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The human genome at ten p649

Nearly a decade on from the completion of the draft sequence of the human genome, researchers should work with the same intensity and focus to apply the results to health.


A new row to hoe p650

The time is right to revitalize US agricultural research.



Research Highlights

Climate science: No solar fix p652


Genomics: DNA packaging unravelled p652


Addiction: Junk-food junkies p652


Photonics: Carbon light catcher p652


Neurodevelopment: Baby talk p652


Metabolism: Fat from fructose p653


Ecology: Mothers stress kids out p653


Nanotechnology: Small salt superconducts p653


Neuropsychology: Morality of murder p653



Journal Club

Journal club p653

Leonid Padyukov




News briefing: 1 April 2010 p654

The week in science.


Geoengineers get the fear p656

Researchers fail to come up with clear guidelines for experiments that change the planet's climate.

Jeff Tollefson


River reveals chilling tracks of ancient flood p657

Water from melting ice sheet took unexpected route to the ocean.

Quirin Schiermeier


Space probe set to size up polar ice p658

Europe's ice-monitoring project gets a second chance after 2005 launch mishap.

Quirin Schiermeier


Synching Europe's big science facilities p659

Momentum grows for body to coordinate the continent's research infrastructure.

Cristina Jiménez


Japan plans nuclear power expansion p661

Proposal for eight new reactors and nuclear fuel reprocessing faces public opposition.

David Cyranoski


Rule poses threat to museum bones p662

Law change will allow Native American tribes to reclaim ancient bones found close to their lands.

Rex Dalton


Gene flaw found in induced stem cells p663

Key difference between reprogrammed adult mouse cells and embryonic stem cells discovered.

Elie Dolgin



Correction p663



News Features

Human genone at ten: Life is complicated p664

The more biologists look, the more complexity there seems to be. Erika Check Hayden asks if there's a way to make life simpler.


Human genome at ten: The human race p668

What was it like to participate in the fastest, fiercest research race in biology? Alison Abbott talks to some of the genome competitors about the rivalries and obstacles they faced then — and now.


Human genome at ten: The sequence explosion p670




World view: Missing weapons p672

The US defence department should be at the centre of the nation's energy policy, says Daniel Sarewitz.

Daniel Sarewitz




Sceptics and deniers of climate change not to be confused p673

Jeremy Kemp, Richard Milne & Dave S. Reay


Fishermen contribute to protection of marine reserves p673

Joachim Claudet & Paolo Guidetti


Public database for HIV drug resistance in southern Africa p673

Tulio de Oliveira, Robert W. Shafer & Christopher Seebregts




Has the revolution arrived? p674

Looking back over the past decade of human genomics, Francis Collins finds five key lessons for the future of personalized medicine — for technology, policy, partnerships and pharmacogenomics.

Francis Collins


Multiple personal genomes await p676

Genomic data will soon become a commodity; the next challenge — linking human genetic variation with physiology and disease — will be as great as the one genomicists faced a decade ago, says J. Craig Venter.

J. Craig Venter


Point: Hypotheses first p678

There is little to show for all the time and money invested in genomic studies of cancer, says Robert Weinberg — and the approach is undermining tried-and-tested ways of doing, and of building, science. This Opinion piece is part of a linked pair; see also Counterpoint: Data First by Todd Golub.

Robert Weinberg


Counterpoint: Data first p679

Large, unbiased genomic surveys are taking cancer therapeutics in directions that could never have been predicted by traditional molecular biology, says Todd Golub. This Opinion piece is part of a linked pair; see also Point: Hypothesis First by Robert Weinberg.

Todd Golub



Books and Arts

A reality check for personalized medicine p680

Bringing genetic information into health care is welcome but its utility in the clinic needs to be rigorously reviewed, caution Muin J. Khoury, James Evans and Wylie Burke.

