Hunting for the roots of Alzheimer’s and stringing nanoparticles

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New Alzheimer’s disease gene found

An international collaboration involving local genetics researchers has identified a new gene that increases the risk of Alzheimer’s disease in the elderly.

Working with researchers in Toronto, New York, and other locations, Lindsay Farrer and colleagues at Boston University helped define two variants of the SORLA gene that are more common in people with Alzheimer’s disease.

Previous studies in cell cultures have shown that lower levels of the SORLA protein are associated with the increased production of toxic amyloid proteins, which are presumed to cause the brain damage and memory loss seen in Alzheimer’s patients.

To investigate whether changes in SORLA protein production actually contribute to the disease in Alzheimer’s patients, the researchers analyzed the DNA of nearly 6,000 people, some with the disease and others without, from different ethnic groups around the world. They looked for single nucleotide changes in certain genes, including the SORLA gene.

While they didn’t find a telltale mutation that caused the disease, they did find that several of the gene variants produced lower levels of the SORLA protein in blood cells. If that holds true in the brain, it suggests that one function of SORLA may be to protect cells against amyloid build-up.

The researchers caution that their test subjects came from a limited number of carefully selected families, so the results will need to be replicated in the general population.

The report was published online in Nature Genetics. Pat McCaffrey

Getting a grip on nanospheres

Coating nanoparticles with molecular “hair” is a quick and easy way to make them bind together in a controlled way, a new MIT study in Science shows.

Nanotechnology holds promise for creating materials customized at the atomic level, its supporters say. But to join nanoparticles together, researchers need a way to link them directly in a more controlled fashion. Current methods use enzymes and antibodies to connect nanoparticles in a somewhat haphazard way.

A new, simpler method comes from Francesco Stellacci and colleagues at MIT, who coated gold nanospheres with two kinds of molecular “hair”: one containing a nine-carbon chain, the other a stubby benzene ring.

These molecules automatically arranged themselves into alternating rows, but at the poles, one or two individual hairs stuck out, making them more reactive.

(Credit: Science)

Stellaci’s team exploited this property by attaching chemical handles to these hairs at either pole. Then, using a simple reaction, the researchers were able to join the nanospheres end to end, like pearls on a string, creating long chains.

They were also able to make woven sheets of these nanospheres. Stellacci hopes this kind of controlled linkage between nanoparticles will be useful in creating materials with tailor-made properties, such as filters with small, precisely sized holes. Mason Inman

Doing chemistry on paper, how one reef smells differently than another, and discovering a new regulator of the immune system

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Lab on a sheet of paper

Call it litmus paper for the 21st century. Paper with lines of chemicals printed on it can direct fluids across its surface, allowing basic chemical tests to occur right on the paper, a new Harvard study shows. This extremely low-cost “lab on paper” could make chemical tests feasible in less-industrialized countries.

Researchers are working on so-called lab-on-a-chip devices, which have tiny channels etched into small blocks of glass or plastic. These chips move nanoliters of liquid through the channels to bring about controlled chemical reactions. But these chips can cost hundreds of dollars each and often require expensive equipment to operate them.

As a low-tech, cheaper alternative, George Whitesides’ group of chemists at Harvard laid down a pattern of water-repellent chemicals, which act like walls to channel liquids, on the surface of chromatography paper. This paper is designed to separate out different molecules, but is cheap and readily available.

Their prototype has one inlet for loading a sample (at the bottom in the photo below). Capillary action draws the liquid up into each of three separate lobes (at the top in the photo below), which are laced with chemicals that react with the fluid. In this test, the left lobe showed the presence of glucose in the fluid, the right lobe showed the presence of proteins, and the center was a control.

This “lab on paper,” about five centimeters across, could be a cheap, portable way of running chemical tests.

Credit: Scott Phillips, Harvard University

The researchers showed that the paper could also act as a filter. When they loaded it with a liquid sample containing dirt, pollen, and graphite powder, they found that the contaminants stayed put while only the fluid moved up into the lobes. Each piece of patterned paper might cost less than a penny to mass-produce, they estimate. Mason Inman

Reef-dwelling fish smell their way home

Tiny fish larvae follow their noses home in Australia’s Great Barrier Reef, according to research by Gabriele Gerlach and colleagues from the Marine Biological Laboratory in Woods Hole and Boston University.

Half-inch-long cardinal fish larvae are washed from the reef soon after their birth and spend two weeks drifting on ocean currents. Researchers have thought that larvae from one reef spread widely to other nearby reefs. But DNA testing of fish from different but closely spaced reefs showed that each location hosted its own genetically distinct adult groups.

Cardinal fish (Ostorinchus doederleini)

Credit: Gabriele Gerlach

That discovery suggested that the dispersed baby fish eventually made their way back to the same spot where they were born. The investigators hypothesized that the larvae might be able to smell their home reef, in the same way that salmon follow odor cues to return to their spawning grounds.

To demonstrate this, coauthor Jelle Atema devised a flow chamber where fish could choose to swim in water collected from their home reef or from a different reef. Consistently, they chose their home water.

The behavior looks like a form of olfactory “learning”; the odors the fish encounter upon hatching are the same ones they seek out later in life. The researchers don’t know what the odor is—the fish might detect the smell of its own community or local variations in reef life. Only a few species of fish have known sniffing abilities.

This homing instinct supports the formation of genetically distinct clans of cardinal fish on reefs just a few miles apart. This contributes to the rich biodiversity of reefs, the researchers say.

The work was published in this week’s online edition of the Proceedings of the National Academy of Sciences. Pat McCaffrey

Defending and protecting your gut

Our intestines teem with bacteria, an environment that calls for an aggressive immune response. Fortunately, normal intestinal cells rarely get attacked, but the reason has remained a mystery. Now, local researchers have identified a new class of protective cells that help the immune system distinguish friend from foe in this immunological war zone.

Previously thought to have no function in regulating the immune system, the so-called stromal cells sit in the lymph nodes where other immune cells reside. There, the researchers found, they produce intestinal proteins, which they display to passing T cells. The T cells that recognize these proteins as foreign are picked out and eliminated before they can reach the intestine and cause trouble.

The stromal cells make up a large of part of lymph nodes throughout the body and may play a role in suppressing autoimmune responses in other tissues, too. They could point out new ways of preventing or treating autoimmune diseases.

