Immunology: ‘Belt and braces’ antibodies fight HIV

Summaries of newsworthy papers include: Safeguarding our water; Translating cancer research into personalized care; Growth opportunities; Triple entanglement of superconducting quantum bits; Oceanography: Mixing it up; Cancer: RANKL rankles; Hints of exotic pairing in an ultracold gas

This press release contains:

· Summaries of newsworthy papers:

Ecology: Safeguarding our water

Cancer: Translating cancer research into personalized care

Genetics: Growth opportunities

Cancer: RANKL rankles

Quantum physics: Triple entanglement of superconducting quantum bits

Oceanography: Mixing it up

Immunology: ‘Belt and braces’ antibodies fight HIV

Physics: Hints of exotic pairing in an ultracold gas

And finally… Still waters run deep

· Mention of papers to be published at the same time with the same embargo

· Geographical listing of authors

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[1] Ecology: Safeguarding our water (pp 555-561; N&V)

A global-scale analysis that might aid the identification of areas at most risk of water security failures is reported in Nature this week.

Water is one of the most essential of natural resources, yet freshwater systems are directly threatened by human activities such as urbanization, industrialization and engineering schemes like reservoirs and irrigation. It also stands to be further affected by anthropogenic climate change.

Devising methods to reverse these trends first requires frameworks that diagnose the primary threat to water security on both a local and global level. Charles Vörösmarty and colleagues report a spatial accounting framework that provides a global analysis of threats to fresh water that, for the first time, considers human water security and aquatic biodiversity simultaneously. As well as weighing up which threats are the biggest, they also combine a range of individual threats into a collective incident threat index. From this, they show that investment by high-income countries benefits 850 million people and lowers their exposure to high levels of incident threat by 95%. In comparison, minimal investment in developing countries means that their vulnerability to incident threat remains high.

The team suggest that combining their current approach with ocean-based assessments will help to identify where improved freshwater and land management would benefit the world’s impaired coastal zones. However, the need to mobilize financial resources to support approaches remains urgent and the authors warn that without major policy and financial commitments, stark contrasts in human water security will continue to separate the rich from the poor.

Author contact
Charles Vörösmarty (City College of New York, NY, USA)
Tel: +1 212 650 7042
E-mail: [email protected]

Margaret Palmer (University of Maryland, Solomons, MD, USA) N&V author
Tel: +1 410 326 7241
E-mail: [email protected]

[2] Cancer: Translating cancer research into personalized care (pp 543-549)

The painfully slow process of cancer drug development needs a rethink, according to a Perspective in this week’s Nature. The article, which highlights practical pointers for accelerating the process, envisages an era of effective, specific cancer medicines tailored to the individual, and a marked improvement in cancer patient care.

Most anticancer drugs are developed via a series of lengthy, expensive clinical trials involving large groups of patients with molecularly uncharacterized forms of the disease. This ‘one size fits all’ strategy is hindering the goal of effective, targeted therapeutics for molecularly defined tumours, J. S. de Bono and Alan Ashworth say.

The duo outline a series of changes they believe will expedite the development of effective cancer therapies. Drug design, they argue, requires a strong biological and genetic basis. With the aid of improved animal models, fine-tuned biological hypotheses can then be tested in more rationally designed, biomarker-driven clinical trials, and information from these can then be fed back to the lab.

There is a need to raise the bar of what is expected from clinical and translational research, and, they argue, the rapid evolution and decreasing cost of increasingly high-throughput molecular technologies should lead to a ‘personalized’ or ‘stratified’ medicine, hypothesis-testing approach.

Author contact
Alan Ashworth (The Institute of Cancer Research, London, UK)
Tel: +44 20 7153 5333
E-mail: [email protected]

[3] Genetics: Growth opportunities (AOP)
DOI: 10.1038/nature09410

***This paper will be published electronically on Nature's website on 29 September at 1800 London time / 1300 US Eastern Time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included it on this release to avoid multiple mailings it will not appear in print on 30 September, but at a later date.***

Hundreds of genetic variants in at least 180 loci have been identified as having an influence on adult human height, thanks to a large genome-wide association (GWA) study. The findings, reported in this week’s Nature, provide biological insights into human growth and may also shed light on the architecture of complex genetic traits more generally.