Muin J. Khoury, James Evans & Wylie Burke review Personal Genomics and Personalized Medicine by Hamid Bolouri


How ocean stirring affects climate p681

Stefan Rahmstorf reviews The Great Ocean Conveyor: Discovering the Trigger for Abrupt Climate Change by Wally Broecker


Lost curve hits a nerve p681

Alison Abbott reviews Die Helmholtz Kurven: auf der Spur der verlorenen Zeit (The Helmholtz Curves: In Search of Lost Time) by Henning Schmidgen


Books in brief p682

Joanne Baker



News and Views

Cell biology forum: Genome-wide view of mitosis p684

An exceptionally large-scale project aimed at assigning function to all protein-coding genes in the human genome is reported on page 721 by Neumann et al.. Here are two complementary views on the experimental design and analysis, and on how useful the findings will be to cell biologists.

Jason R. Swedlow, Cecilia Cotta-Ramusino & Stephen J. Elledge


See also: Editor's summary

Quantum mechanics: The surf is up p685

Researchers have long wanted to be able to control macroscopic mechanical objects in their smallest possible state of motion. Success in achieving that goal heralds a new generation of quantum experiments.

Markus Aspelmeyer


See also: Editor's summary

Stem cells: Skin regeneration and repair p686

Different types of stem cell maintain the skin's epidermis and contribute to its healing after damage. The identity of a stem-cell type that gives rise to different epidermal-cell lineages has just been revealed.

Cédric Blanpain


Early Earth: Faint young Sun redux p687

Given that the Sun was dimmer in its youth, our planet should have been frozen over for much of its early history. That it evidently wasn't is a puzzle that continues to engage the attention of Earth scientists.

James F. Kasting


See also: Editor's summary

Drug discovery: Fat-free proteins kill parasites p689

The addition of a fatty acid to certain proteins is vital for the survival of protozoa that cause sleeping sickness and of their mammalian hosts. Compounds that target this process in the protozoa are now reported.

George A. M. Cross


See also: Editor's summary

Physiology: There is no single p p691

Why metabolic rates do not vary in direct proportion to body mass has long been the subject of debate. Progress has been made with the realization that no universal scaling exponent can be applied to them.

Craig R. White


See also: Editor's summary

50 & 100 years ago p693


Exotic matter: Another dimension for anyons p693

Non-Abelian anyons are hypothesized particles that, if found, could form the basis of a fault-tolerant quantum computer. The theoretical finding that they may turn up in three dimensions comes as a surprise.

Chetan Nayak


Astrophysics: Cosmic acceleration confirmed p694

Ana Lopes


Obituary: Joanne Simpson (1923–2010) p696

Meteorologist who brought the study of clouds to the forefront of Earth science.

Robert A. Houze, Jr



Brief Communications Arising

FTO effect on energy demand versus food intake pE1

John R. Speakman


Fischer et al. reply pE2

Julia Fischer, Linda Koch, Christian Emmerling, Jeanette Vierkotten, Thomas Peters, Jens C. Brüning & Ulrich Rüther




Quantum ground state and single-phonon control of a mechanical resonator p697

Quantum mechanics provides an accurate description of a wide variety of physical systems but it is very challenging to prove that it also applies to macroscopic (classical) mechanical systems. This is because it has been impossible to cool a mechanical mode to its quantum ground state, in which all classical noise is eliminated. Recently, various mechanical devices have been cooled to a near-ground state, but this paper demonstrates the milestone result of a piezoelectric resonator with a mechanical mode cooled to its quantum ground state.

A. D. O’Connell, M. Hofheinz, M. Ansmann, Radoslaw C. Bialczak, M. Lenander, Erik Lucero, M. Neeley, D. Sank, H. Wang, M. Weides, J. Wenner, John M. Martinis & A. N. Cleland


See also: Editor's summary | News and Views by Aspelmeyer

Origins and functional impact of copy number variation in the human genome p704

Much genetic variation among humans can be accounted for by structural DNA differences that are greater than 1 kilobase in size. Here, using tiling oligonucleotide arrays and HapMap samples, a map of 11,700 copy number variations (CNVs) bigger than 443 base pairs has been generated. About half of these CNVs were also genotyped in individuals of different ancestry. The results offer insight into the relative prevalence of mechanisms that generate CNVs, their evolution, and their contribution to complex genetic diseases.

