Nature 430, 815 (2004). doi:10.1038/430815a

With the death of Francis Crick, biology is mourning one of its deepest thinkers. A work of futurology, published in 1970, reveals the extent of his prescience — and suggests challenges for today's theorists.

Nature 430, 815 (2004). doi:10.1038/430815b

Americans should worry less about their neighbour and more about the prestige of regulators who protect public health.

Nature 430, 817 (2004). doi:10.1038/430817a

Author: Jonathan Knight

Talk of disease cures obscures challenges facing cloning teams

Nature 430, 818 (2004). doi:10.1038/430818a

Author: K. S. Jayaraman

Indian scientists say China is denying access to dammed river

Nature 430, 818 (2004). doi:10.1038/430818b

Author: Emma Marris

Regional study ushers in new generation of forecasts

Nature 430, 819 (2004). doi:10.1038/430819a

Author: Geoff Brumfiel

Biblical musings reveal another side of the father of modern science

Nature 430, 819 (2004). doi:10.1038/430819b

Author: Erika Check

RNA technology on track for first clinical trials

Nature 430, 820 (2004). doi:10.1038/430820a

Author: Geoff Brumfiel

Troubled repository embroiled in US election race

Nature 430, 820 (2004). doi:10.1038/430820b

Author: Quirin Schiermeier

Rising carbon dioxide levels could devastate marine ecosystems

Nature 430, 821 (2004). doi:10.1038/430821a

Author: David Osumi-Sutherland

Confusion surrounds cause of veterans' ill-health

Nature 430, 821 (2004). doi:10.1038/430821b

Author: Mark Peplow

Physics celebrations will cause light pollution, say astronomers

Nature 430, 822 (2004). doi:10.1038/430822a

Did extra label cause the scare that shut down Los Alamos?WashingtonA pair of ‘missing’ computer disks that sparked a security scandal at the Los Alamos National Laboratory in New Mexico may never have existed, according to a senator who oversees the laboratory.The

Nature 430, 824 (2004). doi:10.1038/430824a

Author: Alison Abbott

CERN, the centre for particle physics in Europe, has been smashing its way through the subatomic world for the past 50 years. Alison Abbott finds out what's in store for the future.

Nature 430, 828 (2004). doi:10.1038/430828a

Author: Michael Hopkin

Archaeologists have failed to learn the secrets of Mexico's largest ancient monument. Particle physicists might save the day, says Michael Hopkin.

Nature 430, 829 (2004). doi:10.1038/430829a

Author: Edward H. Allison

Government could hone its use of science but scientists need to understand the issues.

Nature 430, 829 (2004). doi:10.1038/430829b

Author: Tadashi Hirata

SirAs reported in your News story “Institute doomed by loss of interest in basics” (Nature430, 282; 200410.1038/430282a), Japan's Biomolecular Engineering Research Institute (BERI) will disband sometime next year. Unfortunately, for various reasons, including the fact that the board

Nature 430, 829 (2004). doi:10.1038/430829c

Author: Emanuel Epstein

SirSean Nee is right in drawing attention to the invisible world of microbial life in his Commentary “More than meets the eye” (Nature429, 804–805; 2004). That netherworld of life is not the only one to suffer neglect

Nature 430, 831 (2004). doi:10.1038/430831a

Author: Robert M. May

How to create a research council that is a Champions League for science.

Nature 430, 833 (2004). doi:10.1038/430833a

Author: Sidney C. Wolff

The Gemini project typifies the growth of astronomy into ‘big science’.

Nature 430, 834 (2004). doi:10.1038/430834a

Author: Robert Olby

Recollections can be vivid, as when Francis Crick looked back to a moment in February 1953: “Jerry Donohue and Jim Watson were by the blackboard and I was by my desk, and we suddenly thought, ‘Well, perhaps we could explain 1:1 ratios by pairing the

Nature 430, 834 (2004). doi:10.1038/430834b

Author: Bernadette Bensaude-Vincent

The name of Dmitrii Mendeleev is forever associated with the periodic table, which is found in chemistry laboratories and classrooms around the world. Yet this famous invention, which made sense and order out of the elements, was just one of Mendeleev's numerous achievements. Michael Gordin,

Nature 430, 835 (2004). doi:10.1038/430835a

Author: Giovanni F. Bignami

The Italian scientific revolution, championed by Galileo in the seventeenth century, shares its roots with the mathematical beauty of Renaissance architecture. Galileo, for example, found that studies by the sixteenth-century master architects Giorgio Vasari and Michelangelo came in handy for computing the height of mountains

Nature 430, 836 (2004). doi:10.1038/430836a

Author: Richard Gregory

An eye-opening experience of the wonders of perception.