Many human traits, including adult height, have a polygenic pattern of inheritance where the phenotype is influenced by the genetic variants at multiple loci. Joel Hirschhorn and colleagues report a GWA study of over 180,000 individuals. They identify over 100 new loci, bringing the total to 180, which in total account for about 10% of variation in human height. The loci were not clustered randomly but were enriched for genes involved in growth-related processes, which influence adult height.

The authors point out that their findings demonstrate that GWA studies are able to identify large numbers of loci that implicate potential causal genes. However, different approaches, including those targeting less common variants, will be needed to understand more fully the genetic component of complex human traits.

Author contact
Joel Hirschhorn (Broad Institute, Boston, MA, USA)
Tel: +1 617 919 2129
E-mail: [email protected]

[4] & [5] Cancer: RANKL rankles (AOP)
DOI: 10.1038/nature09387
DOI: 10.1038/nature09495

***These papers will be published electronically on Nature's website on 29 September at 1800 London time / 1300 US Eastern Time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included them on this release to avoid multiple mailings they will not appear in print on 30 September, but at a later date.***

A protein best known for its role in bone metabolism may have a key role in the development of hormone-driven breast cancers. The finding, reported in two Nature papers this week, highlights a novel target for therapeutic development.

Progestins, used in hormone replacement therapy and contraceptives, have been linked to the development of breast cancer. Teams lead by Josef Penninger and William Dougall now show that the process is mediated by the protein RANKL. Treating mice with a RANKL inhibitor dramatically reduces the incidence of progestin-driven breast cancer in a mammary tumour mouse model.

Drugs that block RANKL have already been tested in human clinical trials for osteoporosis, with promising results. So it is hoped that this will aid the testing of RANKL-based therapies for the prevention and treatment of human breast cancers.

Author contact
Josef Penninger (Austrian Academy of Sciences, Vienna, Austria) – Author paper [4]
Tel: +43 1 79044 ext 4700
E-mail: [email protected]

William Dougall (Amgen, Seattle, WA, USA) – Author paper [5]
Tel: +1 206 265 7553
E-mail: [email protected]

[6] & [7] Quantum physics: Triple entanglement of superconducting quantum bits (pp 570-578)

Two papers published in this week’s Nature cross an important threshold for quantum computation, by demonstrating the entanglement of three quantum bits (‘qubits’) in an engineered solid-state system. Three-part entanglement of qubits is necessary for quantum error correction, and is an important step towards large-scale quantum computers.

The ability to create and measure entangled states is a fundamental requirement for quantum communication and computation. In superconducting devices, entangled states of two qubits have been used to implement quantum algorithms; and in systems of nuclear spins, ions and photons, entanglement has been extended to three, eight and ten qubits, respectively. But until now, the multi-qubit entanglement needed for quantum error correction has not been demonstrated in an engineered system.

Two independent teams have now provided such a demonstration, using superconducting circuits. Leonardo DiCarlo and colleagues produce three-qubit entangled states known as Greenberger–Horne–Zeilinger (GHZ) states, and show how this production method can be used as the first step of a simple quantum error correction code. John Martinis and colleagues use a similar type of circuit to create GHZ states, and also demonstrate an efficient way of producing a different type of three-qubit entangled state, called the W state. The results of both papers bode well for the scalability of quantum information processing using superconducting devices.

Author contact
Leonardo DiCarlo (Yale University, New Haven, CT, USA) – Author paper [6]
Tel: +1 617 620 4343
E-mail: [email protected]

John Martinis (University of California, Santa Barbara, CA, USA) – Author paper [7]
Tel: +1 805 893 3910
E-mail: [email protected]

[8] Oceanography: Mixing it up (550-554; N&V)

Nitrogen to phosphorus ratios of oceanic plankton and ratios of the seawater concentrations of the nutrients nitrate and phosphate are consistently close to a mean value of 16:1. In Nature this week, a study reveals large-scale gradients in plankton nutrient utilization ratios in the Southern Ocean, an important region for global ocean productivity and carbon storage.

Thomas Weber and Curtis Deutsch model oceanic circulation and observed nutrient distribution in the Southern Ocean. They find that the nitrogen/phosphorus ratio of nutrient removal in the surface waters varies with latitude — from 12:1 in the polar ocean to 20:1 in the sub-Antarctic zone. They show that this variation results from differences in the species composition of the plankton community, rather than from adaptations across populations of similar species.

The findings will need to be taken into account when considering how major climate driven changes in the Southern Ocean might affect the carbon cycle.