Donald F. Conrad, Dalila Pinto, Richard Redon, Lars Feuk, Omer Gokcumen, Yujun Zhang, Jan Aerts, T. Daniel Andrews, Chris Barnes, Peter Campbell, Tomas Fitzgerald, Min Hu, Chun Hwa Ihm, Kati Kristiansson, Daniel G. MacArthur, Jeffrey R. MacDonald, Ifejinelo Onyiah, Andy Wing Chun Pang, Sam Robson, Kathy Stirrups, Armand Valsesia, Klaudia Walter, John Wei, The Wellcome Trust Case Control Consortium, Chris Tyler-Smith, Nigel P. Carter, Charles Lee, Stephen W. Scherer & Matthew E. Hurles


See also: Editor's summary

Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls p713

Copy number variants (CNVs) account for a major proportion of human genetic diversity and may contribute to genetic susceptibility to disease. Here, a large, genome-wide study of association between common CNVs and eight common human diseases is presented. The study provides a wealth of technical insights that will inform future study design and analysis. The results also indicate that common CNVs that can be 'typed' on existing platforms are unlikely to contribute much to the genetic basis of common diseases.

The Wellcome Trust Case Control Consortium


See also: Editor's summary

Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes p721

High-throughput microscopy combined with gene silencing by RNA interference is a powerful method for studying gene function. Here, a genome-wide method is presented for phenotypic screening of each of the ~21,000 human protein-coding genes, using two-day imaging of dividing cells with fluorescently labelled chromosomes. The method enabled the identification of hundreds of genes involved in biological functions such as cell division, migration and survival.

Beate Neumann, Thomas Walter, Jean-Karim Hériché, Jutta Bulkescher, Holger Erfle, Christian Conrad, Phill Rogers, Ina Poser, Michael Held, Urban Liebel, Cihan Cetin, Frank Sieckmann, Gregoire Pau, Rolf Kabbe, Annelie Wünsche, Venkata Satagopam, Michael H. A. Schmitz, Catherine Chapuis, Daniel W. Gerlich, Reinhard Schneider, Roland Eils, Wolfgang Huber, Jan-Michael Peters, Anthony A. Hyman, Richard Durbin, Rainer Pepperkok & Jan Ellenberg


See also: Editor's summary | News and Views by Swedlow et al.

N-myristoyltransferase inhibitors as new leads to treat sleeping sickness p728

African sleeping sickness, caused by Trypanosoma brucei species, is responsible for some 30,000 human deaths each year. Available treatments are limited by poor efficacy and safety profiles. However, a new molecular target for potential treatments has now been identified. The protein target is T. bruceiN-myristoyltransferase. In further experiments, lead compounds have been discovered that inhibit this protein, kill trypanosomes in vitro and in vivo, and can cure trypanosomiasis in mice.

Julie A. Frearson, Stephen Brand, Stuart P. McElroy, Laura A. T. Cleghorn, Ondrej Smid, Laste Stojanovski, Helen P. Price, M. Lucia S. Guther, Leah S. Torrie, David A. Robinson, Irene Hallyburton, Chidochangu P. Mpamhanga, James A. Brannigan, Anthony J. Wilkinson, Michael Hodgkinson, Raymond Hui, Wei Qiu, Olawale G. Raimi, Daan M. F. van Aalten, Ruth Brenk, Ian H. Gilbert, Kevin D. Read, Alan H. Fairlamb, Michael A. J. Ferguson, Deborah F. Smith & Paul G. Wyatt


See also: Editor's summary | News and Views by Cross



Intense star formation within resolved compact regions in a galaxy at z = 2.3 p733

Massive galaxies in the early Universe have been shown to be forming stars at high rates. Probing the properties of individual star-forming regions is beyond the resolution and sensitivity of existing telescopes. Here, however, observations are reported of the galaxy SMMJ2135–0102 at redshift z=2.3259, which has been gravitationally magnified by a factor of 32 by a galaxy cluster lens in the foreground. The physics underlying star formation here is similar to that in local galaxies, but the energetics are very different.