Nature 430, 837 (2004). doi:10.1038/430837a

Author: David A. Tirrell

By taking advantage of the cell's carbohydrate metabolism, reactive sugar analogues can be used to tag specific cells, potentially singling them out for imaging studies or drug delivery.

Nature 430, 838 (2004). doi:10.1038/430838a

Author: Paul M. O'Neill

A remarkable set of antimalarial drug candidates has been developed by an international collaboration of scientists, using the age-old Chinese herbal medicine artemisinin as a template.

Nature 430, 839 (2004). doi:10.1038/430839a

Author: David R. Nelson

In high-temperature superconductors, quantized vortex filaments can be twisted up into a DNA-like double helix. An experiment is proposed to test how easily these vortex lines cut through each other.

Nature 430, 840 (2004). doi:10.1038/430840a

Author: Bruce Bowerman

During cell division everything must happen at the right time, or errors occur. A common cellular control device, protein phosphorylation, is now shown to time the assembly of a key part of the division machinery.

Nature 430, 841 (2004). doi:10.1038/430841a

100 YEARS AGOInaugural address by the Right Hon. A. J. Balfour: Reflections suggested by the New Theory of Matter.If we jump over the century which separates 1804 from 1904, and attempt to give in outline the world-picture as it now presents itself

Nature 430, 842 (2004). doi:10.1038/430842a

Authors: Trond M. Dokken & Kerim H. Nisancioglu

During the last glacial period, climatic variation in the Northern and Southern Hemispheres was evidently linked. Modelling work points to freshwater discharge into the North Atlantic as a driving factor.

Nature 430, 843 (2004). doi:10.1038/430843a

Authors: James G. Bann & Scott J. Hultgren

An atomic picture of how anthrax toxin binds to its host's cells reveals that the toxin commandeers a host receptor protein and tricks it into helping the toxin enter the cell.

Nature 430, 843 (2004). doi:10.1038/430843b

Author: Heike Langenberg

During the Beagle's visit to the Galapagos Islands in 1835, Charles Darwin noted that the local climate was far less warm than would be expected from the islands' position on the Equator. The air-conditioning effect is due to the cooling influence of the surrounding

Nature 430, 845 (2004). doi:10.1038/430845a

Authors: Alexander Rich & Charles F. Stevens

Alexander Rich and Charles F. Stevens, respectively an early collaborator of Crick's and a long-standing colleague at the Salk Institute, describe the life and work of one of the great thinkers of twentieth-century biology.

Nature 430, 848 (2004). doi:10.1038/430848a

MicrobiologyHow to stomach a stomach infectionScience305, 1003–1006 (2004)Researchers might have discovered why most people infected with the stomach bug Helicobacter pylori never become ill. Masatomo Kawakubo et al. have found a naturally occurring antibiotic that might offer protection

Nature 430, 849 (2004). doi:10.1038/430849a

Authors: Rupert Ursin, Thomas Jennewein, Markus Aspelmeyer, Rainer Kaltenbaek, Michael Lindenthal, Philip Walther & Anton Zeilinger

A real-world experiment marks a step towards worldwide quantum communication.Efficient long-distance quantum teleportation is crucial for quantum communication and quantum networking schemes. Here we describe the high-fidelity teleportation of photons over a distance of 600 metres across the River Danube in Vienna, with the optimal efficiency that can be achieved using linear optics. Our result is a step towards the implementation of a quantum repeater, which will enable pure entanglement to be shared between distant parties in a public environment and eventually on a worldwide scale.