Author contact
Thomas Weber (University of California, Los Angeles, CA, USA)
Tel: +1 310 206 5641
E-mail: [email protected]

Raymond Sambrotto (Columbia University, Palisades, NY, USA) N&V author
Tel: +1 845 365 8402
E-mail: [email protected]

[9] Immunology: ‘Belt and braces’ antibodies fight HIV (pp 591-595; N&V)

An unusual form of antibody binding may form part of our immune response to HIV infection, a Nature paper suggests. The find has implications for vaccine design.

Our bodies produce antibodies in response to infection. Most are highly specific, binding to just one antigen, but less specific polyreactive antibodies can bind to a range of antigens. In the case of HIV, specific and polyreactive binding can be combined to increase the binding strength of antibody to target, Michel Nussenzweig and colleagues report.

The team studied 134 different antibodies all directed at the HIV envelope glycoprotein gp140 and cloned from 6 patients. Three-quarters of the antibodies were polyreactive, binding with high affinity to one gp140 site and low affinity to any number of other sites on the viral surface.

Author contact
Michael Nussenzweig (Rockefeller University, New York, NY, USA)
Tel: +1 212 327 8098
E-mail: [email protected]

Andreas Plückthun (University of Zürich, Switzerland) N&V author
Tel: +41 1 635 5570
E-mail: [email protected]

[10] Physics: Hints of exotic pairing in an ultracold gas (pp 567-569; N&V)

Observations of an ultracold gas of lithium atoms confined in one-dimensional ‘tubes’ have provided tantalizing hints of an exotic state of matter that was proposed more than forty years ago. The results, reported this week in Nature, may signal the existence of ‘polarized superconductivity’, and illustrate the use of ultracold trapped atoms as a versatile tool for investigating the behaviour of complex quantum systems.

Superconductivity and magnetism do not generally coexist, because the prevalence of one electron spin orientation (which gives rise to magnetism) disrupts the normal process by which electrons of opposite spin and momentum combine to form superconducting pairs. In the 1960s, four physicists (known by their initials as FFLO) proposed an exotic pairing mechanism, which allows superconducting and spin-polarized (magnetized) regions to coexist on a microscopic scale. Despite many efforts to observe polarized FFLO superconductivity, it has remained elusive — in part because, in a normal three-dimensional system, this state is predicted to give way to other phases in most conditions.

In contrast, in a one-dimensional system the FFLO state is predicted to occupy a large part of the phase diagram. Yean-an Liao and colleagues accordingly designed an experiment in which ultracold lithium atoms in two different spin states were confined in an array of one-dimensional regions formed by an optical trap. The authors were able to map out a phase diagram for this system that is consistent with theories of FFLO physics, giving hope that the FFLO state will be soon be observed.

Author contact
Yean-an Liao (Rice University, Houston, TX, USA)
Tel: +1 713 348 2663
E-mail: [email protected]

Immanuel Bloch (Max Planck Institute for Quantum Optics) N&V author
Tel: +49 89 32905 238
E-mail: [email protected]

[11] And finally… Still waters run deep (pp 579-582)

A glacier can hold a substantial volume of water within crevasses that extend tens of metres from its base deep into the overlying ice, reports a Nature paper. The findings will help scientists to model glacier movement more accurately, in order to reconstruct past ice-sheet behaviour and predict future ice stability and sea level rise.

Water within glaciers and ice sheets could strongly influence ice velocity and ultimately the rate of sea level rise, but direct measurement of the magnitude and characteristics of water stored within glaciers has proved difficult.

Joel Harper and colleagues carried out a suite of field experiments on Bench Glacier in Alaska, a temperate valley glacier about seven kilometres long and up to 200 metres thick. Using a combination of direct borehole observations and radar and seismic imaging they reveal an extensive network of interconnected basal crevasses filled with water. The crevasses hold a volume of water equivalent to a ten-centimetre-deep layer of water covering the bed of the glacier, enough to be an important factor for future ice-sheet modelling, and indicating that the glacier’s basal drainage system is much more three-dimensional than previously thought, extending high into the overlying ice mass.

