Tạp chí khoa học số 2006-09-15

15 September 2006 | $10 www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1529 CONTENTS CONTENTS continued >> DEPARTMENTS 1535 Science Online 1537 This Week in Science 1542 Editors’ Choice 1546 Contact Science 1547 NetWatch 1549 Random Samples 1569 Newsmakers 1647 New Products 1648 Science Careers COVER Moonlit silhouette of the North American black cottonwood Populus trichocarpa. Because this tree has a small genome and has long been the subject of commercial and ecological studies, P. trichocarpa was selected as the first woody perennial plant to have its genome sequenced. See page 1596. Photo: David Hiser/Getty Images EDITORIAL 1541 Animal Activism: Out of Control by Donald Kennedy 1560 LETTERS Cuts in Homeland Security Research F. Busta et al. 1571 Public Access Success at PubMed D. C. Beebe Support for the NIH Public Access Policy M. A. Rogawski and P. Suber Ongoing Controversy Over Debye’s WWII Role The Executive Board of Utrecht University Response M. Enserink Bias About Climate Change L. Neal BOOKS ET AL. Bonds of Civility Aesthetic Networks and the Political 1575 Origins of Japanese Culture E. Ikegami, reviewed by C. Turner Economic Origins of Dictatorship and Democracy 1576 D. Acemoglu and J. A. Robinson, reviewed by R. Wacziarg POLICY FORUM Death in Darfur 1578 J. Hagan and A. Palloni PERSPECTIVES A Metabolic Push to Proliferate 1581 D. L. Brasaemie >> Report p. 1628 Titan’s Polar Weather 1582 F. M. Flasar >> Report p. 1620 Mycobacteria’s Export Strategy 1583 B. Ize and T. Palmer >> Report p. 1632 The Organic Approach to Asymmetric Catalysis 1584 B. List and J. W. Yang Dynamic Visions of Enzymatic Reactions 1586 M. Vendruscolo and C. M. Dobson >> Report p. 1638 Detecting and Controlling Electron Correlations 1587 M. Büttiker Volume 313, Issue 5793 1578 NEWS OF THE WEEK Endgame for the U.S.–Russian Nuclear Cities Program 1550 Claim of Oldest New World Writing Excites 1551 Archaeologists >> Research Article p. 1610 Space Mission to Shine a Light on Solar Flares 1553 SCIENCESCOPE 1553 Extensively Drug-Resistant TB Gets Foothold 1554 in South Africa Campaign Heats Up for WHO Director-General 1554 Ground the Planes During a Flu Pandemic? 1555 Studies Disagree Poplar Tree Sequence Yields Genome Double Take 1556 >> Research Article p. 1596 Pulsars’ Gyrations Confirm Einstein’s Theory 1556 >> Science Express Research Article by M. Kramer et al. Mild Climate, Lack of Moderns Let Last Neandertals 1557 Linger in Gibraltar Microarray Data Reproduced, But Some Concerns 1559 Remain Foreign Enrollment Rebounds After 3-Year Slump 1559 NEWS FOCUS Radiocarbon Dating’s Final Frontier 1560 A Stressful Situation 1564 The Galápagos Islands Kiss Their Goat Problem 1567 Goodbye www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1531 CONTENTS continued >> SCIENCE EXPRESS www.sciencexpress.org PHYSICS Coherent Dynamics of Coupled Electron and Nuclear Spin Qubits in Diamond L. Childress et al. Electron spins in a nitrogen vacancy in diamond are coupled to the nuclear spins of surrounding carbon atoms, allowing both to be manipulated for information processing. 10.1126/science.1131871 ASTROPHYSICS Tests of General Relativity from Timing the Double Pulsar M. Kramer et al. Precise timing measurements of a double radio pulsar for nearly 3 years provide four tests of general relativity under strong gravitational fields and show that it holds to 0.05 percent. >>News story p. 1556 10.1126/science.1132305 GENETICS Herpes Simplex Virus Encephalitis in Human UNC-93B Deficiency A. Casrouge et al. Although multiple genes are generally thought to control an individual’s resistance to infection, only one gene determines susceptibility to a herpesvirus. 10.1126/science.1128346 ATMOSPHERIC SCIENCE A Combined Mitigation/Geoengineering Approach to Climate Stabilization T. M. L. Wigley Global warming might be reduced by injecting sulfate aerosol precursors into the atmosphere, thus increasing cloudiness and allowing more time to reduce CO 2 emissions. 