A. M. Swinbank, I. Smail, S. Longmore, A. I. Harris, A. J. Baker, C. De Breuck, J. Richard, A. C. Edge, R. J. Ivison, R. Blundell, K. E. K. Coppin, P. Cox, M. Gurwell, L. J. Hainline, M. Krips, A. Lundgren, R. Neri, B. Siana, G. Siringo, D. P. Stark, D. Wilner & J. D. Younger


See also: Editor's summary

Generation of electron beams carrying orbital angular momentum p737

Light beams can be engineered to carry orbital angular momentum, with application as, for instance, optical 'spanners' — essentially a 'twisted' variant of the more familiar optical tweezers. Here it is shown that it is, in principle, possible to engineer similar behaviour into an electron beam. Such a beam could find use in a variety of spectroscopy and microscopy techniques.

Masaya Uchida & Akira Tonomura


See also: Editor's summary

Identification of Younger Dryas outburst flood path from Lake Agassiz to the Arctic Ocean p740

Our current concepts of abrupt climate change are influenced by palaeoclimate evidence for events such as the Younger Dryas cold interval, in which massive climate changes occurred essentially instantaneously. It is thought that an injection of fresh water from the retreating Laurentide Ice Sheet altered the Atlantic meridional overturning circulation and triggered the Younger Dryas, but convincing geological evidence has been elusive. Here, a major flood event that is chronologically consistent with the Younger Dryas has been identified—through the MacKenzie River into the Arctic Ocean.

Julian B. Murton, Mark D. Bateman, Scott R. Dallimore, James T. Teller & Zhirong Yang


See also: Editor's summary

No climate paradox under the faint early Sun p744

It has been inferred that, during the Archaean eon, there must have been a high concentration of atmospheric CO2 and/or CH4, causing a greenhouse effect that would have compensated for the lower solar luminosity at the time and allowed liquid water to be stable in the hydrosphere. Here it is shown, however, that the mineralogy of Archaean sediments is inconsistent with such high concentrations of greenhouse gases. Instead it is proposed that a lower albedo on the Earth helped to moderate surface temperature.

Minik T. Rosing, Dennis K. Bird, Norman H. Sleep & Christian J. Bjerrum


See also: Editor's summary | News and Views by Kasting

Hominins on Flores, Indonesia, by one million years ago p748

Evidence for hominin activity on Flores, Indonesia, has been thought to go back at least 800,000 years, as shown by fission-track dating at Mata Menge in the Soa Basin. However, new research at another locality in the Soa Basin uses the more accurate technique of 40Ar/39Ar dating to show that hominins were living on Flores at least a million years ago.

Adam Brumm, Gitte M. Jensen, Gert D. van den Bergh, Michael J. Morwood, Iwan Kurniawan, Fachroel Aziz & Michael Storey


See also: Editor's summary

Curvature in metabolic scaling p753

It has been thought that the basal metabolic rate of organisms increases as body mass is raised to some power, p. But the value of p has proved controversial, with both 2/3 and 3/4 being proposed. It is found here that the relationship between mass and metabolic rate does not follow a pure power law at all, and requires a quadratic term to account for curvature. Taking temperature and phylogeny into account, this explains why different data sets have produced different exponents when a power law has been fitted.

