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Volume 453 Issue 7197, 12 June 2008

A low tissue pH is often associated with disease - for example cancer, ischaemia and inflammation - so a technique that could image tissue pH would have considerable potential for disease diagnosis and for monitoring response to treatment. A new, non-invasive method of pH imaging has now been devised, and demonstrated by monitoring the extracellular pH in living mice. It combines magnetic resonance imaging (MRI) and the intravenous injection of carbon-13-labelled bicarbonate - made extremely sensitive to detection by the use of dynamic nuclear polarization. Bicarbonate is a natural buffer in mammalian tissues, resisting pH change via interconversion with carbon dioxide in the reaction catalysed by carbonic anhydrase. The ratio of labelled bicarbonate to carbon dioxide can be used to calculate pH from the Henderson-Hasselbalch equation. Images of mice with implanted tumours confirmed a reduced tumour pH, and suggest that clinical application of the new technique is a realistic proposition. On the cover, colur in the images represents pH. Cover graphic: Mikko Kettunen & Rebekah McLaughlin.

Editorial

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    Translational medicine is a key addition to the biomedical research enterprise. Policy-makers and research leaders now must build the infrastructure to take discoveries from the bench to application.

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    ITER will cost more to build than previously thought. Now is the time to be honest about how much.

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    The use of 'dignity' as the foundation for an ethical law in Switzerland is compromising research.

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    A chasm has opened up between biomedical researchers and the patients who need their discoveries. Declan Butler asks how the ground shifted and whether the US National Institutes of Health can bridge the gap.

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    Results can be thrust from bench to bedside, but there is also much to be learned by pushing the other way. Heidi Ledford tells tales of clinical trials that have prompted a change in tack.

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    The Ludwig Institute for Cancer Research is focused on translating research into cures. Helen Pearson investigates whether its sometimes unusual methods are producing results.

    • Helen Pearson

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    If Japan is to become a front-runner in pharmaceutical development, it must not only speed up its approval of new drugs, but also enhance its own research capabilities, argue Kaori Tsuji and Kiichiro Tsutani.

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    Michael Barron explores how physics, psychology and fashion have influenced concert hall acoustics.

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    Protease enzymes cut other proteins into pieces, but some can be blocked by inhibitors. One such inhibitor binds to the substrate rather than the enzyme, suggesting a new tactic for drug discovery.

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    A long-sought but short-lived molecule has been made and characterized for the first time. This compound decays at low temperatures using an unusual trick — a mechanism known as quantum tunnelling.

    • Markku Räsänen
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    A monkey model of Huntington's disease created by gene transfer is only a work in progress. But as a technological feat it offers great promise for fathoming this devastating condition.

    • Stéphane Palfi
    • Bechir Jarraya
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    Periodic oscillations have been observed in what should be straightforward exponential decay curves of two radioactive isotopes. An entirely mysterious phenomenon, its proposed cause seems equally exotic.

    • Philip M. Walker
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    In a disordered medium, a quantum particle can literally stop itself in its tracks. This localization phenomenon can be observed directly using the coldest known form of matter, caught in a laser trap.

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