University of Groningen, the Netherlands

A chronobiologist makes sense of circadian dysfunction in illness.

When my grandfather was dying of cancer, he found himself up most nights with my grandmother, who was succumbing to Alzheimer’s disease. A nasty side effect of some neurodegenerative diseases is the loss of a regular sleep–wake cycle. Our circadian biological clock is manifest in every one of our cells, which show daily rhythms in gene expression; cellular clocks synchronise to become organ clocks, and these determine the whole organism clock.

When Jennifer Morton at the University of Cambridge, UK, and her colleagues investigated the timing of gene expression in tissues from mouse models of Huntington’s disease, they found daily ups and downs — at least in some genes — that were similar to those in healthy animals (E. Maywood et al. J. Neurosci. 30, 10199–10204; 2010). But the mice slept and woke at random even when exposed to regular light–dark cycles. Interestingly, the researchers found that rhythmic behaviour could be restored to Huntington’s mice through another stimulus — feeding the animals at a specific time of day.

I am intrigued by this work because it highlights the relevance of chronobiology to neurodegenerative disease. The authors show that in Huntington’s, the disease disrupts behavioural manifestation of the clock; in a bizarre feedback, the progression of the disease may be exacerbated by clock dysfunction through disruption in expression of a subset of clock-controlled genes.

This work also reminds me that non-photic clock stimuli are powerful tools and can be used to set the clock when light cannot. These alternatives will be important as we try to keep the clock synchronized in our increasingly unnatural modern environment — and as we try to improve the health and quality of life for both grandmothers and grandfathers

University of Illinois at Urbana-Champaign

A materials scientist comments on two methods for three-dimensional nanofabrication.

Methods for nanofabrication are crucially important to research in all areas of nanoscience and nanotechnology because they allow for the creation of functional structures — a key step towards useful applications and devices. Many techniques are available, but all have significant shortcomings and few are compatible with true, high-volume manufacturing modes. As the director of a centre for nanomanufacturing funded by the US National Science Foundation, I am deeply interested in emerging developments in this area.

Two papers on nanofabrication caught my attention. Both use sharp, scanning tips to form three-dimensional (3D) nanostructures. This 3D capability is important because it is unavailable in established techniques such as those used in the semiconductor industry.

In one paper, Jie Hu and Min-Feng Yu at the University of Illinois at Urbana-Champaign use nanometre-scale glass nozzles with engineered shapes to electroplate metal onto solid surfaces (J. Hu and M.F. Yu Science 329, 313–316; 2010). The positions of the nozzle and substrate are precisely controlled, enabling directed ‘writing’ of nanometre-scale conducting wires in freely suspended 3D arrangements.

In the second paper, Armin Knoll at IBM Research in Zurich and his colleagues use sharp tips as sources of heat to locally strip material from thin films of molecular glasses and thereby sculpt 3D shapes with nanometre-scale accuracy (D. Pires et al. Science 328, 732–735; 2010). The authors fabricate diverse structures, including a 25-nanometre-high replica of the Matterhorn, one of the Alps’ highest peaks.

Both techniques offer valuable capabilities in nanofabrication that seem to be scalable for practical use. Successful outcomes of efforts such as these will have central roles in the translation of new knowledge in nanoscience into meaningful forms of nanotechnology.

University of Hawaii, Honolulu

A physicist and biogeochemist gets a kick out of the problem of Brownian motion and diffusion.

The movement of a particle in a gas or fluid, known as Brownian motion, exhibits two different regimes: the ballistic and the diffusive. For illustration, imagine a drunken sailor staggering back to his ship. While taking a few rapid steps, his instantaneous velocity may be quite high (ballistic regime), but his average ‘random walk’ velocity may be rather low (diffusive regime). If we were to monitor the sailor with a coarse-resolution Global Positioning System device, we would conclude that he is walking leisurely towards the docks, but we wouldn’t be able to detect his rapid motions on much shorter timescales.

Until recently, a similar problem applied to observing a Brownian particle’s instantaneous velocity. Now, Mark Raizen and his colleagues at the University of Texas at Austin have followed the ballistic motion of micrometre-sized particles on microsecond timescales, using lasers (T. Li et al. Science 328, 1673–1675; 2010). Their results not only confirm the equipartition theorem, but may also be critical to observing certain quantum effects.

