New method devised for protecting private data

Companies and organizations that keep sensitive personal information on millions of Americans have become attractive targets for hackers in recent years, resulting in billions of dollars in losses for U.S. businesses and misery for countless consumers.

But now Amit Sahai, an associate professor of computer science at the UCLA Henry Samueli School of Engineering and Applied Science, and his colleagues have devised a new data-protection method they hope will put Internet criminals out of business.

"We want to change the rules of the game on hackers and even out the playing field," Sahai said.

Along with co-authors Brent Waters, a UCLA computer science alumnus, and Jonathan Katz of the University of Maryland, Sahai has come up with a mathematical system -- known as functional encryption -- that will not only help to simplify the encryption of data in servers but will also allow access to the data in an intuitive way, making it much harder for hackers to gain access to sensitive information but much easier for programmers to secure it.

While the method is not yet available for public use, it has received close attention from the data-encryption community. The authors' study, chosen as one of the top four papers at Eurocrypt 2008 -- one of two flagship international conferences in cryptography -- was presented this week at the conference in Istanbul.

In it, Sahai and his colleagues suggest that the biggest problem in data security today is that the world relies on "trusted servers" to store and secure data.

"This 'trusted server' model is a simple model," Sahai said. "It's easy to implement. It's easy to put into practice. Information is placed in the server at face value and the server itself is simply given the task of deciding who to give the data to. Because of the simplicity in programming, these servers have become ubiquitous and are prime targets -- everyone wants to attack them."

An additional problem with trusted servers, the authors say, is the current trend toward replicating data on a wide scale.

"To create robustness and availability, data is stored on several trusted servers as backups," said Waters, currently with the nonprofit research institute SRI. "If one server goes down, another can be accessed. There is a trade-off between data availability and security. The more replicated servers there are, the more targets there are for hackers."

The results of this lack of security speak for themselves. According to a 2007 FBI analysis, Internet crime costs U.S. businesses some $67 billion annually, including the indirect expense of repairing hacked systems. TJX, the parent company of discount clothing chains T.J. Maxx and Marshalls, revealed that during a recent 18-month period, hackers had stolen 45.6 million credit card numbers and other sensitive customer information. For every two Americans, one private record has been stolen through computer data breaches alone.

Cryptography, the practice and study of hiding information, is considered to be a branch of both mathematics and computer science and is closely tied to information theory, computer security and engineering. And while the technology of encryption has been around a long time, encrypting data and then deciding how to allow access to hundreds or even thousands of people has been a dilemma, Sahai said.

"Imagine current encryption technology as a lock and key -- the data is locked, and to allow different people access, many copies of the key need to be made," he said. "One record might need to be accessed by 10,000 people, so you make 10,000 copies of that key. With millions of documents and thousands of keys per document, you can imagine how very, very complicated it gets. It becomes much too complicated to manage. So even though we've had very strong encryption technology now for decades, it's just not used, or it is used incorrectly."

The study authors' new functional encryption method allows a programmer to simply plug in his criteria for the information. The mathematical system will then produce an encrypted record that only people matching the criteria can decrypt. The complex system of managing many keys is now simplified, and servers hold encrypted data that the servers themselves can't read. The information looks like gibberish to hackers.

In addition, the new mathematical system allows for keys to be personalized -- only one key is needed to unlock all the information that is available to that person.

"This is the key innovation in our system," Sahai said. "We have this mathematical method for randomization of personalizing keys so that your key doesn't just depend on what attributes you have, like what your name is. Further, there is some mathematical hardening that is personalized to you, so that you can't combine it with anyone else's keys to do anything meaningful."

The system severely restricts what a hacker can do. If he is an insider, he is limited by what access he legitimately has, and since keys are personalized, it becomes much easier to trace who accessed and released the information in the first place.

Sahai and Waters are considered the founders of the area of functional encryption. Sahai recently won a prestigious 2007 Okawa Research Grant Award from Japan's Okawa Foundation for his work in this area.

"Some of this work is already being implemented and is actually being incorporated into some research systems," Sahai said. "It's making its way closer to practice. Brent and I were able to apply for a patent on the very initial work we did, which was bought by a company called Voltage Security. There certainly is interest from the U.S. military and the U.S. Department of Homeland Security as well."

"Our goal is to rethink what encryption is," Waters said. "Over the years, people have taken on a somewhat rigid view of what encryption is. What we're hoping to do is show that we can build simpler and more powerful systems by changing the way we think. Eventually, we hope to get rid of complex infrastructures and do things in a simpler manner that is also more secure and cost-effective."

VIA

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Gene variant increases risk of asthma

A tiny variation in a gene known as CHI3L1 increases susceptibility to asthma, bronchial hyperresponsiveness and decline in lung function, researchers report early online in the New England Journal of Medicine. (The printed version will appear in the April 17 issue). The gene variant causes increased blood levels of YKL-40, a biomarker for asthma. A slightly different version of the genetic variation lowers YKL-40 levels and protects against asthma.

Although the original discovery came from a study of a genetically isolated population, the Hutterites of South Dakota, the researchers were able to confirm the same connections between the CHI3L1 variations, YKL-40 levels and asthma susceptibility in three genetically diverse Caucasian populations from Chicago; Madison, Wisconsin; and Freiberg, Germany.

This gene, "may have important implications in the early identification of, susceptibility to, and prevention and treatment of asthma,” said Elizabeth G. Nabel, M.D., director, the National Heart, Lung, and Blood Institute.

"This is exciting because it connects asthma susceptibility to a whole new pathway at the protein and the genetic levels," said study author Carole Ober, professor of human genetics at the University of Chicago Medical Center. "There is a good deal more we need to find out about this connection, but now we know where to look."

"This is also the most significant genetic discovery based on our years of gathering data on asthma in the Hutterites," Ober added. "This is a group with enormous potential to advance our understanding of the genetic underpinnings of disease. We now have a remarkable collection of data, which we expect will lead us to many more insights."

Ober and colleagues at the University of Chicago had long been searching for genetic factors that could influence the risk of common diseases, such as asthma. To simplify this quest, they have focused since 1994 on the Hutterites, a genetically isolated U.S. religious community descended from about 90 people. The Hutterites came to the United States in 1874 and settled in small communal farming colonies in what is now South Dakota. Today Hutterite communities are present in the Dakotas, Minnesota, Montana, Washington and Canada.

They provide an ideal community for genetic studies because they are all members of a large pedigree that is known back to the 1700's and they live communally, sharing resources and maintaining a traditional lifestyle. "They eat the same food, live off the same allowance and have the same education," said Ober, who has been working with them since 1979. They have similar, but not identical genomes. "So the genes that make a difference are easier to detect."

In 1996 and 1997, Ober's team gathered clinical data about asthma from more than 700 members of the Hutterite communities, and stored blood samples that were recently used to measure YKL-40 levels. About 11 percent of Hutterites had asthma and another 12 percent had bronchial hyperresponsiveness.

The genetic studies took on a sharper focus in 2007, when a team led by Geoffrey Chupp of Yale University showed that, on average, patients with asthma had higher levels of the protein YKL-40 in their blood than people without asthma, and that those with more severe asthma had even higher levels.

YKL-40, a natural suspect as a cause of asthma, belongs to a family of enzymes called chitinases. These enzymes are part of the innate immune system's response to chitin, a common biologic polymer found especially in insects – including dust mites and cockroaches, which have been associated with asthma – as well as in certain disease-causing organisms, including fungi and parasitic worms. The chitinases help break down chitin. They also trigger inflammation, which is a central component of asthma.

Working with Chupp's laboratory, Ober found that mean YKL-40 levels were also increased among Hutterites with asthma or hyperresponsive airways. Ober's group also showed that these elevated YKL-40 levels were handed down from generation to generation, indicating that differences between individuals were due nearly entirely to genetic differences.

So they began looking for variations in the CHI3L1 gene on chromosome 1 that codes for YKL-40. They found one very slight genetic difference between those with asthma and those without. Hutterites with asthma were more likely to have a small but consistent variation in one part of the gene, called a promoter, which regulates when the gene is expressed.

That variation changes one DNA base pair, out of the 3 billion in the human genome, at a location in the CHI3L1gene known as -131C/G. Those with asthma were more likely to have a cytosine (C), rather than guanine (G) at this location.

Those inheriting two copies of a C at -131 had higher YKL-40 levels and an asthma prevalence of 0.20. Those with CG had intermediate YKL-40 levels and an asthma prevalence of 0.12. Those with GG had the lowest YKL-40 levels and a prevalence of only 0.08, less than half that of the CC allele.

To see if these results could be generalized from the genetically isolated Hutterite population to a more diverse group, the researchers tested the same variations in the CHI3L1 gene in 178 Caucasian children enrolled in prospective birth cohort, known as COAST, a collaboration led by Robert Lemanske of the University of Wisconsin at Madison.