Tom Kolokotrones, Van Savage, Eric J. Deeds & Walter Fontana


See also: Editor's summary | News and Views by White

The genome of a songbird p757

The genome of the zebra finch — a songbird and a model for studying the vertebrate brain, behaviour and evolution — has been sequenced. Comparison with the chicken genome, the only other bird genome available, shows that genes that have neural function and are implicated in the cognitive processing of song have been evolving rapidly in the finch lineage. Moreover, vocal communication engages much of the transcriptome of the zebra finch brain.

Wesley C. Warren, David F. Clayton, Hans Ellegren, Arthur P. Arnold, LaDeana W. Hillier, Axel Künstner, Steve Searle, Simon White, Albert J. Vilella, Susan Fairley, Andreas Heger, Lesheng Kong, Chris P. Ponting, Erich D. Jarvis, Claudio V. Mello, Pat Minx, Peter Lovell, Tarciso A. F. Velho, Margaret Ferris, Christopher N. Balakrishnan, Saurabh Sinha, Charles Blatti, Sarah E. London, Yun Li, Ya-Chi Lin, Julia George, Jonathan Sweedler, Bruce Southey, Preethi Gunaratne, Michael Watson, Kiwoong Nam, Niclas Backström, Linnea Smeds, Benoit Nabholz, Yuichiro Itoh, Osceola Whitney, Andreas R. Pfenning, Jason Howard, Martin Völker, Bejamin M. Skinner, Darren K. Griffin, Liang Ye, William M. McLaren, Paul Flicek, Victor Quesada, Gloria Velasco, Carlos Lopez-Otin, Xose S. Puente, Tsviya Olender, Doron Lancet, Arian F. A. Smit, Robert Hubley, Miriam K. Konkel, Jerilyn A. Walker, Mark A. Batzer, Wanjun Gu, David D. Pollock, Lin Chen, Ze Cheng, Evan E. Eichler, Jessica Stapley, Jon Slate, Robert Ekblom, Tim Birkhead, Terry Burke, David Burt, Constance Scharff, Iris Adam, Hugues Richard, Marc Sultan, Alexey Soldatov, Hans Lehrach, Scott V. Edwards, Shiaw-Pyng Yang, XiaoChing Li, Tina Graves, Lucinda Fulton, Joanne Nelson, Asif Chinwalla, Shunfeng Hou, Elaine R. Mardis & Richard K. Wilson


See also: Editor's summary

Impaired hippocampal–prefrontal synchrony in a genetic mouse model of schizophrenia p763

A deletion on human chromosome 22 (22q11.2) is one of the largest genetic risk factors for schizophrenia. Mice with a corresponding deletion have problems with working memory, one feature of schizophrenia. It is now found that these mice also show disruptions in synchronous firing between neurons of the prefrontal cortex and of the hippocampus, an electrophysiological phenomenon that has been linked to learning and memory and which is also thought to be disrupted in schizophrenia patients.

Torfi Sigurdsson, Kimberly L. Stark, Maria Karayiorgou, Joseph A. Gogos & Joshua A. Gordon


See also: Editor's summary

Understanding mechanisms underlying human gene expression variation with RNA sequencing p768

There is much interest in understanding the genetic mechanisms that underlie individual variations in gene expression. Here, RNA sequencing has been used to study gene expression in lymphoblastoid cell lines derived from Nigerian individuals for whom extensive genotype information is known. Numerous genetic determinants of variation in gene expression were identified, including variation in transcription, splicing and allele-specific expression.

Joseph K. Pickrell, John C. Marioni, Athma A. Pai, Jacob F. Degner, Barbara E. Engelhardt, Everlyne Nkadori, Jean-Baptiste Veyrieras, Matthew Stephens, Yoav Gilad & Jonathan K. Pritchard


See also: Editor's summary

Transcriptome genetics using second generation sequencing in a Caucasian population p773

Here, sequencing has been used to characterize the mRNA fraction of the transcriptome in Caucasian individuals, to provide a fine-scale view of transcriptomes and to identify genetic variants that affect alternative splicing. Measuring allele-specific expression identified rare expression quantitative trait loci (eQTLs) and allelic differences in transcript structure, revealing new properties of genetic effects on the transcriptome.

