeded out by graduate schools’ reliance on standardized assessments and grades as a measure of scientific prospects? Hazari et al. led a second round of Project Crossover, a study designed to examine the transition from graduate student to independent researcher in chemistry and physics, and developed a 145-question survey to assess individuals’ goal orientation. Respondents were asked to indicate from a list of 20 options what had been the two most important factors in their decision to attend graduate school. Respondents identifying “received good grades in science” and “received a fellowship” as factors influencing their decision were classified as performance-oriented, whereas those responding with “enjoyed thinking about science” were classified as learning-oriented. Learning-oriented respondents proved significantly more successful in attaining grant funding and primary author publications than the average respondent. No significant effects were seen for performance-oriented individuals in this domain. These results suggest that nurturing the personal engagement of students is something to be considered seriously by science educators at all levels.

Phys. Rev. ST Phys. Educ. Res. 6, 10107 (2010).

Psychology:

Dark Chocolate

Gilbert Chin Doing nothing often seems harder than doing something, even if that something is effortful and serves no apparent purpose. Hsee et al. demonstrate how little is needed to motivate students to take a 15-minute walk to drop off a survey instead of waiting in a room and dropping off the survey next door. Offering them a choice of milk versus dark chocolates at the two locations increased the percentage of ambulatory students from a third to more than half. Furthermore, in the group of subjects who were offered the same kind of chocolate at both locations (and thus could not justify the trip on the basis of preferring the faraway chocolate) the few who walked were happier than the many who waited. Finally, when students were obligated to make the short journey, they were happier being active for those 15 minutes rather than remaining idle. Hence, in the absence of constructive goals there still seems to be a happy preference for busyness.

Psychol. Sci. 21, 10.1177/0956797610374738 (2010).

标签：科学杂志

COVER Sergey Nenov gives thanks at a church in Odessa, Ukraine. HIV, tuberculosis, and injecting drug use are tightly linked in Eastern Europe, the only region in the world with a growing HIV/AIDS epidemic. Nenov is one of the few people with access to treatment for both infections and opiate dependency. See the special section on HIV/AIDS beginning on page 159 and at www.sciencemag.org/special/aids2010/. Photo: Malcolm Linton

天下美食   麻辣烫配方   珍珠奶茶   四季食补   凉茶配方

This Week in Science
Highlights of Research in This Issue

Volume 329, Number 5988, Issue of 09 July 2010
©2010 by The American Association for the Advancement of Science.

Going Multicellular

CREDIT: ARMIN HALLMANN

The volvocine algae include both the unicellular Chlamydomonas and the multicellular Volvox, which diverged from one another 50 to 200 million years ago. Prochnik et al. (p. 223) compared the Volvox genome with that of Chlamydomonas to identify any genomic innovations that might have been associated with the transition to multicellularity. Size changes were observed in several protein families in Volvox, but, overall, the Volvox genome and predicted proteome were highly similar to those of Chlamydomonas. Thus, biological complexity can arise without major changes in genome content or protein domains.

 

Out of the Oort Cloud

Long-period comets originate from the Oort cloud, a vast reservoir of icy bodies that surrounds the solar system. These bodies are thought to be remnants from the formation of the solar system. But did they all form in the Sun’s protoplanetary disk, or could they have been generated in the protoplanetary disks of other stars in the cluster where the Sun probably formed? Levison et al. (p. 187, published online 10 June) used detailed numerical simulations to investigate what fraction of comets might transfer from the outer reaches of one stellar system to another. The simulations suggest that a substantial number of comets can be captured through this mechanism, which may explain why the number of bodies in the Oort cloud is larger than models predict.

 

BK Channel Cytoplasmic Domain

CREDIT: YUAN ET AL.

BK channels are potassium ion channels found on the surface of a variety of cell types that are essential for the regulation of several key physiological processes, including smooth muscle tone and neuronal excitability. BK channels are regulated by both membrane voltage and intracellular Ca²⁺. The channel comprises an integral membrane pore, an integral membrane voltage sensor domain, and a large cytoplasmic region that confers Ca²⁺ sensitivity. Now Yuan et al. (p. 182, published online 27 May; see the Perspective Weyand and Iwata) have determined the crystal structure of the cytoplasmic domain of the human BK channel. Four cytoplasmic regions form a gating ring at the intracellular membrane surface with four Ca²⁺ binding sites on the outer perimeter.