They also looked for correlations between asthma and SNP -131C/G in two clinical samples, one from the Children's University Hospital in Freiberg, Germany (344 children with asthma and 294 without), and one from the asthma clinics at the University of Chicago Medical Center (99 children and adults with asthma and 197 without).

In the two clinical samples, those with the CC configuration at position 131 were more likely to have asthma, with CG intermediate and GG the lowest risk of the disease. In the COAST cohort, many subject were still too young to have developed asthma, but the genetic patterns was closely associated with YKL-40 levels, and this association was already present at birth.

The authors suspect that the change from C to G at this site reduces expression of the gene, resulting in lower levels of YKL-40 and protection from asthma.

Although variation in CHI3L1 appears to be one of the most significant genetic triggers yet discovered for susceptibility to asthma, it is far from the sole cause of the disease, the researcher caution. In the Hutterites, it explains 9.4 percent of the variance in YKL-40 levels, suggesting that additional genetic variants also influence these levels. Finding those variations "could identify additional genes," they add, "with significant impact on asthma risk and lung function."

"This evolutionarily ancient pathway involving the innate immune system plays a surprisingly important role in asthma pathogenesis," said Ober, "and a single genetic variant in the CHI3L1 gene may account for most of this risk."

This could have a significant impact on drug development, she added. "For some people, if you block YKL-40 you might dramatically reduce the severity of the disease. Knowing the genotype at SNP -131C might identify those who most likely to benefit from such a treatment."

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Scientists show first 3-D image of antibody gene

Using a multidisciplinary mix of geometry, biological research and techniques developed to solve problems on supercomputers, scientists at the University of California, San Diego have shown for the first time how a genome is organized in three-dimensional space.

The 3-D structure of the immunoglobulin locus in B cells is shown, with the relative positions of the different portions of the immunoglobulin genes. Grey objects indicate constant regions. Blue objects indicate proximal variable regions. Green objects indicate distal variable regions. Red line indicates the linker connecting the proximal variable and joining regions.

Researchers led by Cornelis Murre, a professor of biology at UC San Diego, and Steve Cutchin, senior scientist for visualization services at the San Diego Supercomputer Center (SDSC), used the gene encoding the immunoglobulin heavy chain locus — responsible for generating diverse kinds of antibodies — to demonstrate the structure of the genome.

The observations, the researchers say, permit an insight into the structure of the human genome, which until now has remained elusive.

Their results, “The 3-D Structure of the Immunoglobulin Heavy Chain Locus: Implications for Long-Range Genomic Interactions,” are published in the April 18 issue of the journal Cell.

Because the genome is the most essential part of the cell for storing and accessing genetic information, the complete DNA sequence of a wide variety of genomes has been revealed in studies performed in a large number of laboratories — “a tremendous success that has provided insight into mechanisms that underpin the development of a wide variety of diseases,” the authors say.

However, Murre said, “it has remained unclear as to how the genome is organized in three-dimensional space. This is an important issue since the regulation of gene expression is controlled by interactions of genomic elements that are separated by large genomic distances. Thus, our team wanted to determine how the genome is structured within the nucleus.”

The experiments described in the Cell paper, he said, provide a first glimpse into this question. “As a model system, we used the gene encoding for the immunoglobulin heavy chain locus, because it is responsible for generating the wide diversity of antibodies.”

Having measured the distances that separate the various parts of the gene, Murre said, the researchers, in collaboration with Cutchin at the SDSC, then used geometry to resolve the first structure of a genetic locus.

His work, said Cutchin, involved computational geometry, scientific visualization, computational methods and numerical methods.

“The resulting structure shows that the antibody gene is organized into ‘flower-like’ structures that are connected by linkers,” said Murre. “These flowers contain the various parts that ultimately generate the wide variety of antibodies. This is the first time that geometry has been used to determine the structure of a genetic locus. Ultimately, the same approach should be used to elucidate the structure of the entire human genome.”

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Release of Darwin’s papers includes first draft of Theory of Evolution

The first draft of Charles Darwin’s Theory of Evolution is among thousands of his private papers made accessible online for the very first time.

For decades these were only available to scholars at Cambridge University Library.

But they can now be seen free of charge by anyone around the globe at Darwin Online (http://darwin-online.org.uk/).

The publication of Darwin’s private papers is the largest in history, totalling about 20,000 items in nearly 90,000 images.

As well as the first draft of his theory of evolution, the vast collection of Darwin-related items includes thousands of notes and drafts of his scientific writings, notes from the voyage of the Beagle - with his musings on Galapagos birds - and his first recorded doubts about the permanence of species. It also contains photographs of Darwin and his family, newspaper clippings, reviews of his books and much more.

On a less scientific note, there is material revealing Victorian family life such as Emma Darwin’s recipe book. Contained within are delicacies such as 'Ilkley pudding'; and a rudimentary recipe for boiling rice, scrawled in Darwin’s own handwriting.

Dr John van Wyhe, Director of The Complete Work of Charles Darwin Online at Cambridge University, said: “Charles Darwin is one of the most influential scientists in history. The collection of his papers now online is extremely important and therefore very exciting.

“This release makes his private papers, mountains of notes, experiments, and research behind his world-changing publications available to the world for free.

“His publications have always been available in the public sphere - but these papers have until now only been accessible to scholars.”

The immensity of the collection means even if you viewed one image per minute, it would still take more than two months to see all of the material made available today.

Covering Darwin’s life from childhood, the papers also feature his boyhood notes on birds, proofs of his Origin of Species, as well as caricatures and obituaries and much more.

Dr van Wyhe added: “Darwin changed our understanding of nature forever. His papers reveal how immensely detailed his researches were. The release of his papers online marks a revolution in the public's access to - and hopefully appreciation of - one of the most important collections of primary materials in the history of science.”

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Genome analysis reveals new protein associated with breast cancer progression

A novel systems-based approach that combines comprehensive gene expression profiling with genome-wide transcription factor analysis and protein-protein interaction has led researchers to an important genetic marker that can help physicians know which breast cancer patients are at highest risk and will require more aggressive treatment, a research team based at the University of Chicago Medical Center reports in the April 15, 2008, issue of the journal Molecular Systems Biology.

The researchers found that high expression of a protein known as H2A.Z, which is associated with the expression of genes within the nucleus, can help physicians predict which patients are most at risk for disease spread and death. It could also serve as a new target for therapy.

“Elevated H2A.Z expression is significantly associated with metastasis and shorter survival, and it could quickly help doctors make better predictions and treatment choices for their patients,” said study director Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology at the University of Chicago and Argonne National Laboratory. “It could also provide clues to new therapies.”

“But, perhaps more important,” he added, “we think we have developed an integrated approach to genomic analysis that can be applied to a wide range of cancers.”

Instead of a standard whole-genome analysis, looking for genetic variations that correlate with disease risk, White and colleagues integrated multiple genetic technologies to measure the effects of estrogens, which play a crucial role in many breast cancers, on multiple cellular pathways, what they refer to as a “transcriptional regulatory cascade.”

The female hormone estrogen acts by binding to the estrogen receptor, which carries the hormone’s signal to a cell’s nucleus, where it activates many other genes. One of those genes is a known cancer-related gene called c-MYC, which in turn regulates its own cascade of gene targets.

White’s team set out to map out the many sequential genetic events that occur in breast cancer cells after estrogen binding, using a series of innovative technologies. They ultimately found that estrogen-stimulated c-MYC enhanced production of H2A.Z, which altered the positioning and activation of various genes in ways that increased the odds that a cancer would spread to the lymph nodes and ultimately to distant sites, often resulting in the patient’s death.

This is not a simple process. In tumor cells from patients with estrogen-dependent breast cancers, the researchers found estrogen affected 1,615 genetic regions. One of those was the promoter for the gene for c-MYC, which, when activated, could bind another set of overlapping 311 genetic regions.

Both estrogen and c-MYC interact with the gene for H2A.Z, leading to increased production of this protein in breast cancer cells. When the researchers looked at tumor tissue samples collected from 500 patients, they found that elevated levels of H2A.Z were highly correlated with the spread of the cancer to lymph nodes and decreased patient survival. Adding H2A.Z expression to other known risk factors provided “significant prognostic information,” the authors note, “beyond what these factors alone provide.”

“Although it has been implicated in genomic stability and gene transcription, H2A.Z has never been reported to be associated with cancer,” said White. “We would not have found this clinically important factor without taking such a large-scale integrated approach.”

“We suspect this integrated systems approach will lead us to a number of previously unsuspected genes that play a role in disease initiation and progression,” he said. “Many of these could become targets for new treatments.”

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Less sleep, more TV leads to fat toddlers

Infants and toddlers who sleep less than 12 hours a day are twice as likely to become overweight by age 3 than children who sleep longer. In addition, high levels of television viewing combined with less sleep elevate the risk, so that children who sleep less than 12 hours and who view two or more hours of television per day have a 16 percent chance of becoming overweight by age 3.

“Mounting research suggests that decreased sleep time may be more hazardous to our health than we imagined,” says Elsie Taveras, assistant professor in Harvard Medical School’s Department of Ambulatory Care and Prevention and lead author on the study. “We are now learning that those hazardous effects are true even for young infants.”

