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Scientists convert modern enzyme into its hypothesized ancestor Single amino acid substitution supports theory of common origin some 2.5 billion years ago UPTON, NY - By making a single substitution in the amino acid sequence of a modern enzyme, scientists have changed its function into that of a theoretical distant ancestor, providing the first experimental evidence for the common origin of the two distinct enzyme types. The research, conducted by a team that includes scientists from the U.S. Department of Energy's Brookhaven National Laboratory and the Karolinska Institute in Stockholm, Sweden, will be published online the week of October 30, 2006, by the Proceedings of the National Academy of Sciences. "It's as if we turned back the clock nearly 2.5 billion years, to the time when oxygen first appeared in Earth's atmosphere, to get a snapshot of how enzymes evolved to deal with reactive oxygen species," said Brookhaven biochemist John Shanklin, lead author on the paper. Oxygen, while essential for many life processes, can also exist in potentially toxic forms, such as superoxide and hydroxyl radicals, as well as hydrogen peroxide. After the first photosynthetic organisms appeared on Earth some 2.5 billion years ago, pumping oxygen into the atmosphere, organisms with enzymes capable of deactivating these reactive oxygen species had an increased chance of survival. Scientists have theorized that the first oxygen-detoxifying enzymes were simple oxidases, which combine reactive forms of oxygen, such as peroxide, with hydrogen ions (protons) and electrons to yield water (H2O). While these enzymes have little in common with more modern biosynthetic enzymes that mediate oxygen chemistry, they share certain structural and sequence characteristics around their active sites - namely, a pair of iron atoms for binding oxygen within a similar four-helix bundle. These similarities suggested the possibility of a common origin, but experimental evidence was lacking - until now. The Brookhaven/Karolinska team had previously performed a structural comparison of the active site of a modern desaturase enzyme (which uses activated oxygen to remove two hydrogens from fatty acids) with that of a simple peroxidase. They used a stand-in for oxygen binding in the active site (because oxygen itself does not stay bound long enough for studies) and produced molecular-level crystal structures using high intensity beams of x-rays at the National Synchrotron Light Source at Brookhaven Lab and the MAX Lab at the University of Lund Synchrotron in Sweden. These crystal structures revealed remarkable similarities, with the single major difference being a change in one amino acid residue adjacent to the oxygen- binding site: The oxidase had an acidic residue capable of donating protons to the oxygen to form water while the desaturase did not. Based on this difference, the scientists hypothesized that if they engineered a "desaturase" with an acidic amino acid residue in place of the non-reactive one, they would convert the desaturase to an oxidase. Using the tools of molecular biology, this is exactly what they did. "Substituting aspartic acid at this site on the desaturase made a huge change," Shanklin said. The new enzyme's desaturase activity decreased 2000-fold while its oxidase activity increased 31-fold compared with the original desaturase. New crystal structures, derived at the European Synchrotron Radiation Facility in France, revealed that the substitution placed the acid group into the ideal position for donating protons to the oxygen. "Usually, when enzymes evolve from a common ancestor, there are many amino acids that change to change the function," Shanklin said. "So it is remarkable

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Scientists convert modern enzyme into its hypothesized ancestorSingle amino acid substitution supports theory of common origin some 2.5 billion years

agoUPTON, NY - By making a single substitution in the amino acid sequence of a modern enzyme, sci-entists have changed its function into that of a theoretical distant ancestor, providing the first experimental evidence for the common origin of the two distinct enzyme types. The research, conducted by a team that includes scientists from the U.S. Department of Energy's Brookhaven National Laboratory and the Karolinska Institute in Stockholm, Sweden, will be published online the week of October 30, 2006, by the Proceedings of the National Academy of Sciences.

"It's as if we turned back the clock nearly 2.5 billion years, to the time when oxygen first ap-peared in Earth's atmosphere, to get a snapshot of how enzymes evolved to deal with reactive oxygen species," said Brookhaven biochemist John Shanklin, lead author on the paper.

Oxygen, while essential for many life processes, can also exist in potentially toxic forms, such as superoxide and hydroxyl radicals, as well as hydrogen peroxide. After the first photosynthetic organisms appeared on Earth some 2.5 billion years ago, pumping oxygen into the atmosphere, organisms with enzymes capable of deactivating these reactive oxygen species had an in-creased chance of survival.

Scientists have theorized that the first oxygen-detoxifying enzymes were simple oxidases, which combine reactive forms of oxygen, such as peroxide, with hydrogen ions (protons) and electrons to yield water (H2O). While these enzymes have little in common with more modern biosynthetic enzymes that mediate oxygen chemistry, they share certain structural and se-quence characteristics around their active sites - namely, a pair of iron atoms for binding oxygen within a similar four-helix bundle. These similarities suggested the possibility of a common ori-gin, but experimental evidence was lacking - until now.

The Brookhaven/Karolinska team had previously performed a structural comparison of the ac-tive site of a modern desaturase enzyme (which uses activated oxygen to remove two hydro-gens from fatty acids) with that of a simple peroxidase. They used a stand-in for oxygen binding in the active site (because oxygen itself does not stay bound long enough for studies) and pro-duced molecular-level crystal structures using high intensity beams of x-rays at the National Synchrotron Light Source at Brookhaven Lab and the MAX Lab at the University of Lund Synchro-tron in Sweden.

These crystal structures revealed remarkable similarities, with the single major difference be-ing a change in one amino acid residue adjacent to the oxygen-binding site: The oxidase had an acidic residue capable of donating protons to the oxygen to form water while the desaturase did not.

Based on this difference, the scientists hypothesized that if they engineered a "desaturase" with an acidic amino acid residue in place of the non-reactive one, they would convert the desat-urase to an oxidase. Using the tools of molecular biology, this is exactly what they did.

"Substituting aspartic acid at this site on the desaturase made a huge change," Shanklin said.The new enzyme's desaturase activity decreased 2000-fold while its oxidase activity increased

31-fold compared with the original desaturase. New crystal structures, derived at the European Synchrotron Radiation Facility in France, revealed that the substitution placed the acid group into the ideal position for donating protons to the oxygen.

"Usually, when enzymes evolve from a common ancestor, there are many amino acids that change to change the function," Shanklin said. "So it is remarkable that changing the identity of a single amino acid in an enzyme of 400 amino acids can make such a dramatic switch in the chemical reaction it performs. This finding, that such a simple change can dramatically alter function, provides experimental support for the hypothesis that these two enzyme groups share a common origin."

-----------------------These studies are part of an ongoing effort at Brookhaven Lab to investigate the basic science underlying fatty acid modification reactions, which are some of the highest energy transformations known in nature. Knowledge of how these enzymes work is being incorporated into efforts to engineer desaturase enzymes to produce renewable sources of materials currently obtained from petrochemicals.This study was funded by the Office of Basic Energy Sciences within the U.S. Department of Energy's Of-fice of Science, by the Swedish Foundation for International Cooperation in Research and Higher Educa-tion, and by the Swedish Research Council.

The power behind insect flight: Researchers reveal key kinetic componentFindings provide new insight into heart disease and the evolution of flight

Troy, N.Y. – Researchers from Rensselaer Polytechnic Institute and the University of Vermont have discovered a key molecular mechanism that allows tiny flies and other "no-see-ums" to whirl

their wings at a dizzying rate of up to 1,000 times per second. The findings are being reported in the Oct. 30-Nov. 3 online early edition of the Proceedings of the National Academy of Sciences (PNAS).

"We have determined important details of the biochemical reaction by which the fastest known muscle type-insect flight muscle-powers flight," said Douglas Swank, assistant professor of biology at Rensselaer and lead author of the PNAS paper.

The findings will help scientists gain a better understanding of how chemical energy is con-verted into muscle movements, such as human heart muscle pumping blood. The research also could lead to novel insights into heart disease, and might ultimately serve in the development of gene therapies targeted toward correcting mutations in proteins that detrimentally alter the speed at which heart muscle fibers contract.

Since insects have been remarkably successful in adapting to a great range of physical and bi-ological environments, in large part due to their ability to fly, the research also will interest sci-entists studying the evolution of flight, Swank noted. The project is supported by a three-year $240,000 grant from the National Institutes of Health and a four-year $260,000 grant from the American Heart Association.

The research is focused on a key component of muscle called myosin, the protein that powers muscle cell contraction. Swank's team focused its efforts on the fruit fly and asked a basic ques-tion: Why are fast muscles fast and slow ones slow? The researchers discovered that the reac-tion mechanism in insect flight muscle on the molecular level is different from how slower mus-cle types work.

"Most research has focused on slower muscle fibers in larger animals," Swank said. "By inves-tigating extreme examples, e.g. the fastest known muscle type, the mechanisms that differenti-ate fast and slow muscle fiber types are more readily apparent."

In general, myosin breaks down adenosine triphosphate (ATP), the chemical fuel consumed by muscles, and converts it into force and motion. To do this, myosin splits ATP into two com-pounds, adenine diphosphate (ADP) and phosphate. Each compound is released from myosin at different rates. In slow-muscle contraction, ADP release is the slowest step of the reaction, but in the fastest muscle fibers, Swank's team has discovered that phosphate release is the slowest step of the reaction.

This finding is significant because the overall chemical reaction rate is set by the slowest step of the reaction. "What we have found is that in the fastest muscle type, ADP release has been sped up to the point where phosphate release is the primary rate-limiting step that determines how fast a muscle can contract," Swank said.

The next step, according to the researchers, is to experiment with other fast muscle types, such as the rattlesnake shaker muscle and fast mammalian muscle fibers. "By broadening our research, we will be able to determine if the phosphate release rate contributes to setting mus-cle speed in fast muscle types from other species," according to Swank.

------------------------Swank's collaborators on the project are Vivek K. Vishnudas and David W. Maughan of the Department of Molecular Physiology and Biophysics at the University of Vermont.First evidence to show elephants, like humans, apes and dolphins, recognize themselves in mir-ror

New finding suggests convergent evolution with humansATLANTA-Elephants have joined a small, elite group of species-including humans, great apes and dolphins-that have the ability to recognize themselves in the mirror, according to a new finding by researchers at the Yerkes National Primate Research Center, Emory University, and the Wildlife Conservation Society (WCS) in New York. This newly found presence of mirror self-recog-nition in elephants, previously predicted due to their well-known social complexity, is thought to relate to empathetic tendencies and the ability to distinguish oneself from others, a characteris-tic that evolved independently in several branches of animals, including primates such as hu-mans.

This collaborative study by Yerkes researchers Joshua Plotnik and Frans de Waal, PhD, director of Yerkes' Living Links Center, and WCS researcher Diana Reiss, PhD, published in the early on-line edition of the current issue of Proceedings of the National Academy of Sciences of the United States of America, was conducted as part of a wide array of cognitive and behavioral evolution research topics at Yerkes' Living Links Center.

"We see highly complex behaviors such as self awareness and self-other distinction in intelli-gent animals with well established social systems," said Plotnik. "The social complexity of the elephant, its well-known altruistic behavior and, of course, its huge brain, made the elephant a logical candidate species for testing in front of a mirror."

In the study, researchers exposed three female elephants housed at the Bronx Zoo in New York to a jumbo-sized mirror measuring eight feet high by eight feet wide inside the elephants' yard. During the exposure, the elephants tested their mirrored images by making repetitive body movements and using the mirror to inspect themselves, such as by moving their trunks to inspect the insides of their mouths, a part of the body they usually cannot see. Further, the ani-mals did not react socially to their images, as many animals do, and did not seem to mistake their reflection for that of another elephant.

"Elephants have been tested in front of mirrors before, but previous studies used relatively small mirrors kept out of the elephants' reach," said Plotnik. "This study is the first to test the an-imals in front of a huge mirror they could touch, rub against and try to look behind."

One elephant also passed a standard test known as the mark test. Each elephant was marked with visible paint on its forehead-a place it could not see without a mirror-and also received a sham mark of colorless face paint. The sham mark controlled for tactile and odor cues to ensure touching the visible mark was due to seeing its reflection and not to the feel or smell of the paint. This test produced the same results as when great apes and human children are pre-sented with the mark test.

"As a result of this study, the elephant now joins a cognitive elite among animals commensu-rate with its well-known complex social life and high level of intelligence," said de Waal. "Al-though elephants are far more distantly related to us than the great apes, they seem to have evolved similar social and cognitive capacities making complex social systems and intelligence part of this picture. These parallels between humans and elephants suggest a convergent cogni-tive evolution possibly related to complex sociality and cooperation."

Scientists have tested mirror self-recognition in a variety of animals other than humans and great apes, but invariably failed, with the exception of the bottlenose dolphin. "After the recent discovery that dolphins are capable of recognizing themselves in the mirror, elephants seemed the next logical species for testing," said Reiss. "Humans, great apes, dolphins and elephants, well known for their superior intelligence and complex social systems, are thought to possess the highest forms of empathy and altruism in the animal kingdom."

Further research on elephant cognition will be conducted by Yerkes' Living Links Center to ex-plore topics in behavioral and cognitive evolution, specifically social complexity in Asian ele-phants, including cooperation and conflict resolution.

Researchers cast doubt on hypothesis that stigma fuels HIV epidemicThe dominant view in the public health community is that the stigma of being HIV positive fu-

els the HIV epidemic, and yet there is a lack of evidence to support this view, say two re-searchers in a provocative essay in PLoS Medicine.

In a 2002 report, UNAIDS declared that the stigma associated with HIV was one of the "great-est barriers" to preventing new HIV infections and alleviating the impact of the disease. The standard argument for the link between HIV stigma and the global HIV epidemic, say Daniel Rei-dpath (Brunel University, UK) and Kit Yee Chan (Deakin University, Australia) is that stigma un-dermines HIV prevention efforts by making a person afraid to engage in safe behavior or seek testing for fear that these acts would themselves raise suspicion in the minds of others about the person's HIV status.

Reidpath and Chan say that there is no good evidence to support this argument. "To establish a causal link between HIV stigma and epidemic progression," they say, "requires longitudinal data on rates of infection and levels of HIV stigma. Weaker, but nonetheless potentially persua-sive, evidence could also be found in an observed correlation between levels of HIV-related stigma and rates of HIV infection across contexts--such as between countries. Currently, no such evidence is available."

An alternative hypothesis, they say, is that stigma may in fact help to slow the epidemic. "It is plausible," they say, "that a social control mechanism, such as stigma, could reduce opportuni-ties for contact between high- and low-risk groups."

"In writing this essay," say the authors, "our aim was neither to diminish the suffering of peo-ple living with AIDS in the eyes of the reader nor to advocate for the use of HIV stigma as a mechanism to control the spread of the epidemic. Our objective was to draw attention to the lack of evidence supporting the current dominant view on the relationship between stigma and the global spread of HIV."Citation: Reidpath D, Chan KY (2006) HIV, sigma, and rates of infection: A rumor without evidence. PLoS Med 3(10): e435.PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.-doi.org/10.1371/journal.pmed.0030435

Test reveals effectiveness of potential Huntington's disease drugs

DALLAS - A test using cultured cells provides an effective way to screen drugs against Hunting-ton's disease and shows that two compounds - memantine and riluzole - are most effective at keeping cells alive under conditions that mimic the disorder, UT Southwestern Medical Center re-searchers report.

"These drugs have been tested in a variety of Huntington's disease models and some HD hu-man trials and results are very difficult to interpret," said Dr. Ilya Bezprozvanny, associate pro-fessor of physiology and senior author of the study, available online and published in today's is-sue of Neuroscience Letters. "For some of these drugs conflicting results were obtained by differ-ent research groups, but it is impossible to figure out where the differences came from because studies were not conducted in parallel.

"We systematically and quantititatively tested the clinically relevant drugs side-by-side in the same HD model. That has never been done before," said Dr. Bezprozvanny.

Huntington's disease is a fatal genetic disorder, manifesting in adulthood, in which certain brain cells die. The disease results in uncontrolled movements, emotional disturbance and loss of mental ability. The offspring of a person with Huntington's have a 50 percent chance of inher-iting it.

More than 250,000 people in the United States have the disorder or are at risk for it. There is no cure, but several drugs are used or are being tested to relieve symptoms or slow Huntington's progression.

The disease affects a part of the brain called the striatum, which is involved in the control of movement and of "executive function," or planning and abstract thinking. It primarily attacks nerve cells called striatal medium spiny neurons, the main component of the striatum.

Dr. Bezprozvanny's group previously demonstrated that Huntington's striatal neurons are oversensitive to glutamate, a compound that nerve cells use to communicate with each other.

In the latest UT Southwestern study, the researchers cultured striatal spiny neurons from the brains of mice genetically engineered to express the mutant human Huntington gene. As pre-dicted, glutamate killed the Huntington's neurons, but the scientists also tested five clinically rel-evant glutamate inhibitors to assess their protective ability.

Folic acid has been suggested as a treatment for people with Huntington's because it interacts with homocysteine, a compound that makes nerve cells more vulnerable to glutamate. Gabapentin and lamotrigine, both glutamate inhibitors, are used in epilepsy treatment and as a mood stabilizer, respectively. These three compounds did not significantly protect the cultured cells.

However, a drug called memantine, which is used to treat Alzheimer's disease, and riluzole, used in amyotrophic lateral sclerosis, did protect the cells. Memantine demonstrated a stronger effect in the study. Memantine has also shown evidence of retarding the progression of Hunting-ton's in people, while riluzole has helped relieve some symptoms.

"Our results provide the first systematic comparison of various clinically relevant glutamate pathway inhibitors for HD treatment and indicate that memantine holds the most promise based on its in vitro efficacy," Dr. Bezprozvanny said. "Whole animal studies of memantine in an HD mouse model will be required to validate these findings."

Other UT Southwestern researchers involved in the study were Drs. Jun Wu, research asso-ciate in physiology, and Tie-Shan Tang, instructor in physiology.The work was supported by the Robert A. Welch Foundation, the High Q Foundation and the National Insti-tute for Neurological Diseases and Stroke.

Adults who go to bed lonely get stress hormone boost next morningEVANSTON, Ill.-A new study that takes a rare look at the physiological, social and emotional dynam-ics of day-to-day experiences in real-life settings shows that when older adults go to bed lonely, sad or overwhelmed, they have elevated levels of cortisol shortly after waking the next morning.

Elevated levels of cortisol-a stress hormone linked to depression, obesity and other health problems when chronic-actually cue the body on a day-to-day basis that it is time to rev up to deal with loneliness and other negative experiences, according to Northwestern University's Emma K. Adam, the lead investigator of the study.

The study, "Day-to-day experience-cortisol dynamics," will be published online the week of Oct. 30 by the Proceedings of the National Academy of Sciences (PNAS).

"You've gone to bed with loneliness, sadness, feelings of being overwhelmed, then along comes a boost of hormones in the morning to give you the energy you need to meet the de-mands of the day," said Adam, assistant professor of education and social policy and faculty fel-low at the Institute for Policy Research.

The morning cortisol boost could help adults who went to bed with troubled or overwhelming feelings go out in the world the next day and have the types of positive social experiences that help regulate hormone levels, she said.

Adam also is a faculty fellow at C2S: The Center on Social Disparities and Health. C2S is a new center within the Institute for Policy Research that is reaching across Northwestern's two cam-puses and a number of social, life and biomedical disciplines to offer a 21st century look at how biological, social and cultural dynamics intersect and affect health throughout the life span.

Cortisol is often characterized as a negative hormone because of evidence, mostly in animal models, that long-term elevations could be potentially harmful to physical health. But in the short term the stress hormone is adaptive and helpful, according to Adam.

"Cortisol helps us respond to stressful experiences and do something about them," she said. "It is necessary for survival-fluctuations in this hormone assist us in meeting the changing de-mands we face in our daily lives."

The first of its type, the study shows that it is not just on average that people who have more negative emotions have higher levels of cortisol. Rather, with its detailed and intricate methodol-ogy, the study shows a sensitive day-to-day dance between experience and cortisol. Experience influences stress hormones, and stress hormones influence experience, the study shows.

"Cortisol responds to and interacts with our daily experiences in subtle and important ways," Adam concluded.

Cortisol levels are generally high immediately upon waking, increase in the first 30 minutes after waking and then decline to low values at bedtime.

Adam, with her colleagues John T. Cacioppo and Louise C. Hawkley at the University of Chicago, and Brigitte M. Kudielka from the University of Trier, Germany, showed that changes in this pattern from one day to the next are closely interwoven with changes in our daily experi-ences.

The study, based on data from the Chicago Health, Aging, and Social Relations Study (CHASRS) at the University of Chicago includes 156 older adults living in Cook County who were born between 1935 and 1952 and represent a range of socioeconomic classes. Their cortisol lev-els were measured from small samples of saliva provided three times a day for three consecu-tive days. Study participants reported their feelings each night in a diary, and researchers looked at whether cortisol levels on a particular day were predicted by experiences the day before or were predictive of experiences that same day.

In addition to noting that loneliness the night before predicted higher cortisol the next morn-ing, Adam and colleagues found that people who experience anger throughout the day have higher bedtime levels of cortisol and flatter overall levels of the stress hormone, typically consid-ered a risk factor for disorder. "High levels of cortisol in the evening are a kind of biological sig-nature of a bad day," Adam noted.

The study also provided evidence that, in addition to simply being at the mercy of your daily experiences, cortisol also plays a role in influencing them. Individuals with lower levels of cortisol in the morning experienced greater fatigue during the day, a result with potential implications for understanding chronic fatigue.

In all of her work, Adam is interested in how people's changing social environments get under the skin to influence their biology and health. "Stress systems are designed to translate social experience into biological action," she said. "They are designed to be a conduit from the outside world to our internal worlds so that we can better respond to our social context. The overarching question of my studies of these systems in a variety of contexts is whether overuse of these sys-tems plays a role in disease outcomes."

Herbal medicine silymarin may help sugar-control in people with type II dia-betes

Research news published in the journal Phytotherapy ResearchDiabetes is a growing health problem. Giving antioxidants is recognised as one way of helping

people with diabetes to control their blood sugar levels.The herbal medicine extracted from seeds of the Milk Thistle, Silybum marianum (silymarin) is

known to have antioxidant properties and research published this week in Phytotherapy Re-search shows that this extract can help people significantly lower the amount of sugar bound to haemoglobin in blood, as well as reducing fasting blood sugar levels.

Silymarin contains a number of active constituents called flavolignans which are also used to help protect the liver from poisoning.

"We don't know the exact mechanism of action for this effect, but this work shows that sily-marin could play an important role in treating type II diabetes," says lead author Fallah Huseini, who works at the Institute of Medicinal Plants, which is based in Tehran, Iran.

The data came from a randomized double-blind clinical trial involving 51 people who had had type II diabetes for at least 2 years. One group of 25 patients received 200 mg of silymarin three times a day for 4 months, while the remaining 26 received a placebo treatment. All of the pa-tients continued to use conventional oral hypoglycaemic treatment during the trial. Patients were examined at monthly intervals.

Compared with the beginning of the trial, the treatment group had a significant reduction in fasting blood glucose levels (p<0.001), and a reduction in glycosylated haemoglobin (p<0.001). Both of these measures rose significantly in the placebo group (p<0.0001). There were also non-significant decreases in blood lipids in the treatment group.

"The results are very encouraging, and we now need to do further large multi-centre studies," says Huseini.

