Nature Journal Club - Blog Posts

Jan Zaanen

clok — 2009-11-05T22:17:48+00:00

Leiden University, the Netherlands

A theoretical physicist journeys to a hairy black hole's horizon.

Rumour has it that Steven Spielberg is producing the ultimate science fiction movie, using state-of-the-art general-relativity simulations to create a realistic image of the warped space-time near a black hole. But wouldn't it be great to see such worlds in real life? In fact, you can: by extending your eyesight with 'AdS/CFT', a mathematical result of string theory that describes a 'through the looking-glass' experience that would embarrass the imagination of Lewis Carroll.

AdS/CFT states that information about the strange world of the black hole is, in a very indirect way, encoded in or 'imaged' by the properties of certain quantum-weird forms of matter. Scientists realized recently that these 'quantum critical' states of matter are routinely produced in condensed-matter laboratories. But a particular prediction of AdS/CFT made the string theorists nervous: the event horizon of the special black hole that is imaged by the quantum critical electrons seems to imply that the latter should show a macroscopic entropy at zero temperature. It has further been predicted that the black hole would be unstable and would eventually suck up 'stuff' from its surroundings, covering its horizon with 'hair' (S. A. Hartnoll et al. J. High Energy Phys. 2008, 015; 2008). In the electron system, out of the blue and at a quite low temperature, some unexpected order will set in that removes the ground-state entropy, giving it a unique ground state.

Intriguingly, I learned the other day that condensed-matter experimentalists, unaware of the string theorists' nervousness, are now in the grip of the same idea. The latest thermodynamic experiments on quantum-critical electrons are suggestive (albeit inconclusive) of a developing zero temperature entropy — for the experimentalists, a catastrophe — interrupted at a very low temperature by the onset of an exotic quantum liquid crystalline order (Z. Fisk Science 325, 1348–1349; 2009). It may be that we don't need spacecraft or Spielberg to visit black holes, just a little patience with the condensed-matter experimentalists.

Jonathan Weissman

clok — 2009-10-29T20:13:51+00:00

University of California, San Francisco

A biochemist looks at how DNA sequencing can reveal more than just sequences.

Huge advances in DNA sequencing have allowed us to readily determine the sequence of almost any living (and a few extinct) species. Yet arguably, most biological insight comes from work on five model organisms: Escherichia coli, baker's yeast, roundworms, fruitflies and mice. Unfortunately, many important biological processes are not captured in these creatures.

Papers from two groups, one led by Andrew Camilli of Tufts University in Boston, Massachusetts, the other by Brian Akerley at the University of Massachusetts in Worcester, describe new genetic tools that allow the quantitative dissection of gene function in a wide range of microorganisms (T. van Opijnen et al. Nature Methods 6, 767–772; 2009; and J. D. Gawronski et al. Proc. Natl Acad. Sci. USA 106, 16422–16427; 2009). These studies combine exhaustive transposon mutagenesis — whereby thousands of small DNA segments, or transposons, are introduced into the genome to mutate many genes — with massively parallel, or 'deep' sequencing of transposon/chromosome junctions to monitor the consequences of the loss of single or pairs of genes on the organisms' traits.

The real power of the approaches comes from the deep sequencing, which tracks the abundance of individual transposon mutants after they have been subjected to a stress. Knowing by how much each mutant has grown or suffered under the stress provides a measure of the relative roles that the mutated genes have.

I find it particularly gratifying that the advances in deep sequencing that have allowed us to catalogue so many genes from so many organisms can now be harnessed to help us figure out what these genes actually do.

Corinne Le Quéré

clok — 2009-10-23T21:50:06+00:00

University of East Anglia, UK and the British Antarctic Survey

An oceanographer marvels at the good timing of shrimp.

For many marine organisms, the timing of egg hatching is key to species survival because the time window in which larvae can survive is very short. If eggs hatch too early, they starve before their food source — the spring phytoplankton — blooms. If they hatch too late, they also miss the bloom.

