68
Cancer drug slows muscular dystrophy in mice Roxanne Khamsi An experimental cancer drug has slowed muscular dystrophy in mice with the disease, raising hopes that a simple pill could one day treat the fatal condition in humans. “The results the researchers are reporting are very dramatic and impressive,” says Jeff Chamberlain at the University of Washington School of Medicine in Seattle, US. The researchers caution that the results are preliminary, but say that the approach might offer advantages over other medicines for muscular dystrophy currently in clinical trials. There are many forms of the muscle-wasting disease, but no cure for any of them. The most common form of the illness among children, known as Duchenne muscular dystrophy, involves a mutation for a muscle protein known as dystrophin. Without functioning copies of this protein, muscles weaken, leading to breathing problems and, ultimately, death in the victims' teens or early twenties. Counteracted deterioration Pier Puri at the Burnham Institute in La Jolla, California and colleagues tried to boost muscle function in mice carrying a mutation in the dystrophin gene, by treating the animals with a cancer drug called trichostatin A (TSA). The compound, which is being tested as a treatment for melanoma, causes a change in certain proteins. Puri says that these changes somehow affect the production of a molecule known as follistatin, which can indirectly cause muscle growth and counteract the deterioration caused by faulty dystrophin. Muscle-boost abolished The team gave the mutant mice a daily dose of TSA for three months, after which the rodents underwent a fitness test on a treadmill. Those on TSA managed to last 20 minutes on the treadmill, compared to just 12.5 minutes for the control group. In a second part of the experiment, Puri’s team gave the mice a compound that blocks the effects of follistatin. This had the effect of abolishing the muscle-boosting power of TSA, demonstrating that the cancer treatment works against the symptoms of muscular dystrophy by boosting follistatin, Puri says. An advantage of TSA is that it can be taken in simple pill form, unlike some of the other treatments in development, such as those involving gene therapy. But experts stress that, unlike gene therapy, it would have to be continuously administered. “You would have to give this for the lifespan of the patient,” Chamberlain notes, adding that the potential side effects of long-term TSA use are unknown. Journal reference: Nature Medicine (DOI: 10.1038/nm1479) Invention: Triple-standard DVD Barry Fox Triple-standard disc The electronics industry is in a fine mess, with two blue- laser disc standards (Blu-ray and HD-DVD) competing to succeed ordinary red-laser DVDs. On 26 September, Warner will be the first studio to release a movie, Lake House, on all three disc standards simultaneously. Meanwhile, however, two top Warner engineers, Alan Bell and Lewis Ostrover, have been working on a cheaper and more elegant solution. Blu-ray uses a 405-nanometre wavelength laser to read data from tracks 0.1-millimetres-deep on the top surface of a disc. HD-DVD, on the other hand, uses the same wavelength to read recordings at a depth of 0.6 mm. Warner’s plan is to create a disc with a Blu-ray top layer that works like a two-way mirror. This should reflect just enough blue light for a Blu-ray player to read it okay. But it should also let enough light through for HD-DVD players to ignore the Blu-ray recording and find a second HD-DVD layer beneath. 1 3/7/2022

Cancer drug slows muscular dystrophy in mice · Web viewCancer drug slows muscular dystrophy in mice Roxanne Khamsi An experimental cancer drug has slowed muscular dystrophy in mice

  • Upload
    ngodiep

  • View
    213

  • Download
    0

Embed Size (px)

Citation preview

Cancer drug slows muscular dystrophy in miceRoxanne Khamsi

An experimental cancer drug has slowed muscular dystrophy in mice with the disease, raising hopes that a simple pill could one day treat the fatal condition in humans.

“The results the researchers are reporting are very dramatic and im-pressive,” says Jeff Chamberlain at the University of Washington School of Medicine in Seattle, US.

The researchers caution that the results are preliminary, but say that the approach might offer advantages over other medicines for muscular dystrophy currently in clinical trials.

There are many forms of the muscle-wasting disease, but no cure for any of them. The most common form of the illness among children, known as Duchenne muscular dystrophy, involves a mutation for a mus-cle protein known as dystrophin.

Without functioning copies of this protein, muscles weaken, leading to breathing problems and, ultimately, death in the victims' teens or early twenties.Counteracted deterioration

Pier Puri at the Burnham Institute in La Jolla, California and colleagues tried to boost muscle function in mice carrying a mutation in the dys-trophin gene, by treating the animals with a cancer drug called tricho-statin A (TSA).

The compound, which is being tested as a treatment for melanoma, causes a change in certain proteins.

Puri says that these changes somehow affect the production of a mol-ecule known as follistatin, which can indirectly cause muscle growth and counteract the deterioration caused by faulty dystrophin.Muscle-boost abolished

The team gave the mutant mice a daily dose of TSA for three months, after which the rodents underwent a fitness test on a treadmill. Those on TSA managed to last 20 minutes on the treadmill, compared to just 12.5 minutes for the control group.

In a second part of the experiment, Puri’s team gave the mice a com-pound that blocks the effects of follistatin. This had the effect of abolish-ing the muscle-boosting power of TSA, demonstrating that the cancer treatment works against the symptoms of muscular dystrophy by boost-ing follistatin, Puri says.

An advantage of TSA is that it can be taken in simple pill form, unlike some of the other treatments in development, such as those involving gene therapy.

But experts stress that, unlike gene therapy, it would have to be con-tinuously administered. “You would have to give this for the lifespan of the patient,” Chamberlain notes, adding that the potential side effects of

long-term TSA use are unknown. Journal reference: Nature Medicine (DOI: 10.1038/nm1479)

Invention: Triple-standard DVDBarry Fox

Triple-standard discThe electronics industry is in a fine mess, with two blue-laser disc

standards (Blu-ray and HD-DVD) competing to succeed ordinary red-laser DVDs.

On 26 September, Warner will be the first studio to release a movie, Lake House, on all three disc standards simultaneously.

Meanwhile, however, two top Warner engineers, Alan Bell and Lewis Ostrover, have been working on a cheaper and more elegant solution.

Blu-ray uses a 405-nanometre wavelength laser to read data from tracks 0.1-millimetres-deep on the top surface of a disc. HD-DVD, on the other hand, uses the same wavelength to read recordings at a depth of 0.6 mm.

Warner’s plan is to create a disc with a Blu-ray top layer that works like a two-way mirror. This should reflect just enough blue light for a Blu-ray player to read it okay. But it should also let enough light through for HD-DVD players to ignore the Blu-ray recording and find a second HD-DVD layer beneath.

An ordinary DVD recording could be put on the other side, so that con-ventional DVD players can read the disc as well.

Although the triple-standard disc will cost more to make, it should still be cheaper than pressing three, and shops should be pleased not to have their shelves overloaded with so many different discs.The "bad hair day" brush

Thanks to Japan's Kao Corporation you may soon be able to rate a "bad hair day" on a scale of 1 to 10. The company is developing a smart hairbrush, which can quantify the damage caused by treatments such as hair dyes and bleaches.

The hairbrush analyses sound as hair is brushed. This reveals a sur-prising amount about the state of the hair, according to five inventors from the company.

To make the brush, an aluminium bar a few micrometers long is pol-ished and sandblasted and then buried amongst the prongs of the brush. A microphone attached to the bar then picks up vibrations as hair is dragged over the bar. A built-in strain gauge also records the resis-tance caused by brushing.

A USB connection feeds these measurements to a PC which compares the sound and the pulling strain. Tests carried out in a Tokyo hair salon showed that hair in good condition makes far less noise than dirty hair with split ends. Loud sound at high frequencies also indicates too much

1 5/10/2023

bleaching, the inventors say. The brush could help hairdressers work out the appropriate treatment for a person in their care.Enzyme sensor

Intel has plans to move into medicine. A patent application from the world's biggest microchip-maker reveals a method for using tried-and-tested silicon fabrication techniques to mass produce low cost biosen-sors for home or hospital use. Putting many sensors on a single chip should reduce the power needed to drive such a device.

To make the biosensors, identical pairs of piezoelectric electrodes are deposited on a silicon wafer and some of the silicon beneath each elec-trode is etched away to create an identical pair of resonant cavities. When a current is passed through the electrodes, they vibrate with iden-tical resonance.

An enzyme such as glucose oxidase is then attached to one of the two electrodes. When the chip is exposed to blood sugar, this binds with the enzyme making the electrode underneath heavier. The two electrodes then vibrate differently, which an on-chip sensor can easily detect. And comparing its resonance to a stored database provides a quick blood-sugar reading.

If the electrodes are coated with antibodies or DNA instead of en-zymes, the chip could also provide early warning of an infection.

Ancient Greeks invented 'quantum dot' dyeAncient Greek hairdressers could teach us a thing or two about nan-

otechnology.When hair is dyed using a lead-based dye popular 2000 years ago,

crystals of lead sulphide just 5 nanometres across form within the mi-crostructure of the hair fibres, according to a team led by Phillipe Walter at the French Museums' Research and Restoration Centre in Paris.

A hair-like scaffold could be used to grow "quantum dots" - tiny crys-tals which confine a handful of electrons in a way that makes it possible to exploit their quantum properties, such as spin, for use in emerging quantum computing systems. Existing methods for producing quantum dots create defects. The work will be reported in Nano Letters.

'Spectrum of empathy' found in the brainRowan Hooper

Ever wondered how some people can “put themselves into another person's shoes” and some people cannot? Our ability to empathise with others seems to depend on the action of "mirror neurons" in the brain, according to a new study.

Mirror neurons, known to exist in humans and in macaque monkeys, activate when an action is observed, and also when it is performed. Now new research reveals that there are mirror neurons in humans that fire when sounds are heard. In other words, if you hear the noise of some-

one eating an apple, some of the same neurons fire as when you eat the apple yourself.

So-called auditory mirror neurons were known only in macaques. To determine if they exist in humans Valeria Gazzola, at the school of be-havioural and cognitive neurosciences neuroimaging centre at the Uni-versity of Groningen, the Netherlands, and colleagues, put 16 volunteers into functional magnetic resonance imaging (fMRI) scanners and ob-served their brains as they were played different noises.

The volunteers heard noises such as a sheet of paper being torn, or of someone crunching potato chips. Then the same subjects were scanned again, this time whilst tearing a piece of paper, or eating potato chips.Vicarious crunching

“We combined the data from listening and execution and looked to see if the activity in the brain overlaps,” says Gazzola’s colleague Chris-tian Keysers, also at the University of Groningen. Sure enough, it did overlap. Motor neurons associated with mouth actions (crunching) and hand actions (ripping) were activated in both cases.

The overlap occurred in areas of the brain such as the bilateral tempo-ral gyrus and the superior temporal sulcus.

“The mirror system is a particular form of Pavlovian association,” says Keysers, referring to the classic behavioural experiments where dogs were trained to associate food with the noise of a bell. “Each time you crunch a potato chip you hear yourself crunching the chip, and now when you hear someone else crunching it activates your own action neurons.”Spectrum of difference

The phenomenon has been exploited by advertisers for years – think of the Coca-cola commercials comprising of just the noise of a bottle of Coke being opened, the fizz of the drink and the sound of the drinking. And intriguingly, subjects in the study who scored higher in empathy tests also showed higher levels of mirror neuron activation.

Differences in empathy scores and mirror neuron activity have been observed between autistic and non-autistic people, says Keysers, but this is the first time a spectrum of difference has been found in non-autistic people. “How empathetic we are seems to be related to how strongly our mirror neuron system is activated,” he says.

“It’s exciting because we can start to look at the diversity of experi-ences of other people. Some people see others through themselves, and some are more objective about it.” Journal reference: Current Biology (vol 16, p 1824)

Novel drug joins fight against drug-resistant malariaRoxanne Khamsi

A potential new drug against malaria has been identified, which has cured mice with a drug-resistant form of the disease.

2 5/10/2023

The synthetic compound, called XC11, works by preventing the malar-ial parasite, Plasmodium falciparum, from reproducing, researchers say.

Malaria claims more than one million lives each year, many of them children. The mosquito-borne disease is becoming increasingly resistant to treatment – the affordable drug chloroquine is no longer effective throughout Africa, for example.

Jun Liu at Johns Hopkins School of Medicine in Baltimore, Maryland, US, and colleagues screened 175,000 compounds before identifying XC11. The compound acts in a different way to other treatments, by dis-rupting the malarial parasite’s ability to make certain proteins crucial to its replication.Completely cured

The researchers gave XC11 to mice with a rodent form of chloroquine-resistant malaria. After four days of treatment, the average percent of parasite-infected red blood cells in the XC11-treated animals had dropped to 6% - about one-tenth the level seen in the control mice. And giving XC11 in combination with chloroquine reduced the parasite load to just 2%.

All of the mice that received the drug combination survived infection were still alive three months later – whereas 40% of mice in the control group died. 80% of the mice that received XC11 were completely cured – meaning they were disease free and remained so for at least three months after treatment.

David Sullivan, who collaborated in the study, says that while XC11 may not be as effective as some other drugs, it has potential because it exploits a different pathway to other drugs so may not be as vulnerable to resistant strains.Unlimited production

Artemisinin is the main weapon against chloroquine-resistant malaria, but because it is plant derived there is the threat of shortage. Com-pounds derived from XC11 would be synthetic and so potentially have unlimited, cheaper production.

Other drugs do exist to treat chloroquine-resistant malaria but many are very expensive, and experts fear that the organism will soon show resistance even to these drugs.

“You might potentially find a strain of malaria for which no amount of money can buy you a drug that works,” says Anthony James at the Uni-versity of California, Irvine, US. “So, I think any new drug is a big deal.”

The team is currently working towards a modified version of XC11 that works with even greater effectiveness. Journal reference: Proceedings of the National Academy of Sciences (DOI: 10.1073/pnas.0604101103)

Instant messaging worm builds menacing 'botnet'Will Knight

A computer worms that spreads via instant messaging is being used to build an extensive "botnet" of remote-controlled PCs, a US security firm has warned.

Security experts at US company FaceTime identified the worm as "W32.pipeline" and warned that it spreads via AOL's instant messenger program.

The worm disguises a malicious executable program as a Jpeg image, which is attached to an instant message that appears to come from someone on the recipient's AOL "buddy list".

Typically, the picture is accompanied by the message, "hey would it be ok if I upload this picture of you to my blog?" although another simi-lar message may also be used.Ultimate goal

If the recipient tries to open the image, the executable installs a pro-gram on their PC. This forwards the executable on to other contacts on their buddy list and also enables connections to several remote comput-ers. It then tries to download another program that allows an outsider control the infected machine.

FaceTime's director of malware research Chris Boyd says the goal ap-pears to be creating a huge network of remote-controlled machines, known as a "botnet". As of Thursday, Boyd estimates W32.pipeline had amassed botnet between 1000 and 2000 machines.

Botnets may be used to send out huge quantities of junk e-mail or at-tack business websites with an avalanche of data, in a so-called distrib-uted "denial-of-service" attack, which may be linked to extortion.Click fraud

Botnets can also be used to commit "click fraud", which involves or-dering the zombie machines to repeatedly click internet advertisements, to generate money for a company's that is paid per click.

"The ultimate goal of the W32.pipeline is to create a sophisticated bot-net that can be used for a range of malicious purposes," FaceTime said in a security alert issued on Tuesday.

Boyd and other researchers posted details of the worm, including screenshots and "attack scenarios" to the company's blog – http://blog.spywareguide.com.

They note that the botnet created using the worm, which is controlled via Internet Relay Chat (IRC) servers, is particularly sophisticated and uses a complicated "install chain" to schedule file uploads to infected machines.

Fish Used to Detect Terror AttacksBy THE ASSOCIATED PRESS Published: September 19, 2006

3 5/10/2023

SAN FRANCISCO (AP) -- A type of fish so common that practically every American kid who ever dropped a fishing line and a bobber into a pond has probably caught one is being enlisted in the fight against terrorism.

San Francisco, New York, Washington and other big cities are using bluegills -- also known as sunfish or bream -- as a sort of canary in a coal mine to safeguard their drinking water.

Small numbers of the fish are kept in tanks constantly replenished with water from the municipal supply, and sensors in each tank work around the clock to register changes in the breathing, heartbeat and swimming patterns of the bluegills that occur in the presence of toxins.

''Nature's given us pretty much the most powerful and reliable early warning center out there,'' said Bill Lawler, co-founder of Intelligent Au-tomation Corporation, a Southern California company that makes and sells the bluegill monitoring system. ''There's no known manmade sen-sor that can do the same job as the bluegill.''

Since Sept. 11, the government has taken very seriously the threat of attacks on the U.S. water supply. Federal law requires nearly all commu-nity water systems to assess their vulnerability to terrorism.

Big cities employ a range of safeguards against chemical and biologi-cal agents, constantly monitoring, testing and treating the water. But electronic protection systems can trace only the toxins they are pro-grammed to detect, Lawler said.

Bluegills -- a hardy species about the size of a human hand -- are con-sidered more versatile. They are highly attuned to chemical distur-bances in their environment, and when exposed to toxins, they experi-ence the fish version of coughing, flexing their gills to expel unwanted particles.

The computerized system in use in San Francisco and elsewhere is de-signed to detect even slight changes in the bluegills' vital signs and send an e-mail alert when something is wrong.

San Francisco's bluegills went to work about a month ago, guarding the drinking water of more than 1 million people from substances such as cyanide, diesel fuel, mercury and pesticides. Eight bluegills swim in a tank deep in the basement of a water treatment plant south of the city.

''It gave us the best of both worlds, which is basically all the benefits that come from nature and the best of high-tech,'' said Susan Leal, gen-eral manager of the San Francisco Public Utilities Commission.

New York City has been testing its system since 2002 and is seeking to expand it. The New York City Department of Environmental Protection reported at least one instance in which the system caught a toxin before it made it into the water supply: The fish noticed a diesel spill two hours earlier than any of the agency's other detection devices.

They do have limitations. While the bluegills have successfully de-tected at least 30 toxic chemicals, they cannot reliably detect germs.

And they are no use against other sorts of attacks -- say, the bombing of a water main, or an attack by computer hackers on the systems that control the flow of water.

Still, Lawler said more than a dozen other cities have ordered the anti-terror apparatus, called the Intelligent Aquatic BioMonitoring System, which was originally developed for the Army and starts at around $45,000.

San Francisco plans to install two more bluegill tanks.''It provides us an added level of detection of the unknown,'' said Tony

Winnicker, a spokesman for the city's Public Utilities Commission. ''There's no computer that's as sophisticated as a living being.''Sniffing out relatives, bluegill sunfish use self-referencing

to recognize kinMany animal societies involve highly promiscuous mating behavior,

making it potentially complicated for individuals to recognize and prefer-entially help their relatives. Researchers have now shown that offspring of promiscuous male bluegill sunfish compare the odor of nest-mates to their own genetically determined odor, and prefer to associate only with individuals that smell like themselves. This finding may explain how so-cial behavior operates in promiscuous animal societies. The new work is reported by Tim Hain and Bryan Neff of the University of Western On-tario and appears in the September 19th issue of Current Biology, pub-lished by Cell Press.

Most animals, including humans, are able to recognize their relatives. This is commonly accomplished by remembering the individuals one as-sociates with during early development, such as nest-mates. However, it is now well known that many animals are also highly promiscuous and thus that nest-mates are not always kin (that is, full siblings). A so-called self-referencing kin-recognition mechanism, where individuals use some aspect of their own appearance, odor, or other characteristic to recog-nize kin, had been proposed for several animals, but past studies had not yet eliminated the possibility that such cases might involve kin recognition based on learning early in development.

In the new work, the researchers studied the ability of bluegill sunfish larvae to recognize kin. Using in vitro fertilization techniques, the re-searchers created mixed broods in which nest-mates were not reliably kin--some were full siblings and others were unrelated. They then used behavioral experiments and DNA analysis to show that offspring of the promiscuous "cuckolder" males actively sought and associated with the odor of siblings that they had never encountered previously. This ability to recognize unfamiliar relatives provides compelling evidence for the use of kin recognition through a process in which an individual matches

4 5/10/2023

its own physical characteristics to those of others, and it confirms the importance of kinship in social behavior.

Iowa Company Turns to Ammonia for FuelBy THE ASSOCIATED PRESS Published: September 19, 2006

DES MOINES, Iowa (AP) -- An Iowa alternative fuel engine manufacturer has reached an agreement with an irrigation pump maker in California to make the world's first ammonia-powered irrigation pump system.

The system will help meet California's new strict emissions require-ments scheduled to go into effect in 2010, the companies said.

Hydrogen Engine Center Inc., of Algona, said Tuesday its is working with Corcoran, Calif.-based Sawtelle & Rosprim Inc. to integrate HEC am-monia-powered engines with Sawtelle's pumps ''to complete a prototype system for testing and evaluation.'' The prototype system will be de-signed to run 24 hours a day. It will be tested during California's 2007 ir-rigation season.

If testing is successful, HEC plans to begin selling ammonia-powered irrigation systems in California in 2008.

''We believe that the demonstration of this engine will complete years of development work and will allow the sale of our systems worldwide without concerns about hydrogen storage, cost, availability or permit-ting,'' says Ted Hollinger, HEC President.

He said the company hopes to market ammonia-fueled engines into the generator market.

The engines developed by HEC run on anhydrous ammonia, or NH3, which has been used by farmers for many years as a fertilizer.

Sawtelle & Rosprim President Terry Kwast said most of his customers who need irrigation systems already are accustomed to handling, stor-ing and working with anhydrous ammonia, so it presents none of the problems that hydrogen would.

Anhydrous ammonia contains no carbon, stores like propane and is the second most prevalent chemical in the world, Hollinger said. Ammo-nia contains more hydrogen per cubic foot than liquid hydrogen. Hollinger frequently refers to ammonia as the other hydrogen.

He said using ammonia to power engines has advantages:--An infrastructure for storage and transportation is already in place.--Usage and safety regulations for ammonia are already in place, there-fore, the process of obtaining a permit to use ammonia is usually rela-tively simple.--Ammonia pipelines can be found in many areas of the United States, including Iowa, and distribution of the fuel is already established.

Kwast said he's been searching for years for alternatives to the diesel engines currently used in irrigation systems. With federal and state air quality regulations making it increasingly more expensive to reduce the

engine emissions, alternative fuels such as ammonia are becoming more cost effective.

''The agriculture industry out here needs to do something to comply with the new air emissions standards that will be coming,'' he said Tues-day. ''This ammonia system looks pretty promising because you don't have the emissions issues you have with diesel, it's a green cycle. The only question at this point is whether economically, it will be a solution. I believe it will be.''

Anhydrous ammonia is currently derived mostly from natural gas and as a result, it's price is tied to natural gas prices, which have been high in the past few years.

However, new ways of extracting anhydrous from coal through a gasi-fication process, are becoming more common.

Kwast said the engines provided by HEC will be tested to determine efficiency and its combustion rates compared to diesel to determine how much more costly it will be to run pumping systems on ammonia rather than diesel.

''We're pretty excited about the prospects,'' he said. ''This is a real world solution,''

HEC manufactures and sells its brand named Oxx Power internal com-bustion engines capable of running on a multitude of fuels, including ammonia, hydrogen, propane, natural gas, ethanol and gasoline.

The company's products are marketed to power generation, agricul-tural, industrial, airport ground support, vehicular and home and busi-ness customers.

HEC shares were up 25 cents, or 6.3 percent, at $4.25 on the over-the-counter bulletin board.On the Net: Hydrogen Engine Center Inc.: http://www.hydrogenenginecenter.-comSawtelle & Rosprim Inc.: http://www.sawtellerosprim.com

Science Group Backs NASA Lunar PlansBy THE ASSOCIATED PRESS Published: September 19, 2006

WASHINGTON (AP) -- A panel of scientists strongly endorsed NASA's plans to return to the moon, saying in a report Tuesday that lunar exploration will open the way toward broader studies of the Earth and solar system.

''The moon is priceless to planetary scientists,'' declared the special National Research Council panel of the National Academy of Sciences.

The scientists were asked to evaluate and give guidance to the Na-tional Aeronautics and Space Administration's plans for robotic and hu-man exploration of the moon over the next two decades.

President Bush two years ago vowed to return astronauts to the moon and establish an ''extended presence there'' in preparation for exploring Mars. He called on NASA to devote $12 billion over five years for the be-

5 5/10/2023

ginning of the program with a goal of landing on the moon between 2015 and 2020, and eventually landing on Mars.

The Academy panel said the moon holds a deep geological record of early planetary evolution and provides great opportunities for a sus-tained program of both robotic and human exploration of space.

''Only by returning to the moon to carry out new scientific exploration can we hope to close the gaps in understanding and learn the secrets that the moon alone has kept for eons,'' the 15-member panel said.

The committee was made up of academics, a journalist and retired members of private industry involved in space programs. The congres-sionally chartered Academy advises the government on scientific and technical matters.

The scientists urged NASA to stimulate lunar research along two pro-grams: one for fundamental lunar research and the other focusing on analyzing lunar data to advance research elsewhere in the solar system.

Among the priorities the panel outlined were determining the compo-sition and structure of the lunar interior, better understanding the lunar atmosphere, evaluating the moon's potential as ''an observation plat-form'' for studying the Earth, the relationship of the sun and Earth, and broader astronomy and astrophysics.

The scientists said NASA should provide astronauts with the best pos-sible technical systems for exploring the moon using both robotic, tele-operated systems and robot-assisted human exploration.

Tuesday's report was described as interim, with a more detailed report to be released in mid-2007.

The federal space agency and space enthusiasts outside of NASA long have hungered for a return to the moon. Bush's outline for exploration of the moon and later Mars represented the boldest space goal since Presi-dent Kennedy called in the early 1960s for landing Americans on the moon, a goal that was accomplished in 1969.

Two weeks ago, NASA announced it had awarded Lockheed Martin Corp. the multibillion-dollar contract to build the Orion manned lunar space craft. NASA anticipates building eight of the reusable spaceships through 2019, replacing the space shuttle.On the Net: Copy of report at National Academies Press: http://www.nap.eduNational Aeronautics and Space Administration: http://www.nasa.gov

A Chip That Can Transfer Data Using Laser LightBy JOHN MARKOFF

SAN FRANCISCO - Researchers plan to announce on Monday that they have created a silicon-based chip that can produce laser beams. The advance will make it possible to use laser light rather than wires to send data be-tween chips, removing the most significant bottleneck in computer de-sign.