-----------------Notes to the Editor:Huseini, H.F: The Efficacy of Silybum marianum (L.) Gaertn. (Silymarin) in the Treatment of Type II Dia-betes: A Randomized, Double-blind, Placebo-controlled, Clinical Trial

Football referees do favour home teams, study showsAcademics have proved what Premiership football managers have been complaining about for

years – that referees are inconsistent and favour home teams.Analysing over 2,500 English Premiership matches, researchers discovered that referees were

statistically more likely to award yellow and red cards against the away team – even when home advantage, game importance and crowd size were taken into account.

They also found clear evidence of inconsistency between referees – with some referees signifi-cantly more likely to punish players than others.

The academics behind the study, which has been accepted for publication in the Journal of the Royal Statistical Society Series A, hope that their research will give the football authorities the firm evidence they need to help improve football refereeing.

“The decisions made by referees can influence the result of games and their actions can have important financial consequences for the clubs and individuals involved,” said Dr Peter Dawson, a Wigan fan and lecturer in Economics at the University of Bath.

“Managers have been right to highlight inconsistencies and controversial decisions in games, but without a proper analysis of refereeing decisions over a period of time, their comments look like the usual post-match gripe, especially if they are on the losing side.

“The evidence we have collected and analysed provides a firm factual foundation that will help football’s authorities debate what positive action they might take to ensure fair and equi-table refereeing of matches in the future.

“This could include encouraging referees to avoid what is presumably unintentional home team bias in their decision making, and examining the extent to which corrective action is al-lowed to vary between officials.”

Researchers, from the universities of Bath, Otago (New Zealand), St Andrews and Wales, Ban-gor, analysed all 2,660 matches occurring in the English Premiership seasons from 1996/97 - 2002/3 for disciplinary offences (in terms of the number of yellow and red cards awarded) for home and away teams.

They then developed equations to account for the many different variables that could account for the variation in the number of disciplinary offences. For example, they allowed for teams to play better when they were at home and more aggressively when away, for games, such as top-of-the-table clashes, to be more keenly contested, and for larger crowds to (potentially) exert more influence on referees.

As well as finding a distinct home bias in refereeing disciplinary action and inconsistency be-tween referees, the research also highlighted that:

* underdogs tend to incur a higher rate of disciplinary sanction than favourites* the number of disciplinary offences tends to be higher in matches between evenly-balanced

teams, in matches with end-of-season outcomes at stake and in matches with higher atten-dances

* home teams appear to play more aggressively in front of larger crowds* the crowd size did not appear to influence the incidence of disciplinary sanction against the

away team* there was no evidence that the behaviour of either teams or referees is any different when

the match is televised.“The football pitch is like a laboratory for crime economists,” said Dr Dawson, from the Univer-

sity's Department of Economics & International Development.

“You can introduce a new rule or increase the severity of a punishment and then see how long it takes for the referees and the players to adjust their behaviour.

“In many ways this mirrors criminal behaviour on the streets where it takes criminals and law enforcers time to adjust to the implementation of a new law.

“One example highlighted in our findings is the introduction of the automatic red card for tackles from behind in the 1998/9 season.

“This season saw a rise in the number of bookings and sending-offs, but by the end of the sea-son referees had learned how to implement the rules effectively and players had adjusted their behaviour accordingly.”

This kind of learning behaviour has also been observed in college basketball in North America. When two referees were introduced there was an immediate tail-off in the number of fouls called in a game, suggesting that as referee competence increased, with fewer fouls being missed, the actual ‘crime rate’ must have decreased by even more than is suggested by the fall in the num-ber of fouls called.

Such increased monitoring of games, including the use video replays, is clearly something the governing bodies of football need to look into despite the obvious costs involved.

“Football needs the same kind of in-depth analysis if we are to see improvements in the con-sistency of the important decisions made by referees,” said Dr Dawson.

Phoenix rising: Scientists resuscitate a 5 million-year-old retrovirusVILLEJUIF, France-A team of scientists has reconstructed the DNA sequence of a 5-million-year-old retrovirus and shown that it is able to produce infectious particles. The retrovirus--named Phoenix--is the ancestor of a large family of mobile DNA elements, some of which may play a role in cancer. The study, which is the first to generate an infectious retrovirus from a mobile ele-ment in the human genome, is considered a breakthrough for the field of retrovirus research. The findings are reported in Genome Research.

"Phoenix became frozen in time after it integrated into the human genome about 5 million years ago," explains Dr. Thierry Heidmann, lead investigator on the project. "In our study, we've recovered this ancestral state and shown that it has the potential for infectivity."

Retroviruses, whose genomes consist of RNA, can create DNA "copies" of the RNA genomes and incorporate them into the genomes of their hosts. Phoenix belongs to a sub-category of retroviruses--known as HERVs (human endogenous retroviruses)--which inserted copies into the human germline millions of years ago. These copies were subsequently passed on from genera-tion to generation. Remnants of HERVs now comprise nearly 8% of the human genome, but most were rendered inactive long ago by mutations.

Heidmann and his colleagues set out to re-activate one family of HERVs, called the HERV-K(HML2) family, an evolutionarily "young" family of retroviral elements. They aligned HERV-K(HML2) elements, determined their consensus sequence, and then constructed a retrovirus--Phoenix--from the consensus sequence by mutating existing HERV-K(HML2) copies.

In addition, the researchers showed that Phoenix could form particles capable of infecting mammalian cells in culture. Infectivity was very low, presumably because host cells have evolved mechanisms to resist uncontrolled virus propagation, as has been repeatedly observed for retroviruses from experimental animals.

"Phoenix has produced some 'genomic offspring' that may be responsible for the synthesis of the retroviral particles that can be observed in some human cancers such as germline tumors and melanomas," says Heidmann. "This work will be helpful in tracking down the role of retro-viruses in these human diseases."

---------------------------The work was conducted by Heidmann's group at the Institut Gustave-Roussy in collaboration with Gérard Pierron from the Institut André Lwoff. Dr. Marie Dewannieux, formerly with Heidmann and now a postdoc at the University College of London, is the first author on the paper. The work was funded by the CNRS (Centre National de la Recherche Scientifique), the Institut Gustave Roussy, the Université Paris XI, and the Ligue Nationale contre le Cancer (Equipe Labellisée).

Scientists: Skull Proves Early AutopsyBy THE ASSOCIATED PRESS

PORTLAND, Maine (AP)-The earliest confirmed autopsy in North America was conducted more than 400 years ago by French colonists desperate to determine what was killing them as they en-dured a rugged winter on St. Croix Island, scientists concluded.

A team of forensic anthropologists from the United States and Canada confirmed that the skull of a man buried on the island over the winter of 1604-05 showed evidence of having undergone an autopsy, scientists said.

Nearly half of the 79 settlers led by explorers Pierre Dugua and Samuel Champlain died over that winter from malnutrition and the harsh weather.

The skull in question was discovered during excavations by the National Park Service in June 2003. The top of the skull had been removed to expose the brain; the skull cap was replaced be-fore the body was buried, the scientists said.

''This is the same procedure that forensic pathologists use to conduct autopsies today,'' said Thomas Crist from Utica College in upstate New York, who led the team of forensic anthropolo-gists analyzing the remains.

The conclusion, announced by the National Park Service, will be the subject of a program on the Discovery Health Channel series ''Skeleton Stories'' on Nov. 10.

The findings fit with the writings of Champlain, who described a dire situation in his memoirs published in 1613. He wrote that his barber-surgeon was ordered to ''open several of the men to determine the cause of their illness.''

Dugua, a nobleman known as Sieur de Mons, chose the small island in the St. Croix River that separates what's now Maine and New Brunswick. The settlers cleared a site, planted gardens and erected dwellings including a kitchen, storehouse, blacksmith shop and chapel.

But the winter was harsh, with the first snow falling in October, not long after Champlain re-turned from a historic voyage to Mount Desert Island. Thirty-five of the settlers died and were buried on the island.

Scientists using modern techniques have concluded that the French settlers died from scurvy, which is caused by a lack of vitamin C.

A ship arrived in June with supplies. Dugua then moved the settlement to Nova Scotia at a spot Champlain named Port Royal.

The St. Croix settlement turned out to be short-lived but it gave the French credit for beating the English to establish a permanent presence in the New World.

The graves were originally excavated in 1969 by a team from Temple University. Decades later, the remains were re-interred by the National Park Service after consultation with the French and Canadian governments.

The excavation project, in 2003, was led by Steven Pendery from the National Park Service's Northeast Region Archaeology Program.

It was during that process of reburial that the team members were at the site discussing Champlain's journal reference to autopsy, said Marcella Sorg, Maine state forensic anthropolo-gist, who was part of the team.

Sorg said she looked down and noticed the skull with the autopsy cuts that apparently had been overlooked during previous excavations. ''It was beautifully done, a very straight cut, and very accurate,'' she said.

There have been written references suggesting earlier autopsies as Jacques Cartier explored what's now Quebec in the 1500s, but there's no skeletal evidence, said Sorg, who works with the University of Maine's Margaret Chase Smith Policy Center.

In addition to Sorg, Crist was assisted by his wife Molly Crist, also a professor at Utica College. The other team member was Robert Larocque, physical anthropologist from Universite Laval in Quebec.

St. Croix Island is protected by the National Park Service as part of Saint Croix Island Interna-tional Historic Site.

Delegates from the United States, Canada and France gathered in 2004 to commemorate the 400th anniversary of the settlement.Personal HealthWorld Enough and Time for ‘a Good Death’By JANE E. BRODY

As sudden deaths from heart attacks continue to decline and more people leave this life after a protracted illness, the concept of “a good death” has become ever more important to both the dying and those who survive them.

But what is a good death, and is it really the same for everyone? And what are the conse-quences of different approaches to death for those left behind?

Nearly four decades ago, Dr. Elisabeth Kübler-Ross outlined what she recognized as five stages people go through after the diagnosis of an incurable illness: denial, anger, bargaining, depression and finally acceptance of their impending death. She recognized that people ap-proaching the end of life might seesaw between the various stages, but that those who reached “acceptance” were most likely to die in peace with the least trauma to their survivors. Indeed, hospice care practically demands that people who are dying reach acceptance, since they must accept only comfort care and give up all treatments aimed at staving off their demise.

Still, there are many people who choose to continue fighting for life, leaving no therapeutic stone unturned, until they take their last breath. There are people who will not acknowledge that they have a fatal illness, remaining in denial even as their bodies shrink under the onslaught of disease. There are people who weather their medical storm in fury because they are being robbed of their future. There are people who cannot emerge from depression over the prospect of losing everyone they love.

Can these people, who never achieve acceptance, also have a good death? The answer seems to be yes, although the consequences for survivors may sometimes be less than desirable.Nails Polished to the End

Dr. Joseph Sacco, a palliative care specialist at Bronx-Lebanon Hospital Center in New York, tells about a patient, Mrs. Santana, in his book, “On His Own Terms,” the story of his father’s los-ing battle against lung cancer. Mrs. Santana had terminal cancer and was near death, but she never uttered the words “cancer” or “death.” During her final hospital stay, she maintained her lifelong elegance and dignity, polishing her nails, grooming her hair, always cheerful and calm, until the day she died.

Dr. Sacco’s father, Joe, on the other hand, kept insisting he would “beat this thing,” even as his breathing became ever more labored and his weight dropped by half. Though Dr. Sacco, based on his training, thought his father should come to accept his fate, he felt he had no choice but to humor the dying man and play along.

Joe’s death was peaceful enough, occurring as it did on his terms. But it took its toll on Dr. Sacco, who laments: “Had my father not been frozen by fear, he might have been able to talk openly and reaffirm his knowledge that his son really did love him. Instead, paralyzed by the im-plication that death was imminent, he brushed me aside with a wave of the hand and the com-ment that he wasn’t going to die.”

Dr. Greg A. Sachs’s father-in-law, Al, who also had lung cancer, chose to have no treatment for his disease and spent not one day of his remaining 18 months in the hospital. As Dr. Sachs told it in The Journal of the American Medical Association (Nov. 15, 2000), Al spent the year “straightening out files; reconciling accounts and labeling everything in the house, including fuse boxes and cabinet drawers, so that his wife would be able to find everything when he was gone.” According to an agreed-upon plan, Al died peacefully at home surrounded by his loving family, with his distressing end-of-life symptoms assuaged by morphine, anti-anxiety medication and oxygen.No Easing Existential Suffering

But as Dr. Sachs tells it, Al’s equanimity about dying, his methodical preparations and his gen-tle demise did not ease the family’s pain as he lay dying, for they knew Al didn’t want to die and nobody in the family wanted to lose him.

Dr. Sachs explained that for survivors, “some of the suffering is existential or spiritual” and even the best end-of-life care cannot ease that kind of suffering.

He cautioned his fellow physicians against “painting too rosy a picture of end-of-life care” and creating unreasonable expectations of “spiritual growth” and “transcendence.”

But while no one is likely to rejoice at losing a loved one, having people die in accordance with their wishes is, in my experience, far less painful than the alternative, which all too often in-volves futile medical rescue efforts that patients do not want and that can get in the way of com-forting end-of-life conversations and reconciliations.

When my mother-in-law’s cancer recurred four years after treatment, she chose, at 84, not to have anything done that might prolong her life. And no one dared to contradict this decision by a woman who had always lived life on her own terms and was determined to die that way.A Chance to Say Goodbye

Living will in hand and fully in control of her faculties, she entered the hospital hemorrhaging, and at her request a “Do Not Resuscitate” notice was posted on her door. The family was called, and all had a chance to say goodbye unimpeded by machines, tubes and medical personnel. Twelve hours later, she was gone, leaving behind a sad but grateful family. Her minister, at her bedside until the end, said he had never before seen such a peaceful death.

Dr. Karen E. Steinhauser and colleagues at the Veterans Affairs Medical Center in Durham, N.C., examined the constituents of a good death for patients, their families and health care providers. The 85 study participants had no trouble describing a “bad death” - having inade-quately treated pain while receiving aggressive but futile cure-directed therapy.

Patients felt disregarded, family members felt perplexed and concerned about suffering, and providers felt out of control and feared that they were not providing good care. Decisions not previously discussed usually had to be made during a crisis. Families unprepared for what hap-pens when death is imminent often panicked and rushed the patient to the hospital, where last-

ditch and usually futile attempts at resuscitation were made, when both patient and family would have preferred a home death.

The study identified six components of a good death, described in The Annals of Internal Medicine of May 16, 2000: * Pain and symptom management. Pain, more so than dying itself, is too often the cause of acute anxiety among patients and their families.* Clear decision making. Patients want to have a say in treatment decisions.* Preparation for death. Patients want to know what to expect as their illness progresses and to plan for what will follow their deaths.* Completion. This includes reviewing one’s life, resolving conflicts, spending time with family and friends, and saying good-bye.* Contribution to others. Many people nearing death achieve a clarity as to what is really impor-tant in life and want to share that understanding with others.* Affirmation. Study participants emphasized the importance of being seen as a unique and whole person and being understood in the context of their lives, values and preferences.

This study says that dying can, and should, be a much less painful experience for many more people and their loved ones than it now is.

What Pilots Can Teach Hospitals About Patient SafetyBy KATE MURPHY

Wearing scrubs and slouching in their chairs, the emergency room staff members, assembled for a patient-safety seminar, largely ig-nored the hospital’s chief executive while she made her opening re-marks. They talked on their cellphones and got up to freshen their coffee or snag another danish.

But the room became still and silent when an airline pilot who used to fly F-14 Tomcats for the Navy took the lectern. Handsome, upright and meticulously dressed, the pilot began by recounting how in 1977, a series of human errors caused two Boeing 747s to collide on a foggy runway in the Canary Islands, killing 583 people. Riveted, a surgeon gripped his pen with both hands as if he might break it, an anesthetist stopped maniacally chewing his gum, and a wide-eyed nurse bit her lip.

An attention grabber, yes, but what does an airplane crash have to do with patient safety?A growing number of health care providers are trying to learn from aviation accidents and,

more specifically, from what the airlines have done to prevent them. In the last five years, sev-eral major hospitals have hired professional pilots to train their critical-care staff members on how to apply aviation safety principles to their work.

They learn standard cockpit procedures like communication protocols, checklists and crew briefings to improve patient care, if not save patients’ lives. Though health care experts disagree on how to incorporate aviation-based safety measures, few argue about the parallels between the two industries or the value of borrowing the best practices.

Spurred by a 1999 report by the Institute of Medicine, an arm of the National Academies, ti-tled “To Err Is Human,” which estimated that as many as 98,000 patients die annually from pre-ventable medical errors, and by more recent bad publicity from mistakes like amputations of the wrong limbs, many health care providers are redoubling their efforts to improve patient safety.

“We’re where the airline industry was 30 years ago” when a series of fatal mistakes increased scrutiny and provoked change, said Dr. Stephen B. Smith, chief medical officer at the Nebraska Medical Center in Omaha, the teaching hospital for the University of Nebraska.

It is well established that, like airplane crashes, the majority of adverse events in health care are the result of human error, particularly failures in communication, leadership and decision-making.

“The culture in the operating room has always been the surgeon as the captain at the controls with a crew of anesthesiologists, nurses and techs hinting at problems and hoping they will be addressed,” Dr. Smith said. “We need to change the culture so communication is more orga-nized, regimented and collaborative, like what you find now in the cockpit of an airplane.”

After the Canary Islands accident, NASA convened a panel to address aviation safety and came up with a program called Cockpit or Crew Resource Management. The Federal Aviation Ad-ministration requires that all pilots for commercial airlines and the military undergo the training. They learn, among other things, to recognize human limitations and the impact of fatigue, to identify and effectively communicate problems, to support and listen to team members, resolve conflicts, develop contingency plans and use all available resources to make decisions.

Recognizing the positive impact of the program on the aviation industry’s safety record, the Institute of Medicine in 2001 recommended similar training for health care workers. The National Academies, the Agency for Healthcare Research and Quality and the Institute for Healthcare Im-provement also advocate the training, as well as the use of other aviation-inspired practices like pre- and post-operative briefings, simulator training, checklists, annual competency reviews and incident reporting systems.

The British medical journal BMJ, The Journal of the American Medical Association and The Jour-nal of Critical Care have also published research suggesting that hospitals that adopt these mea-sures have fewer malpractice suits and postsurgical infections. Patient recovery times tend to be lower, and employee satisfaction is higher.

With these endorsements, and with the airline industry cutting salaries, benefits and flight time, many pilots have become part-time health care consultants. For fees that range from $7,000 to $40,000, they offer training and help devise and put in place systemwide safety proto-cols and procedures. Among the growing number of health care institutions that have hired avia-tion consultants or adopted aviation safety practices in the last five years are Vanderbilt Univer-sity Medical Center; Johns Hopkins Medical Institutions; Cedars-Sinai Medical Center in Los Ange-les; Vassar Brothers Medical Center in Poughkeepsie, N.Y.; the University of Nebraska; and the University of Texas Medical Branch at Galveston.

“The trend is not surprising given the similarities between health care and aviation,” said Dr. David M. Gaba, associate dean of immersive and simulation-based learning at the Stanford Uni-versity School of Medicine in Palo Alto, Calif.

“Both involve hours of boredom punctuated by moments of sheer terror,” he said.In addition to sometimes having to make life-and-death decisions in seconds, pilots and physi-

cians also tend to be highly skilled, Type A personalities, who rely heavily on technology to do their jobs.

Even so, some hospital administrators and experts in human factors argue that aviation safety principles are not wholly transferable to health care. “Medicine is a more complex environment with more professionals interacting than in aviation,” said Robert Helmreich, professor of psy-chology at the University of Texas at Austin and director of its Human Factors Research Project, which studies team performance and the influence of culture and behavior in aviation and health care.

The definition of an error in health care, Professor Helmreich said, is “fuzzier” than in aviation, where it is easier to identify a “foul-up” and who was responsible. Health care providers’ fear of litigation and losing their medical licenses also hinders the honest reporting of mistakes, whereas aviators are often inoculated against punishment if they promptly report incidents to the authorities. Training programs developed by pilots without knowledge of health care realities can be “appallingly bad,” he said.

More successful are programs developed by consulting firms like LifeWings in Memphis and the Surgical Safety Institute in Tampa, Fla., both of which have professional pilots and physicians developing their training materials and serving on their advisory boards.

Some institutions, like Johns Hopkins, have created their own in-house training programs and safety structures based on aviation. “Aviation provided us with the ideas, which we then modi-fied for health care as well as our particular situation,” said Dr. Peter Pronovost, the director of the Center of Innovation in Quality Patient Care at Johns Hopkins.

Employees who work at hospitals that have adopted these kinds of aviation-based safety pro-grams are mostly enthusiastic. Many say they are more confident doing their jobs thanks to posted checklists, which, for example, include reminders to wash their hands, confirm the iden-tity of the patient and check for drug allergies. They appreciate the fact that they are now not only encouraged to speak up if they are concerned about something, but also required to do so.

“Communication is so much better,” said Shelly Schwedhelm, a nurse and director of periop-erative and emergency services at Nebraska Medical Center, which instituted aviation-style safety measures a year ago.

“We now have debriefings after every surgery, during which we identify what we could do bet-ter but also what went right,” she said. “I’m hearing compliments and acknowledgment, which has really boosted morale.”

Still, some doctors balk at the rote quality of the procedures, claiming that they are unneces-sary and undermine their authority.

“I had one surgeon tell me that checklists are for the lame and weak,” said Professor Helmre-ich of the University of Texas.

Even the most recalcitrant tend to come around, however, when a safety check catches one of their mistakes, possibly saving a patient and preventing a malpractice suit.

“I’m seeing errors caught virtually every day” in the operating room, said Dr. Timothy Dowd, the chairman of the anesthesiology department at Vassar Brothers, where critical-care staff members underwent aviation-based patient-safety training six months ago.

“Even the most curmudgeonly surgeon has to admit this is a better way,” he said.Scientist at Work Claudia I. HenschkeWhen It Comes to Lung Cancer, She Doesn’t Believe in WaitingBy DENISE GRADY

Even people who think she’s wrong hope she turns out to be right.Since 1999, Dr. Claudia I. Henschke, a soft-spoken professor of radiology at Weill Cornell Medi-

cal College in New York, has been waging a relentless campaign. She has been trying to con-vince the medical establishment that smokers and former smokers should be offered routine CT scans to detect lung cancer when tumors are still small enough to be cured. By her estimate, the scans could prevent 80 percent of the 160,000 deaths a year from lung cancer in the United States.

She and her colleagues have had their findings published in prestigious medical journals like The Lancet and, last week, The New England Journal of Medicine. The day their study appeared in The Journal, doctors stopped in the corridors to shake her hand, a waiter in the faculty dining room said, “Dr. Henschke, you’re all over the TV and radio!” and an assistant collected newspa-pers reporting on her research.

“She has singlehandedly brought this issue of the disease and early detection and prevention to the forefront,” said Dr. Peter B. Bach, a pulmonologist and epidemiologist at Memorial Sloan-Kettering Cancer Center and a cancer policy adviser for Medicare and Medicaid. “People had completely given up on it. She has rejuvenated interest in early detection. That alone is a tremendous achievement, regardless of anything else.”