Results are published in the April 2008 issue of Archives of Pediatric & Adolescent Medicine.

The study team identified 915 mother-infant pairs from Project Viva, a long-term study of the effects of diet and other lifestyle factors on maternal and child health over time. Infant weight and measurements were taken at several in-person visits up to 3 years of age. Mothers reported how many hours their child slept per day on average at 6 months, 1 year, and 2 years postpartum.

Parents were also asked to report the average number of hours their children watched television on weekdays and weekends.

The combination of low levels of sleep and high levels of television viewing appeared to be synergistic and was associated with markedly higher body mass index (BMI) scores and increased odds of becoming overweight.

“Although previous studies have shown a similar link between sleep restriction and overweight in older children, adolescents, and adults, this is the first study to examine the connection in very young children,” says Matthew Gillman, Harvard Medical School associate professor and director of the Obesity Prevention Program in the Department of Ambulatory Care and Prevention. Gillman is also the study’s senior author.

Television viewing is also a known risk factor for children becoming overweight.

These study results support efforts to reduce television viewing and to promote adequate sleep to help reduce unhealthy childhood weight gain. Children who are overweight are often at higher risk for obesity and related conditions, such as hyperlipidemia, hypertension, asthma, and type 2 diabetes.

“Getting enough sleep is becoming more and more difficult with TV, Internet, and video games in the rooms where children sleep,” says Taveras. “Our findings suggest that parents may wish to employ proven sleep hygiene techniques, such as removing TV from children’s bedrooms, to improve sleep quality and perhaps sleep duration.”

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Arizona Cancer Center Studying Benefits of Green Tea Extract

The Arizona Cancer Center at The University of Arizona is studying the effects of Polyphenon E, a green tea extract, on prostate cancer prevention. This study will determine whether Polyphenon E affects cancer-related biomarkers in blood and/or prostate tissue in men with prostate cancer.

Tea is one of the world’s most consumed beverages. Polyphenon E is a chemically defined, decaffeinated, catechin-enriched green tea extract. Catechins are plant chemicals that are considered powerful antioxidants and have multiple beneficial biological effects that could lead to cancer prevention.

Prostate cancer is the most common type of cancer found in American men, other than skin cancer. The American Cancer Society estimates that there will be about 186,320 new cases of prostate cancer in the United States in 2008.

Past and ongoing research in numerous experimental studies and in one clinical trial provide evidence that green tea or green tea extracts such as Polyphenon E may have the potential to lower the risk of prostate cancer in the human population. However, rigorous clinical investigations are needed to determine whether green tea extracts such as Polyphenon E are effective at preventing prostate cancer.

The three-year study at the Arizona Cancer Center will recruit men with a recent diagnosis of organ-confined prostate cancer and scheduled to have the prostate removed within three to six weeks from the start of the study.

Eligible participants will take either four Polyphenon E capsules or a matched placebo each morning with food up to the day of their surgery. They will provide blood samples prior to capsule intake and again right before surgery. In addition, they will complete a diary and calendar of the capsules and other medications taken, illnesses and hospitalizations. All qualified participants will be compensated for their role in this study.

Following their surgery, tissue from their prostates will be analyzed to determine whether any of the tea components can be detected.

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Heart Dieases predetermined by oxygen levels in the Womb

The amount of oxygen available to a baby in the womb can affect their susceptibility to developing cardiovascular disease later in life.

Research from scientists at the University of Cambridge indicates that your risk of developing cardiovascular disease can be predetermined before birth, not only by your genes, but also by their interaction with the quality of the environment you experience in the womb. Their research was presented this week at the annual Society for Endocrinology, British Endocrine Society meeting. The Cambridge researchers, led by Dr Dino Giussani, examined the role that oxygen availability in the womb plays in programming your susceptibility to different diseases. His group found that babies that don’t receive enough oxygen in the womb, e.g. due to pre-eclampsia (high-blood pressure during pregnancy) or placental insufficiency, are more likely to suffer from cardiovascular disease when they are adult. A reduction of oxygen levels in the womb can lead to reduced growth rates in the baby and to changes in the way that their cardiovascular, metabolic and endocrine systems develop. Combined, these alterations to the development of key systems in the body can leave the baby more prone to developing cardiovascular disease later in life. Dr Giussani’s research also indicates methods by which we can potentially combat this problem. The detrimental effects of low oxygen levels on the development of the fetus’ cardiovascular system appear to be due to the generation of oxidative stress. Treatment with antioxidants in animal pregnancies complicated by low oxygenation can reverse these effects on the developing cardiovascular system and this could form the basis for new therapeutic techniques to prevent the early origin of heart disease in complicated human pregnancy. Cardiovascular disease is the most common cause of death in the UK, accounting for 4 in every 10 deaths. Almost 2.6 million people are affected by heart and circulatory conditions in the UK, with someone having a heart attack every 2 seconds. Dr Giussani said: “We have known for a while that changes in maternal nutrition can affect fetal development and influence disease susceptibility later in life, but relatively little work has investigated how low oxygen levels in the womb may affect infant development. Our research shows that changes to the amount of oxygen available in the womb can have a profound influence on the development of the fetus in both the short and long term, and trigger an early origin of heart disease. “Interestingly, the adverse effects on the developing heart and circulation of poor fetal oxygenation are due to oxidative stress. This gives us the opportunity to combat prenatal origins of heart disease by fetal exposure to antioxidant therapy. This may halt the development of heart disease at its very origin, bringing preventative medicine back into the womb.”

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Phytoplankton species deviates from norm: No CO2 absorbed in photosynthesis

A widespread species of ocean-dwelling microorganisms has been found to employ a never-before-seen alternative method of photosynthesis.

The discovery has implications not only for scientists' basic understanding of photosynthesis—arguably the most important biological process on Earth—but also for the amount of carbon dioxide that phytoplankton pull from the atmosphere.

Until now, it was thought that all the photosynthetic algae and bacteria living in the ocean drew carbon dioxide out of the air and used it to build sugars and other carbon-rich molecules to use as fuel. But two new studies by researchers at Stanford and the Carnegie Institution show that Synechococcus, a type of cyanobacteria (formerly called blue-green algae) that dominates much of the world's oceans, has evolved a mechanism that short-circuits photosynthetic carbon-dioxide fixation while still producing energy. The alternate approach is found in regions of the ocean where some of the ingredients necessary for traditional photosynthesis are in short supply.

"The amount of carbon dioxide being drawn down by the phytoplankton in nutrient-poor oceans might turn out to be significantly lower than we thought," said Shaun Bailey, a postdoctoral researcher working in the Carnegie Institution's Department of Plant Biology with Arthur Grossman, a staff scientist at the institution and a professor, by courtesy, in Stanford's Biology Department.

Bailey is the lead author of the paper describing part of the work in Biochimica et Biophysica Acta 1777 (2008). Kate Mackey, a graduate student in civil and environmental engineering at Stanford, is lead author of a second paper describing the work, currently in press at Limnology and Oceanography.

Until now, researchers have estimated marine photosynthetic activity by analyzing satellite images of the world's oceans to determine how much chlorophyll was in the water. Since chlorophyll is needed for photosynthesis, it was thought that measuring its concentration would be a straightforward way of estimating the amount of photosynthesis that would occur and therefore how much carbon dioxide would be consumed, or "fixed," by the phytoplankton. But the new work suggests that the relationship between the amount of chlorophyll in the water and the amount of carbon dioxide fixation by phytoplankton is not consistent throughout the world's oceans.

"There is a new twist on photosynthesis here, and that has to be accounted for when it comes to CO2 modeling," Bailey said, adding that, in some cases, the models may overestimate the amount of carbon fixation that occurs in nutrient-poor waters.

It is not yet clear what the finding might mean to studies of long-term global warming, he said, but it will have to be incorporated into any models that include carbon fixing by phytoplankton as a factor.

Synechococcus caught the interest of Grossman and his team because it thrives in vast areas of the ocean that are relatively deficient in iron, an element that is critical for certain reactions in the normal process of photosynthesis. How Synechococcus could maintain its abundance in the face of that deficiency was a puzzle.

"It seems that Synechococcus in the oligotrophic [nutrient-poor] oceans has solved the iron problem, at least in part by short-circuiting the standard photosynthetic process," Grossman said. "Much of the time this organism bypasses stages in photosynthesis that require the most iron. As it turns out, these are also the stages in which CO2 is taken from the atmosphere."

"We realized very quickly that there was something different about the Synechococcus that we were studying," said Bailey, the lead postdoctoral fellow working on the project. "The uptake of CO2 and the photosynthetic activities didn't match, so we knew that something other than CO2 was being consumed by photosynthesis, and it turned out to be oxygen." The researchers have tentatively identified the enzyme involved in this process to be plastoquinol terminal oxidase, or PTOX.