10.1126/science.1131728 CONTENTS TECHNICAL COMMENT ABSTRACTS VIROLOGY Comment on “Large-Scale Sequence Analysis of 1573 Avian Influenza Isolates” E. C. Holmes, D. J. Lipman, D. Zamarin, J. W. Yewdell full text at www.sciencemag.org/cgi/content/full/313/5793/1573b Response to Comment on “Large-Scale Sequence Analysis of Avian Influenza Isolates” J. C. Obenauer, Y. Fan, C. W. Naeve full text at www.sciencemag.org/cgi/content/full/313/5793/1573c REVIEW CELL BIOLOGY Vesicle Formation at the Plasma Membrane and 1591 Trans-Golgi Network: The Same but Different M. A. McNiven and H. M. Thompson BREVIA APPLIED PHYSICS Near-Field Microscopy Through a SiC Superlens 1595 T. Taubner et al. Combining near-field optical microscopy with superlensing allows imaging of the internal structure of manmade or biological objects at a subwavelength scale. RESEARCH ARTICLES GENOMICS The Genome of Black Cottonwood, 1596 Populus trichocarpa (Torr. & Gray) G. A. Tuskan et al. The poplar genome was duplicated 60 to 65 million years ago, marking the emergence of this tree family, but overall has evolved more slowly than that of Arabidopsis. >>News story p. 1556 CELL BIOLOGY Opposing Activities Protect Against Age-Onset 1604 Proteotoxicity E. Cohen, J. Bieschke, R. M. Perciavalle, J. W. Kelly, A. Dillin The insulin/insulin-like receptor pathway can detoxify protein aggregates in worms engineered to express excess protein in their muscles, perhaps partly explaining its role in aging. ARCHAEOLOGY Oldest Writing in the New World 1610 M. del C. Rodriguez Martinez et al. A stone block containing unknown symbols and dating to the first millennium B.C.E. has been discovered in Veracruz, Mexico, a center of the Olmec civilization. >>News story p. 1551 1582 & 1620 www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1533 CONTENTS CONTENTS continued >> REPORTS APPLIED PHYSICS Probing Nanoscale Ferroelectricity by Ultraviolet 1614 Raman Spectroscopy D. A. Tenne et al. Ultraviolet Raman spectroscopy reveals the temperature at which thin films become ferroelectric and can guide the addition of layers to tune this transition. CHEMISTRY Near-Threshold Inelastic Collisions Using Molecular 1617 Beams with a Tunable Velocity J. J. Gilijamse et al. Slowing down OH radicals to specific, precise velocities allows detailed study of the quantum mechanical effects on their low-energy collisions with noble gas atoms. PLANETARY SCIENCE Evidence for a Polar Ethane Cloud on Titan 1620 C. A. Griffith et al. Cassini has detected a polar cloud on Titan that may trap ethane produced in its atmosphere, explaining the lack of liquid ethane on the surface. >> Perspective p. 1582 CLIMATE CHANGE Early Reactivation of European Rivers During 1623 the Last Deglaciation G. Ménot et al. The flow of the huge river system that drained Europe through what is now the English Channel increased abruptly and dramatically during the last deglaciation. NEUROSCIENCE High Gamma Power Is Phase-Locked to 1626 Theta Oscillations in Human Neocortex R. T. Canolty et al. A characteristic, low-frequency brain wave modulates ultrahigh-frequency oscillations, thereby allowing communication among areas of the cortex that support behavior. CELL BIOLOGY Caveolin-1 Is Essential for Liver Regeneration 1628 M. A. Fernández et al. Mice lacking a protein that helps cells internalize other proteins and signaling molecules seem to be normal, but their livers cannot regenerate after being damaged. >> Perspective p. 1581 SCIENCE (ISSN 0036-8075) is published weekly on Friday, except the last week in December, by the American Association for the Advancement of Science, 1200 New York Avenue, NW, Washington, DC 20005. Periodicals Mail postage (publication No. 484460) paid at Washington, DC, and additional mailing offices. Copyright © 2006 by the American Association for the Advancement of Science. The title SCIENCE is a registered trademark of the AAAS. 