Anything else? Well, said Dr. Bach, who considers himself a friend, Dr. Henschke’s estimate that CT screening could reduce deaths by 80 percent is “an outrageous and implausible claim.” But, he added, “it really got people to pay attention.”

Even so, much of the cancer establishment says that Dr. Henschke has yet to prove her point. Sure, they say, CT scans are great at picking up small tumors, but do they really save lives? Could they harm people by raising false alarms that prompt lung biopsies or even surgery? Until those questions are answered to their satisfaction, influential bodies like the American Cancer Society and the National Cancer Institute have refused to endorse the scans, and have thrown the giant wet blanket of “needs further study” over her results.

“I don’t get what the resistance is,” Dr. Henschke said.To her, it is a matter of simple logic: the earlier cancer is found, the better the odds of a cure. CT finds lung cancer early. So why not use it?

No one disputes that the scans find small tumors. The study published last week involved 31,567 people scanned at more than 30 hospitals around the world. The scans found cancer in 484, often early; 85 percent were at Stage I. Without CT scans, lung cancer is usually found later, too late to cure.

With surgery, the researchers estimated the patients’ 10-year survival rate at 88 percent - a huge increase over the usual survival rate for Stage I, 70 percent at 5 years. Eight patients in the study who had Stage I tumors but refused treatment died within 5 years.

Other experts want the one thing that Dr. Henschke and her team have not provided - a study comparing two sets of patients, a group given CT scans and a control group given chest X-rays or no screening at all, to see whether the scans really do lower the death rate from lung cancer in the long run.

Such studies, randomized controlled trials, are generally considered the gold standard in med-ical research. “They are a standard,” Dr. Henschke said. But she and her colleagues argue that randomized controlled trials are not the best way to study lung cancer screening because they require too many patients, cost too much and take too long to provide answers. In addition, Dr. Henschke said, CT technology is advancing so rapidly that scanners can become obsolete even before a study is done.

Some experts agree that studies of screening take too long. Dr. Robert Smith, director of screening at the American Cancer Society, said, “Those of us who have the responsibility to eval-uate have to find a way to get answers about efficacy much faster than in 10 to 15 years.”

It may be reasonable to insist on randomized controlled trials for treatments, but not for diag-nostic tests, Dr. Henschke says. Her views are unconventional, to say the least. Some re-searchers say she is trying to rewrite the rules of science.Dr. Barnett Kramer, associate director for Disease Prevention at the National Institutes of Health, took vigorous exception to her asser-

tions, insisting that randomized controlled trials are the only way to find out for sure whether a test or a treatment really works.

“This could affect so many people,” he said. “You want to be sure you have your answer right.”

Dr. Henschke’s career has not exactly been conventional or rule-bound. She comes from a family of doctors and scientists. Her parents were radiologists, and her father had a doctorate in physics as well.

Her family moved from Germany when she was a child, first to Ohio and later New York, where her father worked at Sloan-Kettering and her mother at St. Vincent’s Hospital. Her father kept a seaplane in the Bronx and taught her to fly.

She graduated from high school at 16, and her father urged her to become a doctor, but she refused. Instead, she went to college in Texas, in part because it was a good place to fly, and majored in math and French. By 19, she had a flight instructor’s certificate and gave lessons to help pay her way through school. She earned a master’s degree from Southern Methodist Uni-versity and, in 1969, a doctorate in mathematical statistics from the University of Georgia.During the 1970s she flew her father from clinic to clinic in Africa, where he set up equipment to provide radiation treatment for cancer patients. She also began working as an adviser in statistics at the National Institutes of Health. But she said, “Nobody would listen to you unless you had an M.D.”

By then, her father was teaching at Howard University in Washington, and her sister was al-ready in medical school there. She enrolled, graduated in 1977 and did her residency in radiol-ogy at Harvard. She still found time to travel to Africa with her father and got some medical training in Tanzania.

On a trip there without her in 1980, her father was killed when the small plane on which he was a passenger crashed into the Ngorongoro crater.

In 1983, Dr. Henschke joined the Cornell medical school and New York Hospital as a specialist in chest radiology.

Around 1990, a colleague there, David A. Yankelevitz, approached Dr. Henschke to discuss re-search from the 1970s on using chest X-rays to detect lung cancer. Over all, the studies had sug-gested that X-rays did not find cancer early enough to help patients, and the medical profession had quit recommending them.

But CT was more sensitive, and so they began studying the scans. Dr. Yankelevitz also be-came convinced that they could prevent deaths.

Some experts worry that screening tests like this one can take hold without anyone knowing for sure whether they really save lives. The issue is not just the scan itself, but the mounting risks and costs of the biopsies and operations that follow when tumors are found.

Once they hear that a test can find tumors early, many people want it. And then the test can become hard to study, because nobody wants to be in the control group.

Cancer experts say lung CT screening has two major pitfalls. One is that it may detect tiny cancers that would never have progressed and lead to risky procedures like biopsies and lung surgery that are not really needed. Some patients could die from the surgery, or have their lives shortened by complications.

But Dr. Henschke’s team has tried to minimize needless biopsies, by using certain traits like size, growth rate and appearance to decide which abnormalities should be tested and which ones left alone.

“It’s one thing I think they deserve a lot of credit for,” Dr. Smith said.The second pitfall is harder to address. Some tumors, despite being tiny, may be so aggres-

sive and deadly that surgery simply cannot be done soon enough to prolong a person’s life. As a result, lung CT is not likely to save as many lives as its proponents claim, Dr. Smith said. But, he said, it does have “potentially an opportunity to reduce deaths.”

Aware of the concerns - and prodded by Dr. Henschke’s work - the National Cancer Institute is spending $300 million on a study to compare CT and chest X-ray in 50,000 people. Some results are expected by 2009.

But Dr. Henschke questions whether the study will be definitive. It may be too short, and even 50,000 patients may not be enough, she said. She has also challenged the study on moral grounds, asking if it is ethical to give some patients only chest X-rays when it is already known that CT picks up more tumors.

“She is smart, passionate, serious,” Dr. Bach said. “She has worked so hard on this. You can’t imagine the logistical challenges of coordinating a study like she’s coordinated. I am incredibly impressed by her devotion to this, and I hope she’s right. But we differ on what needs to be done to find out if she is right. It’s an honest disagreement.”Essay

Computing, 2016: What Won’t Be Possible?By STEVE LOHR

Computer science is not only a comparatively young field, but also one that has had to prove it is really science. Skeptics in academia would often say that after Alan Turing described the concept of the “universal machine” in the late 1930’s - the idea that a computer in theory could be made to do the work of any kind of calculating machine, including the human brain - all that remained to be done was mere engineering.

The more generous perspective today is that decades of stunningly rapid advances in pro-cessing speed, storage and networking, along with the development of increasingly clever soft-ware, have brought computing into science, business and culture in ways that were barely imag-ined years ago. The quantitative changes delivered through smart engineering opened the door to qualitative changes.

Computing changes what can be seen, simulated and done. So in science, computing makes it possible to simulate climate change and unravel the human genome. In business, low-cost com-puting, the Internet and digital communications are transforming the global economy. In culture, the artifacts of computing include the iPod, YouTube and computer-animated movies.

What’s next? That was the subject of a symposium in Washington this month held by the Computer Science and Telecommunications Board, which is part of the National Academies and the nation’s leading advisory board on science and technology. Joseph F. Traub, the board’s chairman and a professor at Columbia University, titled the symposium “2016.”

Computer scientists from academia and companies like I.B.M. and Google discussed topics in-cluding social networks, digital imaging, online media and the impact on work and employment. But most talks touched on two broad themes: the impact of computing will go deeper into the sciences and spread more into the social sciences, and policy issues will loom large, as the tech-nology becomes more powerful and more pervasive.

Richard M. Karp, a professor at the University of California, Berkeley, gave a talk whose title seemed esoteric: “The Algorithmic Nature of Scientific Theories.”

Yet he presented a fundamental explanation for why computing has had such a major impact on other sciences, and Dr. Karp himself personifies the trend. His research has moved beyond computer science to microbiology in recent years. An algorithm, put simply, is a step-by-step recipe for calculation, and it is a central concept in both mathematics and computer science.

“Algorithms are small but beautiful,” Dr. Karp observed. And algorithms are good at describ-ing dynamic processes, while scientific formulas or equations are more suited to static phenom-ena. Increasingly, scientific research seeks to understand dynamic processes, and computer sci-ence, he said, is the systematic study of algorithms.

Biology, Dr. Karp said, is now understood as an information science. And scientists seek to de-scribe biological processes, like protein production, as algorithms. “In other words, nature is computing,” he said.

Social networks, noted Jon Kleinberg, a professor at Cornell, are pre-technological creations that sociologists have been analyzing for decades. A classic example, he noted, was the work of Stanley Milgram of Harvard, who in the 1960’s asked each of several volunteers in the Midwest to get a letter to a stranger in Boston. But the path was not direct: under the rules of the experi-ment, participants could send a letter only to someone they knew. The median number of inter-mediaries was six - hence, the term “six degrees of separation.”

But with the rise of the Internet, social networks and technology networks are becoming inex-tricably linked, so that behavior in social networks can be tracked on a scale never before possi-ble.

“We’re really witnessing a revolution in measurement,” Dr. Kleinberg said.The new social-and-technology networks that can be studied include e-mail patterns, buying

recommendations on commercial Web sites like Amazon, messages and postings on community sites like MySpace and Facebook, and the diffusion of news, opinions, fads, urban myths, prod-ucts and services over the Internet. Why do some online communities thrive, while others de-cline and perish? What forces or characteristics determine success? Can they be captured in a computing algorithm?

Social networking research promises a rich trove for marketers and politicians, as well as soci-ologists, economists, anthropologists, psychologists and educators.

“This is the introduction of computing and algorithmic processes into the social sciences in a big way,” Dr. Kleinberg said, “and we’re just at the beginning.”

But having a powerful new tool of tracking the online behavior of groups and individuals also raises serious privacy issues. That became apparent this summer when AOL inadvertently re-leased Web search logs of 650,000 users.

Future trends in computer imaging and storage will make it possible for a person, wearing a tiny digital device with a microphone and camera, to essentially record his or her life. The potential for communication, media and personal enrichment is striking. Rick Rashid, a computer scientist and head of Microsoft’s research labs, noted that he would like to see a recording of the first steps of his grown son, or listen to a conversation he had with his father many years ago. “I’d like some of that back,” he said. “In the future, that will be possible.”

But clearly, the technology could also enable a surveillance society. “We’ll have the capability, and it will be up to society to determine how we use it,” Dr. Rashid said. “Society will determine that, not scientists.”Books on Science An Evolutionary Theory of Right and WrongBy NICHOLAS WADE

Who doesn’t know the difference between right and wrong? Yet that essential knowledge, generally assumed to come from parental teach-ing or religious or legal instruction, could turn out to have a quite dif-ferent origin.

Primatologists like Frans de Waal have long argued that the roots of human morality are evident in social animals like apes and monkeys. The animals’ feelings of empathy and expectations of reciprocity are essential behaviors for mammalian group living and can be regarded as a counterpart of human morality.

Marc D. Hauser, a Harvard biologist, has built on this idea to propose that people are born with a moral grammar wired into their neural circuits by evolution. In a new book, “Moral Minds” (HarperCollins 2006), he argues that the grammar generates instant moral judgments which, in part because of the quick decisions that must be made in life-or-death situations, are inaccessi-ble to the conscious mind.

People are generally unaware of this process because the mind is adept at coming up with plausible rationalizations for why it arrived at a decision generated subconsciously.

Dr. Hauser presents his argument as a hypothesis to be proved, not as an established fact. But it is an idea that he roots in solid ground, including his own and others’ work with primates and in empirical results derived by moral philosophers.

The proposal, if true, would have far-reaching consequences. It implies that parents and teachers are not teaching children the rules of correct behavior from scratch but are, at best, giving shape to an innate behavior. And it suggests that religions are not the source of moral codes but, rather, social enforcers of instinctive moral behavior.

Both atheists and people belonging to a wide range of faiths make the same moral judgments, Dr. Hauser writes, implying “that the system that unconsciously generates moral judgments is immune to religious doctrine.” Dr. Hauser argues that the moral grammar operates in much the same way as the universal grammar proposed by the linguist Noam Chomsky as the innate neu-ral machinery for language. The universal grammar is a system of rules for generating syntax and vocabulary but does not specify any particular language. That is supplied by the culture in which a child grows up.

The moral grammar too, in Dr. Hauser’s view, is a system for generating moral behavior and not a list of specific rules. It constrains human behavior so tightly that many rules are in fact the same or very similar in every society - do as you would be done by; care for children and the weak; don’t kill; avoid adultery and incest; don’t cheat, steal or lie.

But it also allows for variations, since cultures can assign different weights to the elements of the grammar’s calculations. Thus one society may ban abortion, another may see infanticide as a moral duty in certain circumstances. Or as Kipling observed, “The wildest dreams of Kew are the facts of Katmandu, and the crimes of Clapham chaste in Martaban.”

Matters of right and wrong have long been the province of moral philosophers and ethicists. Dr. Hauser’s proposal is an attempt to claim the subject for science, in particular for evolutionary biology. The moral grammar evolved, he believes, because restraints on behavior are required for social living and have been favored by natural selection because of their survival value.

Much of the present evidence for the moral grammar is indirect. Some of it comes from psy-chological tests of children, showing that they have an innate sense of fairness that starts to un-fold at age 4. Some comes from ingenious dilemmas devised to show a subconscious moral judg-ment generator at work. These are known by the moral philosophers who developed them as “trolley problems.”

Suppose you are standing by a railroad track. Ahead, in a deep cutting from which no escape is possible, five people are walking on the track. You hear a train approaching. Beside you is a lever with which you can switch the train to a sidetrack. One person is walking on the sidetrack. Is it O.K. to pull the lever and save the five people, though one will die?

Most people say it is.Assume now you are on a bridge overlooking the track. Ahead, five people on the track are at

risk. You can save them by throwing down a heavy object into the path of the approaching train. One is available beside you, in the form of a fat man. Is it O.K. to push him to save the five?

Most people say no, although lives saved and lost are the same as in the first problem.Why does the moral grammar generate such different judgments in apparently similar situa-

tions? It makes a distinction, Dr. Hauser writes, between a foreseen harm (the train killing the person on the track) and an intended harm (throwing the person in front of the train), despite the fact that the consequences are the same in either case. It also rates killing an animal as more acceptable than killing a person.

Many people cannot articulate the foreseen/intended distinction, Dr. Hauser says, a sign that it is being made at inaccessible levels of the mind. This inability challenges the general belief that moral behavior is learned. For if people cannot articulate the foreseen/intended distinction, how can they teach it?

Dr. Hauser began his research career in animal communication, working with vervet monkeys in Kenya and with birds. He is the author of a standard textbook on the subject, “The Evolution of Communication.” He began to take an interest in the human animal in 1992 after psychologists devised experiments that allowed one to infer what babies are thinking. He found he could re-

peat many of these experiments in cotton-top tamarins, allowing the cognitive capacities of in-fants to be set in an evolutionary framework.

His proposal of a moral grammar emerges from a collaboration with Dr. Chomsky, who had taken an interest in Dr. Hauser’s ideas about animal communication. In 2002 they wrote, with Dr. Tecumseh Fitch, an unusual article arguing that the faculty of language must have developed as an adaptation of some neural system possessed by animals, perhaps one used in navigation. From this interaction Dr. Hauser developed the idea that moral behavior, like language behavior, is acquired with the help of an innate set of rules that unfolds early in a child’s development.

Social animals, he believes, possess the rudiments of a moral system in that they can recog-nize cheating or deviations from expected behavior. But they generally lack the psychological mechanisms on which the pervasive reciprocity of human society is based, like the ability to re-member bad behavior, quantify its costs, recall prior interactions with an individual and punish offenders. “Lions cooperate on the hunt, but there is no punishment for laggards,” Dr. Hauser said.

The moral grammar now universal among people presumably evolved to its final shape during the hunter-gatherer phase of the human past, before the dispersal from the ancestral homeland in northeast Africa some 50,000 years ago. This may be why events before our eyes carry far greater moral weight than happenings far away, Dr. Hauser believes, since in those days one never had to care about people remote from one’s environment.

Dr. Hauser believes that the moral grammar may have evolved through the evolutionary mechanism known as group selection. A group bound by altruism toward its members and rigor-ous discouragement of cheaters would be more likely to prevail over a less cohesive society, so genes for moral grammar would become more common.

Many evolutionary biologists frown on the idea of group selection, noting that genes cannot become more frequent unless they benefit the individual who carries them, and a person who contributes altruistically to people not related to him will reduce his own fitness and leave fewer offspring.

But though group selection has not been proved to occur in animals, Dr. Hauser believes that it may have operated in people because of their greater social conformity and willingness to punish or ostracize those who disobey moral codes.

“That permits strong group cohesion you don’t see in other animals, which may make for group selection,” he said.

His proposal for an innate moral grammar, if people pay attention to it, could ruffle many feathers. His fellow biologists may raise eyebrows at proposing such a big idea when much of the supporting evidence has yet to be acquired. Moral philosophers may not welcome a biolo-gist’s bid to annex their turf, despite Dr. Hauser’s expressed desire to collaborate with them.

Nevertheless, researchers’ idea of a good hypothesis is one that generates interesting and testable predictions. By this criterion, the proposal of an innate moral grammar seems unlikely to disappoint.

New study shows teenage girls' use of diet pills doubles over five-year spanBy early adulthood 20 percent use weight loss pills

MINNEAPOLIS/ST. PAUL (10/30/2006) –A study released today by the University of Minnesota's "Project EAT" (Eating Among Teens) shows startling results of 2,500 female teenagers studied over a five-year period. The study found that high school-aged females' use of diet pills nearly doubled from 7.5 to 14.2 percent. By the ages of 19 and 20, 20 percent of females surveyed used diet pills.

"These numbers are startling, and they tell us we need to do a better job of helping our daughters feel better about themselves and avoid unhealthy weight control behaviors," U of M professor and study researcher Dianne Neumark-Sztainer said.

Other results from the study include: * 62.7 percent of teenage females use "unhealthy weight control behaviors" * 21.9 percent of teenage females use "very unhealthy weight control behaviors"

Very unhealthy weight control behaviors include the use of diet pills, laxatives, vomiting or skipping meals. Of the 2,500 teenage males studied, their rates were half of the females'.

"We have found that teenage females who diet and use unhealthy weight control behaviors are at three times the risk of being overweight," said Neumark-Sztainer. "Teens who feel good about their bodies eat better and have less risk of being overweight. Parents can play a key role in helping their children to build a positive body image and engage in healthy eating and physi-cal activity behaviors."

The study also shows that by teenage years, females' physical activity drops dramatically to only 3.93 hours per week, whereas males in the same age group spend 6.11 hours.

-----------------------------Neumark-Sztainer is also author of the book, "I'm, Like, So Fat!" (2005 Guilford Press). She has been fea-tured nationally as an expert in her field and is available nationwide to discuss the study and teen eating.For a complete copy of the study, Neumark-Sztainer's book, biography or to schedule an interview, contact David Ruth at (612) 624-1690 or [email protected] .

It's in your head: The brain's own globin defends you from shock and strokeNew article in the FASEB Journal provides details of a new protein: Neuroglobin

The next generation of treatments for shock or stroke could be based on a protein that is al-ready in our heads – neuroglobin. In a review article to be published in the November issue of The FASEB Journal, scientists from University of Rome describe this protein, which may be the key to unlocking new therapies to minimize brain damage and improve recoveries for patients.

The Italian researchers suggest that neuroglobin is involved in the brain's response to oxygen deprivation and plays a protective role against brain damage. Structurally similar to hemoglobin (blood) and myoglobin (skeletal muscle), neuroglobin is found in neurons and is most prevalent in areas of the brain that have adapted to physiological stress, such as stroke. Unlike hemoglo-bin or myoglobin, however, neuroglobin's primary function does not appear to involve transport-ing oxygen. Instead, the authors suggest that neuroglobin is more likely to usher in nitric oxide to protect neuron survival and recovery in areas where oxygen supply is reduced.

"Understanding that our brains have a hemoglobin-like molecule in our head that protects and helps restore function in the brain is an important step toward helping people who experience strokes or similar problems," said Gerald Weissmann, MD, Editor-in-Chief of The FASEB Journal. "Hemoglobin carries oxygen to all the body; neuroglobin defends our brain when it needs air. This article provides the first analysis of this exciting finding in brain research."

A potential biological cause for sudden infant death syndromeDefective serotonin pathways in the brainstem may increase infants' vulnerability

New autopsy data provide the strongest evidence yet that sudden infant death syndrome (SIDS) is not a "mystery" disease but has a concrete biological basis. In the November 1 issue of JAMA, researchers at Children's Hospital Boston document abnormalities in the brainstem – a part of the brain that regulates breathing, blood pressure, body heat, and arousal – in babies who died from SIDS.

SIDS is the leading cause of death in American infants after the newborn period, affecting 0.67 in 1,000 live-born babies. Although epidemiologic studies have identified risk factors for SIDS, such as putting babies to sleep on their stomachs, and protective factors like pacifier use, there has been little understanding of SIDS's biologic basis.

"Researchers led by neuropathologist Hannah Kinney, MD, and neuroscientist David Paterson, PhD, at Children's Hospi-tal Boston and Harvard Medical School examined brain autopsy specimens from 31 infants who had died from SIDS and 10 who had died acutely from other causes, provided by the San Diego Chief Medical Examiner's office. Examining the lowest part of the brainstem, known as the medulla oblongata, they found abnor-malities in nerve cells that make and use serotonin, one of over 100 chemicals in the brain that transmit messages from one nerve cell to another.

Infants who died from SIDS had significantly more serotonergic neurons (neurons that make and release serotonin) in their brainstem as compared with controls, particularly in

the area known as the midline raphé nucleus (blue dots).Based on their findings, Kinney, Paterson and colleagues hope to develop a diagnostic test to

identify infants at risk for SIDS. They also envision a drug or other type of treatment to protect infants who have abnormalities in their brainstem serotonin system.

The brainstem serotonin system is thought to help coordinate breathing, blood pressure, sen-sitivity to carbon dioxide, and temperature during waking and sleep. When babies sleep face-down or have their faces covered by bedding, they are thought to re-breathe exhaled carbon dioxide, therefore breathing in less oxygen. Normally, the rise in carbon dioxide activates nerve cells in the brainstem, which in turn stimulate respiratory and arousal centers in the brain so that the baby doesn't asphyxiate.

"A normal baby will wake up, turn its head, and start breathing faster when carbon dioxide levels rise," explains Kinney.

But in babies who die from SIDS, defects in the serotonin system may impair these reflexes, the researchers believe.

Kinney previously documented serotonin receptor abnormalities in two other popula-tions of SIDS infants, including American In-dian infants in the Northern Plains, whose SIDS rate is among the highest in the world. The current study confirms those findings in a third population and, for the first time, pinpoints multiple defects in the serotonin system other than those in sero-tonin receptors: deficiencies in a particular type of serotonin receptor (called 5HT1A), an abnor-mally high number of serotonergic neurons (neurons that make and release serotonin), a pre-ponderance of immature serotonergic neurons, and evidence for insufficient amounts of the serotonin transporter protein, which "recycles" serotonin so that nerve cells can reuse it.