Nature 430, 850 (2004). doi:10.1038/430850a

Authors: C. D. Wilga & G. V. Lauder

The tail of most sharks has an elongated upper lobe that differs from the externally symmetrical tail structure common among bony fishes, but the hydrodynamic purpose of this asymmetric tail shape is unclear. Here we quantify water flow patterns in the wakes of freely swimming dogfish sharks and find that they have a ring-within-a-ring vortex structure, in contrast to the single rings shed by symmetrical fish tails. The branched-ring vortex is generated by the inclined angle of the tail's trailing edge and by its motion at an angle to the horizontal body axis; the vortex directs water backwards and downwards, which may increase the shark's vertical manoeuvrability.

Nature 430, 851 (2004). doi:10.1038/nature02786

Authors: R. Knutti, J. Flückiger, T. F. Stocker & A. Timmermann

The climate of the last glacial period was extremely variable, characterized by abrupt warming events in the Northern Hemisphere, accompanied by slower temperature changes in Antarctica and variations of global sea level. It is generally accepted that this millennial-scale climate variability was caused by abrupt

Nature 430, 857 (2004). doi:10.1038/nature02806

Authors: Xinwei She, Julie E. Horvath, Zhaoshi Jiang, Ge Liu, Terrence S. Furey, Laurie Christ, Royden Clark, Tina Graves, Cassy L. Gulden, Can Alkan, Jeff A. Bailey, Cenk Sahinalp, Mariano Rocchi, David Haussler, Richard K. Wilson, Webb Miller, Stuart Schwartz & Evan E. Eichler

An understanding of how centromeric transition regions are organized is a critical aspect of chromosome structure and function; however, the sequence context of these regions has been difficult to resolve on the basis of the draft genome sequence. We present a detailed analysis of the

Nature 430, 865 (2004). doi:10.1038/nature02832

Authors: Matthew J. Holman, J. J. Kavelaars, Tommy Grav, Brett J. Gladman, Wesley C. Fraser, Dan Milisavljevic, Philip D. Nicholson, Joseph A. Burns, Valerio Carruba, Jean-Marc Petit, Philippe Rousselot, Oliver Mousis, Brian G. Marsden & Robert A. Jacobson

Each giant planet of the Solar System has two main types of moons. ‘Regular’ moons are typically larger satellites with prograde, nearly circular orbits in the equatorial plane of their host planets at distances of several to tens of planetary radii. The ‘irregular’ satellites (which are typically smaller) have larger orbits with significant eccentricities and inclinations. Despite these common features, Neptune's irregular satellite system, hitherto thought to consist of Triton and Nereid, has appeared unusual. Triton is as large as Pluto and is postulated to have been captured from heliocentric orbit; it traces a circular but retrograde orbit at 14 planetary radii from Neptune. Nereid, which exhibits one of the largest satellite eccentricities, is believed to have been scattered from a regular satellite orbit to its present orbit during Triton's capture. Here we report the discovery of five irregular moons of Neptune, two with prograde and three with retrograde orbits. These exceedingly faint (apparent red magnitude mR = 24.2–25.4) moons, with diameters of 30 to 50 km, were presumably captured by Neptune.

Nature 430, 867 (2004). doi:10.1038/nature02792

Authors: T. Haugan, P. N. Barnes, R. Wheeler, F. Meisenkothen & M. Sumption

Following the discovery of type-II high-temperature superconductors in 1986 (refs 1, 2), work has proceeded to develop these materials for power applications. One of the problems, however, has been that magnetic flux is not completely expelled, but rather is contained within magnetic fluxons, whose motion prevents larger supercurrents. It is known that the critical current of these materials can be enhanced by incorporating a high density of extended defects to act as pinning centres for the fluxons. YBa2Cu3O7 (YBCO or 123) is the most promising material for such applications at higher temperatures (liquid nitrogen). Pinning is optimized when the size of the defects approaches the superconducting coherence length (∼ 2–4 nm for YBCO at temperatures ≤77 K) and when the areal number density of defects is of the order of (H/2) × 1011 cm-2, where H is the applied magnetic field in tesla. Such a high density has been difficult to achieve by material-processing methods that maintain a nanosize defect, except through irradiation. Here we report a method for achieving a dispersion of ∼8-nm-sized nanoparticles in YBCO with a high number density, which increases the critical current (at 77 K) by a factor of two to three for high magnetic fields.

