Science Roundup


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REPORT: Pattern in Escalations in Insurgent and Terrorist Activity

Abstract: In military planning, it is important to be able to estimate not only the number of fatalities but how often attacks that result in fatalities will take place. We uncovered a simple dynamical pattern that may be used to estimate the escalation rate and timing of fatal attacks. The time difference between fatal attacks by insurgent groups within individual provinces in both Afghanistan and Iraq, and by terrorist groups operating worldwide, gives a potent indicator of the later pace of lethal activity.
Supporting online material


BREVIA: A Biological Screw in a Beetle's Leg

Abstract: The coxa-trochanteral joints on the legs of the weevil Trigonopterus oblongus (Pascoe) work as a biological screw-and-nut system. The apical portions of the coxae closely resemble nuts with well-defined inner threads covering 345°. The corresponding trochanters have perfectly compatible external spiral threads of 410°.
Supporting online material


RESEARCH ARTICLE: Widespread RNA and DNA Sequence Differences in the Human Transcriptome

Abstract: The transmission of information from DNA to RNA is a critical process. We compared RNA sequences from human B cells of 27 individuals to the corresponding DNA sequences from the same individuals and uncovered more than 10,000 exonic sites where the RNA sequences do not match that of the DNA. All 12 possible categories of discordances were observed. These differences were nonrandom as many sites were found in multiple individuals and in different cell types, including primary skin cells and brain tissues. Using mass spectrometry, we detected peptides that are translated from the discordant RNA sequences and thus do not correspond exactly to the DNA sequences. These widespread RNA-DNA differences in the human transcriptome provide a yet unexplored aspect of genome variation.
Supporting online material


INTRODUCTION TO SPECIAL ISSUE: A Universe of Galaxies

Full Text: It wasn't until the 1920s that astronomers realized that there were other galaxies in the universe besides our own. Using the 100-inch telescope at Mount Wilson in California, Edwin Hubble determined the distance to Andromeda (M31) and to the Triangulum (M33) and concluded that each was an "isolated system of stars and nebulae, lying far outside the limits of the galactic system." Before that, these and other galaxies were classified as nebulae, extended objects other than planets or comets; although their location was a matter of great debate, they were generally thought to be within our galaxy.


PERSPECTIVE: Sex, Death, and the Red Queen

Summary: Sex is hard to explain. Since males can't reproduce by themselves and often contribute nothing except genes to offspring, a population of asexual females can grow at double the rate of a population that reproduces sexually. Why then, given this “cost of males,” do most plants and animals indulge in biparental sex? One possible solution is that sex accelerates adaptation; the Red Queen hypothesis, for example, proposes that sex gives plants and animals an edge in the never-ending battle against their coevolving parasites. Although researchers have collected empirical field data consistent with the Red Queen hypothesis from a range of natural host-parasite systems, direct experimental evidence that coevolving parasites select for sex in their hosts has proven elusive. On page 216 of the 8 July 2011 of issue Science, Morran et al. pin down some of that direct evidence. In laboratory experiments, they grew several populations of nematode worms, some with and some without a bacterial parasite, to provide the most definitive support yet for the Red Queen's answer to why sex evolved.
Related Article


REPORT: A Pericyte Origin of Spinal Cord Scar Tissue

Abstract: There is limited regeneration of lost tissue after central nervous system injury, and the lesion is sealed with a scar. The role of the scar, which often is referred to as the glial scar because of its abundance of astrocytes, is complex and has been discussed for more than a century. Here we show that a specific pericyte subtype gives rise to scar-forming stromal cells, which outnumber astrocytes, in the injured spinal cord. Blocking the generation of progeny by this pericyte subtype results in failure to seal the injured tissue. The formation of connective tissue is common to many injuries and pathologies, and here we demonstrate a cellular origin of fibrosis.
Related Podcast


NEWS & ANALYSIS: Searching for the Google Effect on People's Memory

Summary: In four cleverly designed experiments reported online in the 14 July 2011 of issue Science, psychologists explore how the Internet may be changing the way people handle information. The results, the researchers say, confirm a growing belief that people are using the Internet as a personal memory bank: the so-called Google effect. What surprised the researchers most was not people's reliance on online information but their ability to find it.


