University of Chicago, Illinois

A human geneticist explores the ways that genes are regulated.

Gene expression is the cellular process that decodes the genetic information in DNA and converts it into proteins. It is regulated at many levels: when messenger RNA is transcribed from DNA; when mRNA is translated into proteins; and at the epigenetic level, when the structure of chromatin, coils of DNA wound around histone proteins, is altered. Although most discussion of gene expression focuses on the regulation of transcription, the other components of the process are also crucial. Yet little is known about how they are integrated.

Work by Tom Misteli at the National Cancer Institute in Bethesda, Maryland, and his team provides a striking example of the integration of seemingly disparate components in gene-expression regulation (R. F. Luco et al. Science 327, 996–1000; 2010). They describe how patterns of alternative splicing of newly made RNA, a key regulatory mechanism, can themselves be regulated by specific chemical modifications in the chromatin. They also found that a given set of modifications to histones predicts patterns of RNA splicing. The authors conservatively estimate that this mechanism occurs in dozens to hundreds of genes in the human genome.

This remarkable study makes a connection between a quintessential transcription-regulation mechanism, histone modification, and a post-transcriptional process, alternative splicing. It shows that chromatin can regulate not only how much of a protein, but also which protein, is made in a cell.

We have seen a surge of intriguing studies suggesting that molecules that were thought to regulate transcription also direct epigenetic modifications, modify alternative-splicing patterns and participate in the intracellular transport of RNA. These findings and the work of Misteli and colleagues provide insight into how the components of gene regulation are integrated.

University of Cambridge, UK

A comparative cognitive scientist considers the effects of high-calorie diets on the brain.

It is well established that an excessive intake of high-calorie foods, unless coupled with plenty of exercise, leads to obesity, which is a growing public-health concern. As a dancer and a scientist, I am well aware of the intimate connection between the body and the brain, and not at all surprised by the recent accumulation of evidence showing that a high-calorie diet leads to a suite of cognitive impairments, particularly in memory. What is striking, however, is how quickly the effects can occur and how selective they are.

Scott Kanoski and Terry Davidson at Purdue University in West Lafayette, Indiana, studied the effects of a high-energy diet on the memory performance of rats trained in a radial-arm maze (S. E. Kanoski and T. L. Davidson J. Exp. Psychol. Anim. Behav. Proc. 36, 313–319; 2010). They found that maintaining rats on a high-energy diet for just 72 hours was sufficient to result in a marked impairment in spatial memory. Deficits in non-spatial memory took much longer to detect, emerging only after 30 days. Spatial skills are therefore particularly vulnerable.

This finding has important implications for our own lifestyle. Clearly, consuming an excessively high-calorie diet can result in marked decreases in cognitive abilities, especially in spatial memory. The fact that this occurs in such a short space of time, prior to any significant gain in body weight, suggests that diet-induced cognitive impairments could contribute to, rather than simply be a consequence of, obesity. So hide the high-calorie foods — if out of sight is out of mind, it might just save your brain!

University of Oxford, UK

A biogeochemist weighs up the climatic influence of carbon dioxide.

Carbon dioxide constitutes a vanishingly small fraction of our atmosphere, but punches well above its weight in terms of greenhouse warming. So just how potent is it?

The geological record provides clues because, over time, Earth has oscillated between greenhouse and icehouse climates. But reconstructing coincident atmospheric CO2 concentrations is notoriously difficult. Modelling and proxy calculations are starting to converge on a single picture of atmospheric CO2 during greenhouse episodes, except for one fly in the ointment: estimates derived from the ratio of carbon isotopes in soil-precipitated carbonates are always higher than those derived from any other source.

Daniel Breecker, now at the University of Texas at Austin, and two co-workers confirm that these estimates are too large (D. O.Breecker et al. Proc. Natl Acad. Sci. USA 107, 576–580; 2010). The numbers relied on measurements of CO2 in soil pores, thought to reflect the growing-season mean. But the creation of soil carbonates is more likely during the driest and warmest parts of the growing season, when the release of CO2 from plant respiration is at a minimum.

