On the cover: Eukaryotic cells rely on aerobic mitochondrial metabolism to generate ATP. Here, Cárdenas et al. (pp. 270–283) demonstrate that constitutive low-level Ca2+ release through endoplasmic reticulum InsP3 receptor release channels (yellow flashes), in close proximity to mitochondria, is essential for mitochondria to produce sufficient ATP and to maintain normal cell bioenergetics. The image is modified from the original artwork of Odra Noel, with her permission (http://www.odranoel.eu).

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In This Issue

Available online 22 July 2010.

Mapping Glycosylation Disease Back to the Starting Line

PAGE 203Congenital disorders of glycosylation (CDGs) are a rare but incurable class of developmental syndromes caused by defects in N-linked protein glycosylation. Cantagrel et al. now report that the steroid 5α-reductase type 3 (SRD5A3) gene is mutated in a new type of human CDG. They show that SRD5A3 is required for the synthesis of a critical glycolipid that donates polysaccharides to proteins during glycosylation. Thus, this study sheds new light on an early step of protein N-glycosylation conserved from yeast to humans while also pinpointing a genetic cause of CDG.

TRF2 Cops a Topological Feel during Replication

PAGE 230

Telomeres are essential for chromosome stability. TRF2, a human DNA-binding protein involved in telomere end protection, and its associated exonuclease Apollo are required for telomere integrity during S phase. Ye et al. now report that TRF2 binds to positively supercoiled DNA during replication and functions in conjunction with Apollo to modulate the amount of topoisomerase 2 needed to release the positive superhelical stress created by fork progression. These findings link telomere end protection with replication via sensing of DNA topology.

Circumventing RA Resistance in Neuroblastoma

PAGE 218

Retinoic acid (RA) induces differentiation of neuroblastoma cells, but its clinical benefit is variable. Hölzel et al. identify crosstalk between the tumor suppressor NF1 and RA-induced differentiation in neuroblastoma. Loss of NF1 activates RAS-MEK signaling, which in turn represses ZNF423, a critical transcriptional coactivator of the RA receptors. Neuroblastomas with low levels of NF1 and/or ZNF423 fail to respond to RA and have an extremely poor outcome. Inhibition of MEK signaling downstream of NF1 restores responsiveness to RA, suggesting a therapeutic strategy to overcome RA resistance in NF1-deficient neuroblastomas.

Dmc Runs Cold to Hot in Crossovers

PAGE 243

Meiotic crossovers are important for proper homolog segregation and are initiated by DNA double-strand breaks (DSBs). Despite the concentration of DSBs in hotspots, crossovers are distributed relatively uniformly along chromosomes. Hyppa and Smith report that in fission yeast this incongruence is due in large part to the use of the sister chromatid, rather than the homolog, for DSB repair at hotspots. Conversely, the homolog is used in regions with few DSBs, so called cold regions. DSB repair in cold regions requires the meiosis-specific strand-transfer protein Dmc1 that is dispensable at hotspots. Partner choice for repair thereby leads to distributed crossover events.

ER Estate Lawyer

PAGE 256

The endoplasmic reticulum (ER) is a gateway for folding and maturation of virtually all secreted and membrane proteins of the cell. ER cannot be generated de novo and must be inherited by daughter cells. Now Babour et al. find that the functional quality of inherited ER is assured during each round of cell division through an ER surveillance mechanism. Cells lacking this mechanism can only sustain a few further rounds of cell division, indicating a critical need for cells to inherit a functionally sound ER.

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Calcium Supplement Gives an Energy Boost

PAGE 270

Most eukaryotic cells rely on mitochondrial oxidative phosphorylation as their major source of ATP. Here, Cárdenas et al. demonstrate that constitutive Ca²⁺ release from the ER to mitochondria mediated by the InsP₃R channel has an essential role in maintaining normal levels of oxidative phosphorylation. In its absence, cellular ATP levels fall, inducing AMP kinase-dependent autophagy as a survival mechanism. Constitutive mitochondrial uptake of InsP₃R-released Ca²⁺ is required to maintain sufficient mitochondrial NADH production to support respiration.

---

 

Pathogen Effectors Surf into Host Cells on PI3P

PAGE 284

Pathogens of plants and animals produce effector proteins that enter the cytoplasm of host cells to suppress host defenses and enable disease. Now Kale et al. show that effectors of plant pathogens bind cell surface phosphatidylinositol-3-phosphate (PI3P) in order to enter host cells via lipid microdomain-mediated endocytosis. Surprisingly, PI3P was also found on human cells where it could mediate effector entry, suggesting that human and animal pathogens might exploit the same effector entry mechanism. PI3P inhibitors blocked entry into plant and human cells, suggesting new therapeutic strategies against eukaryotic pathogens.

Boning Up on Glucose Homeostasis

PAGE 296 and PAGE 309

Osteocalcin is an osteoblast-derived hormone that promotes insulin secretion and regulates fat deposition. Whether insulin in turn affects osteocalcin activity has been unclear. Now two studies by Fulzele et al. and Ferron et al. demonstrate that insulin signaling in osteoblasts is necessary for whole-body glucose homeostasis and bone resorption via regulation of osteocalcin activity. The authors propose the existence of a bone-pancreas endocrine loop through which insulin signaling in the osteoblast integrates bone remodeling and energy metabolism.