Infants who died from SIDS had significantly fewer 5-HT1A receptors than controls, as shown in this brainstem tissue section. The red color indicates the greatest density of re-

ceptors."We provide strong evidence that SIDS is a biological problem, and that the brainstem sero-

tonin system is a good place to focus continued research efforts," says Paterson.He and Kinney believe that the abnormalities they observed begin during early fetal develop-

ment, and that prenatal insults like maternal smoking and alcohol use may adversely affect de-velopment of the brainstem serotonin system during this time. More research is needed to ex-plain what causes the abnormalities and how they can be prevented.

The findings also provide a biological explanation for why SIDS occurs twice as often in males than females – male SIDS infants had significantly fewer 5-HT1A receptors than female SIDS in-fants.

In addition, serotonin abnormalities help explain why infants under 6 months are most vulner-able to SIDS. At birth, babies must adjust from being totally dependent on their mother to breathing on their own and maintaining their own blood pressure. If the brainstem serotonin sys-tem is defective or still immature, this transition to total independence in the control of vital functions may be impaired during the crucial first six months of life.

"We think that the control systems for vital or homeostatic functions reach full maturity only towards the end of the first year of life," Kinney says.

The researchers note that despite the national Back to Sleep campaign, which urges care-givers to put babies to bed on their backs, 65 percent of the SIDS infants in this study were found sleeping on their stomach or side.

------------------------------The study, with coauthors from San Diego Children's Hospital and New England Research Institutes, was funded by the National Institute of Child Health and Human Development. Additional funding came from private SIDS foundations such as the CJ Foundation for SIDS, the First Candle/SIDS Alliance, the CJ Murphy Foundation, the Barrett Fellowship for SIDS Research and the Scottish Cot Death Foundation.Rehabilitation technique for stroke patients effective in improving arm, hand

movementTherapy that includes restraining the less-impaired arm or hand of a stroke patient appears

effective in improving movement and functional use of the paralyzed arm or hand, according to a study in the November 1 issue of JAMA.

Each year, more than 730,000 Americans experience a new or recurrent stroke, with resulting direct health care costs totaling $35 billion, according to background information in the article. Up to 85 percent of the approximately 566,000 stroke survivors experience hemiparesis (partial paralysis affecting only one side of the body), resulting in impairment of an upper extremity im-mediately after stroke, and between 55 percent and 75 percent of survivors continue to experi-ence upper-extremity functional limitations, which are associated with diminished health-related quality of life, even 3 to 6 months later.

One rehabilitation approach involves restraining the less-impaired upper extremity (arm or hand; usually by placing the entire arm in a sling or placing the hand in a mitt for most waking hours), thereby encouraging usage of the more-affected extremity (often referred to as "forced use"). This type of rehabilitation, called constraint-induced movement therapy (CIMT), includes

work with a clinician and repetitive task practice. Single-site studies have suggested that a 2-week program of CIMT can improve upper-extremity function.

Steven L. Wolf, Ph.D., P.T., of the Emory University School of Medicine, Atlanta, and colleagues compared the effects of a 2-week multisite program of CIMT vs. usual care on improvement in upper-extremity function among patients who had a first stroke within the previous 3 to 9 months. The Extremity Constraint Induced Therapy Evaluation (EXCITE) Trial, a randomized, mul-tisite clinical trial, was conducted at 7 U.S. academic institutions between January 2001 and Jan-uary 2003. The study included 222 individuals with predominantly ischemic stroke. Participants were assigned to receive either CIMT (n = 106; wearing a restraining mitt on the less-affected hand while engaging in repetitive task practice and behavioral shaping with the hemiplegic [par-tially paralyzed] arm and hand) or usual and customary care (n = 116; ranging from no treat-ment after concluding formal rehabilitation to pharmacologic or physiotherapeutic interven-tions).

Patients were evaluated using the Wolf Motor Function Test (WMFT), a measure of laboratory time and strength based ability and quality of movement (functional ability); and the Motor Ac-tivity Log (MAL), a measure of how well and how often 30 common daily activities are performed.

The researchers found that from baseline to 12 months, the CIMT group showed greater im-provements than the control group in both the WMFT Performance Time, with a between-group difference of 34 percent reduction in time to complete a task; and in the MAL measurements. The CIMT group also achieved a 65 percent increase in the proportion of tasks performed with the partially-paralyzed arm, and a greater decrease in self-perceived hand function difficulty, compared to the control group.

"In summary, among patients who had experienced stroke between 3 and 9 months prior, ad-ministration of CIMT resulted in statistically significant and clinically relevant improvements in paretic arm motor ability and use compared with participants receiving usual and customary care. Improvements were present following the 2-week intervention, persisted for up to 1 year, and were not influenced by age, sex, or initial level of paretic arm function. These findings sug-gest that further research exploring central nervous system changes that accompany the ob-served motor gains and research on alternate models of CIMT delivery are warranted," the au-thors write.

Microwave pre-cooking of French fries reduces cancer chemicalsResearch news from the Journal of the Science of Food and Agriculture

Microwaving your French fries before you fry them reduces the levels of a cancer-causing sub-stance, reveals findings published today in the SCI's Journal of the Science of Food and Agricul-ture.

The discovery of acrylamide - a possible carcinogenic in humans – has led to much research being done to investigate the benefits of alternative cooking methods. Acrylamide forms during processes such as frying, baking and roasting where high-temperature and low-moisture condi-tions exist.

Although numerous studies have been conducted to explore the possibilities of reducing acryl-amide levels in French fries, a team of researchers from Turkey has shown that by reducing the frying time and hence the acrylamide formation by microwave pre-cooking of potato strips prior to frying.

Publishing their work in the Journal of the Science of Food and Agriculture, the researches showed that microwave application prior to frying resulted in a marked reduction of the acryl-amide level in the surface region. When the potato strips were subjected to frying after a mi-crowave pre-cooking step, acrylamide content in the whole potato strip was reduced by 36%, 41% and 60% for frying at 150, 170 and 190oC respectively.

"Microwaving French fries before cooking takes little time and in fact, microwave pre-cooked samples fried to the same degree of cooking appeared to have a more acceptable colour, proba-bly due to the more gentle heat treatment they experienced during frying," says lead author Ko-ray Palazoglu, of the University of Mersin, Turkey.White blood cells of cancer-resistant mice overwhelm natural defenses of cancer cells

WINSTON-SALEM, N.C. – The discoverers of the unique mouse line that is resistant to cancer have begun to pin down how the process works and found that white blood cells in these mice overwhelm normal defenses of cancer cells.

In a report in Cancer Immunity, a journal of the Academy of Cancer Immunology, posted on line today, Zheng Cui, M.D., Ph.D., and Mark C. Willingham, M.D., of Wake Forest University School of Medicine and colleagues said that several types of white blood cells in the mice attack cancer cells by sensing, finding and surrounding them, forming a "rosette," and then killing them.

"Apparently, the mutation in the cancer-resistant mice renders the white blood cells capable of sensing unique diffusible and surface signals from cancer cells and responding to those sig-nals by migration and physical contact," they said.

The researchers said that in ordinary mice, the white blood cells are suppressed by self-defen-sive signals coming from the cancer cells and don't attack the cancer. But the mutated gene or genes in the cancer-resistant mouse changes the white blood cells so they interpret those same signals from the cancer cells as an invitation to attack.

"Identifying the mutated gene (or genes) will likely explain this unique resistance to cancer through immunity," said Cui, associate professor of pathology.

Earlier this year, the same team reported in the Proceedings of the National Academy of Sci-ences that white blood cells taken from these cancer-resistant mice cured advanced cancers in ordinary mice and also protected those normal mice from what should have been lethal doses of highly aggressive new cancers.

But while pursuing the ability of these white blood cells to cure cancer in ordinary mice, and beginning to explore whether the same process could work in humans, the researchers have also continued to investigate how the original mutation works, a mutation that protects the cancer-resistant mice from a wide variety of injected cancer cells.

Cui and Willingham said the killing of the cancer cells in the cancer-resistant mouse requires three distinct steps:

* First, the white blood cells migrate to the site of cancer cells after sensing their presence. * Second, they recognize unique properties on the surface of the cancer cells and closely sur-

round those cells. * Third, a lethal dose of each white-blood-cell type's cancer-killing compound is delivered to

the cancer cells. The killing molecule varies with the white-cell type.The ordinary mice lack the first two steps.The researchers found that the anti-tumor response involved white blood cells of the so-called

innate immune system, which the body ordinarily employs to fight off bacteria, but which had not been thought to be effective in fighting off cancer. Instead, in these cancer-resistant mice, three white-blood-cell types of the innate immune system – neutrophils, macrophages and natu-ral killer cells – all infiltrate the tumor site in a multi-pronged killing response.

"Each cell type had independent killing activity against the cancer cells," the authors said, us-ing different molecules. Macrophages, for instance, have to be in physical contact with the can-cer cell before unleashing its combination of killer molecules.

White blood cells from the cancer-resistant mice apparently have the same ability to attack a range of tumors when transplanted to ordinary mice.

Cui and Willingham also want to explore how this one process can detect a wide range of can-cer cells of so many different types. The dogma of cancer fighters has always postulated that there are many different cancers. "This new research in mice suggests that there may be some things that most cancers have in common," said Willingham, a pathologist and head of the Sec-tion on Tumor Biology.

-------------------------------------Support for the research came from the Cancer Research Institute and the National Cancer Institute. Coau-thors include Amy M. Hicks, Ph.D., Wei Du, M.D., Changlee S. Pang, M.D., all of Wake Forest, and Lloyd J. Old, M.D., of the Ludwig Institute for Cancer Research.

New strain of H5N1 bird flu emerges in China* 22:00 30 October 2006

* NewScientist.com news service* Debora MacKenzie

A new strain of H5N1 bird flu has emerged in China that is poised to start yet another global wave of infection.

Nearly three times as many Chinese poultry are infected with H5N1 now than last year, de-spite China’s insistence that all poultry be vaccinated. In fact, vaccination may be the reason for the increase in infections, researchers say.

Yi Guan and colleagues at the University of Hong Kong have been testing poultry in markets across southern China for flu for years, the only such long-term monitoring in the world. Between mid-2004 and mid-2005 they found 0.9% of market poultry were carrying H5N1, including 2% of ducks, a major carrier of the virus.

Between then and June 2006, however, they found it in 2.4% of market poultry on average, a near-threefold increase. It now infects 3.3% of ducks. The team found the virus in chickens dur-ing 11 months of the year, up from four previously.

The reason, the researchers say, is a new “Fujian-like” strain of the virus, descended from one first seen in a duck in Fujian, China, in 2005. It caused 3% of poultry infections in September 2005, but 95% by June 2006.Unrecognised cases

More infected – yet apparently healthy – birds in Chinese markets for more of the year means more risk for humans. All but one of China’s reported human cases of H5N1 happened after the Fujian strain started its rise, and some lived far from any known outbreak in poultry, but close to urban poultry markets.

There could be many more unrecognised cases. Serious cases of flu in humans, in China and elsewhere, are only tested for H5N1 if nearby poultry has suddenly died. But seemingly healthy, infected birds may cause human cases that are not tested – while the spread of the virus in the poultry also goes unsuspected.

“If death of poultry is used as the only indication of H5N1 infection, but the emergence of hu-man cases is ignored, the consequence will be increased transmission of the virus in poultry,” says Guan.

The team has no evidence that the virus is more virulent or more likely to transmit among hu-mans than previous strains, he says. But it has caused one human death in Thailand, and the five Chinese cases for which the team has virus samples. “As far as I know all 20 human cases recognised since November 2005 were caused by this virus,” Guan told New Scientist.

Based on what previous H5N1 viruses in China have done, the team warns, the Fujian strain seems poised to start a third epidemic wave, after the first in 2004, and H5N1’s spread across Eurasia in 2005. Fujian virus has so far spread to Thailand, Malaysia and Laos.Surging infection

In November 2005 China ordered compulsory vaccination of all poultry. The law has been im-perfectly applied – Guan and colleagues found vaccine-induced antibodies in only 16% of the birds they tested. But they also found that those vaccine-induced antibodies do not recognise the Fujian virus, although they do attack the virus strains that Fujian has now replaced.

This means the Fujian strain has a selective advantage in vaccinated birds. “This novel variant may have become dominant because it was not as easily affected as other strains by the current avian vaccine,” says Guan. That may also be why H5N1 infection in Chinese poultry has surged, rather than decreased, despite increased poultry vaccination.

Worryingly, the antibodies being used to develop human vaccines for H5N1 have been in-duced from 2004 strains of the virus – these antibodies do not recognise the Fujian strain. This means the current experimental pandemic vaccine would not work against any pandemic virus that emerged equipped with Fujian surface proteins.

Guan and colleagues want comprehensive influenza surveillance in both people and animals throughout the region, both to provide updates for vaccine developers and to track the real spread of the virus.Journal reference: Proceedings of the National Academy of Sciences (DOI:0:1073/pnas.0608157103)

New Hubble instruments would illuminate early universe* 14:22 31 October 2006

* NewScientist.com news service* David Shiga

The Hubble Space Telescope will be able to see further back in time than ever before if it is fit-ted with two new instruments in a shuttle servicing mission.

Hubble needs new gyroscopes and batteries to keep it working properly. Its existing gyro-scopes, which allow Hubble to point steadily at a target, could expire by 2008 and its batteries could die by 2010.

NASA is considering sending astronauts on a space shuttle mission to replace these parts in early 2008. A decision is expected to be announced at 1000 EST (1500 GMT) on Tuesday (see Hubble's fate being decided by NASA).

A servicing mission would not only extend Hubble's lifetime to at least 2013 but would also see two powerful new instruments installed that would give Hubble unprecedented abilities.

One, called the Wide Field Camera 3 (WFC3), can see a broad range of wavelengths including ultraviolet, visible and infrared and should be especially useful in studying the early universe. To make room for it, the Wide Field Planetary Camera 2, which was installed on Hubble in 1993, would be removed.

WFC3's sensitivity and wide field of view would make it 15 to 20 times more efficient at searching for faint, distant galaxies than Hubble's Near Infrared Camera and Multi-Object Spec-trometer (NICMOS), which has previously been used for this sort of work.Turning point

That would allow it to see fainter, more distant and more ancient objects than any previous Hubble instrument. Currently, there is tentative evidence it has observed objects that appear as they were about 800 million years after the big bang, says Hubble scientist Malcolm Niedner of NASA's Goddard space Flight Center in Greenbelt, Maryland, US.

"With WFC3 all this would be a lot more definitive and crisper and in much greater numbers," he told New Scientist.

WFC3 would also be useful for trying to understand what caused primordial hydrogen gas to be stripped of its electrons early in the universe's history in a process called reionisation. This crucial turning point made the universe more transparent to light and affected the growth of early galaxies.

"The WFC3 infrared channel would be just the right instrument for this investigation and, in fact, perhaps the only way of studying the end of reionisation until the James Webb Space Tele-scope is launched in 2013," says Massimo Stiavelli of the Space Telescope Science Institute in Baltimore, Maryland, US.Restore vision

The second instrument that would be installed, called the Cosmic Origins Spectrograph (COS), would measure the light spectrum of objects at ultraviolet wavelengths.

It would restore some abilities lost when Hubble's Space Telescope Imaging Spectrograph (STIS) stopped working in 2004 (see Shelved instrument could restore Hubble's UV vision).

COS would be especially useful for studying the gas that floats between galaxies, Niedner says. This would help astronomers survey the diffuse gas in space and understand how star for-mation and supernovae have affected it. The instrument would also help astronomers study de-veloping stars.

Martin Barstow, an astronomer at the University of Leicester, UK, and a member of Hubble's user committee, says a servicing mission would give Hubble "a dramatic new lease on life".

Phone creates interactive maps from snapshots* 17:32 31 October 2006

* NewScientist.com news service* Tom Simonite

Cellphones that add interactive information to printed maps could soon provide a simple way to find local points of interest.

Researchers have created a system that processes a snapshot of a printed map, captured on cameraphone, and forwards an interactive version of the same map back to the handset.

Symbols representing points of interest such as restau-rants, hotels and festivals can be displayed, along with im-ages, contact details and web links.

"If someone is out walking and reaches a town, they'll be able to simply point their phone at the map and find out places they could go for lunch, or other information not on the map," says Paul Lewis, of Southampton University in the UK, who developed the system with colleague Jonathan Hare.Ordinary phones

Lewis admits that cellphones fitted with GPS (Global Posi-tioning System) receivers will not need the technology. But until these become ubiquitous, he believes the system, dubbed Map Snapper, could prove useful for people armed with ordinary cameraphones. Lewis and Hare developed the Map Snapper in cooperation with Ordnance Survey, the UK government's agency responsible for producing maps.

Map Snapper software on a user's phone first sends a photo of a section of map to a central server via GPRS. "The server uses the image to generate a unique signature for that area of the map," Hare explains, "and then finds matches in a data-base of signatures for all the [Ordnance Survey] maps published."

An interactive map, with clickable icons, is returned to a phone by a central server (Im-age: Layla Gordon/Ordnance Survey)

A signature is generated by analysing areas with a rich complexity of edges and colours. Con-centrating on these regions makes it possible to create an identifying signature that is much smaller, in data terms, than the original image. When the map's signature has been matched to an area on file, the system adds local information and sends an interactive version of the map back to the user.

User-generated contentAlong with permanent landmarks, these maps can feature temporary events, such as local

music festivals. The developers also plan to let users add their own information through an on-line interface.

"It's a great idea," says Steve Coast, a UK mapping expert and founder of OpenStreetMap, a community-driven mapping project. "This is a good way of adding value to paper maps."

Coast says user-generated content could make Map Snapper very popular. "One obvious use is pub and bar ratings, because people like playing with their phones in those places," he adds.

However, he agrees that GPS is likely to make Map Snapper become obsolete before long. "I think they have maybe three years until people leave paper maps behind," he says, adding that the relatively high cost of mobile data transfer in the UK might also deter users before then.

The Ordnance Survey is currently seeking commercial partners willing to bundle Map Snapper with cellphone handsets.

Cave fossils are early EuropeansArchaeologists have identified fossils belonging to some of the earliest modern humans to set-

tle in Europe.The research team has dated six bones found in the Pestera Muierii cave, Romania, to 30,000

years ago.The finds also raise questions about the possible place of Neanderthals in modern human an-

cestry.Details of the discoveries appear in the US journal Proceedings of the National Academy of

Sciences.The human bones were first identified at the Pestera Muierii (Cave of the Old Woman) cave in

1952, but have now been reassessed.Interesting mix

Only a handful of modern human remains older than 28,000 years old are known from Europe.Erik Trinkaus from Washington University in St Louis and colleagues obtained radiocarbon

dates directly from the fossils and analysed their anatomical form.The results showed that the fossils were 30,000 years old and had the diagnostic features of

modern humans ( Homo sapiens ).But Professor Trinkaus and his colleagues argue, controversially, that the bones also display

features that were characteristic of our evolutionary cousins, the Neanderthals ( Homo nean-derthalensis ).

Neanderthals appear in the European fossil record about 400,000 years ago. At their peak, these squat, physically powerful hunters dominated a wide range, spanning Britain and Iberia in the west to Israel in the south and Uzbekistan in the east.

Modern humans are thought to have entered Europe about 40,000 years ago, and within 10,000 years, the Neanderthals had largely disappeared from the continent.

By 24,000 years ago, the last survivors vanished from their refuge in the Iberian Peninsula.Ice Age liaisons?

While many researchers think Neanderthals were simply driven to extinction - either by cli-mate change or competition with the moderns - a handful of scientists believe they interbred with the incomers and contributed to the modern human gene pool.

Professor Trinkaus and his co-researchers point to several anatomical features of the Roma-nian bones that are either primitive-looking or characteristic of Neanderthals.

These include a large "occipital bun", a bump or bulge at the back of the skull, as well as other features of the lower jaw and shoulder blade.

"These data reinforce the mosaic nature of these early modern Europeans and the complex dynamics of human reproductive patterns when modern humans dispersed westward across Eu-rope," Professor Trinkaus and his colleagues wrote in Proceedings of the National Academy of Sciences.

"Strict population replacement of the Neanderthals is no longer tenable."Rugged looks

Dr Katerina Harvati, a palaeoanthropologist from the Max Planck Institute for Evolutionary An-thropology in Leipzig, Germany, said the finds would further the understanding of early moderns in Europe.

She added that some traits in the fossils were either "archaic", which means they were char-acteristic of the ancestors both of modern humans and Neanderthals, or that their evolution, presence and absence in modern humans was poorly understood.

"Both the author's description and the few photographs provided in the article show a multi-tude of derived modern human traits and an overwhelmingly modern morphology of the de-scribed remains," she explained.

Professor Clive Gamble, from Royal Holloway in London, UK, said the discoveries would yield valuable information about early modern humans in Europe; but he was cautious about the evi-dence for interbreeding with Neanderthals.

"We've known for some time that the earliest modern humans in Europe are a funny-looking bunch. They are a distinctive looking lot - very heavily built, particularly in the skulls," he told the BBC.

"The question is whether these robust features show that they were up to no good with Nean-derthal women behind boulders on the tundra, or whether they were just a very rugged popula-tion.

"I think, really, the only way to tell would be to look at their ancient DNA. When DNA was ex-tracted from the classic Neanderthal skeleton, the last ancestor between modern humans and Neanderthals turned out to have lived 600,000 years ago."

Similar claims have also surrounded early human skulls from Mladec in the Czech Republic and the skeleton of a male child unearthed in 1998 at the Abrigo do Lagar Velho rockshelter in Portugal.

The Lagar Velho boy, who died about 25,000 years ago, has been described as a "hybrid", with a mixture of modern and Neanderthal features.Story from BBC NEWS: http://news.bbc.co.uk/go/pr/fr/-/2/hi/science/nature/6099422.stm

Bone research that grows on youRapid and guided healing of bones has moved a step closer with research by two biomedical

engineering students who have found new ways to deliver bone growth enhancers directly to broken or weakened bones.

Major ongoing research at Queensland University of Technology focuses on biodegradable ma-terials that carry bone growth enhancing substances to encourage bones to heal quickly with much less intervention.

The research is ultimately aimed at repairing fractured bones or replacing bone weakened or lost from osteoporosis, cancer or trauma with minimal intervention and without painful and ex-pensive bone grafts or pins and plates.

Fourth year biomedical engineering student Wayne Shaw has developed tiny biodegradable spheres made from polymers that can be loaded with calcium phosphate compounds - known bone growth facilitators - and placed on bone defects.

"As the microspheres degrade the calcium phosphate compounds are absorbed and encour-age the bone to grow quickly into the area and build new bone," Mr Shaw said.

"The microspheres, which are highly porous, range in size from 50 to 500 microns and have calcium phosphate abundantly deposited throughout the pores, can be used in a variety of ways.

"They could be used to fill bone defects or cavities, to coat load bearing implants, and to make scaffolds for the regeneration of bone."

Mr Shaw won joint best exhibit in the National 2006 Engineering and Physical Sciences in Medicine conference at Noosa in September.

Fellow fourth year biomedical engineering student Achi Kushnir has developed a load bearing ceramic material capable of carrying the same bone growth enhancing chemicals and of being absorbed by the body.