The findings, from Shannon Turley and colleagues at the Dana-Farber Cancer Institute, were published in Nature Immunology. Pat McCaffrey

The neuroscience of shopping, the darkness of dark matter, and the link between stress and heart disease

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To buy or not to buy…shoppers base their decision on immediate pleasure—and pain

If you’re starting 2007 with a financial hangover—a large credit card bill from all your holiday shopping—then next year, you might want to consider paying with cash to reign in your spending. That’s one conclusion from a study on the neuroeconomics of shopping by MIT researcher Drazen Prelec and collaborators at Stanford and Carnegie Mellon University, published yesterday in Neuron.

The researchers used functional magnetic resonance imaging to map the brain activity of 26 male and female subjects as they shopped, with real cash, via a computer for small items like DVDs, games, and books. The results challenge the accepted economic model of decision-making.

The researchers found that as the subjects were deciding whether to buy or not, they displayed changes in brain activity in two opposing neural centers: one that anticipates the pleasure of buying a desired object, and another that registers the immediate pain of parting with cash. Neural circuits involved in assessing the long-term impacts of the decision weren’t active. Based on these changes, the researchers could accurately predict whether a subject would subsequently buy the item or not.

Current economic thinking is that consumers weigh the instant rewards of acquisition against the possibility of future gratification that comes with holding onto their money.

Instead, consumers’ buying decisions are influenced by more immediate effects—such as the loss of cash—rather than by long-term impacts, the researchers say.

This internal struggle may explain why people tend to overspend on credit cards. Putting it on plastic provides the rush of buying while deferring the discomfort of paying—at least for a month, that is. Pat McCaffrey

Dark matter could be even darker

Dark matter, the mysterious glue thought to hold galaxies together, may be even harder to spot than previously thought, a new study suggests.

The matter we see in the universe doesn’t supply enough gravitational pull to hold spinning galaxies together. So physicists have hypothesized for decades that unseen matter is keeping the universe together. They estimate that there’s five times as much dark matter in the universe as normal matter.

But dark matter is hard to detect since it doesn’t give off or reflect light. No one has spotted any dark matter particles yet, but physicists are intent on finding them. They have one class of particles in their scopes: WIMPs or weakly interacting massive particles.

Now physicists Daniel Feldman and Pran Nath at Northeastern University think there could be a new, unsuspected form of dark matter: extremely weakly interacting particles, or XWIMPs. In a paper with Boris Kors of CERN in Geneva, Switzerland, they show that these particles could interact with normal matter even more weakly than previously thought—at least 10 times less.

If dark matter is made of XWIMPS, then attempts now underway to directly detect dark matter particles could face an even bigger challenge than expected, the study says. Mason Inman

The heartbreak of posttraumatic stress

Veterans with symptoms of posttraumatic stress disorder (PTSD) are at a higher risk of heart disease as they age, according to a study from researchers at the Harvard School of Public Health and Boston University.

The researchers write that their study is the first to find a link between PTSD and cardiovascular disease, adding heart disease to the list of physical and psychiatric afflictions that can plague soldiers long after their military service ends.

Laura Kubzansky and colleagues examined the health records of nearly 2,000 veterans from the greater Boston area who were assessed in 1986 or 1990 for symptoms of PTSD. They identified 255 who experienced fatal or nonfatal heart attacks or chest pain in the following 10 to 15 years.

They found that for each PTSD symptom a subject had, his chances of heart disease increased by 20 percent, even after controlling for other possible risk factors like smoking, drinking, and depression.

The paper appears in the January issue of the Archives of General Psychiatry. Pat McCaffrey

Mapping malaria, deriving stem cells from unfertilized eggs, and sequencing DNA on a stick

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A study of malaria genomes reveals the pathogen’s hidden diversity

A research team from the Harvard School of Public Health and the Broad Institute has mapped the genomes of more than 50 different samples of the malaria parasite from around the world, revealing a surprising amount of genetic diversity in this deadly organism.

Malaria kills nearly two million people worldwide every year, mostly children in Africa, and the parasite is growing increasingly resistant to antimalarial drugs. The diversity map gives researchers a valuable tool to get a handle on the 60 percent of malaria genes whose functions are not yet known. It also provides insight on how the organism can rapidly change to evade natural immune defenses and drugs.

The researchers, led by Dyann Wirth, a professor at the Harvard School of Public Health and co-director of the Broad Institute Initiative on Infectious Disease, completely sequenced two Plasmodium falciparum isolates, from Central America and Asia, and compared them to the first malaria genome sequenced in 2002. Working with colleagues in Senegal, the researchers then did a less detailed analysis of dozens of additional isolates from around the world.

In all, they found nearly 50,000 differences in the DNA sequence between the various samples, about twice as many as they expected. They discovered an additional 37,000 spots where DNA was inserted or deleted, generating even more diversity.

Their study revealed that the genes for cell surface proteins, which are recognized by the immune system, showed the highest diversity. And by comparing the genomes of parasites exposed to different antimalarial drugs, they confirmed the location of genes that enable resistance to chloroquine, a common antimalarial. They also discovered a new region that appeared to carry resistance genes for another drug, pyrimethamine.

The work was published online this week in Nature Genetics, along with two other large-scale studies of the P. falciparum genome by other groups. They used similar data to trace the evolution of the parasite worldwide and to select promising new vaccine targets. Pat McCaffrey

Mouse eggs yield transplantable stem cells

Local researchers have reported a new method for producing and transplanting mouse embryonic stem cells that, if proven to work in humans, could lead to the production of genetically compatible tissue for the repair of diseased tissues.

But men shouldn’t get their hopes up—the technique starts with unfertilized eggs, so even if it does work in humans, the approach would only be an option for women. And the researchers have not yet proven that the derived cells, which lack important contributions from sperm, would function like normal embryonic stem cells, or that they would be safe to transplant into humans.

The researchers, led by George Daley at Children’s Hospital Boston, showed they could use unfertilized eggs from mice to produce embryonic stem cells that genetically match the egg donor. They stimulated the eggs, which had half of the maternal chromosomes, to begin development without the addition of paternal chromosomes from sperm.

During this process, called parthenogenesis, the maternal chromosomes were essentially duplicated, giving the resulting stem cells the complete set of chromosomes. The researchers were able to isolate stem cells, grow them into mature tissues, and transplant them back into mice with no sign of immune rejection.

The derived stem cells were not completely genetically identical to the egg donor, so it was possible that the immune system would treat them as foreign. But they turned out to be close enough. Further analysis of the stem cells showed that many carried the full complement of genes coding for key proteins that protect cells from immune rejection.