Sirtuin Regulates APP Cleavage

PAGE 320

A hallmark of Alzheimer’s disease (AD) is the accumulation of plaques containing Aβ peptides. The production of Aβ peptides is avoided by cleavage of APP by the α- and γ-secretases. Here Donmez et al. show that production of Aβ peptides in a mouse model of AD is reduced by overexpressing the NAD-dependent deacetylase SIRT1 in brain and is increased by removing SIRT1. SIRT1 activates the gene encoding the α-secretase, ADAM10. These findings indicate that SIRT1 activation may be a viable strategy to combat AD.

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标签：细胞杂志

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

A population of the hibernating mammal Marmota flaviventris — the yellow-bellied marmot — has provided a unique data set that illustrates the effect of climate change on the annual events of animal life. Data from the past 33 years of a long-term study show that the animals, living in a subalpine habitat in the Upper East River Valley, Colorado, now emerge earlier from hibernation than they used to. This gives them a longer growing season so that they are now heavier when they start to hibernate again. At the same time, the fitness of large individuals has increased, leading to a rapid increase in population size. On the cover, a yellow-bellied marmot photographed in the Rocky Mountains. Photo credit: Mary Plage/Photolibrary.

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Nature | Research Highlights

Sexual selection: Networking for mates

Cited research Am. Nat. doi:10.1086/655216 (2010)

Male birds trying to woo females may improve their chances by socializing more, effectively boosting their relative attractiveness.

Kevin Oh, currently at Cornell University in Ithaca, New York, and Alexander Badyaev at the University of Arizona in Tucson studied house finches (Carpodacus mexicanus) in Arizona, where males’ breast feathers range from pale yellow to deep red (pictured, with a female).

The duo analysed the birds’ social networks and found that during the non-breeding season, less elaborate males shifted more often between social groups than ornate ones did. Highly social birds were more successful at finding a mate than were comparably adorned males that did not change groups as much.

Cancer biology: Leukaemia lockdown

Cited research Cancer Cell 18, 74–87 (2010)

The primary therapy for chronic myeloid leukaemia (CML), a blood cancer, is the drug Gleevec (imatinib mesylate), which targets a protein thought to be causative in the disease. But many patients relapse when treatment is stopped. To find additional drug targets, James DeGregori at the University of Colorado School of Medicine in Aurora and his colleagues looked for genes essential to keeping CML cells alive.

They found that a gene-regulating protein, NFAT, helped CML cells to survive even during treatment with Gleevec or similar drugs. Moreover, cyclosporin, a drug widely used to suppress the immune system, blocked NFAT’s effects in mice, and might help patients if combined with current therapies.

Virology: HIV spread in 3D

Cited research Proc. Natl Acad. Sci. USA doi:10.1073/pnas.1003040107 (2010)

One route HIV takes to infecting the immune system’s T cells is through dendritic cells, which present antigen on their surface. Researchers have captured three-dimensional images of single viral particles being transmitted between the two cell types (pictured, T cell in green).

Sriram Subramaniam at the National Institutes of Health in Bethesda, Maryland, and his co-workers used three-dimensional electron microscopy to show that the surface membrane of the dendritic cell first extends and, like a veil, envelops the T cell. This provides a protected area in which the membranes of the two cells form protrusions that come together like interlocking fingers. Viral particles are seen at the tips and along the T-cell protrusions. The T cells’ CD4 receptors mediate HIV transmission.

This shielding of T cells at these junctions could limit the ability of HIV-neutralizing antibodies to block T-cell infection.

Neuroscience: Versatile vision

Cited research Neuron 67, 49–60 (2010)

Perception of patterns in the eye has long been attributed solely to two types of retinal cell — the rods and cones — but a study suggests that they are not alone in having this ability.

Neuroscientists had thought that intrinsically photosensitive retinal ganglion cells (ipRGCs) could respond only to the presence or absence of light in regulating certain activities, such as circadian rhythms. But Samer Hattar at Johns Hopkins University in Baltimore, Maryland, David Berson at Brown University in Providence, Rhode Island, and their colleagues show that, in mice, these cells are more abundant and diverse than previously thought. In addition, they project into more areas of the brain — including those responsible for visual perception.

Mice engineered to lack the rod and cone biochemical pathways, but with their ipRGC pathways intact, could still distinguish patterns in a visual test. However, it took them double the number of trials to achieve a normal level of performance.

Molecular evolution: Sperm-making origins

Cited research PLoS Genet. 6, e1001022 (2010)

A gene similar to one in humans linked to sperm production has been found in representative organisms from each of the major animal lineages. This suggests that some components of sperm production have been conserved for at least 600 million years and that sperm generation in animals has a common origin.

Eugene Xu and his colleagues at Northwestern University in Chicago, Illinois, analysed DNA sequences in animals ranging from mice to snails, and found a gene very similar to BOULE, a human reproductive gene. A closer look at mice, chickens and sea urchins revealed that the gene was expressed mainly in the testis. Deleting the gene in mice resulted in sterility only in males, which was due to a lack of sperm in the testes.

Neuroscience: Brain breathing

Cited research Science doi:10.1126/science.1190721 (2010)

Long thought simply to provide support to neurons, star-shaped brain cells called astrocytes may also be important in regulating breathing.

Alexander Gourine at University College London, Sergey Kasparov at the University of Bristol, UK, and their colleagues engineered rats in which they could control and monitor astrocyte activity. They found that astrocytes can sense pH changes in the blood, which result from changes in carbon dioxide levels. On detecting these pH shifts, the astrocytes release the small molecule ATP. The team thinks that this ATP stimulates respiratory neurons to enhance breathing.

标签：自然杂志

    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

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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).

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