Mr Kushnir has integrated a dense ceramic core with a porous ceramic layer that can be used in place of metal implants for some clinical situations because it will attach to and integrate with bone and eventually degrade away.

"The dense core has high compressive strength for load-bearing applications such as for the long bones of the legs or arms," Mr Kushnir said.

"The unique core structure of the material will provide the mechanical properties needed for load-bearing bones and the outside porous layer will assist with the bone repair."

"Bioactive ceramics are known to be body-friendly but until now they have been limited by lack of mechanical properties including compressive strength for carrying loads."

The students' work was supervised by Associate Professor Simon X. Miao who said their find-ings had advanced the search for simple, cost effective, and minimally invasive methods of heal-ing bones. This bone research has been supported by the Medical Device Domain of QUT's Insti-tute of Health and Biomedical Innovation led by Professor Mark Pearcy.

Nanotechnology goes out on a wingInsect wings used to pattern nanoscale structures

What does a colorful and noisy backyard insect have to do with nanotechnology? Plenty, ac-cording to Jin Zhang and Zhongfan Liu, both professors at Peking University. A team of re-searchers led by Zhang and Liu have used the wings of cicadas, ubiquitous insects best known for their acoustic skills, as stamps to pattern polymer films with nanometer-sized structures. The wings of these insects are characterized by highly ordered arrays of closely spaced microscopic pillars. When these wings are pushed down upon a smooth polymer film, they create a negative imprint of the array pattern.

Zhang, Liu, and their co-workers from Peking University and Nanotechnology Industrialization Base of China have found that the insect wings possess sufficient rigidity and chemical stability and have a low enough surface tension to be used as stamps to pattern polymer films on silicon substrates. A low surface tension is necessary so that the wings do not stick to the substrate and can be released without destroying the imprinted structures.

Quite remarkably, the wings have a waxy coating, which imparts an intrinsically low surface tension to these structures, making them ideal for use as stamps. An ordered array of micro-scopic wells can be obtained on the polymer film by using the pillar array on the wings. This pat-tern can be transferred to silicon by an etching process, leading to the formation of 'nano-wells' on a silicon chip. Silicon wafers patterned with 'nano-wells' show promising anti-reflective prop-erties. Arrays of microscopic gold pillars can also be obtained by using the imprinted molds. These pillar arrays are almost exact replicas of the structures found on the insect wings and may be useful for optical imaging or the detection of molecules by Raman spectroscopy.

"This technique is a powerful demonstration of how natural nanostructures existing in the en-vironment can be used to pattern microscopic structures not easily accessible by conventional microfabrication technology", said Zhang. "There is a lot that nature can teach us about nan-otechnology", added Liu, citing examples of butterfly wings and lotus leaves, which are charac-terized by exquisitely ordered arrays of microscale and nanoscale structures.

-----------------------------Author: Jin Zhang, Zhongfan Liu, Peking University (P.R. China), http://www.chem.pku.edu.cn/NanoChem-istry/EN/staff/staff_Detail.asp?EmployeeId=39&GradeState=1Title: Cicada Wings: A Stamp from Nature for Nanoimprint Lithography Small 2006, 2, No. 12, 1440–1443, doi: 10.1002/small.200600255

New cancer-fighting virus kills invasive brain cellsBest results when VSV injected intravenously

CALGARY – Researchers funded by The Terry Fox Foundation and the Canadian Cancer Society have found that a cancer-fighting virus called VSV kills the most malignant form of brain cancer in mice.

The team also discovered that the virus can be given intravenously and targets invasive tu-mour cells.

The research team first modified the virus by altering one of the genes to make it safer in nor-mal cells but still able to kill cancer cells. They then used a new way of delivering the virus – in-travenously instead of directly into the tumour – and were able to target the main tumour as well as the tumour cells that had spread from the main mass.

The study was led by Dr. Peter Forsyth, a medical oncologist with the Alberta Cancer Board and a professor of oncology, neurosciences, biochemistry and molecular biology at the Univer-sity of Calgary. The study is published in the Nov. 1 issue of the Journal of the National Cancer In-stitute.

The brain tumour cells that invade into the surrounding normal brain are usually "hidden" from current treatments and are the ones that usually lead to a disease recurrence. The re-search using the vesicular stomatitis virus (VSV) was conducted on mice as well as on tumour specimens from patients with an aggressive form of brain cancer called malignant glioma.

"These findings are an excellent example of the great value of scientific collaboration," says Darrell Fox, national director of The Terry Fox Foundation. "Dr. Forsyth is part of a pioneering group of researchers that are sharing their expertise and benefiting from the knowledge of oth-ers working in this exciting new area of anti-cancer treatment."

"Research into viruses that target cancer is a promising new avenue in the fight against this disease," says Dr. Barbara Whylie, CEO of the Canadian Cancer Society. "We look forward to the possibility of this research leading to more effective treatments for this devastating disease."

Despite dramatic advances in the treatment of malignant glioma, one of the most common types of nervous system cancers in adults, the prognosis of patients has not improved substan-tially in the past 30 years. While there is typically initial success in treatment, the cancer cells usually spread beyond the main tumour and the disease recurs in another part of the body. When this happens, the disease often becomes resistant to standard chemotherapy treatment.

"An ideal cancer-fighting virus should have effective delivery into multiple sites within the tu-mour, evade the body's immune responses, reproduce rapidly, spread within the tumour and in-fect cells that have spread. In this study, that's exactly what we found that VSV has done when injected intravenously," says Dr. Forsyth.

The researchers tested VSV on 14 cell lines of malignant glioma and found that the virus in-fected and killed all cell lines. The normal cell lines – those that did not contain malignant glioma cells – were not affected.

"One of the limitations to the use of these viruses in patients is the difficultly in getting a suffi-cient amount of virus to the cancer," says Dr. Forsyth. "While these are very early results, we are very encouraged to find that delivering VSV intravenously attacks the cancer cells and not nor-mal cells. From a patient's point of view, it is obviously a lot easier to be treated with a few intra-venous treatments rather than having several surgeries to inject the treatment directly into your brain."

In 2006, an estimated 2,500 Canadians will be diagnosed with brain cancer and 1,670 will die of it. Even with the best available treatments – usually surgery and chemotherapy or radiation – patients with malignant glioma survive, on average, just one year.

-----------------------------The Terry Fox Foundation's mission is to maintain the principles of Terry Fox while raising money for can-cer research through the annual Terry Fox Run, memoriam donations and planned gifts. This year, the Foundation, through the National Cancer Institute of Canada, is funding $20 million in research across the country.

Study finds periodontal treatment does not lower preterm birth riskScientists supported by the National Institute of Dental and Craniofacial Research, part of the

National Institutes of Health, report in this week's New England Journal of Medicine that pregnant women who received non-surgical treatment for their periodontal, or gum, disease did not also significantly lower their risk of delivering a premature or low-birthweight baby.

These results come from the largest clinical trial to date to evaluate whether treating peri-odontal disease during pregnancy reduces a women's risk of early delivery, an idea that has emerged as a possibility in recent years. Non-surgical, or standard, periodontal treatment in-volves thoroughly cleaning the teeth above and below the gums, commonly called scaling and root planing.

The study, called the Obstetrics and Periodontal Therapy Trial (OPT), also evaluated the safety of general dental care during pregnancy. It found that dental treatment through the second trimester - both general and periodontal care – did not increase the number of adverse events for women during pregnancy.

Until now, little research had been conducted on the subject, although dentists generally pro-vide limited dental care to women only during the second trimester when the fetus has reached a more stable developmental stage and before treatment becomes too physically cumbersome for the mother.

"Dental care during pregnancy has long been an issue dominated by caution more than data," said NIDCR director Dr. Larry Tabak. "The finding that periodontal treatment during pregnancy did not increase adverse events is important news for women, especially for those who will need to have their periodontal disease treated during pregnancy."

In the United States, more than one-half million - or about one in eight - babies are born pre-maturely, which is defined as a birth that occurs before 37 weeks of pregnancy. Extremely preterm babies can be so small and underdeveloped that they must remain hospitalized for months, and, if they survive, spend years battling chronic health problems.

This has spurred scientists to identify several risk factors associated with premature births. These include smoking, low-income status, hypertension, diabetes, alcohol use, and genitouri-nary tract infections.

However, the list remains incomplete. As many as half of all preterm births occur without any clear explanation, and that has left scientists searching for additional susceptibility factors to help more mothers and ultimately reduce the estimated $26.2 billion annual cost to the nation for preterm births.

Over the last two decades, scientists have generated data in observational studies that sug-gest periodontal disease during pregnancy might be one of those elusive risk factors. The theory is based on the idea that bacteria associated with periodontal disease may spread to the womb and help to induce preterm births. Results of a previous small-scale clinical trial further sup-ported this idea, but what's been missing are more definitive data from larger, randomized clini-cal trials.

To fill this public-health need, the NIDCR funded two large, randomized clinical trials. The first to publish its results is the OPT, which included four participating centers: Hennepin County Med-ical Center in Minneapolis, University of Kentucky in Lexington, University of Mississippi/Jackson Medical Mall in Jackson, Miss., and Harlem Hospital/Columbia University in New York City.

Launched in March 2003, OPT enrolled a total of 823 women with periodontal disease, all of whom were between 13 and 17 weeks pregnant upon entry into the study. Each woman was ran-domly assigned to receive either: (1) scaling and root planing of the teeth prior to the 21st week of pregnancy, then monthly tooth polishings or (2) scaling and root planing after delivery, mean-ing women in this group did not have their periodontal disease treated during their pregnancies. All women were 16 years or older to participate, and basic dental care was provided to everyone in the study.

According to Dr. Bryan Michalowicz, a periodontist at the University of Minnesota and the lead author of the study, one of the OPT's strengths is its four regional centers generally provide pre-natal care to low income, underserved women of all races, who are recognized as being at par-ticularly high risk for early delivery.

"When trying to define risk factors for preterm birth, it's difficult to control for characteristics that may differ between full and preterm mothers, such as socioeconomic status or access to health and dental care," said Michalowicz. "By randomly assigning women from the same high-risk populations to receive treatment either before or after delivery, we could minimize such dif-ferences between groups."

As reported this week, the OPT data show:Birth Outcomes: Forty nine (12.0 percent) women in the treatment group had pregnancies

ending before 37 weeks compared to 52 (12.8 percent) of those in the control, or delayed treat-ment group. Nineteen miscarriages occurred, although the numbers were not indicative of a sta-tistically significant trend in either group. These included: Six spontaneous abortions (two in the treatment group, four in the control group) and 13 stillbirths (three in the treatment arm, 10 in the control group. A spontaneous abortion was defined as a loss of the baby before 20 weeks, while a stillbirth was considered to occur from 20 weeks to 36 weeks and six days. The re-searchers also found no significant differences among the two groups in the proportion of infants who were of low birthweight, defined as weighing less than 2500 grams, or about five and half pounds.

Periodontal Disease: Most women had early to moderate periodontal disease. The re-searchers found that the treatment improved all clinical measures of periodontal disease. These included the bleeding of gums when probed, the probing depth between the tooth and gum, and measuring tooth attachment. As additional evidence, the researchers found no difference in risk for preterm birth when they compared treatment and control women who had the most exten-sive bleeding of the gums, a sign of inflammation, or more advanced periodontal disease at en-try. They also found no differences when they examined a subset of women in the treatment group whose periodontal disease had improved the most during the study.

Safety of Periodontal Therapy: Women in both groups had similar rates of adverse medi-cal events, such as hospitalization of more than 24 hours for labor pains. This is an indication that periodontal therapy had no obvious effect on pregnancy.

"This study highlights the power of merging disciplines, in this case dentistry and obstetrics, to pursue a public-health question," said Dr. Virginia Lupo, an author on the study and an obste-trician at the Hennepin County Medical Center in Minneapolis. "We literally set up dental prac-tices within our obstetrics clinics, and that was a very unique and needed approach."

Although OPT is now the largest study to publish on the subject, the NIDCR-supported Mater-nal Oral Therapy to Reduce Obstetric Risk (MOTOR) study is ongoing. "It's just good science to conduct more than one large clinical trial on any public health question," said Dr. Jane Atkinson, program director of NIDCR's Clinical Trials Program. "If periodontal disease plays any role in preterm birth, we want to cast a wide enough investigational net to determine which women are at risk."

Atkinson said the 1,800-patient MOTOR study is designed a little differently than OPT. It in-volves a broader socio-economic cross section of women, provides fewer basic dental services, and includes women with slightly less severe periodontal disease. MOTOR will likely report its re-sults within the next two years.

--------------------------------The article is titled "Treatment of Periodontal Disease and The Risk of Preterm Birth" and appears in the November 2, 2006 issue of the New England Journal of Medicine. The authors are: Bryan S. Michalowicz, James S. Hodges, Anthony J. DiAngelis, Virginia R. Lupo, M. John Novak, James E. Ferguson, William Buchanan, James Bofill, Panos N. Papapanou, Dennis A. Mitchell, Stephen Matseoane, and Pat A. Tschida.

I honestly didn’t want to do another story about wine – or alcohol – but this one seemed important, so…

Single molecule extends fat mice lives by reversing gene pathways associated with

disease in obeseStudy has broad implications for treatment of diabetes, heart disease and other age-re-

lated diseasesBoston, MA--Researchers have used a single compound to increase the lifespan of obese mice,

and found that the drug reversed nearly all of the changes in gene expression patterns found in mice on high calorie diets--some of which are associated with diabetes, heart disease, and other significant diseases related to obesity. The research, led by investigators at Harvard Medical School and the National Institute on Aging, is the first time that the small molecule resveratrol has been shown to offer survival benefits in a mammal. The study is reported in the November 1 advanced online edition of Nature.

"Mice are much closer evolutionarily to humans than any previous model organism treated by this molecule, which offers hope that similar impacts might be seen in humans without negative side-effects," says co-senior author David Sinclair, HMS associate professor of pathology, and co-director of the Paul F. Glenn Labs for the Biological Mechanisms of Aging.

"After six months, resveratrol essentially prevented most of the negative effects of the high calorie diet in mice," said Rafael de Cabo, Ph.D., the study's other co-senior investigator from the National Institute on Aging's Laboratory of Experimental Gerontology, Aging, Metabolism, and Nutrition Unit. "There is a lot of work ahead that will help us better understand resveratrol's roles and the best applications for it."

Resveratrol is found in red wines and produced by a variety of plants when put under stress. It was first discovered to have an anti-aging properties by Sinclair, other HMS researchers, and their colleagues in 2003 and reported in Nature. The 2003 study showed that yeast treated with resveratrol lived 60 percent longer. Since 2003, resveratrol has been shown to extend the life-span of worms and flies by nearly 30 percent, and fish by almost 60 percent. It has also been shown to protect against Huntington's disease in two different animal models (worms and mice).

"The "healthspan" benefits we saw in the obese mice treated with resveratrol, such as in-creased insulin sensitivity, decreased glucose levels, healthier heart and liver tissues, are posi-tive clinical indicators and may mean we can stave off in humans age-related diseases such as type 2 diabetes, heart disease, and cancer, but only time and more research will tell," says Sin-clair, who is also a co-founder of Sirtris, a company with an author on this paper and which is currently in a phase 1b trial in humans with diabetes using an enhanced, proprietary formulation of resveratrol. [Harvard has license and equity interests with Sirtris, which is not a public com-pany.]

Investigators identified resveratrol while looking for compounds that activate Sir2, an enzyme linked to lifespan extension in yeast and other lower organisms. For the last 70 years, scientists have been able to increase the lifespan of a variety of species by reducing their normal food con-sumption by 30 to 40 percent - a diet known as calorie restriction. Through this research, scien-tists identified Sir2 as a key contributor to life extension. Without Sir2, for example, fruit flies see none of the benefits from either calorie restriction or treatment by resveratrol. The mammalian version of the Sir2 gene is SIRT1, which has the same enzymatic activity as Sir2, but modifies a wider variety of molecules throughout cells. Indicators in this study show that resveratrol might also be activating SIRT1 in mice, as well as other known longevity pathways.How the Study Was Done

This study examined three groups of mice, one on a standard diet (SD), another on a high calorie diet (HC) with 60 percent of calories coming from fat, and a third group of mice on the same high calorie diet but also treated with resveratrol (HCR). At middle age, or roughly 52 weeks of life, the researchers put the mice on the different diets.Survival Benefit

At 60 weeks of age, the survival rates of HC and HCR fed mice groups began to diverge and remained separated by a three to four month span. At 114 weeks of age, 58 percent of the HC fed mice had died, compared to 42 percent of the HCR and SD groups. Presently, the team has found resveratrol to reduce the risk of death from the HC diet by 31 percent, to a point where it is not significantly increased over the SD group. [Note: Given that mice are still living, final calcu-lations can't be made.] "The median lifespan increase we are seeing is about 15 percent at this point," says Sinclair. "We won't have final lifespan numbers until all of the mice pass away, and this particular strain of mouse generally lives for two-and-a-half-years. So we are around five

months from having final numbers, but there is no question that we are seeing increased longevity.

The team also found that the HCR fed mice had a much higher quality of life, outperforming the HC fed mice on motor skill tests. "The mice on resveratrol have not been just living longer," says Sinclair. "They are also living more active, better lives. Their motor skills actually show im-provement as they grow older. "Reversing Genetic Pathways Triggered by High Calorie Diet

The research team also wanted to see if resveratrol could reverse the changes in gene ex-pression patterns triggered by high calorie diets. Using liver tissue of five mice at 18 months of age from each group, the team performed a whole-genome microarray and identified which genes were turned on or off. The researchers then used a database generated by the Broad In-stitute that groups individual genes into common functional pathways to see where there were major differences.

"We made a striking observation," says Sinclair. "Resveratrol opposed the effects of high caloric intake in 144 out of 153 significantly altered pathways. In terms of gene expression and pathway comparison, the resveratrol fed group was more similar to the standard diet fed group than the high calorie group."Improved Health Biomarkers: Glucose and Insulin

In humans, high calorie diets can increase glucose and insulin levels leading to diabetes, car-diovascular disease, and non-alcoholic fatty liver disease. In the HC fed mice, researchers found biomarkers that might predict diabetes, including increased levels of insulin, glucose and insulin-like growth factor-1 (IGF-1). Conversely, the HCR fed group had significantly lower levels of these markers, paralleling the SD group. For example, a standard diabetes glucose test on the HCR fed group found considerably higher insulin sensitivity, meaning the HCR group had a lower disposi-tion toward diabetes than the HC fed group. Lower insulin levels also predict increased lifespan in mice.Organ Protection: Heart and Liver

Three pathologists examined heart tissue from the SD, HC, and HCR mice, and while not knowing which organ belonged to which mouse group, they looked for subtle changes in the abundance of fatty lesions, degeneration and inflammation. On a relative scale of 0-4, the as-sessment produced mean scores of 1.6 for the SD group, 3.2 for the HC group, and 1.2 for the HCR group.

The researchers also found that the livers of mice at 18 months of age on the HC diet were greatly increased in size and weight. Liver tissue studies of these mice showed a loss of cellular integrity, and a build-up of lipids, which is common to high fat diets. In contrast, the HCR group had normal, healthy livers.Links to Calorie Restriction Lifespan Model

The researchers also looked for metabolic ties to resveratrol's impact: pathway changes that mimicked those caused by calorie restriction. They examined AMP-activated kinase (AMPK), a metabolic regulator that promotes insulin sensitivity and fatty acid oxidation. It's been shown in previous work that the lifespan of worms has been extended by the addition of copies the AMPK gene, and chronic activation of AMPK is seen on calorie-restricted diets. The researchers exam-ined the livers of the HCR fed group and found a strong tendency for AMPK activation, as well as two downstream indicators of its activity.

Calorie restriction and exercise have also been previously shown to increase the number of mitochondria in the liver. Mitochondria generate energy in cells. Through electron microscopy, investigators showed that the livers of the HCR fed mice had considerably more mitochondria than the HC group, and were not significantly different from those of the SD group.Links to SIRT1

The team also asked if SIRT1 was activated by resveratrol in mice, as Sir2 is in lower organ-isms. To determine this, they looked at the amount of a specific chemical modification (acetyla-tion) on the molecule PGC-1alpha. Removal of the "acetyl" chemical groups on PGC-1alpha acti-vates this protein so that it can turn on certain genes that generate mitochondria and turn mus-cle into the type suited for endurance. The only enzyme known to remove the acetyl chemical groups on PGC-1alpha is SIRT1, and therefore the activity of PGC-1alpha is one of the most reli-able and specific markers of SIRT1 activity in mammals. The research team found that levels of PGC-1alpha were three-fold lower in the HCR fed mice than in the HC mice, consistent with what would be expected when SIRT1 was being activated by resveratrol.

"This work demonstrates that there may be tremendous medical benefits to unlocking the se-crets behind the genes that control our longevity," says Sinclair, "No doubt many more remain to be discovered in coming years."

-------------------------------------This study was supported by Paul F. Glenn and the Glenn Foundation for Medical Research, the U.S. Na-tional Institutes of Health and the National Institute of Aging, the Ellison Medical Research Foundation, the American Heart Foundation, and the American Diabetes Association.

Heel to healNew stretch relieves pain from plantar fasciitis

A new stretch is proving quite effective to help treat and potentially cure plantar fasciitis, a condition that affects nearly 2.5 million Americans each year. In a study recently published in Journal of Bone and Joint Surgery, researchers found that patients suffering from the painful heel spur syndrome had a 75 percent chance of having no pain and returning to full activity within three to six months of performing the stretch. In addition, patients have about a 75 percent chance of needing no further treatment.

The study is a two-year follow-up on 82 patients with plantar fasciitis, all of whom were part of an original clinical trial of 101 patients in 2003. The patients were taught a new stretch, specifi-cally targeting the plantar fascia, that was developed by Benedict DiGiovanni, M.D., associate professor of orthopaedic surgery at the University of Rochester and author of the study, and Deborah Nawoczenski, P.T., Ph.D., professor of physical therapy at Ithaca College.

The stretch requires patients to sit with one leg crossed over the other, and stretch the arch of the foot by taking one hand and pulling the toes back toward the shin for a count of 10. The ex-ercise must be repeated 10 times, and performed at least three times a day, including before taking the first step in the morning and before standing after a prolonged period of sitting. More than 90 percent of the patients were totally satisfied or satisfied with minor reservations, and noted distinct decrease in pain and activity limitations. The most common cause of heel pain, plantar fasciitis occurs when the plantar fascia, the flat band of tissue that connects your heel bone to your toes, is strained, causing weakness, inflammation and irritation. Common in mid-dle-aged people as well as younger people who are on their feet a lot, like athletes or soldiers, people with plantar fasciitis experience extreme pain when they stand or walk. Plantar fasciitis can be a frustrating experience, as the chronic cycle of reinjury and pain can last for up to one year. DiGiovanni likens it to pulling a hamstring, and continuing to run without proper stretching. "Walking without stretching those foot tissues is just re-injuring yourself," he said.

Most physicians will recommend a non-surgical approach to treating plantar fasciitis, advising a regimen of anti-inflammatory medications, foot inserts, and stretches. Surgery occurs in about 5 percent of all cases, and has a 50 percent success rate of eliminating pain and allowing for full activity.