As a result, chip makers may be able to put the high-speed data com-munications industry on the same curve of increased processing speed and diminishing costs - the phenom-enon known as Moore’s law - that has driven the computer industry for the last four decades.

The development is a result of re-search at Intel, the world’s largest chip maker, and the University of California, Santa Barbara. Commer-cializing the new technology may not happen before the end of the decade, but the prospect of being able to place hundreds or thousands of data-carrying light beams on stan-dard industry chips is certain to shake up both the communications and computer industries.

Lasers are already used to trans-mit high volumes of computer data over longer distances - for example, between offices, cities and across oceans - using fiber optic cables. But in computer chips, data moves at great speed over the wires inside, then slows to a snail’s pace when it is sent chip-to-chip inside a com-puter.

With the barrier removed, com-puter designers will be able to re-think computers, packing chips more densely both in home systems and in giant data centers. Moreover, the laser-silicon chips - composed of a spider’s web of laser light in addition to metal wires - portend a vastly more powerful and less expensive national computing infrastructure. For a few dollars apiece, such chips could transmit data at 100 times the speed of laser-based communica-

6 5/10/2023

tions equipment, called optical transceivers, that typically cost several thousand dollars.

Currently fiber optic networks are used to transmit data to individual neighborhoods in cities where the data is then distributed by slower con-ventional wire-based communications gear. The laser chips will make it possible to send avalanches of data to and from individual homes at far less cost.

They could also give rise to a new class of supercomputers that could share data internally at speeds not possible today.

The breakthrough was achieved by bonding a layer of light-emitting indium phosphide onto the surface of a standard silicon chip etched with special channels that act as light-wave guides. The resulting sandwich has the potential to create on a computer chip hundreds and possibly thousands of tiny, bright lasers that can be switched on and off billions of times a second.

“This is a field that has just begun exploding in the past 18 months,” said Eli Yablonovitch, a physicist at the University of California, Los An-geles, a leading researcher in the field. “There is going to be a lot more optical communications in computing than people have thought.”

Indeed, the results of the development work, which will be reported in a coming issue of Optics Express, an international journal, indicate that a high-stakes race is under way worldwide. While the researchers at In-tel and Santa Barbara are betting on indium phosphide, Japanese scien-tists in a related effort are pursuing a different material, the chemical el-ement erbium.

Although commercial chips with built-in lasers are years away, Lux-tera, a company in Carlsbad, Calif., is already selling test chips that in-corporate most optical components directly into silicon and then inject laser light from a separate source.

The Intel-Santa Barbara work proves that it is possible to make com-plete photonic devices using standard chip-making machinery, although not entirely out of silicon. “There has always been this final hurdle,” said Mario Paniccia, director of the Photonics Technology Lab at Intel. “We have now come up with a solution that optimizes both sides.”

In the past it has proved impossible to couple standard silicon with the exotic materials that emit light when electrically charged. But the uni-versity team supplied a low-temperature bonding technique that does not melt the silicon circuitry. The approach uses an electrically charged oxygen gas to create a layer of oxide just 25 atoms thick on each mate-rial. When heated and pressed together, the oxide layer fuses the two materials into a single chip that conducts information both through wires and on beams of reflected light.

“Photonics has been a low-volume cottage industry,” said John E. Bow-ers, director of the Multidisciplinary Optical Switching Technology Center

at the University of California, Santa Barbara. “Everything will change and laser communications will be everywhere, including fiber to the home.”

Photonics industry experts briefed on the technique said that it would almost certainly pave the way for commercialization of the long-sought convergence of silicon chips and optical lasers. “Before, there was more hype than substance,” said Alan Huang, a former Bell Laboratories re-searcher who is a pioneer in the field and is now chief technology officer of the Terabit Corporation, a photonics start-up company in Menlo Park, Calif. “Now I believe this will lead to future applications in optoelectron-ics.”

Another Reason City Never Sleeps: More BedbugsBy SEWELL CHAN

New York City is experiencing a dramatic resurgence in bedbugs - those pesky oval insects that hide in the crevices of furniture and feast on human blood at night - and officials are confounded about how best to respond.

Moreover, city officials revealed yesterday that state regulators had failed to publish standards for sanitizing used mattresses and box springs before they can be resold - even though such standards were supposed to be developed years ago. The proliferation of secondhand furniture is believed to be one factor in the rise in bedbug infestations.

Although bedbugs are not considered a major health threat because they do not transmit disease, they can cause itchy welts and often re-quire expensive exterminations. In the last fiscal year, the city’s Depart-ment of Housing Preservation and Development received 4,638 com-plaints about bedbugs in rental housing - nearly five times as many as in the previous year.

At a City Council hearing yesterday on the issue, entomologists and exterminators said that bedbugs have been proliferating at levels not seen in decades. The cause of the resurgence is not certain, but experts have speculated that increased international travel, a recent ban on powerful pesticides and the market in used furniture have been factors.

A bill by Councilwoman Gale A. Brewer of Manhattan would ban the sale of reconditioned mattresses - old mattresses with a new fabric cover sewn onto them, often with the original upholstery and padding underneath - and create a task force to study the issue and make rec-ommendations within a year.

The International Sleep Products Association, the trade association for mattress manufacturers, said yesterday that it supported a ban on the sale of reconditioned mattresses. “The filth from the used mattress that lies just beneath the new fabric cover of a reconditioned product can be astounding,” said Ryan Trainer, a lawyer for the association.

7 5/10/2023

Andrew Eiler, director of legislation for the city’s Department of Con-sumer Affairs, however, expressed uncertainty about the bill. A twin-size mattress without a box spring can be bought for $40 from the Salvation Army, or about $50 less than a new mattress. “While $50 may not ap-pear as a significant difference to some, it may be an unbridgeable gap to consumers with limited incomes,” he said.

Under a 1996 law, manufacturers of used bedding must certify that they have sanitized the bedding, using standards developed by the state’s Department of State, in consultation with the Department of Health. The law was later expanded to cover sellers of used bedding - there are currently 261 registered with the state - as well.

The problem, Mr. Eiler said, is that the state has never published sani-tization standards. “Since there are no rules, the certifications are rela-tively meaningless,” he said.

In a telephone interview after the hearing, Eamon Moynihan, a spokesman for the Department of State, confirmed that “there were no standards promulgated.” The reasons why were not entirely clear, he said, but it seems that when the staff looked at the 1996 law, they con-cluded that to enforce it would have made reconditioned mattresses so expensive as to effectively outlaw them.

Mr. Moynihan said the department had no plan to revisit the issue.The city does not directly regulate the sale of used mattresses. It li-

censes 3,795 dealers in secondhand goods, not counting used-car deal-ers, Mr. Eiler said, but it has no way to know how many of those dealers sell used mattresses. There is just not enough information, he said, to know whether banning the sale of used mattresses in the city would pre-vent the spread of the pests.

Richard J. Pollack, an expert in parasitic insects at the Harvard School of Public Health who testified at the hearing, said he doubted that the proposed ban would be effective. “As long as used mattresses have value, they will remain a commodity despite attempts to regulate their movements,” he said.

The resurgence of bedbugs appears to be affecting the city as a whole. “There is no clear pattern, or neighborhood that’s particularly at risk, at least that I’m aware of,” Daniel Kass, director of environmental surveillance and policy for the city’s Department of Health and Mental Hygiene, said at the hearing.

Exterminators have been grappling with how to suppress the infesta-tions. Several of them testified yesterday, and Cindy Mannes, of the Na-tional Pest Management Association, said in a telephone interview that it recorded a 71 percent increase from 2000 to 2005 in the number of ex-terminators who had received calls about bedbugs.

Councilman Leroy G. Comrie Jr. of Queens, who presided over the hearing, said that residents often blame themselves for infestations. The insects easily crawl between homes through walls, floors and ceilings.

Louis N. Sorkin, an entomologist at the American Museum of Natural History, said there was an urgent need to raise public awareness. “In some cases, people are using old remedies that may be dangerous to one’s health, such as spraying a mattress with gasoline or kerosene to kill bedbugs,” he said.

Dr. Pollack said, “We shouldn’t be too hysterical when dealing with bedbugs.” At one point, he showed a slide of a 1793 pamphlet on how to control bedbugs. ‘We keep trying to throw things at them, but they are outwitting us,” he said.Vital SignsTemper Tracking: Angry Outbursts May Take a Toll on the LungsBy NICHOLAS BAKALAR

Men who are chronically hostile and angry may face a future of sharply diminishing lung function, new research suggests.

In 1986, scientists administered a questionnaire to 670 men ages 21 to 80 to assess their hostility. Each then received a pulmonary exam within one year of completing the questionnaire. The men were tracked for an average of 8.22 years, with comprehensive physical examinations every 3 to 5 years, including an average of three pulmonary function tests.

After controlling for age, weight, height, smoking status and other variables, the scientists found a consistent association between high hostility and lower levels of lung function. Among more hostile men, pul-monary function was worse at every exam over a 10-year period when compared with less hostile subjects. The study appears online in Thorax.

Since levels of lung function were in the normal range at the start of the study, the researchers say, the possibility that poor lung function led to hostility rather than the other way around is unlikely. They acknowl-edge, however, that an unknown factor could cause both hostility and poor lung function.

Still, Dr. Rosalind J. Wright, an assistant professor of medicine at Har-vard and the senior author of the study, said there was no doubt that emotions could cause physical changes, some of which could be detri-mental.

“When you experience physical symptoms around negative emotions, your heart rate goes up, you start sweating, and so on,” Dr. Wright said. “Changes in bodily functions - nervous system, immune function - need to occur for you to feel these things. It is possible that similar processes are going on more locally, say in the lungs, which over many years may cause inflammation that affects lung function.”

8 5/10/2023

Personal HealthShock Therapy Loses Some of Its Shock ValueBy JANE E. BRODY

For an older woman I know who was suffering from “implacable de-pression” that refused to yield to any medications, electroconvulsive therapy - popularly called shock therapy - was a lifesaver. And Kitty Dukakis, wife of the former governor of Massachusetts and 1988 Demo-cratic presidential nominee, says ECT, as doctors call it, gave her back her life, which had been rendered nearly unlivable by unrelenting de-spair and the alcohol she used to assuage it.

Neither woman has experienced the most common side effect of ECT: memory disruption, though Mrs. Dukakis recalls nothing of a five-day trip to Paris she took after her treatment.

The television host Dick Cavett, who also had the treatment, wrote in People magazine, “In my case, ECT was miraculous.”

Mr. Cavett added, “It was like a magic wand.”But for a man I know who was suicidally depressed and given ECT as a

last resort, it did nothing to relieve his depression but destroyed some of his long-term memory.

Such differences in effectiveness and side effects are not unusual in medicine and psychiatry, and they are not played down in a new book called “Shock,” which Mrs. Dukakis wrote with Larry Tye, a former Bos-ton Globe reporter. The book, in which Mrs. Dukakis details her experi-ence with depression and ECT, explores the history, effectiveness and downsides of this nearly 70-year-old treatment, a remedy that has been repeatedly portrayed in film and literature as barbaric, inhuman, even torturous.

Few people seem to know that ECT has undergone significant changes in recent decades, placing it more in line with widely accepted treat-ments like those used to restart a stopped heart or to correct an abnor-mal heart rhythm. After a rather precipitous decline in the 1960’s when effective antidepressant drugs became available, ECT since the 1980’s has experienced something of a comeback, and is used primarily in these circumstances:• When rapid reversal of a severe or suicidal depression is needed.• When depression is complicated by psychosis or catatonia.• When antidepressants and psychotherapy fail to alleviate a crippling depression.• When antidepressants cannot safely be used, such as during preg-nancy.• When mania or bipolar disorder do not respond to drug therapy.

Though there is no official count, experts estimate that more than 100,000 patients undergo ECT each year in the United States.

ECT was developed in the 1930’s by an Italian neurologist, Ugo Cer-letti, who “tamed” difficult mental patients with electric shocks to the brain after noting that such shocks given to hogs before slaughter ren-dered them unconscious but did not kill them. In its first decades of use, ECT was administered to fully conscious patients, causing them to lose consciousness and experience violent seizures and uncontrolled muscle movements that sometimes broke bones. It was sometimes used in pa-tients without their consent, or at least without informed consent.

And while evidence for its effectiveness did not extend much beyond depression, for a time ECT was applied to patients with all kinds of emo-tional disturbances, including schizophrenia. It was also widely used in mental hospitals to punish or sedate difficult patients, as was graphically depicted by Jack Nicholson in the movie “One Flew Over the Cuckoo’s Nest.”

Some people may also recall that Ernest Hemingway, who suffered from life-long and often self-medicated depression, committed suicide in 1961 shortly after undergoing ECT. He had told his biographer: “Well, what is the sense of ruining my head and erasing my memory, which is my capital, and putting me out of business? It was a brilliant cure, but we lost the patient.”A Modified Treatment

Though the impression of ECT left in the public mind by such films and writings persists, ECT today is a far more refined and limited therapy. Most important, perhaps, is the use of anesthesia and muscle relaxants before administering the shock, which causes a 30-second convulsion in the brain without the accompanying movements. Thus, there is no phys-ical damage. The pretreatment also leaves no memory of the therapy it-self.

The amount of current used today is lower and the pulse of electricity much shorter - about two seconds - reducing the risk of post-treatment confusion and memory disruption. While memory losses still occur in some patients, now the most serious risk associated with ECT is that of anesthesia.

Most patients require a series of six to eight treatments, delivered over several weeks. As my friend discovered, however, it is not univer-sally effective. About three-fourths of patients are relieved of their debil-itating symptoms at least temporarily. The remaining one-quarter are not helped, and some may be harmed.

Despite its long history, no one knows how ECT works to ease depres-sion and mania. There is some evidence that it reorders the release of neurotransmitters, favoring an increase of substances like serotonin, which counters depression. Some experts view it as a pacemaker for the brain that disrupts negative circuitry.

9 5/10/2023

The beauty of ECT is the speed with which it works. Antidepressants can take as long as six weeks to relieve serious depression. Mrs. Dukakis reported that she had begun to feel better after the first in an initial se-ries of five outpatient ECT treatments given over a two-week period.A Stopgap Measure

But - and this is a big but - ECT is not a cure for depression. It is more like a stopgap measure that brings patients to a point where other ap-proaches, including antidepressants and cognitive behavioral therapy, can work to stave off relapses. Although some ECT patients never re-lapse, most are like Mrs. Dukakis, who over the course of four years has come back for seven more rounds of ECT. She explained that while she used to deny the early signs of a recurring depression, she now calls her doctor “as soon as I spot the gathering clouds.”

“ECT has wiped away that foreboding,” she wrote, and “given me a sense of control, of hope.” It has also helped her get off antidepressants, which had side effects like bowel, sexual and sleep disturbances and an inability to experience “the full range of my feelings.”

ECT should not be administered without the patient’s (or the patient’s surrogate’s) fully informed consent, which includes consideration of all possible side effects. The most common side effects are headache, mus-cle soreness and confusion shortly after the procedure, as well as short-term memory loss, which usually improves over a period of days to months.

But according to the American Psychiatric Association, there is no evi-dence that ECT causes brain damage. Abuse of the procedure has de-clined strikingly. Today fewer than 2 percent of patients hospitalized in psychiatric facilities in New York State receive ECT. Properly used, it can be lifesaving.

Though there is not nearly the money to be made from ECT that there is in selling antidepressants, work on improvements continues. Modern ECT is sometimes delivered to only one side of the brain, reducing the chances of memory deficits.

Another new approach uses a magnetically induced current that can be aimed at specific regions of the brain, possibly altering them perma-nently. An advantage of this treatment, however, is that it does not re-quire the use of anesthesia.ObservatoryFinding a Feeding Frenzy Among Baby LeechesBy HENRY FOUNTAIN

Anyone who grew up in a large family knows the kinds of sibling com-petition that can arise. Among these are dinner-table fights over who gets the extra piece of chicken, say, or the last potato.

Sibling competition over food occurs in other animals as well, particu-larly birds, and scientists suggest that food size can make a difference. If

the pieces of food are small, the most aggressive offspring can snatch most of them, to the detriment (sometimes even the death) of the oth-ers. But if the pieces are large, no one sibling can monopolize the feed-ings. (To put it in dinner-table terms, it’s easy for the older brother to swipe the last drumstick, but not a whole roast chicken.)

Researchers in Australia have found the same behavior in a very dif-ferent animal: a leech.

Martin Burd, a professor at Monash University in Melbourne, and col-leagues studied Helobdella papillornata, a quarter-inch-long leech that does not live on blood. Like some other leeches it tends to its young, carrying up to 60 juveniles on its underside and feeding them snails.

Dr. Burd wondered if the young leeches might be competing for the snail tissue, so he, Fredric R. Govedich and Laura Bateson carefully se-lected the size of the snails. Some leeches had only snails with large shell openings, while others had snails with small openings. The thinking was that more of the offspring could reach into the large snails to eat, but that with the smaller snails, the most aggressive young leeches would crowd out the others.

The animals are microscopic, so it was difficult to see what was going on. “We can see that they don’t all get their heads into the snail at the same time,” Dr. Burd said. “But we can’t be sure it’s the same ones get-ting the first crack at them.”

So the researchers used an indirect method to determine if the young leeches were competing: they weighed them. Their findings, published in Proceedings B of the Royal Society, showed a greater disparity of weights among those fed smaller snails.

Dr. Burd said they hadn’t expected to see such competitive behavior since, unlike birds, leeches don’t have to eat immediately after hatch-ing. “They can just hang out and not grow,” he said. “But even when you leap across the boundaries into these indeterminate growers and cold-blooded things, you see the same competitive behavior.”Synchronized Migration

Bird migrations are remarkable events, with thousands upon thou-sands of individuals of the same species departing for or returning from breeding grounds over the same periods year after year.

While most migrating species are known for their consistent timeta-bles as a whole, less is known about how consistent individuals are from year to year in their departures and arrivals.

A study of bar-tailed godwits, a shorebird that makes one of the long-est migrations of any bird, shows that they are quite consistent. Almost all the birds studied left for their breeding grounds within the same week from year to year.

10 5/10/2023

The bar-tailed godwits in the study breed in Alaska and spend winter in New Zealand and Australia, making for a migration of about 9,000 miles by way of the Yellow Sea off China and the Korean Peninsula.

Phil F. Battley of Otago University in New Zealand banded godwits in the Firth of Thames in New Zealand and watched roosts in March and April over three years to determine departure dates for specific birds. His findings were published in Biology Letters.

Migration dates can be affected by external factors, like weather and food availability (since birds have to fuel up before heading off). But the study suggests that with godwits, at least, departure is set according to a strict internal schedule. Dr. Battley also studied the birds’ appearance and found that males were very consistent from year to year in how much they molted - lost their drab color for richer breeding plumage - before taking off. If external factors were more important in determining departure date, such consistency in appearance would not be expected.Titan’s Ethane

Saturn’s largest moon, Titan, is different. As with Earth, the largest component of its atmosphere is nitrogen. But after that things get weird. Methane is the second-most-abundant gas on Titan, and it is broken down by sunlight, creating lots of ethane.

That’s the idea, at least, but scientists have been puzzled by a basic mystery: Where is all the ethane? If methane has been breaking down for as long as Titan has existed (roughly 4.5 billion years), there should be oceans and clouds of ethane everywhere.

Scientists still haven’t found any oceans, but there is now strong evi-dence of a vast ethane cloud at Titan’s north pole. If this ethane con-denses and freezes during the winters (and at the south pole, as well) that could help explain the lack of ethane oceans elsewhere.

Caitlin A. Griffith of the University of Arizona and other researchers found evidence of ethane at an altitude of 20 to 30 miles from 51 de-grees to 68 degrees north latitude using data from a mapping spectrom-eter on board the Cassini spacecraft. The findings are reported in the journal Science.

The spectrometer has yet to obtain data from the pole itself, but the researchers say the evidence suggests that the band of ethane they are seeing is the fringe of an enormous cloud over the poles, created as the atmosphere subsides, or sinks, at high latitudes.

Winter polar temperatures are cold enough for ethane to freeze, so there could be much ethane ice at the polar caps. But the northern cap has not been adequately studied yet, and the data from the southern cap are inconclusive. So plenty of mystery remains.Searching Mars

Mars has plenty of mystery, too, although it has been visited by many more spacecraft than Titan.

The latest Martian probe, the Mars Reconnaissance Orbiter, has now achieved its working polar orbit, ranging from about 155 miles near the south pole to about 200 miles near the north. That’s not bad given that about six months ago the highest point of the spacecraft’s orbit was 28,000 miles.

The altitude was reduced using a combination of thrusters and atmo-spheric braking, slowing the spacecraft as it passed through the fringes of the Martian atmosphere over and over again.

The orbiter will begin its search for water on Mars in November.Really?The Claim: Never Remove a Barb From a Stingray InjuryBy ANAHAD O’CONNORTHE FACTS The death of Steve Irwin, the famed “crocodile hunter,” this month came as a shock to his legions of fans. But for some, it also raised a question: What to do if attacked by a stingray?

In general, attacks by venomous stingrays are rare and usually occur when a person accidentally steps on one in shallow water. Most nonfatal injuries are to the legs or feet, and doctors recommend washing the wound in hot water to destroy any venom and to relieve pain. Then, seek medical help.

But an attack in which a stingray’s barb not only pierces the heart but becomes detached - as was the case with Mr. Irwin, who reportedly re-moved the barb - is even more unusual, said Christopher Lowe, a stingray expert at California State University, Long Beach.

In that case, the potential for complications is so great that only a doc-tor should attempt removal. Because barbs are serrated, they tear at flesh when removed, and it’s unlikely that pulling them out will lower ex-posure to any venom. Sharp objects can also act as plugs that stem ex-cessive bleeding until help arrives, said Dr. Adam E. Saltman, a cardio-thoracic surgeon at Maimonides Medical Center in Brooklyn.

Only two cases of people surviving cardiac stingray injuries are known; both were described in a 2001 report in the Medical Journal of Australia. An adult swimmer was struck in his right coronary artery. He was oper-ated on quickly. In the other case, a fisherman had a barb removed from his right ventricle.THE BOTTOM LINE If embedded, a stingray barb should be removed by a

doctor.EssayIn Science-Based Medicine, Where Does Luck Fit In?By BARRON H. LERNER, M.D.

11 5/10/2023

Several years ago, an obese, diabetic patient of mine insisted on knee-replacement surgery against the wishes of her doctors, who be-lieved that it would be too dangerous. She came through with flying col-ors.

While everyone rightly praised the efforts of her surgeon and physical therapist, another factor in her recovery was ignored: luck. Why are doc-tors and patients so reluctant to discuss a phenomenon that permeates medicine every day?

The likeliest reason that luck - good or bad - is so often disregarded is that at first glance, it appears contrary to the scientific basis of medicine. That is, doctors employ the best scientific knowledge avail-able to diagnose and treat disease. How well patients do thus reflects this acumen.

Luck seems to have become particularly anathema in an era of evi-dence-based medicine, in which physicians and patients are encouraged to learn the latest relevant data to guide decisions. Dr. Peter A. Ubel, a University of Michigan internist and author of “You’re Stronger Than You Think,” believes that his patients prefer biological explanations of why they are sick, rather than hearing that they have bad genes or bad luck.

But given the biological variability within given diseases, like cancer, and the fact that variable genetic makeup leads different individuals to respond differently to diseases and therapies, even better scientific knowledge will not eliminate the role played by luck. Chance, the British physician R. J. Epstein wrote in the Quarterly Journal of Medicine, en-sures different outcomes within given sick populations.

A few examples? Roughly 1 percent of North American whites are highly resistant to H.I.V. infection because they lack a certain cell sur-face protein. Lucky. Roughly 5 percent of people infected with the hep-atitis B virus develop chronic active hepatitis, an often serious liver dis-ease. Unlucky.

This phenomenon can be seen in individual cases of disease as well. When the cyclist Lance Armstrong was given a diagnosis of testicular cancer in 1996, it had already metastasized throughout his body, includ-ing his brain. His doctors gave him less than a 50 percent chance of sur-vival.

Mr. Armstrong’s subsequent cure can surely be attributed to the chemotherapy he received, but the fact is that other men with similar cases of testicular cancer died despite the same regimen. He has noted his good fortune, saying that his survival was mostly “a matter of blind luck.”

But others shy away from identifying either good or bad luck. In her recent book “The Year of Magical Thinking,” Joan Didion describes the death of her husband, John Gregory Dunne, from a heart attack. Noting

that he had a long history of heart problems, she declined to attribute his death to bad luck.

But it seems that Mr. Dunne was unlucky - twice. First, he had inher-ited heart disease. And second, it had killed him at 71, even though oth-ers with his disease, coronary atherosclerosis, now live into their 80’s and 90’s. Of course, those who died of heart disease at ages even younger than Mr. Dunne’s were unluckier.

A more frank acknowledgment of the role luck plays has another virtue: eliminating the tendency to second-guess and blame patients. Medicine today puts a huge emphasis on modifying risk factors for dis-eases, urging patients to take medications for diabetes and high choles-terol, for example, and to improve their diets.

But risk reduction is not risk elimination. Even well-established inter-ventions, like regular screening mammograms in women over 50 and antihypertensive pills for high blood pressure, lower the risk of death by 30 percent at most. That means that plenty of patients who are 100 per-cent compliant with their doctors’ wishes will still die of breast cancer or complications of hypertension, like heart attacks or strokes. These are the unlucky ones.

And then there are always those patients who constantly disregard medical recommendations and seemingly suffer no ill effects. You guessed it: lucky.

This is not to say that patients might better spend their time wishing on stars than taking pills. As the cases of Lance Armstrong and my knee-replacement patient demonstrate, seeking out the best medical care surely increases one’s chances of doing well. There are just no guaran-tees.

Even Joan Didion, who played down the role of bad luck in her hus-band’s death, realized there was no value in revisiting what more might have been done to save his life. Multiple medical interventions, she wrote, had already postponed his death. When he died in their living room, no action by her “could have given him even one more day.”

And what of my patient? She did well for several months after her surgery. Then one day, while she was at the hospital getting a routine X-ray, she suddenly slumped over from a heart attack, a complication of diabetes. The staff could not resuscitate her, and she died. Her luck had run out.Dr. Barron H. Lerner teaches medicine and public health at Columbia Uni-versity.