REVIEW: Trophic Downgrading of Planet Earth

Abstract: Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind's most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of their disappearance in marine, terrestrial, and freshwater ecosystems worldwide. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles. These findings emphasize the urgent need for interdisciplinary research to forecast the effects of trophic downgrading on process, function, and resilience in global ecosystems.
Supporting online material


REPORT: Precise Manipulation of Chromosomes in Vivo Enables Genome-Wide Codon Replacement

Abstract: We present genome engineering technologies that are capable of fundamentally reengineering genomes from the nucleotide to the megabase scale. We used multiplex automated genome engineering (MAGE) to site-specifically replace all 314 TAG stop codons with synonymous TAA codons in parallel across 32 Escherichia coli strains. This approach allowed us to measure individual recombination frequencies, confirm viability for each modification, and identify associated phenotypes. We developed hierarchical conjugative assembly genome engineering (CAGE) to merge these sets of codon modifications into genomes with 80 precise changes, which demonstrate that these synonymous codon substitutions can be combined into higher-order strains without synthetic lethal effects. Our methods treat the chromosome as both an editable and an evolvable template, permitting the exploration of vast genetic landscapes.
Supporting online material


NEWS FOCUS: Why Do Parrots Talk? Venezuelan Site Offers Clues

Summary: The world's longest-running study of wild parrots is entering its 24th year, making it the parrot equivalent of Jane Goodall's long-term study of chimpanzees in Tanzania and Cynthia Moss's elephant project in Kenya. And just as those studies tracking individual animals changed our understanding of chimpanzees and elephants, this one is opening new windows into the minds and behaviors of parrots. Researchers have discovered details of the parrotlets' ecology and life histories, and the project has now entered a new phase focusing on their communicative skills. Last week, researchers reported that the contact calls of wild parrotlet nestlings—vocalizations that function much like a name—are not genetically programmed. Instead, they learn these calls from their parents, almost like human children learning their names. It is the first study to provide experimental evidence for learned vocalizations in wild parrots.
Podcast Interview


REPORT: Cilia-Like Beating of Active Microtubule Bundles

Abstract: The mechanism that drives the regular beating of individual cilia and flagella, as well as dense ciliary fields, remains unclear. We describe a minimal model system, composed of microtubules and molecular motors, which self-assemble into active bundles exhibiting beating patterns reminiscent of those found in eukaryotic cilia and flagella. These observations suggest that hundreds of molecular motors, acting within an elastic microtubule bundle, spontaneously synchronize their activity to generate large-scale oscillations. Furthermore, we also demonstrate that densely packed, actively bending bundles spontaneously synchronize their beating patterns to produce collective behavior similar to metachronal waves observed in ciliary fields. The simple in vitro system described here could provide insights into beating of isolated eukaryotic cilia and flagella, as well as their synchronization in dense ciliary fields.
Supporting online material


REPORT: Experimental and Theoretical Differential Cross Sections for a Four-Atom Reaction: HD + OH → H2O + D

Abstract: Quantum dynamical theories have progressed to the stage in which state-to-state differential cross sections can now be routinely computed with high accuracy for three-atom systems since the first such calculation was carried out more than 30 years ago for the H + H2 system. For reactions beyond three atoms, however, highly accurate quantum dynamical calculations of differential cross sections have not been feasible. We have recently developed a quantum wave packet method to compute full-dimensional differential cross sections for four-atom reactions. Here, we report benchmark calculations carried out for the prototypical HD + OH → H2O + D reaction on an accurate potential energy surface that yield differential cross sections in excellent agreement with those from a high-resolution, crossed–molecular beam experiment.
Supporting online material