"Plantar fasciitis is everywhere, but we really haven't had a good handle on it," said DiGio-vanni. "The condition often causes chronic symptoms and typically takes about nine to 10 months to burn itself out, and for people experiencing this pain, that's way too long to suffer through it."

DiGiovanni should know. He's experienced plantar fasciitis first-hand. Deciding to get some extra exercise on a golf outing one recent afternoon, he carried his clubs around all 18 holes in-stead of taking an easy-going ride in a golf cart. The next morning, he woke up with severe heel pain, which brought the topic of his study close to home.

"We need to further optimize non-operative treatments prior to considering surgical options," DiGiovanni said. "If you look at the results of the study, I think we've succeeded."

ASU researchers test antibacterial effects of healing claysNational Institutes of Health fund humanitarian response

Clay is most commonly associated with the sublime experience of the European spa where visitors have been masked, soaked and basted with this touted curative since the Romans ruled. If ASU geochemist Lynda Williams and microbiologist Shelley Haydel’s research on the antibacte-rial properties of clays realizes its full potential, smectite clay could one day rise above cosmetic use to take its place comfortably with antibacterial behemoths like penicillin.

“We use maggots and leeches in hospitals, so why not clay?” Haydel poses. “I had a professor in graduate school say, ‘Maybe perhaps once in your life, in your scientific career, you’ll come across something that can change the world.’ Sometimes I think: Is this it? Will this help some people?”

Theirs is an unusual research pairing. They are female scientists, each in the College of Liberal Arts and Sciences, yet pursuing different lines of scientific discovery. Williams is an associate re-search professor in the School of Earth and Science Exploration and studies clay mineralogy. Haydel is an assistant professor and expert in tuberculosis in the School of Life Sciences and with the Center for Infectious Disease and Vaccinology in the Biodesign Institute at Arizona State University.

“People are interested in natural cures and I think that there is a lot of nature that we don’t understand yet,” Williams says. “What if we discover a mechanism for controlling microbes that had never been discovered before? It is these avenues, at the boundaries of scientific discovery, at the edges of my field and knowledge (and Shelley’s), where such discoveries are made.”

National Institutes of Health (NIH) program directors agreed. They awarded a $438,970 grant over two years to Williams and Haydel for the study of clay mineral alternative treatment for Bu-ruli ulcer. What makes this award even more interesting is the rarity for a geochemist to net a NIH grant.National Center encourages alternative studies

The National Center for Complementary and Alternative Medicine at NIH was established in 1998 for just this kind of study. One of the 27 Institutes making up NIH, the Center funds scien-tific research and technologies that examine herbal remedies, such as dandelion, green tea, va-lerian, and horse chestnut, and practices like acupuncture, Tai Chi, and Reiki that fall outside conventional medicines.

The ASU duo will examine the mechanisms that allow two clays mined in France to heal Buruli ulcer, a flesh-eating bacterial disease found primarily in central and western Africa. Buruli ulcer has been declared to be “an emerging public health threat” by the World Health Organization (WHO). Related to leprosy and tuberculosis, the Mycobacterium ulcerans produces a toxin, le-sions, and destroys the fatty tissues under the skin.

“The toxin is immunosuppressant; the patients feel no pain and the body mounts no response to infection. It leads to disfigurement, isolation, not unlike that seen in leprosy,” Haydel explains. “Traditional antibiotics can only make a difference at the very earliest stages of the disease, so treatments have, in the past, been largely confined to amputations or surgical excision of the in-fected sites.”

This means if the clays are antibacterial in nature and the locus for that activity can be iso-lated, they may represent a new form of treatment, one that goes beyond the capacity of exist-ing antibiotics. “And they could be produced and distributed cheaply,” Williams notes.Humanitarians answer Internet challenge

So how did a clay mineralogist whose background is in low temperature geochemistry become involved with a health care project centered in the Ivory Coast? The scientific equivalent of an online dating or matchmaking service: “I answered a posting on the Clay Mineral Society’s list serve placed by Thierry Brunet de Courssou. He was asking to have someone take high resolu-tion scanning electron micrographs of the clays,” Williams explains. “I confess that we all ig-nored him initially.”

According to the Brunet de Courssou Web site, the family has been operating health clinics on the Ivory Coast and in New Guinea. For a decade, Madame Line Brunet de Courssou, Thierry’s mother, had been importing two French clays to treat people with Buruli ulcer and was getting startling results, while her use of native clays had no effect. Williams reviewed the mother’s work and notes that “Line Brunet de Courssou was a careful observer.” However, Madame Brunet de Courssou was not a scientist. The mother, who is now deceased, approached the WHO in 2002 at its fifth advisory group meeting on Buruli ulcer, having documented more than 50 cases of suc-cessful healing with the clay treatments. WHO documents indicate that the organization was re-ceptive, calling her results “impressive,” yet, Williams notes, funding was denied for lack of sci-entific study.

Williams, from a family of physicians, says that it was really the second message that finally drew her to the project. “He said, ‘I guess that no American scientists are interested in helping poor people in Africa.’”

He guessed wrong. Armed with 100 grams of green powder (clay high in reduced iron), Williams not only took the micrographs of the minerals, she went a step further and examined their crystal structure and chemical compositions. She recruited Haydel to the project before the microbiologist arrived at ASU in 2005. Haydel brought more than 13 years of experience with pathogenic bacteria, in particular tuberculosis, to the project. Within two months of Haydel’s ar-rival, they submitted the grant proposal to the NIH.

“I approached this work from the viewpoint of a clinical microbiologist,” Haydel says. “I or-dered bacterial strains that pharmaceutical companies use to test their antimicrobials.”

Haydel and Williams tested both of the French clays that Brunet de Courssou had been im-porting. One completely inhibited pathogenic Escherichia coli, Salmonella typhimurium, Pseu-domonas aeruginosa (often a problem as an opportunistic infection in burn wards) and Mycobac-terium marinum (related to Mycobacterium ulcerans, which causes Buruli ulcer disease). The clay was also found to partially inhibit the growth of pathogenic Staphylococcus aureus, includ-

ing a multi-drug resistant variety. “The other clay actually helps the bacteria to grow,” Haydel adds.

What makes one clay kill bacteria, and the other promote growth? And why do most clays tested have no effect? Research like that being done by Williams and Haydel can answer such questions. “Clay can be as variable as the bacteria we are studying. There is a lot to be learned yet,” Williams notes.Clay’s properties fuel interest

Williams’ career fascination with clay started when she was a mineral exploration geologist looking for ore deposits. She worked with ‘the father of clay mineralogy,’ Bob Reynolds, at Dart-mouth College. Later, as a research associate at Louisiana State University, a colleague was studying geophasia – eating clay, a behavior seen in animals and people, since the time of the aborigines.

“In the South Appalachian Mountains, poor women would eat the local clay to help soothe nausea and stomach ailments, particularly during pregnancy. The clay was rich in kaolinite. (Kaolinite is the major ingredient in the over the counter remedy Kaopectate). But one day, they ran out of clay and moved over to another mountain and people began dying. We wanted to know why.”

The key to clay’s variable nature seems to be its structure. “Clay is a mineral; it has a crys-talline structure that is both flexible and fluid,” Williams says. She likens them to very thin, two-nanometer-thick slices of bread in a “peanut butter and jelly sandwich.” The “bread” is com-posed of three regions, two silicate layers with tetrahedral rings bounding an octahedral core. The “peanut butter” is the charged cations, for example, potassium, that stick to the negatively charged tetrahedral ring surface. And the jelly? Organic compounds or other species of any or no charge are possible. This interlayer, as the peanut butter and jelly are termed, can vary in width and composition depending on the kinds of waters and elements present when it was formed. It is this interlayer where much of the elemental variability between clays can be found. And the interlayer surface area is huge (greater than 100 square meters per gram of clay – bigger than a football field). As a result, surface chemical reactions from these sites have an enormous impact on the geochemistry of the local environment.

Williams is passionate about her subject: “Clays are as individual in character as people are in personality. They can be as old as Precambrian time (probably older, since meteorites contain clay minerals from other celestial bodies) or as young as I can make them in my lab in a few hours. They form when the chemistry, temperature and pressure conditions are right. In the case of the two French clays we are testing, their chemical structures are almost identical, but the different trace element chemistry of the interlayer records an older geologic condition, from a time when the antimicrobial property was likely inherited.”

Crystal structure, the interlayer, the way other materials, metals, ions bind to clays, the ab-sorptive characteristics of clays, all could potentially play a role in the antibacterial activity they find in the one French clay. And, while preliminary results suggest that the antibacterial activity is associated with the interlayer, crystal size and structure also seem to play a role.

It is a mystery that engages both research partners: “It’s fascinating,” Haydel says. “Here we are bridging geology, microbiology, cell biology – transdisciplinary sciences, exactly what (ASU President) Michael Crow has been promoting. A year ago, I’d look at the clay and say, ‘well that’s dirt.’ Now I know a little something about clay structure; Lynda knows a little bit about microbiol-ogy. Alone, we each would have had to study for years; together we are partnering these disci-plines with synergy that really works.”

Nap a day makes doctors OK, Stanford study findsSTANFORD, Calif. - Give emergency room doctors a nap, and not only will they do a better job, they'll also be nicer to you, according to a new study from Stanford University School of Medicine.

The findings, to be published in the November issue of Annals of Emergency Medicine, showed improved mood, a higher alertness level and the ability to complete a simulated I.V. insertion more quickly among doctors and nurses who were allowed a short nap while working the night shift in an emergency room.

"Napping is a very powerful, very inexpensive way of improving our work," said one of the study's authors, Steven Howard, MD, associate professor of anesthesia and expert on sleep de-privation and fatigue.

Howard has taken the results of the study one step further and begun implementing an official napping program at the hospital at the Veterans Affairs Palo Alto Health Care System. "This is the first time a napping program has been instituted to try to get at the problem of fatigue in the workplace for health-care workers," he said.

According to statistics on America's need for sleep, plenty of people could use a nap. More than 50 percent of Americans are sleep-deprived.

Scientific research has documented the need for naps to mitigate drowsiness and improve performance and alertness in pilots and truckers, but no previous study has looked specifically at the possible benefits for health-care workers, said the first author of the study, Rebecca Smith-Coggins, MD, associate professor of surgery (emergency medicine).

"I've been really worried about physicians," said Smith-Coggins, whose research has focused on sleep deprivation and its effects on health-care workers for the past two decades. "Everyone was complaining around me, 'I'm so tired.'"

The study's authors hope that by providing scientific data that supports the benefits of nap-ping, more hospitals and other employers will consider policy changes that include nap breaks to help improve safety and performance levels.

"Being up for 24 hours has the same effects as being legally drunk," said Howard. "Caffeine and nicotine mask the effects of sleepiness, but naps actually replace lost sleep. It's totally dif-ferent mechanistically."

To determine just how much a nap would help alleviate sleep deprivation, researchers re-cruited 49 subjects - 24 nurses and 25 doctors - who worked through the night from 7:30 p.m. to 7:30 a.m. in the emergency room at Stanford Hospital. They divided the subjects into two groups. One group worked straight through the night as usual, while the other subjects were al-lotted a 40-minute nap break at 3 a.m. in the middle of their shift.

"They fell asleep really fast," said Smith-Coggins. "Half fell asleep in less than 10 minutes. They were tired!"

At the end of their shift at 7:30 a.m., both groups underwent a series of tests including a 40-minute simulated car drive, a 10-minute written memory recall test, a computer-based I.V. inser-tion simulation and a questionnaire developed by NASA that measured different mood states in-cluding anger, confusion, depression, fatigue, tension and vigor.

The nap group scored fewer performance lapses, reported more vigor, less fatigue and less sleepiness. The doctors and nurses who napped also tended to complete more quickly the simu-lated intravenous insertion, and they were safer drivers in the tests.

By contrast, many of those without naps would "crash over and over again" in the driving sim-ulations, Smith-Coggins said. Their cars would often leave the road or collide with oncoming ve-hicles. "I felt so badly after seeing how tired they were."

Another test measured facial alertness to assess drowsy driving. Researchers scored video-tapes of the subjects' faces while performing the driving simulation. If their heads bobbed or they closed their eyes for longer than five seconds, they were labeled dangerous drivers. Again, those with naps scored better than those without.

Despite an accumulation of scientific evidence showing the benefits of napping for workers, little has been done in the United States to implement any institutionalized napping programs, primarily due to a cultural bias, Howard said. Battling this bias and finding a comfortable napping spot as close as possible to the work station have been the primary challenges he's faced while implementing the new napping program at the VA-Palo Alto.

"The social connotation of someone who naps is lazy, slothful," Howard said. "Attitudes toward people who nap are hard to break."

Mate like crazy and let the sperm fight it out* 01 November 2006

* From New Scientist Print Edition. Subscribe and get 4 free issues.* Emma Young

Have sex and die: that's the lot of a shrew-like marsupial that can't afford to waste time pick-ing out the ideal mate but seems to produce great offspring all the same. It looks like the trick might be down to some high-performance sperm.

Antechinus stuartii is a small Australian marsupial with a bizarre sex life. Males gather in a nest, wait for females to turn up and then attempt to mate with as many as possible in what for both sexes is a once-in-a-lifetime sexual orgy. Two weeks later, the males' immune systems fail and they die, while the females go on to produce what is usually their one and only litter before dying a few months later.

When Diana Fisher of the Australian National University in Canberra and colleagues took wild animals and allowed females to mate either once with each of three males, or three times with just one male, they found females with multiple mates had three times as many offspring that survived till weaning.

Promiscuous these animals may be, but that doesn't mean anything goes genetically speak-ing. Paternity tests and follow-up experiments revealed that some males sired far more surviving offspring than others.

That would make sense, say the researchers, if better-quality males also produce sperm that is able to outcompete the sperm of other males. If so, females do not need to pick out the best males: instead, they can mate with multiple partners and let the males' sperm fight it out (Na-ture, vol 44, p 89). "There have been clues that this might happen in other animals, but this is the first time this has been shown in a comprehensive way," says Fisher.

Could the same processes be at work in other mammals? Females are thought to select male partners to reduce the chances of contracting disease and because they tend to invest more in fewer offspring compared with males. Antechinus's unusual reproductive habits make it an odd-ity, with more evolutionary pressure than usual for "good sperm" to win out. However, the bene-fits of multiple mating shown in this study are striking and suggest that females of other species might also benefit from such behaviour, says evolutionary biologist Tom Tregenza of the Univer-sity of Exeter in the UK.

Study Sees ‘Global Collapse’ of Fish SpeciesBy CORNELIA DEAN

If fishing around the world continues at its present pace, more and more species will vanish, marine ecosystems will unravel and there will be “global collapse” of all species currently fished, possibly as soon as midcentury, fisheries experts and ecologists are predicting.

The scientists, who report their findings today in the journal Science, say it is not too late to turn the situation around. As long as marine ecosystems are still biologically diverse, they can recover quickly once overfishing and other threats are reduced, the researchers say.

But improvements must come quickly, said Boris Worm of Dalhousie University in Nova Scotia, who led the work. Otherwise, he said, “we are seeing the bottom of the barrel.”

“When humans get into trouble they are quick to change their ways,” he continued. “We still have rhinos and tigers and elephants because we saw a clear trend that was going down and we changed it. We have to do the same in the oceans.”

The report is one of many in recent years to identify severe environmental degradation in the world’s oceans and to predict catastrophic loss of fish species. But experts said it was unusual in its vision of widespread fishery collapse so close at hand.

The researchers drew their conclusion after analyzing dozens of studies, along with fishing data collected by the United Nations Food and Agricultural Organization and other sources. They acknowledge that much of what they are reporting amounts to correlation, rather than proven cause and effect. And the F.A.O. data have come under criticism from researchers who doubt the reliability of some nations’ reporting practices, Dr. Worm said.

Still, he said in an interview, “there is not a piece of evidence” that contradicts the dire conclusions.

Jane Lubchenco, a fisheries expert at Oregon State University who had no connection with the work, called the report “compelling.”

“It’s a meta analysis and there are challenges in interpreting those,” she said in an interview, referring to the technique of collec-tive analysis of disparate studies. “But when you get the same pat-terns over and over and over, that tells you something.”

But Steve Murawski, chief scientist of the Fisheries Service of the National Oceanic and Atmospheric Administration, said the re-searchers’ prediction of a major global collapse “doesn’t gibe with trends that we see, especially in the United States.”

He said the Fisheries Service considered about 20 percent of the stocks it monitors to be overfished. “But 80 percent are not, and that trend has not changed substantially,” he said, adding that if any-thing, the fish situation in American waters was improving. But he conceded that the same can-not necessarily be said for stocks elsewhere, particularly in the developing world.

Mr. Murawski said the Bush administration was seeking to encourage international fishery groups to consider adopting measures that have been effective in American waters.

Twelve scientists from the United States, Canada, Sweden and Panama contributed to the work reported in Science today.

“We extracted all data on fish and invertebrate catches from 1950 to 2003 within all 64 large marine ecosystems worldwide,” they wrote. “Collectively, these areas produced 83 percent of global fisheries yields over the past 50 years.”

In an interview, Dr. Worm said, “We looked at absolutely everything - all the fish, shellfish, in-vertebrates, everything that people consume that comes from the ocean, all of it, globally.”

The researchers found that 29 percent of species had been fished so heavily or were so af-fected by pollution or habitat loss that they were down to 10 percent of previous levels, their definition of “collapse.”

This loss of biodiversity seems to leave marine ecosystems as a whole more vulnerable to overfishing and less able to recover from its effects, Dr. Worm said. It results in an acceleration of environmental decay, and further loss of fish.

Dr. Worm said he analyzed the data for the first time on his laptop while he was overseeing a roomful of students taking an exam. What he saw, he said, was “just a smooth line going down.” And when he extrapolated the data into the future “to see where it ends at 100 percent collapse, you arrive at 2048.”

“The hair stood up on the back of my neck and I said, ‘This cannot be true,’ ” he recalled. He said he ran the data through his computer again, then did the calculations by hand. The results were the same.

“I don’t have a crystal ball and I don’t know what the future will bring, but this is a clear trend,” he said. “There is an end in sight, and it is within our lifetimes.”

Dr. Worm said a number of steps could help turn things around.Even something as simple as reducing the number of unwanted fish caught in nets set for

other species would help, he said. Marine reserves would also help, he said, as would “doing away with horrendous overfishing where everyone agrees it’s a bad thing; or if we banned de-structive fishing in the most sensitive habitats.”

Josh Reichert, who directs the environmental division of the Pew Charitable Trusts, called the report “a kind of warning bell” for people and economies that depend on fish.

But predicting a global fisheries collapse by 2048 “assumes we do nothing to fix this,” he said, “and shame on us if that were to be the case.”U of M researchers invent 'flashy' new process to turn soy oil, glucose into hy-

drogenProcess could significantly improve the efficiency of fuel production from renewable en-

ergy sourcesAnyone who's overheated vegetable oil or sweet syrup knows that neither oil nor sugar evapo-

rates--oil smokes and turns brown, sugar turns black, and both leave a nasty film of carbon on the cookware. Now, a University of Minnesota team has invented a "reactive flash volatilization process" that heats oil and sugar about a million times faster than you can in your kitchen and produces hydrogen and carbon monoxide, a mixture called synthesis gas, or syngas, because it is used to make chemicals and fuels, including gasoline. The new process works 10 to 100 times faster than current technology, with no input of fossil fuels and in reactors at least 10 times smaller than current models. The work could significantly improve the efficiency of fuel produc-tion from renewable energy sources. It will be published Nov. 3 in Science.

"It's a way to take cheap, worthless biomass and turn it into useful fuels and chemicals," said team leader Lanny Schmidt, a Regents Professor of chemical engineering and materials science at the university. "Potentially, the biomass could be used cooking oil or even products from cow manure, yard clippings, cornstalks or trees."

One up-and-coming fuel is biodiesel, which is produced from soy oil. Currently, the key step in conversion of the oil to biodiesel requires the addition of methanol, a fossil fuel. The new process skips the biodiesel step and turns oil straight into hydrogen and carbon monoxide gases by heat-ing it to about 1,000 degrees C. About 70 percent of the hydrogen in the oil is converted to hy-drogen gas. Similarly, using a nearly saturated solution of glucose in water, the process heats the sugar so fast that it, too, breaks up into syngas instead of its usual products: carbon and wa-ter.

A difficulty in turning plant material into usable fuels has been breaking down the chemical bonds in cellulose--the material that gives plant cell walls their stiffness--to liberate simple sug-ars that can be fermented into ethanol or turned into other fuels. That requires special enzymes and lots of time. But the high heat of the new process breaks those bonds with ease, meaning cellulose and similar plant materials can possibly be used as feedstocks.

Schmidt and his university colleagues--graduate students James Salge, Brady Dreyer and Paul Dauenhauer--have produced a pound of synthesis gas in a day using their small-scale reactor.

Here's how the new process works: The oil and sugar water are sprayed as fine droplets from an automotive fuel injector through a tube onto a ceramic disk made of a catalyst material--the elements rhodium and cerium--that guides the breakup of the feedstock molecules toward the production of syngas and away from water and carbon "gunk." Because the catalytic disk is por-ous, the syngas passes through it and is collected downstream in the tube. No external heat is needed, because the chemical reactions that produce syngas release enough heat to break up subsequent molecules of oil or sugar.

"The secret is ultrafast flash volatilization [vaporization]," said Schmidt. "It happens here be-cause we vaporize the fuel and mix it with oxygen before it sees the catalyst so it doesn't burn to char. This is potentially 100 times faster than what is currently available to make syngas and hydrogen."

Schmidt gained national attention in February 2004, when a team he headed invented a simi-lar apparatus to produce hydrogen from ethanol.

---------------------------------The work was supported by the Department of Energy and the University of Minnesota Initiative for Re-newable Energy and the Environment.

Reduced body temperature extends lifespan in study from the Scripps Re-search Institute

Lifespan lengthened without dietary restriction"Our study shows it is possible to increase lifespan in mice by modest but prolonged lowering

of core body temperature," said Bruno Conti, an associate professor at Scripps Research who led the study. "This longer lifespan was attained independent of calorie restriction."

Prior to this study, researchers had known that core body temperature and aging were related in cold-blooded animals. Scientists had also known that lifespan could be extended in warm-blooded animals by reducing the number of calories they consumed, which also lowered core body temperature. But the degree of calorie restriction needed to extend lifespan is not easy to achieve, even in mice.

Prior to the current study, critical questions about the relation between calorie restriction, core body temperature, and lifespan remained unanswered. Was calorie restriction itself respon-sible for longer lifespan, with reduced body temperature simply a consequence? Or was the re-duction of core body temperature a key contributor to the beneficial effects of calorie restriction? Conti and colleagues wanted to find out.

To tackle the problem, the scientists decided to try to lower core body temperature directly, without restricting food intake. In cold-blooded animals, such as roundworms (C. elegans) and fruitflies (Drosophila), this task is straight-forward--core body temperature can be lowered simply by changing the temperature of the environment. But for warm-blooded animals, the task is much more challenging.