I'm amazed by how often nature gets things right. In most of the North Atlantic, shrimp eggs hatch just a few days before the spring bloom. Peter Koeller of the Bedford Institute of Oceanography in Dartmouth, Nova Scotia, showed that the development and hatching time of shrimp are influenced by local deep-ocean temperature (P. Koeller et al. Science 324, 791–793, 2009). This is not surprising, because eggs develop in the deep ocean and their growth rate depends on temperature.

What is surprising is that the shrimp spawn on the right day of the year across the North Atlantic, even though temperatures in the deep ocean vary from one area to the next and do not influence the timing of the spring bloom. Through evolution, the shrimp have adapted to local temperature patterns to spawn at just the right time.

However, this could prove to be a problem for shrimp and the many other zooplankton, fish and shellfish species that have adapted their spawning habits to local conditions. What will the survival rate of larvae be if deep-ocean temperatures rise, or if the spring bloom occurs earlier? How much time do organisms need to sense and adapt to such changes? These new data will help us to understand the complex interdependence of marine ecosystems, and possibly help to detect potential mismatches between egg hatching and food-source availability.

Sam Wang

clok — 2009-10-15T15:15:08+00:00

Princeton University, New Jersey

A neuroscientist explores the energy efficiency of the brain.

Considering its substantial processing capacity, the human brain consumes remarkably little power — about as much as an idling laptop computer. So I was interested to learn that action potentials — the electrical 'spikes' that are the fundamental units of neuronal activity — are likewise remarkably energy efficient (H. Alle et al. Science 325, 1405–1408; 2009).

During a spike, the voltage across a neuron's membrane is reversed when sodium ions flow into the cell and potassium ions move out. This reversal spreads as a wave down the neuron's axon towards its terminals, where it triggers synaptic transmission to other neurons.

Henrik Alle of the Max Planck Institute for Brain Research in Frankfurt, Germany, and his colleagues recorded charge movements at axon terminals in mammalian hippocampal neurons. They found that sodium and potassium ions flow at largely non-overlapping times, with more than 75% of all charge contributing unopposed to the rise or fall of a spike.

Such efficiency comes as a surprise. These axons outperform the much-studied squid giant axon by a factor of three. If the findings apply to other mammalian neurons, brain tissue may support more firing than suspected. The authors suggest that synaptic transmission may dominate the energy budget of brain tissue.

These results have implications for functional magnetic resonance imaging, which measures increases in blood oxygenation in the brain as an indicator of neural activity. What causes the blood-oxygen boost is unknown: suggested triggers include synaptic transmission and action potentials. This paper is evidence for the former, because energy-intensive events such as synaptic signalling are more likely to be oxygen-hungry and to stimulate blood flow. The idea is supported by other recent evidence — a wonderful convergence.

Judith E. Mank

clok — 2009-10-07T23:47:15+00:00

Edward Grey Institute, Department of Zoology, University of Oxford, UK

An evolutionary biologist compares genomic complexity to modern art.

Like many students of evolutionary biology, I was taught that genes encode physical traits, or 'phenotypes', that are the focus of natural selection — a model with clear, direct links and few, if any, complications. Over the past few years, I have found it increasingly difficult to reconcile this simple model connecting genes and the organisms they encode with the burgeoning data of systems biology, which show the genome as a heaving tangle of interconnections. Given the complexity of the genome, how can selection target any single gene without unintended consequences?

Trudy Mackay at North Carolina State University in Raleigh and her collaborators have begun to resolve the opposing genomic and evolutionary world views by examining the systems genetics that underlie phenotypes in the fruitfly Drosophila melanogaster (J. F. Ayroles et al. Nature Genet. 41, 299–307; 2009). They do this by comparing data on the abundance of more than 10,000 DNA transcripts with whole-organism traits, such as fitness and lifespan, in 40 fruitfly lines.

The researchers show that aggregates of genes correlate with distinct characteristics in flies, and that these modules are connected, with groups of genes associated with multiple phenotypic traits. This elegant complexity is best conveyed by the figures in the paper, some of which look as though they were lifted off the walls of a modern-art gallery.

The group's work provides a post-genomic framework for dissecting the intricate underpinnings of organismal biology. More importantly, the paper demonstrates that key topics in traditional evolutionary studies, such as heritability, and more recent concepts, such as pleiotropy (whereby one gene affects multiple traits), are related. As such, they must be considered together to build a complete understanding of how selection acts through the phenotype to sculpt the genome.