Nature 430, 870 (2004). doi:10.1038/nature02817

Authors: Ayako Hashimoto, Kazu Suenaga, Alexandre Gloter, Koki Urita & Sumio Iijima

Atomic-scale defects in graphene layers alter the physical and chemical properties of carbon nanostructures. Theoretical predictions have recently shown that energetic particles such as electrons and ions can induce polymorphic atomic defects in graphene layers as a result of knock-on atom displacements. However, the number of experimental reports on these defects is limited. The graphite network in single-walled carbon nanotubes has been visualized by transmission electron microscopy (TEM) and their chiral indices have been determined. But the methods used require a long image acquisition time and intensive numerical treatments after observations to find an ‘average’ image, which prevents the accurate detection and investigation of defect structures. Here we report observations in situ of defect formation in single graphene layers by high-resolution TEM. The observed structures are expected to be of use when engineering the properties of carbon nanostructures for specific device applications.

Nature 430, 873 (2004). doi:10.1038/nature02791

Authors: Jennifer A. Prescher, Danielle H. Dube & Carolyn R. Bertozzi

Cell surfaces are endowed with biological functionality designed to mediate extracellular communication. The cell-surface repertoire can be expanded to include abiotic functionality through the biosynthetic introduction of unnatural sugars into cellular glycans, a process termed metabolic oligosaccharide engineering. This technique has been exploited in fundamental studies of glycan-dependent cell–cell and virus–cell interactions and also provides an avenue for the chemical remodelling of living cells. Unique chemical functional groups can be delivered to cell-surface glycans by metabolism of the corresponding unnatural precursor sugars. These functional groups can then undergo covalent reaction with exogenous agents bearing complementary functionality. The exquisite chemical selectivity required of this process is supplied by the Staudinger ligation of azides and phosphines, a reaction that has been performed on cultured cells without detriment to their physiology. Here we demonstrate that the Staudinger ligation can be executed in living animals, enabling the chemical modification of cells within their native environment. The ability to tag cell-surface glycans in vivo may enable therapeutic targeting and non-invasive imaging of changes in glycosylation during disease progression.

Nature 430, 877 (2004). doi:10.1038/nature02780

Authors: Ai Ning Loh, James E. Bauer & Ellen R. M. Druffel

Seawater dissolved organic matter (DOM) is the largest reservoir of exchangeable organic carbon in the ocean, comparable in quantity to atmospheric carbon dioxide. The composition, turnover times and fate of all but a few planktonic constituents of this material are, however, largely unknown. Models of ocean carbon cycling are thus limited by the need for information on temporal scales of carbon storage in DOM subcomponents, produced via the ‘biological pump’, relative to their recycling by bacteria. Here we show that carbohydrate- and protein-like substances in the open Atlantic and Pacific oceans, though often significantly aged, comprise younger fractions of the DOM, whereas dissolved lipophilic material exhibits up to ∼90 per cent fossil character. In contrast to the millennial mean ages of DOM observed throughout the water column, weighted mean turnover times of DOM in the surface ocean are only decadal in magnitude. An observed size–age continuum further demonstrates that small dissolved molecules are the most highly aged forms of organic matter, cycling much more slowly than larger, younger dissolved and particulate precursors, and directly links oceanic organic matter age and size with reactivity.

Nature 430, 881 (2004). doi:10.1038/nature02808

Authors: Martin Edwards & Anthony J. Richardson

Phenology, the study of annually recurring life cycle events such as the timing of migrations and flowering, can provide particularly sensitive indicators of climate change. Changes in phenology may be important to ecosystem function because the level of response to climate change may vary across functional groups and multiple trophic levels. The decoupling of phenological relationships will have important ramifications for trophic interactions, altering food-web structures and leading to eventual ecosystem-level changes. Temperate marine environments may be particularly vulnerable to these changes because the recruitment success of higher trophic levels is highly dependent on synchronization with pulsed planktonic production. Using long-term data of 66 plankton taxa during the period from 1958 to 2002, we investigated whether climate warming signals are emergent across all trophic levels and functional groups within an ecological community. Here we show that not only is the marine pelagic community responding to climate changes, but also that the level of response differs throughout the community and the seasonal cycle, leading to a mismatch between trophic levels and functional groups.