In Science Signaling

RESEARCH ARTICLE: Targeting Lysosomes to Limit Inflammation

Editor's Summary: Chloroquine, which inhibits lysosome function, is best known for its use as an antimalarial agent. However, it has also been clinically used to treat inflammation. He et al. showed that agents that inhibit lysosome function or biogenesis promoted glucocorticoid-mediated regulation of gene expression and that this enhancement of glucocorticoid signaling was associated with an increase in the stability and abundance of the glucocorticoid receptor. Other receptors of the nuclear receptor family, but not other transcription factors, were also stabilized by inhibition of lysosomal function, suggesting that a lysosomal pathway contributes to the degradation of this family of receptors and may present a target for development of treatment strategies for autoimmune and inflammatory diseases, as well as diseases associated with aberrant nuclear receptor signaling.
Related Podcast


RESEARCH RESOURCE: Real-Time Imaging of Notch Activation with a Luciferase Complementation-Based Reporter

Abstract: Notch signaling regulates many cellular processes during development and adult tissue renewal. Upon ligand binding, Notch receptors undergo ectodomain shedding followed by γ-secretase–mediated release of the Notch intracellular domain (NICD), which translocates to the nucleus and associates with the DNA binding protein CSL [CBF1/RBPjκ/Su(H)/Lag1] to activate gene expression. Mammalian cells contain four Notch receptors that can have both redundant and specific activities. To monitor activation of specific Notch paralogs in live cells and in real time, we developed luciferase complementation imaging (LCI) reporters for NICD-CSL association and validated them as a specific, robust, and sensitive assay system that enables structure-function and pharmacodynamic analyses. Detailed kinetic analyses of various mechanistic aspects of Notch signaling, including nuclear translocation and inhibition of the activities of γ-secretase and ADAM metalloproteases, as well as agonist- and ligand-dependent activation, were conducted in live cells. These experiments showed that Notch-LCI is an effective approach for characterizing modulators that target Notch signaling and for studying pathway dynamics in normal and disease contexts.
Supplementary material


RESEARCH ARTICLE: PreTCR and TCR γδ Signal Initiation in Thymocyte Progenitors Does Not Require Domains Implicated in Receptor Oligomerization

Abstract: Whether thymocytes adopt an αβ or a γδ T cell fate in the thymus is determined at the β selection checkpoint by the relatively weak or strong signals that are delivered by either the pre–T cell receptor (preTCR) or the γδ TCR, respectively. Signal initiation at the β selection checkpoint is thought to be independent of ligand engagement of these receptors. Some reports have suggested that receptor oligomerization, which is thought to be mediated by either the immunoglobulin (Ig)–like domain of the preTCRα (pTα) chain or the variable domain of TCRδ, is a unifying mechanism that initiates signaling in early CD4‾CD8‾ double-negative (DN) thymocyte progenitors. Here, we demonstrate that the extracellular regions of pTα and TCRδ that are implicated in mediating receptor oligomerization were not required for signal initiation from the preTCR or TCRγδ. Indeed, a truncated TCRγδ that lacked all of its extracellular Ig-like domains still formed a signaling-competent TCR that drove cells through the β selection checkpoint. These observations suggest that signal initiation in DN thymocytes is simply a consequence of the surface-pairing of TCR chains, with signal strength being a function of the abundances of surface TCRs. Thus, processes that regulate the surface abundances of TCR complexes in DN cells, such as oligomerization-induced endocytosis, would be predicted to have a major influence in determining whether cells adopt an αβ versus γδ T cell fate.
Supplementary material


EDITORS' CHOICE: Use It, Then Lose It

Abstract: Pathogenic bacteria encode effector proteins that AMPylate (covalently attach adenosine monophosphate to) target host factors, such as Rho or Rab guanosine triphosphatases. AMPylation interferes with downstream signaling events, thereby promoting microbial infection. How AMPylation of host factors is regulated during infection and whether it can be reversed within cells is unclear. Neunuebel et al. have now discovered that Legionella pneumophila, in addition to secreting an AMPylation enzyme, also translocates a de-AMPylase, SidD, into host cells. SidD thus represents the missing link between the processes of early Rab1 accumulation and subsequent Rab1 removal from Legionella-containing vacuoles during infection.
Supporting online material