Bruce R. Conklin

clok — 2009-09-30T20:18:58+00:00

Gladstone Institute of Cardiovascular Disease, San Francisco, California

A geneticist wonders why we need to sleep.

Scientists can have a love–hate relationship with sleep. We know that it is vital for our health, but not the reasons why. We celebrate dreams that provide inspiration, but often dismiss sleep as a chore.

Yet deep sleep can provide insight into vexing problems. In 1920, pharmacologist Otto Loewi famously had a recurring dream that suggested how he could demonstrate neurotransmission in the lab. The key experimental details escaped him until he captured the dream in a bedside notebook. Later that day, he performed his Nobel-prizewinning experiments with the aid of a few frog hearts and a water bath.

Now, a team led by Ying-Hui Fu reports that a single mutation in a gene called DEC2 can cause people to sleep for only about six hours per night instead of the usual eight (Y. He et al. Science 325, 866–870; 2009). This mutation seems to be exceedingly rare, with only two carriers found so far. Only by introducing this mutation into transgenic mice and fruitflies could the researchers show compelling evidence of the mutation's effect. These two additional waking hours each day are quite remarkable when you consider that, over 80 years, this would add up to more than 8 years of extra productivity!

Why are extreme short sleepers so rare? Surely evolutionary pressures should favour less sleep? In prehistoric times, short sleepers would have had more time to hunt, gather food and guard against predators. In modern society, we must constantly balance home, work and other demands. Sleep is often sacrificed, so a drug that could provide hours of extra productivity would be hugely popular.

A better understanding of the reasons for sleep could provide a rationale for getting more of it. In the meantime, I will keep a notebook by my bedside as a dream catcher.

Mikiko C. Siomi

clok — 2009-09-23T22:56:47+00:00

Keio University School of Medicine, Tokyo, Japan

A biologist praises a mouse model of autism inheritance.

Autism, a neurodevelopmental disorder that affects people's social abilities, has both genetic and non-genetic causes. Chromosomal abnormalities account for 10–20% of autism cases, with duplication of a long stretch of chromosome 15 being the most common. I was excited to read that a mouse model with a similar chromosomal duplication has been generated (J. Nakatani et al. Cell 137, 1235–1246; 2009). These mice exhibit the inflexible behaviour, social abnormalities and increased anxiety often observed in people with autism. However, whereas the engineered mice inherit the duplication from their fathers, human autism cases caused by such a duplication are usually inherited maternally. Further genomic analysis in the mice should find the reason for this discrepancy.

This model deserves special attention as the chromosomal duplication is stably maintained between generations. Also, genes in the duplicated regions seem to work; that is, the expression levels of genes — including HBII52, which affects the function of serotonin, a molecule that has cognitive roles in mood, memory and learning — are higher in the mice, as would be expected with a gene duplication.

Accumulated evidence shows that variations in gene-copy number, such as the chromosomal duplication in this model, are associated with susceptibility to various human diseases; cancer cells, for example, tend to have high gene-copy numbers. Thus, this mammalian model may help us to understand the molecular basis of autism and to investigate the contribution of gene duplication in other genetic diseases. This should encourage many researchers to produce other model systems for copy-number variation using similar techniques; systems that may clarify the contribution of chromosomal duplication, or even the lack of it, in common diseases such as diabetes.

Rusty Feagin

bmaher — 2009-09-17T15:37:12+00:00

Texas A&M University, College Station, Texas

A coastal ecologist sees the hidden effects of hurricanes.

As part of my job, I often drive around looking at the impacts of hurricanes in coastal areas. The one thing that stands out from such trips is that the devastation always looks the same, regardless of where I am — the boats perched on the streets, the newly house-less stilts near the beach, the furniture on a lawn covered in mould.

I realized though, after reading a recent article by Hongcheng Zeng of Tulane University in New Orleans, Louisiana and his colleagues (H. Zeng et al. Proc. Natl Acad. Sci. USA 106, 7888–7892; 2009), that I need to be concerned with the damage that I cannot see — the bleeding of carbon from the landscape, and the loss of future carbon stores.