Bailey worked with Synechococcus in the laboratory, but recently this newly discovered phenomenon was shown to occur in nature by Mackey, who made direct measurements of photosynthesis in field samples from the Atlantic and Pacific oceans.

"The low-nutrient, low-iron environments account for about half of the area of the world's oceans, so they represent a large portion of the Earth's surface available for photosynthesis," Mackey said. "Our findings show that this novel cycle occurs in two major ocean basins and suggest that a substantial amount of energy from sunlight gets re-routed away from carbon fixation during photosynthesis. This may mean that less CO2 is being removed from the atmosphere by the open ocean photosynthetic organisms than was previously believed."

"This discovery represents a paradigm shift in our view of photosynthesis by organisms in the vast, nutrient-starved areas of the open ocean," said Joe Berry of the Carnegie Institution's Department of Global Ecology. "We had assumed that like higher plants, the goal was to make carbohydrates from CO2 and store them for later use as a source of energy for any number of cellular functions or growth. We now know that some organisms short-circuit this complicated process, using light in a minimalist way to power cellular processes directly with a far simpler and cheaper—in terms of scarce nutrients such as iron—photosynthetic apparatus. We don't know the full significance of this finding yet, but it is certain to change the way we interpret optical measurements of photosynthetic pigments in the ocean and the way we model ocean productivity."

Wolf Frommer, director of the Carnegie Institution's Department of Plant Biology, agreed on the discovery's ground-breaking importance. "If we thought we have understood photosynthesis, this study proves that there is much to be learned about these basic physiological processes," he said.

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Study shows that stimuli unrelated to decision can still influence men’s choices

Attractive women plus cool cars equal brisk sales for auto dealers as men snap up those cars, prompted—or so advertising theory goes—by the association. But is the human male really so easily swayed? Can the irrelevant image of an alluring female posing by the merchandise actually encourage a heterosexual man to purchase it?

Possibly, according to a new study by Stanford researchers.

The study showed that when heterosexual men are exposed to positive emotional stimuli—in this case, erotic photos of a man and woman—an area of the brain associated with anticipation of reward is stimulated. In the immediate aftermath of that stimulation, men are consistently more likely to take bigger financial risks than they otherwise would, said Brian Knutson, assistant professor of psychology.

"This is the first study to demonstrate that emotional stimuli can influence financial risk-taking," said Knutson, lead author of a paper describing the research in the current issue of NeuroReport. The hard evidence was gathered by functional magnetic resonance imaging (fMRI) of participants' brains as they viewed photographs of positive, negative or neutral subjects and then had to quickly make a decision to choose one of two levels of financial risk in a required gamble.

Knutson and collaborator Camelia Kuhnen (who received her PhD from the Stanford Graduate School of Business in 2006 and is now assistant professor of finance at Northwestern University) had already shown in a 2005 study using fMRI that brain activity could be used to predict whether people were about to take a financial risk. When they were, an area of the brain called the nucleus accumbens showed increased activation. When they were about to choose to avoid the risk, a different area called the insula showed increased activation.

"We knew that we should be looking at [the nucleus accumbens] from the previous study. But what we didn't know is whether we could somehow control the activation in that area by presenting some completely irrelevant stimulus," Knutson said. "And whether that would change activation in that area and actually change behavior."

Knutson and his colleagues studied heterosexual male undergraduate college students. The images the men viewed were intended to stimulate an emotional response. Erotic images were used to elicit a positive response, snakes and spiders to prompt a negative response, and office supplies to trigger a neutral response.

In case any of the subjects found office supplies more repellent than snakes and spiders, the researchers had the men rate each image after the scans. They then derived personalized ratings from each of the participants, which were used to make sure that whatever brain activation they observed was properly correlated with the actual emotional response of the viewer.

After viewing each image, the participants immediately had to decide whether to take the high-risk option of gambling a dollar or the low-risk option of gambling a dime. Regardless of their choice, they had a 50-50 chance of winning or losing. Knutson and his colleagues gave each man $10 to gamble with prior to entering the MRI scanner. "We wanted them to care," Knutson said. Depending on the men's gambles and the random outcomes, they won or lost. "We took that money back if they lost it," he said.

"What we saw is that when they viewed the erotic pictures, the activation in their nucleus accumbens increased compared to the other stimuli, and also that they had increased activation in that region before choosing the high-risk gamble," Knutson said.

The researchers then applied a statistical analysis to determine whether the activation in the nucleus accumbens accounted for some of the behavioral effect. "The answer was yes, at least in the case of the positive stimuli," Knutson said. "After people had seen those erotic pictures, they tended to pick the high-risk gamble more often, especially if they had been picking the low-risk gamble before.

"The interesting finding from an economic standpoint is that these completely irrelevant stimuli, these pictures that have nothing to do with the gambles or the history of outcomes that people have experienced with these gambles, still influence behavior," he said. "They seem to do so at least partially by influencing activation of these brain regions."

The findings have implications for what might make emotional appeals effective or ineffective in applications ranging from advertising to finance to politics and, perhaps not surprisingly, gambling.

"If you go to the casinos, people are wearing skimpy costumes, they're giving you free alcohol, there are bells and lights and things like that, which don't necessarily seem related to the odds of the gambling," Knutson said. "But these are cues that might activate brain regions that encourage risk-taking and therefore get people to gamble more."

So does draping a seductive woman over the hood of a car in an advertisement really help sell that car?

"Well, yes and no," Knutson said. "It may work sometimes under some conditions."

"Our trials are happening relatively fast, changing on a second-to-second basis," he noted. "We're forcing people to immediately make a decision, and the emotional stimuli appear in close temporal proximity to the decision itself.

"If you have these kinds of appeals, you'd better make it easy for people to make an immediate decision. You should put them under time pressure," he said.

Knutson emphasized that there is still ample work to be done in deciphering the effects of emotional stimuli on behavior. He plans to study women's responses in the future, as well as to examine other types of emotional stimuli. He also intends to examine the influence of time, to see how transient or lasting the influences of various emotional stimuli might prove to be.

"This is just a first step," he said. "It's an existence proof that some irrelevant emotional stimuli can influence some immediate financial decisions and that we can track down one brain basis for this influence."

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Discovery of the First Sex Chromosome Gene Tied to Male Infertility

A team of scientists led by University of Pennsylvania veterinary researchers have identified a gene, TEX11, located on the X chromosome, which when disrupted in mice renders the males sterile and reduces female fecundity. This is the first study of the genetic causes of infertility that links a particular sex chromosome meiosis-specific gene to sterility.

As with mice, the TEX11 gene is also located on the human X chromosome. Given that disruption of TEX11 causes azoospermia, or non-measurable sperm levels in mice, mutations in the human TEX11 gene may be a genetic cause of infertility in men. Because men have only one X chromosome that they inherit from their mother and thus only one copy of the TEX11 gene, any mutation could theoretically lead to sterility. Like other X-linked disorders such as color blindness and muscular dystrophy, genetic mutation causing a son’s infertility could be passed from his mother.

Researchers hypothesize that a screening of the TEX11 gene may provide a pre-birth diagnosis for infertility in men.

The study, published in the March issue of Genes & Development, also reports the first meiosis-specific factor ever found on the X chromosome. Meiosis is the process of cell division that produces gametes in both sexes. During meiosis, homologous chromosomes undergo pairing, synapsis, recombination and faithful segregation. Meiosis allows the exchange of genetic material between paternal and maternal genomes to produce genetically diverse gametes (sperm or eggs). Therefore, defects in meiosis are a leading cause of both infertility and birth defects.

An estimated 15 percent of couples are affected by infertility worldwide, yet the genetic causes of male infertility remain largely unknown. For decades, conventional wisdom stated that the X chromosome had little to do with meiosis or infertility because the X chromosome is silenced during male meiosis. This thinking led to fertility studies that focused on the Y chromosome and autosomes.

In fact, Jeremy Wang, assistant professor in the Department of Animal Biology at the University of Pennsylvania’s School of Veterinary Medicine, and his team revealed in an earlier study of mouse male germ cells that nearly one third of the germ cell-specific genes they identified are located on the X-chromosome.

Wang and his team found that sex chromosomes did play a role in meiosis. Although these X-linked, germ cell-specific genes undergo inactivation during later stages of male meiosis, they play a role in the early stages. Specifically, researchers found that TEX11 forms discrete foci on meiotic chromosomes and appears to be a novel constituent of the meiotic recombination machinery. The team genetically engineered male mice such that they lacked TEX11 function and found that this caused chromosomal asynapsis during the process of gamete formation.

This means that homologous chromosomes failed to pair together during meiosis and chromosomes formed fewer crossovers, i.e. sites where they recombine, during the initial stages of meiosis. These failures led to elimination of spermatocytes at later stages in the genetic recombination process and, ultimately, male infertility.

Researchers hypothesize that because TEX11 interacts with SYCP2, an integral component of the protein complex that mediates synapsis during meiosis, TEX11 promotes both synapsis and genetic recombination and may provide a physical link between these two meiotic processes.