Bias Is Hurting Women in Science, Panel ReportsBy CORNELIA DEAN Published: September 19, 2006

Women in science and engineering are hindered not by lack of ability but by bias and “outmoded institutional structures” in academia, an ex-pert panel reported yesterday. The panel, convened by the National

12 5/10/2023

Academy of Sciences, said that in an era of global competition the na-tion could not afford “such underuse of precious human capital.” Among other steps, the report recommends altering procedures for hiring and evaluation, changing typical timetables for tenure and promotion, and providing more support for working parents.

“Unless a deeper talent pool is tapped, it will be difficult for our coun-try to maintain our competitiveness in science and engineering,” the panel’s chairwoman, Donna E. Shalala, said at a news conference at which the report was made public. The report, “Beyond Bias and Barri-ers: Fulfilling the Potential of Women in Academic Science and Engineer-ing,” is online at www.nationalacademies.org.

Dr. Shalala, a former secretary of health and human services who is now president of the University of Miami, said part of the problem was insufficient effort on the part of college and university administrators. “Many of us spend more energy enforcing the law on our sports teams than we have in our academic halls,” she said.

The panel dismissed the idea, notably advanced last year by Lawrence H. Summers, then the president of Harvard, that the relative dearth of women in the upper ranks of science might be the result of “innate” in-tellectual deficiencies, particularly in mathematics.

If there are cognitive differences, the report says, they are small and irrelevant. In any event, the much-studied gender gap in math perfor-mance has all but disappeared as more girls enroll in demanding classes. Even among very high achievers, the gap is narrowing, the pan-elists said.

A spokesman for Mr. Summers said he was out of the country and could not be reached for comment.

Nor is the problem a lack of women in the academic pipeline, the re-port says. Though women leave science and engineering more often than men “at every educational transition” from high school through col-lege professorships, the number of women studying science and engi-neering has sharply increased at all levels.

For 30 years, the report says, women have earned at least 30 percent of the nation’s doctorates in social and behavioral sciences, and at least 20 percent of the doctorates in life sciences. Yet they appear among full professors in those fields at less than half those levels. Women from mi-nority groups are “virtually absent,” it adds.

The report also dismisses other commonly held beliefs - that women are uncompetitive or less productive, that they take too much time off for their families. Instead, it says, extensive previous research showed a pattern of unconscious but pervasive bias, “arbitrary and subjective” evaluation processes and a work environment in which “anyone lacking the work and family support traditionally provided by a ‘wife’ is at a seri-ous disadvantage.”

Along with Dr. Shalala, the panel included Elizabeth Spelke, a profes-sor of psychology at Harvard who has long challenged the “innate differ-ences” view, and Ruth J. Simmons, the president of Brown University, who established a widely praised program for aspiring engineers when she was president of the all-female Smith College.

The report was dedicated to another panelist, Denice Denton, an elec-trical engineer who until her suicide this summer was chancellor of the University of California, Santa Cruz, and a forceful advocate for women, gay men and lesbians, and minority members in science and engineer-ing.

The 18-member panel had one man: Robert J. Birgeneau, chancellor of the University of California, Berkeley. But Dr. Shalala noted that the Na-tional Academy of Sciences committee that reviewed the report had 10 men.

“Nothing was a foregone conclusion,” she said, adding that the com-mittee was surprised at the strength of evidence supporting the report’s conclusions. In an interview, Dr. Simmons of Brown said: “The data don’t lie. There are lots of arguments one could have mounted 30 years ago, but 30 years later we have incontrovertible data that women do have the ability to do science and engineering at a very high level.”

She said the more relevant question was, “Why aren’t they electing these fields when the national need and the opportunities in the fields are so great?”

Leveling the playing field does not mean giving women an unfair ad-vantage, another panelist, Maria Zuber said yesterday. Dr. Zuber, a geo-physicist at M.I.T., said for example that scholarly journals might elimi-nate the identity of authors when they sent out manuscripts for pre-pub-lication review. That way, she said, work would be judged on its merits, rather than by the prominence of its authors.

Ana Mari Cauce, a psychologist at the University of Washington and another panelist, said at the news conference, “This is about more ex-cellence; this is not about changing the bar or lowering the bar.”

Ben A. Barres, a neuroscientist at Stanford who was not connected to the effort but who published a commentary on women in science last summer in the journal Nature, echoed the report’s assertion that small administrative changes could produce big differences for women in sci-ence.

He pointed to the Pioneer award program for young researchers run by the National Institutes of Health. Dr. Barres, who has been a judge for the awards, said that even making it known that scientists could nomi-nate themselves helped make the pool of winners more diverse.

Dr. Shalala began the report’s preface by recalling that when she was in graduate school in political science in the 1960’s and as a young pro-

13 5/10/2023

fessor, she was told that fellowships or tenure would never be hers be-cause she was a woman.

Overt discrimination like that is now rare, she wrote, but progress has been too slow. “We need overarching reform now,” she said yesterday.

Bitter taste identifies poisons in foodsScientists at the Monell Chemical Senses Center report that bitter

taste perception of vegetables is influenced by an interaction between variants of taste genes and the presence of naturally-occurring toxins in a given vegetable. The study appears in the September 19 issue of Cur-rent Biology.

Scientists have long assumed that bitter taste evolved as a defense mechanism to detect potentially harmful toxins in plants. The Current Bi-ology paper provides the first direct evidence in support of this hypothe-sis by establishing that variants of the bitter taste receptor TAS2R38 can detect glucosinolates, a class of compounds with potentially harmful physiological actions, in natural foods.

"The findings show that our taste receptors are capable of detecting toxins in the natural setting of the fruit and vegetable plant matrix," said senior author Paul Breslin, a Monell sensory scientist.

Glucosinolates act as anti-thyroid compounds. The thyroid converts io-dine into thyroid hormones, which are essential for protein synthesis and regulation of the body's metabolism. Glucosinolates inhibit iodine uptake by the thyroid, increasing risk for goiter and altering levels of thyroid hormones. The ability to detect and avoid naturally-occurring glucosino-lates would confer a selective advantage to the over 1 billion people who presently have low iodine status and are at risk for thyroid insuffi-ciency.

In the study, 35 healthy adults were genotyped for the hTAS2R38 bitter taste receptor gene; the three genotypes were PAV/PAV (sensitive to the bitter-tasting chemical PTC,) AVI/AVI (insensitive), and PAV/AVI (intermediate).

Subjects then rated bitterness of various vegetables; some contained glucosinolates while others did not. Examples of the 17 glucosinolate-containing vegetables include watercress, broccoli, bok choy, kale, kohlrabi, and turnip; the 11 non-glucosinolate foods included radicchio, endive, eggplant and spinach. Subjects with the sensitive PAV/PAV form of the receptor rated the glucosinolate-containing vegetables as 60% more bitter than did subjects with the insensitive (AVI/AVI) form. The other vegetables were rated equally bitter by the two groups, demon-strating that variations in the hTAS2R38 gene affect bitter perception specifically of foods containing glucosinolate toxins.

Together, the findings provide a complete picture describing individual differences in responses to actual foods at multiple levels: evolutionary,

genetic, receptor, and perceptual. "The sense of taste enables us to de-tect bitter toxins within foods, and genetically-based differences in our bitter taste receptors affect how we each perceive foods containing a particular set of toxins," summarizes Breslin.

Breslin notes, "The contents of the veggies are a double-edged sword, depending upon the physiological context of the individual eating them. Most people in industrialized cultures can and should enjoy these foods. In addition to providing essential nutrients and vitamins, many are re-ported to have anti-cancer properties."

Lead author Mari Sandell comments on additional nutritional and prac-tical implications of the study, "Taste has a great impact on food accept-ability and choice. A comprehensive understanding how food compo-nents contribute to taste is necessary to develop modern tools for both nutritional counseling and food development."Prostate cancer treatment increases risk of diabetes and

heart diseasePhysicians and patients should be aware of potential risks associ-

ated with GnRH agonist therapyBOSTON -- A treatment mainstay for prostate cancer puts men at in-

creased risk for diabetes and cardiovascular disease, according to a large observational study published in the Sept. 20 Journal of Clinical Oncology.

"Men with prostate cancer have high five-year survival rates, but they also have higher rates of non-cancer mortality than healthy men," says study author Nancy Keating, MD, MPH, assistant professor of health care policy and of medicine at Harvard Medical School. "This study shows that a common hormonal treatment for prostate cancer may put men at significant risk for other serious diseases. Patients and physicians need to be aware of the elevated risk as they make treatment decisions."

The principal systemic therapy for prostate cancer involves blocking testosterone production. This is done either by removal of the testes (bi-lateral orchiectomy), or more commonly, by regular injections of a go-nadotropin-releasing hormone (GnRH) agonist drug. GnRH agonists are the main therapy for metastatic prostate cancer and may also improve survival for some men with locally-advanced cancers.

However, little is known about the efficacy of GnRH agonists in treat-ing men with less-advanced local or regional prostate cancer, many of whom receive this therapy. Earlier studies have found GnRH agonists to be associated with obesity and insulin resistance, a precursor to dia-betes.

"Our study found that men with local or regional prostate cancer re-ceiving a GnRH agonist had a 44 percent higher risk of developing dia-betes and a 16 percent higher risk of developing coronary heart disease

14 5/10/2023

than men who were not receiving hormone therapy," says Keating, who is also a physician at Brigham and Women's Hospital.

"Doctors should think twice about prescribing GnRH agonists in situa-tions for which studies have not demonstrated improved survival until we better understand the risks of treatment," says co-author Matthew Smith, MD, PhD, associate professor of medicine at HMS and a medical oncologist at Massachusetts General Hospital. "For men who do require this treatment, physicians may want to talk with their patients about strategies, such as exercise and weight loss, which may help to lower risk of diabetes and heart disease."

Given the number of men receiving GnRH agonists, often for many months or years, these increased risks can have important implications for the health of prostate cancer survivors, says Keating. Additional studies are needed to fully understand the biological mechanisms re-sponsible for these increased risks.

Prostate cancer is the most frequently diagnosed cancer among men, affecting more than 200,000 men in the United States every year. With prostate cancer's favorable prognosis, however, decisions about treat-ments are particularly important because adverse effects and complica-tions of treatments may impact overall health and quality of life more than prostate cancer itself.

The study assessed whether androgen deprivation therapy was associ-ated with an increased incidence of diabetes, coronary heart disease, myocardial infarction, or sudden cardiac death by examining data from approximately 73,000 men age 66 or older who were diagnosed with lo-cal or regional prostate cancer.

Mirrors in the mind: New studies elucidate how the brain reflects onto itself the actions of others

In three new independent studies, researchers have deepened our un-derstanding of the remarkable ability of some specialized areas of the brain to activate both in response to one's own actions and in response to sensory cues (such as sight) of the same actions perpetrated by an-other individual. This ability is thought to be based in the activity of so-called mirror neurons, which have been hypothesized to contribute to skills such as empathy, socialized behavior, and language acquisition. The new findings contribute to our understanding of how conceptually related instances of language and action, and sound and action, are linked in the brain, and how the brain distinguishes actions perpetrated by "self" and by "other." The studies are reported by three independent research groups: Lisa Aziz-Zadeh (now at USC) and colleagues at the University of Parma, Italy, UCLA; Christian Keysers and colleagues at the University of Groningen, The Netherlands and UC Berkeley; and Simone Schütz-Bosbach and colleagues at University College London, the Max

Planck Institute for Human Cognitive and Brain Sciences in Germany, and the University of Rome. The papers appear in the September 19th issue of Current Biology, published by Cell Press.

Mirror neurons were first identified in the cortex of macaque monkeys: A particular subset of these neurons fire when, for example, a monkey picks up a banana, and when the monkey observes a human picking up a banana in a similar way. Mirror-neuron activity appears to be highly specific, such that a somewhat different set of mirror neurons would fire if a banana were poked, for example, rather than picked up. There is also evidence that mirror neurons link actions not only with visual stim-uli, but also with other types of sensory cues. Technical limitations have impeded identification of individual mirror neurons in humans, but brain-imaging studies support the existence of these neurons.

In the new work from Lisa Aziz-Zadeh and colleagues, researchers used a brain-imaging technique to investigate how literal phrases de-scribing actions performed by the mouth, hand, or foot influenced corti-cal neurons that are activated by the sight of actions being performed by mouth, hand, or foot.

The researchers found a significant concordance between activation of certain cortical areas in response to linguistic descriptions and observed actions relating to the different body parts carrying out the actions. For example, when individuals read literal phrases such as "biting the peach" or "biting the banana," some brain areas activated that were also stimulated by videos of fruit being bitten. Similar findings were ob-tained for hand actions (for example, grasping a pen) and foot actions (for example, pressing a piano pedal). Together, the findings suggest that mirror neurons play a key role in the mental "re-enactment" of ac-tions when linguistic descriptions of those actions are conceptually pro-cessed.

In the study reported by Christian Keysers, Valeria Gazzola, and col-leagues, researchers investigated a different question: how mirror neu-rons might contribute to our understanding of auditory cues. Past work had shown that in monkeys, so-called auditory mirror neurons activate when monkeys perform certain actions and when they hear the same actions being performed. In the new work, the researchers report new evidence for an auditory mirror system existing in humans as well.

When subjects were presented with sounds corresponding to mouth actions (such as crunching candy, kissing, or emptying a soda can with a straw) and hand actions (such as ripping a sheet of paper or opening a zipper), brain areas are activated that overlap with areas activated by the execution of those actions by the subjects themselves. Within this area, a subregion was preferentially activated when mouth actions were either heard or performed, and another subregion was preferentially ac-

15 5/10/2023

tivated when hand actions were heard or performed. In addition, the re-searchers found that most of this mirror system was also responsive to the sight of these actions being performed, suggesting that a particular area of the brain can respond similarly to execution of an action and its representation in different types of sensory cues.

Intriguingly, the researchers also found that of the subjects taking part in the experiment, those that scored higher on tests for empathy acti-vated the system more strongly than those who scored lower on the em-pathy evaluation. While the relationship between motor mirror systems and empathy skills is far from clear, these findings are consistent with the existence of a link between the two.

Though mirror neurons appear to relate--and, potentially, equate--the actions of oneself with those of another, we are in fact highly adept at distinguishing our own actions from those of someone else. The basis for this distinction is explored in the study reported by Simone Schütz-Bosbach, Patrick Haggard, and colleagues, who used an established method--the so-called rubber-hand illusion--for experimentally manipu-lating the sense of body ownership. This approach was useful because without such illusion, it is difficult to identify meaningful differences in how the brain responds to actions performed by oneself or others--the two scenarios involve significant differences in, for example, visual view-point and familiarity, and other sensory inputs.

Past work had used the rubber-hand illusion to show that when a rub-ber hand is seen being stroked at the same time that the viewer's own (unseen) hand is synchronously stroked, the viewer feels that the rubber hand becomes part of his or her body.

In the new work, the researchers used this illusion--though in this case, the rubber hand was replaced by a real hand of an experimenter--to control whether a subject experienced that an experimenter's hand was the subject's own or not. This allowed the researchers to investigate whether finger movements made by the experimenter's hand were able to facilitate the subject's own finger movements--this facilitation was measured by the ability of benign stimulation of a particular brain region to promote motor signals (corresponding to those finger movements) in the subject's own hand.

The researchers found that such facilitation did occur, but, curiously, it occurred when the illusion was not effective, and subjects felt that the experimenter's hand was not their own. Observing actions interpreted as one's own tended to suppress motor facilitation. Taken together, the findings indicate that the observation of others facilitates the motor sys-tem. The authors point out that the findings also suggest that the neural mechanisms that underlie action observation are intrinsically "social"--that the neural mechanisms map the actions of others onto one's own

body, rather than initially treating all observed action (whether perpe-trated by one's self or by others) as essentially neutral in ownership. These findings inform our understanding of the motor system's role in social cognition, and support previous suggestions that the motor sys-tem may have strongly influenced developments in human social evolu-tion.

About 5 percent of adults with insomnia use alternative therapies

More than 1.6 million U.S. adults are estimated to use complementary and alternative therapies to treat insomnia or trouble sleeping, accord-ing to the results of a national survey published in the September 18 is-sue of Archives of Internal Medicine, a theme issue on sleep.

Approximately 10 to 34 percent of Americans regularly experience difficulty sleeping, also known as insomnia, according to background in-formation in the article. Treatment options include prescription and non-prescription medications, antidepressants and cognitive behavioral ther-apy. Complementary and alternative medicine (CAM) therapies, defined as those practices that are not scientifically proven and are not currently considered part of conventional medicine, also are used to treat insom-nia. Such therapies include herbal medicines and relaxation techniques.

Nancy J. Pearson, Ph.D., and colleagues at the National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, Md., analyzed data from a national survey of 31,044 adults conducted in 2002. Respondents answered one question about whether they regularly had insomnia or trouble sleeping in the past 12 months and completed a 10-minute supplemental survey on the use of 27 types of CAM therapies. The interview also included questions on over 50 other health conditions. Four items assessed behavior and motivation for using CAM therapies.

Of the adults interviewed, 17.4 percent reported that they regularly had insomnia or trouble sleeping in the past year. Difficulty sleeping was more common in women than men, most prevalent between ages 45 and 64, and was associated with obesity, hypertension, congestive heart failure and anxiety or depression, but not diabetes. Of those with insom-nia or trouble sleeping, 4.5 percent reported that they had used CAM to treat the condition, which is equal to about 1.62 million adults in the general population. Survey respondents who were younger and who had a higher level of education were more likely to use CAM to help them sleep.

Among those who use CAM therapies for their insomnia, 60.7 percent told their conventional physician. Sixty-five percent used biological methods, which include herbal medicines, diet interventions and vitamin therapy, and mind-body therapies such as meditation were used by 39

16 5/10/2023

percent. Fifty-six percent reported that the therapy was very important to their health and well-being.

Forty-nine percent of those who used herbal medicine and 48 percent of those who used relaxation therapy reported that CAM helped alleviate their condition. "Although the question asking whether the CAM therapy helped provides useful information on the public's perception of effec-tiveness of CAM therapies for insomnia or trouble sleeping, it does not directly address the efficacy of the CAM therapy," the authors write. "A positive answer to this question could be due to a placebo effect, the natural history of the condition or other unidentified influences rather than efficacy of the CAM treatment." The survey results provide valuable information about the use of CAM that can guide future studies of whether these therapies are effective, they conclude.Psst! Coffee drinkers: Fruit flies have something to tell you

about caffeineIn their hunt for genes and proteins that explain how animals discern

bitter from sweet, a team of Johns Hopkins researchers began by testing whether mutant fruit flies prefer eating sugar over sugar laced with caf-feine. Using a simple behavioral test, the researchers discovered that a single protein missing from the fly-equivalent of our taste buds caused them to ignore caffeine's taste and consume the caffeine as if it were not there.

"No, you won't see jittery Drosophila flitting past your bananas to slurp your morning java anytime soon," says Craig Montell, Ph.D., a professor of biological chemistry in the Institute of Basic Biomedical Sciences at Hopkins. "The bottom line is that our mutant flies willingly drink caffeine-laced liquids and foods because they can't taste its bitterness -- their taste receptor cells don't detect it."

The Hopkins flies, genetically mutated to lack a certain taste receptor protein, have been the focus of studies to sort out how animals taste and why we like the taste of some things but are turned off by the taste of others.

By color-coding sweet and bitter substances eaten by fruit flies and examining the coloring that shows up in their translucent bellies, the Hopkins team hoped to learn whether flies missing a specific "taste-re-ceptor" protein changed their taste preferences.

"Normally," Montell explains, "when given the choice between sweet and bitter substances, flies avoid caffeine and other bitter-tasting chemi-cals. But flies missing this particular taste-receptor protein, called Gr66a, consume caffeine because their taste-receptor cells don't fire in response to it."

The discovery, which is the first ever example of a protein required for both caffeine tasting and caffeine-induced behavior, will be published Sept. 19 in Current Biology.

For the study, Montell and his colleagues kept 50 fruit flies away from food overnight and for breakfast gave the starved flies 90 minutes to eat as much as they wanted of either or both of two concoctions: a blue-col-ored mixture of sugar and agar and a red-colored mixture of caffeine, sugar and agar. The researchers then flipped the flies onto their backs and looked at the color of their bellies to see what they ate - blue indi-cating a preference for eating sugar, red indicating a preference for bit-ter caffeine, and purple indicating no preference.

Flies missing the critical taste receptor protein Gr66a consumed the bitter caffeine solution to the same extent as the sugar-only solution. Montell and colleagues conclude that Gr66a is crucial for the normal caffeine avoidance behavior and without it, flies are seemingly indiffer-ent to the bitter taste.

The researchers went on to examine whether this indifference to bitter was due to the taste nerves on the fly's "tongue" or some malfunction in the fly's brain. Chemical stimulants trigger taste receptor cells to send an electrical current to the brain where the information is processed and often leads to a change in behavior, such as the decision to eat or avoid.

With fine tools, the research team recorded electrical currents in those cells known to contain the Gr66a caffeine taste receptor in the fly's equivalent of the taste buds - dubbed the taste bristles.

Applying sugar to the taste bristles of normal flies, or to mutant flies missing the Gr66a protein, causes the neurons to produce electrical cur-rent "spikes" at a frequency of about 20 spikes per second. Other bitter compounds like quinine generated electrical current spikes at about the same frequency in the mutants.

Only flies missing the Gr66a taste receptor protein were unable to generate any current spikes when given caffeine. "This is a clear demon-stration that Gr66a is functioning in the taste receptor cells and is not a 'general sensor' for bitter compounds, but is required more specifically for the caffeine response," says Montell.

"This indicates that flies have different receptors for the response to other types of bitter compounds," he says.

"We also tested whether the flies avoided the related bitter com-pounds found in tea and cocoa -- chocolate -- and found that Gr66a also is required for the response to the compound in tea, but not for the one in chocolate," he says.

Fruit flies often are used as experimental organisms because they grow quickly and are easy to manipulate genetically. Now that Montell and his colleagues have a mutant fly that is unable to taste caffeine, they hope to further examine the other genes and molecules involved in

17 5/10/2023

the caffeine response and better understand the biochemistry behind caffeine-induced behavior in other organisms, namely humans.

Brain's action center is all talkCollaboration between USC, UCLA, UC Berkeley and Italian Univer-

sity finds strong mental link between actions and wordsNeuroscience is tackling a problem that obsessed Hamlet: What is the

difference in our minds between talk and action?Less than you would expect, an international research group reports in

the Sept. 19 issue of Current Biology.The brain's premotor cortex shows the same activity pattern when

subjects observe an action as when they hear words describing the same action, the study's authors said.

"If you hear the word 'grasp,' it's actually the premotor cortex that's active, not just a separate, abstract semantic area in the brain," said lead investigator Lisa Aziz-Zadeh, assistant professor of occupational sciences with a joint appointment in the Brain and Creativity Institute of the USC College of Letters, Arts and Sciences.

The premotor cortex has long been identified as a center of activity for actions. The notion that it could also process verbal descriptions of those actions has met some resistance.

"Neuroscience is coming around to this idea, but there hasn't been much data supporting it," Aziz-Zadeh said.

To change that, Aziz-Zadeh recruited 12 volunteers and used func-tional magnetic resonance imaging (fMRI) to compare the same areas of the premotor cortex in the same subject as the person observed an ac-tion and heard language describing the action.

The premotor area involved during observation of a specific action, such as kicking, also lit up when the subject heard the corresponding word. This was the first study to make such a direct comparison, Aziz-Zadeh said.

Other studies found activity in the same areas during execution of an action, Aziz-Zadeh added, offering indirect evidence for the existence of "mirror neuron" systems that activate both when a person performs a task and when the person watches someone else perform the task.

"The study does demonstrate the intimate linkage between the way we talk about actions and the neural machinery that supports those ac-tions. That's very intriguing," said USC University Professor Michael Ar-bib.

Arbib also noted the sharp difference between the subjects' responses to literal action statements (such as "biting the peach") and metaphori-cal actions ("biting off more than you can chew" or "kicking off").

"Metaphor seems not to activate the action areas as much as a direct action statement," he said, predicting that in future studies the premo-tor cortex will respond more strongly to novel images than to "frozen

metaphors," otherwise known as clichés – a finding unlikely to floor any-one, knock their socks off or cause their jaw to drop.

Arbib carried out one of the first studies of mirror neurons in humans with Giacomo Rizzolatti of the Universita di Parma in Italy.

In 1998, he and Rizzolatti co-wrote "Language Within Our Grasp," a frequently cited article that proposed mirror neurons are involved in lan-guage. (Arbib also edited "From Action to Language Via the Mirror Sys-tem," an upcoming book from Cambridge University Press.)

Rizzolatti, who discovered mirror neurons in 1996, collaborated with Aziz-Zadeh on her current study. The other co-authors are Stephen Wil-son and Marco Iacoboni from UCLA.

Therapeutic role found for carbon monoxideGas is shown to reverse symptoms of pulmonary hypertension

BOSTON – In a medical case of Jekyll and Hyde, carbon monoxide – the highly toxic gas emitted from auto exhausts and faulty heating systems – has proven effective in treating the symptoms of pulmonary arterial hypertension (PAH), an extremely debilitating condition that typically leads to right heart failure and eventual death.

The new findings, made in an animal study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and the University of Pitts-burgh, are described in the September 2006 issue of The Journal of Ex-perimental Medicine (JEM).

The paradoxical theory that carbon monoxide (CO), the colorless, odorless gas often dubbed "the silent killer," could be used to prevent the onset of certain inflammatory conditions was first proposed in 1998. Since then, numerous studies have shown that when administered at low, non-toxic concentrations prior to such procedures as organ trans-plant surgery or balloon angioplasty, CO provides potent protective ef-fects against organ rejection or blockage of the carotid arteries.

But, with these latest findings, explains senior author Leo Otterbein, PhD, it now appears that carbon monoxide can also be used to treat and reverse existing disease.

"Our results offer the exciting possibility that in extremely low concen-trations and for brief intermittent exposures of one hour per day, CO gas might be effectively used as a therapy to treat PAH in a clinical setting," says Otterbein, an investigator in the Transplantation Center at BIDMC and Associate Professor of Surgery at Harvard Medical School.

Pulmonary arteries – the blood vessels that carry blood from the heart's right ventricle to the small arteries in the lungs -- are made up primarily of endothelial cells and smooth muscle cells. PAH develops when, for unknown reasons, the smooth muscle cells rapidly and uncon-trollably proliferate, leading to "remodeling," in which blood vessel walls thicken and gradual stenosis of the arteries occurs. Ultimately, the ves-

18 5/10/2023

sels thicken to the point that blood can no longer be effectively pumped through them, resulting in serious cardiopulmonary complications and in many cases, heart attack. There is no cure for the disease.

