Cancer biology: Skeleton key
Proc. Natl Acad. Sci. USA 103, 9643–9648 (2006)
Researchers in France have identified a promising new target for treating patients with breast cancer that has spread to their bones.
When cancer cells settle in bone they secrete signalling molecules known as cytokines that trigger the bone's destruction, so helping the tumour to grow. Olivier Peyruchaud from the INSERM U664 institute at the University of Lyon and his colleagues have previously found that lysophosphatidic acid (LPA), a lipid produced by blood platelets, stimulates the production of cytokines.
Now they show that LPA's action is mediated through one specific receptor, LPA1, on the surface of the cancer cells. Blocking this receptor reduced the progression of bone metastases in mice.
Neuroscience: Look who's thinking
Nature Neurosci. doi:10.1038/nn1729 (2006)
Researchers in Sweden suggest that mirror neurons — which fire both when an action is performed and when it is observed — may underlie the development of certain thinking skills in infants.
Terje Falck-Ytter of Uppsala University and his colleagues studied how well adults, 12-month- and 6-month-old babies were able to predict the outcome of a simple human action. They showed the subjects a video of a hand transferring objects into a box. Adults and 12-month-olds predicted the outcome by directing their gaze at the box; 6-month-olds did not. The shift in prediction skills coincides with the age at which infants learn to perform the action themselves. So, the researchers say, the results are consistent with the idea that mirror neurons, trained by use, form the basis of developmental milestones such as understanding others' actions.
Physics: Electron rebellion
Phys. Rev. Lett. 96, 236804 (2006)
Tantalizing evidence for negative electrical resistance has been gathered by physicists in the United States. The phenomenon, in which an electrical current moves against the applied voltage, is theoretically possible but is hard to observe.
Michael Zudov of the University of Minnesota in Minneapolis and his colleagues looked for the effect using two beams of microwaves to vary the resistance felt by electrons in a semiconductor. The current changed smoothly until one of the beams was tuned to a frequency believed to induce negative resistance, when the current in the semiconductor dropped dramatically. The researchers suggest that this may be evidence of a negative-resistance state interacting with the state set up by the second beam.
Neurobiology: Cut to the point
Cell 125, 1179–1191 (2006)
Exactly how the mutated huntingtin protein causes the hereditary brain condition Huntington's disease has long been a mystery. Now, researchers pin the blame on a process in which an enzyme cuts the protein at a particular point.
Michael Hayden at the University of British Columbia, Canada, and his colleagues studied mice carrying the abnormal huntingtin gene. Previous work had shown that enzymes known as caspases cut the huntingtin protein and linked this to the disease. This team found that, if they altered the gene so that its protein could no longer be cut by caspase-6, the mice did not develop Huntington's. This suggests that the cutting triggers the neurodegeneration typical of the disease and makes caspase-6 a good target for therapy.
Palaeontology: First of the modern crocs
Proc. R. Soc. Lond. B doi:10.1098/rspb.2006.3613 (2006)
The common ancestor of crocodiles and alligators probably arose in the ancient supercontinent of Gondwana, say researchers who have unearthed the earliest known member of the group in the Australian outback. The fossil (pictured right) dates from between 95 million and 98 million years ago, around the time the group that contains today's species was beginning to diverge.
The new species, Isisfordia duncani, was relatively small at just 1.1 metres long, report Steven Salisbury of the University of Queensland in Brisbane and his colleagues. The build of its limbs suggests that the beast was equally at home in and out of water. This flexibility may have helped crocodyliforms to survive the mass extinction that wiped out their fellow reptiles, the dinosaurs, 65 million years ago.
Astronomy: Swell colour
Astrophys. J. 644, 1–20 (2006)
Two uncertainties that dogged the original discovery of ‘dark energy’, the unseen force driving the expansion of the Universe, have been deflated by a new analysis.
Measurements of the brightness of Type 1a supernovae, the ‘standard candles’ of the cosmos, provided the first evidence of the Universe's ballooning. But astronomers were unsure whether more mundane phenomena, such as intergalactic dust or a fundamental difference in character between supernovae now and those in the past, might explain the results. Now Alex Conley of the University of Toronto, Canada, and his colleagues from the Supernova Cosmology Project use a technique known as colour-magnitude intercept calibration (CMAGIC) to analyse the colour of light coming from such supernovae, instead. This provides independent confirmation that the Universe is swelling in line with current dark-energy predictions.