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Authorization to photocopy material for internal or personal use under circumstances not falling within the fair use provisions of the Copyright Act is granted by AAAS to libraries and other users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, provided that $18.00 per article is paid directly to CCC, 222 Rosewood Drive, Danvers, MA 01923. The identification code for Science is 0036-8075. Scienceis indexed in the Reader’s Guide to Periodical Literature and in several specialized indexes. MICROBIOLOGY C-Terminal Signal Sequence Promotes Virulence 1632 Factor Secretion in Mycobacterium tuberculosis P. A. DiGiuseppe Champion et al. The pathogen that causes tuberculosis tags proteins for processing by its unusual secretory system with an unstructured carboxyl terminal sequence. >> Perspective p. 1583 MICROBIOLOGY An Alternative Bactericidal Mechanism of Action 1636 for Lantibiotic Peptides That Target Lipid II H. E. Hasper et al. A new class of antibiotics has an unusual target—a molecule needed for bacterial cell wall synthesis—and may be especially useful against resistant microbes. BIOCHEMISTRY The Dynamic Energy Landscape of Dihydrofolate 1638 Reductase Catalysis D. D. Boehr, D. McElheny, H. J. Dyson, P. E. Wright An enzyme progresses through its reaction cycle by fluctuating between the ground state and the higher-energy states of each kinetic intermediate. >> Perspective p. 1586 CELL BIOLOGY Imaging Intracellular Fluorescent Proteins at 1642 Nanometer Resolution E. Betzig et al. Proteins of interest can be labeled with fluorescent tags and located by photoactivated localization microscopy (PALM) in thin sections and fixed cells at near-molecular resolution. 1626 Bio-Rad and RNAi. Come have a look. From design to detection, Bio-Rad supports your RNAi research. With a broad range of proven delivery technologies, award-winning detection systems, and a suite of high-quality support products, it’s clear that Bio-Rad has a vision for RNAi. ■ High-performing potent siRNA for ≥85% knockdown with as low as 5 nM siRNA ■ Greatest choice of delivery technologies ■ RNA and protein purification products ■ Automated microfluidic RNA analysis ■ Sensitive, optimized cDNA synthesis kits ■ Systems for protein and mRNA detection For a close look at Bio-Rad’s tools for RNAi, visit us on the Web at www.bio-rad.com/rnai/ RNAi Solutions Visit us on the Web at discover.bio-rad.com Call toll free at 1-800-4BIORAD (1-800-424-6723); outside the US, contact yourlocal sales office. MCF-7 cells transfected using siLentFect ™ reagent. RNA p urified and analyzed using the Aurum ™ total RNA kit and Experion ™ system. Real-time PCR detection performed using iScript ™ cDNA synthesis kit. New siLentMer ™ siRNA! Check out our new validated and pr edesigned 27- mer siRNA duplexes Practice of the polymerase chain reaction (PCR) mayrequire a license. www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1535 ONLINE SCIENCE’S STKE www.stke.org SIGNAL TRANSDUCTION KNOWLEDGE ENVIRONMENT PERSPECTIVE: Crosslinking Transglutaminases with G Protein–Coupled Receptor Signaling S. E. Iismaa, G. E. Begg, R. M. Graham Transglutaminases use multiple mechanisms to regulate G protein–coupled receptors. PROTOCOL: Simultaneous Optical Measurements of Cytosolic Ca 2+ and cAMP in Single Cells M. C. Harbeck, O. Chepurny, V. O. Nikolaev, M. J. Lohse, G. G. Holz, M. W. Roe FRET biosensors can be combined with Fura-2 to investigate interactions between Ca 2+ and cAMP signaling. E-LETTER: Improved PRMT Substrate Detection R. B. Denman Read this modification to the STKE Protocol on methods for the analysis of protein arginine methylation. SCIENCENOW www.sciencenow.org DAILY NEWS COVERAGE A Human Spin on Hurricanes Human-induced climate change linked to hurricane severity. Hey Honey, I’m No Bee Beetle larvae fool male bees by