The study was performed by Wang and Fang Yang in the Department of Animal Biology in Penn’s School of Veterinary Medicine; Katarina Gell and Christer Höög of the Department of Cell and Molecular Biology at the Karolinska Institutet; Godfried W. van der Heijden and David C. Page of the Howard Hughes Medical Institute, Whitehead Institute and Department of Biology of the Massachusetts Institute of Technology; Sigrid Eckardt, N. Adrian Leu and K. John McLaughlin of the Center for Animal Transgenesis and Germ Cell Research at Penn Vet’s New Bolton Center; Ricardo Benavente of the Department of Cell and Developmental Biology at the University of Würzburg; and Chengtao Her of the School of Molecular Biosciences and Center for Reproductive Biology at Washington State University.
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Common aquatic animals show resistance to radiation

Scientists at Harvard University have found that a common class of freshwater invertebrate animals called bdelloid rotifers are extraordinarily resistant to ionizing radiation, surviving and continuing to reproduce after doses of gamma radiation much greater than that tolerated by any other animal species studied to date.

Because free radicals such as those generated by radiation have been implicated in inflammation, cancer, and aging in higher organisms, the findings — published this week in the Proceedings of the National Academy of Sciences by Harvard’s Matthew Meselson and graduate student Eugene Gladyshev — could stimulate new lines of research into these medically important problems.

“Bdelloid rotifers are far more resistant to ionizing radiation than any of the hundreds of other animal species for which radiation resistance has been examined,” says Meselson, Thomas Dudley Cabot Professor of the Natural Sciences in Harvard’s Faculty of Arts and Sciences. “They are able to recover and resume normal reproduction after receiving a dose of radiation that shatters their genomes, causing hundreds of DNA double-strand breaks which they are nevertheless able to repair.”

Meselson and Gladyshev found that the bdelloid rotifers Adineta vaga and Philodina roseola remained reproductively viable after doses of radiation roughly five times greater than other classes of rotifers and other animals could endure.

Such radiation resistance appears not to be the result of any special protection of DNA itself against breakage, the researchers say, but instead reflects bdelloid rotifers’ extraordinary ability to protect their DNA-repairing machinery from radiation damage.

Roughly a half-millimeter in size and commonly observed under microscopes in high school biology classes, bdelloid rotifers are highly unusual in several regards: They appear to be exclusively asexual, have relatively few transposable genes, and can survive and reproduce after complete desiccation at any stage of their life cycle. Meselson and Gladyshev hypothesize that it’s this last property that explains bdelloids’ apparently unique resistance to radiation.

Bdelloid rotifers have been widely studied since at least 1702, when the renowned Dutch scientist and microscopy pioneer Anton van Leeuwenhoek added water to dust retrieved from a rain gutter on his house and observed the organisms in the resulting fluid. He subsequently described the creatures in a letter to Britain’s Royal Society, which still counts an envelope of van Leeuwenhoek’s rain-gutter dust among its holdings.

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Gene's 'selective signature' helps scientists identify instances of natural selection in microbial evolution

Microbes, the oldest and most numerous creatures on Earth, have a rich genomic history that offers clues to changes in the environment that have occurred over hundreds of millions of years.

While scientists are becoming increasingly aware of the many important environmental roles played by microbes living today--they process the food in our intestines, they keep carbon moving through the ocean food web, they can be harnessed to process sewage and build specific proteins--they still know little about these tiny critters, particularly marine microbes, which generally are classified into species based on their ecological niche. For instance, two species of marine microbe might look very similar physically, but one may have adapted to life in a particularly dark part of the ocean, while its sister species may have adapted to feeding off a nutrient that is rare in most parts of the ocean, but exists in abundance in one small area.

Scientists at MIT who are trying to understand existing microbes by studying their genetic history recently created a new approach to the study of microbial genomes that may hasten our collective understanding of microbial evolution.

The researchers have reversed the usual order of inquiry, which is to study an organism, then try to identify which proteins and genes are involved in a particular function. Instead, they have come up with a simple mathematical formula that makes it possible to analyze a gene family (a single type of gene or protein that exists in many creatures) simultaneously in a group of ecologically distinct species.

This means that we can begin to identify occurrences of natural selection in an organism's evolution simply by looking at its genome and comparing it with many others at once. This would allow them to take advantage of the nearly 2,500 microbes whose genomes have already been sequenced.

The new method determines the "selective signature" of a gene, that is, the pattern of fast or slow evolution of that gene across a group of species, and uses that signature to infer gene function or to map changes to shifts in an organism's environment.

"By comparing across species, we looked for changes in genes that reflect natural selection and then asked, 'How does this gene relate to the ecology of the species it occurs in?'" said Eric Alm, the Doherty Assistant Professor of Ocean Utilization in the Departments of Civil and Environmental Engineering and Biological Engineering. Natural selection occurs when a random genetic mutation helps an organism survive and becomes fixed in the population. "The selective signature method also allows us to focus on a single species and better understand the selective pressures on it," said Alm.

"Our hope is that other researchers will take this tool and apply it to sets of related species with fully sequenced genomes to understand the genetic basis of that ecological divergence," said graduate student B. Jesse Shapiro, who coauthored with Alm a paper published in the February issue of PLoS Genetics.

Their work also suggests that evolution occurs on functional modules--genes that may not sit together on the genome, but that encode proteins that perform similar functions.

"When we see similar results across all the genes in a pathway, it suggests the genomic landscape may be organized into functional modules even at the level of natural selection," said Alm. "If that's true, it may be easier than expected to understand the complex evolutionary pressures on a cell."

For example, in Idiomarina loihiensis, a marine bacterium that has adapted to life near sulfurous hydrothermal vents in the ocean floor, the genes involved in metabolizing sugar and the amino acid phenylalanine underwent significant changes (over hundreds of millions of years) that may help the bacterium obtain carbon from amino acids rather than from sugars, a necessity for life in that ecological niche. In one of I. loihiensis' sister species, Colwellia psychrerythraea, some of those same genes have been lost altogether, an indication that sugar metabolism is no longer important for Colwellia.

Shapiro and Alm focused on 744 protein families among 30 species of gamma-proteobacteria that shared a common ancestor roughly one to two billion years ago. These bacteria include the laboratory model organism E. coli, as well as intracellular parasites of aphids, pathogens like the bacteria that cause cholera, and soil and plant bacteria. They mapped the evolutionary distance of each species from the ancestor and incorporated information about the gene family (for instance, important proteins evolve more slowly than less-vital ones) and the normal rate of evolution in a particular species' genome in order to determine a gene's selective signature.

"These are experiments we could never perform in a lab," said Alm. "But Mother Nature has put genes into an environment and run an evolutionary experiment over billions of years. What we're doing is mining that data to see if genes that perform a similar function, say motility, evolve at the same rate in different species. To the extent that they differ, it helps us to understand how change in core genes drives functional divergence between species across the tree of life."

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New research provides insight into menopause

nsight into why females of some species undergo menopause while others do not has proven elusive despite an understanding of the biological mechanisms behind the change.

However, new research by scientists at the Universities of Cambridge and Exeter suggests that menopause is an adaptation to minimize reproductive competition between generations of females in the same family unit.

Even in 'natural fertility' human societies (i.e., those without access to modern medicine or technology) women typically survive for many years after they have ceased to reproduce. Menopause represents an evolutionary puzzle because theory suggests that there should be no selection for genes which promote survival past the end of reproduction. The current explanation was proposed 50 years ago and is known as the 'grandmother hypothesis': Natural selection can favour post-reproductive survival if older non-breeding women can help their children survive and reproduce.

The problem is that data from natural fertility societies suggests that grandmothering benefits are too small to favour switching off reproduction by age fifty in order to help. So while the grandmother hypothesis can explain why women continue to survive after they have stopped breeding, it can't explain why they stop breeding in the first place.

In this paper, published today in the journal PNAS, the researchers propose that the timing of reproductive cessation in humans is best understood as an evolutionary adaptation to reduce reproductive competition between generations of females in the same family unit.

Reproductive competition is ubiquitous in other cooperative vertebrates, but up to now its potential role in human life history evolution has been overlooked. The research demonstrates that humans are unique among primates because there is almost no overlap of reproductive generations. In natural fertility populations, women on average have their first baby at 19 years and their last baby at 38 years; in other words, women stop breeding when the next generation starts to breed.

Moreover, the scientists go on to demonstrate that this pattern is expected given the female-dispersal system thought to characterize ancestral humans. Female dispersal means that reproductive competition in ancestral human families would have involved 'mothers-in-law' competing with 'daughters-in-law'. In these circumstances younger females have a decisive advantage in competition because a mother-in-law is related to her daughter-in-law's offspring (and therefore share's an interest in her reproductive success), but not vice versa.

The researchers developed a simple mathematical model of this competition which predicts that older women should cease breeding when younger women in the same social unit start to breed. This hypothesis and model can thus explain the observed timing of reproductive cessation in humans, and so contributes to a much better understanding of how menopause evolved.