Nature 430, 884 (2004). doi:10.1038/nature02776

Authors: Susan Kalisz, Donna W. Vogler & Kristen M. Hanley

The evolution of self-fertilization in hermaphrodites is opposed by costs that decrease the value of self progeny relative to that of outcross progeny. However, self-fertilization is common in plants; 20% are highly selfing and 33% are intermediate between selfing and outcrossing. Darwin proposed an adaptive benefit of self-pollination in providing reproductive assurance when outcrossing is impossible. Moreover, if outcross pollen receipt is inconsistent within or between years, these conditions likewise favour self-pollination, and this can result in a mixture of self and outcross seed production (mixed mating). Despite wide acceptance, the reproductive assurance hypothesis has lacked the support of complete empirical evidence to show that variable pollination can create both the ecological and genetic conditions favouring self-pollination. We recently showed in Collinsia verna that during periods of infrequent pollinator visits, autonomous self-pollination boosted seed output per flower, the key ecological condition. Here we show low inbreeding depression and marker-based estimates of selfing, demonstrating that when the pollination environment in wild populations necessitates reproductive assurance, selfing rates increase. We provide a complete demonstration of reproductive assurance under variable pollination environments and mechanistically link reproductive assurance to intermediate selfing rates through mixed mating.

Nature 430, 887 (2004). doi:10.1038/nature02781

Authors: Pietro Piffanelli, Luke Ramsay, Robbie Waugh, Abdellah Benabdelmouna, Angélique D'Hont, Karin Hollricher, Jørgen Helms Jørgensen, Paul Schulze-Lefert & Ralph Panstruga

Barley (Hordeum vulgare) has played a pivotal role in Old World agriculture since its domestication about 10,000 yr ago. Barley plants carrying loss-of-function alleles (mlo) of the Mlo locus are resistant against all known isolates of the widespread powdery mildew fungus. The sole mlo resistance allele recovered so far from a natural habitat, mlo-11, was originally retrieved from Ethiopian landraces and nowadays controls mildew resistance in the majority of cultivated European spring barley elite varieties. Here we use haplotype analysis to show that the mlo-11 allele probably arose once after barley domestication. Resistance in mlo-11 plants is linked to a complex tandem repeat array inserted upstream of the wild-type gene. The repeat units consist of a truncated Mlo gene comprising 3.5 kilobases (kb) of 5′-regulatory sequence plus 1.1 kb of coding sequence. These generate aberrant transcripts that impair the accumulation of both Mlo wild-type transcript and protein. We exploited the meiotic instability of mlo-11 resistance and recovered susceptible revertants in which restoration of Mlo function was accompanied by excision of the repeat array. We infer cis-dependent perturbation of transcription machinery assembly by transcriptional interference in mlo-11 plants as a likely mechanism leading to disease resistance.

Nature 430, 891 (2004). doi:10.1038/nature02798

Authors: Hongkyun Kim, Matthew J. Rogers, Janet E. Richmond & Steven L. McIntire

Muscular dystrophies are among the most common human genetic diseases and are characterized by progressive muscle degeneration. Muscular dystrophies result from genetic defects in components of the dystrophin–glycoprotein complex (DGC), a multimeric complex found in the muscle cell plasma membrane. The DGC links the intracellular cytoskeleton to the extracellular matrix and is thought to be important for maintaining the mechanical integrity of muscles and organizing signalling molecules. The exact role of the DGC in the pathogenesis of disease has, however, remained uncertain. Mutations in Caenorhabditis elegans DGC genes lead to specific defects in coordinated movement and can also cause muscle degeneration. Here we show that mutations in the gene snf-6 result in phenotypes indistinguishable from those of the DGC mutants, and that snf-6 encodes a novel acetylcholine/choline transporter. SNF-6 mediates the uptake of acetylcholine at neuromuscular junctions during periods of increased synaptic activity. SNF-6 also interacts with the DGC, and mutations in DGC genes cause a loss of SNF-6 at neuromuscular junctions. Improper clearing of acetylcholine and prolonged excitation of muscles might contribute to the pathogenesis of muscular dystrophies.