The authors caution that the cells are not normal and more studies will be needed to assure their safety. They are now trying to replicate their results with human eggs.

The paper appeared online this week in Science. Pat McCaffrey

Next-generation DNA sequencing with carbon nanotubes

Wrap a strand of DNA around a nanometer-sized hollow tube of carbon and you’ve got a system for ultrafast DNA sequencing, suggests a new study from Harvard.

With today’s technology, DNA sequencing is time consuming and expensive, partly because the DNA of interest must be copied millions of times in order to be sequenced. One faster and cheaper approach could be to directly read the sequence from a single DNA strand—say, by threading the DNA through a tiny pore outfitted with sensors. So far, though, no such method has made it into biology labs.

Now, Efthimios Kaxiras and colleagues at Harvard and at the University of Ioannina in Greece have proposed another way to do this kind of direct sequencing, using existing scanning microscopes. Single-stranded DNA will naturally wrap itself around carbon nanotubes—rolled-up sheets of carbon just one atom thick—while leaving the DNA bases A, G, C, and T exposed. A powerful scanning tunneling microscope could then read off the individual bases one at a time, Kaxiras’s team says.

A scanning tunneling microscope (STM) has an extremely sharp metal tip that shoots electrons into a sample, enabling it to measure the local density of electrons in a part of a molecule—thus deducing its chemical structure—with a resolution of two angstroms, the width of a couple of hydrogen atoms.

Carbon nanotubes would not only hold the DNA steady in front of the microscope but, because they are conductive, would also ease the flow of electrons from the microscope to the DNA.

Based on computer simulations of the interactions between DNA and carbon nanotubes, Kaxiras’s team concluded that the sequencing plan should work, since each base should look sufficiently different to the STM. The researchers estimate that this method could theoretically sequence perhaps 10,000 bases per second, several orders of magnitude faster than today’s methods. The limitation would be how quickly the researchers can move the DNA strand past the STM tip without breaking it.

The study appeared online last week in Nano Letters. Mason Inman

Improving yeast as biofuel factories, overcoming genetics with a healthy environment, and cooling the quantum way

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Yeast genes conspire to produce more biofuel

Researchers at MIT have engineered a new strain of yeast that can pump out ethanol with increased efficiency. Applying their findings to industrial yeast strains could help overcome some of the problems in the production of biofuels from corn and other plant materials, and help increase the supply of these alternative fuels.

Ethanol, which is most often mixed with gasoline for use in vehicles, is produced in large bioreactors by yeast that ferment plant sugars. But high initial glucose concentrations and later high ethanol levels inhibit the growth of the organisms. Attempts to create strains resistant to these harsh conditions by modifying one gene at a time has not worked, so postdoctoral researcher Hal Alper, who works in the lab of chemical engineering professor Gregory Stephanopoulos, decided to take a more expansive approach: altering many genes at once. To do this, he introduced multiple random mutations into a gene coding for a protein that regulates many genes in the yeast Saccharomyces cerevisiae.

The approach paid off. By generating a large number of yeast with mutated versions of a global gene regulator, called the TATA-binding protein, and growing the yeast in high glucose and ethanol, the researchers found a winner. The top performing strain proved able to withstand ethanol concentrations of 20 percent (the parent strain failed to grow in 6 percent ethanol). And the strain pumped out 50 percent more ethanol per hour than the original yeast.

This high performance was the result of complex reprogramming of the yeast genome, involving changes in the activity of hundreds of genes. The researchers identified the three key mutations in the TATA-binding protein gene required to soup up the organism.

The researchers say that, in theory, this technique could be applied to other organisms to generate optimized strains for a variety of industrial and medical uses.

The work appears today in Science. Pat McCaffrey

Environment trumps genes in young mice with learning problems

Providing laboratory mice with deluxe accommodations—more space and a chance to exercise and play with toys—helps them overcome a genetic defect that affects the ability of mice raised in a standard lab environment to learn and remember.

The results, from Tufts University Medical School researcher Larry Feig, show that mice in the enriched environment use additional biochemical pathways to achieve the neuronal changes necessary for learning and memory formation. This flexibility has not been observed in conventionally housed mice.

There’s no question that environmental enrichment or deprivation alters brain development, but exactly what happens in the brain during this process has not been well understood.

Feig and his collaborator, Dean Hartley of Harvard Medical School, had previously found that mice raised in conventional cages and lacking certain proteins called Ras-GRF, which are involved in key biochemical pathways, have defects in their ability to strengthen the connections between certain neurons in response to stimulation, a necessary process for learning and memory formation.

In the new study, the researchers placed these mice in more-spacious cages with toys for six hours a day over a two-week period. By studying slices of the mice’s brains, they found that those defects had disappeared. With further probing, they revealed that the mice activated an additional signaling pathway to compensate for the missing Ras-GRF proteins.

They also found that animals that were deprived early in life but placed in the enriched environment as adults could not overcome the lack of the Ras-GRF proteins.

The researchers speculate that their findings could be relevant to people, suggesting how optimal environments for infants and young children might maximize the ability for the brain to compensate for genetic weaknesses.

The paper appeared this week in Current Biology. Pat McCaffrey

How to cool quantum computers

As computers run faster, they run hotter, calling for ever-more-powerful cooling mechanisms. In today’s issue of Science, researchers led by Sergio Valenzuela of MIT reveal tricks of quantum physics that could give quantum computers their first direct cooling mechanism.

Quantum computers exploit properties of quantum physics to run many more operations in parallel than current computers, theoretically increasing computing speeds. So far, though, only simple prototypes exist, capable of small feats like multiplying 3 by 5.

Researchers are hard at work on the basic computing elements of these computers, called quantum bits or qubits. Unlike traditional computer bits, which exist in one of two states—either 0 or 1—qubits can be in two or more states. Qubits can inadvertently switch states due to heat, light, and other disturbances, so keeping them cool is important for the development of quantum computing. So far, the only method of cooling qubits has been to keep them immersed in liquid helium.

Now the MIT researchers have demonstrated a new way of cooling qubits directly. They used a 10-micrometer wide loop of niobium, a superconducting material, as a qubit and ran an electric current through the loop. In its lowest quantum energy state, the current circulated only in one direction, clockwise. But inevitably the material absorbed some heat from its surroundings; in this more energetic state, part of the current began circulating counter-clockwise.