mimicking a female’s scent. A Plethora of Alien Seas New models predict that Earth-like worlds may not be needles in a haystack. SCIENCE CAREERS www.sciencecareers.org CAREER RESOURCES FOR SCIENTISTS US: Tooling Up—Conducting an Authentic Job Search D. Jensen Technical professionals don’t have to be insincere when hunting for jobs. US: How to Get Hired in Academia A. Fazekas What are hiring committees at colleges and universities looking for in faculty-job applicants? UK: Careers in Forensics Research N. Anscombe Forensics caseworkers have a high profile these days, but some forensic scientists work behind the scenes. MISCINET: Dissecting Dialects R. Arnette Jennifer Bloomquist studies linguistic variation among residents of the Appalachian Mountains. Job searching for real. Separate individual or institutional subscriptions to these products may be required for full-text access. www.sciencemag.org Transglutaminases and GPCR signaling. Listen to the 15 September Science Podcast to hear about the oldest writing in the New World, testing general relativity, the first tree genome, and more. www.sciencemag.org/about/podcast.dtl SCIENCEPODCAST K. lactis Protein Expression Kit E1000 Kit components sold separately K. lactis GG799 Competent Cells C1001 pKLAC1 Vector N3740 effortless at any scale. The K. lactis Protein Expression Kit provides a simple method to clone and express your gene of interest in the yeast Kluyveromyces lactis.This system offers many advantages over bacterial systems and eliminates the methanol containing medium and antibiotic requirements of Pichia pastoris. Witheasy-to-use protocols and highly compet ent K. lactis cells included, this system can take you from bench top to large scale production withease. ■ New EnglandBiolabs Inc. 240 County Road,Ipswich, MA 01938 USA 1- 800-NEB-LABS Tel. (978) 927-5054 Fax (978) 921-1350 info@neb.com ■ Canada Te l. (800) 387-1095 info@ca.neb.com ■ Germany Tel. 0800/246 5227 info@ de.neb.com ■ UK Tel. (0800) 318486 info@uk.neb.com ■ China Tel. 010-82378266 beijing@neb-china.com For more information and international distribution network, please visit www.neb.com the leader in enzyme technology NEW ENGLAND BIOLABS K. lactis Protein Expression Kit from New England Biolabs YEAST PROTEIN EXPRESSION MADE EASY Advantages: ■ High yield protein expression ■ Rapid high cell density growth ■ Methanol- free growth media ■ Plasmid integration enhances stability ■ Acetamide selection enriches for multi-copy integrants, enhancing yield ■ Tight control of geneexpression enables expression of toxic genes ■ Access to eukaryotic protein folding and glycosylation machinery ■ Simultaneous expression of multiple proteins ■ Ease-of-use for those inexperienced with yeast systems ■ Yeast competent cells included ■ No license required for research use Quick comparison of K. lactis and P. pastoris expression systems. flow through an enormous river that flowed into the Atlantic Ocean through what now is the English Channel, called the Channel River. Ménot et al. (p. 1623) present a record of Channel River activity between about 30,000 and 5,000 years before the present. Its flow began to swell around 22,000 years ago, reached a peak between 19,000 and 17,000 years ago, and ended abruptly then at the start of Heinrich Event 1. This record should help allow models to determine what effect the melting of European glaciers at the end of the Last Glacial Maximum had on ocean cir- culation, as has been done for the melt- ing of the Laurentide Ice Sheet on the other side of the Atlantic Ocean. Seeking the Genome for the Trees Although the genomes of some model plants such as Arabidopsis and rice have been sequenced, they are different in many key ways from their long-lived, woody rela- tives, the trees. Tuskan et al. (p. 1596; see the cover and the news story by Stokstad) present the genome sequence of the black cottonwood, Populus trichocarpa, which has undergone