Based on CO's successful track record in helping to prevent vascular disease, Otterbein and first author Brian Zuckerbraun, MD, of the Univer-sity of Pittsburgh, hypothesized that the gas might prove beneficial in treating pulmonary arterial hypertension.

To test this hypothesis, the scientists first exposed a PAH mouse model to a short, daily regimen of CO (in a modest concentration, equiv-alent to what a cigarette smoker might inhale) of one hour per day. As predicted, their results showed that the gas did indeed reverse PAH in the animals, resulting in the restoration of both normal pressures and heart weights (indicative of reversal of imminent heart failure).

The scientists next identified how this was happening."We determined that CO was exerting these effects by both arresting

growth of the vessels' smooth muscle cells and inducing apoptosis, or cell death," he adds. Consequently, as the smooth muscle cells died, both the pulmonary blood vessels and right heart were restored to their normal size, what Otterbein describes as a case of "retro-remodeling."

"However, what we found most intriguing was that CO did not induce the death of all of the smooth muscle cells in the blood vessels, but rather selected out for destruction only the population that was prob-lematic," he adds.

It was in the final arm of their study that the authors discovered how CO was able to selectively target the troublesome smooth muscle cells: It was relying on a second gas, nitric oxide (NO), for assistance.

"When we first started these experiments, we had the cells separated into two separate culture dishes – endothelial cells in one, smooth mus-cle cells in the other," explains Otterbein. But, he adds, when they ex-posed these cultures to carbon monoxide, nothing happened. The cells behaved normally.

"We eventually asked ourselves, 'What if we're not seeing results in these two separate dishes because in the body, the two aren't sepa-rated. What if these two cell types somehow act in concert and need to communicate with one another as they otherwise would in vivo in order for CO to exert its beneficial effects?'"

To address this question, coauthor Beek Yoke Chin, PhD, developed a simulated blood vessel by growing the cells on a semi-permeable mem-brane, which enabled the two cell types to "communicate" with one an-other through pores. And that, says Otterbein, was when the scientists observed that in this "co-culture" setting, CO was able to induce death of the smooth muscle cells without adversely affecting the viability of the endothelial cells.

"We discovered that endothelial cells must be present – and be able to generate NO via nitric oxide synthase [NOS3] -- in order for CO to induce the death of the smooth muscle cells and reverse the symptoms of PAH," explains Otterbein. To further test the role of the nitric oxide, the co-culture was treated with a select inhibitor of NOS3. Under these con-ditions, he adds, CO was unable to induce death to the same degree as in control-treated co-cultures.

"We concluded that the physical interaction between the two cell types plus the ability to generate NO was crucial for the positive CO ef-fects," he says, adding that studies are now underway to determine the mechanism by which CO exposure leads to the increase in NO genera-tion.

"Our hope is that CO will find a place in the clinic as a therapeutic op-tion for the treatment of disease," concludes Otterbein. "CO has been around since before life began on earth and, in fact, it is thought to have contributed to the origin of life. Perhaps this was a sign of its necessary role in biology."

Road wends its way through stomachA computer model or "virtual stomach" revealed a central "road" in

the human stomach, dubbed the Magenstrasse, that could explain why pharmaceuticals sometimes have a large variability in drug activation times, according to a team creating computer simulations of stomach contractions.

"We are predicting variables that we wish we could measure, but we cannot," says Dr. James G. Brasseur, professor of mechanical engineer-ing, bioengineering and mathematics at Penn State. "Now that we know the Magenstrasse exists, we can look for it, but, it will not be easy to measure its existence and could require expensive technology."

Brasseur, working with Anupam Pal, research associate, Penn State and Bertil Abrahamsson, AstraZeneca, was interested in how the stom-ach empties its contents and how material passes from the stomach into the small intestines.

"The sphincter between the stomach and the small intestine is interac-tive," said Brasseur. "The sphincter opens and closes in a controlled way to regulate the flow of nutrient to the small intestines. Sensor cells in the intestines modulate the opening and closing."

Two types of muscle contractions control food movement in the stom-ach. One type of contraction, antral contractions, occur in the lower por-tion of the stomach and break down and mix stomach contents. The other type of contraction, fundic contractions, is over the upper surface of the stomach. It was thought that the fundic contractions move food from the top of the stomach where it enters from the esophagus, to the bottom of the stomach where the chyme leaves and enters the small in-

19 5/10/2023

testine. The assumption was that particles left the stomach in the same order they entered the stomach.

The researchers modeled the stomach contents and discovered that a narrow path forms in the center of the stomach along which food exits the stomach more rapidly than the regions near the walls of the stom-ach. They used MRI data from human subjects to create the proper ge-ometry of the muscle contractions.

"We looked at a ten-minute window of digestion and we tagged all the particles as they left the virtual stomach," said Brasseur. "We then re-versed the flow on the computer and saw where the particles came from."

In essence they ran the simulation backwards and were surprised to see a central road appear. Those particles in the virtual stomach that were on the central road, exited the stomach in 10 minutes. The Magen-strasse extended all the way from the stomach's exit up to the top of the stomach's fundus. Material that entered the stomach off this Magen-strasse could remain in the stomach a long time, even hours in the real stomach.

"This discovery might explain observed high variability in drug initia-tion time, and may have important implications to both drug delivery and digestion," the researchers report online in the Journal of Biome-chanics. The paper will appear in a print edition in 2007.

Because most drugs target the small intestines for absorption, a pill disintegrates in the stomach and activates in the small intestines. With this new understanding of how the stomach works, where in the stom-ach a pill or capsule disintegrates becomes very important. Drug deliv-ery times may differ from 10 minutes to hours depending on location.

"Therefore, drugs released on the Magenstrasse will enter the duode-num rapidly and at a high concentration," the researchers report. "Drug released off the gastric emptying Magenstrasse, however, will mix well and enter the duodenum much later, at low concentration."

For some drugs, rapid release is important, for others, slow release over long periods of time is the desired outcome.

"If you do not know a Magenstrasse exists, you will not factor it into the designs," says Brasseur. "Now that we know, perhaps researchers can design pills with higher densities to sit around at the bottom of the stomach, outside the Magenstrasse, and let the drug out slowly."

Cabernet sauvignon red wine reduces the risk of Alzheimer's disease

A new study directed by Mount Sinai School of Medicine has found that moderate red wine consumption in a form of Cabernet Sauvignon may help reduce the incidence of Alzheimer's Disease (AD). The study entitled "Moderate Consumption of Cabernet Sauvignon Attenuates â-

amyloid Neuropathology in a Mouse Model of Alzheimer's Disease" is in press, and will be published in the November 2006 issue of The FASEB Journal. The breakthrough study will also be presented at the "Society for Neuroscience Meeting" held in Atlanta, Georgia, October 14-18, 2006.

"Our study is the first to report that moderate consumption of red wine in a form of Cabernet Sauvignon delivered in the drinking water for ~7 months significantly reduces AD-type â-amyloid neuropathology, and memory deterioration in ~11-month-old transgenic mice that model AD," reported researchers Dr. Giulio Maria Pasinetti and Dr. Jun Wang at Mount Sinai. "This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia."

"This new breakthrough is another step forward in Alzheimer's re-search at Mount Sinai and across the globe for this growing health con-cern that has devastating effects," say Giulio Maria Pasinetti, M.D., Ph.D., Professor of Psychiatry and Neuroscience, Director of the Neuroin-flammation Research Center at Mount Sinai School of Medicine and lead author of the study and Dr. Jun Wang, Assistant Professor of Psychiatry and co-Author of the study. "These findings give researchers and mil-lions of families a glimpse of light at the end of the long dark tunnel for future prevention of this disease."

People with AD exhibit elevated levels of beta-amyloid peptides that cause plaque buildup in the brain, which is the main characteristic of AD. An estimated 4.5 million Americans have AD. Presently, there are no known cures or effective preventive strategies. While genetic factors are responsible in early-onset cases, they appear to play less of a role in late-onset-sporadic AD cases, the most common form of AD. However, lifestyle factors such as diet and now moderate wine consumption are receiving increasing attention for its potential preventative impact on AD.

Using mice, with AD-type â-amyloid (Aâ) neuropathology, researchers at Mount Sinai tested whether moderate consumption of the red wine Cabernet Sauvignon changes AD-type neuropathology and cognitive de-terioration. The wine used was delivered in a final concentration of ap-proximately 6% ethanol. It was found that Cabernet Sauvignon signifi-cantly reduced AD-type deterioration of spatial memory function and Aâ neuropathology in mice relative to control mice that were treated with either a comparable amount of ethanol or water alone. Cabernet Sauvi-gnon was found to exert a beneficial effect by promoting non-amyloido-genic processing of amyloid precursor protein, which ultimately prevents the generation of AD â-amyloid neuropathology.

20 5/10/2023

"No time to exercise" is no excuseA new study, published in The Journal of Physiology, shows that short

bursts of very intense exercise - equivalent to only a few minutes per day - can produce the same results as traditional endurance training.

"The most striking finding from our study was the remarkably similar improvements in muscle health and performance induced by two such diverse training strategies," says Martin Gibala, an associate professor of kinesiology at McMaster University.

Gibala's team made headlines last year when they suggested that a few minutes of high-intensity exercise could be as effective as an hour of moderate activity. However, their previous work did not directly com-pare sprint versus endurance training.

The new study was conducted on 16 college-aged students who per-formed six training sessions over two weeks. Eight subjects performed between four and six 30-second bursts of "all out" cycling separated by 4 minutes of recovery during each training session. The other eight sub-jects performed 90-120 minutes of continuous moderate-intensity cy-cling each day. Total training time commitment including recovery was 2.5 hours in the sprint group, whereas the endurance group performed 10.5 hours of total exercise over two weeks. Despite the marked differ-ence in training volume, both groups showed similar improvements in exercise performance and muscle parameters associated with fatigue resistance.

"Our study demonstrates that interval-based exercise is a very time-efficient training strategy," said Gibala. “This type of training is very de-manding and requires a high level of motivation. However, short bursts of intense exercise may be an effective option for individuals who cite ‘lack of time’ as a major impediment to fitness."Global view shows strong link between kidney cancer, sun-

light exposureUsing newly available data on worldwide cancer incidence to map can-

cer rates in relation to proximity to the equator, researchers at the Moores Cancer Center at University of California, San Diego (UCSD) have shown a clear association between deficiency in exposure to sunlight, specifically ultraviolet B (UVB), and kidney cancer.

UVB exposure triggers photosynthesis of vitamin D3 in the body. This form of vitamin D also is available through diet and supplements. Previ-ous studies from this core research team have shown an association be-tween higher levels of vitamin D3 and a lower risk of cancers of the breast, colon and ovary.

"Kidney cancer is a mysterious cancer for which no widely accepted cause or means of prevention exists, so we wanted to build on research by one of the co-authors, William Grant, and see if it might be related to

deficiency of vitamin D," said study co-author Cedric Garland, Dr. P.H., professor of Family and Preventive Medicine in the UCSD School of Medicine, and member of the Moores UCSD Cancer Center.

There will be approximately 208,500 cases and 101,900 deaths from kidney cancer worldwide in 2006, including 39,000 new cases and 12,700 deaths in the United States, according to the International Agency for Research on Cancer and the American Cancer Society.

The study, published in the International Journal of Cancer's online edi-tion dated September 15, is the research team's newest finding relating exposure to the sun as a source of vitamin D, and estimated vitamin D deficiency to higher rates of several major types of cancer.

This paper used worldwide data only recently available through a new tool called GLOBOCAN, developed by the World Health Organization's In-ternational Agency for Research on Cancer. GLOBOCAN is a database of cancer incidence, mortality and prevalence for 175 countries.

The researchers created a graph with a vertical axis for renal cancer incidence rates, and a horizontal axis for latitude. The latitudes range from -90 for the southern hemisphere, to zero for the equator, to +90 for the northern hemisphere. They then plotted incidence rates for 175 countries according to latitude. The resulting chart was a parabolic curve that looks like a smile (see accompanying images).

"The plot points created a curve roughly resembling a smile, with countries with high incidence rates at the left and right, and those with low incidence rates in the center, just a few degrees from the equator," said Garland. "Countries with the highest cancer rates were places like New Zealand and Uruguay in the southern hemisphere and Iceland and the Czech Republic in the northern hemisphere. Clustered at the bottom of the curve with lowest incidence rates were Guam, Indonesia and other equatorial countries on most continents, including many varied equatorial cultures."

In addition to UVB, the researchers analyzed cloud cover and intake of calories from animal sources for their association to kidney cancer. The scientists were able to determine the contributions of each indepen-dently. After accounting for cloud cover and intake of animal protein, UVB exposure still showed a significant independent association with in-cidence rates.

"Because the distinctive "smiley" parabolic curve is present for both sexes, it is unlikely that the international differences are due to occupa-tional exposures, which usually vary according to gender, " said co-au-thor Sharif B. Mohr, M.P.H.

In the paper, the authors discuss and account for other possible vari-ables such as ozone, aerosols and obesity.

21 5/10/2023

"This was a study of aggregates, or countries, rather than individuals. Findings that apply to aggregates may not apply to individuals," said co-author Edward D. Gorham, M.P.H., Ph.D.

"Since ecological studies may not be able to control for all relevant confounding factors, observational studies of the effect of vitamin D from sunlight, diet and supplements on the risk of kidney cancer in indi-viduals would be desirable," Gorham added.

Early to bed, early to riseGenetics of the morning lark

In an upcoming G&D paper, a team of German scientists presents a genetic basis for understanding human morning lark behavior. Dr. Achim Kramer (Charité Universitaetsmedizin Berlin) and colleagues have un-covered a genetic cause for the human familial advanced sleep phase syndrome (FASPS), which causes people to both go to sleep and wake up very early.

"Being a morning lark or a night owl is something encoded in people's genes and we here made substantial progress to uncover the molecular basis for that," explains Dr. Kramer.

FASPS is a dominantly inherited circadian rhythm disorder in which pa-tients' inborn biological clock (or circadian clock as it is known by scien-tists) runs ahead of normal. Circadian clocks are found in organisms ranging from bacteria to humans. They keep our bodies' daily activities, like sleeping and eating, on a roughly 24 hour schedule, or period. FASPS patients' periods are about 4 hours advanced, causing the pa-tients to retire at 6 or 7pm and rise by 4am. In 1999, it was discovered that a mutated gene, called PERIOD2 (PER2) is mutated in many cases of FASPS.

Dr. Kramer and colleagues mapped phosphorylation sites on the PER2 protein. They identified 21 sites, one of which (Serine 659), was impli-cated in FASPS. By monitoring the bioluminescence cycles of cell lines, the researchers demonstrated that mutation of Serine 659 causes a shortening of the luminescence period and recapitulates the FASPS phe-notype. The researchers determined that the mutated form of Serine 659, which does not get phosphorylated, leads to PER2's destabilization and earlier clearance from the cell nucleus.

The research team went on to show that mutations of other PER2 phosphorylation sites have differential effects on PER2 protein stability, circadian period length, and organismal behavior. In fact, using a simple mathematical algorithm modeled after their work, the researchers suc-cessfully explained how different PER phosphorylation defects result in the behaviors displayed by well-known circadian mutants in hamsters and fruit flies.

Dr. Kramer adds that "This is the first example where the regulation of a complex human behaviour could be really nailed down to its genetic basis and molecular mechanism."Can a vitamin alleviate chronic, progressive multiple scle-

rosis?Ongoing nerve-fiber damage, disability prevented in animal studyResearchers have found a possible way to protect people with multiple

sclerosis (MS) from severe long-term disability: increase nervous-system levels of a vital compound, called nicotinamide adenine dinucleotide (NAD), by giving its chemical precursor – nicotinamide, a form of vitamin B3.

Current therapies for MS mainly address the relapsing-remitting phase of the disease, but some of these have severe side effects, and most pa-tients eventually enter a chronic progressive phase for which there is no good treatment. Using a mouse model of MS, researchers in the Neuro-biology Program at Children's Hospital Boston found strong evidence that nicotinamide may protect against nerve damage in the chronic pro-gressive phase, when the most serious disabilities occur. Their findings appear in a cover article in the September 20 Journal of Neuroscience.

MS is a neurologic disorder in which nerve fibers, or axons, are dam-aged through inflammation, loss of their insulating myelin coating, and degeneration. This damage disrupts nerves' ability to conduct electrical impulses to and from the brain, causing such symptoms as fatigue, diffi-culty walking, pain, spasticity, and emotional and cognitive changes. Current treatments mainly protect against inflammation and myelin loss, but do not completely prevent long-term axon damage.In mice with MS-like disease, nicotinamide delayed and reduced neurologic disability as indicated by behavioral scores (1 indicating mild weakness only in the tail; 4, paralysis involving all four limbs). Mice receiving placebo (saline) had the most disability, while mice receiving high-dose nicotinamide had the least. Wlds mice (which more readily convert nicotinamide to NAD) benefited most from treatment. Credit: Courtesy Shinjiro Kaneko, MD, Neurobiology Pro-gram, Children's Hospital Boston

A team led by Shinjiro Kaneko, MD, a research fellow at Children's, and senior investigator Zhigang He, PhD, also from Children's, worked with mice that had an MS-like disease called experimental autoimmune encephalitis (EAE). Through careful experiments, they showed that nicotinamide protected the animals' axons from degeneration – not only preventing axon inflammation and myelin loss, but also protecting axons that had already lost their myelin from further degradation.

Intriguingly, mice with EAE who received daily nicotinamide injections under their skin had a delayed onset of neurologic disability, and the severity of their deficits was reduced for at least eight weeks after treat-

22 5/10/2023

ment. The greater the dose of nicotinamide, the greater the protective effect. [See accompanying figure.]

On a scale of 1 to 5 (1 indicating mild weakness only in the tail, 4 indi-cating paralysis involving all four limbs, and 5, death from the disease), mice receiving the highest doses of nicotinamide had neurologic scores between 1 and 2, while control mice had scores between 3 and 4. All differences between treated groups and controls were statistically sig-nificant.

Mice with the greatest neurologic deficits had the lowest levels of NAD in their spinal cord, and those with the mildest deficits had the highest NAD levels. Mice that had higher levels of an enzyme that converts nicotinamide to NAD (known as Wlds mice) responded best to treat-ment.

Moreover, nicotinamide significantly reduced neurologic deficits even when treatment was delayed until 10 days after the induction of EAE, raising hope that it will also be effective in the later stages of MS. "The earlier therapy was started, the better the effect, but we hope nicoti-namide can help patients who are already in the chronic stage," says Kaneko.

In other experiments, the researchers demonstrated that nicotinamide

works by increasing levels of NAD in the spinal cord and that NAD levels decrease when axons degenerate. Finally, they showed that giving NAD directly also prevented axon degeneration.

NAD is used extensively by cells to produce energy through the break-down of carbohydrates. Its chemical precursor, nicotinamide, has sev-

eral characteristics that make it a promising therapeutic agent: it readily crosses the blood-brain barrier, is inexpensive and available in any drug-store, and its close relative, vitamin B3, is already used clinically to treat pellagra (vitamin B3 deficiency), high cholesterol, and other disorders. Although nicotinamide is thought to have few side effects, the doses used in mice would translate to much higher human doses than are nor-mally used clinically, so would need to be tested for safety.

"We hope that our work will initiate a clinical trial, and that nicoti-namide could be used in real patients," Kaneko says. "In the early phase of MS, anti-inflammatory drugs may work, but long-term you need to protect against axonal damage."Aromatase inhibitors: A treatment of choice for advanced

breast cancer patientsAromatase inhibitors improve the survival of advanced breast cancer

patients compared to standard hormone therapies like tamoxifen, a re-searchers report in the September 20 issue of the Journal of the National Cancer Institute.

Many advances in breast cancer research have improved therapy for early-stage breast cancer patients, but more research is needed on ther-apeutic treatments for advanced breast cancer patients. Treatment with aromatase inhibitors in place of traditional hormonal therapies is being explored for advanced breast cancer patients.

John P.A. Ioannidis, M.D., of the University of Ioannina School of Medicine in Greece, and colleagues identified trials that examined the treatment of advanced breast cancer patients with aromatase inhibitors or standard hormone therapies. They found 23 trials with a total of 8,504 patients: 4,559 received treatment with aromatase inhibitors, and 3,945 received standard hormone therapy.

The authors found that third-generation aromatase inhibitors--includ-ing vorozole, letrozole, examestane, and anastrazole--increased the sur-vival time for patients with advanced breast cancer. They suggest that aromatase inhibitors should be used as an initial therapy for these pa-tients.

"The meta-analysis offers strong evidence for the use of third-genera-tion aromatase inhibitors and inactivators in the treatment of advanced breast cancer," the authors write.

In an accompanying editorial, Daniel F. Hayes, M.D., and Catherine H. Van Poznak, M.D., of the University of Michigan Health and Hospital Sys-tem in Ann Arbor, write, "We believe that this study was well executed

and that the results are acceptable. The statistical power of this meta-analysis is high because of the large amount of compiled data, and the results support what is already a strong bias in the clinical community."

Common garden plant threatened by climate change23 5/10/2023

Cyclamen, a common, pretty garden flower, is at risk of extinction be-cause of climate change. In a study published today in the open access journal BMC Evolutionary Biology (http://www.biomedcentral.com/bm-cevolbiol/), researchers show, using mathematical modelling, that the ideal climate for Cyclamen will become increasingly rare and might have totally disappeared by the 2050's. Some species of Cyclamen are adapt-able enough and could survive climate change, but many would proba-bly disappear.

Chris Yesson and Alastair Culham, from the University of Reading in the UK built mathematical models based on the cur-rent distribution of the 21 different species of Cyclamen, in order to predict the impact of climate change on Cyclamen within the next 50 years.Yesson and Culham identified distinct cli-

matic niches – geographic areas with the ideal climate - for different species of Cy-clamen. Most Cyclamen species thrive in a typical Mediterranean climate, with hot, dry summers and cool, wet winters, but many are found in areas with much harsher climatic conditions. Yesson and

Culham show that climatic niches are likely to decrease for all species of Cyclamen, and by more than 60% for most species.

Yesson and Culham conclude: "Many of these species are considered to be at high risk of extinction due to climate change."Risks of gastrointestinal ulcers linked to aspirin use might

outweigh its benefits for the heartDoctors should consider whether patients are at high risk of stomach

ulcers before prescribing aspirin treatment. A study published today in the open access journal BMC Medicine reveals that low-dose aspirin treatment may be responsible for one extra case of gastrointestinal complications, which include ulcer bleeding or perforation, in every 50 aspirin users per year in susceptible groups, such as older men with a history of peptic ulcer. The authors conclude that for some patients tak-ing aspirin to reduce their risk of heart attack, the risk of gastrointestinal complications might outweigh the cardioprotective effects of the drug.

Sonia Hernández-Díaz and Luis García Rodríguez analysed two anony-mous databases of patient information, the General Practice Research Database in the UK and the Base de Datos para la Investigación Farma-coepidemiológica en Atención Primaria in Spain, to characterise patients taking low-dose aspirin as a preventive measure against heart attack, in

terms of major gastrointestinal risk factors. Risk factors for upper gas-trointestinal tract complications include advanced age, male sex, prior ulcer history and use of other non-steroidal anti-inflammatory drugs (NSAIDs). The researchers then estimated the excess gastrointestinal risk caused by aspirin use in patients with and without these risk factors.

Hernández-Díaz and García Rodríguez find that 88% of aspirin users are over 60 and that 52-54% of them are male. From 3.8% to 5.9% of them have a history of gastrointestinal ulcer. Across all risk groups, as-pirin use is responsible for an extra 5-6 cases of upper gastrointestinal tract complications per 1,000 aspirin users per year. This excess risk is larger in populations that are at high risk of gastrointestinal complica-tions, such as older men or patients with a history of peptic ulcer. The authors estimate that aspirin use might be responsible for 20 extra cases per 1,000 aspirin users per year in men older than 70 with a past history of peptic ulcer. On the other hand, the excess risk is smaller in populations that are at low risk of gastrointestinal complications.Penn critical-care physicians recommend strategies when

facing requests to end supplemental oxygenNew ethical dilemma emerges in medicine: Commentary in JAMA addresses concerns of withdrawing this life-sustaining measure(Philadelphia, PA) - Critical care physicians with the University of Penn-

sylvania Health System address a newly-emerging ethical dilemma in medicine - what should health care professionals do when faced with a request from a patient to end the use of life-sustaining supplemental oxygen? Scott Halpern, MD, PhD, a fellow in the Division of Pulmonary, Allergy and Critical Care Medicine and senior fellow with the Center for Bioethics at Penn, along with John Hansen-Flaschen, MD, chief of the Di-vision of Pulmonary, Allergy and Critical Care Medicine at Penn, have co-authored a guide for physicians faced with such requests. The commen-tary - which examines concerns physicians may have in removing such a minimally invasive and potentially palliative therapy, and suggests strategies for physicians to overcome them -- is in the September 20th issue of JAMA, the Journal of the American Medical Association.

Halpern explains, "Informed patients with decision-making capacity have well-established rights to forgo any and all forms of life-sustaining therapy. However, there is no clear definition of what constitutes a life-sustaining therapy. We tend to think of invasive medical therapies such as mechanical ventilation, kidney dialysis or tube feeding. When admin-istered by face mask or nasal prongs, high flow oxygen is not at all inva-sive, yet it clearly serves a life-sustaining role for an increasing number of patients with advanced lung, heart, or cancer-related diseases. Many of these patients would lose consciousness and die within hours or even minutes if their supplemental oxygen was withdrawn."

24 5/10/2023

Advances in medicine have made it so that many more patients with end-stage diseases are living longer, and now the technology is avail-able to provide high flow supplemental oxygen both in the hospital and at home, often providing a limited quality of life for patients. "So this is yet another ethical dilemma in medicine born of technological advance-ments," adds Halpern.

Both Halpern and Hansen-Flaschen have received requests from pa-tients to stop their flow of supplemental oxygen, resulting in death. Halpern first grappled with the difficulty of withdrawing oxygen from an awake and alert patient when, as a first year medical resident, he was treating a hospitalized patient suffering from advanced lung disease and cancer. One morning, the patient said he'd "had enough" and tugged on his mask but was too weak to remove it and asked for Halpern's help to do so. Halpern debated this request with the attending physician who was concerned that the patient would experience air hunger and fear af-ter oxygen was removed, necessitating high doses of sedating drugs. He worried this might constitute a form of euthanasia.