To cool the qubit back down, Valenzuela and colleagues used a method that seems paradoxical: they shot the qubit with a microwave photon. At a specific frequency, the photon boosted the already-excited current to an even higher energy state. This energized current flowed clockwise, just as in the lowest state. Because of the properties of these energy states, this energized current could much more easily “decay” back to its lowest energy state. In the process, the qubit shot out a photon—one more energetic than the photon it originally absorbed. This way, it cooled down to a chilly three millikelvin.

The researchers say this cooling method could work for most other kinds of qubits built from a solid material. And they say it could be useful in a practical quantum computer; one use would be to “reset” qubits to their lowest energy state between calculations, which would also keep them cool. Mason Inman

Pinpointing stem cells of the heart and the genetics of aggression

Pat McCaffrey

Heart stem cells isolated

Two local research groups today report the isolation of two types of heart stem cells that together give rise to all three main tissue types in the heart.

The cells can mature into cardiac muscle tissue and can also turn into the cells that make up the smooth muscle tissue and the heart’s blood vessels. The discovery changes current ideas about how the heart forms and brings researchers one step closer to the use of stem cell therapy to repair heart tissue.

Researchers have wondered whether the different parts of the heart grow from different stem cells that come together during early embryonic development, or whether one local stem cell generates all the tissues in the organ. The finding that one cell can initiate the whole program could simplify the repair of damaged heart tissue; replacement of one master cell type may be sufficient to mend muscle, blood vessels, and the heart’s pacemaker cells.

Kenneth Chien of Massachusetts General Hospital and collaborators identified the precursor cells in the embryonic mouse heart and showed that they grew into muscle or blood vessel cells. The team then produced the stem cells in the lab from embryonic stem cell cultures. If human cells behave in the same way, this could provide a source of stem cells for transplants.

Another group, led by Stuart Orkin at Children’s Hospital Boston, independently identified a slightly different stem cell in mice that could form either cardiac or smooth muscle cells, but did not appear to give rise to blood vessel cells.

It’s not clear yet how the two types of stem cells are related, but the researchers hope to work that out soon. The first author on Orkin’s paper, Sean Wu, has accepted a position in Chien’s Cardiovascular Research Center at MGH. Both Chien and Orkin are also affiliated with the Harvard Stem Cell Institute.

The two papers appear today in the online edition of Cell.

Battle of the sexes reversed in fruit flies by gene swap

Edward Kravitz of Harvard Medical School has spent the last five years watching fruit flies fight, with the aim of figuring out how genes control aggressive behaviors. He’s found that males and females forced to fight over food have vastly different pugilistic styles. Females usually butt and shove, while males prefer to lunge and box.

That difference is hardwired into the fly genome, according to the latest results from Kravitz’s fruit fly fight club. Collaborating with researchers at the Institute of Molecular Pathology in Vienna, the Harvard researchers have shown that swapping just one gene between males and females completely altered the flies’ fighting styles.

Male flies with the female version of the gene tended to pick fights with females and to be less aggressive with other males. When fighting, they showed more head butting and shoving and none of the boxing behavior favored by normal males. Conversely, when females carried the male version of the gene, they displayed far more aggressive fighting styles.

Trading the gene caused the flies some confusion in the romantic realm as well. Male flies with the female gene tended to fight with females rather than court them, and female flies with the male gene courted other females and fended off males.

This result is in keeping with previous studies that implicated the gene, called fruitless, in sex-specific mating behavior. By watching flies fight and mate with each other, researchers are hoping to figure out the neuronal circuitry behind these opposing instincts.

Their paper appeared this week in Nature Neuroscience online.

Watching evolution in action, a germ-fighting surface, and a new role for RNA

Pat McCaffrey

Natural selection rapidly tunes lizard leg length

Evolution in animals is usually thought of as a process occurring over eons. Research in this realm has tended to focus on the descriptive tracking of the fossil records of long-dead creatures.

But scientists from Harvard and the University of California, Davis, who staged a survival-of-the-fittest scenario among lizards on small islands in the Bahamas, found they could study natural selection at work on a far more compressed time scale and in living animals. Their results show that not only can researchers observe evolution in action, but also that the effects of natural selection can change unexpectedly in a complex natural setting.

In the study appearing in today’s Science, Jonathan Losos of Harvard and colleagues first caught and tagged brown anoles on a dozen small islands around Great Abaco in 2003. They measured the hind leg length of all the reptiles. Then they imported an anole predator, the Northern curly tail lizard, to half of the islands.

Six months later, they found fewer anoles on the predator-inhabited islands than on the control islands. Predators presumably killed the missing ones. The anoles that survived on the predator-inhabited islands were the ones that started out with slightly longer legs. The results fit with the idea that longer legs helped the mainly ground-dwelling reptiles to outrun the terrestrial predator.

Surprisingly, in the next six months, selective pressure did a U-turn to favor decreased leg length as the anoles began to climb trees to escape. The shift from living on the ground to living in trees and bushes is a well-known behavioral response to predators, and lizards with shorter legs fare better at arboreal life.

Were the anoles to be left alone with the predator, the authors predict, they would evolve into a shorter-legged species. But nature had other plans—the experiment ended abruptly in 2004 when Hurricane Frances inundated the islands. Efforts are underway to set up another study over a longer observation period, Losos says.

Polymer coating keeps surfaces germfree

MIT researchers have developed a polymer coating that is deadly to influenza viruses and disease-causing bacteria. The polymer destroys the organisms on contact by poking long, spiky molecular “tentacles” through their protective outer coats. A simple one-step application of the polymer could render common surfaces like doorknobs, elevator buttons, and phones permanently self-sterilized and provide a way to slow the spread of flu and other illnesses.

The polymer, developed by researchers in the lab of Alexander Klibanov, is a water-insoluble hydrocarbon chain with long branches. The researchers painted the substance onto the surface of a glass microscope slide, anchoring the molecules at one end to the slide.

The polymer works quickly—it killed all of the flu viruses within five minutes of contact. With bacteria, the researchers found that the polymers do their damage by penetrating and physically disrupting the cell membrane. Flu viruses have a different kind of outer coat, but the polymers can also penetrate it.

The MIT team found that different polymers were also effective, providing that they were long enough to extend well out from the surface of the slide. In addition to the flu virus, the coated slides also killed disease-causing E. coli and Staphylococcus bacteria.

The article appeared online this week in the Proceedings of the National Academy of Science.