In Science Translational Medicine

COMMENTARY: Reengineering Translational Science: The Time Is Right

Abstract: Despite dramatic advances in the molecular pathogenesis of disease, translation of basic biomedical research into safe and effective clinical applications remains a slow, expensive, and failure-prone endeavor. To pursue opportunities for disruptive translational innovation, the U.S. National Institutes of Health (NIH) intends to establish a new entity, the National Center for Advancing Translational Sciences (NCATS). The mission of NCATS is to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics across a wide range of diseases and conditions. The new center's activities will complement, and not compete with, translational research being carried out at NIH and elsewhere in the public and private sectors.


RESEARCH ARTICLE: Rational Design of a Meningococcal Antigen Inducing Broad Protective Immunity

Abstract: The sequence variability of protective antigens is a major challenge to the development of vaccines. For Neisseria meningitides, the bacterial pathogen that causes meningitis, the amino acid sequence of the protective antigen factor H binding protein (fHBP) has more than 300 variations. These sequence differences can be classified into three distinct groups of antigenic variants that do not induce cross-protective immunity. Our goal was to generate a single antigen that would induce immunity against all known sequence variants of N. meningitides. To achieve this, we rationally designed, expressed, and purified 54 different mutants of fHBP and tested them in mice for the induction of protective immunity. We identified and determined the crystal structure of a lead chimeric antigen that was able to induce high levels of cross-protective antibodies in mice against all variant strains tested. The new fHBP antigen had a conserved backbone that carried an engineered surface containing specificities for all three variant groups. We demonstrate that the structure-based design of multiple immunodominant antigenic surfaces on a single protein scaffold is possible and represents an effective way to create broadly protective vaccines.
Supplementary material


RESEARCH ARTICLE: A Common Mutation in the Defensin DEFB126 Causes Impaired Sperm Function and Subfertility

Abstract: A glycosylated polypeptide, β-defensin 126 (DEFB126), derived from the epididymis and adsorbed onto the sperm surface, has been implicated in immunoprotection and efficient movement of sperm in mucosal fluids of the female reproductive tract. Here, we report a sequence variant in DEFB126 that has a two-nucleotide deletion in the open reading frame, which generates an abnormal mRNA. The allele frequency of this variant sequence was high in both a European (0.47) and a Chinese (0.45) population cohort. Binding of the Agaricus bisporus lectin to the sperm surface glycocalyx was significantly lower in men with the homozygous variant (del/del) genotype than in those with either a del/wt or a wt/wt genotype, suggesting an altered sperm glycocalyx with fewer O-linked oligosaccharides in del/del men. Moreover, sperm from del/del carriers exhibited an 84% reduction in the rate of penetration of a hyaluronic acid gel, a surrogate for cervical mucus, compared to the other genotypes. This reduction in sperm performance in hyaluronic acid gels was not a result of decreased progressive motility (average curvilinear velocity) or morphological deficits. Nevertheless, DEFB126 genotype and lectin binding were correlated with sperm performance in the penetration assays. In a prospective cohort study of newly married couples who were trying to conceive by natural means, couples were less likely to become pregnant and took longer to achieve a live birth if the male partner was homozygous for the variant sequence. This common sequence variation in DEFB126, and its apparent effect of impaired reproductive function, will allow a better understanding, clinical evaluation, and possibly treatment of human infertility.

IMAGE CREDITS (In order of appearance): NASA/JPL-CALTECH, NICHOLAS SLY


Sponsored by:

AAAS + U = Δ

Give your friend or loved one the gift of Science and a AAAS Membership!
Includes 51 issues of Science, Science online, and all AAAS member benefits.

When you give someone the gift of a AAAS membership, they get a subscription to Science, and so much more. Your gift goes to support real world programs that are making an impact in areas including: science policy, diplomacy, public engagement and dialogue, workforce development and diversity, and education.