University of St Andrews, UK

An optical physicist sees beyond fluorescent labels.

Many a molecular biologist likes to watch molecules move around inside living cells, particularly in real time. The job is usually done by tethering a fluorescent tag to interesting biological molecules and following their movements by means of the tag's glow. But fluorescent tags are often bigger than the molecules they label, so frequently perturb their movements. Better to watch intracellular dramas without millstones around the actors' necks. But how?

A twist on 'Raman scattering' may hold the answer. Normally, when a laser is shone at a molecule, the molecule scatters most of the light at the same frequency at which it was emitted by the laser. A tiny amount — Raman scattered light — is scattered at different frequencies. These frequencies indicate the chemical bonds in the molecule, and can thus identify it as a fingerprint identifies a person. If only Raman signals were stronger, they would be suitable for real-time microscopy on a molecular scale.

A second laser provides the twist — and the necessary amplification. Sunney Xie of Harvard University and his colleagues have found that another laser can enhance the contrast of an image, improving the sensitivity over previous studies by four orders of magnitude (C. W. Freudiger et al. Science 322, 1857–1861; 2008). For this to work, the two lasers must coincide on the sample, and the difference in their frequencies must exactly match that of a specific molecular vibration of a certain chemical bond in the sample. The background noise is eliminated and the signal is amplified.

This method is both versatile and powerful; the authors used it to observe the uptake of omega-3 fatty acids by human lung-cancer cells and the changing distribution of two drugs as they were absorbed by mouse skin. I think this could spur the development of tag-free molecular movie machines for all.

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Old Dominion University, Norfolk, Virginia

An astrobiologist considers life's oldest oxygen.

The presence of atmospheric oxygen would have been necessary for the evolution of eukaryotes — organisms that group their genetic material into a membrane-bounded nucleus — so the question of when oxygen first became available is important in dating their rise. The availability of such oxygen is linked to the evolution of cyanobacteria, oxygen-producing microbes that appeared early in Earth's history and exist to this day.

Fossil microbial mats preserved in the Pongola Supergroup, a rock succession in South Africa, suggest that cyanobacteria were already highly diverse 2.9 billion years ago. But conclusive proof of their presence can be provided only by the presence of hydrocarbon biomarkers — stable chemical compounds found in the walls of single-celled organisms.

Work by Jacob Waldbauer at the Woods Hole Oceanographic Institution in Massachusetts and his colleagues focuses on biomarkers from shallow-marine deposits in the younger, 2.6-billion-year-old sedimentary rocks preserved in South Africa's Transvaal Supergroup. Detailed laboratory analyses extracted biomarkers called hopanes, possibly attributable to cyanobacteria, as well as steranes, biomolecules typically found in eukaryotes (J. R. Waldbauer et al. Precamb. Res.10.1016/j.precamres.2008.10.011; 2008). The biosynthesis of steranes requires free oxygen; therefore, the fossil steranes imply that oxygen was readily available 2.6 billion years ago. This is at least 200 million years before a persistent oxygen-containing atmosphere is thought to have arisen.

Waldbauer et al. show that cyanobacteria had colonized the floor of Earth's ancient oceans by 2.6 billion years ago at the latest. Free oxygen has been available in the atmosphere ever since, and set the stage for the evolution of more complex organisms.

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US Geological Survey, Pasadena, California

A seismologist considers a new method of earthquake prediction.

I am acutely aware that numerous methods of earthquake prediction at one time held great promise, but fell apart under proper scrutiny. In recent years, I have heard about many studies purporting to uncover evidence of electromagnetic precursors, almost all of which involved weak or non-existent statistical analysis.

But occasionally I come across research that is not so easy to dismiss. For example, data from the French micro-satellite DEMETER, which was launched in 2003 to investigate electromagnetic perturbations in the ionosphere, have been analysed by a team of French and Czech researchers (F. Nmec et al. Geophys. Res. Lett. doi:10.1029/2007GRL032517; 2008). These authors find that there are very-low-frequency electromagnetic fluctuations in the ionosphere above the epicentres of moderate and large earthquakes that occur a day or two before the ground starts to shake.

Nmec and colleagues' results could be fatally flawed. If electromagnetic disturbances are generated when earthquakes occur, what are apparently true signals of one earthquake could actually be signals related to a preceding shock. Or the analysis might go awry because of subtle data-selection biases. But if there are fatal flaws, they are not obvious.

In any case, as the authors themselves emphasize, the significance of the DEMETER results can be demonstrated only when data from many earthquakes are averaged. This highlights a key point: it is entirely possible for precursors to be real but of no use for prediction. If earthquake scientists can separate consideration of earthquake precursors from the highly charged debates about earthquake prediction, the research community might just learn something about earthquake processes.