My interest in the story is more practical. I am currently using molecular dynamics to calculate ionic diffusion coefficients. It was a great pleasure to see that the underlying theory and the new experimental results agree flawlessly.

In response to the authors’ observation, the media stated that Einstein had been wrong because he had predicted such an observation to be impossible. He wasn’t. As a German-speaker, I have been able to read the early landmark papers in physics, often originally in German. They include Einstein’s 1907 paper on Brownian motion. He stated that observing the instantaneous velocity of ultra-microscopic particles is impossible. He didn’t rule out the possibility of studying microscopic particles — as Li et al. have done.

Medical Research Council, University of Leicester, UK

A cancer biologist weighs up p53, metabolism and cancer.

The classic tumour-suppressor gene, p53, plays a pivotal part in halting the cell cycle and inducing programmed cell death in response to DNA damage. However, recent data suggest that it also has a role in cellular metabolism. I have become intrigued by the possibility that the inactivation of p53, which is common in tumours, also contributes to a cellular shift from a metabolic pathway called oxidative phosphorylation to a less efficient one known as glycolysis. This shift, called the Warburg effect, is characteristic of tumour cells.

Two papers shed light on this possibility. Both show that GLS2, an enzyme involved in oxidative phosphorylation, is regulated by p53 under stressed and non-stressed conditions. Arnold Levine at the Institute for Advanced Study in Princeton, New Jersey, and his colleagues also show that GLS2 increases the respiration rate in the cell’s energy-producing organelles, the mitochondria, resulting in increased generation of the cell’s fuel source, ATP (W. Hu et al. Proc. Natl Acad. Sci. USA 107, 7455–7460; 2010).

Meanwhile, Carol Prives at Columbia University in New York and her co-workers find that GLS2 expression is lost, or greatly decreased, in liver cancers, and that overexpression of GLS2 reduces the number of tumour cell colonies formed (S. Suzuki et al. Proc. Natl Acad. Sci. USA 107, 7461–7466; 2010). The results reveal that GLS2 is an important component in mediating a novel function of p53: the regulation of energy metabolism.

This is an attractive and provocative hypothesis. There are some understandable discrepancies in the data, which suggests that additional mechanisms may be contributing to the metabolic changes. Nevertheless, these two papers provide a potential mechanism linking the metabolic and genetic characteristics of tumours

Ohio State University, Columbus

A glaciologist ponders iceberg calving from a safe distance.

If the sea level rises catastrophically, it will be due to rapid retreat of Earth’s ice sheets. At the perimeter of these sheets, where warm, saline waters meet flowing ice, complex processes occur, including the fracturing of ice to form icebergs — a process known as calving. Calving is poorly understood owing to a lack of detailed observations: researchers willing to install instruments in frigid water beneath a continually collapsing wall of ice that is prone to frequent floods of meltwater have been scarce.

To better understand calving, Jason Amundsen at the University of Alaska Fairbanks and his colleagues took a clever, and much safer, approach. They deployed an impressive array of instruments several kilometres from the calving front on and near Jakobshavn Isbræ, one of Greenland’s largest glaciers. They then ‘listened’ to the sounds of calving using sophisticated audio equipment, ‘watched’ the motion of the ice with time-lapse photography and ‘felt’ the rumble of icebergs using seismometers and tide gauges.

By combining these remote observations with straightforward theory, they found that the ice front behaves similarly to road traffic, with dense packs of icebergs and sea ice forming a jam. Once this icy mélange weakens, large bergs capsize, pushing others out of the way, and the calving wall retreats. Calving continues until the front migrates far enough inland that the ice is too thick to fracture all the way through, putting on the brakes (J. M. Amundson et al. J. Geophys. Res. doi:10.1029/2009JF001405; 2010).

The results are encouraging to those interested in modelling ice-sheet behaviour because they provide a mechanism to explain relationships between ice thickness, fracturing and retreat. They also provide a great example of how a diverse arsenal of observational tools can solve the most formidable problems in Earth science.