two whole genome duplication events, one of which occurred at the same time as in Arabidopsis. The Populus genome has evolved more slowly than Arabidopsis, with reduced rates of nucleotide substitution, tandem gene duplication, and gross structural rearrangements of chromo- somes. Comparisons of the gene families Ethereal Ethane Scientists predicted that Titan’s surface should be awash with liquid ethane, but the low and mid-latitudes of this saturnian moon are merely moist, and dunes prevail rather than seas. Griffith et al. (p. 1620; see the Perspective by Flasar) argue that a large cloud near the north pole of Titan spotted by Cassini’s Visual Infrared Mapping Spectrometer may harbor the missing ethane. Similar to Earth, cold air downwells near the winter pole and causes the formation of stratospheric polar clouds. Solid ethane snow may frost the surface at the pole if the condi- tions are cold enough. Themes and Variations in Secretion and Endocytosis Cells need to secrete a variety of proteins from the cell surface and also need to internalize some of these surface proteins, as well as other external proteins. McNiven and Thompson (p. 1591) review the mechanisms involved in the formation of coated exocytic transport vesicles as they are exported from the Golgi complex en route to the plasma membrane and compare and contrast them with the formation of coated endocytic vesicles. European Meltwaters At the height of the last glaciation, a combina- tion of low sea level and the position of the Fennoscandian and British ice sheets caused much of the runoff from continental Europe to between Populus and Arabidopsis reveal a com- plex pattern, with Populus expansions in disease resistance, meristem development, metabolite transport, and cellulose and lignin biosynthesis. Reducing Crashes to Taps During the past 30 years, molecular beam tech- niques have uncovered numerous details of molecular collisions and reactions. A major limita- tion, however, has been the inherent velocity spread in these beams, which hinders the study of collisions at very low energy. This regime is of interest because of the complexes that can form when weakly attractive forces are not over- whelmed by transla- tional momentum. Gilijamse et al. (p. 1617) use inho- mogeneous electric fields to slow down a beam of OH radicals through Stark deceleration, while maintaining a very nar- row velocity spread. The rotational-state depend- ence of OH scattering events with a beam of xenon atoms was determined for a collision-energy range extending below 1 kilocalorie per mole. Of Aging and Aggregation Protein aggregation that is associated with late age-onset diseases such as Alzheimer’s and EDITED BY STELLA HURTLEY AND PHIL SZUROMI www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1537 CREDITS (TOP TO BOTTOM): RODRÍGUEZ MARTÍNEZ ET AL.; GILIJAMSE ET AL. << Old Olmec Writing The Olmec civilization of Central America [~1200 to 400 years before the common era (BCE)] may have been the precursor to later complex societies such as the Maya (100 to 600 CE) and Aztec (1200 to 1500 CE), yet unambiguous evidence of earliest Olmec writing is lacking. Rodríguez Martínez et al. (p. 1610; see the news story by Lawler) report the discovery of a stone block from Veracruz, Mexico, inscribed with an unknown system of writing. Taken from a gravel quarry, the block has been dated to the first millennium CE, which is earlier than previous finds. The glyphs, still undeciphered, bear similarity to other Olmec imagery, and the pattern is consistent with a system of writing. Continued on page 1539 EDITED BY STELLA HURTLEY AND PHIL SZUROMI Leap ahead of your co mpetition with cutting-edge genomics instruments and reagents from Roch e Applied Science. Generate data faster and easier than ever before with inno vative products for innovative research. Genome Sequencer 20 – Real Technology, Real Results Accelerate genetic analysis of de