Nature 430, 896 (2004). doi:10.1038/nature02753

Authors: Cecilia Bouzat, Fernanda Gumilar, Guillermo Spitzmaul, Hai-Long Wang, Diego Rayes, Scott B. Hansen, Palmer Taylor & Steven M. Sine

Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains, how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.

Nature 430, 900 (2004). doi:10.1038/nature02779

Authors: Jonathan L. Vennerstrom, Sarah Arbe-Barnes, Reto Brun, Susan A. Charman, Francis C. K. Chiu, Jacques Chollet, Yuxiang Dong, Arnulf Dorn, Daniel Hunziker, Hugues Matile, Kylie McIntosh, Maniyan Padmanilayam, Josefina Santo Tomas, Christian Scheurer, Bernard Scorneaux, Yuanqing Tang, Heinrich Urwyler, Sergio Wittlin & William N. Charman

The discovery of artemisinin more than 30 years ago provided a completely new antimalarial structural prototype; that is, a molecule with a pharmacophoric peroxide bond in a unique 1,2,4-trioxane heterocycle. Available evidence suggests that artemisinin and related peroxidic antimalarial drugs exert their parasiticidal activity subsequent to reductive activation by haem, released as a result of haemoglobin digestion by the malaria-causing parasite. This irreversible redox reaction produces carbon-centred free radicals, leading to alkylation of haem and proteins (enzymes), one of which—the sarcoplasmic-endoplasmic reticulum ATPase PfATP6 (ref. 7)—may be critical to parasite survival. Notably, there is no evidence of drug resistance to any member of the artemisinin family of drugs. The chemotherapy of malaria has benefited greatly from the semi-synthetic artemisinins artemether and artesunate as they rapidly reduce parasite burden, have good therapeutic indices and provide for successful treatment outcomes. However, as a drug class, the artemisinins suffer from chemical (semi-synthetic availability, purity and cost), biopharmaceutical (poor bioavailability and limiting pharmacokinetics) and treatment (non-compliance with long treatment regimens and recrudescence) issues that limit their therapeutic potential. Here we describe how a synthetic peroxide antimalarial drug development candidate was identified in a collaborative drug discovery project.

Nature 430, 905 (2004). doi:10.1038/nature02763

Authors: Eugenio Santelli, Laurie A. Bankston, Stephen H. Leppla & Robert C. Liddington

Anthrax toxin consists of the proteins protective antigen (PA), lethal factor (LF) and oedema factor (EF). The first step of toxin entry into host cells is the recognition by PA of a receptor on the surface of the target cell. Subsequent cleavage of receptor-bound PA enables EF and LF to bind and form a heptameric PA63 pre-pore, which triggers endocytosis. Upon acidification of the endosome, PA63 forms a pore that inserts into the membrane and translocates EF and LF into the cytosol. Two closely related host cell receptors, TEM8 and CMG2, have been identified. Both bind to PA with high affinity and are capable of mediating toxicity. Here, we report the crystal structure of the PA–CMG2 complex at 2.5 Å resolution. The structure reveals an extensive receptor–pathogen interaction surface mimicking the non-pathogenic recognition of the extracellular matrix by integrins. The binding surface is closely conserved in the two receptors and across species, but is quite different in the integrin domains, explaining the specificity of the interaction. CMG2 engages two domains of PA, and modelling of the receptor-bound PA63 heptamer suggests that the receptor acts as a pH-sensitive brace to ensure accurate and timely membrane insertion. The structure provides new leads for the discovery of anthrax anti-toxins, and should aid the design of cancer therapeutics.

Nature 430, 908 (2004). doi:10.1038/nature02767

Authors: Masanori Mishima, Visnja Pavicic, Ulrike Grüneberg, Erich A. Nigg & Michael Glotzer