Regulatory role for antisense RNA discovered in yeast

The surprise of the past decade for biologists has been the emergence of RNA’s role as a key regulator of gene activity. The discovery that small, interfering RNA molecules control the fate of larger, protein-coding messenger RNAs landed University of Massachusetts researcher Craig Mello this year’s Nobel Prize.

However, the function of other types of noncoding RNAs has remained more of a mystery. Now, Whitehead Institute researchers have found that a different kind of RNA, antisense RNA, can also regulate gene expression.

Antisense RNA is one type of RNA that is made from DNA during the first step in protein synthesis. One strand of the DNA, the sense strand, is used to make messenger RNA (or sense RNA). The other, noncoding strand is used as a template for antisense RNA. Antisense RNAs are abundant in cells, but their function was unknown.

In a paper published in this week’s Cell, Gerald Fink and colleagues showed that antisense RNA produced from a gene, IME4, regulates that gene in yeast cells and ultimately determines the type of cells they become. This gene is needed for cells to undergo meiosis, a kind of cell division required for reproduction. The researchers found that when high levels of antisense RNA were produced from this gene, sense RNA production was diminished and the cells did not undergo meiosis.

These results should spur interest in antisense RNAs. It could be that these widespread but poorly understood molecules represent a new level of gene regulation.

Mapping protein interactions in stem cells, modeling how proteins take shape, and the benefits of low-carb diets

Pat McCaffrey

Protein network keeps stems cells at their peak

Harvard researchers have mapped a network of interacting proteins in mouse embryonic stem cells that seems to keep the cells in their early, unspecialized state, where they maintain their capacity to form any tissue in the body.

Revealing the regulatory circuit in stem cells could help scientists reach their goal of reprogramming already specialized adult cells to an embryonic state. This could provide human stem cells for research and medical uses, without the ethical controversies surrounding the current methods of creating embryonic stem cell lines.

Other researchers had already identified genes involved in maintaining stem cells. But to understand the complete regulatory process, they need to find out how the products of those genes work together in the cell.

The researchers, in the lab of Stuart Orkin at Harvard Medical School, constructed the map starting with the critical stem cell regulator protein, Nanog. To find other proteins in mouse embryonic stem cells that were in direct contact with Nanog, they used a specially tagged version of the protein as “bait” to fish for interacting proteins. Then they repeated the experiment using several of the newly discovered partner proteins as bait to expand the map of the network.

In the end, they found an interconnected web of 37 proteins, many of which were already known as players in early development. Much of the network seems to function by squelching the expression of genes that trigger stem cells to turn into more specialized cells.

Researchers have known that stem cells that have begun to specialize produce many of the proteins in the network at lower levels. This suggests that finding ways to boost the production of such proteins would be a useful strategy for reprogramming adult cells.

While the work was done using mouse cells, the researchers suspect the same basic network will be found in human cells.

The study appeared online earlier this week in Nature.

Computer program predicts protein structure

Harvard researchers reported this week the first computer simulation of the complete folding of a small protein molecule. The modeling program they developed not only predicted the final structure of a test protein almost perfectly, but also identified key intermediate structures during the folding process.

The biological activity of proteins depends on successful folding, and the accumulation of badly folded proteins is now believed to cause many neurological disorders such as Alzheimer’s and Parkinson’s diseases. Computer simulations could be a faster and simpler way of determining protein structure than existing laborious laboratory methods.

So far, the complexity of protein folding—which has millions of intermediate steps—has prevented the development of computer models for all but a few short, simple protein-folding schemes.

The new program uses a very efficient computing method to simulate protein-folding events over microsecond intervals. That’s about a thousand times longer than previous methods and close to the time it takes some proteins to fold in cells.

The program was good at predicting the final shape of a test protein based on its amino acid sequence. In 4,000 separate trials, the computed end structure closely matched the atomic structure solved previously by other techniques. By determining which intermediate structures showed up most often in the multiple simulations, the researchers also arrived at a likely chronology of folding in atomic-level detail.

The paper, from the lab of Eugene Shakhnovich of Harvard, appeared this week in the Proceedings of the National Academy of Science online.

Low-carb diets not harmful, says long-term study

Low-carbohydrate diets, like the popular Atkins regime, help people lose weight in the short term, but because they tend to be heavy in fat, some physicians have suspected they might not be heart healthy. A 20-year study from the Harvard School of Public Health suggests that this is not the case, at least in women. On the contrary, some high-carbohydrate diets may raise the risk of heart disease, the researchers found.

The study, published this week in the New England Journal of Medicine, analyzed the diets and health outcomes of 82,801 women in the Nurses Health Study, a long-running survey of lifestyle factors and disease. Based on data from food questionnaires the women filled out, the researchers divided the women into groups according to the percentage of calories they ate from carbohydrate, fat, and protein.

In the 20-year follow-up, nearly 2,000 of the women developed heart disease. There was no difference in the risk of heart disease for women on low-carbohydrate diets compared with women eating high-carbohydrate diets, even though they consumed more fat.

While the total amount of fat consumed did not seem to affect the women’s cardiovascular health, the kind of fat did. Among women with low carbohydrate intake, those who ate mostly vegetable fat had a 30 percent lower risk of heart disease than those who ate mainly animal fat, according to senior author Frank Hu.

And no matter what their diet, over the course of 20 years, women in every group gained enough weight to bump the average body mass index up a few points.

Untangling the mysteries of spider silk, figuring out the role of an infamous breast cancer gene, and why students take illicit stimulants.

Pat McCaffrey

Spinning a tale of spider silk

By studying the behavior of minute quantities of liquid silk harvested from the spinning glands of the golden silk orb-weaving spider, MIT researchers are unraveling the secrets of this strong and durable material. Their goal is to create synthetic silk, a long-sought prized polymer that could find use in artificial tendons and ligaments, parachutes, and bulletproof vests.

The golden silk spider spins one of the strongest webs in the spider world—in some cases, strong enough to catch small birds. Researchers Nikola Kojic and Gareth McKinley and colleagues at MIT set out to study the flow properties of the protein-rich liquid silk in order to see if they could understand how it irreversibly transforms into tough fibers as it exits the spider.

But native liquid silk is not easy to come by—a good harvest from the spider consists of one to five microliters, not enough to perform the necessary viscosity and flow tests. So the researchers built microsized analytical instruments to study tiny volumes of the liquid.