Using field, satellite and modelled data, Zeng and his colleagues detail how damaging winds over the past 150 years have greatly reduced forest biomass through tree mortality, subsequent wood decay and carbon release. They estimate that between 1980 and 1990, 9–18% of the amount of carbon stored yearly by US forests was lost due to destruction caused by tropical cyclones. The carbon dioxide loss is cumulative because once a tree is lost, it cannot sequester CO2 in the future. Thus, an extreme event such as Hurricane Katrina in 2005 or the Indian Ocean tsunami in 2004 could radically reduce carbon sequestration in the areas affected for several decades.

These findings force me to consider more than just the visible effects of hurricanes; I realize that tree loss is in effect altering the global carbon cycle. This paper also makes me wonder about the cumulative impact of cyclones on CO2 in other ecosystems, such as grasslands that have been damaged by salt-water inundation, or even possible forest growth due to storm-induced rainfall inland.

Elena B. Pasquale

bmaher — 2009-09-10T00:38:28+00:00

Burnham Institute for Medical Research, La Jolla, California

A biologist is gratified to find reconciliation for a conflicted receptor.

When giving talks on the involvement of the Eph family of receptor tyrosine kinases in cancer, I sometimes include a slide of the two-faced Roman god, Janus, to signify the dichotomies of Eph function in cancer cells. Most proteins have a clear-cut function. Some 'moonlighting' proteins carry out two unrelated functions. It is, however, rare for a protein to toggle between opposing activities. The Eph receptors are proving to be such outliers.

High expression of Eph receptors has been correlated with a poor cancer prognosis, but so has Eph silencing. Accordingly, there is good evidence that the Eph receptors can promote as well as inhibit tumour development. In a reconciliation reminiscent of Hegelian synthesis, a recent paper begins to explain how the EphA2 receptor can both promote and inhibit cancer cells' migratory and invasive abilities.

EphA2 activation by ephrin ligands seems to be minimal in most types of cancer cell. Hui Miao and Bingcheng Wang of Case Western Reserve University in Cleveland, Ohio, and their co-workers have shown that the protein Akt — which can be powerfully cancer-promoting — hijacks EphA2 by phosphorylating one of its serine residues, enabling its pro-metastatic activities (H. Miao et al. Cancer Cell 16, 9–20; 2009).

Remarkably, binding by the ephrin-A1 ligand erases this phosphorylation and transforms EphA2 into an anti-invasive molecule.

These findings lead to the counterintuitive proposition that we should encourage rather than inhibit EphA2's ligand-dependent function. It will be interesting to see whether analogous switches convert other Eph receptors between malignant and benign phenotypes.

Richard Bennett

bmaher — 2009-09-02T21:35:30+00:00

Brown University, Providence, Rhode Island

A microbiologist wonders what turns us on.

An Internet search for the words 'pheromone attractant' pulls up products ranging from human aphrodisiacs to control measures for the Colorado potato beetle.

But sexual chemistry is not only important to humans and beetles, it is also relevant to many fungi. Fungal peptide pheromones are often released by one mating type to attract a partner of the opposite sex, thereby initiating the programme of sexual differentiation. This signalling is often highly specific so that pheromones attract only potential partners and not unwanted suitors.

Work by Joseph Heitman and his colleagues at Duke University in Durham, North Carolina, provides a new spin on pheromone signalling in fungi (Y.-P. Hsueh et al. EMBO J. 28, 1220–1233; 2009). While studying the fungal pathogen Cryptococcus neoformans, the authors became curious about the function of an uncharacterized pheromone-receptor-like gene.

It turns out that this gene, CPR2, encodes a constitutively active receptor that stimulates downstream mating events in both the presence and absence of pheromones. During sexual differentiation, expression of CPR2 is upregulated and supplements the activity of conventional pheromone receptors. A single amino-acid substitution in the Cpr2 protein, in a transmembrane domain that is highly conserved among pheromone receptors, was shown to be responsible for constitutive signalling activity.

This demonstrates that the sexual lifestyles of unicellular organisms can be much more complicated than they first seem. Furthermore, constitutively active receptors have been implicated in many signal-transduction processes in mammalian cells. It remains to be seen whether sexual activity in more complex organisms also involves signalling components that are continuously turned on.