The bipolar mitotic spindle is responsible for segregating sister chromatids at anaphase. Microtubule motor proteins generate spindle bipolarity and enable the spindle to perform mechanical work. A major change in spindle architecture occurs at anaphase onset when central spindle assembly begins. This structure regulates the initiation of cytokinesis and is essential for its completion. Central spindle assembly requires the centralspindlin complex composed of the Caenorhabditis elegans ZEN-4 (mammalian orthologue MKLP1) kinesin-like protein and the Rho family GAP CYK-4 (MgcRacGAP). Here we describe a regulatory mechanism that controls the timing of central spindle assembly. The mitotic kinase Cdk1/cyclin B phosphorylates the motor domain of ZEN-4 on a conserved site within a basic amino-terminal extension characteristic of the MKLP1 subfamily. Phosphorylation by Cdk1 diminishes the motor activity of ZEN-4 by reducing its affinity for microtubules. Preventing Cdk1 phosphorylation of ZEN-4/MKLP1 causes enhanced metaphase spindle localization and defects in chromosome segregation. Thus, phosphoregulation of the motor domain of MKLP1 kinesin ensures that central spindle assembly occurs at the appropriate time in the cell cycle and maintains genomic stability.

Nature 430, 913 (2004). doi:10.1038/nature02813

Authors: Changwook Lee, BumSoo Hong, Jung Min Choi, Yugene Kim, Saori Watanabe, Yukio Ishimi, Takemi Enomoto, Shusuke Tada, Youngchang Kim & Yunje Cho

To maintain chromosome stability in eukaryotic cells, replication origins must be licensed by loading mini-chromosome maintenance (MCM2–7) complexes once and only once per cell cycle. This licensing control is achieved through the activities of geminin and cyclin-dependent kinases. Geminin binds tightly to Cdt1, an essential component of the replication licensing system, and prevents the inappropriate reinitiation of replication on an already fired origin. The inhibitory effect of geminin is thought to prevent the interaction between Cdt1 and the MCM helicase. Here we describe the crystal structure of the mouse geminin–Cdt1 complex using tGeminin (residues 79–157, truncated geminin) and tCdt1 (residues 172–368, truncated Cdt1). The amino-terminal region of a coiled-coil dimer of tGeminin interacts with both N-terminal and carboxy-terminal parts of tCdt1. The primary interface relies on the steric complementarity between the tGeminin dimer and the hydrophobic face of the two short N-terminal helices of tCdt1 and, in particular, Pro 181, Ala 182, Tyr 183, Phe 186 and Leu 189. The crystal structure, in conjunction with our biochemical data, indicates that the N-terminal region of tGeminin might be required to anchor tCdt1, and the C-terminal region of tGeminin prevents access of the MCM complex to tCdt1 through steric hindrance.

Nature 430, 917 (2004). doi:10.1038/nature02790

Authors: Matthew J. Wood, Gisela Storz & Nico Tjandra

The ability of organisms to alter their gene expression patterns in response to environmental changes is essential for viability. A central regulator of the response to oxidative stress in Saccharomyces cerevisiae is the Yap1 transcription factor. Upon activation by increased levels of reactive oxygen species, Yap1 rapidly redistributes to the nucleus where it regulates the expression of up to 70 genes. Here we identify a redox-regulated domain of Yap1 and determine its high-resolution solution structure. In the active oxidized form, a nuclear export signal (NES) in the carboxy-terminal cysteine-rich domain is masked by disulphide-bond-mediated interactions with a conserved amino-terminal α-helix. Point mutations that weaken the hydrophobic interactions between the N-terminal α-helix and the C-terminal NES-containing domain abolished redox-regulated changes in subcellular localization of Yap1. Upon reduction of the disulphide bonds, Yap1 undergoes a change to an unstructured conformation that exposes the NES and allows redistribution to the cytoplasm. These results reveal the structural basis of redox-dependent Yap1 localization and provide a previously unknown mechanism of transcription factor regulation by reversible intramolecular disulphide bond formation.

Nature 430, 921 (2004). doi:10.1038/nature02812

Authors: Jaymie M. Matthews, Rainer Kuschnig, David B. Guenther, Gordon A. H. Walker, Anthony F.J. Moffat, Slavek M. Rucinski, Dimitar Sasselov & Werner W. Weiss

Nature430, 51–53 (2004).In this Letter, Rainer Kuschnig's surname was misspelled as ‘Kusching’ in the author list. In addition, the numbering of the reference list was incorrect. References 1 to 26 should be, respectively: 1, 10–16, 2, 3,

Nature 430, 921 (2004). doi:10.1038/nature02892

Authors: Frédéric Picard, Martin Kurtev, Namjin Chung, Acharawan Topark-Ngarm, Thanaset Senawong, Rita Machado de Oliveira, Mark Leid, Michael W. McBurney & Leonard Guarente

Nature429, 771–776 (2004).It has been drawn to our attention by Vincent Keng that the image in the bottom-left frame of Fig. 1c of this Letter presents identical data to the one above it on the right.