They found that freshly harvested silk solution is highly viscous, three million times thicker than water. But when they applied force to the liquid, mimicking its propulsion through the spider’s narrow spinneret channel, its viscosity dropped dramatically. The researchers attribute this to the alignment of the long protein molecules in the solution as the spider squeezes the solution through its spinneret.

The researchers used another small instrument to pull on the viscous solution and found that the liquid silk dried quickly in fine fibers with the protein molecules aligned, making the fiber very strong.

The study appeared this week in the Journal of Experimental Biology.

Breast cancer gene keeps chromosomes in line

Women who carry mutations in the breast cancer genes BRCA1 or BRCA2 are three to five times more likely to develop breast or ovarian cancer in their lives than women without those mutations. Researchers have some clues as to how normal BRCA proteins might fend off tumors—the proteins help repair DNA damage, for one—but other protective functions have not been apparent.

A new paper in this week’s Cell shows that the BRCA1 protein plays a larger role, ensuring that newly divided cells get the right complement of genetic material. Without BRCA1, cells can end up with extra or too few chromosomes, or ones that are broken. This type of disarray contributes to tumor development.

The work, from the labs of David Livingston at the Dana-Farber Cancer Institute and Johannes Walter at Harvard Medical School, reveals a surprising role for BRCA1 in the formation of the mitotic spindle. This structure, present only in dividing cells, ensures that chromosomes line up properly and are allocated correctly to the two newly forming nuclei.

The researchers discovered the link between the BRCA1 protein and spindle formation by studying cell extracts that normally display orderly spindle formation and precise separation of chromosomes. When they removed the BRCA1 protein or its partner protein BARD1 from the extracts, the spindle structure became less organized and chromosomes moved in a less coordinated fashion.

The lack of BRCA1 didn’t stop the whole process of division, but produced two unevenly sized nuclei carrying either too few or too many chromosomes.

The results could explain why cancer cells with BRCA1 mutations show widespread chromosomal abnormalities. The importance of BRCA1 as a watchdog of cell division is apparent from this sobering statistic: half of all women with a defect in the BRCA1 gene will develop breast cancer by the age of 50.

College students take illicit drugs seriously

A study of illicit use of prescription stimulants among college students has found that the primary reason students gave for using the drugs was to improve concentration and enhance academic performance. Less than a third of users reported taking the drugs to get high.

The study, from Christian Teter at Northeastern University, used a self-administered Web survey to sample 4,580 undergraduate college students at a large Midwestern university last year. Overall, 6 percent of students reported using stimulants—normally prescribed for attention-deficit-hyperactivity disorder (ADHD)—without medical authorization.

More than 75 percent of college students who reported using the stimulants illicitly chose amphetamine-dextroamphetamine products, like Adderall, over methylphenidate products, like Ritalin.

The researchers suggest one reason for this difference may be that Adderall is an extended-release drug with effects lasting 10 to 12 hours, whereas Ritalin and similar stimulants may produce a “roller coaster” response with effects lasting six hours or less. The high rate of use may also reflect the fact that Adderall is the most commonly prescribed brand-name stimulant in the United States.

Understanding how and why students use psychostimulants is necessary to effectively combat their improper use, the authors say.

The study appeared in the October issue of the journal Pharmacotherapy.

Why pain is more painful to some and the benefits of moderate drinking (even for the already heart-healthy)

Pat McCaffrey

Gene determines susceptibility to pain

Some people can bear physical pain that stops others in their tracks, a feat often attributed to mental toughness. But resistance to pain can also be genetic, according to a report published online this week in Nature Medicine from researchers at Massachusetts General Hospital.

The scientists identified a common genetic variation in humans that affects pain sensitivity. People who inherit a protective form of the gene feel acute pain less, and are resistant to developing chronic pain after an injury or surgery.

Researchers found that activity of an enzyme called GCH1 increased after nerve injury in rats, resulting in higher levels of a metabolite called BH4. BH4 is required to make a number of pain-producing neurotransmitters in rats and humans. Giving the rats a GCH1 inhibitor resulted in the animals showing fewer signs of pain, while injecting them with BH4 made them display more signs of pain.

These results led the researchers to look for genetic differences in GCH1 activity in people reporting varying levels of chronic pain. They studied 168 patients who had undergone back surgery and found that one variant of the GCH1 gene was significantly more common in those who did not report persistent postsurgery pain. It was less frequent in those who developed chronic discomfort.

The variant also affected the experience of acute pain. Healthy volunteers who carried the protective sequence showed reduced production of BH4. They could also withstand being poked, exposed to heat, or subjected to a tourniquet on their arm longer before asking the researchers to stop.

The work uncovers a previously unknown pain pathway, say the researchers, led by Clifford Woolf of MGH. Chronic persistent pain following surgery, injury, or stemming from arthritis affects as many as 50 million people in the United States. The study opens up the possibility of genetic screening for susceptible individuals and the development of new pain medication targeting GCH1 activity.

Bottoms up for heart health

Men sticking to a heart-healthy lifestyle by exercising, eating right, and not smoking can still benefit from adding a daily drink or two to their routine, according to a new study from researchers at Beth Israel Deaconess Medical Center and the Harvard School of Public Health.

Studies have previously shown that men who drink moderately have a lower risk of heart attacks, but it has not been clear if the reason was the drinking or other aspects of their lifestyle. Men who drink moderately may also exercise and eat in moderation, confounding attempts to detect only the effects of alcohol.

To get around that issue, Kenneth Mukamal and colleagues studied a group of 8,867 male health workers chosen for their admirable lifestyles. The men were not overweight; they exercised daily, didn’t smoke, ate a healthy diet, and took multivitamins. The researchers tracked the subjects’ alcohol consumption for 16 years and compared the incidence of heart attack among men with different levels of alcohol intake.

They found that men who consumed between one-half and two drinks daily had a 40 to 60 percent reduction in risk of heart attack compared to those who had fewer drinks or didn’t drink at all. There was a limit, though. More than two drinks per day all but erased the benefits.

The benefits attributed to drinking in this healthy group were as large as those measured in other studies for the general population and were as large as the positive effects of diet, exercise, or maintaining a healthy weight.

“Our results suggest that moderate drinking could be viewed as a complement, rather than an alternative, to these other lifestyle interventions,” the authors write in the Archives of Internal Medicine.

Packaging DNA for delivery, making sense of a migraine, and an endoscope the width of a human hair.

