Martha Merrow

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

John A. Rogers

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.

Richard Zeebe

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.

Gerry Melino

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

Ian Howat

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.

Dov Sax

Brown University, Providence, Rhode Island

A conservation biologist considers the role of nature reserves in a warming world.

Over the next 100 years, climate change is expected to extirpate many species from their current locations. As a scientist who studies these effects, I was surprised by the magnitude of a recent projection. Of the nearly 500 protected reserves in the San Francisco Bay area of California, more than 98% are expected to have entirely different summer temperatures going forwards, with no overlap between the warmest conditions found within these areas now and the coolest conditions in the future.

David Ackerly at the University of California, Berkeley, and his team studied the pace of climate change in the western United States (D. D. Ackerly et al. Divers. Distrib. 16, 476–487; 2010). By mapping current temperatures and those projected by a moderate warming scenario, they found that the geographical locations of specific temperatures will move by as much as 4.9 kilometres per year. This means that conditions currently experienced at a particular location could shift by hundreds of kilometres in just 50 years.

These findings have important implications for the design and management of protected areas. With climate change, most reserves will not maintain conditions that are suitable for the set of species that exists there at present. To survive, many species will need to move, either on their own or with human assistance. Accommodating this will require a major change in the perceived role of nature reserves. Traditionally, these have been managed as ‘museums’ that maintain historically accurate compositions of species and ecosystems. In the future, we may need some reserves to function as ‘way stations’, with transient compositions of species. This may be the only way to promote the long-term conservation of species that can no longer survive in their present locales.

Kenji Doya

Okinawa Institute of Science and Technology, Japan

A neuroscientist explores what brain imaging can reveal about deliberative and intuitive decision-making.

When you pick a dish from a menu, do you select it for its taste or its calculated nutritional benefits? The decision-making processes of intuition and deliberation can be considered as, respectively, model-free learning, which involves trial and error, and model-based learning — evaluating future outcomes using a pre-learned model of the results of choices. A big question is how these complementary processes are realized in the brain.

Using functional magnetic resonance imaging (fMRI) in humans, Jan Gläscher at the California Institute of Technology in Pasadena and his co-authors found neural signatures for these two modes of learning (J. Gläscher et al. Neuron 66, 585–595; 2010). The team scanned the brains of volunteers as they learned a two-step choice task. During the first part of the study, volunteers were presented with an abstract image and had to choose a left- or right-button press. Depending on which button they chose, they were then presented with another image and asked to make a second left-or-right choice to see a third image.

Over many trials, the volunteers learned the probability of a certain image resulting from a particular choice. During the half-time break, they were told that each final image would have a specific monetary reward (0, 10 or 25 cents). During the second half of the study, volunteers could use what they had learned in the first half to make profitable choices.

Analysis of the fMRI data revealed involvement of the brain’s intraparietal and lateral prefrontal cortices in model-based learning, and the ventral striatum in model-free learning. The study paints a new picture of the neuroscience of deliberation versus intuition. We should now be able to ask not only where in the brain but also by what algorithms we make decisions.

François Fuks

Free University of Brussels

A cancer biologist marvels at how key gene regulators are still revealing hidden talents.

What a difference time makes! It does not seem long since I learned, as a university student and as if it was a closed topic, that the regulation of fruitflies’ ‘homeotic’ genes — which control developmental patterns — is carried out by the Polycomb group of proteins. However, over the past couple of years, thanks to the booming field of epigenetics, these proteins have been given a new lease of life in research labs. They are proving to be multifaceted and dynamic in a range of cellular activities, including cancer progression.

In this light, work by Danny Reinberg at the New York University School of Medicine and his team captured my attention (G. Li et al. Genes Dev. 24, 368–380; 2010). The group addressed one of the burning questions in the field: how exactly does the Polycomb-repressive complex 2 (PRC2), which comprises these Polycomb proteins, recognize and home in on the genes that it regulates? The authors show that the protein encoded by the gene Jarid2, which is also important for development, forms a key component of the PRC2 complex and is involved in its recruitment to target DNA sequences. A slew of recent studies from other groups report similar observations.

The jury is still out on the precise mechanism by which JARID2 aids in the recruitment of PRC2 to its target genes. It is already evident that Jarid2 is only one piece of an elaborate puzzle, and we can expect many exciting discoveries of the remaining pieces. Clearly, Polycomb proteins, which have been well studied since they were discovered more than 50 years ago, are still yielding new insight into gene regulation and other cell activities — and are thus a formidable force to be reckoned with, in both biology and medicine.

Jean Braun

Joseph Fourier University, Grenoble, France

A geoscientist ponders possible links between erosion and Earth’s climate.

Mountain ranges have been eroding at an increasing rate over the past 60 million years — seemingly in response to a cooling climate. Some researchers have proposed that this higher rate of erosion has increased the rate at which tectonic plates move at Earth’s surface, suggesting that there is a link between Earth’s climate and its tectonics.

As a member of the Earth science community who studies the relationship between these factors, I was interested in findings by Anthony Dosseto of Macquarie University in Sydney, Australia, and his co-authors. They measured the change in the sediment erosion rate over the past 100,000 years, a period that includes the last glacial cycle (A. Dosseto et al. Geology 38, 395–398; 2010). By dating sediments from several locations in the Murrumbidgee River catchment of southeastern Australia, they discovered that the residence time — the length of time for which sediments remain on the landscape before they are eroded away — varied over geological time. The residence time was longer during warmer periods (such as around 100,000 years ago and today) and shorter during colder periods (such as around 15,000 years ago).

The authors interpret this change in residence time as a consequence of variations in vegetation type. The absence of trees in the higher parts of the catchment during cold periods resulted in an increased erosion rate, whereas the eucalyptus forest that was present during the warm periods slowed the erosion rate.

These results provide a rare quantitative estimate of the influence of vegetation and climate on erosion. This link might also be relevant to estimating how the current anthropogenic changes to Earth’s climate and vegetation affect soil erosion.

Tecumseh Fitch

University of Vienna

A cognitive biologist foresees breakthroughs in understanding vocal learning.

Vocal learning — the capacity to reproduce sounds heard in the environment — is key to human speech. Humans are alone among primates in having vocal-learning abilities, but a surprising variety of non-primates, such as songbirds and parrots, are also excellent vocal learners. The list of mammals with the ability is comparatively short, comprising humans, some whales and seals, and probably elephants. Now research on tropical bats has added another creature to the list.

Mirjam Knörnschild at the University of Erlangen-Nuremberg in Germany and her colleagues studied sac-winged bats (Saccopteryx bilineata) in Costa Rica (M. Knörnschild et al. Biol. Lett. 6, 156–159; 2010). Male Saccopteryx produce elaborate courtship displays that include complex songs. Surprisingly, young bats also produce songs, and acoustic analysis showed that as the bats grew older, their songs became more like those of the local territorial male. For about half the pups, the local male was not their father, ruling out simple genetic effects. Moreover, pups’ songs often became less species-typical over time, ruling out simple maturation. This research thus provides the first clear evidence for complex vocal learning in bats.

The finding is exciting for several reasons. First, the species is the only mammalian vocal learner that could conveniently be kept and eventually bred in the lab, opening the door to detailed scientific investigation. Second, previous work suggests that the FOXP2 gene, which is known to be involved in vocal learning in humans and birds, has also been under strong selection in bats, although we don’t yet know why. Echolocation is probably part of the answer, but this study suggests that social communication could be another. I believe that research on Saccopteryx will usher in an era of increased understanding of mammalian vocal learning.