Nature 430, 923 (2004). doi:10.1038/430923a

“Unless we fully embrace country and community ownership, we will be inviting chaos ten years down the road. We need to accelerate investments in desperately needed vaccines, as well as better treatments. Now is the time to combine long-term investments with crisis management.”So said

Nature 430, 925 (2004). doi:10.1038/430925a

Author: Pascoal Mocumbi

“It is high time we addressed the widening inequities that characterize our planet today. We need to focus our energies towards achieving basic healthcare for all.”Pascoal Mocumbi, former prime minister of Mozambique

Nature 430, 926 (2004). doi:10.1038/430926a

Author: Brian Greenwood

Campaigns against malaria are multiplying, but so are malaria deaths. Brian Greenwood asks what can be done to turn the tide.

Nature 430, 928 (2004). doi:10.1038/430928a

Author: Declan Butler

In Africa, where malaria hits hardest, scientists are crying out for countries to take matters into their own hands, says Declan Butler.

Nature 430, 930 (2004). doi:10.1038/430930a

Authors: Richard Klausner & Pedro Alonso

To win the fight against malaria we will need to scale up existing programmes and develop new weapons, say Richard Klausner and Pedro Alonso.

Nature 430, 932 (2004). doi:10.1038/430932a

Author: Amir Attaran

International agencies have failed to meet their own malaria performance targets and should be held to account, says Amir Attaran.

Nature 430, 934 (2004). doi:10.1038/430934a

Author: Robert W. Snow

We need to know how bad the malaria situation is before we can make it better, says Robert Snow.

Nature 430, 935 (2004). doi:10.1038/430935a

Author: Apoorva Mandavilli

Hampered by bureaucracy, politics and ineffectual policies, critics claim that the international Roll Back Malaria (RBM) partnership is failing, and is a long way off its goal of halving malaria deaths by 2010. Few of the 44 African countries that signed up to its main

Nature 430, 936 (2004). doi:10.1038/430936a

Author: Janet Hemingway

The malaria vector is back in scientists' sights, says Janet Hemingway, with insecticides and transgenic insects offering fresh hope.

Nature 430, 937 (2004). doi:10.1038/430937a

Authors: Julie Clayton & Declan Butler

Documentary makers can get as close to the war zones of disease as doctors and researchers — perhaps even closer. Julie Clayton and Declan Butler talk to Kevin Hull about his experiences.

Nature 430, 938 (2004). doi:10.1038/430938a

Authors: Melinda Moree, Sarah Ewart & Carter Diggs

The world must increase collaboration to meet the pressing need for a malaria vaccine, argue Carter Diggs, Sarah Ewart and Melinda Moree.

Nature 430, 940 (2004). doi:10.1038/430940a

Author: Stephen Hoffman

Creating a malaria vaccine will be tough. But Africa needs one now more than ever, says Stephen Hoffman.

Nature 430, 942 (2004). doi:10.1038/430942a

Authors: Robert Ridley & Yeya Toure

We have the science to make new antimalarials, say Robert Ridley and Yeya Toure, but we need better mechanisms and resources to develop drugs and deliver them.

Nature 430, 944 (2004). doi:10.1038/430944a

Author: Daniel Carucci

The malaria and mosquito genomes will allow us to find new drug and vaccine targets, says Daniel Carucci.

Nature 430, 947 (2004). doi:10.1038/nj7002-947a

Author: Paul Smaglik

Aaron Marcus has reason to celebrate. Last month, the physician scientist got his grant renewed for another five years — on work he started in 1955. The renewal makes him one of the longest continuously funded recipients of a grant from the US National Institutes

Nature 430, 948 (2004). doi:10.1038/nj7002-948a

Author: Tim Chapman

Chemical biology, using chemical tools to solve biological problems, is awakening interest among students and creating a new breed of researcher, says Tim Chapman.