Hansen-Flaschen received a similar request from an outpatient who suffered from an advanced lung disease and was living at home. He could no longer get out of bed and his quality of life had seriously deteri-orated. The patient wanted to stop his oxygen therapy and asked Hansen-Flaschen to help him avoid a sense of suffocation afterwards. "I had to ask myself, is this participating in a patient's death or is it simply respecting a patient's request? Plus, there's no way to predict an individ-ual's response to removing supplemental oxygen and how much they will suffer."

Hansen-Flaschen notes "Two-thirds of critical care patients in this country are cared for by general physicians or others without special training in critical care." In light of this, Halpern said he hoped that this commentary "will provide a place for physicians to turn when faced with this particular dilemma. We hope that our recommendations may allow physicians to heed requests for the withdrawal of life-sustaining oxygen as readily as they may heed requests for the withdrawal of other life-sustaining therapies, such as mechanical ventilation and dialysis."

The commentary addresses specific concerns physicians may have about withdrawing oxygen, including how to balance the burdens and benefits of supplemental oxygen; whether withdrawing oxygen might appear neglectful; how to determine whether patients retain decision-making capacity; when it is acceptable to use sedation in lieu of oxygen; and concerns about patients' motivations for discontinuing oxygen.

Halpern and Hansen-Flaschen offer this four-step approach to help physicians overcome these concerns:1) Physicians should assure themselves, and other health care profes-sionals involved in the patient's care, as well as the patient's family

members and close friends that supplemental oxygen is a form of life-sustaining medical treatment. As such, requests to discontinue oxygen should be honored with the same judiciousness as requests to withdraw other forms of life support.2) Physicians should ensure that patients requesting the terminal with-drawal of oxygen are free from undue influences, including family mem-ber's wishes, economic considerations or treatable depression.3) Physicians should ensure that the patient has the capacity to make medical decisions by documenting that patients show consistency, un-derstanding, and rationality in making such requests.4) Physicians should ensure that patients and their family members un-derstand the difficulty of predicting patients' experiences after oxygen withdrawal.This commentary is in the September 20th issue of Journal of the Ameri-can Medical Association (wwww.jama.ama-assn.org/). The article is titled "Terminal Withdrawal of Life-Sustaining Supplemental Oxygen."Editor's Notes:For more information on the Penn Lung Center, go on-line to: www.pennhealth.com/lung/servicesFor more information on the University of Pennsylvania Center for Bioethics, go on-line to: www.bioethics.upenn.eduJohn Hansen-Flaschen, MD -- on-line bio: http://pennhealth.com/Wagform/MainPage.aspx?config=provider&P=PP&ID=1183Photos of Hansen-Flaschen and Halpern are available upon request.PENN Medicine is a $2.9 billion enterprise dedicated to the related missions of medical education, biomedical research, and high-quality patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.Penn's School of Medicine is ranked #2 in the nation for receipt of NIH re-search funds; and ranked #3 in the nation in U.S. News & World Report's most recent ranking of top research-oriented medical schools. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recog-nized worldwide for its superior education and training of the next genera-tion of physician-scientists and leaders of academic medicine.The University of Pennsylvania Health System includes three hospitals [Hos-pital of the University of Pennsylvania; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center]; a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.

You don't need a big lottery win for long term happi-ness… but a few thousand helps

Researchers at the University of Warwick and Watson Wyatt have been examining just how much money one needs to win in the lottery to

25 5/10/2023

have a long term impact on personal happiness. Unsurprisingly the re-searchers found that small wins in tens or hundreds of pounds made lit-tle long term difference, but they also found one did not need to win the jackpot to gain a significant increase in long-term mental wellbeing.

In work to be published in the Journal of Health Economics, re-searchers Professor Andrew Oswald from the University of Warwick and Dr Jonathan Gardner from Watson Wyatt showed that medium-sized lot-tery wins ranging from around just £1000 to £120,000 had a long term sustained impact in the overall happiness of those winners. On average, two years after their win medium-sized lottery winners had a mental wellbeing GHQ score 1.4 points better than previously - meaning loosely that two years after their win they were just over 10% happier than the average person without a win or only a tiny lottery win.

Intriguingly the researchers also found that this increased happiness is not obvious immediately after the medium-sized win and takes some time to show through. Economist Professor Andrew Oswald from the Uni-versity of Warwick said:

"This delay could be due the short term disruptive effect on one's live of actually winning, but a more plausible explanation of the delay is that initially many windfall lottery funds are saved and spent later."

The researchers studied 14 years of longitudinal data from the British Household Panel Survey (BHPS) which tracks 5,000 British households.

Note for editors: The full paper entitled "Money and Mental Wellbeing : A Longitudinal Study of Medium-Sized Lottery Wins" is available online at:This link to full paperFirst evidence that musical training affects brain develop-

ment in young childrenResearchers have found the first evidence that young children who

take music lessons show different brain development and improved memory over the course of a year compared to children who do not re-ceive musical training.

The findings, published today (20 September 2006) in the online edi-tion of the journal Brain [1], show that not only do the brains of musi-cally-trained children respond to music in a different way to those of the untrained children, but also that the training improves their memory as well. After one year the musically trained children performed better in a memory test that is correlated with general intelligence skills such as lit-eracy, verbal memory, visiospatial processing, mathematics and IQ.

The Canadian-based researchers reached these conclusions after measuring changes in brain responses to sounds in children aged be-tween four and six. Over the period of a year they took four measure-ments in two groups of children – those taking Suzuki music lessons and those taking no musical training outside school – and found develop-

mental changes over periods as short as four months. While previous studies have shown that older children given music lessons had greater improvements in IQ scores than children given drama lessons, this is the first study to identify these effects in brain-based measurements in young children.

Dr Laurel Trainor, Professor of Psychology, Neuroscience and Behav-iour at McMaster University and Director of the McMaster Institute for Music and the Mind, said: "This is the first study to show that brain re-sponses in young, musically trained and untrained children change dif-ferently over the course of a year. These changes are likely to be related to the cognitive benefit that is seen with musical training." Prof Trainor led the study with Dr Takako Fujioka, a scientist at Baycrest's Rotman Research Institute.

The research team designed their study to investigate (1) how audi-tory responses in children matured over the period of a year, (2) whether responses to meaningful sounds, such as musical tones, ma-tured differently than responses to noises, and (3) how musical training affected normal brain development in young children.

At the beginning of the study, six of the children (five boys, one girl) had just started to attend a Suzuki music school; the other six children (four boys, two girls) had no music lessons outside school.

The researchers chose children being trained by the Suzuki method for several reasons: it ensured the children were all trained in the same way, were not selected for training according to their initial musical tal-ent and had similar support from their families. In addition, because there was no early training in reading music, the Suzuki method pro-vided the researchers with a good model of how training in auditory, sensory and motor activities induces changes in the cortex of the brain. Brain activity was measured by magnetoencephalography (MEG) while the children listened to two types of sounds: a violin tone and a white noise burst. MEG is a non-invasive brain scanning technology that mea-sures the magnetic fields outside the head that are associated with the electrical fields generated when groups of neurons (nerve cells) fire in synchrony. When a sound is heard, the brain processes the information from the ears in a series of stages. MEG provides millisecond-by-millisec-ond information that tracks these stages of processing; the stages show up as positive or negative deflections (or peaks), called components, in the MEG waveform. Earlier peaks tend to reflect sensory processing and later peaks, perceptual or cognitive processing.

The researchers recorded the measurements four times during the year, and during the first and fourth session the children also completed a music test (in which they were asked to discriminate between same and different harmonies, rhythms and melodies) and a digit span mem-

26 5/10/2023

ory test (in which they had to listen to a series of numbers, remember them and repeat them back to the experimenter).

Analysis of the MEG responses showed that across all children, larger responses were seen to the violin tones than to the white noise, indicat-ing that more cortical resources were put to processing meaningful sounds. In addition, the time that it took for the brain to respond to the sounds (the latency of certain MEG components) decreased over the year. This means that as children matured, the electrical conduction be-tween neurons in their brains worked faster.

Of most interest, the Suzuki children showed a greater change over the year in response to violin tones in an MEG component (N250m) re-lated to attention and sound discrimination than did the children not tak-ing music lessons.

Analysis of the music tasks showed greater improvement over the year in melody, harmony and rhythm processing in the children studying music compared to those not studying music. General memory capacity also improved more in the children studying music than in those not studying music.

Prof Trainor said: "That the children studying music for a year im-proved in musical listening skills more than children not studying music is perhaps not very surprising. On the other hand, it is very interesting that the children taking music lessons improved more over the year on general memory skills that are correlated with non-musical abilities such as literacy, verbal memory, visiospatial processing, mathematics and IQ than did the children not taking lessons. The finding of very rapid matu-ration of the N250m component to violin sounds in children taking music lessons fits with their large improvement on the memory test. It sug-gests that musical training is having an effect on how the brain gets wired for general cognitive functioning related to memory and atten-tion."

Dr Fujioka added: "Previous work has shown assignment to musical training is associated with improvements in IQ in school-aged children. Our work explores how musical training affects the way in which the brain develops. It is clear that music is good for children's cognitive de-velopment and that music should be part of the pre-school and primary school curriculum."

The next phase of the study will look at the benefits of musical train-ing in older adults.Making the grade: Immigrant children keep academic pace

with peersTALLAHASSEE, Fla. -- Far from being a burden on the educational system, research from Florida State University shows immigrant children perform as well or better than their same-race, American-born counterparts.

FSU Sociology Professor Kathryn Harker Tillman found that first- and second- generation children are no more likely than their third-genera-tion peers to have to repeat a grade despite the many social and eco-nomic disadvantages they face. The finding is true for immigrant youth of all racial and ethnic backgrounds or countries of origin. The study, co-authored by colleagues Guang Guo and Kathleen Mullan Harris from the University of North Carolina at Chapel Hill, was published in the journal Social Science Research.

"Immigrant children are more successful navigating the educational system than would be expected," Tillman said. "Against the odds, these children are performing as well as or better than their same-race, third-generation peers."

The researchers used both the Panel Study of Income Dynamics and the National Longitudinal Study of Adolescent Health to look at grade re-tention among a total of nearly 20,000 school-age children. They fo-cused on grade retention rather than more traditional markers of educa-tional performance, such as high school graduation, dropout rates or grades in order to see how immigrant children navigate the educational system, not just the end result.

Not only are immigrant children no more likely to have to repeat a grade than American-born children, first-generation boys are 54 percent less likely to be held back than their male peers of similar demographic, family background and ability/language characteristics, according to the study. There is no such distinction among girls. Tillman found that girls of all generations and backgrounds have the same rate of being held back.

"Our findings run counter to expectations derived from traditional as-similation theory, which posits that outcomes should improve across time and generation spent in the United States," Tillman said. "The find-ings also run counter to expectations based upon immigrant children's over-representation in high-risk background categories and general pub-lic perceptions of immigrant students."

The results suggest that immigrant children are able to overcome many of the disadvantages that have been found to place children at high risk for grade retention, such as being a racial or ethic minority, having parents with very low levels of education, having low levels of English proficiency and attending schools in urban areas. The re-searchers theorized that immigrant children may benefit from factors such as higher than average levels of ambition and motivation, high parental expectations, strong beliefs in the importance of education, and/or high levels of family and community support for educational achievement.

"Our finding that males tend to experience more of an immigrant ad-vantage than females leads us to question, however, whether the family

27 5/10/2023

and community contexts of immigrant children are equally beneficial for girls and boys," Tillman said. "Given the traditional gender ideologies of many immigrant groups' native cultures, high expectations and high lev-els of encouragement and support for educational endeavors may be aimed disproportionately at male children."

Although other researchers have found that immigrant children gener-ally do as well as non-immigrants in school, this is the first nationally representative study to show that it is not achieved at the cost of addi-tional years of schooling because of grade failure or policies that hold back students who are adjusting to a new language and culture, she said. Instead, immigrant students succeed while keeping pace with their American-born peers.

About one-fifth of the children in this country are either immigrants or the children of immigrants. This group is expected to account for more than 50 percent of the growth in the school-aged population between 1990 and 2010.

"If we can gain a better understanding of the mechanisms that cur-rently protect socio-economically disadvantaged immigrant children from grade failure we could incorporate that knowledge into the curricu-lum, policies and intervention strategies and enhance the academic suc-cess of all children," Tillman said.

UCI scientists discover a new healthy role for fatFat droplets play protective role inside cells

Too much body fat may be a bad thing, but there is increasing evi-dence that too little fat also may have some surprisingly negative conse-quences.

Researchers at UC Irvine have found that fat droplets – tiny balls of fat that exist in most cells – appear to have an intriguing role to play when it comes to regulating excess proteins in the body. In a study with fruit flies, developmental biologist Steven Gross and colleagues found that these fat droplets served as storage depots for a type of protein used primarily by the cell to bind DNA and organize it in the nucleus. The fat keeps this extra protein out of the way until it is needed so that it does not cause harm within the cell. The findings imply that fat droplets could also serve as storage warehouses for other excess proteins that might otherwise cause harm if not sequestered. The study appears in the cur-rent issue of Current Biology.

“We were surprised to find that these droplets appear to be a mecha-nism for cleaning up excess proteins before they cause trouble,” said Gross, associate professor of developmental and cell biology. “Obvi-ously, everything in the body should be balanced. There is no doubt that huge amounts of fat tax your system in a lot of ways. But there now ap-

pears to be growing evidence that fat is also important for keeping us healthy.”

Researchers used fruit flies in their experiments because of strong similarities between the fat droplets in the flies and in mammals. They purified the droplets in fruit fly embryos and used mass spectrometry to look at what, if any, proteins were associated with the droplets. They were surprised to find histones, a protein that is used by the cell to fold DNA within the nucleus. Even though histones appear to serve no pur-pose outside the nucleus, the scientists found that 50 percent of all the histones present in the cell were in the fat droplets. Interestingly, the amount of histones in the droplets dropped as the embryo moved from early development to later stages, indicating that the histones moved from the droplets to the nucleus as they were needed. In essence, the fat droplets acted as a warehouse where the proteins could be stored until needed by the nucleus of the cell.

Gross and his colleagues believe the droplets serve this purpose not just for histones, but for other excess proteins, as well. This has implica-tions for how fat may be helping fight certain diseases when too much of certain proteins are produced.

“In prion diseases, such as Mad Cow Disease, for example, proteins in the brain are misshapen,” Gross said. “They become abnormal, clump together and accumulate on brain tissue. Although we have no evidence yet that fat droplets could help with this, prion diseases are one area in which we can explore further to see if these droplets are helping keep excess bothersome proteins out of the way.”

Gross emphasized that clinical trials would be needed to evaluate whether storage of proteins on fat droplets is important for human health.

Collaborating on the study with Gross were Silvia Cermelli of UCI, and Michael Welte and Yi Guo of Brandeis University. The study was funded by National Institute of General Medical Sciences and the National Insti-tutes of Health.

A spicy solution for colon cancer?GALVESTON, Texas -- Looking for a cancer cure? Try the spice rack.

In the last few years, that tactic has proved productive for researchers investigating turmeric, a curry spice used for centuries in Indian tradi-tional medicine.

They've found that turmeric's active ingredient, curcumin, works in the lab to fight skin, breast and other tumor cells. In fact, human clinical trials employing curcumin have already been launched.

Now, working with cell cultures in a laboratory, scientists at the Uni-versity of Texas Medical Branch at Galveston (UTMB) have discovered that curcumin blocks the activity of a gastrointestinal hormone impli-

28 5/10/2023

cated in the development of colorectal cancer, the country's second leading cancer killer with nearly 60,000 deaths annually. In a paper pub-lished in the current issue of Clinical Cancer Research, the UTMB re-searchers link the gastrointestinal hormone neurotensin, which is gener-ated in response to fat consumption, to the production of IL-8, a potent inflammatory protein that accelerates the growth and spread of a vari-ety of human cancer cells, including colorectal and pancreatic tumor cells.

"We found that in colon cancer cells, neurotensin increases not just the rate of growth but also other critical things, including cell migration and metastasis," said UTMB surgery professor B. Mark Evers, senior au-thor of the article and director of UTMB's Sealy Center for Cancer Cell Bi-ology. "The fact that all that can be turned off by this natural product, curcumin, was really remarkable."

Evers' group, including lead author and UTMB research associate Xi-aofu Wang, probed curcumin's effect on the process by which neu-rotensin stimulates colon cancer cells to generate IL-8 in detail.

Neurotensin's influence, they found, depends on biochemical signaling pathways inside the cell. Their experiments showed that curcumin damped down those signals, reducing the production of IL-8. Experi-ments also showed that neurotensin increased the migration of colorec-tal cancer cells, and that curcumin could suppress this migration -- pos-sibly reducing the ability of colorectal cancer to spread to other loca-tions in the body.

"Our findings suggest that curcumin may be useful for colon cancer treatment, as well as potential colon cancer suppression, in cells that re-spond to this gastrointestinal hormone, neurotensin," Evers said. "About a third of all colorectal cancer cells have the receptor for neurotensin. Thus, the concept would be sort of like what we do for breast and prostate cancer, where the main therapy involves blocking hormones. We hope to do similar things with gastrointestinal cancers that respond to this hormone."

A wolf in sheep’s clothing: plague bacteria reveal one

of their virulence tricksThe bacterium that causes the

plague belongs to a virulent family of bacteria called Yersinia, a group that also includes a pathogen re-sponsible for food poisoning. These bacteria insert into their host cells proteins and other virulence fac-tors, which kill by - among other

things - disrupting the cells' normal structure. One of these proteins, called YpkA, attacks a cell’s internal skeleton. Now, a study published by Rockefeller University researchers in the most recent issue of Cell shows exactly how YpkA does this, proving the protein’s mechanism from the atomic to the organismal level and providing a potential target for new antibiotic drugs.

C. Erec Stebbins, associate professor and head of the Laboratory of Structural Microbiology, and graduate student Gerd Prehna solved the structure for one region of the YpkA protein, a “binding domain” where it interlocks with another protein on the host cell’s membrane. By looking at the crystal structure of this protein-protein complex, Prehna discov-ered that the configuration looked just like one formed by some of the host’s own signaling proteins. And it’s this mimicry, he found, that leads to a signaling shutdown and deregulation of the cell’s normal structure.A plague's protein. A structural image of the protein-protein com-plex formed when YpkA (green and pink) binds to the Rac1 protein of the host cell (yellow and purple)

After establishing this effect, Prehna set about disrupting it by muta-tion. Using the structure to guide him, he changed three amino acids of YpkA that contacted host proteins, and then looked at how the mutated bacteria affected human cells compared to the original wild-type Yersinia. His results confirmed the hypothesis from the structural study: While the wild-type YpkA wreaked havoc on their host cells’ cytoskele-tons, the mutant left the actin-based skeleton intact.

Then, the researchers took it one step further. Stebbins and Prehna worked with collaborators at Stony Brook University, who created Yersinia bacteria with Prehna’s mutations. The Stony Brook researchers then injected mice with the wild-type and mutant strains of Yersinia. All the mice infected with the wild-type bacteria died within nine days of ex-posure. But the group that received the YpkA mutant had an 80 percent survival rate, showing that Prehna’s mutation drastically lowered Yersinia’s harmful effects. “Altering this binding site not only impairs the bacteria’s ability to disrupt the host cytoskeleton,” Stebbins says, “but it decreases its virulence significantly.”

“It’s rare to find something that has such a strong effect that you can hit one protein so specifically, knock out essentially half its activity, and have such a dramatic result,” he says. “Not only did we have a mecha-nistic explanation, but we could connect what we were seeing in animal studies all the way down to what was happening at the atomic level.” Cell 126: 869-880 (September 8, 2006)

Red Is for Hummingbirds; Yellow for Moths

29 5/10/2023

By Kim McDonaldBiologists at the University of California, San Diego have discovered

that the future of red and yellow varieties of a San Diego wildflower may depend on the fates of two different animals. They report in the current issue of the Journal of Evolutionary Biology that monkeyflow-ers have two different animal pollinators. The red form, common along the coast, is strongly preferred by hummingbirds, while yellow monkeyflowers,

found east of I-15, are favored by hawkmoths.The researchers suspect the recent increase in San Diego’s humming-

bird population, fueled by the growth of suburban developments and gardens, will eventually favor the red over the yellow variety. “Hum-mingbirds are now three times as dense inland as they were on the coast 50 years ago,” said Joshua Kohn, an associate professor of biology at UCSD, who conducted the study with Matthew Streisfeld, now a re-

searcher at Duke University. “This increase in hum-mingbirds may be tipping the balance of selection from favoring yellow to favoring red flowers.”“The shift between the red- and yellow-flowered forms can be seen along any road running from the coast inland in San Diego county and is one of the sharpest natural patterns residents can view while driving in the late spring,” he adds. “We have shown that this shift is very likely due to selection by differ-

ent types of pollinators. The abundance of at least one of these pollina-tors, hummingbirds, has recently increased dramatically and may well favor an eastern expansion of the red-flowered form.”

“The striking geographic pattern of flower color-where we never see a red-flowered plant in the east or a yellow-flowered plant along the coast-speaks wonders of the power of natural selection to maintain these dif-ferences,” said Streisfeld.

Enzyme shreds Alzheimer's proteinAn enzyme found naturally in the brain snips apart the protein that

forms the sludge called amyloid plaque that is one of the hallmarks of Alzheimer's disease (AD), researchers have found. They said their find-ings in mice suggest that the protein, called Cathepsin B (CatB), is a key part of a protective mechanism that may fail in some forms of AD. Also, they said their findings suggest that drugs to enhance CatB activity could break down amyloid deposits, counteracting one of the central pathologies of AD.Li Gan and colleagues published their findings in the September 21, 2006, issue of the journal Neuron, published by Cell Press.

Their experiments were prompted by previous studies showing that the cysteine protease CatB--an enzyme that snips apart proteins--closely associated with the amyloid-ß (Aß) protein that forms the amyloid plaques, a hallmark of AD. However, those studies had not determined whether CatB was "good" or "bad"--that is, whether it acted to produce Aß from a longer protein, called amyloid precursor protein (APP), or whether it broke down Aß.

In their experiments, Gan and colleagues determined that CatB was the latter--breaking down Aß, apparently to enable other enzymes to fur-ther degrade the protein for the cell's protein "garbage deposal" system.

They found that knocking out the CatB gene increased plaque deposi-tion in a mouse model of AD in which mice expressed the human form of APP. They also found that CatB tended to accumulate within amyloid plaques and that it acted to reduce Aß levels in neurons. And they found that introducing a pathological form of Aß, called Aß1-42, into neurons increased CatB in young and middle-aged mice with human APP, but not old mice. "Thus, upregulation of CatB may represent a protective mech-anism that fails with aging," wrote the researchers, and such failure may play a role in late-onset sporadic AD.

Their test tube studies showed that CatB biochemically degrades Aß by snipping one end of the protein, called the C-terminal end. What's more, the enzyme also degrades the long strings of Aß that form amy-loid plaque, they found.

Finally, they found that increasing levels of CatB in aging mice with human APP markedly reduced plaque deposits in the animals' brains.

Gan and colleagues concluded that "our findings suggest that inhibi-tion or loss of CatB function could interfere with its protective function and promote the development of AD, whereas overexpression of CatB could counteract Aß accumulation and aggregation. Thus, pharmacologi-cal activation of CatB could downregulate Aß1-42 assemblies through C-terminal truncation, offering an approach to the treatment of AD."

Moon 'priceless' for explorationNasa's lunar exploration plans have been strongly endorsed by an in-

fluential panel of US scientists.The Moon provided great opportunities for robotic and human space

exploration, said a report by the National Academy of Sciences.The 15-member panel was asked to evaluate and give advice on

Nasa's lunar research programme.President Bush vowed two years ago to return astronauts to the Moon,

with the eventual goal of landing on Mars.He told the US space agency (Nasa) to devote $12.5bn (£9.5bn) over

five years for the early stages of the programme, with a goal of landing astronauts on the Moon between 2015 and 2020.

30 5/10/2023

Some scientists have criticised the plans, saying they divert funds from research programmes that have no direct bearing on long-distance human spaceflight.

But a special National Research Council panel of the National Academy of Sciences said in an interim report that the Moon was "priceless to planetary scientists".

"Only by returning to the Moon to carry out new scientific exploration can we hope to close the gaps in understanding and learn the secrets that the Moon alone has kept for eons," it said.Apollo 11 bootprint (Nasa) One of the first

steps taken on the Moon in 1969Lunar 'platform'

The committee was made up of academics, a journalist and retired members of private industry involved in space programmes.

The experts outlined a number of priorities, including: * determining the composition and structure of the interior of the Moon * gaining a better understanding of the Moon's "atmosphere", the very thin whisps of gas at surface level * evaluating the Moon's potential as a platform for studying Earth, the relationship of the Sun and Earth, and astronomy and astrophysics in general

The final version of the report is due to be released in mid-2007.Nasa announced in August that the Lockheed Martin Corporation will

build the next US spaceship to take humans to the Moon.It awarded a multi-billion-dollar contract to the group to develop the

Orion vehicle, which will replace the space shuttle when it retires in 2010.

Ethiopia's pride in 'Lucy' findBy Pallab Ghosh Science correspondent, BBC News, Addis Ababa

A tropical storm beats against the national museum in Addis Ababa. The violent thunder and lashing rain contrasts with the serene activity within.

Inside a solitary figure is cleaning up a 3.3-million-year-old skull.Dr Zeresenay Alemseged has spent five

years removing sandstone, grain by grain, from his precious find.Illuminated by a single focussed beam of

light, this is intricate, delicate work: one mis-take and crucial scientific detail could be lost forever.

Alemseged showed me that what has emerged are the delicate fea-tures of a creature that was part ape and part human.Zeresenay Alemseged and the skull of "Lucy's baby"

"What you have here is the backbone and the thoracic and all the ribs, the shoulder blades the collar bones. But in addition, what you have here is a compete face and the sandstone impression of the brain of a 3.3-million-year-old infant."Early sound

Six years ago Alemseged set off toward the north-eastern deserts of Ethiopia. Working in the blistering heat, his team discovered what he thought was the skull of a creature that was one of the first apes to have walked on two feet.