Electrochemistry: Post production
Nature Mater. doi:10.1038/nmat1672 (2006)
A rusty electrode doesn't sound terribly good news for a battery, but Patrice Simon of the Paul Sabatier University in Toulouse, France, and his co-workers find that an iron oxide can work wonders for rechargeable lithium cells — if the material is nanostructured.
With a negative electrode made from a forest of copper nanopillars coated with Fe3O4, their lithium battery produces six times more power per unit area than one in which the electrode is a flat slab of the same material — which in turn beats the capacity of the graphite electrodes in current commercial cells.
A porous ceramic membrane provides a template for the copper posts, and the product is cheap and non-toxic.
Palaeontology: Ancient embryos
Science 312, 1644–1646 (2006)
Bilaterally symmetric animals existed much earlier than once thought, say researchers. Fossilized embryos indicate the presence of developmental processes unique to such animals some 40 million years before the Cambrian period.
Jun-Yuan Cheng of Nanjing University and his colleagues isolated 248 embryos from the Precambrian Doushantuo Formation deposits in Guizhou Province, China. The 580-million-year-old embryos were preserved performing their first cell divisions, which feature a lobed structure protruding from one of the cells as it divides. Some modern creatures, including certain molluscs, still use this strategy.
The lobe delivers molecules to one of the resulting cells of an early division, which turn it into a different kind of cell from its counterpart.
Genomics: World's smallest genome
Proc. Natl Acad. Sci. USA 103, 9566–9571 (2006)
With just 373,000 base pairs and a mere 331 genes, it's the smallest genome known — and it has just been sequenced.
Researchers led by Geoffrey McFadden of the University of Melbourne, Australia, have unravelled the DNA of the ‘nucleomorph’ of Bigelowiella natans, a single-celled organism of the group known as chlorarachniophytes.
The nucleomorph is an evolutionary vestige that was originally the nucleus of a eukaryotic cell. The eukaryotic cell swallowed a cyanobacterium to acquire a photosynthetic ‘plastid’ organelle, and that cell was in turn engulfed by another cell to produce B. natans as we know it. Now, most of the nucleomorph's genome is concerned with its own maintenance, and just 17 of its genes still exert any control over the plastid. Its small size suggests it is heading for evolutionary oblivion.
Neurobiology: Follow the guidelines
Development 133, 2487–2495 (2006)
Developmental biologists want to find out how growing neurons wire up correctly using cues from a chemical gradient. Tiny chips printed with guidance molecules may help.
Martin Bastmeyer of the University of Karlsruhe, Friedrich Bonhoeffer of the Max-Planck Institute for Developmental Biology, Tübingen, and their colleagues used a process known as micro-contact printing to effectively create tiny, stripy rubber stamps. They used these to stamp an ‘ink’ made of ephrinA5 guidance molecules on to glass coverslips (shown blue in picture).
By varying the width and spacing of the stripes, the team shows that chick retinal neurons (yellow) figure out where to stop based on both the local ephrin concentration and the total amount of ephrin encountered on their journey.
Howard Hughes Medical Institute, University of California, Los Angeles
One hit or two? A cancer biologist reviews the shifting focus in drug discovery.
Spurred by the success of imatinib — the anticancer drug better known as Gleevec — most drug-discovery companies now have programmes to look for similar, molecularly targeted therapies.
Imatinib blocks a certain class of enzyme, the tyrosine kinases. In the search for other kinase inhibitors, I am struck by the shift from a laser-like focus on the selectivity of the molecule's binding to interest in molecules that have several targets.
The rationale comes, in part, from the recent clinical success of drugs that target multiple kinases. But is this approach justified?
My views are heavily influenced by clinical studies showing that resistance to kinase inhibitors occurs principally through mutations that impair drug binding. The mutations are always tracked to a single kinase. For example, resistance to imatinib in leukaemia patients arises exclusively through mutations in the kinase ABL, despite the fact that the kinases KIT and PDGFR are also inhibited. I see this as genetic evidence that the therapeutic effect can be explained by the drug's action on a single target.
However, a recent report (Qi-Wen Fan et al. Cancer Cell 9, 341–349; 2006) convinces me that hitting two targets may sometimes be better than hitting one.
In a study of various PI(3)-kinase inhibitors, the authors noted that antitumour efficacy requires inhibition of both PI(3)Kα and another kinase, mTOR. The logic underlying this result is particularly compelling because both kinases function in the same signalling pathway with multiple levels of feedback.
This study gives me hope that we can move from accidental to rational multi-kinase-inhibitor drug design.