Paul Riley

bmaher — 2009-08-26T22:18:00+00:00

University College London

A molecular cardiologist looks into getting to the heart of his inner fish.

Newts do it, fish do it, but sadly humans and other mammals cannot repair or regenerate damaged heart tissue as adults.

Despite the modern-day promotion of healthier lifestyles (such as bans on smoking in public places and pro-fitness campaigns in the run-up to London 2012), cardiovascular disease is still on the up worldwide and, not unlike swine flu, is a true pandemic that respects no borders. As a result, and for some time now, I and others have been asking how we might become more newt-like or fish-like and repair our own hearts after a heart attack.

We have favoured looking at small resident progenitor cells which, when stimulated, might make new heart muscle and blood vessels. But a study by Bernhard Kühn and his colleagues at the Children's Hospital Boston in Massachusetts shows us another way (K. Bersell et al. Cell 138, 257–270; 2009).

They simply asked whether or not existing heart muscle can be instructed to divide and make more of the same. Apparently it can, with the help of the epidermal growth factor neuregulin (famed for its role in the nervous system), and its Erb4 receptor. While under the influence of neuregulin, some mature heart cells in mice disassemble their scaffold, re-enter the cell cycle, divide and regenerate injured muscle.

Of course, the devil is in the detail: the trick, it seems, is to have not only plenty of neuregulin, but also more heart muscle cells with one nucleus instead of two, because only the former responded to the growth factor. Unfortunately, this presents something of a conundrum where mammals are concerned. Mammalian heart-muscle cells generally become binuclear shortly after birth. Thus, for a complete fix, we are left heading back in the direction of the drawing board.

Heather Stoll

bmaher — 2009-08-20T05:11:27+00:00

Department of Geology, University of Oviedo, Spain

A biogeochemist sees the value of diversity in a changing ocean.

Ocean acidification in response to excess carbon dioxide in the atmosphere could become a problem for marine organisms, especially those that make skeletons or shells out of calcium carbonate. Corals and clams are at risk, as are the coccolithophorids — microscopic algae that are, by volume, the most important shell producers.

These algae have been the guinea pigs in a series of lab studies measuring their response to acidified seawater. But I worry about whether these studies give us an accurate picture of the future. They typically start with clones — descendants of a single cell — grown in acidified conditions for only a few weeks. This set-up precludes the kind of natural selection and adaptation that might occur over decades and centuries in the ocean.

To cloud the waters further, different labs often obtain conflicting results on the same species, a situation some attribute to subtle differences in methods. Fortunately, a recent study by Gerald Langer of the Autonomous University of Barcelona in Spain and his colleagues provides a more satisfying and ultimately more optimistic explanation (G. Langer et al. Biogeosci. Discuss. 6, 4361–4383; 2009). These reserachers grew four different strains of a calcifying algae, Emiliania huxleyi, at different seawater pH levels, and showed that the response to acidification varies significantly among the strains. They argue convincingly that these diverse responses have a genetic basis.

Identifying diverse responses among strains of a species puts us one step closer to capturing the true potential of adaptation in this group of organisms. It would be naive to assume that this puts coccolithophorids out of harm's way. However, diversity is good insurance in a changing ocean. Moreover, I am hopeful that scientific experiments are starting to take that into account.

Omar Tonsi Eldakar

bmaher — 2009-08-13T13:04:13+00:00

Center for Insect Science, University of Arizona

An evolutionary biologist learns how to be remembered: cheat someone.

What makes someone unforgettable? Is it their charm? Their looks? Or is it that they once stiffed you on the bill?

Like many others, I have trouble remembering people's names, even as I am being introduced to them, but certain names remain etched in my mind forever. Few, for example, will forget Bernard Madoff, the New York financier convicted of defrauding people out of billions of dollars in a giant Ponzi scheme.

Raoul Bell and Axel Buchner at the Institute of Experimental Psychology in Düsseldorf, Germany, have explored this bias in memory (R. Bell and A. Buchner. Evol. Psychol. 7, 317–330; 2009). They reveal that humans have a greater propensity to remember the names of individuals associated with cheating than names associated with trustworthiness or other unrelated behaviours.