Pat McCaffrey

Biodegradable polymers deliver DNA to cells

The biggest challenge to the field of gene therapy remains the problem of delivery. Replacing faulty genes with normal ones in cells to treat disease requires safe methods for getting the therapeutic DNA into diseased cells. Viruses have been most commonly used for gene delivery, but a spate of leukemias in one French gene therapy trial and the death of a young man in a 1999 Philadelphia study have left researchers looking for better, safer vehicles.

Taking an engineering approach, Robert Langer of MIT and his colleagues have been developing synthetic polymers with the aim of supplying DNA to cells in a nontoxic, biodegradable package. Their newest polymers, described in this week’s issue of the Journal of the American Chemical Society, bind free DNA to form highly stable nanoparticles that are readily taken up by cells. Conditions inside the cell appear to favor the release of the DNA and the degradation of the polymer.

The work shows that the polymers delivered DNA to human cells as efficiently as the best research reagents available. And they are less toxic. Previous polymers developed by Langer and other researchers delivered less DNA to fewer cells.

The polymers are long strings of positively charged groups that grab onto highly negatively charged DNA. But the novel structures also allow for the easy attachment of other kinds of chemicals, including sugars, amino acids, and proteins. The researchers took advantage of this feature to improve the naked polymer. By adding positively charged amino acids, they showed that they could bind more DNA to the polymer, improving its efficiency in ferrying genes to cells.

The researchers also showed that they could tag the polymer with a short peptide that recognizes a specific receptor protein on the surface of blood vessel cells. This opens the door to the targeting of, for example, anticancer agents to blood vessels that feed tumors. Experiments underway will show whether the tagged particle will selectively enter those cells.

This is your brain with a migraine

Why people get migraine headaches remains a mystery, even though about 15 percent of the population suffers from this severe and sometimes disabling condition.

One contributing factor to migraines could be structural differences in the brain, according to work published this week in PLoS Medicine from Nouchine Hadjikhani and colleagues at Harvard Medical School and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. Using magnetic resonance imaging (MRI), the researchers discovered that people with migraines have physical changes in two related brain regions responsible for processing visual information. The study doesn’t say for sure if the changes are a cause or an effect of the migraines, but the abnormalities could account for some of the odd neurological symptoms experienced by some migraine sufferers.

Those symptoms include aura or preheadache visual disturbances, such as flashing lights, zigzag lines, and the experience of blind spots. Not all people with migraine experience aura, but they all have abnormal perception of movement, which often leads to motion sickness.

Given these migraine symptoms, the investigators decided to take a close look at the regions in the brain that handle visual inputs. They scanned the brains of 12 subjects who have migraines with aura, 12 with migraines without aura, and 15 normal controls. Performing two kinds of MRI allowed the researchers to pick up subtle changes. They found that migraine patients, whether they experienced aura or not, had a thickening of the outer brain layer, the cortex, in the visual areas of the brain. They also displayed abnormalities in their connections to adjacent regions compared to the control subjects.

For the first time, researchers have pinpointed a structural brain change in migraine sufferers, and finding the same changes in patients with or without aura indicates that these distinct manifestations of headache are in fact the same disease.

Endoscopes get smaller to go farther

Researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital have developed a flexible fiber-optic probe, slightly thicker than a human hair, which can provide three-dimensional, high-resolution images of the body’s innermost cavities.

In a report published this week in Nature, Guillermo Tearney and colleagues demonstrate a prototype of the diminutive instrument, which uses a single optical fiber to deliver real-time images taken in spaces as small as a mouse’s belly. In their work, the researchers inserted the probe into the abdominal cavity of a mouse using a thin needle. The device clearly revealed tiny tumors, just a few millimeters in diameter, on the inner abdominal wall.

Endoscopes—flexible probes that doctors thread into body cavities—make diagnostic procedures and surgeries cheaper and less invasive. But one limitation of endoscopy has been the size of the devices. The traditional combination of a small lamp and a camera creates a cord the width of a pencil. This is fine for colonoscopies, but is too large to access smaller internal cavities. Smaller scopes, consisting of bundled optical fibers, have suffered from low resolution.

To miniaturize the instrument while maintaining resolution, the researchers went with a single fiber and a multicolored light source. After shining multiple wavelengths of light onto the tissue surface, the fiber transmitted the reflected light to external instruments for analysis.

With its flexibility and smaller size, the endoscope may allow physicians to venture more confidently into tight spaces like mammary ducts, Fallopian tubes, and delicate parts of the nervous system. The technique could also be useful in children and even for fetal procedures, and may enable delicate diagnostic and microsurgical procedures in currently inaccessible areas of the body.

Putting estrogen on the map; homing in on Huntington’s disease

Pat McCaffrey

A map of estrogen action in breast cancer

Nearly three-quarters of breast cancers depend on estrogen to drive their growth, and blocking estrogen action is the most common therapy for these deadly tumors. This week, Dana-Farber Cancer Institute researchers unveiled a complete genomic map of estrogen action, revealing thousands of previously unknown receptor sites where the hormone interacts with breast cancer cells. The map may help researchers zero in on estrogen-responsive genes that may contribute to breast cancer, which could eventually lead to better treatments for women with the disease.

Estrogen is a master gene regulator in breast cancer cells, binding to the estrogen receptor (ER) protein inside the cells. The ER protein then migrates into the nucleus, seeking regulatory regions in the DNA where it binds to switch certain genes on or off. While researchers have pinpointed a handful of these regulatory sites on estrogen-responsive genes, Myles Brown, Shirley Liu and their coworkers wanted to identify all the spots along the entire genome where the ER touched down.

To achieve that goal, the researchers treated breast cancer cells with estrogen and then used antibodies to fish out the ER proteins, along with their corresponding pieces of DNA. Through genome-wide DNA microarray analysis, they identified the precise sequences of DNA where the ER protein made contact. Their analysis revealed 3,665 unique ER binding sites regulating more than 1,000 genes.

Looking at the whole genome, the researchers were surprised to find that most of these regulatory sites are far from the genes they control. Previously, researchers looking for such sites have stayed close to known genes and so have missed much of the story of estrogen’s role in breast cancer. The discovery of all these ER binding sites gives researchers a chance to piece together a complete picture of the behavior of breast cancer cells.

Already in the works is the analysis of other important cancer targets, such as the androgen receptor in prostate cancer. The research appears in Nature Genetics.