Conti and colleagues decided to focus their efforts on the preoptic area of the hypothalamus, a structure in the brain that acts as the body's thermostat and is crucial to temperature regula-tion. Just as holding something warm near the thermostat in a room can fool it into thinking that the entire room is hotter so that the air conditioning turns on, the Scripps Research team rea-soned that they could reset the brain's thermostat by producing heat nearby.

To do so, they created a mouse model that produced large quantities of uncoupling protein 2 in hypocretin neurons in the lateral hypothalamus, which is near the preoptic area. The action of uncoupling protein 2 produced heat, which diffused to other brain structures, including the pre-optic area. And, indeed, the extra heat worked to induce a continuous reduction of the core body temperature of the mice, lowering it from 0.3 to 0.5 degrees Celsius.

The scientists were then able to measure the effect of lowered core body temperature on life-span, finding that the mice with lowered core body temperature had significantly longer median lifespan than those that didn't. While this effect was observed in both males and females, in this study the change was more pronounced in females-median lifespan was extended about 20 per-cent in females and about 12 percent in males.

The researchers performed several experiments to make sure that other factors were not con-tributing to the lowered core body temperature. They confirmed that the experimental mice were normal in their ability to generate fever, and that these mice moved around about the same amount as normal mice. In addition, the researchers verified that the hypocretin neurons producing uncoupling protein 2 were not involved in temperature regulation.

Importantly, the mice in this study were allowed to eat as much food as they wished, and the experimental and control mice ate the same amount. The weight of the female experimental and control mice did not differ significantly. However, experimental male mice weighed about 10 per-

cent more than the control group, most likely reflecting the reduced energy required to maintain a lower core body temperature, according to the paper.

"Our model addresses something more basic than the amount of food," said Tamas Bartfai, who is chair of the Molecular and Integrative Neurosciences Department, director of the Harold L. Dorris Neurological Research Center at Scripps Research, and an author of the paper. "It works at the level of the thermoregulatory set point that is governed by intra-brain temperature and neurotransmitters. This mechanism, we believe, will be a good target for pharmacological manip-ulation or heating."

The idea to manipulate the temperature set-point came when Conti and Bartfai joined Scripps Research in the year 2000. Both scientists share common interests in neuroimmunology and the mechanisms of fever. It took over five years of work to conclude this study.

The researchers are now working to identify the precise mechanisms that are responsible for the beneficial effects of reduced core body temperature. They are also investigating whether their findings can be applied to research on obesity.

-------------------------------The findings appear in a paper in the journal Science on November 3.Other authors on the study include Manuel Sanchez-Alavez, Raphaelle Winsky-Sommerer, Maria Concetta Morale, Jacinta Lucero, Sara Brownell, Veronique Fabre, Salvador Huitron-Resendiz, Steven Henriksen, Eric P. Zorilla, and Luis de Lecea, all of Scripps Research.The study was supported by The Harold Dorris Neurological Research Institute, The Ellison Medical Foun-dation, and the National Institutes of Health.

Intact tonsils triple risk of recurrent strep throatROCHESTER, Minn.-Children with recurrent strep throat whose tonsils have not been removed are over three times more likely to develop subsequent episodes of strep throat than children who undergo tonsillectomy, according to a Mayo Clinic study published in the Nov. 2 issue of Laryn-goscope.

"These results suggest that tonsillectomy is a useful therapy for treating children with recur-rent strep throat infections," says Laura Orvidas, M.D., Mayo Clinic ear, nose and throat surgeon and senior study investigator. "It should decrease the amount of infections experienced by this subset of children and therefore diminish the number of missed school days and hopefully im-prove overall quality of life."

Dr. Orvidas and colleagues conducted a population-based retrospective cohort study of chil-dren between ages 4 and 16 who received three or more diagnoses of strep-related tonsillitis or pharyngitis at least one month apart, within 12 months. Within this group, children who subse-quently underwent a tonsillectomy were compared with an age- and sex-matched sample of chil-dren who had not had a tonsillectomy. The date of the tonsillectomy for the matched pair was defined as the index date. All strep infections were recorded for both groups of children.

The study population comprised 290 children (145 who received a tonsillectomy and 145 who did not). In the tonsillectomy group, 74 children experienced at least one strep infection after the index date and before age 16. Among those who did not receive a tonsillectomy, 122 experi-enced at least one strep infection during the follow-up. The time before first subsequent strep in-fection was much longer for those who had a tonsillectomy, a median of 1.1 years as compared to 0.6 years for children whose tonsils had not been removed. By one year after the index date, the cumulative incidence of a strep infection was 23.1 percent among the children who had a tonsillectomy compared to 58.5 percent among the children who had not.

Researchers used the Rochester Epidemiology Project to identify children for the study, which was limited to children who resided in Olmsted County, Minn., between Jan. 1, 1994, and Dec. 31, 1998. The Rochester Epidemiology Project has developed an index for the records of virtually all providers of medical care in Olmsted County. Olmsted County is served by a largely unified medical care system, including Mayo Clinic, that has accumulated comprehensive clinical records since the early 1900s.

"The use of the Rochester Epidemiology Project resource was unquestionably one of the strengths of the study," says Dr. Orvidas. "This resource allowed us to access complete medical records on a geographically defined pediatric population and minimized potential referral and participation biases."

The next step of the research phase, according to Dr. Orvidas, would be a prospective ran-domized trial investigating the use of tonsillectomy for recurrent strep throat infections. Such an investigation could judge outcomes based on the number of subsequent infections and on qual-ity of life issues, she says.

Pharyngitis and tonsillitis are among the most commonly diagnosed pediatric illnesses, ac-counting for approximately 18 million physician office visits per year. Strep infections are re-

sponsible for 15 percent to 30 percent of all cases of pharyngitis. In addition, 20 percent to 30 percent of children who are diagnosed with strep pharyngeal infection may experience a second infection within 60 days of the initial episode.

--------------------------Study authors also include Jennifer L. St. Sauver, M.D., and Amy L. Weaver.

Dopamine Used to Prompt Nerve Tissue to RegrowTeam led by Georgia Tech/Emory researchers induces nerve growth using dopamine-

based polymerATLANTA - When Yadong Wang, a chemist by training, first ventured into nerve regeneration two years ago, he didn’t know that his peers would have considered him crazy.

His idea was simple: Because neural circuits use electrical signals often conducted by neuro-transmitters (chemical messengers) to communicate between the brain and the rest of the body, he could build neurotransmitters into the material used to repair a broken circuit. The neuro-transmitters could coax the neurons in the damaged nerves to regrow and reconnect with their target organ.

Strange though his idea might have seemed to others in his field, Wang, an assistant profes-sor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University, discovered that he could integrate dopamine, a type of neurotransmitter, into a poly-mer to stimulate nerve tissues to send out new connections. The discovery is the first step to-ward the eventual goal of implanting the new polymer into patients suffering from neurological disorders, such as Alzheimer's, Parkinson’s or epilepsy, to help repair damaged nerves. The find-ings were published online the week of Oct. 30 in the Proceedings of the National Academy of Sciences (PNAS).

“We showed that you could use a neurotransmitter as a building block of a polymer,” said Wang. “Once integrated into the polymer, the transmitter can still elicit a specific response from nerve tissues.”

The “designer” polymer was recognized by the neurons when used on a small piece of nerve tissue and stimulated extensive neural growth. The implanted polymer didn’t cause any tissue scarring or nerve degeneration, allowing the nerve to grow in a hostile environment post injury.

When ready for clinical use, the polymer would be implanted at the damaged site to promote nerve regeneration. As the nerve tissue reforms, the polymer degrades.

Wang’s team found that dopamine’s structure, which contains two hydroxyl groups, is vital for the material’s neuroactivity. Removing even one group caused a complete loss of the biological activity. They also determined that dopamine was more effective at differentiating nerve cells than the two most popular materials for culturing nerves - polylysine and laminin. This ability means that the material with dopamine may have a better chance to successfully repair dam-aged nerves.

The success of dopamine has encouraged the team to set its sights on other neurotransmit-ters.

“Dopamine was a good starting point, but we are looking into other neurotransmitters as well,” Wang said.

The team’s next step is to verify findings that the material stimulates the reformation of synapses in addition to regrowth.

“A successful nerve regeneration will require the nerve to synapse with the target organ,” Wang said. “Since we’ve written this paper, we’ve also been able to get the nerves to form ex-tensive synapses, which is a step in the right direction.”

Major breakthrough in the mechanism of myelin formationMontréal-The group of Dr. Michel Cayouette, researcher at Institut de recherches cliniques de Montréal (IRCM), and Dr. Jonah Chan, collaborator at the University of Southern California, will publish in the next issue of the prestigious scientific journal Science, the results of their study that could have a major impact on the treatment of diseases such as multiple sclerosis, and pe-ripheral neuropathies.

At a basic level, our nervous system is like a collection of wires that transmit electrical signals encoding our thoughts, feelings, and actions, both conscious and unconscious. The connections in our brain are formed by neurons that extend to each other and to muscles long wires called axons. Just as an electrical wire needs insulation, our axons require an insulating sheath (myelin) that helps to propagate the electrical signal and maximize the efficiency and velocity of these signals in our brain and body. It is this property (myelination) that facilitates the long-distance communication in our nervous system across junctions called synapses, such that a thought can result in the movement of a finger or a toe. Diseases and injury that compromise the integrity of myelin such as multiple sclerosis, or peripheral neuropathies, have dramatic consequences like

paralysis, uncoordinated movements, and neuropathic pain. The discovery reported in this study sheds light on the mechanisms that control how myelin is formed during development of the nerves. The article, which will be published in the November 3rd issue of Science, constitutes an important step forward in our understanding of the process of myelination, and opens the way to new research in this field.

More specifically, the study showed that a protein called Par-3 is at the base of the myelina-tion process. This protein becomes localized to one side of the myelin-forming cells called Schwann cell, upon contact with the axon that is to be myelinated. Par-3 acts as a sort of molec-ular scaffold to set-up an "organizing centre", which brings together key proteins essential for myelination, in particular a receptor for a molecule secreted by the neurons. The scientists found that when they disrupted this organizing centre, cells could not form myelin normally. Impor-tantly, their discovery demonstrates that Schwann cells need to become polarized so that they know which side of the cell is in contact with the axon so that they can initiate wrapping and bring essential molecules to this critical interface. These studies open the way to new research, which should help to identify other components that are recruited at the organizing centre set-up by Par-3. Importantly, in conditions such as multiple sclerosis or after injury, it is believed that Schwann cells could be used to re-myelinate axons. But so far this approach has proved to be relatively inefficient. Therefore, these experiments bring about the possibility that manipulating the Par-3 pathway in Schwann cells might allow for more efficient re-myelination of damaged or diseased nerves.

-------------------The article can be accessed at www.sciencemag.org

Space Sunshade Might Be Feasible in Global Warming EmergencyBy Lori Stiles

The possibility that global warming will trigger abrupt climate change is something people might not want to think about.

But University of Arizona astronomer Roger Angel thinks about it.Angel, a University of Arizona Regents' Professor and one of the world's foremost minds in

modern optics, directs the Steward Observatory Mirror Laboratory and the Center for Astronomi-cal Adaptive Optics. He has won top honors for his many extraordinary conceptual ideas that have become practical engineering solutions for astronomy.

For the past year, Angel has been looking at ways to cool the Earth in an emergency. He's been studying the practicality of deploying a space sunshade in a global warming crisis, a crisis where it becomes clear that Earth is unmistakably headed for disastrous climate change within a decade or two.

Angel presented the idea at the National Academy of Sciences in April and won a NASA Insti-tute for Advanced Concepts grant for further research in July. His collaborators on the grant are David Miller of the Massachusetts Institute of Technology, Nick Woolf of UA's Steward Observa-tory, and NASA Ames Research Center Director S. Pete Worden.

Angel is now publishing a first detailed, scholarly paper, "Feasibility of cooling the Earth with a cloud of small spacecraft near L1," in the Proceedings of the National Academy of Sciences. The plan would be to launch a constellation of trillions of small free-flying spacecraft a million miles above Earth into an orbit aligned with the sun, called the L-1 orbit.

The spacecraft would form a long, cylindrical cloud with a diameter about half that of Earth, and about 10 times longer. About 10 percent of the sunlight passing through the 60,000-mile length of the cloud, pointing lengthwise between the Earth and the sun, would be diverted away from our planet. The effect would be to uniformly reduce sunlight by about 2 percent over the entire planet, enough to balance the heating of a doubling of atmospheric carbon dioxide in Earth's atmosphere.

Researchers have proposed various alternatives for cooling the planet, including aerosol scat-terers in the Earth's atmosphere. The idea for a space shade at L1 to deflect sunlight from Earth was first proposed by James Early of the Lawrence Livermore National Laboratory in 1989.

"The earlier ideas were for bigger, heavier structures that would have needed manufacture and launch from the moon, which is pretty futuristic," Angel said. "I wanted to make the sun-shade from small 'flyers,' small, light and extremely thin spacecraft that could be completely as-sembled and launched from Earth, in stacks of a million at a time. When they reached L1, they would be dealt off the stack into a cloud. There's nothing to assemble in space."

The lightweight flyers designed by Angel would be made of a transparent film pierced with small holes. Each flyer would be two feet in diameter, 1/5000 of an inch thick and weigh about a gram, the same as a large butterfly. It would use "MEMS" tech-nology mirrors as tiny sails that tilt to hold the flyers position in the orbiting constellation. The flyer's transparency and steering mechanism prevent it from being blown away by radiation pres-sure. Radiation pressure is the pressure from the sun's light it-self.

The total mass of all the fliers making up the space sunshade structure would be 20 million tons. At $10,000 a pound, conven-tional chemical rocket launch is prohibitively expensive. Angel proposes using a cheaper way developed by Sandia National Laboratories for electromagnetic space launchers, which could bring cost down to as little as $20 a pound.

The graphic shows the 2 foot-diameter flyers at L1. They are transparent, but blur out transmitted light into a donut, as shown for the background stars. The transmitted sunlight is also spread out, so it misses the Earth. This way of removing the

light avoids radiation pressure, which would otherwise degrade the L1 orbit. (Illustration: Courtesy of Roger Angel, UA Steward Observatory)

The sunshade could be deployed by a total 20 electromagnetic launchers launching a stack of flyers every 5 minutes for 10 years. The electromagnetic launchers would ideally run on hydro-electric power, but even in the worst-case environmental scenario with coal-generated electric-ity, each ton of carbon used to make electricity would mitigate the effect of 1000 tons of atmo-spheric carbon.

Once propelled beyond Earth's atmosphere and gravity with an electromagnetic launcher, the flyer stacks would be steered to L-1 orbit by solar-powered ion propulsion, a new method proven in space by the European Space Agency's SMART-1 moon orbiter and NASA's Deep Space 1 probe.

"The concept builds on existing technologies," Angel said. "It seems feasible that it could be developed and deployed in about 25 years at a cost of a few trillion dollars. With care, the solar shade should last about 50 years. So the average cost is about $100 billion a year, or about two-tenths of one percent of the global domestic product."

He added, "The sunshade is no substitute developing renewable energy, the only permanent solution. A similar massive level of technological innovation and financial investment could en-sure that.

"But if the planet gets into an abrupt climate crisis that can only be fixed by cooling, it would be good to be ready with some shading solutions that have been worked out."

Four-finned Japanese dolphin an evolutionary throwback, researchers sayA bottlenose dolphin captured last month off western Japan has an extra set of fins, providing

further evidence that ocean-dwelling mammals once had four legs and lived on land, Japanese researchers said Sunday.

Fishermen netted the four-finned dolphin off the coast of Wakayama Prefecture on Oct. 28, and alerted the nearby Taiji Whaling Museum, ac-cording to museum director Katsuki Hayashi.

The second set of fins-much smaller than the dolphin's front fins-are about the size of adult human hands and protrude from near the tail on the dolphin's underside. The dolphin is 2.72 meters long and is about five years old, according to the museum.

Although dolphins and whales with odd-shaped protrusions near their tails have been caught in the past, researchers think this is the first one found with well-developed, symmetrical fins, Hayashi said.

"I believe the fins may be remains from the time when dolphins' ancient ancestors lived on land ... this is an unprecedented discovery," said Seiji Osumi, an adviser at Tokyo's Institute of Cetacean Research, at a news conference televised Sunday.

Divers with the four-finned dolphin. (Mainichi)Hayashi said he couldn't tell from watching the dolphin swim in a museum tank whether it

uses its back fins to maneuver.

Fossil remains indicate that dolphins and whales were four-footed land animals about 50 million years ago and share a common ancestors with the hippopotamus and deer. Scien-tists believe they later transitioned to an aquatic lifestyle and lost their hind limbs.

Whales and dolphin fetuses show signs of hind protrusions but they disappear before birth.

A freak mutation may have caused the ancient trait to re-assert itself, Osumi said.

The dolphin will be kept at the Taiji museum to undergo X-ray and DNA tests, according to Hayashi. (AP)

The dolphin's "legs." (Mainichi)EssayTwilight of the IdolsBy PETER DIZIKES

In 1676, Isaac Newton explained his accomplish-ments through a simple metaphor. “If I have seen far-ther it is by standing on the shoulders of giants,” he wrote. The image wasn’t original to him, but in using it Newton reinforced a way of thinking about scientific progress that remains popular: We learn about the world though the vi-sion of a few colossal figures.

This idea has a literary corollary: the scientific biography, a genre that dates at least to the early 18th century and is flourishing today. Kai Bird and Martin J. Sherwin won this year’s Pulitzer Prize in biography for “American Prometheus,” their portrait of J. Robert Oppenheimer, while at least two dozen English-language biographies of Albert Einstein have been published in the past 10 years alone. Recent works like James Gleick’s “Isaac Newton” and W. W. Norton’s “Great Dis-coveries” series, which includes volumes on Copernicus and Darwin, provide compact profiles of major figures, while waves of science writers have followed Dava Sobel, author of the 1995 smash hit “Longitude,” in chronicling lone mavericks whose insights have - supposedly - changed the world. Three centuries after Newton, we’re still learning our science one genius at a time.

Yet the biography exists in a state of tension with contemporary science, which has become increasingly oriented around massive, collaborative research projects. Today’s insights are not so much perceived from the shoulders of giants as glimpsed from a mountain of jointly authored papers announcing results from large labs, and rapidly circulated through journals, conferences and the Internet. So is the end of the traditional science biography in sight? The genre may be a lens magnifying portions of the history of science, but in time it could seem as antique as Galileo’s telescope. At the least, changes in science itself may demand that science biographers adapt or become extinct.

Paradoxically, one of the biggest problems is the abundance of good scientists. Immediately after the Civil War, there were perhaps 2,000 scientists in the United States. Today American universities award roughly 14,000 science doctorates per year, forming a sea of competence that engulfs even the most distinguished researchers. As James Gleick put it in “Genius,” his 1992 biography of the physicist Richard Feynman, “the world has grown too vast and multifari-ous for the towering genius of the old kind.”

Contemporary science is also far more collaborative than non-scientists may imagine. A giant new particle collider soon to open in Switzerland, for example, will have more than 7,000 physi-cists participating in its experiments. “If you try to understand that kind of work through a biog-raphy,” Peter Galison, a historian of science at Harvard, said in a recent interview, “you’re really cutting the wood against the grain, and you can easily end up making invisible the collective work that’s so crucial for that kind of accomplishment.”

This trend applies even to theorists, who, in the mode of Newton or Einstein, still tackle prob-lems in relative isolation. “The main difference today is there are so many people working on

these deep problems,” the physicist Brian Greene said recently. In one 15-page span of his best-selling book “The Elegant Universe” (1999), Greene mentions 24 scientists whose work prefig-ured a rich period in the development of string theory, the dominant idea in theoretical physics for the past 20 years. Faithfully untangling these various threads makes it harder for any writer to create a linear narrative of discovery, in which a few key influences on one scientist lead to a singular insight.

Indeed, science biography has sometimes distorted its subject by ignoring the communal as-pects of scientific thought. Geology once had a great-man history in which 18th- and 19th-cen-tury British iconoclasts like James Hutton and William Smith discerned the antiquity of the earth, an idea that was absorbed in turn by the geologist Charles Lyell, and then set the stage for Dar-win’s theory of evolution. But as the historian of science Martin Rudwick has shown, a whole net-work of European scientists was advancing geological research in this period. Daniel Kevles, a historian of science at Yale, said recently, “What’s happened in the last 15 or 20 years is that we’ve learned how even the very greatest scientists - Newton, Darwin, Einstein - were always engaged in collaboration of a very important, fundamental nature with their contemporaries.”

For now, Kevles believes, many promising subjects remain untouched: he mentions Sydney Brenner and Paul Berg, two creators of molecular biology; the geologist Harry Hess, who helped develop the revolutionary theory of plate tectonics; and the planetary scientist Carl Sagan. Even contemporary physics, for all its collaboration, still has a few important figures yet to be chroni-cled, like Edward Witten, who - usually working alone - unified disparate ideas in string theory, and produces papers distinctive enough that colleagues like Greene say they would recognize Witten’s work even if it were published anonymously.

And yet any list of possible new science biographies will produce figures whose significance is, effectively, merely scientific. By contrast, physicists like Einstein, Oppenheimer and Werner Heisenberg (the subject of multiple biographies published in the 1990’s that renewed a long-run-ning debate concerning his role in Nazi Germany’s atomic bomb program) did not just create a remarkably productive scientific epoch, but led especially eventful and consequential lives.

How can writers interest audiences in lives rather less resembling Greek dramas? “It may be there’s another side of biography that drops the idea of the heroic figure, but looks at the exem-plary figure,” Galison said. “It could take some retooling to tell that kind of story, where the ac-tors see what they’re doing in more moment-to-moment, pragmatic terms.” Writers may have to look farther outside the scientific pantheon, and abandon comfortable biographical tropes, like the protagonist as an outsider crashing the gates of science - an image that applies to Newton and Einstein, and was self-consciously adopted by Feynman and by James Watson and Francis Crick.

It may also be necessary to portray scientists less often as timeless embodiments of applied reason and more as emblems of contemporary developments. Our era of for-profit biomedical re-search means that momentous discoveries - an AIDS vaccine, new cancer treatments - could place scientists squarely within, say, entrepreneurial sagas in the biotechnology business, a situ-ation already seen in the biologist and entrepreneur Craig Venter’s attempt to profit from genome sequencing. We may make fewer visits to Mount Olympus, but gain more penetrating looks at science in action.

Profiles of scientists may also have to be written increasingly within their lifetimes, and re-searched through interviews, as the epistolary tradition withers and the papers and letters that have so enriched recent scientific biography go “the way of the delete button,” as Kevles puts it. Already, some science writers have used a more limited, journalistic notion of biography to good effect. Jonathan Weiner’s “Time, Love, Memory” (1999) combines a concise portrait of geneticist Seymour Benzer with a survey of the field of behavioral genetics, while John McPhee’s writings on geology, collected as “Annals of the Former World” (1998), outline our understanding of the earth’s history through a series of sketches of little-known but engaging geologists. Books like these create an inversion of biography’s traditional rationale by embracing subjects who are not public figures; there is fascinating work everywhere in science, they imply.