Elucidating Turbulent Flow

When needing to mix two fluids rapidly, turbulent flow can be beneficial. However, in most cases, the churning and tumbling motions of a fluid during turbulent flow reduce the efficiency of a device or process. When fluid flows past a solid object, the bulk of the turbulent motion is concentrated at the surface boundary, but it is unclear to what extent these inner motions are influenced by flow far from the boundary. Marusic et al. (p. 193; see the Perspective by Adrian) demonstrate a nonlinear connection between inner-layer motions and the large-scale outer-layer motions in wind tunnel experiments. A simple model was able to describe the relationship mathematically while accurately mapping the experimental data.

 

Switching Basins

Most of the densest, deepest water at the bottom of the oceans comes from two regions, the North Atlantic and the circum-Antarctic. Have other regions been able to produce significant quantities of deep water in the past? For decades, researchers have looked, with limited success, for evidence of deepwater formation in the North Pacific since the time of the Last Glacial Maximum, about 23,000 years ago. Okazaki et al. (p. 200) combine published observational evidence from the North Pacific with model simulations to suggest that deep water did form in the North Pacific during the early part of the Last Glacial Termination, between about 17,500 and 15,000 years ago. The switch between deep-water formation in the North Atlantic and the North Pacific is likely to have had an important effect on heat transport and climate.

 

Nanorod Polymers

Nanoparticles and colloids have been used to model crystallization and melting phenomena. Liu et al. (p. 197) studied the polymerization kinetics of nanoparticles. Functionalized arrowhead nanorods acted as linkable units that joined together in solvent-tuned assembly. The results resembled common processes of chemical polymerization: Growth was controlled kinetically and could be interpreted by formulas for step-growth polymerization and branching. Furthermore, some isomerization phenomena were observed, as was the formation of cyclic “macromolecules.”

 

Quake Control

Large earthquakes occur at the margins of two colliding plates, where one plate subducts beneath the other at a shallow angle. These megathrust earthquakes often cause destructive tsunamis owing to the displacement of large volumes of water at the fault along the plate boundary. Two related studies of the seismic structure of subduction zones attempt to reveal the underlying mechanisms of megathrust earthquakes (see the Perspective by Wang). Kimura et al. (p. 210) compared seismic reflection images and microearthquake locations at the Philippine Sea plate where it subducts obliquely beneath Japan. The locations of repeating microearthquakes correspond to active transfer of material from the subducting plate to the continent—a process only previously assumed from exhumed metamorphic rocks. Dean et al. (p. 207) observe an expansive structure in the sea-floor sediment near the location of the 2004 and 2005 Sumatra earthquakes in Indonesia that suggests sediment properties may influence the magnitude of megathrust ruptures and their subsequent tsunamis.

Offsetting the Cost of Parasitism

Fruit flies, like most animals, are vulnerable to infection by a range of organisms, which, in co-infections, can interact with sometimes surprising effects. Jaenike et al. (p. 212) discovered that a species of Spiroplasma bacterium that is sometimes found in flies, and that is transmitted from mother to offspring, protects its host from the effects of a nematode worm parasite, Howardula aoronymphium. The worm sterilizes the female flies and shortens their lives, but when flies were experimentally infected with Spiroplasma, their fertility was rescued. Similarly, in wild populations of fruit flies infected with worms, those also infected with Spiroplasma had more eggs in their ovaries. The bacterium inhibits the growth of the adult female worms, but such is the advantage of this bacterial infection in offsetting the burden of nematodes on reproductive fitness, Spiroplasma appears to be spreading rapidly through populations of fruit flies in North America.

 

Separating Under Strain

CREDIT: LAI ET AL.

Complex oxides, such as cuprate superconductors and perovskites, often exhibit microscopic phase separation, where two or more phases coexist on the macroscopic scale but are spatially separated on the microscopic scale. Lai et al. (p. 190) studied a configuration often found in technological applications, a strained manganite thin film placed on a substrate. Microwave impedance microscopy, which differentiates between conducting and insulating areas on the thin film, allowed visualization of the phase separation as the magnetic field was varied. A network of conducting domains was observed whose orientation and characteristic length scales suggest that the substrate-exerted strain was involved in network formation.