novo genomes, complex populations, SNPs, tags, miRNA, and more. Generate data in days – not months or years – with the newest revolution in sequencing technology. LightCycler ® 480 Plate-Based Real-Time PCR System – The Versatile Alternative Count on the speed and accuracy you have come to expect from the leader in rapid real-time PCR – in a more convenient and versatile 96- or 384-well plate format. Universal ProbeLibrary – Simplifying and Improving qPCR with Novel Technologies Design a new gene expression qPCR assay in seconds and run it tomorrow. Obtain the benefits of hydrolysis probe assays at a fraction of the cost. Genome Sequencer 20: RESTRICTION ON USE: Purchaser is only authorized to use the Genome Sequencer 20 Instrument with PicoTiterPlate devices supplied by 454 Life Sciences and in conformity with the procedures contained in the Operator's Manual. LIGHTCYCLER is a trademark of Roche.For general laboratory use. Not for use in diagnostic procedures. This LightCycler ® 480 Real-Time PCR System is licensed under U.S. Patent 6,814,934 and corresponding claims in its non- U.S. counterparts and under one or more of U.S. Patents Nos. 5,038,852, 5,656,493, 5,333,675, or corresponding claims in their non-U.S. counterparts, for use in life science, by implication or by estoppel under any patent claims or for any other implication. Parts of the Software used for the LightCycler ® 480 System are licensed from Idaho Technology Inc., Salt Lake City,UT,USA. The product is covered in-part by US 5,871,908, co-exclusively licensed from Evotec OAI AG. PROBELIBRARY is a registered trademark ofExiqon A/S, Vedbaek, Denmark. This product is a Licensed Probe. Its use with an Authorized Core Kit and Authorized Thermal Cycler provides a license for the purchaser’s own internal research and development under the 5' nuclease patents and basic PCR patents of Roche Molecular Systems, Inc. and F. Hoffmann-La Roche Ltd. No real-time apparatus or system patent rights or any other patent rights owned by Applera Corporation, and no rights for any other application, including any in vitro diagnostic application under patents owned by Roche Molecular Systems, Inc. and F. Hoffmann-La Roche Ltd claiming homogeneous or real-time amplification and detection methods, are conveyed expressly, by implication or by estoppel. ProbeLibrary is covered by US and other patent applications owned by Exiqon A/S. Locked Nucleic Acids (LNA) are covered by U.S. Patents No US 6,794,499, US 6,670,461, US 6,268,490 & US 6,770,748 and other patents and patent applications owned by Exiqon A/S and Prof. Takeshi Imanishi. The quencher used in the probes is covered by patent applications owned by Exiqon A/S. Other brands or product names are trademarks of their respective holders. © 2006Roche Diagnostics GmbH. All rights reserved. Roche Diagnostics GmbH Roche Applied Science 68298 Mannheim Germany Searchi ng for Innovation? Look no further www.roche-applied-science.com Innovative Genomic Analysis For more information about these and other innovative products, visit us at www.roche-applied-science.com today. www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1539 CREDIT: HASPER ET AL. This Week in Science Parkinson’s has toxic effects. Cohen et al. (p. 1604) show, in a worm model of amyloidosis, that the aging process is linked to toxic protein aggregation. Molecules associated with the insulin signaling pathway—a cascade that is linked to aging—also influence aggregation and toxicity. The transcription factor DAF-16 and heat shock protein HSF-1 function to promote aggregation or disaggregation, respectively, of β-amyloid peptides. The authors propose a cellular mechanism hinging on these two factors whereby toxic aggregates are identified and prepared for disaggregation and degradation. The Rhythm in the Brain Spontaneous cortical oscillations facilitate synaptic plasticity; correlate with attention and percep- tual binding; and