Illuminating those overlooked sources of fascination may be an important part of the genre’s future. “The science biography ... is critical in an era when science gets ever farther afield from everyday experience,” Greene said. “Our human link to that is through the process of discovery, through human stories, so that remains an element that I think has to be preserved.” If our dis-coveries no longer come from the realm of giants, the science biography may have to be con-structed to a more human scale as well.Peter Dizikes is a Boston-based journalist who writes about science.

Futures market maps US mid-term elections winners* 17:01 02 November 2006

* NewScientist.com news service* Will Knight

Predicting the outcome of any election is a gamble, but computer scientists hope the betting instincts of thousands of election watchers could help forecast the results of the 7 November mid-terms.

Researchers from the University of Chicago, US, and Yahoo's research labs have created a map) that aims to predict the election results, based on a simulated market trading system.

The map is linked to a market operated by Irish company Tradesports. This lets users buy or sell shares in different election results, and reap a financial pay out if their hunch proves correct. While no individual user may be able to predict the outcome correctly, the idea is that the "wis-dom of crowds" could produce an accurate forecast.

Lance Fortnow, a computer scientist at the University of Chicago, created the market-tracking map with help from Daivd Pennock and Yiling Chen of Yahoo Research. Fortnow says the ap-proach has proved very accurate in the past.

"In 2004, these markets correctly predicted all but one of the senate races and every state correctly in the electoral collage," Fornow says. "We put the map together to highlight the importance of these markets and let people get a quick view of what the markets say."Success forecast

So-called "prediction markets" have a long history but have grown in prominence in recent years. Some com-panies, including Google, Microsoft and HP, use internal market systems to forecast the likely success of a new product, for example.

Yahoo also runs a prediction market called Tech Buzz), that lets users buy shares in search engine queries using pretend money, thus predicting the future "popularity" of the terms involved.

The election map provides a quick picture of the market predictions as they stand today (Image: Lance Fortnow)

In 2003 the US Pentagon created a futures exchange designed to predict political develop-ments, including terrorist attacks, which was widely criticised and swiftly cancelled (see Penta-gon cancels futures market on terror).

Despite this controversy, Pennock believes prediction markets are gradually increasing their credibility. "This area is definitely gaining traction, both in the academic world and maybe even more so in the corporate world," he says.

Some experts question the reliability of prediction markets. One concern is wilful manipula-tion. During the 2004 presidential elections Tradesports users allegedly tried to sway the predic-tion market by selling shares for an artificially low price. This attempt failed, however, and other studies have found evidence that prediction markets are surprisingly resilient to such efforts.

Alzheimer's progress 100 years onOne hundred years since Alzheimer's disease was first described, scientists are still strug-

gling to find a cure for it, a group of experts has said.There is much that can be done to dampen its effects, but the prospect of defeating the dis-

ease remains elusive, they say in the Lancet medical journal.The core principles of care remain the same - support and compassion, the article says.But scientists remain hopeful that a cure is around the corner.

100 years agoOne hundred years ago, German neurologist Alois Alzheimer described the case of his patient

Auguste D, a woman who developed dementia in her 50s and died in 1906.He documented: "Auguste D suffered from constant restlessness and anxious confusion."At night she was usually put in an isolation room because she could not fall asleep in the

main ward; she went to other patients' beds and woke them."His care plan included "afternoon rest, early dinners and evening bowel evacuations", as well

as soothing baths and alcohol and mild sedation to aid sleep, all given in a tolerant and appropri-ately stimulating environment.Today

A century on, experts understand more about the disease and can spot it earlier. There is even promise of an Alzheimer's blood test.

But there is still no cure, or way to prevent the onset of the disease. In our lifetime, some level of cure is possible

Professor Simon Lovestone, of the Alzheimer's Research TrustThe practice of care may also have changed, but the core principles remain the same, Profes-

sor Alistair Burns, from the University of Manchester, and international colleagues argue in The Lancet.

Professor Burns explains: "The main differences from the care delivered in Frankfurt 100 years ago would result from the diagnostic precision now available, the evidence-based drug treat-ments developed over the past 20 years, and the availability of support to educate and advise carers.

"Nevertheless, in 2006 disease management would hinge, as it did 100 years ago, on the ef-fects of a compassionate team of professionals' working with the patient and her family to achieve the best possible outcome.Incurable?

Professor Simon Lovestone, chairman of the Alzheimer's Research Trust's scientific advisory board, is optimistic that the disease will soon be curable.

He said: "In our lifetime, some level of cure is possible."While we may not completely regain what has been lost in brain function, some effects of

Alzheimer's disease will be reversible. And many, many more lives will be vastly improved."But Dr Hugh Pearson, from the University of Leeds, says major obstacles to curative treat-

ments exist. ALZHEIMER'S DISEASE FACTSA progressive, degenerative and irreversible brain disorderSymptoms include memory problems and difficulty performing everyday tasksThere is no single diagnostic test

He explained: "These are lack of a very early diagnosis of the disorder and the fact that the death of neurones in the brain cannot easily be reversed. If these two obstacles can be over-come then the disease can be beaten."

Professor Seth Love, director of the South West Dementia Brain Bank in the University of Bris-tol, is also cautious.

He believes that because of the complex nature of Alzheimer's disease, it is unrealistic to ex-pect that a single drug or other intervention will be effective in preventing or curing the disease.

"However, by encouraging people to make changes to their lifestyles, such as diet, to lower their risk, and by targeting interventions against the final common pathways involved in the de-velopment of Alzheimer's, I believe we shall steadily make progress in preventing and treating the disease."

In Science Magazine, US experts say many new therapies directly targeting the mechanisms underlying Alzheimer's disease are in the pipeline.

These include drugs to block the formation of the protein-rich brain lesions or plaques that characterise the disease.Protection

Rebecca Wood, chief executive of the Alzheimer's Research Trust, says much research now is focused on how to prevent Alzheimer's.

"We are doing two big studies on diet. One is looking at B vitamins for lowering homocysteine levels, which appear to be linked to Alzheimer's as well as heart disease. The other is looking at omega three fish oils.

"Also there is a lot of work showing that exercise, particularly being taken in middle age, can make a difference.

"If we can persuade people to have a much better diet and increase their exercise level and keep their brain active by doing things like crosswords, that will help to stave off the risk of Alzheimer's."

With aging populations, particularly in the UK, the need to prevent and find a cure for Alzheimer's has never been more pressing, she said.

"The number of people with Alzheimer's is going to double in the next 20 to 30 years," she warned.

An estimated 25 million people worldwide have Alzheimer's disease.Story from BBC NEWS: http://news.bbc.co.uk/go/pr/fr/-/2/hi/health/6109086.stm

Web inventor fears for the futureBy Pallab Ghosh

Science correspondent, BBC NewsThe British developer of the world wide web says he is worried about the way it could be used

to spread misinformation and "undemocratic forces".The web has transformed the way many people work, play and do business.

But Sir Tim Berners-Lee told BBC News he feared that, if the way the internet is used is left to develop unchecked, "bad things" could happen.

He wants to set up a web science research project to study the social implications of the web's development.

The changes experienced to date because of the web are just the start of a more radical transformation of society, he said.

But Sir Tim is concerned about the way it could end up being used.He told the BBC: "If we don't have the ability to understand the web as it's now emerging, we

will end up with things that are very bad."Certain undemocratic things could emerge and misinformation will start spreading over the

web."Studying these forces and the way they're affected by the underlying technology is one of

the things that we think is really important," he said.Social phenomenon

He insisted his new web science research initiative would be more than just computer science.He said he wanted to attract researchers from a range of disciplines to study it as a social as

well as technological phenomenon.Sir Tim added that he hoped it would create a new science for studying the web, which he be-

lieves would lead to newer and more exciting systems."All kinds of disciplines are going to have to converge. People with all kinds of skills are going

to have to work together to build a new web which is going to be even better," he said.He also said employers were now beginning to complain that there were not enough people

who fully understood the web."There aren't any courses at the moment and it hasn't really been brought together."We're hearing complaints from companies when they need people that really understand the

medium from both the technological and social side."When you look at university courses, web science isn't there - it seems to fall through the

cracks."So we'd like to put it on the curriculum so that there are a lot more people who understand

this."Social challenges

The US-based Massachusetts Institute of Technology and the University of Southampton, UK, will launch the long-term research collaboration that will have a direct influence on the future development of the world wide web.

The Web Science Research Initiative will chart out a research agenda aimed at understanding the scientific, technical and social challenges underlying the growth of the web.

Of particular interest is the growing volume of information on the web that documents more and more aspects of human activity and knowledge.

The project will examine how we access this information and assess its reliability.Story from BBC NEWS: http://news.bbc.co.uk/go/pr/fr/-/2/hi/technology/6108578.stm

Global Warming Could Trigger Insect Population BoomBy Abigail W. Leonard

Special to LiveScienceA rise in the Earth’s temperature could lead to an increase in the number of insects world-

wide, with potentially dire consequences for humans, a new study suggests.New research shows that insect species living in warmer areas are more likely to undergo

rapid population growth because they have higher metabolic rates and reproduce more fre-quently. The finding has scientists concerned that global warming could give rise to more fast-growing insect populations and that we could see a spike in the number of six-legged critters.

The consequences could be more serious than just a few extra bug bites each summer. “If they’re crop species, we could count on needing to use more pesticides and it could be very costly,” said Melanie Frazier, a doctoral student at the University of Washington and lead author of the study.

Insect-borne diseases are also a worry. Malaria, Lyme Disease and a host of others rely on in-sect vectors to spread among humans, and a swell in their populations could mean more infec-tions.

Already, scientists have observed a widening of malarial zones with new cases appearing in previously unaffected areas. The change is thought to be due to rising temperatures and an ex-pansion of areas habitable for mosquitoes. The new research, detailed in the October issue of The American Naturalist, shows rising temperatures would mean insects would not only spread out, but also multiply more quickly.

Still, Frazier says it’s too soon to predict which species will adapt and which might even face extinction. She and her colleagues looked at 65 insect species and found a correlation between warm climes and population growth across the board – but, she cautioned, the scientists have no way of predicting which species will eventually adapt to new, warmer areas.

We won’t have to wait long to find out. Insects adapt quickly, so we will likely see changes within our lifetime, Frazier says.

Bright Idea: Light Bulb Burns Away TumorsBy Charles Q. Choi

Special to LiveScienceBeams of light concentrated from a light bulb could soon help burn away tumors in surgical

operations that are as effective as laser surgery but 100 times cheaper, scientists in Israel now report.

Laser surgery pumps beams through optical fibers to zap diseased cells. The method is both highly effective and minimally invasive, but is unavailable to many patients worldwide "due to exorbitant cost," researcher Jeffrey Gordon, a physicist at Ben-Gurion University of the Negev in Sede Boqer, Israel, told LiveScience. Current laser fiber-optic surgical systems commonly cost upward of $100,000, he explained.

In place of expensive lasers, Gordon and his colleagues harnessed light from more common-place sources. Initially, the researchers experimented with sunlight because it's free, but sun-light is only available during the daytime and is dependent on weather conditions.

Instead, Gordon and a team of engineers, physicists, surgeons and pathologists turned to xenon short-arc discharge lamps, the ultra-bright kind now used in movie projectors. In their sys-tem, a series of mirrors collects and focuses light from the lamp down a flexible optical fiber into an operating theater, where it emerges as cones of rays from the millimeter-sized tip of a sur-geon's tool [image].

Gordon and his colleagues have now for the first time demonstrated their system in proof-of-principle operations on the livers and kidneys of live rats [image], showing efficacy comparable to laser fiber optic treatments.

Future research will test this system against malignant growths."A Singaporean company, Ray Medical Private, is currently embarking upon commercialization

of our lamp surgery invention in close collaboration with us," Gordon said. Optimistically, they could have surgeon-friendly units in a year or two for testing, he added.

Gordon and his colleagues published their findings online October 24 in the Journal of Biomedical Optics Letters.

Novel experiment documents evolution of genome in near-real timeResearchers identified all the changes in a bacterium's complete set of genes during a 44-

day evolution experimentA team led by bioengineering researchers at UC San Diego report in the November issue of

Nature Genetics rapid evolutionary changes in a bacterial genome, observed in near-real time over a few days. Scientists have previously published static "snapshots" of the genome se-quences of more than 100 bacterial species, from the harmless to those that cause plague, but this new report shows how these genomes are moving targets.

"Paleontologists look at the fossil record to study how evolution of dinosaurs and other ani-mals occurred over millions of years, but in the case of the E. coli bacterium, new technology has given us the ability to observe evolution as it is occurring over a matter of days," said Bernhard Ø. Palsson, the senior author of the study and professor of bioengineering at UCSD. "The pub-lished genomic sequences of bacteria are like a fossil record and our experiments confirm that these genomes can change quickly as bacteria adapt to new conditions."

Because of past technical limitations, biologists have historically made inferences about rapid bacterial evolution by carefully observing changes in a handful of genes at a time or by monitor-ing the visible characteristics, or phenotypes, as the organisms adapt. Palsson's team used com-parative genome sequencing technology developed by NimbleGen Systems Inc., a Madison, WI-based biotech firm, to identify changes that occurred during the experiment in the bacterium's complete set of genes.

In a paper scheduled for online publication Nov. 5 on Nature Genetics's Website, the re-searchers report that they grew E. coli in an environment that favored the emergence of mu-tants: the organism was fed a poorly metabolized carbon and energy source called glycerol. The researchers removed samples of cells from the culture and sequenced their entire genomes as a way to find mutations that enabled faster growth.

After six days of growth, mutations appeared in the gene for an enzyme that initiates the process of enzymatically breaking down glycerol. Cells with mutations in the so-called glycerol kinase gene grew 20 to 60 percent faster than those without the mutation.

Mutations also appeared in a second, unrelated gene for an enzyme called RNA polymerase. "That was a surprise to almost everybody because RNA polymerase is involved in one of the core processes of any cell," said Palsson. "You wouldn't expect that gene to change because a wide variety of cellular process would be affected; it's like replacing the wiring system in a building when a light bulb burns out. But we repeated the experiment more than 50 times and mutations in the RNA polymerase gene appeared again and again."

The researchers report that mutations in both genes appeared together in several cases after six to eight days in the glycerol-based cultures, and E. coli cells containing both mutated genes grew 150 percent faster than the starting strain of E. coli. To confirm that the mutants were in-deed responsible for the faster growth, the researchers substituted the two mutant genes into the original strain and duplicated the faster growth rate. "We expected to find many mutated genes and we thought our results would be very difficult to understand, but neither was the case," said Christopher D. Herring, a co-author of the paper and a former member of Palsson's team who is now a research scientist at Mascoma Corp. in Lebanon, NH.

All the mutants arose in the experiments presumably as the result of naturally occurring er-rors in copying DNA into daughter cells during cell division. The precise changes in the sequence of DNA subunits were determined with comparative genomic sequencing technology from Nim-bleGen Systems, and further analyzed with technology from Sequenom Inc., a San Diego-based biotech company.

"This straightforward approach to the study of experimental evolution can be used as a tool for discovery and analysis, and could even be used to discover bacterial capabilities that would benefit humankind in a variety of ways," said Herring. "There may be a number of biotech com-panies that want to use this new approach to help design bacteria to do useful jobs."

UCSD's office of Technology Transfer and Intellectual Property Services has filed U.S. patent applications related to the experimental evolution approach. The approach combines computer modeling techniques with evolutionary design processes to optimize bacteria to perform com-mercially important processes. Aside from its commercial potential, experimental evolution of bacterial strains is also useful for refining the theory of evolution and the related process of nat-ural selection of individuals with traits that convey a selective survival advantage. "Opinion sur-veys indicate that many people don't believe that evolution occurs," said Herring, "but if the skeptics could witness evolution actually occurring, as we did, I think they'd be more likely to be-lieve that it's not just a theory."

Helpful fevers come in from the cold* 18:00 05 November 2006

* NewScientist.com news service* Andy Coghlan

Fevers speed up the identification and neutralisation of infections, new research has shown, raising new questions over whether it is always wise to combat fevers with drugs and cold com-presses.

Doctors already know that bacteria and viruses thrive best at body temperature, so fevers dis-rupt their ability to multiply. Now it has been found that fevers help the body’s immune system identify an infection and raise an army of white blood cells (lymphocytes) against it.

“We’re not advising against cooling fevers, but our results raise questions about the advan-tages of lowering temperature,” says Sharon Evans, who carried out the research with col-leagues at the Roswell Park Cancer Institute in Buffalo, New York, US. “We have found a physio-logical mechanism for improved immune surveillance,” she adds.

Evans’s team artificially created a fever-like state in a group of mice by confining them at 39.5°C – 2.6°C higher than normal. This had the effect of doubling the number of lymphocytes visiting lymph nodes, they found.Killer efficiency

The lymph nodes are the body’s screening tool. Lymphocytes arriving at the nodes are screened for “killer efficiency” using fragments of potentially infectious material. Lymphocytes that respond to the fragments are found, are then selectively multiplied, and then swarm into the bloodstream to seek out and destroy the invader.

The sooner an infectious agent is identified and an “army” of lymphocytes raised to kill it, the sooner an infection can be brought under control. Evans concludes that fever helps by accelerat-ing the surveillance process.

She found that heat activates “gatekeeper” cells in lymph nodes so that they attract and sum-mon more lymphocytes into the nodes than usual. “It’s an attempt to accelerate identification and eradication of infection,” she says.

The gatekeepers – also called high endothelial venule cells – become more “sticky” by produc-ing extra surface proteins which capture passing lymphocytes and draw them into the lymph nodes.

“This study shows the effects fever has at a molecular level, letting more lymphocytes stick to and enter the lymph nodes,” comments Andrew Luster at the Massachusetts General Hospital in Charlestown, US, who was not involved in the research.Fever fashion

The team is now investigating how to fine-tune fever and deploy it in treatment. Fevers usu-ally begin with local inflammation, which makes infected tissue hotter. Signalling chemicals called cytokines are released from the site of inflammation into the bloodstream and reach the hypothalamus in the brain, which acts as the body’s temperature gauge.

If the infection escalates, the hypothalamus can raise the temperature of the entire body, which then activates the accelerated surveillance and response system in the lymph nodes iden-tified by the research team.

Evans says that although it fell out of fashion with the development of modern medicine, the idea of treating disease with heat has a long history: “Hippocrates used to heat patients with cancer,” she says. And a century ago the physician William Coley discovered a cocktail of bacte-ria, dubbed “Coley’s toxins”, which appeared to combat cancer by producing a fever.

Evans cautions against letting fevers run riot, however, as they can cause fits or even kill by overheating organs such as the liver and brain. But she is hopeful that fever-based therapies might be refined to improve existing treatments for infections, auto-immune diseases and can-cer.Journal reference: Nature Immunology (DOI: 10.1038/ni1406)

Zapping sleepers’ brains boosts memory* 18:00 05 November 2006

* NewScientist.com news service* Roxanne Khamsi

Applying a gentle electric current to the brain during sleep can significantly boost memory, re-searchers report.

A small new study showed that half an hour of this brain stimulation improved students’ per-formance at a verbal memory task by about 8%. The approach enhances memory by creating a form of electrical current in the brain seen in deep sleep, the researchers suggest.

Jan Born at the University of Luebeck in Germany, and colleagues, recruited 13 healthy medi-cal students for the study and gave them a list of word associations, such as “bird” and “air”, to learn late in the evening. Afterwards, researchers placed two electrodes on the forehead and one behind each ear of the volunteers and let them sleep.

The students’ various sleep stages were monitored using an electroencephalogram (EEG) ma-chine. When the students entered a period of light sleep, Born’s team started to apply a gentle current in one-second-long pulses, every second, for about 30 minutes. The EEG readings re-vealed that this current had put students into a deeper state of sleep.

The next morning, the students performed about 8% better on the word memory test than when they underwent the same type of memory experiment without brain stimulation.Nerve firing

Born believes this memory boost was due to the pattern of the applied current mimicking that seen in naturally occurring deep sleep, where memory consolidation is thought to take place.

Strong brain currents in this stage of sleep probably cause more intense nerve firing, he says, which might enhance activity in the brain’s memory centre, the hippocampus.

Some researchers are sceptical of Born's "mimicking deep sleep" theory, however. Felipe Fregni at the Harvard Center for Non-invasive Brain Stimulation in Boston, US, says that he and other scientists have shown that brain stimulation with non-sleep-type currents can produce sim-ilar memory enhancements.Potential side effects

There is growing evidence that brain stimulation might one day help improve memory in pa-tients with dementia or other forms of cognitive impairment, experts say.

“It could be very useful to restore function in people with brain injury,” says Daniel Herrera at Weill Medical College of Cornell University in New York, US, who has studied the effects of brain stimulation in rats.

Healthy people might eventually try using this approach to maximise their brainpower, Her-rera says: “I think every single medical student in the country might want to plug into this type of device at home or in the dorm.” But he stresses that applying electrical currents to the brain might have unwanted side effects.

Born also says he would be "a little hesitant” to regularly use brain stimulation during sleep to boost memory: “In the end we don’t know if there are adverse side effects that we just don’t recognise at the moment.”Journal reference: Nature (DOI: 10.1038/nature05278)

Fantastic Images of the SunThe Solar Optical Telescope (SOT) onboard Japan's Hinode spacecraft has opened its doors

and started snapping pictures. Shown below is a "first light" image taken Oct. 23rd. The light and dark blobs are solar granules, masses of hot gas that rise and fall like water boiling atop a hot stove. Each granule is about the size of a terrestrial continent. SOT has no trouble seeing such detail from Earth-orbit 93 million miles away.

"We have confirmed that SOT is achieving a very high angular resolution of 0.2 arcseconds, a primary objective of the instrument," says the Japan Aerospace Exploration Agency (JAXA) in a statement released Oct. 31st. One arcsecond is an angle equal to 1/3600 of a degree - or ap-proximately the width of a human hair held thirty feet away.

Hinode (Japanese for Sunrise, formerly known as Solar B) was launched on Sept 22nd from the Uchinoura Space Center in Kyushu, Japan. "It's on a mission to study the sun - specifically sunspots, which give rise to powerful flares and solar storms," says John Davis, the NASA Solar-B project scientist at NASA's Marshall Space Flight Center. Astronomers have been studying sunspots since the days of Galileo four hundred years ago, but they still don't know how to pre-dict flares. Data from Hinode may solve the mystery.

Hinode carries three advanced space telescopes:The Solar Optical Telescope (SOT) provides crystal-clear im-

ages of features on the sun's surface. A vector magnetograph attached to the SOT will be able to trace sunspot magnetic fields, which harbor energy for explosive flares. (Engineers are still bringing the vector magnetograph online.)

The X-ray telescope (XRT) can see million-degree gas caught in the magnetic grip of sunspots and, higher up, floating in the sun’s atmosphere, the corona. For reasons no one under-stands, the sun's corona is much hotter than the sun's surface - another mystery Hinode may help solve.

First light for the XRT was achieved on Oct 25th: image.The Extreme Ultraviolet Imaging Spectrometer (EIS) is a device that can tune into specific

spectral lines emitted by ions in the sun's atmosphere. By watching these lines shift back and forth (the Doppler Shift), astronomers can keep track of solar material as it moves around. Dy-namic movies from the EIS will not only entertain, but also provide crucial clues to solve the dual mystery of flares and coronal heating. First light for the EIS was obtained on October 28th.