Getting Gametes Together

Despite decades of research, the molecular basis of sperm-egg recognition in mammals remains unresolved. Models in which a glycan ligand in the zona pellucida (ZP) surrounding ovulated eggs binds to a sperm surface receptor have been widely embraced. A more recent model proposes that the cleavage status of a ZP protein, ZP2, renders the structure of the zona matrix either permissive or nonpermissive for sperm binding. Gahlay et al. (p. 216) tested predictions of each model by replacing endogenous zona proteins with either a mutant form of ZP2 that could not be cleaved or of ZP3 that lacked O glycan attachment sites. Sperm-egg recognition depended on the cleavage status of ZP2 rather than on glycan ligands released following fertilization.

 

Righting Repair Pathways

The genetic disease Fanconi anemia (FA) results from mutations in a series of genes involved in a DNA repair pathway that helps process the damage caused by erroneous chemical cross-links between the two strands of the DNA double helix. The double-stranded breaks in DNA that arise from such cross-links can be repaired in an error-free manner or through an error-prone repair pathway. Pace et al. (p. 219, published online 10 June) show that the FA pathway can drive repair through the error-free pathway. The FA FANCC gene shows a genetic interaction with a component of the error-prone repair pathway, Ku70, inhibiting its action and thereby promoting the error-free pathway.

 

Correcting a Liver Problem

The classical form of ₁-antitrypsin (AT) deficiency is caused by a point mutation that alters the folding and causes intracellular aggregation of AT—an abundant liver-derived plasma glycoprotein. AT deficiency is the most common genetic cause of liver disease in childhood and can also lead to cirrhosis and/or hepatocellular carcinoma in adulthood. Carbamazepine is a drug known to be well tolerated in humans that enhances the intracellular degradation process known as autophagy. Now, Hidvegi et al. (p. 229, published online June 3; see the Perspective by Sifers) show that carbamazepine can reduce the severity of liver disease in a mouse model of AT deficiency by enhancing the degradation of misfolded accumulated AT.

Editors’ Choice

Volume 329, Number 5988, Issue of 09 July 2010
©2010 by The American Association for the Advancement of Science.

 

Cell Biology:

Caught Off Balance

Paula A. Kiberstis

Otoconia: normal, abnormal (lower center), absent (lower right).CREDIT: MARIÑO ET AL., J. CLIN. INVEST. 120, 10.1172/JCI42601 (2010)

An episode of dizziness, no matter how brief, reminds us that our body performs important physiological functions that we take for granted. Our sense of balance is dependent on small crystals in the inner ear called otoconia. These crystals are embedded within a fibrous extracellular matrix that couples the force of gravity to the cilia of sensory cells, which in turn send signals to the nervous system. The biosynthesis of otoconia occurs during fetal development when core proteins secreted by vestibular epithelial cells form a proteinaceous matrix that sequesters calcium carbonate. Little is known about the genes and cellular processes involved in otoconial assembly and maintenance.

Mariño et al. have discovered that a degradative cellular process called autophagy is essential for otoconial biogenesis. Mice genetically deficient in a protein that plays a key role in autophagy, Atg4b, showed behaviors consistent with inner ear defects, such as head tilting, circling movements, and disorientation in swimming tests. These behaviors were accompanied by the absence of otoconia or by the presence of morphologically abnormal otoconia. Similar abnormalities were seen in mice deficient in Atg5, which like Atg4 appears to be important in the secretion and assembly of otoconial core proteins. Further mechanistic investigation of how these small but critical crystals are made and maintained throughout life may yield new treatments for balance-related disorders, which are common in the elderly and can also be a side effect of certain antibiotics.

J. Clin. Invest. 120, 10.1172/JCI42601 (2010).

Microbiology:

Restricting Promiscuity

Caroline Ash Although it might seem that many species of bacteria swap DNA promiscuously, in reality, the transfer of genetic information is curtailed by sequence-specific restriction systems. Several such systems have been characterized; the core component is an endonuclease that cleaves unmodified DNA (the host’s own DNA is protected against digestion, usually by methylation). Corvaglia et al. have discovered a new endonuclease in Staphylococcus aureus, which is a potentially pathogenic bacterium carried by up to half the human population. Methicillin-resistant strains of S. aureus (MRSA) were found to carry mutations in this restriction endonuclease, which has tentatively been assigned to the type III family; these mutations probably render these strains hypersusceptible to the uptake of antibiotic-resistance genes from gut bacteria.