Unable to contain his excitement, the scientist called his friend Tefera Ghedamu.

"He said I think I got it! And he knew exactly what he'd got. He's a very cautious person, a very shy person - but then he knew and told himself, 'this is the bone'," Ghedamu recalls.

Alemseged had found the most complete skeleton to date of a species called Australop-ithecus afarensis, thought to be an important pre-cursor to the first true humans.

Not only was it in a fantastic state of preser-vation but the specimen was that of an infant. This combination makes the find a gold mine for those studying human evolution.

It will now be available for other specialists to study; but already Alemseged has made a number of startling discoveries. Although the baby afarensis toddled on two feet like a hu-man child, it also had many important ape-like features.

"The shoulder blades are very gorilla-like and it may ignite old questions about whether afarensis could climb trees or not. But what was really exciting was to find the tongue bone. We will, based on this bone, be able to understand what the voice box was like and about the kind of sound this creature made," he explains.

Initial thoughts suggest the bone is ape-like and that the creature probably sounded like a chimp.

31 5/10/2023

'On the cusp'What really excites Alemseged, however, is his study of the ape-girl's

brain.He believes it is still developing. Slow and gradual development in an

extended childhood is a uniquely human feature - probably to enable our higher functions to fully develop.

So, according to Alemseged, this infant and her like may have been the first to show real human-like characteristics

"It's the earliest girl ever found with a mix of features that are ape-like and human-like at the same time, and this puts her in a special position to play a pivotal role. She is on the cusp of humanity," he says.

The creature is the latest of many recent fossil finds important to the understanding of human evolution - the most famous of which was the first Australopithecus afarensis specimen - and adult nicknamed "Lucy" - in 1974.

It has prompted the Ethiopia's culture minister, Mahmud Dirr Gade, to invite more scientists to come to the African nation to help unearth hu-mankind's origins.

"We welcome researchers to delve into the secrets and mystery of the creation of man in Ethiopia; the 'home of humanity'," he tells me.Home grown

Zeresenay Alemseged is the first Ethiopian to lead a research team that has made such an important discovery.

He is a bright young scientist who has studied in the US and Europe and is currently attached to the Max Planck Institute for Evolutionary An-thropology in Leipzig, Germany.

Human anthropology is a cut-throat field, even for those who have es-tablished themselves and have the backing of big funding bodies.

So, according to Tefera Ghedamu, it is especially remarkable that an outsider like Alemseged has worked his way up and to win the respect of the scientific community - and the pride of his nation.

"From my angle, from an ordinary Ethiopian's point of view, they think it is quite a heritage. They are proud that the discovery has been made in Ethiopia and they are proud that it's been made by one of their own," he says.

'Lucy's baby' found in EthiopiaThe 3.3-million-year-old fossilised remains of a human-like child have

been unearthed in Ethiopia's Dikika region.The female Australopithecus afarensis bones are from the same

species as an adult skeleton found in 1974 which was nicknamed "Lucy".Scientists are thrilled with the find, reported in the journal Nature.

They believe the near-complete remains offer a remarkable opportu-nity to study growth and development in an important extinct human ancestor.

Juvenile Australopithecus afarensis remains are vanishingly rare.The skeleton was first identified in 2000, locked inside a block of sand-

stone. It has taken five years of painstaking work to free the bones.The juvenile specimen is wonderfully preserved"The Dikika fossil is now revealing many secrets about Australopithe-

cus afarensis and other early hominins, because the fossil evidence was not there," said dig leader Zeresenay Alemseged, of the Max Planck In-stitute for Evolutionary Anthropology in Leipzig, Germany.Delicate bones

The find consists of the whole skull, the entire torso and im-portant parts of the upper and lower limbs. CT scans re-veal unerupted teeth still in the jaw, a detail that makes scientists

think the individual may have been about three years old when she died.

Remarkably, some quite delicate bones not normally preserved in the fossilisation process are also present, such as the hyoid, or tongue, bone. The hyoid bone reflects how the voice box is built and perhaps what sounds a species can produce.

Judging by how well it was preserved, the skeleton may have come from a body that was quickly buried by sediment in a flood, the re-searchers said.

"In my opinion, afarensis is a very good transitional species for what was before four million years ago and what came after three million years," Dr Alemseged told BBC science correspondent Pallab Ghosh.

"[The species had] a mixture of ape-like and human-like features. This puts afarensis in a special position to play a pivotal role in the story of what we are and where we come from."Climbing ability

This early ancestor possessed primitive teeth and a small brain but it stood upright and walked on two feet.

There is considerable argument about whether the Dikika girl could also climb trees like an ape.

This climbing ability would require anatomical equipment like long arms, and the "Lucy" species had arms that dangled down to just above

32

HUMAN EVOLUTIONComplex hominid tree (BBC)Different fossil in the 'human story' have been foundNot all will be a direct line to our Homo groupScarce and fragmentary finds complicate the storyScientists expect many more discoveries in Africa

5/10/2023

the knees. It also had gorilla-like shoulder blades which suggest it could have been skilled at swinging through trees.

But the question is whether such features indicate climbing ability or are just "evolutionary baggage".

The Dikika girl had an estimated brain size of 330 cubic centimetres when she died, which is not very different from that of a similarly aged chimpanzee. However, when compared to the adult afarensis values, it forms 63 - 88% of the adult brain size.

This is lower than that of an adult chimp, where by the age of three, over 90% of the brain is formed. This relatively slow brain growth in the Dikika girl appears to be slightly closer to that of humans.

Slow, gradual development in an extended childhood is regarded as a very human trait - probably to enable our higher functions to develop.

Professor Fred Spoor of University College London said the find would give scientists a "detailed insight into how our distant relatives grew up and behaved... at a time of human evolution when they looked a good deal more like bipedal chimpanzees than like us."

Dr Jonathan Wynn of the University of St Andrews, UK, and colleagues at the University of South Florida dated the sediments surrounding the remains and came up with an age of 3.3 million years.

The "Lucy" skeleton, discovered in Hadar, Ethiopia, in 1974 belongs to the same species as the Dikika girl. For more than 20 years it was the oldest human ancestor known to science.

Mosquitoes' sweet tooth targetedMosquitoes' thirst for sugar could prove to be the answer for eliminat-

ing malaria and other mosquito-transmitted diseases, say scientists.A Hebrew University team was able to devastate a local mosquito pop-

ulation by spraying acacia trees with a sugar solution spiked with an in-secticide.

While blood is the main element of a female mosquito's diet, it also likes to feed on plant nectar between meals.

The study features in the International Journal for Parasitology.Malaria kills over a million people a year and is second only to tuber-

culosis in its impact on world health.

It is spread by female mosqui-toes which need a meal of blood before laying their eggs, but de-rive much of their persistent en-ergy from nectar snacks, taken from flowers and nectaries on plant leaves and stems.

Isolated oasisThe Israeli team sprayed acacia trees in an oasis in the southern

desert region of the country with a sugar solution containing the insecti-cide Spinosad.

They chose the oasis because there were few other plants in the area from which mosquitoes could obtain their favourite tipple.

It was also home to a distinct and isolated mosquito population, so the effect could be monitored closely with only a minor risk of mosquitoes from neighbouring areas contaminating the results.

After spraying, almost the entire local population of mosquitoes was wiped out. The few mosquitoes that were trapped after spraying were thought to be newly emerging adults.

Lead researcher Professor Yosef Schlein said planting mosquito-at-tracting trees or bushes in suitable habitats, and spraying them with oral insecticide, could provide a relatively easy and cheap way to tackle the problem of malaria.

He said the technique had particular potential in areas of limited plant growth, such as desert and savannah regions, particularly sub-Saharan Africa, where malaria is becoming a bigger threat.

It might also have some use in areas with a greater variety of flowers, as mosquitoes are very fussy, and only visit a limited number of species.

Spinosad is an environmental "reduced-risk" oral insecticide that has little effect on other insects, birds and mammals.

Pierre Guillet, of the World Health Organization's global malaria pro-gramme, said any strategy that could effectively kill, or the reduce the life expectancy of adult female mosquitoes, had potential as a way to control the spread of malaria.

However, he said the research would have to be replicated before any firm conclusions could be drawn.

New visage for Red Planet 'face'The Mars Express probe has photographed

the classic surface feature on the Red Planet's surface known as "The Face".The mountain, which looks just like a hu-

man head with eyes, mouth and nostrils, was first pictured by the US Viking 1 Orbiter in 1976.The formation instantly became the stuff of

myth and conspiracy theories, with some claiming it was evidence of an ancient Martian civilisation.Mars Express reveals the structure in a striking new pose

The new European images of The Face were taken in July this year.

33

MALARIA300 million clinical cases each year1 million deaths world-wide per yearA child dies of malaria every 30 sec-ondsBiggest number of deaths occur among young children in Africa

5/10/2023

It has been something of a struggle for sci-entists to get a decent shot of the area in mid-northern latitudes referred to as Cydo-nia.The probe was either at too high an altitude

when making a pass or had its view de-graded by dust and haze in the atmosphere. A 22 July fly-over finally provided perfect conditions.

The skull (Esa/DLR/FUBerlin/G.Neukum)The new images even reveal a feature that looks like a skull

The probe used its High Resolution Stereo Camera to picture The Face and other geological structures around it in 3D.

This requires imaging experts at the German space agency to post-process essentially flat, overhead shots to produce perspective images that give the viewer the impression they are flying over the surface in a light aircraft.

The results are some of the most spectacular views of the Red Planet ever seen.

"These images of Cydonia on Mars are truly spectacular," said Dr Agustin Chicarro, project scientist for the European Space Agency's Mars Express mission.

"They not only provide a completely fresh and detailed view of an area famous to fans of space myths worldwide, but also provide an impressive close-up over an area of great interest for planetary geolo-gists, and show once more the high capabil-ity of the Mars Express camera."

Scientists are interested in Cydonia because it tells them about erosive processes on Mars.Cydonia tells scientists about erosion on the surface of Mars

Cydonia is located in the Arabia Terra region and belongs to the transi-tion zone between the southern highlands and the northern plains. This transition is characterised by wide, debris-filled valleys and isolated remnant mounds of various shapes and sizes.

Mars Global Surveyor images taken at the turn of the century proved beyond any doubt that The Face pictured by Viking 1 was nothing more than a trick of the light; there was no evidence there of structures built by an ancient civilisation, as some Red Planet fans had hoped.

Mars Express imaged another popular surface feature earlier this year: the 230km-wide (143 miles) impact crater that looks like a smiley face.

Feinstein Institute's top scientist weighs in on mind-body medicine at conference with Dalai Lama

PHOENICIA, NY – Because he discovered a key link between the mind and the body, Kevin J. Tracey, MD, The Feinstein Institute for Medical Re-search's director and CEO, was invited to speak this morning at "Longevity and Optimal Health: Integrating Eastern and Western Per-spectives." This conference, co-hosted by the Columbia University Inte-grative Medicine Program and Tibet House, has brought together leading scientists, scholars and practitioners to discuss how recent advances in the Western science of aging may reveal how the Indo-Tibetan traditions of meditation, diet and yoga extend life. The XIVth Dalai Lama, Tenzin Gyatso, is the guest of honor and will deliver a summary response inte-grating the discussions at the conclusion of the conference.

Through years of painstaking research on the immune system's re-sponse to injury, Dr. Tracey and his colleagues worldwide made several incremental discoveries that led to a new theory he coined "the inflam-matory reflex." The inflammatory reflex is the foundation for the mind-body connection, as it provides a direct link between the nervous sys-tem and that which normally keeps people healthy -- the immune sys-tem. This morning Dr. Tracey shared his findings and the latest applica-tions of this theory during the panel discussion on "Protection," moder-ated by Erin Olivo, PhD, MPH, director of the Columbia Integrative Medicine Program.

First published in the journal Nature in December 2002, Dr. Tracey's groundbreaking discovery that the brain controls the immune system via the vagus nerve -- the largest nerve in the body that wanders through the major organs -- has gained international acclaim, including a Nobel Conference dedicated to the topic hosted by the renowned Karolinska Institute in Stockholm, Sweden, in September 2004, which he co-chaired.

One of the immune system's weapons against foreign invaders is a molecule called tumor necrosis factor, or TNF. A "big gun," TNF can cause a local response to an injury or infection, such as pain and red-ness. This is good to a point, but in excessive amounts TNF and other like molecules can be so toxic as to cause shock and death.

Dr. Tracey and his team of researchers discovered that the brain sends chemical messages through the vagus nerve to specific sites on immune cells in the body to block TNF release. In other words, the vagus nerve is the conduit through which the brain directly controls the im-mune system -- and prevents excessive TNF, shock and death. This is the inflammatory reflex.

By studying patients with chronic inflammatory diseases, Dr. Tracey is trying to ascertain whether raising their vagus nerve activity with

34 5/10/2023

biofeedback decreases inflammation. The implication is that people with inflammatory diseases such as Crohn's, rheumatoid arthritis and periph-eral vascular disease may be able to "think" their way to feeling better.

Altering brain activity may one day be a strategy to prevent disease, improve health and promote longevity. The inflammatory reflex has di-verse applications for therapeutically targeting systemic inflammation in illnesses ranging from postoperative sepsis to autoimmune diseases to biological threat agents such as anthrax and plague. Because vagus nerve activity can be measured, researchers now have a way to scien-tifically test the effects of many ancient concepts and Indo-Tibetan prac-tices such as meditation and yoga on longevity.New research puts 'killer La Palma tsunami' at distant fu-

tureThe volcanic island of La Palma in the Canaries is much more stable

than is generally assumed, Dutch scientists working at the TU Delft have found. The southwestern flank of the island isn't likely to fall into the sea (potentially causing a tsunami) for at least another 10,000 years, profes-sor Jan Nieuwenhuis states in the September edition of the university's science magazine Delft Integraal.

The TU Delft research findings should be a relief for people living at or near the Atlantic coasts of the US, Africa and Europe. Six years ago, ge-ologists proposed that La Palma is so unstable that it might lose one of its flanks during a volcanic eruption in the near future. This would cause a 'mega tsunami' with massive waves up to hundreds of meters in height. Cities like New York, Boston, Lisbon and Casablanca would be all but wiped from the face of the planet, according to the more pessimistic estimates.

But according to the new TU Delft research, the Cumbre Vieja volcano on the island simply isn't large enough to fall apart… yet. In a first of its kind study, the Dutch researchers modelled the inside of the flank and then simulated several volcanic eruptions and watery 'steam explo-sions'. In every simulation, the volcanic flank stayed firmly in its place. 'This is simply a very stable island', says team leader professor Jan Nieuwenhuis in the September edition of the TU Delft science magazine Delft Integraal.

According to Nieuwenhuis' calculations, it would take the strength of about 600 million modern fighter jet engines to pull the flank apart: at least 12,000 to 28,000 billion Newton. That is much more than can be expected from a volcanic outburst on La Palma, the team concludes. Only under very extreme conditions, the flank could become unstable, Nieuwenhuis has calculated. This would require unusually heavy rainfall during an exceptionally strong magmatic outburst, or some other highly unlikely combination of circumstances. 'Based on what we know now, so

many things must go wrong that a disaster seems very, very unlikely', says Janneke van Berlo, who recently graduated in the group of prof. Nieuwenhuis.

The researchers calculate that the surest way to cause a landslide is to wait for at least another 10,000 years. The Cumbre Vieja volcano steadily grows and this causes the flanks of the volcano to become steeper and less stable. 'A combination of substantial vertical growth and eruption forces will most probably act to trigger failure. To reach substantial growth, a time span in the order of 10,000 years will be re-quired', Van Berlo states.

At a glance, La Palma doesn't look very solid even today. It has lost chunks of its flanks at least twice in prehistoric times already. And dur-ing the last eruption, in 1949, a two kilometer long rip appeared at the top of Cumbre Vieja's southwestern flank. But the Delft researchers point out that the cut is nothing more than the result of an innocent, shallow phenomenon, for example local adaptive settlements of the vol-cano. What's more, the ancient collapses are good evidence La Palma is stable now: the collapses only occurred when La Palma was much higher than today, at least 2,000 and 2,500-3,000 meter respectively.

Even if the volcanic flank did become critically unstable, it isn't likely it will go with a splash. 'Of course the flank won't go in one piece, but break up first', Nieuwenhuis said. 'And it could very well slide down a lit-tle and then settle in a more stable configuration, just like our dykes in Holland often do when they go unstable.' The plunge won't be a fast and sudden event, Nieuwenhuis stresses. 'It will more be like a steam loco-motive powering up. The first meter of movement should take several days.'Now that they have calculated the improbability of this I’m sure Nature will do Her best to confound the scientists! And the wildly contrasting comparisons are interesting – 600 million fighter jets versus a steam locomotive.May I suggest an equivalent number of Back To The Future DeLore-ans?

Walking not enough for significant exercise benefitsWalking is a popular form of exercise, but may not be enough to expe-

rience significant health benefits, a University of Alberta study shows."Generally, low-intensity activity such as walking alone is not likely go-

ing to give anybody marked health benefits compared to programs that occasionally elevate the intensity," said Dr. Vicki Harber, lead author on the Health First study, which was presented recently at the American College of Sports Medicine annual conference.

Dr. Harber and her colleagues, Dr. Wendy Rodgers, Dr. Gordon Bell and Dr. Kerry Courneya of the Faculty of Physical Education and Recre-

35 5/10/2023

ation at the University of Alberta in Edmonton, Canada, were concerned that while people with health issues are encouraged to increase their volume of activity such as walking, there didn't seem to be much focus on the effort that needed to go into the activity.

The University of Alberta study put the popularized pedometer-friendly 10,000-step exercise program to the test against a traditional fitness program which incorporated cardio-based activities on equipment such as treadmills and stationary bicycles. The traditional group was asked to complete exercise at a moderate intensity, a level allowing for one or two sentences of conversation with ease. Intensity was not set for the walking group; they completed their daily exercise at a self-selected pace.

"When we matched the two programs for energy expenditure, we found that the traditional fitness program improved aerobic fitness and reduced systolic blood pressure, more than the 10,000-step lifestyle pro-gram," Dr. Harber said. Of the 128 sedentary men and women who com-pleted the six-month research program, those who took part in a more active traditional fitness regimen increased their peak oxygen uptake, an indicator of aerobic fitness, by 10 per cent. Those who took part in the walking program experienced a four per cent increase. Systolic blood pressure also dropped by 10 per cent for the traditional fitness group, compared to four per cent for the group who just walked.

Other markers of overall health, such as fasting plasma glucose levels, response to a two-hour glucose tolerance test and various blood lipids were unaffected by either exercise program.

"Our concern is that people might think what matters most is the total number of daily steps accumulated, and not pay much attention to the pace or effort invested in taking those steps," Dr. Harber said. "The 10,000-step or pedometer-based walking programs are great for peo-ple--they are motivating, and provide an excellent starting point for be-ginning an activity program, but to increase the effectiveness, one must add some intensity or "huff and puff" to their exercise. Across your day, while you are achieving those 10,000 steps, take 200 to 400 of them at a brisker pace."

"You've got to do more than light exercise and move towards the in-clusion of regular moderate activity, and don't be shy to interject an oc-casional period of time at the vigorous level."'Egg on your face' may be more dangerous than you think

'Here's egg in your eye': a prospective study of blunt ocular trauma resulting from thrown eggs

As the party conference season gets under way in the UK, research in Emergency Medicine Journal shows that lobbing raw eggs at people as a harmless form of protest or prank can actually result in serious eye in-jury.

Between November 2004 and December 2005 researchers at one spe-cialist department monitored more than 18,000 patients requiring eye treatment.

Of these, 13 patients had sustained injuries as a result of being as-saulted by a raw egg. Twelve of the patients were men, whose average age was 27.

Most of the cases were clustered in October, during the period around Halloween.

In nine people, the left eye was injured. In only one person was eye-sight unaffected by the incident.

Three people's injuries were classified as "minor," amounting to bruis-ing and bloodshot eyes. The injuries were classed as moderate in a fur-ther two cases; the remainder were classified as serious.

The serious injuries included tears and severe bruising to the retina, disruption of the light receptor cells in the eye, and raised internal pres-sure, which can damage the optic nerve and cause permanent loss of eyesight, and damage to the macula.

Twelve patients recovered, one of whom needed major surgery to do so.

The authors comment that damage to the eye as a result of being hit by a blunt object, referred to as "blunt ocular trauma," makes up around a third of injuries seen in primary care eye clinics.

"The dimensions of an egg are similar to those of a squash ball, with a considerably greater weight, meaning that eggs as missiles can easily fit into the orbital rim, causing severe blunt injury even when thrown by hand," write the authors.

The belief that this prank is harmless, is misplaced, they warn.Robot infantry ready for the battlefield

"PLEASE put down your weapon. You have 20 seconds to comply." So said the armed robot in Paul Verhoeven's 1987 movie RoboCop.

The suspect drops his weapon but a fault in the robot's software means it opens fire anyway. Nearly two decades later, such fictional weapon-toting robots are looking startlingly close to reality – and New Scientist has discovered that some may eventually help to decide who is friend and who is foe.

Sometime in the coming months, chances are that we'll be seeing TV reports that an armed remote-controlled robot has been used in anger for the first time. "They will appear when they appear. I can't talk about when that may be," says Bob Quinn, genera manager at Foster-Miller of Waltham, Massachusetts, whose machine-gun-equipped robot, called Sword, was certified safe for use by the US forces in June.

Robots have already shown their mettle in defensive roles, detonating improvised bombs in the UK, Israel, Iraq and Afghanistan. Foster-Miller's

36 5/10/2023

Talon robot and its rival PackBot, from the Massachusetts-based com-pany iRobot, are the lightweight robots now used for these tasks. These tracked machines, controlled by an operator sitting in an armoured vehi-cle, are capable of being driven at high speed and use manipulator arms and grippers to place a small explosive charge to disable a suspected bomb.

Now versions of these robots are being developed that will allow troops to manoeuvre and fire a variety of weapons. iRobot has built a prototype equipped with a 20- round shotgun. "It will be able to fire over four dozen different kinds of shotgun ammunition, everything from large slugs that would kill an elephant, to buckshot that would cover a wide area," says Joe Dyer, head of iRobot's military division. Foster-Miller's Sword is a variant of Talon in which the manipulator arm has been re-placed by a rotating machinegun carrier. "It's for urban combat and perimeter security and it's fully controlled by the soldier," Quinn says. Touted uses include checking out a potential ambush.

Both companies stress that there is always a human in control of the robots. Apart from a planned autonomous "return home" function, nei-ther Sword nor the iRobot prototype operates autonomously.

Nevertheless, more complex machines may soon be on the drawing board. A research request issued in August by the Pentagon's Office of Naval Research (ONR) shows that military robots are one day going to be asked to make some important decisions on their own. The ONR wants to engineer mobile robots to "understand cooperative and unco-operative" people, and inform their operator if they seem a threat. It hopes to do this using artificial intelligence software fed with data from a "remote physiological stress monitoring" system, and by using speech, face and gesture recognition. From this it would draw inferences about the threat that person poses.

It's a prospect that is causing some concern. "It is ethically problem-atic to use software that may work in lab conditions but not under a whole range of extreme conditions, such as when you suspect someone might be a suicide bomber," says Kirsten Dautenhahn, an AI expert at the University of Hertfordshire in the UK.

Lucy Suchman, an expert in human-computer interaction at Lancaster University, UK, is even more critical: "This plan is just ridiculous. It in-volves the worst kind of simplistic profiling. It's a fantasy on the part of technology enthusiasts within the Pentagon." Quinn, however, dis-agrees. The ONR is not known for wasting research dollars, he says, and what it funds usually happens – even if it is 10 years away. "Recognition technology is progressing fast. I think it will separate the wheat from the chaff," he predicts.

Let’s hope they aren’t carrying

eggs!Squid Skin Reveals Hidden Messages

MBL scientists find anatomical evidence for a hidden communica-tion channel that remains masked during camouflage

MBL,WOODS HOLE, MA-In the animal world, squid are masters of disguise. Pigmented skin cells enable them to camouflage themselves-almost in-stantaneously-from predators. Squid also produce polarized skin pat-terns by regulating the iridescence of their skin, possibly creating a “hid-den communication channel” visible only to animals that are sensitive to polarized light.

In research published today in the journal Biology Letters, MBL (Marine Biological Laboratory) researchers Lydia Mäthger and Roger Hanlon present evidence that the po-larized aspect of the skin of the longfin inshore squid, Loligo pealeii, is maintained after passing through the pigment cells responsible for camou-flage.While the notion that a few animals produce po-

larization signals and use them in communication is not new, Mäthger and Hanlon’s findings present the first anatomical evidence for a “hidden communication channel” that can remain masked by typical camouflage patterns. Their results suggest that it might be possible for squid to send concealed polarized signals to one other while staying camouflaged to fish or mammalian predators, most of which do not have polarization vision.squid skin

Mäthger notes that these messages could contain information regard-ing the whereabouts of other squid, for example. “Whether signals could also contain information regarding the presence of predators (i.e., a warning signal) is speculation, but it may be possible,” she adds.

Mäthger and Hanlon maintain that the mechanism behind the trans-mission of polarized light through squid pigment cells warrants further study. Likewise, investigation of this masked polarization signaling sys-tem in squid and other cephalopods in natural environments would pro-vide insight into animal camouflage mechanisms and may uncover simi-lar examples in other species.University of Pennsylvania Researchers Discover “Killer” B

Cells; New Link in the Evolution of ImmunityPHILADELPHIA -- Researchers from the University of Pennsylvania School of Veterinary Medicine have discovered a unique evolutionary link between the immune systems of fish and mammals in the form of a primitive ver-sion of B cells, white blood cells of the immune system. Their studies link the evolution of the adaptive immune system in mammals, where B cells

37 5/10/2023

produce antibodies to fight infection, to the more primitive innate immu-nity in fish, where they found that B cells take part in phagocytosis (liter-ally: cell eating), the process by which cells of the immune system in-gest foreign particles and microbes.

The finding, which appears in the online version of Nature Immunology and will be featured on the cover of the October issue, represents a size-able evolutionary step for the mammalian immune system and offers a potential new strategy for developing much-needed fish vaccines.