Energy crisis: Cell death in Huntington’s disease blamed on power shortage

The devastating and eventually fatal symptoms of the neurodegenerative Huntington’s disease may be the result of an energy crunch in just a few brain cells, according to new research from Dimitri Krainc and colleagues at Massachusetts General Hospital.

Huntington’s disease, which robs its victims of the ability to walk, talk, think, and remember, is an inherited condition caused by a mutation in the huntingtin gene. The disease is marked by the death of a small population of neurons in the striatum, deep inside the brain, and high levels of abnormal huntingtin protein, produced by the mutated gene.

But scientists didn’t know how large amounts of mutated huntingtin result in brain cell death. The new work, published in today’s Cell, shows that mutant huntingtin protein shuts down a gene for a metabolic regulator protein called PGC-1alpha, which is responsible for maintaining healthy mitochondria, the cells’ power plants. Without proper mitochondrial function, the cells starve for energy and degenerate over time.

Previously, the researchers had shown they could induce some symptoms of Huntington’s in mice by knocking out the PGC-1alpha gene. That led them, in this study, to look at PGC-1alpha in brain tissue from Huntington’s disease patients, and in mice producing mutated huntingtin protein. In both cases, they found that PGC-1alpha protein levels were lower than normal in the neurons that would eventually die. With further probing, they found that the abnormal huntingtin protein shut down PGC-1alpha gene expression. Because PGC-1alpha regulates mitochondrial genes important for energy production, interfering with the key protein had negative effects for the cells’ energy metabolism.

The researchers went on to try to “reenergize” the neurons. They used a virus as a carrier to deliver PGC-1alpha into the brains of mice producing mutant huntingtin protein and found that no neurons died. There are currently no treatments for Huntington’s disease, so the results suggest that normalizing energy metabolism might be a good strategy for the development of new treatments.

The authors still don’t know why just one kind of neuron dies when the mutant protein is present in all brain cells. They think that striatal neurons might be uniquely sensitive to energy depletion.

What makes stem cells age, a shortcut in chemical synthesis, and sharpening lasers.

Pat McCaffrey

Stem cell burnout blamed on tumor suppressor gene

A gene known for halting cell growth and preventing tumor formation causes stem cells to lose their regenerative capacity in aging mice, according to three papers published in the online edition of Nature Wednesday. Together they suggest that inhibiting this gene might prolong the life of stem cells, promote tissue repair, and delay aging.

Diminishing stem cell numbers and activity with age leads to less tissue renewal and repair, but researchers didn’t know just how the cells grew old. In one of the reports, David Scadden and colleagues at the Harvard Stem Cell Institute and Massachusetts General Hospital show that the decreased ability of bone marrow stem cells to produce new blood cells in adult mice coincides with an increased production of a protein called p16^INK4a^. When the researchers knocked out the p16^INK4a^ gene, grown mice maintained a youthful stem cell population in their bone marrow.

The accumulation of p16^INK4a^ over time affected other stem cells too. A second paper showed that the protein slowed regeneration of the insulin-producing beta cells of the pancreas in aging mice. This declining population of cells might contribute to adult-onset diabetes, write the authors, who include Keith Ligon from Brigham and Women’s Hospital and Angela Koh and Susan Bonner-Weir at the Joslin Diabetes Center. A third group found that p16^INK4a^ played the same role in neuronal stem cells in the brain.

There was one hitch: although mice lacking p16^INK4a^ had spry stem cells, they also got more tumors. Mother Nature apparently has good reason to limit the growth of stem cells, whose uncontrolled growth could lead to tumors.

Getting molecules into shape

If you have ever tried to put a left shoe on your right foot, you understand the chemist’s struggle with enantiomers—pairs of molecules that are mirror images of each other and are not superimposable. When it comes to biological activity, only one of the two molecules interacts properly with a particular protein target. In drug development, this difference can be critical: often, one isomer is helpful as a drug, and the other is harmful. The challenge for chemists is to prepare large amounts of just one type of isomer. Most chemical reactions tend to produce both.

Now, Amir Hoveyda and Mark Snapper of Boston College are addressing the problem with a new catalyst they’ve developed. The reagent adds silicon ‘protecting’ groups to symmetric precursors, but does it in a specific way to produce almost exclusively one enantiomeric isomer, saving the laborious work of purifying isomers from a mixture.

In one synthetic scheme, the researchers replaced a six-step, multi-day process with a single reaction to produce an enantiomer mix with more than 90 percent of the desired isomer. Fewer steps mean a higher yield and less waste. The catalyst, an amino acid derivative, promises a faster, more environmentally friendly, and cheaper way to produce the building blocks needed for many pharmaceuticals. The reactions do require a large amount of the catalyst, but it is easy to prepare from commercially available precursors, and can be recycled several times.

“This procedure is likely to have a significant impact on the efficiency and cost of construction of single-enantiomer products,” wrote Scott Denmark, a chemistry professor from the University of Illinois, Urbana-Champaign, in an accompanying commentary. The research report

appears in this week’s of issue of Nature.

Nanoantenna puts laser light on the spot

By adding a tiny antenna to a commercial diode laser, Harvard University researchers have created a high-resolution laser light source that could one day stuff multiple terabytes of data onto one CD. The nanoantenna technology could also benefit biologists by enabling the production of more powerful microscopes and more precise optical tweezers that could manipulate small molecules.

Diode lasers are common light sources for many applications, ranging from fiber optics to barcode readers and DVD players. Nanoscale applications of diode lasers are limited, however, by the resolution of conventional optics. To solve this problem, the researchers installed an optical antenna on the surface of the diode. The 100-nanometer long antenna, made of a pair of gold nanorods, collects the laser light and concentrates it into an intense spot about 40 nanometers wide, much smaller than the 800-nanometer wavelength of the emitted light. This technology could be the basis for optical microscopes and tweezers whose resolution is not limited by the wavelength of light.

For biologists, who use lasers to sort cells, perform microdissections, and isolate single chromosomes and other large cellular components, the new antenna could take these techniques into the nanorealm. Optical tweezers, which use a focused laser beam to grab particles from 100 nanometers to a few microns in size, have been widely used to study DNA replication and the protein motors that propel organelles and other proteins inside cells. With the new technology, the tweezers could trap even smaller molecules.

The device, developed by Ertugrul Cubuku, Eric Kort, Kenneth Crozier and Federico Capasso of Harvard’s Division of Engineering and Applied Sciences, was described in a paper published last week in Applied Physics Letters.