Proc. Natl. Acad. Sci. U.S.A. 107, 10.1073/pnas.1000489107 (2010).

 

Chemistry:

Ironing Out Formic Acid

Phil Szuromi Some biomass transformations, such as pathways that deoxygenate sugars, produce formic acid as a by-product, and the options for downstream use of large amounts of it have been limited. Boddien et al. now report a photocatalytic route for liberating hydrogen from formic acid. Previous catalysts for this reaction used noble metals, but after screening a range of more abundant transition metals, the authors discovered that effective catalysts formed in situ from an iron carbonyl cluster [Fe₃(CO)₁₂], a polydentate nitrogen-donating ligand, and triphenylphosphine. Under irradiation with the visible light from a 300-W xenon arc lamp, these catalysts generated hydrogen from formic acid solutions stabilized with triethylamine; the best examples had turnover frequencies up to 200 per hour and turnover numbers exceeding 100. Extensive spectroscopic studies implicated photogenerated iron hydrides as active species.

J. Am. Chem. Soc. 132, 10.1021/ja100925n (2010).

 

Physics:

Running in Circles

Jelena Stajic

CREDIT: GRASER ET AL., NAT. PHYS. 6, 10.1038/NPHYS1687 (2010)

While the debate about the origin of high-temperature superconductivity in the cuprates has been raging since their discovery more than 20 years ago, many of these materials have found practical use, most commonly as superconducting magnets and wires. However, a serious limitation exists, especially pronounced in the yttrium barium copper oxide (YBCO) family: Grain boundaries (interfaces between mismatched neighboring crystal orientations), present in the technologically interesting polycrystals, limit the observed supercurrent to values considerably below that attainable in a perfect single crystal. Graser et al. use molecular dynamics simulations and an effective tight binding model to simulate the flow of a supercurrent through a grain boundary in YBCO. They find that, even away from the boundary, the flow is disrupted and can run in closed loops (see arrows in the figure) and even backwards (blue lines). The experimentally established exponential dependence of the supercurrent on the angle of misorientation is recovered; the authors identify the accumulation of charge at the boundary as the primary cause, with the d-wave symmetry of the superconducting gap having, surprisingly, little effect. There are indications that similar behavior might occur in other complex superconductors, such as the ferropnictides.

Nat. Phys. 6, 10.1038/nphys1687 (2010).

标签：科学杂志

COVER Three-dimensional representation of the emission of electrons from a neon atom upon absorption of a photon from an attosecond extreme ultraviolet pulse. The orange surface plot represents the resulting electron energy distribution, which, when probed by an ultrashort light wave (yellow line), reveals an unexpected time delay between the emission of electrons from different atomic orbitals. See page 1658. Image: Christian Hackenberger/Ludwig-Maximilians-Universität, Munich, Germany

美白的奥秘   抗衰化妆品知识   化妆品研发   化妆品品牌故事

This Week in Science
Highlights of Research in This Issue

Volume 328, Number 5986, Issue of 25 June 2010
©2010 by The American Association for the Advancement of Science.

No Dicer for Me

CREDIT: ANTONIO GIRALDEZ

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.

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.

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.

Just Breathe

CREDIT: WYSS INSTITUTE FOR BIOLOGICALLY INSPIRED ENGINEERING

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.

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.

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.

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.

Glacial Gas

Intracellular bacterial pathogens, such as 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.

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.

Hydrated Minerals on Martian Northern Plains

CREDIT: CARTER ET AL.

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.

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.

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.

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.

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 (T_g), 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 T_g is due to a surface mobile layer that dominates the behavior as the films decrease in thickness.

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.

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.

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.

Editors’ Choice

Volume 328, Number 5986, Issue of 25 June 2010
©2010 by The American Association for the Advancement of Science.