"When examining fish B cells we see them actively attacking and eat-ing foreign bodies, which is a behavior that, according to the current dogma, just shouldn't happen in B cells," said J. Oriol Sunyer, a professor in Penn Vet's Department of Pathobiology. "I believe it is evidence for a very real connection between the most primitive forms of immunological defense, which has survived in fish, and the more advanced, adaptive immune response seen in humans and other mammals."

About 400 million years ago, the earliest ancestors of modern fish split off of the evolutionary pathway that became the earliest ancestors of modern mammals. In modern mammals, the B cell is a highly adapted part of the immune system chiefly responsible for, among other things, the creation of antibodies that tag foreign particles and microbes for de-struction. Mammals have phagocytic cells, but they are a specialized few cells identified apart from the complex interactions that drive other white blood cells.

Sunyer and his colleagues discovered this previously unsuspected B cell activity while examining the immune cells of rainbow trout and cat-fish. The researchers determined that these attack B cells account for more than 30-40% of all immune cells in fish, while phagocytic cells only make up a small portion of the total number of immune cells in mam-mals. Further research also showed that a significant portion of amphib-ian B cells retained their digestive traits.

"The immune systems of amphibians and fish are far less advanced than ours," Sunyer said. "When you only have a rudimentary adaptive immune system, it helps to have more phagocytic cells to compensate, which is what has served fish so well over the last 400 million years."

In the past, research on the immune systems of more primitive species has paved the way to the discovery of new molecules and path-ways that are critical to the immune response in humans and other mammals. B cells themselves, for example, were first discovered in chickens in the 1960s. According to Sunyer, the Penn findings are not only important for understanding the evolution and function of immune cells in fish but also may point out to novel roles of B cells in mammals.

At this point, we cannot rule out the possibility that small subpopula-tions of phagocytic B cells, perhaps remnants of those present in fish, are still present in mammals, Sunyer said.

Their findings also have an agricultural implication. The current vac-cines given to farmed salmon, for example, appeal to the fish's adaptive immune response, which this research has now shown to be a smaller part of the overall fish immune system than previously thought.

"If we work to create vaccines that encourage phagocytic B cell to re-spond to infection, then we would play to the strengths of fish immu-nity," Sunyer said. "In the long term, farming is a better, more environ-mentally sound approach to fishing, so better vaccines may make the practice more financially attractive to fisherman and less destructive to fish populations."

There is little doubt that, despite the behavioral differences, the fish B cells represent a less advanced version of mammalian B cells. Sunyer found the very cellular structures that medical science has used to de-fine B cells in humans to be present in fish B cells, which is why they are able to label them as B cells in the first place.

"Here we have a clear picture of where one part of the immune sys-tem, primitive phagocytes, adapted over time to serve a more complex role as part of the immune system that humans enjoy today, Sunyer said. There is still much we can learn about our own health through the ongoing study of immune system evolution among all organisms.Funding for this research was provided by the National Science Foundation and United States Department of Agriculture.

Activating the feeling of being followedEver had the feeling you're being followed? Neuroscientists have acci-

dentally induced this creepy feeling in a woman with epilepsy while elec-trically stimulating the left side of her brain.

The woman described how a shadowy man clasped her in his arms when she hugged her knees, and tried to pull cards out of her hands as she read them (Nature, vol 443, p 287). Olaf Blanke at the University Hospital in Geneva, Switzerland, and his colleagues realised that the "man" was in fact mimicking her own actions.

They believe the stimulated area, which is known to process informa-tion about where our body is, may be affected in psychiatric patients who suffer feelings of paranoia, persecution and alien control.

The point of iciclesContemplating some of nature's cool creations is always fun. Now a

team of scientists from The University of Arizona in Tucson has figured out the physics of how drips of icy water can swell into the skinny spikes known as icicles.

Deciphering patterns in nature is a specialty of UA researchers Martin B. Short, James C. Baygents and Raymond E. Goldstein. In 2005, the team figured out that stalactites, the formations that hang from the ceil-

38 5/10/2023

ings of caves, have a unique underlying shape described by a strikingly simple mathematical equation.

However, stalactites aren't the only natural formations that look like elongated carrots. Once the researchers had found a mathematical rep-resentation of the stalactite's shape, they began to wonder if the solu-tion applied to other similarly shaped natural formations caused by drip-ping water.

So the team decided to investigate icicles. Although other scientists have studied how icicles grow, they had not found a formula to describe their shape.

Surprisingly, the team found that the same mathematical formula that describes the shape of stalactites also describes the shape of icicles.

"Everyone knows what an icicle is and what it looks like, so this re-search is very accessible. I think it is amazing that science and math can explain something like this so well. It really highlights the beauty of na-ture," Short said.

The finding is surprising because the physical processes that form ici-cles are very different from those that form stalactites. Whereas heat diffusion and a rising air column are keys to an icicle's growth, the diffu-sion of carbon dioxide gas fuels a stalactite's growth.

Short, a doctoral candidate in UA's physics department, Baygents, a UA associate professor of chemical and environmental engineering, and Goldstein, a UA professor of physics and the Schlumberger Professor of Complex Physical Systems at the University of Cambridge in England, published their article, "A Free-Boundary Theory for the Shape of the Ideal Dripping Icicle," in the August 2006 issue of Physics of Fluids. The National Science Foundation funded the research.

As residents of cold climates know, icicles form when melting snow be-gins dripping down from a surface such as the edge of a roof. For an ici-cle to grow, there must be a constant layer of water flowing over it.

The growth of an icicle is caused by the diffusion of heat away from the icicle by a thin fluid layer of water and the resulting updraft of air traveling over the surface. The updraft of air occurs because the icicle is generally warmer than its surrounding environment, and thus convec-tive heating causes the air surrounding the icicle to rise. As the rising air removes heat from the liquid layer, some of the water freezes, and the icicle grows thicker and elongates.

"At first, we focused only on the thin water layer covering the icicle, just like we did with stalactites," said Short. "It was only later that we ex-amined the layer of rising air, which is technically more correct. Strangely though, both methods lead to the same mathematical shape for icicles."

The resulting shape turns out to be described by the same mathemati-cal equation that describes stalactites. One could call it the Platonic form.

The team wanted to compare the predicted shape to real icicles. Be-cause icicles are scarce in Tucson, the scientists naturally turned to the Internet. They were able to compare pictures of actual icicles with their predicted shape.

The team found that it doesn't matter how big or small the actual ici-cles were, they could all fit to the shape generated by the mathematical equation.

"Fundamentally, just like in the early stalactite work, it's a result that implies that the shape of an icicle, at least in its ideal, pristine form, ought to be described by this mathematical equation. And we found, ex-amining images of icicles, that it is a very good fit," senior author Gold-stein said.

The team's next step will be to solve the problem of how ripples are formed on the surfaces of both stalactites and icicles.

Better training needed to reduce emergency caesareansEditorial: Caesarean delivery in the second stage of labor

Many emergency caesareans could be prevented by the attendance of a more skilled obstetrician, say senior doctors in this week's BMJ.

They call for better training in instrumental vaginal delivery (use of forceps or ventouse) for obstetric trainees to help reduce rates.

A recent UK study found that decisions made by senior (consultant) obstetric staff are important in determining whether a second stage cae-sarean section is the best method of delivery for women with delay in advanced labour. It found that a consultant obstetrician who performed a vaginal assessment was more likely to reverse a decision made by an obstetric trainee for a caesarean and proceed to a safely conducted in-strumental delivery.

The authors warn that, without increases in junior doctors' experience and recruitment into the specialty, the problems with second stage cae-sareans will rise.

According to the Royal College of Obstetricians and Gynaecologists audit figures, about 35% of caesareans for singleton pregnancies are performed because of failure to progress in labour, of which a quarter occur at full cervical dilatation. In 55% of these cases no attempt was made to achieve a vaginal birth with either forceps or ventouse. In those births where instrumental delivery was attempted, the audit noted a "failed" rate of 35% for ventouse and 2% for forceps.

Breech and twin deliveries can also lead to second stage caesareans. In the absence of an experienced and skilful obstetrician to perform as-

39 5/10/2023

sisted vaginal breech delivery, women are advised to undergo an emer-gency caesarean.

For twin deliveries, currently about 10% of second twins are delivered by caesarean section after the first has been delivered vaginally: 10 years ago, the rate was 5%. As many as two thirds of these caesareans are preventable, say the authors.

Despite problems relating to the inexperience of obstetric trainees, the United Kingdom is making great strides in terms of structured train-ing, assessment of competencies, and consultant delivered intrapartum care, they write. Nevertheless, it is essential to recognise the need for obstetricians to maintain and develop their skills if women are to be of-fered safe alternatives to caesarean section when complications arise in labour.

Stabbings are increasingLetter -- Stabbing: Data support public perception

Serious knife injuries are increasing, say trauma experts at the Royal London Hospital in a letter to this week's BMJ.

Several recent deaths have fuelled the perception that forensic knife injuries have become an epidemic, resulting in a knife amnesty and gov-ernment discussion of new punitive measures, write Charles Knowles and colleagues.

An increase in such injuries is supported by data from regional police forces and the Home Office, with 1200 reported attacks in London last year and 30% of homicides caused by knife injury. Crimes defined as "more serious wounding or other act endangering life" almost doubled nationally from 1995 to 2005.

The authors audited knife injuries at their east London hospital, one of Europe's busiest emergency departments, to establish the size of this problem in a representative urban area.

They analysed data on forensic knife injuries (excluding deliberate self harm) from a database of all trauma calls from July 2004 to June 2006. Overall there were 309 forensic knife injuries; 259 patients were admit-ted, 184 were operated on, and eight died. The chest was the most com-mon area injured, most patients were men, and mean age was 28.

To give a measure of changing incidence over a longer time, they also performed an audit of all cases coded as "stabbing" during the 10 year period from July 1997 to June 2006.

Over both periods, the data show an increase in the overall incidence of stabbings. The increased need for surgical intervention may also re-flect increasing severity of injury, they say.

These data therefore seem to support the general perception that knife injuries are increasing, they conclude.So this is another new issue of worldwide concern. I wonder what

the origins of this could be…Insulin receptor stops progression of Alzheimer's disease

Patients could be treated in early phases of diseaseProvidence, RI – Stimulation of a receptor in the brain that controls insulin responses has been shown to halt or diminish the neurodegeneration of Alzheimer's disease, providing evidence that the disease can be treated in its early stages, according to a study by researchers at Rhode Island Hospital and Brown Medical School.

Researchers have found that peroxisome-proliferator activated recep-tor (PPAR) agonists prevent several components of neurodegeneration and preserve learning and memory in rats with induced Alzheimer's dis-ease (AD). They found that an agonist for PPAR delta, a receptor that is abundant in the brain, had the most overall benefit.

"This raises the possibility that you can treat patients with mild cogni-tive impairment who have possible or probable Alzheimer's disease. This is really amazing because right now, there's just no treatment that works," says lead author Suzanne M. de la Monte, MD, MPH, a neu-ropathologist at Rhode Island Hospital and a professor of pathology and clinical neuroscience at Brown Medical School in Providence, RI.

The study appears in the September issue (Volume 10, Issue 1) of the Journal of Alzheimer's Disease (www.j-alz.com).

In previous studies, the researchers demonstrated that Alzheimer's is a brain-specific neuroendocrine disorder, or a Type 3 diabetes, distinct from other types of diabetes. They showed that insulin and IGF-I recep-tors are produced separately in the brain, and begin to disappear early in Alzheimer's and continue to decline as the disease progresses. As in-sulin signaling breaks down, it leads to increased oxidative stress, im-paired metabolism and cell death – all causing neurodegeneration.

Scientists were also previously able to replicate Alzheimer's in rats with Streptozotocin (STZ), a compound that is known to destroy insulin producing cells in the pancreas and cause diabetes. When injected into the brains of rats, the compound mimicked the neurodegeneration of Alzheimer's disease – plaque deposits, neurofibrillary tangles, dimin-ished brain size, impaired cognitive function, cell loss and overall brain deterioration.

Having created an animal model for Alzheimer's, researchers in this study induced Alzheimer's with STZ and then administered treatment with three classes of PPAR agonists – alpha, gamma and delta. All are found in various tissues and organs in the body, including the brain, and PPAR gamma is already FDA approved as a treatment for Type 2 dia-betes, or adult-onset diabetes. The two other classes of PPAR agonists have not yet been approved for clinical use.

40 5/10/2023

Following treatment, many of the abnormalities associated with Alzheimer's were reduced or nearly disappeared. The agonists affected different regions of the brain, with PPAR delta producing the most strik-ing effect in preserving the hypothalamus and temporal lobes, areas of the brain responsible for memory, learning, and behavior. In these brain regions, PPAR alpha and PPAR gamma were effective in reducing amy-loid gene expression. PPAR delta had the most benefit for reducing ox-idative stress and improving learning and memory.

"That was the most spectacular," de la Monte says, "because every-body wants something for cognitive impairment, and that was the most improved with the PPAR delta agonist."

Researchers were not able to stop the deterioration of insulin and its receptors. However, by administering PPAR, they were able to bypass the defects in insulin signaling and preserve the cells that need insulin to thrive. PPAR molecules go directly to the nucleus of cells and tell DNA to turn on or off genes that are normally regulated by insulin, thus pre-venting them from dying and allowing them to communicate with each other. The major effects of the PPAR treatments were to increase brain size, preserve insulin and IGF-II receptor bearing neurons, and preserve learning and memory.

"The trigger for dementia is the loss of insulin and IGF producing cells. The cells that need those growth factors subsequently die. This study shows you can block the second phase, which is responsible for demen-tia. This is great news for patients since you treat early stages of dis-ease," de la Monte says.

Another promising result for Alzheimer's patients is that these drugs could be given in the form of a pill, de la Monte says. In the study, the drugs were injected to control the amounts administered.

"One of the most exciting findings was that peripheral (intraperi-toneal) injection of the PPAR agonists either partially or completely res-cued the brains from neurodegeneration," the authors write.

Alzheimer's appears to be caused by parallel abnormalities – impaired insulin signaling and oxidative stress, which is regulated by the genes NOS and NOX. The PPAR agonists treatments target both problems. They preserve the cells regulated by insulin and IGF, and they decrease oxidative stress, resulting in fewer lesions in the brain.

"If the diagnosis is suspected or patients are in the early phases of AD, there's a good possibility they could get treatment that will help them. It's possible that in the moderate phase, treatment will also help, but more work needs to be done to show that," de la Monte says.

Treatment is not likely to work in the late stages of the disease, she says, because the cells have already died.

Video games: Medicine for the body

New game prototype released at Games for Health conferenceWASHINGTON DC – The Federation of American Scientists (FAS) will present the newest prototype of its educational game Immune Attack on Friday, 29 September 2006, at 10:00 a.m. at "The Body is a Game,"part of the Games for Health Conference at the University of Maryland School of Medicine in Baltimore.

Immune Attack is a new generation video game that engages students and teaches complex biology and immunology topics in a manner differ-ent from the traditional classroom approach. The goal is to immerse the student in immunology concepts to make learning fun and exciting.

"Immunology is a complicated and difficult subject to learn, which is precisely why it makes such an interesting basis for a video game," said Eitan Glinert, FAS Project Coordinator of Immune Attack. "The challenges in Immune Attack give those who might not otherwise be interested in biology the chance to learn in a fun, hands-on manner they won't find in a text book."

Human body tissue structures serve as the playing field in this first person strategy game where immune cells face off against bacterial and viral infections. A teenaged prodigy with a unique immunodeficiency must teach his immune system how to function properly, or die trying. Using a nanobot and aided by a helpful professor, the teenager explores biologically accurate and visually detailed settings in pursuit of this goal.

"The video game experience is a wonderful complement to the learn-ing that happens in the classroom. The game allowed students to use sights, sounds, and touch to get better acquainted with the immune sys-tem. Students also interacted with each other, having problem-solving discussions to enhance their game-play, and ultimately learning of the subject," said Angelique Bosse, a teacher at Montgomery Blair High School in Silver Spring, MD.

Each subsequent level of Immune Attack features a different infection with a new type of immune cell for the player to train. The player zooms among red blood cells, squeezes through blood vessel walls, and scans and interacts with various objects to train his immune system to fight off the invading pathogens.

"Clearly, computer games hold special interest to a generation who has grown up with them, and as such, they show promise as educational tools. Our educational games program is undertaking research to better understand what features of games can be used to improve learning and to develop guidelines based on that research," said Kay Howell, Vice President of Information Technologies at FAS.

As video games have become a common part of society, FAS is look-ing for ways to produce complex games that provide an environment for learning about history, problem-solving, and managing systems. Games and 3-D interactive simulations will one day revolutionize education and

41 5/10/2023

how people learn. FAS educational games help students and workers learn globally competitive skills in demand by employers.

"Games increase motivation, but it is not entirely clear why. For exam-ple, games typically include competition - either against a human oppo-nent or a computer-generated one. They are often story-based, feature strong characters, and typically 'keep score.' The research challenge is to determine how these features contribute to learning," said Howell.

Lucky find off GalapagosOcean scientists discover how bacteria produce propane in the

deep seafloorDuring an expedition off the South American coast, an international

team of ocean scientists discovered that the gases ethane and propane are widespread, and are being produced by microorganisms in deeply buried sediments. Prof. Kai-Uwe Hinrichs (Research Center Ocean Mar-gins, University of Bremen), co-author Prof. John Hayes (Woods Hole Oceanographic Institution), and colleagues report new findings on the production of energy-laden gases in a paper in this week's online edition of the renowned Proceedings of the National Academy of Sciences of the U.S.A. (PNAS). The findings suggest that microbes in the deeply buried, vast ecosystem below the seafloor carry out hitherto unrecognized pro-cesses, which are highly relevant to both our understanding of global el-ement cycles and the metabolic abilities of Earth's microbial biosphere.

"In a way, the finding was coincidental," Hinrichs states. Onboard the research drilling vessel JOIDES Resolution, the geochemist, now at the University of Bremen but then at Woods Hole Oceanographic Institution (WHOI), analyzed the gases in sediments buried up to 400 meters in the Equatorial Pacific off Peru. "We were swamped with samples: in nearly a thousand samples of up to 40 million-year-old sediment, we analyzed the gas content." Despite work shifts of up to 14 hours, the shipboard scientists soon had a backlog of unanalyzed samples, which turned out to be lucky. "When we later looked at the samples, we noticed that con-centrations of ethane and propane were suspiciously high," Hinrichs adds. Soon the scientists realized that these gases were not artifacts or contaminants, but that they must have slowly escaped from the sedi-ment.

The researchers began to wonder how to account for the presence of these gases. Normally, ethane and propane are known as typical prod-ucts of fossil fuel generation at elevated temperatures and pressure, without direct involvement of microbes. In the PNAS article, the team ar-gues that microbes played a key role in the formation of these hydrocar-bons.

"Sediments contain organic material (the fossil remnant of oceanic plants and animals)," Hinrichs explains. "This material, a key ingredient in the carbon cycle, is the major food used by the deep biosphere. Dur-

ing its decomposition by microbes, acetate--the ionic form of acetic acid--is formed. We think that bacteria use hydrogen to convert acetate into ethane. Addition of inorganic carbon and hydrogen provides a route to propane."

In support of their hypothesis for a biological origin of the gases, the researchers point to several clues: "First, the sampling locations are re-mote from reservoirs of oil and natural gas, so that this source can be eliminated," Hinrichs says. "Moreover, the abundance of stable isotopes of carbon are markedly different from those in gases formed at high temperature," adds co-author John Hayes, a geochemist at Woods Hole Oceanographic Institution (WHOI).

Co-author Wolfgang Bach, geochemist and professor at the Bremer Research Center points out, "We also were able to demonstrate that un-der the conditions prevailing at depth, these processes could yield just enough energy for growth of bacterial communities."

The paper leads to several new questions that will be addressed in fu-ture work. In a current PhD project in the Organic Geochemistry Group at the Research Center Ocean Margins, experiments are being con-ducted to locate the sedimentary sites where the gases are hidden. "In-terlayer spaces of clay minerals are the best candidates right now," Hin-richs says. Other experiments are currently being designed to find out more about how the gases are being formed. He adds, "One important goal right now is to study these processes under controlled conditions in the lab to verify or refine the proposed mechanism." Hinrichs knows that it may not be easy to simulate processes from the deep biosphere, but the geochemist hopes to identify and replicate the conditions needed to stimulate the microbes to produce a lot of these energy carriers.

Ancient birds flew on all-foursBird flight evolved using front and hind limbs as wings, new fossil

study arguesThe earliest known ancestor of modern-day birds took to the skies by

gliding from trees using primitive feathered wings on their arms and legs, according to new research by a University of Calgary paleontolo-gist. In a paper published in the journal Paleobiology, Department of Bio-logical Sciences PhD student Nick Longrich challenges the idea that birds began flying by taking off from the ground while running and shows that the dinosaur-like bird Archaeopteryx soared using wing-like feathers on all of its limbs.

"The discussions about the origins of avian flight have been domi-nated by the so-called 'ground up' and 'trees down' hypotheses," Lon-grich said. "This paper puts forward some of the strongest evidence yet that birds descended from arboreal parachuters and gliders, similar to modern flying squirrels."

42 5/10/2023

The first fossil of the Jurassic-era dinosaur Archaeopteryx lithographica was discovered in Germany in 1861, two years after Charles Darwin published his theory of evolution in On The Origin of Species. Since then, eight additional specimens have been unearthed and Archaeopteryx is considered the best evidence that birds evolved from dinosaurs since it had both feathers and a bird-like wishbone, along with classic reptilian features of a long bony tail, claws and teeth.

Although scientists immediately noticed feather-like structures on the hind limbs, they were dismissed as insulating body feathers that didn't

play a role in the animal's flight. It wasn't until several four-winged di-nosaurs in China were described in 2002 that researchers began to re-examine Archaeopteryx's legs.

"The idea of a multi-winged Ar-chaeopteryx has been around for more than a century, but it hasn't re-ceived much attention," Longrich said. "I believe one reason for this is that people tend to see what they want or expect to see. Everybody

knows that birds don't have four wings, so we overlooked them even when they were right under our noses."

Under the supervision of professor Anthony Russell, Longrich exam-ined Archaeopteryx fossils and determined that the dinosaur's leg feath-ers have an aerodynamic structure that imply its rear limbs likely acted as lift-generating "winglets" that played a significant role in flight.

Farmers Find a 4-Legged ChickenSOMERSET, Pa. (AP)-Henrietta the chicken was living inconspicuously among 36,000 other birds at Brendle Farms for 18 months-until a foreman no-ticed she had four legs.

"It's as healthy as the rest,'' the farm's owner, Mark Brendle, told The Daily American.

Brendle's 13-year-old daughter, Ashley, named the chicken Henrietta after the discovery Thursday. The bird has two normal front legs and, behind those, two more feet. They are of a similar size to her front legs but don't function. The chicken drags her extra feet behind her.

In 30 years of farming, Brendle said, he's never before seen a chicken with four legs.

There's no definitive reason why such deformities happen, said Cliff Thompson, a retired professor of genetics at the University of Pittsburgh at Johnstown. He said it could be an accident of development, akin to a sixth toe on a cat.

Brendle said he jokingly suggested to his family that it sell Henrietta in an Internet auction, but Ashley ob-jected.

Crickets on Hawaiian Island develop silent wings in re-sponse to parasitic attack

Male crickets use ingenious means to mate with females after loss of sexual signal, UCR biologists find

RIVERSIDE, Calif. -- In only a few genera-tions, the male cricket on Kauai, one of the Hawaiian Islands, underwent a mu-tation – a sudden heritable change in its genetic material – that ren-dered it incapable of using song, its sexual signal, to attract female crickets, according to a new study by UC Riverside evolutionary biolo-gists.

In addition, the researchers found that although the new male crick-ets' wings lack the file and scraper apparatus required for producing sound, the males are able to mate successfully with females, thus ensur-ing evolutionary success. They accomplish this by simply altering their behavior in an ingenious manner, suggesting that behavior can help what may seem like a harmful mutation spread.

The research team, led by Marlene Zuk, a professor of biology, found that greater than 90 percent of male field crickets (Teleogryllus oceani-cus) on Kauai shifted in less than 20 generations from having normal wings to mutated "flat wings" that inhibit the crickets from calling. The mutation occurred, the researchers conclude, to protect male crickets from a deadly parasitic fly (Ormia ochracea) that uses the cricket song to locate crickets as hosts.

Upon finding a male cricket, the fly deposits larvae onto it; these then burrow into the cricket, develop inside, and subsequently kill the cricket when they emerge from its body. Of three Hawaiian Islands (Oahu, the Big Island of Hawaii, and Kauai) where the cricket and fly co-occur, Kauai, where the rapid spread of this wing mutation in male crickets was observed, has the highest prevalence of the parasitic fly.

Study results appear in Biology Letters, a scientific journal of the Royal Society in the United Kingdom, publishing short papers from across the biological sciences.

"With each visit we made to Kauai since 1991, we observed fewer crickets," said Zuk, the first author of the paper. "In 2001, we heard only one calling male. But then in 2003, although we heard none of the male crickets calling, we found they were not only in high abundance but

43 5/10/2023

nearly all of them also had female-like wings, lacking the fine structures needed to produce song."

The researchers also found that male cricket populations in Oahu and the Big Island, as well as descendants from eggs collected on Kauai be-fore 2003, continued to show normal wings. Only on Kauai were the mu-tated wings seen in male crickets in 2003.

"Loss of calling clearly seems to be protecting the male crickets from the deadly fly," Zuk said. "But this protection has a heavy price: the loss of its sexual signal. This is obviously a huge loss for the cricket, akin to, say, finding that all peacocks in a forest have lost their tails. One might ask how then do female crickets locate silent flatwing males?"

Zuk and colleagues propose that on Kauai, the flatwings – a term they use to identify male crickets with mutated wings – behave as 'satellites' to the few remaining male crickets that can call. By congregating near the callers, the flatwings enable females to find and mate with them.Parasitized male cricket. Credit: J. Rotenberry, UCR

To test their hypothesis, the biologists performed a field experiment that demonstrated that the flatwings are using the callers as female at-tractors (for details, see below).

"While we were surprised by the extraordinary speed at which the mu-tation spread, what is more interesting is that, ordinarily, you would ex-pect such a change in wing morphology to quickly disappear, because males couldn't attract mates," Zuk said. "Instead, the behavior of the flatwings allows them to capitalize on the few callers that remain, and thus escape the fly and still reproduce. This is seeing evolution at work."