Despite vast differences in wealth, resources, and access to medicine, women in all societies experience menopause. This suggests that the human fertility schedule is hard-wired into our genetic makeup as a consequence of our evolutionary history, prior to more recent cultural and technological advances.

Dr Michael Cant at the University of Exeter explains, “Women everywhere experience a rapid decline in fertility after the age of forty, culminating in menopause around ten years later. Our study helps to explain why this phase of rapid 'senescence' of the reproductive system starts when it does, and why women, on average, stop having children a full ten years before the onset of menopause.”

It also helps to explain why in some societies (particularly in Africa and Asia), women are required by social law to stop having children when their first grandchild is born. A better understanding of the selective forces that have shaped the genetically programmed human fertility schedule may in future provide medical insights into the genetic causes of premature ovarian failure and other diseases of low fertility.

“The grandmother hypothesis was proposed 50 years ago by the American evolutionary biologist George Williams,”says Dr Cant. “However, data on grandmother effects indicate that something key is missing from Williams’ argument. Our study suggests the missing part of the puzzle, and generates a raft of new testable predictions.”

Dr Rufus Johnstone at the University of Cambridge adds, “It should open up new avenues for research on menopause and fertility in humans, and provide new insights into the evolution of menopause in the two other species in which it occurs under natural conditions - killer whales and pilot whales."

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Growth hormone also guides brain wiring

A human hormone known to stimulate the growth of cells throughout the body has a new role - helping to set up the proper nerve connections in the odor center of the brain, according to University of California, Berkeley, scientists.

Airborne scent chemicals (inset) stimulate odor receptors in the nasal cavity, which send signals to the brain's olfactory bulb (yellow) located in the frontal lobe of the brain just above the nasal bone. These connections are set up during early development when sensory nerves in the nose send axons into the brain (blue and gold) that target specific neurons in the bulb to create a map of sensory information that displays a mirror symmetry across the bulb’s midline (dashed line). When IGF signaling is disrupted (right), the blue axons collapse toward the bulb’s midline, resulting in a distortion of this sensory map, demonstrating the critical role played by IGF in wiring the brain. (John Ngai/UC Berkeley; inset courtesy Nobel prize committee)

The hormone, insulin-like growth factor (IGF), is well-known to biomedical researchers and has been tested as a therapy for diabetes and some growth disorders. Until now, decades of research have turned up only one solid role for IGF, however, and that is to makes cells grow and multiply.

Neuroscientist John Ngai, Coates Family Professor of Neuroscience and director of the Functional Genomics Laboratory at UC Berkeley, and his colleagues have now found that IGF plays a critical role in setting up the connections between chemical detectors in the nose and the brain's olfactory centers. These centers, the olfactory bulbs, are a pair of raisin-sized structures in the front part of the brain that analyze signals from the many odor receptors in the nose.

IGF joins a small number of identified molecules known to direct the growth of nerve cells in the brain during its development, making it "another tool in the brain's tool kit for how you wire up the brain," Ngai said.

Aside from what this reveals about how the brain wires itself as it grows, these molecules could become important therapeutically once doctors begin implanting new cells, perhaps stem cells, into the brain to cure neurodegenerative diseases, Ngai said.

"Even if you figure out a way to grow new cells to replace dying cells, those cells still need to make proper connections," Ngai said. "So, anything you know about what drives normal connectivity in the brain will help you figure out how to get those new cells to wire up correctly."

Ngai and colleagues at UC Berkeley, the Shanghai Institutes of Biological Sciences in China and Columbia University Medical Center reported their findings in the March 27 issue of the journal Neuron.

The molecules netrin, ephrin, semaphorin, slit and now IGF are called axon guidance molecules because as nerves stretch their tentacle-like axons out into the brain to connect with other neurons, these molecules act as signposts to steer the axons to the correct brain cells. As the brain grows during early development to some 3 billion nerve cells, each nerve cell makes, on average, 10,000 connections with other nerve cells, so "guidance cues" are critical.

"Cells from the retina of the eye, for example, carry signals into your brain conveying information about the outside world, and these go back into your brain in a very ordered projection such that there is a topographic map of the visual world from the retina at each successive layer of relays in the brain," Ngai said. "Something must order those connections, or otherwise you wouldn't be seeing a coherent image."

So far, these axon guidance cues include chemoattractants that make axons grow toward them, and chemorepellants, which make them turn away. As shown by Ngai's colleagues in China, IGF is an attractant; the growth cones of axons turn toward higher concentrations of the hormone.

Compared to the visual system, the brain's odor system is still poorly understood, but it appears to have its own uniquely ordered connections, Ngai said. The nose contains some 5 million nerve cells, each of which carries only one kind of odor receptor out of about 1,000 different odor receptors, each tuned to detect different chemicals or odorants. Nose nerve cells that detect the same odorant send their axons to the same region of the olfactory bulb, and it appears that neurons that detect similar chemicals, such as different alcohols, send their axons to nearby areas of the bulb.

Scientists previously had discovered that each of our two olfactory bulbs is divided down the middle between two mirror-image representations of the nasal odor receptors. Ngai and his colleagues found that IGF is responsible for setting up these mirror images within the bulb.

"IGF signaling is absolutely required for this mirror symmetry," he said. "In the absence of IGF function, you lose information from the sensory axons of the nose to one half of the bulb."

Axons from the nose appear to express receptors for IGF on their growth cones, which allow the growth cones to essentially sniff out the IGF in the olfactory bulb and follow the trail to the proper target cells. Without the IGF produced in the olfactory bulb, the growing axons do not make the turn-off to the outer half of each bulb, but instead go only to the inner side nearest the midline of the brain.

Both of the IGF protein's forms, dubbed IGF-1 and IGF-2, are expressed by cells in the olfactory bulb, as determined by DNA microarray screens and other techniques.

While IGF appears critical in the early stages of olfactory development, when the basic architecture of the olfactory bulb is being set up in the fetus and perhaps also after birth, other axon guidance cues are no doubt needed to more finely direct the growth of axons, Ngai said. He is continuing to investigate these other cues, and also to map the nose's chemical receptors to specific areas of the bulb. Ngai and his colleagues also are following up on some early leads indicating that IGF may serve as a chemoattractant in other parts of the developing brain.

"We are seeing an emerging picture with IGF," Ngai said. "Over the past three years, there have been studies from others showing a role for IGF signaling in establishing the shape of certain neurons, and other studies showed that IGF is required for how fast axons grow. The present study tells us that IGF is actually being used as a chemoattractant. This is a new role for IGF in development."

Ngai's coauthors are former UC Berkeley graduate students Jonathan A. Scolnick and Cynthia D. Duggan, Kai Cui and Xiao-bing Yuan of the Institute of Neuroscience at the Chinese Academy of Sciences, and Shouhong Xuan and Argiris Efstratiadis of the Department of Genetics and Development at Columbia University Medical Center.

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Low oxygen, molybdenum delayed evolution

A deficiency of oxygen and the heavy metal molybdenum in the ancient deep ocean may have delayed the evolution of animal life on Earth by nearly two billion years, a study led by UC Riverside biogeochemists has found.

The researchers arrived at their result by tracking molybdenum in black shales, which are a kind of sedimentary rock rich in organic matter and usually found in the deep ocean. Molybdenum is a key micronutrient for life and serves as a proxy for oceanic and atmospheric oxygen amounts.

Study results appear in the March 27 issue of Nature.

Following the initial rise of oxygen in the Earth’s atmosphere 2.4 billion years ago, oxygen was transferred to the surface ocean to support oxygen-demanding microorganims. Yet the diversity of these single-celled life forms remained low, and their multicellular ancestors, the animals, did not appear until about 600 million years ago, explained Timothy Lyons, a professor of biogeochemistry in the Department of Earth Sciences and one of the study’s authors.

Suspecting that deficiencies in oxygen and molybdenum might explain this evolutionary lag, Lyons and his colleagues measured abundances of molybdenum in ancient marine sediments over time to estimate how much of the metal had been dissolved in the seawater in which the sediments formed.

The researchers found significant, firsthand evidence for a molybdenum-depleted ocean relative to the high levels measured in modern, oxygen-rich seawater.

“These molybdenum depletions may have retarded the development of complex life such as animals for almost two billion years of Earth history,” Lyons said. “The amount of molybdenum in the ocean probably played a major role in the development of early life. As in the case of iron today, molybdenum can be thought of as a life-affirming micronutrient that regulates the biological cycling of nitrogen in the ocean.

“At the same time, molybdenum’s low abundance in the early ocean tracks the global extent of oxygen-poor seawater and implies that the amount of oxygen in the atmosphere was still low.

“Knowing the amount of oxygen in the early ocean is important for many reasons, including a refined understanding of how and when appreciable oxygen first began to accumulate in the atmosphere,” Lyons said. “These steps in oxygenation are what gave rise ultimately to the first animals almost 600 million years ago – just the last tenth or so of Earth history.”