To understand the implications of this, think of a gin and tonic. If you have less gin than you thought, you must lower the amount of tonic to get the same tasty ratio. Likewise, because there is less carbon than we thought from plant respiration, we lower our estimate of atmospheric carbon to accord with the observed ratio. The newly calculated values align beautifully with the emerging consensus. A mere 1,000 parts per million by volume (just two and a half times current atmospheric levels and similar to those predicted for AD 2100) is sufficient to induce the hottest greenhouse conditions — such as those of the Mesozoic period 251 million to 65 million years ago. CO2 truly is a heavyweight greenhouse gas.

Institute of Molecular Genetics AS CR, Prague

A molecular biologist explores how new genomic tools can be applied to wild animals.

Some time ago, I learned about a bizarre cancer that is decimating populations of the Tasmanian devil (Sarcophilus harrisii), the carnivorous marsupial popularized by the cartoon character ‘Taz’. Devil facial tumour disease (DFTD) is a rapidly progressive and metastasizing facial cancer caused by a genetically altered cell line that is transmitted between devils by biting.

Studying model organisms in the lab can make the ruthlessness of nature seem distant. But when nature is brought into the lab, one can see the power that modern tools hold for exploring a biological problem — and the limited options available for solving such problems.

Elizabeth Murchison, now at the Wellcome Trust Sanger Institute in Hinxton, UK, and her colleagues performed a comprehensive genomic analysis of the DFTD cells (E. P. Murchison et al. Science 327, 84–87; 2010). They examined not only the nuclear genome, but also that of the mitochondria, cells’ energy-generating organelles. And they performed high-throughput sequencing of RNA molecules, including small RNAs.

Their analysis confirms that DFTD is caused by the transmission of genetically identical cells. The authors also found that DFTD probably originated in Schwann cells, which wrap around neurons, and identified a set of genes that could contribute to DFTD pathology. This is an outstanding example of how next-generation sequencing technologies allow for in-depth analysis of a species that has been difficult to study using other genomic tools.

The data provide diagnostic and monitoring tools that will hopefully help in vaccine development. Until then, Taz’s future lies in the hands of natural selection and conservation efforts that aim to protect healthy animals from DFTD carriers.

Institute of Neuroscience, Sant Joan d’Alacant, Spain

A developmental neurobiologist looks at how damage induces cell birth in the adult brain.

The Spanish neuroscientist and 1906 Nobel Laureate Santiago Ramón y Cajal made hundreds of predictions about the organization and function of the nervous system. He was mostly correct, although not where the generation of new neurons in adults was concerned: this he persistently denied. The process is now widely accepted, but I find it fascinating that we have not yet reached consensus on where and when this phenomenon occurs.

Adult neurogenesis has been identified in two brain regions: the olfactory bulb and the hippocampus. Whether it also occurs in the adult neocortex, the region responsible for functions including language and thought, remains highly controversial. So I was intrigued by work by Koji Ohira of Fujita Health University in Toyoake and Takeshi Kaneko of Kyoto University, both in Japan, and their colleagues.

They found a small population of neuronal progenitor or precursor cells in the marginal zone of the adult neocortex (K. Ohira et al. Nature Neurosci. 13, 173–180; 2010). These generate interneurons — cells that modulate and synchronize the activity of principal neurons — that then disperse throughout the neocortex. Although this process is rare in normal circumstances, it is greatly enhanced by ischaemia (restricted blood supply due to damage), the authors show.

The message from Ohira et al. is intriguing and has profound implications. For example, the fact that many of the newborn interneurons express neuropeptide Y, a well-known anti-convulsant and anti-epileptogenic agent, suggests that newly generated neurons might protect the brain from damage. More sophisticated electrophysiological experiments are needed to explain how these interneurons are wired into specific neocortical circuitries and how they modulate neuronal activity.