Field experiment details:The researchers performed experiments in which 2-meter radius cir-

cles were delineated within the habitat of crickets on Oahu, the Big Is-land of Hawaii, and Kauai. After removing and noting the sex, the wing type and the number of all crickets inside the circle, the researchers played an island-specific calling song from a speaker placed in the cir-cle's center. After 20 minutes, the researchers noted the position, sex and wing structure of all crickets inside the circle, and measured the dis-tance from all crickets to the speaker.

Comparing their observations made on the three islands, the re-searchers found that on Kauai, the flatwings arrived much more quickly, and settled closer to the speaker, than normal-winged males on the other two islands, supporting the notion that the new morphs are using the callers as female attractors.

Study by LIJ obstetrician confirms taller women are more likely to have twins

NEW HYDE PARK, NY -- An obstetrician who specializes in multiple-birth preg-nancies has confirmed that taller women are more likely to have twins.

The suspected culprit is insulin-like growth factor, which has been posi-tively linked to both height and twinning. By comparing the heights of women who had given birth to twins or triplets with the average height of women in the United States, Gary Steinman, MD, PhD, an attending physician at Long Island Jewish (LIJ) Medical Center, found that the multi-ple-birth mothers averaged more than an inch taller. The study was pub-lished in the September issue of the Journal of Reproductive Medicine.

"Any circumstance that affects the amount of available insulin-like growth factor so as to modify the sensitivity of the ovary to follicle-stim-ulating hormone appears to govern the rate of spontaneous twinning," said Dr. Steinman.

Insulin-like growth factor (IGF) is a protein that is released from the liver in response to growth hormone. It increases the sensitivity of the ovaries to follicle stimulating hormone, thereby increasing ovulation. Some studies also suggest that IGF may help embryos survive in the early stages of development.

Among its many effects in the body, IGF stimulates cells in the shaft of long bones to grow. Previous studies have demonstrated that people with short stature have significantly lower levels of IGF. Countries with taller women have higher rates of twinning compared to countries with shorter women.

In the current study, Dr. Steinman compared the heights of 129 women who gave birth to identical or fraternal twins or triplets -- 105 had twins and 24 had triplets -- with the average height of women in the United States, as reported by the National Center for Health Statistics. The multiple-birth mothers averaged 5 feet 5 inches tall, more than an inch taller than the U.S. average for adult females of about 5 feet 3 ¾ inches. While the effect of IGF on the ovaries likely involves fraternal, or dizygotic, twins, they were not distinguished from identical, or monozy-gotic, pregnancies in this study. Dizygotic twin pregnancies account for about two-thirds to three-quarters of all spontaneous multiple pregnan-cies in a random population, therefore the results of this study predomi-nantly, but not exclusively, represent fraternal twins.

In the previous study in his series on the mechanisms of twinning, Dr. Steinman found that women who consume animal products, specifically dairy, are five times more likely to have twins. Cows, like humans, pro-duce IGF in response to growth hormone and release it into the blood, and the IGF makes its way into their milk.Dr. Steinman has been invited to speak next month about IGF and twinning at the three-day workshop "Milk, Hormones and Human Health." The meeting, to be held in Boston from Oct. 23-25, is sponsored by the Harvard Center for Can-cer Prevention at the Harvard School of Public Health and the McGill University Centre for Cancer Prevention.

Dinosaurs' climate shifted too, reports show44 5/10/2023

BLOOMINGTON, Ind. -- Ancient rocks from the bottom of the Pacific Ocean suggest dramatic climate changes during the dinosaur-dominated Meso-zoic Era, a time once thought to have been monotonously hot and hu-mid.

In this month's Geology, scientists from Indiana University Blooming-ton and the Royal Netherlands Institute for Sea Research present new evidence that ocean surface temperatures varied as much as 6 degrees Celsius (about 11 degrees Fahrenheit) during the Aptian Epoch of the Cretaceous Period 120 million years ago.

The finding is relevant to the ongoing climate change discussion, IUB geologist Simon Brassell says, because it portrays an ancient Earth whose temperatures shifted erratically due to changes in carbon cycling and did so without human input.

"Combined with data from the Atlantic, it appears clear that climate changes were taking place on a global scale during this time period," said Brassell, who led the study.

A previous study from an Atlantic Ocean site had suggested a change-able climate around the same time period. But it was not known whether the Atlantic data indicated regional climate change unique to the area or something grander.

"We had virtually no data from the middle of the largest ocean at that time period," Brassell said. "The data we collected suggest significant global fluctuations in temperature."

As part of the National Science Foundation's Ocean Drilling Project, the geoscientists voyaged in 2001 to Shatsky Rise, a study site 1,600 kilo-meters (1,000 miles) east of Japan and 3,100 meters below the ocean surface. Shatsky Rise is known to have formed at the end of the Jurassic Period immediately prior to the beginning of the Cretaceous, the last pe-riod of the Mesozoic Era.

The scientists' vessel, the JOIDES Resolution, is specially outfitted with a drill that can be lowered to the sea floor for the collection of rock sam-ples.

The drill bit was driven 566 meters into Shatsky Rise. Rocks freed by the drill were transported directly to the surface for analysis. The rocks corresponding to early Aptian time were extremely rich in organic mate-rial. By analyzing the carbon and nitrogen content of the samples, the geochemists found evidence for changes in carbon cycling and in nitro-gen fixation by ocean biological communities associated with changing climate. A special analysis method targeting certain complex carbon-containing molecules provided values for a measurement called TEX86 that revealed mean temperature variations between 30 deg C (86 deg F) and 36 deg C (97 deg F) with two prominent cooling episodes of approxi-mately 4 deg C (7 deg F) in tropical surface temperatures during the

early Aptian. By comparison, today's tropical sea surface temperatures typically lie between 29 and 30 deg C.

Brassell says that findings of a changeable climate during the Creta-ceous, a time period dominated by dinosaurs and noted for the spread of flowering plants, could influence the current climate change debate.

"One of the key challenges for us is trying to predict climate change," Brassell said. "If there are big, inherent fluctuations in the system, as paleoclimate studies are showing, it could make determining Earth's cli-matic future even harder than it is. We're learning our climate, through-out time, has been a wild beast."

Ancient Pet Cemeteries Found in PeruLIMA, Peru (AP) -- Even in ancient Peru, it seems dogs were a man's best friend. Peruvian investigators have discovered a pre-Columbian culture of dog lovers who built pet cemeteries and buried their pets with warm blankets and even treats for the afterlife.

''They are dogs that were thanked and recognized for their social and familial contribution,'' anthropologist Sonia Guillen said. ''These dogs were not sacrificed.''

Since 1993, researchers have unearthed 82 dog tombs in pet ceme-tery plots, laid alongside human mummy tombs of the Chiribaya people in the fertile Osmore River valley, 540 miles southeast of Lima. The Chiribaya were farmers who lived from A.D. 900 to 1350 before the rise of Peru's Inca Empire.

''We have found that in all the cemeteries, always, in between the hu-man tombs there are others dedicated to the dogs, full-grown and pup-pies,'' said Guillen, who specializes in the study of mummies. ''They have their own grave and in some cases they are buried with blankets and food.''

Guillen, director of the Centro Mallqui, the Bioanthropology Foundation of Peru, said the dogs are known as Chiribaya shepherds for their herd-ing abilities.

She and her team are trying to prove the Chiribaya dogs have Peru-vian descendants that can be classified as an original South American breed.

''This shepherd is still among us,'' she said. ''We have found very simi-lar animals with the same characteristics in Peru's southern valleys and we are starting investigations to determine if we are dealing with a Peru-vian dog.''

But some dog experts expressed caution.Ermanno Maniero, who in 1985 achieved international recognition of

the Peruvian hairless as a distinct breed that evolved over more than 2000 years from Asian ancestors brought across the Bering Strait, said Peru is full of breeds that arrived in recent centuries.

45 5/10/2023

''We have found similar dogs'' to the Chiribaya shepherds, he said. ''But it is better to take precautions before confirming the existence of a type of original animal.''

Ricardo Fujita, a genetics researcher at Lima's San Martin University, said the physical traits suggests a link between today's' short-snouted, long-haired dogs and their possible Chiribaya ancestors. But the jury is still out.

''We are conducting DNA analysis on the ancient dogs to compare them to the new ones, but it will be months before there are results for a final verdict,'' he said.

Rocket Set to Launch From N.M. SpaceportEL PASO, Texas (AP) -- After several delays, the first space-bound rocket is set to launch from a southern New Mexico spaceport.

UP Aerospace plans to launch a SpaceLoft XL rocket early Monday from Spaceport America in Upham, N.M., about 95 miles northwest of El Paso. The 13-minute suborbital flight, among the first from a commercial spaceport in the United States, will hurtle 50 experimental and other payloads about 70 miles above Earth.

SpaceShipOne was the first privately manned rocket to reach space in a 2004 suborbital flight from the Mojave Desert Airport in California.

The rocket to be launched Monday is expected to land at White Sands Missile Range, about 33 miles northeast of the Upham launch site.

Eric Knight, Connecticut-based UP Aerospace CEO, said Monday's flight will also mark the first time the public has ''direct access to space.''

He said payload space on one of his rockets range in price from a few hundred dollars to tens of thousands of dollars, depending on the size. Each SpaceLoft XL rocket can hold about 110 pounds of cargo.

Several other UP Aerospace flights have been scheduled for later this year, including an Oct. 21 flight that is expected to carry the ashes of James Doohan, who gained worldwide notoriety for his portrayal of chief engineer Montgomery ''Scotty'' Scott on the original ''Star Trek'' TV se-ries, Mercury astronaut Gordon Cooper, and several other people.

The Upham launch site is also the planned home of a state-built $225 million spaceport. Richard Branson, the British billionaire founder of the Virgin Group, announced plans last year to headquarter his space tourism company, Virgin Galactic, in New Mexico and launch flights from the spaceport by the end of this decade.

Human Stem Cells Are Found to Help Rats’ VisionBy NICHOLAS WADE

Pointing the way to a possible clinical use of human embryonic stem cells, researchers have improved vision in rats suffering from a disease similar to age-related macular degeneration.

The scientists, at Oregon Health and Science University, used human embryonic stem cells that had spontaneously converted into the special cells that line the base of the retina. The cells, which support the light-sensing rod and cone cells above them, are damaged in some forms of macular degeneration.

A group led by Raymond Lund says members injected these human cells into the retina of a special breed of rat in which the retina degener-ates shortly after birth. The cells rescued the rats’ vision, as judged by several tests, for three months after birth, the researchers report today in the journal Cloning and Stem Cells.

The injected human cells seemed to behave as retinal cells should, and the treated rats retained some six layers of rods and cones in their retinas, as much as half the normal value.

The human retinal lining cells, derived from different cultures of em-bryonic stem cells, were supplied by Advanced Cell Technology, a com-pany with laboratories in Worcester, Mass. Dr. Neal Adams of the Wilmer Eye Institute in Baltimore said the development was important and “shows us some of the hope that regenerative medicine possesses.” But many more stages lie ahead before any clinical test of the cells in pa-tients with macular degeneration could be tried, Dr. Adams added.

Macular degeneration is a good candidate for embryonic stem cell therapy, at least in principle, because the eye is not closely monitored by the immune system. So cells from another individual could be grafted with lesser risk of rejection than at other sites.

A bank of retinal cells derived from 100 embryonic stem cells of differ-ent immunological backgrounds should suffice to provide a good match to most of the American population, said Robert Lanza of Advanced Cell Technology.

Although the experiment suggests a possible treatment for age-re-lated macular degeneration, a disease that affects one-third of the popu-lation older than 75, many uncertainties remain to be addressed. The disease treated in the rats is caused by a genetic defect and is not ex-actly the same as the human disease.

Also, as with many proposals for cell therapy, the replacement cells are liable to be damaged in time by whatever disease process killed the patient’s cells. Dr. Adams said macular degeneration was probably caused by a mix of environmental and genetic factors. Even if replace-ment cells should also fall victim to the disease, he said, they may buy the patient extra time and be a valuable treatment.

Tan stimulant may bronze even the fairest skinsJohn Pickrell

Could it be goodbye to the porcelain-skinned English Rose? A paint-on treatment has been developed that may one day allow a real tan with-out sun, for even very fair skins. The key chemical, a plant extract called

46 5/10/2023

forskolin, protected mice against UV rays and allowed them to develop a natural tan by stimulating pigment-producing cells called melanocytes.

The ability to tan is largely controlled by a hormone called melanocyte-stimulating hormone, which binds to the melanocortin 1 re-ceptor (MC1R) on the outside of melanocytes. Many people with with red hair and fair skin have a defect in this receptor, meaning they find it al-most impossible to tan and are prone to skin cancer.

John D'Orazio of the University of Kentucky College of Medicine in Lex-ington, US, used depilated mice with defective MC1Rs to show that ap-plying forskolin to the skin can restore their ability to produce the skin pigment melanin. When it was applied for four weeks before mice were exposed to UV light, they were subsequently able to tan.

In a second experiment, a particularly cancer-prone strain of mice, also bred to lack effective MC1Rs, were exposed to the equivalent of 1 to 2 hours of midday Florida sunlight each day for 20 weeks. Nine con-trol mice developed 11 tumours and showed other evidence of skin damage, while nine mice treated with forskolin developed just six tu-mours. Their skin also showed less evidence of damage (Nature, vol 443, p 340).

"We see no logical reason why it shouldn't work in humans too," says D'Orazio, although no clinical trials have yet taken place. Because forskolin stimulates melanin production, it could give fair-skinned people a natural tan that would also afford some protection from the sun. Unlike UV-blocking creams, the forskolin tan would have the added benefit of not washing off.

Since forskolin has also been shown to cause a degree of tanning in mice with normal MC1Rs, it might allow sunless tanning for all skin types, says D'Orazio.

NASA officials to make historic trip to ChinaKelly Young

A group of NASA officials is about to begin a historic trip to China in an effort to establish preliminary ties between the Chinese and US space programmes.

"No NASA administrator has been to China," NASA Administrator Michael Griffin said after the recent launch of the space shuttle Atlantis. "We have never had any significant discussions with China about space."

China joined the space elite when it became the third nation to launch its own crewed rocket in 2003 (see Confident China joins space elite).

Laiyan Sun, the administrator of the China National Space Administra-tion, invited Griffin to make the trip, which lasts from Saturday to Thurs-day. Griffin will visit Beijing and Shanghai and tour aerospace facilities around the country.

It is not clear exactly what sort of cooperation will come of the trip, however. Despite the fact that China has repeatedly asked to participate in the International Space Station, the US has always refused.

Some have argued this is because of a reluctance to share technolo-gies that might be co-opted for military purposes, but others say it is simply down to politics, with space the last bastion of Cold War thinking.

For his part, Griffin is keeping expectations low. "This is a get-ac-quainted session, and it is nothing more, and to characterise it as any-thing more would be to create expectations that would be possibly em-barrassing to us or embarrassing to China, and none of us wants to do that," Griffin said about a week ago.

"We want to use this visit to get acquainted and look for and maybe consider opportunities where we could work together," he said.

NASA's Associate Administrator for Space Operations, Bill Gersten-maier; Assistant Administrator for External Relations, Michael O'Brien and astronaut Shannon Lucid will join Griffin on the journey.

Snooze your way to high test scoresIf you are trying to commit something to memory, take a nap. Even a

short daytime snooze could help you learn.A good night's sleep is known to improve people's ability to learn ac-

tions such as mirror writing. REM sleep, when most dreaming occurs, is thought to be particularly important.

The role of sleep in factual learning has been less clear. Now Matthew Tucker at The City University of New York and his colleagues have shown that even a nap with no REM sleep can help.

Volunteers were told to memorise pairs of words (a test of factual learning) and to practise tracing images in a mirror (action learning). When they were tested straight afterwards and 6 hours later, those who had been allowed a nap of up to 1 hour before the re-test scored 15 per cent better in the factual test than the non-nappers, but no better in the action test (Neurobiology of Learning and Memory, vol 86, p 241).

"Traditionally, time devoted to daytime napping has been considered counterproductive," the researchers say. It now seems sleep is "an im-portant mechanism for memory formation".

Tuberculosis Helped Bring Down MastodonsBy Ker Than LiveScience Staff Writer

A tuberculosis pandemic among an ancient mammoth-like creature probably contributed to the great beasts' demise, a new study suggests.

Scientists examining mastodon skeletons found a type of bone dam-age in several of the animal's foot bones that is unique to sufferers of tu-berculosis. The disease would have weakened and crippled the animals, making them more vulnerable to humans and climate change, two fac-

47 5/10/2023

tors that scientists have long speculated were behind their extinction in North America.

Mastodons were ancient elephants that resembled mammoths, but were shorter and less hairy. Both species lived in North America and dis-appeared mysteriously, along with other large mammals, around the time of the last major Ice Age about 10,000 years ago.

A crippling diseaseResearchers Bruce Rothschild of the Northeastern Ohio Universities

College of Medicine and Richard Laub of the Buffalo Museum of Science in New York looked at 113 mastodon skeletons and found signs of tuber-culosis in 59 of them. That's 52 percent.

Tuberculosis is a bacterial infection that commonly infects the lungs. It can also affect other parts of the body, including organs and bones. In humans, only about 1 to 7 percent of infected individuals develop bone damage. The fact that more than half of the mastodon skeletons exam-ined had the bone lesions suggests tuberculosis was a "hyperdisease" that afflicted a large percentage of the North American mastodon popu-lation.

When tuberculosis infects bone, it creates a tell-tale type of damage in which bone beneath cartilage is carved out, or "excavated."

The infected mastodons were different ages and sizes and came from all over North America. They lived at different times, too. The disease appears to have struck the creatures as early as 34,000-years-ago and persisted in the species until as recently as 10,000- years-ago.

That the disease was widespread and yet persisted for so long in the species suggests it was not immediately lethal, Rothschild said. Instead, it was probably a chronic disease, one that gradually weakened rather than killed the animals.Mastadon stressors

In humans, tuberculosis can lay dormant for several years after initial infection, repressed by the body's own immune system. But it can flare up into full-blown disease during times of stress. A similar flare-up prob-ably happened with the mastodons during times of stress, Rothschild said.

Mastadons living at the end of the last Ice Age had reasons to be stressed. They faced not only a drastically changing world brought about by rapid climate change, but also the arrival of a new threat: weapon-wielding humans that hunted them for food.

Together, these three factors-disease, climate change and humans-might have been too much for the creatures. Weakened by tuberculosis, the beasts would have been less able to ward off other diseases, and the crippling bone damage would have affected their ability to walk.

"Extinction is usually not a one-phenomenon event," Rothschild told LiveScience.

A route of infectionBut how did North American mastodons first get tuberculosis, a dis-

ease whose first known documentation is in a 500,000-year-old buffalo in China?

Rothschild thinks he knows the answer. In a separate study, he and Larry Martin from the Natural History Museum in Kansas found similar tuberculosis-caused bone damage in North American bovids, a group of animals that included bison, musk oxen and bighorn sheep.

Tuberculosis appears to have been just as prevalent in the bovids as in the mastodons, but the record of infection for this group of animals stretches back much further-at least 75,000 years.

Bison and other bovids are believed to have originated in Asia and crossed into North America using the Bering Land Bridge, which con-nected the two continents. Humans made the same journey much later.

The researchers speculate that some of the bovids were probably al-ready infected with tuberculosis when they migrated into the New World. Once in North America, the bovids could have spread to mastodons and other species, possibly even humans, Rothschild said.

Both the mastodon and bovid studies will be detailed in upcoming is-sues of the science journal Naturwissenchaften.

Stem Cells Made From 'Dead' Human EmbryoBy MALCOLM RITTER

NEW YORK - Scientists say they have created a stem cell line from a hu-man embryo that had stopped developing naturally, and so was consid-ered dead. Using such embryos might ease ethical concerns about cre-ating such cells, they suggested.

One expert said the technique makes harvesting stem cells no more ethically troublesome than organ donation. But others said it still carries scientific and ethical problems.

Scientists want to use human embryonic stem cells to study diseases and create transplant tissue for treating illnesses such as diabetes and Parkinson's disease. Such cells are taken from human embryos that are a few days old, and the harvesting process destroys the embryo. That raises ethical objections.

The new work, published online Thursday by the journal Stem Cells, comes from Miodrag Stojkovic of the Prince Felipe Research Center in Valencia, Spain, with colleagues there and in England.

They studied embryos donated by an in vitro fertilization clinic with consent of the patients. Part of the work focused on 132 "arrested" em-bryos, those that had stopped dividing for 24 or 48 hours after reaching various stages of development.

Thirteen of these embryos had developed more than the others, reaching 16 to 24 cells before cell division stopped. Scientists were able to create a stem cell line from just one of these embryos.

48 5/10/2023

These stem cells performed normally on a series of tests, Stojkovic said in a telephone interview.

He said he did not know whether the result indicated a solution to eth-ical concerns about embryonic stem cells. The point of the research was to show that such embryos provide an additional source of the cells be-yond healthy embryos, rather than to set up any kind of a competition, he said. Both sources should be used, he said.

Dr. Donald W. Landry, director of the division of experimental thera-peutics at the Columbia University Medical Center in New York, who pro-posed the idea of getting stem cells from arrested embryos in 2004, called the work an important addition to the field.

"Regardless of how you feel about personhood for embryos, if the em-bryo is dead, then the issue of personhood is resolved," Landry said.

"This then reduces the ethics of human embryonic stem cell genera-tion to the ethics of, say, organ donation. So now you're really saying, `Can we take live cells from dead embryos the way we take live organs from dead patients?'"

Landry is part of a consortium that is pursuing the approach.But others said the approach fails to solve the ethical problems.There is no way to prove that an arrested embryo would have stopped

growing if it had been put into a woman's womb rather than a lab dish, said Robin Lovell-Badge of the Medical Research Council's National Insti-tute for Medical Research in London. So that leaves open the possibility that it was the lab conditions that halted their growth, he said.

The Rev. Tad Pacholczyk, director of education for the National Catholic Bioethics Center in Philadelphia, said he believed an embryo may not be dead if individual cells are still alive and able to create stem cell lines.

Landry says an embryo is dead if its cells irreversibly stop working to-gether to function as a single organism. But even under that definition, Pacholczyk said, scientists know too little about early embryos to discern when one is truly dead.

Dr. George Daley of the Harvard Stem Cell Institute said the new pa-per's approach also raises a scientific concern: Stem cells from arrested embryos might carry the risk of some undetected defect.

"If there was something wrong with the embryo that made it arrest, isn't there something wrong with these cells?" that could cause prob-lems with their use, he asked. "We don't know."On the Net: Stem Cells journal: http://stemcells.alphamedpress.org

NASA Chief in China to Discuss Space CooperationBy WARREN LEARY

WASHINGTON - The leader of NASA arrives in China on Sunday for a tour of space agency sites, making him the most senior American space offi-

cial to go to China to discuss possible cooperation between the coun-tries’ programs.

Michael D. Griffin, the administrator of the National Aeronautics and Space Administration, has repeatedly cautioned that the tour, which will include Beijing, Shanghai and a desert launching site in Gansu Province, will be an exploratory visit that will not result in any bilateral space agreements or formal partnerships.

“This is a get-acquainted visit that has no preconditions to it,” he said recently. “We are going to see things and meet people, and see where that takes us.”

China is the third country, after the United States and Russia, to have sent humans into space. It has been seeking more international cooper-ation in aerospace projects, but the United States has been reluctant. Much of China’s program is run by the military, raising concerns about possible technology transfers or other national security issues for any such cooperation.

Working with China in space has also been hampered by other issues under discussion by the two nations, like weapons proliferation, trade agreements, patent and trademark enforcement, and human rights, said a senior adviser at NASA, who spoke on condition that he not be identi-fied.

Recently, though, the American position has begun to shift. When Chi-nese space officials invited the previous NASA administrator, Sean O’Keefe, to visit their operations two years ago, nothing came of the overture. However, when President Hu Jintao of China visited the United States in April and made the same request of Mr. Griffin, President Bush accepted the invitation.

“There has been a policy decision by the Bush White House to do this,” said John Logsdon, the director of the Space Policy Institute at George Washington University. “It’s part of an effort to engage China, to open a dialogue that may influence their policies in other areas. But it’s starting slowly and deliberately.”

Accompanying Mr. Griffin on the trip is William Gerstenmaier, the as-sociate administrator for space operations, Michael F. O’Brien, the assis-tant administrator for external relations, and Shannon Lucid, a veteran astronaut. Ms. Lucid, who is the daughter of Baptist missionaries, was born in Shanghai and is returning to China for the first time since her childhood.

The group will meet Sun Laiyan, the administrator of the China Na-tional Space Administration in Beijing and tour aerospace operations and science centers there before going to Shanghai to visit space manufac-turing plants there.

49 5/10/2023

Also scheduled on the five-day trip is a visit to the Jiuquan Satellite Launch Center, an extensive rocket-launching complex from which the Chinese prepare and fly their manned spacecraft.

The Chinese launched their first manned spacecraft, Shenzhou, in Oc-tober 2003, sending one astronaut into orbit for a day. In 2005, a Shen-zhou with a two-person crew spent five days in orbit. Chinese authorities said their third mission, set for fall 2007, will send up three astronauts and will include spacewalks.

This year, Chinese officials visiting the United States outlined their plans for an extensive program of manned and unmanned programs, in-cluding orbiting a small, staffed space station by 2015 and establishing a moon program that includes sending a robotic orbiter next year, a lu-nar rover in 2012 and a lander that would return a moon sample to Earth in 2017. While there are no immediate plans to do so, Chinese offi-cials also have expressed interest in sending humans to the moon.

Vincent G. Sabathier, a senior fellow on space issues at the Center for Strategic and International Studies in Washington, said that in the past, the United States had tried to contain Chinese ambitions in space but that this was no longer possible. China has major space agreements with Russia, Europe and most other nations with space programs, and is clearly striving to have a major role in the area, he said.

“The Chinese are going their way and have a strategy in place,” Mr. Sabathier said. “They want to work with the United States and be ac-cepted as a major player, and the U.S. is obviously now seeing some po-tential in working with them, which explains Mr. Griffin’s trip.”

Mr. Sabathier and other experts said the composition of Mr. Griffin’s team, including the head of NASA’s human space flight program and Ms. Lucid, whose five trips to space included a long stay aboard the Russian Mir space station, suggests that some type of cooperation in space may be under consideration.

50 5/10/2023