Applied Physics:

Low-Energy Light Switches

Ian S. Osborne

CREDIT: ISTOCKPHOTO.COM

The backbone of high-speed communications consists of optic fibers that carry information as pulses of light. Light-sensitive bistable optical resonators coupled to the fibers are capable of controlling the transmitted light, allowing access to the higher information transfer rates offered by all-optical switching. However, the relatively high amount of energy (or light intensity) required to switch an optical resonator between its two states (transmission ON, transmission OFF) can be a limiting factor with regard to power requirements. Sandhu et al. use numerical simulations to show that coherent control, or pulse shaping, of the switching light pulses can reduce the input energy requirements for switching the optical resonator. Moreover, because the peak energy input to the resonator is dependent on the phase of the input pulse, switching by phase modulation should be possible, thus offering the potential for even higher bit rates than attainable with intensity modulation–based protocols.

Appl. Phys. Lett. 96, 231108 (2010).

Astrophysics:

Whence the Solar System?

Maria Cruz Primitive materials within meteorites hold evidence for processes that occurred during the earliest stages of the solar system. In particular, the inclusion of the daughter products of now-extinct, short-lived radioisotopes tells us that the parent isotopes were active at the time they were incorporated into the solar system’s earliest solids. One such isotope is ⁶⁰Fe, whose origin is attributed to either a core-collapse supernova (the thermonuclear explosion of a massive star) or an intermediate-mass asymptotic giant branch (AGB) star. Sun-like stars end their lives as AGB stars; in the late stages of their evolution, these stars expel their outer envelopes and shine as planetary nebulae as their hot surfaces are exposed and ionize material around them. The ejecta of AGB stars or supernovae drive shock fronts into the interstellar medium, a process posited to have triggered the collapse of the cloud from which the Sun formed and then injected freshly synthesized radioisotopes into it. Using numerical simulations to test both scenarios (supernova versus AGB), Boss and Keiser show that only supernovae have thin enough shock waves to inject the material necessary to match the abundances of short-lived radioisotopes measured in primitive meteorites.

Astrophys. J. 717, L1 (2010).

Biochemistry:

Signaling Without G Proteins

L. Bryan Ray The angiotensin II receptor is a key regulator of blood pressure and other physiological processes. Binding of its ligand activates an associated heterotrimeric guanine nucleotide–binding protein (G protein). Rakesh et al. describe a different signal emitted by this receptor in the mouse heart when it responds to a mechanical stimulus. Usually, the protein β-arrestin acts to limit signaling by G protein–coupled receptors, but it can also promote signaling cascades that are independent of G proteins. Stretching the mouse heart by inflating a balloon within the left ventricle triggered receptor signaling that was independent of its associated G protein but that required β-arrestin 2 and the protein kinases that stimulate the association of β-arrestin 2 with the receptor. Such β-arrestin–dependent signaling by the angiotensin II receptor may turn on protective mechanisms when the heart is under stress. Indeed, the hearts of mice lacking β-arrestin 2 or the angiotensin II receptor showed reduced signaling and increased cell death in response to mechanical stretch.

Sci. Signal. 3, ra46 (2010).

Cell Biology:

The Ins and Outs of Import

Helen Pickersgill

CREDIT: DISHINGER ET AL., NAT. CELL BIOL. 12, 10.1038/NCB2073 (2010)

There are several different mechanisms available for moving proteins to where they need to be. In eukaryotes, nuclear proteins, which are synthesized in the cytoplasm, are transported into the nucleus by means of nuclear localization signals encoded in their amino acid sequence; these signals are recognized by receptors of the importin/karyopherin family, which directionally ferry their protein cargo from the cytoplasm into the nucleus with the aid of the small GTPase Ran. A gradient of accessory proteins across the nuclear membrane produces a corresponding gradient of the GTP- and GDP-bound forms of Ran. In the cytoplasm, where there are low levels of RanGTP, the import receptors bind their cargoes and carry them across the nuclear envelope. Upon reaching the nucleus, the receptors encounter high levels of RanGTP and release their loads.

Dishinger et al. find that this mode of conveyance is also used to transport molecules to a distant part of the cell. They identified a sequence within a kinesin motor protein, KIF17 (green), that targets it to the primary cilium (red), which is an organelle protruding from the cell surface. A RanGTP/GDP gradient between the cilia and the cytoplasm was required for the localization of KIF17 to the cilia. Furthermore, a member of the importin family of receptors bound KIF17, and this interaction was sensitive to RanGTP in vitro, thus revealing shared laborers in nuclear and ciliary import.

Nat. Cell Biol. 12, 10.1038/ncb2073 (2010).

标签：科学杂志