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Kastler Brossel Laboratory, CNRS, France.

A quantum-gas specialist learns about crystals from his own science.

Crystals can behave as electrical insulators or conductors. In a few crystals and under the right conditions, electrons flow perfectly. And in a subset of these superconducting crystals, the minimum temperature for perfect conduction is bizarrely warm.

On the whole, physicists have tried to explain this using models with a small number of parameters, such as the probability of an electron jumping between two sites, and the interaction energy between two neighbouring electrons. Extensive laboratory studies measuring every conceivable property of the curious crystals confirm several predictions of these models, but their general solution is still hotly debated.

Recently, a couple of research groups have been casting around for less obvious ways to understand superconducting crystals, and turned to the field that is my bread and butter: quantum gases. They have modelled electrons zooming through these crystals using gases of cold potassium atoms moving around in a space demarcated by laser beams — a kind of egg box made with light.

In December, a group led by Immanuel Bloch detected cold potassium gas switching to a state with exactly one atom per compartment of the egg box. Such an ordered state is considered a key ingredient for superconductivity. Bloch's team was not the first to see the switch, but the group's measurement of the size of the gas revealed a crucial property of this phase: its incompressibility (U. Schneider et al. Science 322, 1520–1525; 2008).

This means that quantum gases are insulators as well as conductors, making the experimental analogy to superconducting crystals more complete — and making them more useful playthings for scientists studying superconducting crystals.

Posted by Anna Petherick at 03:54 PM | Permalink | Comments (0) | TrackBacks (0)

Imperial College London, UK

An organic chemist highlights an ingenious way to make radiotracers.

In diagnostic medicine, radiotracers are used to image molecules in the body by methods such as positron emission tomography. Radionuclides such as carbon-11, nitrogen-13 or fluorine-18 are incorporated into molecules normally used by the body, such as glucose, or into designer organic molecules that bind to receptor sites within the body and provide valuable information about how they function. But the short half-lives of these radionuclides — 20, 10 and 110 minutes respectively — mean that the chemical reactions used to make the tracers must be speedy.

One step that is often time-consuming is separating out synthesized radiotracers from the large quantities of unreacted precursor molecules used to ensure efficient use of the radionuclide.

A new approach to this problem has been reported that exploits fluorous solid-phase extraction, a technique that separates molecules on the basis of their fluorine content (R. Bejot et al. Angew. Chem. Int. Edn 48, 586–589; 2009). Veronique Gouverneur at the University of Oxford, UK, and her team designed heavily fluorinated precursor molecules — typically containing 13–25 fluorine atoms — that release their fluorine-rich section on reaction with a radionuclide. This generates a mixture of the desired defluorinated radiotracer and undesired fluorine-rich molecules. The mixture is then passed through a bed of fluorinated silica, which retains the heavily fluorinated compounds, leaving the radiotracer to emerge free of contaminants and ready for clinical use.

Gouverneur's work opens the door to the development of a plethora of new synthetic chemistry methods and the creation of new radiotracers for use in areas including tumour imaging and neuroimaging.

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University of California, Davis

A cell biologist looks at the risk and promise of a new insight into stem cells and cancer.

I study both stem and tumour cells, and am fascinated by their close relationship. Both exhibit pluripotency — the capacity to develop into any cell type — and the ability to cause cancer. Even some apparently normal stem cells can cause tumours, whereas others, sometimes from the same culture, lack this power. It seems that not all stem cells are created equal — even in the same dish.

A recent paper from Mickie Bhatia's group (T. E. Werbowetski-Ogilvie et al. Nature Biotechnol. 27, 91–97; 2009) is the first to directly address this heterogeneity in human embryonic stem cell (ESC) cultures. The team found that individual human ESC lines contain significant subpopulations that vary in a number of ways, including in tumorigenicity.

Variant human ESC lines were about 20 times more tumorigenic than the cultures they had been derived from and showed small changes in chromosome structure. These could be identified by array-based comparative genomic hybridization (aCGH), but were not detectable by standard karyotyping. Thus for 'normal' stem cells being considered for use in regenerative medicine, karyotyping is not enough. Screening should also include aCGH, and perhaps an analysis of gene-expression patterns.

This previously covert diversity has implications for both tumour biology and medical applications involving stem cells. It may shed light on the 'locked in' self-renewal that is emerging as an important feature of many sorts of tumour and tumour stem cell.

The heterogeneity of human ESC cultures represents an additional hurdle in terms of producing safe stem-cell-based transplants. At the same time, it may offer a valuable bonus: the chance to purify variant human ESC sub-lines that are less tumorigenic.

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