Earth’s oxygenation

For animal life to commence, survive and eventually expand on Earth, a threshold amount of oxygen – estimated to be on the order of 1 to 10 percent of present atmospheric levels of oxygen – was needed.

Past research has shown that Earth’s oxygenation occurred in two major steps:

The first step, around 2.4 billion years ago, took place as the ocean transitioned to a state where only the surface ocean was oxygenated by photosynthesizing bacteria, while the deep ocean was relatively oxygen-free.

The second step, around 600 million years ago, marked the occasion when the entire ocean became fully oxygenated through a process not yet fully understood.

“We wanted to know what the state of the ocean was between the two steps,” said Clinton Scott, a graduate student working in Lyons’s lab and the first author of the research paper. “By tracking molybdenum in shales rich in organic matter, we found the deep ocean remained oxygen- and molybdenum-deficient after the first step. This condition may have had a negative impact on the evolution of early eukaryotes, our single-celled ancestors. The molybdenum record also tells us that the deep ocean was already fully oxygenated by around 550 million years ago.”

According to Scott, the timing of the oxygenation steps suggests that significant events in Earth history are related. Scientists have long speculated that the evolution of the first animals was linked somehow to the so-called Snowball Earth hypothesis, which posits that the Earth was covered from pole to pole in a thick sheet of ice for millions of years at a time. “The second oxygenation step took place not long after the last Snowball Earth episode ended around 600 million years ago,” Scott said. “So one question is: Did this global glaciation play a role in the increasing abundance of oxygen which, in turn, enabled the evolution of animals?”

Scott and Lyons were joined in the research by A. Bekker of the Carnegie Institution of Washington, DC; Y. Shen of the Université du Québec à Montréal, Canada; S.W. Poulton of Newcastle University, Newcastle upon Tyne, United Kingdom; X. Chu of the Chinese Academy of Sciences, Beijing, China; and A.D. Anbar of Arizona State University, Tempe, Ariz.

The research was supported by grants from the U.S. National Science Foundation Division of Earth Sciences and the NASA Astrobiology Institute.

More about molybdenum as a proxy for ocean chemistry

Molybdenum, a metal abundant in the ocean today but less so at times in the past, is an excellent tracer of ancient chemistry for two reasons. First, the primary source of molybdenum to the ocean is oxidative weathering of continental crust, requiring oxygen in the atmosphere. Second, molybdenum is removed primarily in marine sediments where oxygen is absent and sulfide is abundant. Thus the enrichment of molybdenum in ancient organic-rich shales requires oxygen in the atmosphere but high sulfur and very low or no oxygen in the deep ocean. This combination is relatively rare today but may have been common when oxygen was less abundant in the earlier atmosphere.

When oxygen is available in the atmosphere, the amount of dissolved molybdenum in seawater is determined by the extent of hydrogen-sulfide-containing sediments and bottom waters (the colder, more isolated, lowermost layer of ocean water). Where sulfidic environments are widespread, the pool of molybdenum remaining in seawater is small, growing as the sulfidic environments shrink. The amount of molybdenum in the seawater is reflected in the magnitude of molybdenum enrichment in shales deposited in the deep ocean.

The UCR-led team of researchers estimated the size of the oceanic reservoir, and thus the extent of sulfidic bottom waters and sediments, based on the concentration of molybdenum in ancient black shales. They did so by dissolving the samples in a cocktail of acids and analyzing the dissolved rock for concentration using a mass spectrometer. The amount of this metal in the shales tracks the oxygen state of the early ocean and atmosphere and also points to the varying abundance of this essential ingredient of life. Molybdenum limitations may have delayed the development of eukaryotes, including the first animals, our earliest multicellular cousins.
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Black carbon pollution growing

Black carbon, a form of particulate air pollution most often produced from biomass burning, cooking with solid fuels and diesel exhaust, has a warming effect in the atmosphere three to four times greater than prevailing estimates, according to scientists in an upcoming review article in the journal Nature Geoscience.

Scripps Institution of Oceanography at UC San Diego atmospheric scientist V. Ramanathan and University of Iowa chemical engineer Greg Carmichael, said that soot and other forms of black carbon could have as much as 60 percent of the current global warming effect of carbon dioxide, more than that of any greenhouse gas besides CO2. The researchers also noted, however, that mitigation would have immediate societal benefits in addition to the long term effect of reducing greenhouse gas emissions.

The article, “Global and regional climate changes due to black carbon,” will be posted in the online version of Nature Geoscience on March 23.

“Observationally based studies such as ours are converging on the same large magnitude of black carbon heating as modeling studies from Stanford, Caltech and NASA,” said Ramanathan. “We now have to examine if black carbon is also having a large role in the retreat of arctic sea ice and Himalayan glaciers as suggested by recent studies.”

In the paper, Ramanathan and Carmichael integrated observed data from satellites, aircraft and surface instruments about the warming effect of black carbon and found that its forcing, or warming effect in the atmosphere, is about 0.9 watts per meter squared. That compares to estimates of between 0.2 watts per meter squared and 0.4 watts per meter squared that were agreed upon as a consensus estimate in a report released last year by the Intergovernmental Panel on Climate Change (IPCC), a U.N.-sponsored agency that periodically synthesizes the body of climate change research.

Ramanathan and Carmichael said the conservative estimates are based on widely used computer model simulations that do not take into account the amplification of black carbon’s warming effect when mixed with other aerosols such as sulfates. The models also do not adequately represent the full range of altitudes at which the warming effect occurs. The most recent observations, in contrast, have found significant black carbon warming effects at altitudes in the range of 2 kilometers (6,500 feet), levels at which black carbon particles absorb not only sunlight but also solar energy reflected by clouds at lower altitudes.

Between 25 and 35 percent of black carbon in the global atmosphere comes from China and India, emitted from the burning of wood and cow dung in household cooking and through the use of coal to heat homes. Countries in Europe and elsewhere that rely heavily on diesel fuel for transportation also contribute large amounts.

“Per capita emissions of black carbon from the United States and some European countries are still comparable to those from south Asia and east Asia,” Ramanathan said.

In south Asia, pollution often forms a prevalent brownish haze that has been termed the “atmospheric brown cloud.” Ramanathan’s previous research has indicated that the warming effects of this smog appear to be accelerating the melt of Himalayan glaciers that provide billions of people throughout Asia with drinking water. In addition, the inhalation of smoke during indoor cooking has been linked to the deaths of an estimated 400,000 women and children in south and east Asia.

Elimination of black carbon, a contributor to global warming and a public health hazard, offers a nearly instant return on investment, the researchers said. Black carbon particles only remain airborne for weeks at most compared to carbon dioxide, which remains in the atmosphere for more than a century. In addition, technology that could substantially reduce black carbon emissions already exists in the form of commercially available products.

Ramanathan said that an observation program for which he is currently seeking corporate sponsorship could dramatically illustrate the benefits. Known as Project Surya, the proposed venture would provide some 20,000 rural Indian households with smoke-free cookers and equipped to transmit data. At the same time, a team of researchers led by Ramanathan would observe air pollution levels in the region to measure the effect of the cookers.

Carmichael said he hopes that the paper’s presentation of the immediacy of the benefits will make it easier to generate political and regulatory momentum toward reduction of black carbon emissions.

“It offers a chance to get better traction for implementing strategies for reducing black carbon,” he said.

The National Science Foundation, the National Oceanic and Atmospheric Administration and the National Aeronautics and Space Administration funded the review.

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The “Bambi Factor”

Loveable family entertainment they may be, but when it comes to environmental awareness, Disney films have rarely been seen as contributing much more than a clutch of cuddly talking animals to the cause.

Now a new book by a Cambridge University researcher is suggesting that, far from just cute, Disney icons like Bambi, Nemo and Baloo are the all-singing, unsung heroes of the green lobby.

According to academic David Whitley, Disney’s screen fables have been helping successive generations of children to develop “a critical awareness of contested environmental issues” ever since Snow White in 1937.

Far from offering us sheer escapism, he says, they carry important messages about our relationship with the natural world. Conservation is so central to Bambi, for example, that the film is credited with having inspired many 1960s environmental activists at an early age. It also sparked protests from pro-hunting groups fearful of the “Bambi Factor” before it had even been released.

Snow White and Cinderella’s eponymous heroines give children role models who protect wildlife and care about their natural surroundings, the book says. Later films, on the other hand, are more complex, in keeping with the mood of the era. Finding Nemo – a 2003 box office smash about a fish searching for his lost son – is described as “a fable for our time”, which dramatises the contradictory attitudes and feelings inherent in our interaction with nature.

“Disney films have often been criticised as inauthentic and pandering to popular taste rather than developing the animation medium in a more thought-provoking way,” Whitley said.

“In fact, these films have taught us variously about having a fundamental respect for nature. Some of them, such as Bambi, inspired conservation awareness and laid the emotional groundwork for environmental activism. For decades Disney films have been providing children with potent fantasies, enabling them to explore how they relate to the natural world.”

