Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan

A synthetic chemist takes inspiration from sketching structures.

I enjoy drawing chemical structures of complex natural products and imagining how their polar functional groups, such as –OH and –NH2, interact with biopolymers. I usually first draw a carbon framework of the molecule on paper and then add the required groups. Of course, this order of 'functionalizations' has almost nothing to do with any synthetic scheme I might use for that molecule. Tedious multi-step manipulations are often needed just to introduce one oxygen or nitrogen. Making a molecule will never be as easy as drawing one.

Many research groups are trying to make it easier by devising one-step introductions of complete polar groups into carbon frameworks. One of the latest examples comes from Mark Chen and Christina White (Science, 318, 783–787; 2007). They used a new iron catalyst and hydrogen peroxide to convert specific hydrogens to hydroxyl groups on the carbon skeletons of a variety of molecules.

The catalyst seems to be able to differentiate a site of functionalization from other potentially oxidizable C–H bonds by the balance of two factors: electron-richness and steric accessibility of the bond. Chen and White were able to oxidize the antimalarial natural product (+)-artemisinin at just one predicted position to produce (+)-10-(beta)hydroxyartemisinin. Their work represents a definite advance in the direct functionalization of carbon skeletons.

Every chemist dreams about placing functional groups anywhere they want as easily as drawing them on paper. The direct C–H oxidation reaction should allow us to perform such manipulations and holds great promise for simplifying the synthesis of complex molecules.

Posted by Anna Petherick at 07:53 PM | Permalink | Comments (0) | TrackBacks (0)

Australian Weather and Climate Research, Tasmania, Australia

An oceanographer ponders the difficulty of accurately estimating abyssal-ocean warming.

Estimating how much oceans are warming and where within them heat is stored is a fascinating challenge for me and my fellow oceanographers. So far, most studies comparing observations and models of changing ocean temperatures have focused on the upper 1 kilometre of water. But what about the abyssal depths, from about 3,000 metres to the bottom? Are changes in those waters really so slow as to be essentially irrelevant to atmospheric warming?

The most comprehensive surface-to-bottom measurements of ocean temperature were collected by research ships over many months during the World Ocean Circulation Experiment in the 1990s. By comparing these observations with more recent ones from the World Climate Research Programme's CLIVAR Project, Greg Johnson and his colleagues have shown that the Pacific Ocean's abyssal waters have warmed during the past two decades (G. C. Johnson et al. J. Clim. 20, 5365–5375; 2007).

Although the temperature increase is small — up to about 0.01 °C — compared with the much larger changes in the upper 1,000 metres of the ocean, it has occurred over a thickness of several kilometres, implying a huge quantity of heat storage. The deep warming is strongest in the south-west Pacific, where newly ventilated abyssal waters enter from the south.

The Pacific warming, and abyssal warming elsewhere, means that we should start considering abyssal waters when estimating sea-level rise and the climate's sensitivity to increasing greenhouse-gas concentrations. There is plenty to find out: how does the heat reach abyssal waters? Is the warming human-induced? Designing and implementing an adequate abyssal-water-observing system is a high priority.

Posted by Anna Petherick at 07:40 PM | Permalink | Comments (0) | TrackBacks (0)

Center for the Study of Language and Information, Stanford University, California

A mathematician considers the early signs of mathematical ability.

Have you ever wondered whether there is any reliable way to predict whether a three- or four-year-old child will be good at mathematics when he or she goes to school? Many people find it surprising that an early aptitude for arithmetic is not a terribly good indicator.

A 2004 paper by the psychologist Daniela O'Neill and her colleagues at the University of Waterloo in Ontario, Canada, suggested something better. O'Neill and her team showed three- and four-year-old children a picture book and asked them to tell a story about what they saw. The researchers then measured many parameters of the children's story-telling, including the diversity of vocabulary used and the length of the sentences constructed. Two years later, the team set the same children various tests of academic achievement (D. K. O'Neill et al. First Lang. 24, 149–183; 2004).

O'Neill and her co-workers found that vocabulary and sentence length in the initial study bore little relation to the test performances a couple of years later. However, the sophistication with which the children told their stories was important. The most significant feature of this sophistication was children's ability to switch perspectives as they related the stories. Crucially, the correlation that the researchers found pertained not to later performance in reading, spelling or general knowledge, but to future mathematical ability.

I have long thought that the human capacity for mathematical thinking must predate symbolic arithmetic, because numbers are a relatively recent invention. This study backs up this idea, because it suggests that the ability to solve mathematical problems has co-opted other innate capacities that have been important for much longer in our evolution.

Posted by Brendan Maher at 01:34 PM | Permalink | Comments (0) | TrackBacks (0)

University of Texas Southwestern Medical Center, Dallas

A psychiatrist talks about finding answers that add up across all levels.

Often when we study the brain and behaviour, we fail to tie molecular events to higher-order changes in composition, to shifts in the organ's circuitry, or all the way up to changes in actions or broad mental abilities. Many scientific fields suffer from this problem of scale, but the recent explosion in techniques available for molecular biology and quantitative behavioural analysis has given neurobiology the potential to bridge many conceptual gaps.

An excellent example is a study carried out by Roberto Malinow of Cold Spring Harbor Laboratory, New York, and his colleagues (H. Hu et al. Cell 131, 160–173; 2007). They elucidated a molecular mechanism by which emotional stress and arousal promote long-term memory formation. In doing so, they brought together two well-characterized phenomena: that noradrenaline stimulates memory formation in the brain's hippocampus, and that the trafficking of a type of glutamate receptor is important for a form of plasticity in the same brain region.

Malinow's team shows that, by stimulating noradrenaline release in the hippocampus, emotional stress leads to phosphorylation of glutamate receptors. This boosts the incorporation of these receptors at the synapse — the junction between nerve cells — which, in turn, enhances synaptic function and improves memory formation. Crucially, mice with a mutation that prevents phosphorylation of the relevant part of the glutamate receptor do not show noradrenaline-mediated memory enhancement.

Impressively, this study begins with a clinically important phenomenon — memory enhancement by emotional stress — and establishes a detailed biological pathway that underlies a behavioural endpoint in an animal model. Studies such as this are what the field needs.

Posted by Anna Petherick at 12:46 AM | Permalink | Comments (0) | TrackBacks (0)