Stephen B. Montgomery, Micha Sammeth, Maria Gutierrez-Arcelus, Radoslaw P. Lach, Catherine Ingle, James Nisbett, Roderic Guigo & Emmanouil T. Dermitzakis


See also: Editor's summary

Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells p778

In multicellular organisms, apoptotic cells are removed from tissues by phagocytes, which recognize and engulf the dying cells. The molecular mechanisms underlying the subsequent degradation of the cells have been unclear. Here, two evolutionarily conserved genes have been identified that are required for such processing in Caenorhabditis elegans and mammals. An understanding of these events could lead to new treatments for diseases associated with poor engulfment and destruction of dying cells.

Jason M. Kinchen & Kodi S. Ravichandran


See also: Editor's summary

Spatial control of EGF receptor activation by reversible dimerization on living cells p783

Signalling through the epidermal growth factor receptor (EGFR) is preceded by its dimerization, which has typically been thought to occur through a ligand-induced conformational change. Here, the dimerization dynamics of individual EGFR molecules have been determined in living cells in real time, using a quantum-dot-based approach. Unliganded EGFR molecules undergo spontaneous and reversible dimerization; these pre-formed dimers are primed for ligand binding and signalling and are enriched at the cell periphery.

Inhee Chung, Robert Akita, Richard Vandlen, Derek Toomre, Joseph Schlessinger & Ira Mellman


See also: Editor's summary

NINJA connects the co-repressor TOPLESS to jasmonate signalling p788

In plants, the hormone jasmonoyl-isoleucine (JA-Ile) regulates growth, development and defence against pathogens. Proteins of the JAZ family repress JA-Ile-dependent gene expression, but the mechanism has been unclear. Here, an adaptor protein, NINJA, has been identified, which recruits co-repressor proteins that are known to mediate auxin-responsive gene expression as well. Hence these co-repressors are part of general repression complexes that are recruited to several different signalling pathways.

Laurens Pauwels, Gemma Fernández Barbero, Jan Geerinck, Sofie Tilleman, Wim Grunewald, Amparo Cuéllar Pérez, José Manuel Chico, Robin Vanden Bossche, Jared Sewell, Eduardo Gil, Gloria García-Casado, Erwin Witters, Dirk Inzé, Jeff A. Long, Geert De Jaeger, Roberto Solano & Alain Goossens


See also: Editor's summary

Phosphorylation of histone H3T6 by PKCβI controls demethylation at histone H3K4 p792

The amino-terminal tails of histone proteins are subject to a variety of post-translational modifications; addition or removal of these 'marks' facilitates gene activation or silencing. Here, a mechanism is defined that modulates the activity of the dual-specificity histone demethylase LSD1 during androgen-dependent transcription. Androgen-dependent signalling through protein kinase C beta I leads to phosphorylation of a histone amino acid, which prevents demethylation of an adjacent amino acid by LSD1.

Eric Metzger, Axel Imhof, Dharmeshkumar Patel, Philip Kahl, Katrin Hoffmeyer, Nicolaus Friedrichs, Judith M. Müller, Holger Greschik, Jutta Kirfel, Sujuan Ji, Natalia Kunowska, Christian Beisenherz-Huss, Thomas Günther, Reinhard Buettner & Roland Schüle


See also: Editor's summary




Keystone takes minority views on board p799

Symposia bring young minority scientists into conference-planning process.

Kendall Powell



The method and madness of publishing p799

Publishing papers involves bureaucratic and clerical challenges. Marwan Azar suggests ways to cope.

Marwan Azar


Careers and Recruitment

Gatekeeper's burden p800

It takes a special combination of thick skin and scientific enthusiasm to be a journal editor. Kendall Powell gets tips from a chosen few.

Kendall Powell




The balance scale p804

A matter of life and death.

Shelly Li


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