Cooperation is immensely beneficial to humans, but with cooperation looms the ever-present risk of exploitation. Researchers have proposed that humans have a specialized brain module dedicated to detecting and remembering cheaters, to help them to steer clear of future interactions with such individuals. It has previously been suggested that the cheater memory module is tied only to facial stimuli. But using the same behaviours associated with facial stimuli in previous studies, Bell and Buchner were able to replicate these findings using only names, which suggests a more general module for remembering cheaters.

Associating reputations with names is crucial to maintaining social norms through verbal mechanisms such as gossip. Thus memory bias for the names as well as the faces of cheaters could expand the ability of groups of individuals to avoid exploitation.

Madoff probably won't have much luck if he tries to scam people again.

Douglas Kell

bmaher — 2009-08-05T19:49:55+00:00

The University of Manchester, UK

A systems biologist ponders how disparate ideas can sometimes come together beautifully.

If X alone and Y alone cannot explain a phenomenon, sometimes together they can. As the late biochemist Henrik Kacser remarked: "To understand the whole you must look at the whole."

Prion diseases, for example, are closely associated with the conformational change of the prion protein PrP from its normal form to an aggregating, autocatalysing, pathologic form, PrPSc. But clumping prions don't tell the whole story. Their levels often correlate poorly with disease progression, and it is far from clear how a simple conformational change leads to the holes in brain tissue seen in late-stage disease.

It is also clear that poorly liganded iron is highly neurotoxic, mainly because it can spur the production of the highly reactive and toxic hydroxyl radical OH* — heavily involved in the progression of many other degenerative diseases and ageing. Neena Singh at Case Western Reserve University in Cleveland, Ohio, and her colleagues have now tied these two disparate threads together.

PrPSc, they found, can sequester cellular iron in insoluble PrPSc–ferritin complexes, making it bio-unavailable, leading to increased iron uptake and an overall excess of iron in brain tissue (A. Singh et al., PLoS Pathog. 5, e1000336; 2009). Modified iron metabolism is found in both scrapie and sporadic Creutzfeldt–Jakob disease, and such work stresses that it is not only the total amount of Fe(II) and Fe(III) that matters but their speciation. It is yet to be shown whether PrPSc–ferritin complexes catalyse OH* production directly, but if they do, this could account for the massive damage observed. Recognition of this could have a colossal effect on our thinking and provide new therapeutic (and dietary) options based on iron chelation for these and other syndromes.

Pavel Jungwirth

bmaher — 2009-07-29T19:10:27+00:00

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic

A chemist realizes that popularity is no measure of strength.

Urea, the water-soluble organic compound found in mammalian urine, has been known for its ability to denature — or unfold — proteins for more than 100 years. To this day, it is among the most widely used protein denaturants. So one could be forgiven for taking it for granted that we know in gory detail what happens when we pour urea into a protein solution. But, alas, nailing down the individual molecular interactions between urea and the chemical groups at a protein's surface is exceedingly difficult.

Experiments and simulations suggest that urea interacts primarily with amide groups in the protein backbone, but every such group in a given protein has its own local environment, leading to fuzzy signals in spectroscopic studies. Paul Cremer's group at Texas A&M University came up with a good means by which to address the problem. They employed a popular protein proxy, poly(N-isopropylacrylamide), in which all of the amide groups are chemically equivalent (L. B. Sagle et al. J. Am. Chem. Soc. 131, 9304–9310; 2009). Using infrared spectroscopy combined with measurements of hydrophobic collapse, they showed that urea interacts only weakly with this polymer.

Essentially, Cremer and colleagues' measurements suggest that one needs buckets of urea to see any effect. This is exactly the same situation as that observed for proteins, in which high concentrations of urea are necessary for denaturation. Thus one of the most common denaturants is actually a shockingly weak one. In fact, the strength of its interactions with the protein is little greater than those of harmless water molecules.

In the end, the key to the denaturating mechanism may be the fact that urea is a larger molecule than water — which has subtle entropic consequences — rather than that the two have different hydrogen-binding abilities.