Author contact
Joel Harper (University of Montana, Missoula, MT, USA)
Tel: +1 406 243 5867
E-mail: [email protected]

ALSO IN THIS ISSUE…

[12] Decay of aftershock density with distance does not indicate triggering by dynamic stress (pp 583-586)

[13] Two enzymes bound to one transfer RNA assume alternative conformations for consecutive reactions (pp 612-616)

ADVANCE ONLINE PUBLICATION

***These papers will be published electronically on Nature's website on 29 September at 1800 London time / 1300 US Eastern Time (which is also when the embargo lifts) as part of our AOP (ahead of print) programme. Although we have included them on this release to avoid multiple mailings they will not appear in print on 30 September, but at a later date. ***

[14] U1 snRNP protects pre-mRNAs from premature cleavage and polyadenylation
DOI: 10.1038/nature09479

[15] Structural basis for semaphorin signalling through the plexin receptor
DOI: 10.1038/nature09473

GEOGRAPHICAL LISTING OF AUTHORS…

The following list of places refers to the whereabouts of authors on the papers numbered in this release. For example, London: 4 - this means that on paper number four, there will be at least one author affiliated to an institute or company in London. The listing may be for an author's main affiliation, or for a place where they are working temporarily. Please see the PDF of the paper for full details.

AUSTRALIA
Albany: 1
Brisbane: 3
Crawley: 3
Lismore: 1
Melbourne: 3
Nathan: 1
Nedlands: 3
Parkville: 3
Perth: 3
Sydney: 4

AUSTRIA
Vienna: 4

CANADA
Hamilton: 3
Montreal: 3
Toronto: 4
Waterloo: 6

CROATIA
Split: 3
Zagreb: 3

ESTONIA
Tartu: 3

FINLAND
Helsinki: 3
Nijmegen: 3
Oulu: 3
Rovaniemi: 3
Seinajoki: 3
Tampere: 3
Turku: 3
Vasa: 3

FRANCE
Palaiseau: 10
Paris: 3

GERMANY
Berlin: 9
Cologne: 4
Erlangen: 4
Greifswald: 3
Kiel: 3
Leipzig: 3
Lübeck: 3
Munich: 3
Neuherberg: 3
Regensburg: 3
Stechlin: 1

HONG KONG
Hong Kong: 1

ICELAND
Kopavogur: 3
Reykjavik: 3

ITALY
Bolzano: 3
Cagliari: 3
Milan: 3
Sassari: 3

JAPAN
Kanagawa: 13
Kyoto: 12
Osaka: 15
Tokyo: 13
Tsukuba: 7
Yokohama: 15

NETHERLANDS
Amsterdam: 3
Groningen: 3
Leiden: 3
Rotterdam: 3

NORWAY
Trondheim: 3

SINGAPORE
Singapore: 3, 10

SPAIN
Barcelona: 3, 5

SWEDEN
Gothenburg: 3
Malmö: 3
Stockholm: 3
Uppsala: 3

SWITZERLAND
Lausanne: 3

UNITED KINGDOM
Bath: 3
Cambridge: 3
Edinburgh: 3
Exeter: 3
Glasgow: 3
Leeds: 3
Leicester: 3
London: 2, 3
Oxford: 3
Sutton: 2

UNITED STATES OF AMERICA

Alabama
Huntsville: 3

California
Los Angeles: 3, 8
Menlo Park: 12
Oakland: 3
Riverside: 12
San Francisco: 3
Santa Barbara: 7
Stanford: 3
New Haven: 6

Idaho
Boise: 11

Illinois
Chicago: 9, 15
Evanston: 3

Maryland
Baltimore: 3
Bethesda: 3, 9
Frederick: 3

Massachusetts
Boston: 3, 9
Cambridge: 3, 5, 9
Framingham: 3
Waltham: 5

Michigan
Ann Arbor: 1, 3

Mississippi
Jackson: 3

Missouri
St Louis: 3

Montana
Missoula: 11

New Hampshire
Durham: 1

New York
Bronx: 3
Ithaca: 10
New York: 1, 9

North Carolina
Chapel Hill: 3
Winston-Salem: 3

Pennsylvania
King of Prussia: 3
Philadelphia: 14

Texas
Houston: 3, 10

Washington
Seattle: 1, 3, 5

Wyoming
Laramie: 11

PRESS CONTACTS…

From North America and Canada
Neda Afsarmanesh, Nature New York
Tel: +1 212 726 9231
E-mail: [email protected]

From Japan, Korea, China, Singapore and Taiwan
Mika Nakano, Nature Tokyo
Tel: +81 3 3267 8751
E-mail: [email protected]

From the UK
Rebecca Walton, Nature, London
Tel: +44 20 7843 4502
E-mail: [email protected]

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Published: 29 Sep 2010

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