may play a role in transient, long-range coordination of distinct brain regions. Exactly how these transient oscillations influence each other and coordinate processing at both the single neuron and population levels is still not understood. Canolty et al. (p. 1626) show that the amplitude and phase of cortical theta rhythms modulate the power of high gamma band neuronal oscillations in the human electrocorticogram. High gamma activity directly reflects the activation of a local cortical area and is correlated with the functional magnetic resonance imaging blood oxygen level dependent−signal. The much slower theta rhythm is more distributed across the cortex and is associated with novelty, attention, working memory, and exploratory behavior. Importantly, the strength of this theta-gamma coupling is correlated with variations in a battery of cognitive tasks. Two Ways to Kill a Bacterium In bacterial peptidoglycan synthesis, lipid II is required for the transport of cell-wall subunits across the bacterial cytoplasmic membrane. Lipid II is a target for antibiotics like vancomycin and lantibiotics, such as nisin and mutacin, which are small peptides bearing lanthionine rings. These drugs act by contrasting mechanisms. Van- comycin binds to the pentapeptide of lipid II, whereas lantibiotics bind to the pyrophosphate of lipid II via the lanthionine rings. Hasper et al. (p. 1636) have discov- ered that although some lantibiotics aggregate to form pores in membranes, others kill bacterial cells without forming pores. Instead, immobilization of lipid II prevents it from reaching sites where peptidoglycan synthesis occurs, such as at the septum of dividing cells, and blocking cell-wall synthesis. Caveolin and Liver Regeneration Caveolin is a key component of caveolae, cell surface invaginations involved in the internalization of a variety of signaling molecules and the uptake of certain viruses. Surprisingly enough, when caveolin knockout mice were generated a few years ago, they appeared to be healthy. Fernández et al. (p. 1628; see the Perspective by Brasaemle) have now examined these mice in more detail and discovered a phe- notype in these animals—a profound defect in liver regeneration leading to reduced survival after par- tial hepatectomy. Problems uncovered included changes in lipid metabolism and cell cycle progression. Treating mutant mice with glucose could circumvent the defect and improve survival after liver damage. Perfecting Pathogenic Potential The human pathogen Mycobacterium tuberculosis does not have recognizable homologs of secretion machines that are essential for the virulence of many bacterial pathogens. Instead, the ESX-1 system is required for growth of M. tuberculosis in macrophages and for controlling host cell response to infection. This system secretes a pair of virulence factors, ESAT-6 and CFP-10, that are essential for M. tuberculosis virulence. DiGiuseppe Champion et al. (p. 1632; see the Perspective by Ize and Palmer) identified a C-terminal signal sequence required for directing the ESAT-6/CFP-10 virulence factor complex for secretion from M. tuberculosis. Mutations in this signal sequence that prevented interaction with the secretion machine also prevented secretion. The CFP-10 signal sequence also drove secretion of an unrelated protein. Continued from page 1537 . $10 www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1529 CONTENTS CONTENTS continued >> DEPARTMENTS 1535 Science Online 1537 This Week in Science 1542 Editors’ Choice 1546 Contact Science 1547. Islands Kiss Their Goat Problem 1567 Goodbye www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1531 CONTENTS continued >> SCIENCE EXPRESS www.sciencexpress.org PHYSICS Coherent Dynamics of. products, visit us at www.roche-applied -science. com today. www.sciencemag.org SCIENCE VOL 313 15 SEPTEMBER 2006 1539 CREDIT: HASPER ET AL. This Week in Science Parkinson’s has toxic effects. Cohen