The book, entitled The Idea Of Nature In Disney Animation, focuses on two periods in the corporation’s history; 1937-’67 (when Walt Disney himself was at its helm) and the 1984-2005 “Disney revival” in which Michael Eisner was President and CEO.

Both “saw themselves as having a sustained and strong commitment to wild nature and the environment,” the book explains, but in different ways. Disney projected a “folksy and homespun” relationship with nature in his films. Eisner, on the other hand, was a cosmopolitan city-dweller and co-founder of the Environmental Media Association, whose work is more politicised and self-conscious.

As a result, different films express a concern with the environment in different ways. Early productions like Snow White, Cinderella, Bambi and Sleeping Beauty are rooted in the tradition of classical pastoral, albeit in popularised forms, showing the natural world as an idyllic retreat, vulnerable to incursion from a debased and threatening civilisation.

Friendly animals ally themselves to the films’ heroes and heroines. In keeping with the role of nature in other American folk tales, the wilderness is seen as a place of renewal where the central characters undergo a process of self-discovery. Young viewers at the time were being encouraged to side with nature and protect it, like their role models in the films.

Later pictures, starting with The Jungle Book and stretching to The Lion King and Finding Nemo take the genre a step further. Often these have a more exotic setting – a “tropical dreamscape” in which a more harmonious relationship with the natural world could be imagined. Humans tend not to restore order to the natural world in these films; rather, they are a part of the order themselves.

Competing attitudes to the natural world are played out to a fuller extent in these films than in Disney’s early offerings and, in some cases, even left unresolved. In The Jungle Book, for example, the rivalry between Baloo and Bagheera echoes disputes over the consumption of natural resources which, at the time of the film’s making in 1967, also divided counter-cultural movements such as hippies from their more cautious elders.

“If you can accept their sentimentality, it becomes possible to see that these films are giving young audiences a cultural arena within which serious environmental issues can be rehearsed and explored,” Whitley added.

“Popular art often does more than we think to shape our feelings and our ideas about certain themes. Disney may well be telling us more about the environment and the way we relate to it than we tend to accept.”

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Study shows indicator for cardiovascular events

Gene panels may someday identify patients needing more intense monitoring, treatment

A study appearing in this week’s (March 19) New England Journal of Medicine (NEJM) confirms that a combination of gene variants previously associated with cholesterol levels does reflect patients’ cholesterol levels and can signify increased risk of heart attack, stroke, or sudden cardiac death. Led by researchers from the Massachusetts General Hospital (MGH) cardiology division, the study’s findings are a first step toward the ability to identify individuals who might benefit from earlier use of cholesterol-lowering medications and other measures to combat elevated risk.

“The prospect of personalized medicine has received much hype, but until recently, there has been little hard evidence to support the promise,” says Sekar Kathiresan, MGH director of preventive cardiology, the paper’s lead author. “We feel that our data provides two insights. First, we provide a foundation for the possibility that a panel of gene variants will eventually be useful in preventive cardiac care. Second, we show that the combinations of multiple variants related to cholesterol importantly contribute to the genetic risk for heart attack.”

It is estimated that about half the variation in high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels is inherited, rather than being caused by lifestyle factors such as diet and exercise. While studies have associated several gene variants with cholesterol levels, exactly how those variants impact the risk of cardiovascular disease is unclear. The current study was designed to explore the influence of those variants on the risk of cardiovascular events — heart attack, stroke, or sudden cardiac death — and whether measuring such variants could help predict risk better than simply measuring HDL and LDL levels.

Because the effects of individual gene variants appear slight, the research team looked at a combination of nine single-nucleotide polymorphisms (SNP) previously associated with cholesterol levels. They analyzed data from 5,414 Swedish adults who participated in a major prospective epidemiological study and correlated data — including standard measurements of HDL and LDL cholesterol and the presence of the nine gene variants — with information on the participants’ subsequent medical histories available from a registry of information collected on all Swedish citizens. After the initial genotyping of participants not receiving lipid-lowering therapy, participants were assigned a genotype score ranging from zero to 18, based on how many copies of the unfavorable SNPs they carried. Of the participants who had no cardiovascular events before enrolling in the study, 238 suffered a heart attack, stroke, or cardiac death during the subsequent 10.6 years.

Higher genotype scores did reflect higher LDL (“bad”) cholesterol and lower HDL (“good”) cholesterol levels. Importantly, those with genotype scores of 11 or higher had a 63 percent greater risk of a cardiovascular event than did those with scores of 9 or lower. Although testing for the panel of nine SNPs was not better than standard risk factors for predicting cardiac events in the overall population, among participants classified at intermediate risk by standard measures, adding the nine-SNP panel significantly improved the ability to distinguish truly elevated or reduced risk levels.

“A current clinical dilemma is how early to start patients on cholesterol-lowering medications, like statins, that can reduce the risk of heart attack. Our data suggest that those individuals classified as higher risk based on a genetic test may deserve more intense pharmacological and lifestyle treatments,” says Kathiresan. “But before we can move from our pilot data to information that can impact the care of patients with or at risk for cardiovascular disease, we need to discover all the risk-related variants — and there will probably be 50 to 100 — and then conduct clinical studies confirming that this information can reliably guide patient care.” Earlier this year Kathiresan, an instructor in medicine at Harvard Medical School, and colleagues from the Broad Institute of MIT and Harvard began this gene-discovery process and identified six new cholesterol-associated gene variants in a separate study published in Nature Genetics.

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A Gecko's Tail

UC Berkeley biologists report that geckos rely on their tails to keep from falling off vertical surfaces and, if they do fall, to right themselves in midair and maneuver like a skydiver gliding to a safe landing.

The discovery is already helping engineers design better climbing robots and may aid in the design of unmanned gliding vehicles or spacecraft. Perhaps, the researchers say, an "active" tail could help astronauts maneuver in space.

According to senior author Robert J. Full, professor of integrative biology at UC Berkeley, previous experiments on geckos have focused on their unique toes as the key to running up a wall and hanging onto ceilings. Full discovered six years ago that, while claws help geckos climb rough surfaces, millions of microscopic toe hairs make it possible for them to climb smooth ones.

Only when engineers began building gecko-like robots, such as Boston Dynamics Inc.'s RiSE (Robot in Scansorial Environment), the University of Pennsylvania's DynaClimber and Stanford University robots Spinybot and Stickybot - all inspired by Full's findings - did they discover that a tail might be necessary to prevent the robot from pitching backward and falling when it slips on a vertical surface.

When Full and UC Berkeley graduate student Ardian Jusufi went back to the lab to look at how geckos, specifically the flat-tailed house gecko, Cosymbotus platyurus, of Southeast Asia, use their tails, they discovered that the tail is critical for dealing with slippery surfaces.

"When we ran all of our geckos on perfect surfaces, they never slipped, and they didn't use their tails," Full said. "But when we put in a slippery patch, we found that they have an active tail that functions like a fifth leg to keep them from tipping backward. This is an undiscovered function for tails that tells us a lot about how active tails could affect the performance of vertebrates."

With the help of high-speed video, the researchers discovered that when a gecko loses traction with one leg, it taps its tail on the surface to prevent pitch-back until the toes can grab hold again. This all happens in milliseconds, since geckos can run up a wall at speeds of 3 feet per second, stepping and peeling off their toes 30 times per second.

If a gecko loses traction with more than one foot, the researchers found, it will often flatten its tail to the surface to prevent a fall in a move that has the effect, says Full, of a bicycle kickstand. Using either the tail-tapping or tail-flattening technique, nearly all geckos were able to navigate across slippery patches on a vertical wall.

"We were really surprised to see that they could pitch back up to 60 degrees, return to the vertical surface and still traverse the slippery patches," Jusufi said.

The engineers with whom Full collaborates are now devising active tails for their robots to replicate these moves, which in a gecko are probably reflexive, Full said.

The researchers acknowledged the usefulness of tails in other animals: kangaroos lean on theirs; chameleons, lemurs and New World monkeys grasp with theirs; and dinosaurs may have used theirs for balance while running and walking. Unlike these more static uses, however, the gecko's tail actively helps in high-speed vertical climbing and gliding.

During the slippery wall experiments, Jusufi and Full noticed something else about the geckos when they fell. They nearly always made a four-point landing after using their tails to reorient themselves in mid-air. Using high-speed video to record geckos falling upside down from a fake leaf, they found that the geckos rotated their tails so that their bodies counter-rotated to face downward, then spread their legs and toes to parachute. This mid-air maneuver was possible because of the gecko's typically large tail, which can be filled with fat.

While this parachuting had been noticed before by other researchers, the role of the tail was first recognized by Full and Jusufi.

"Air righting in mammals is characterized by a bending and twisting of the spine," Jusufi said. Cats, whose mid-air twists have been particularly well studied since 1894, are able to land on four paws with or without a tail. In contrast, he said, "the gecko is keeping its limbs and spine absolutely immobile in nearly 70 percent of all trials, and only rotates its tail until it turns around."

Moreover, after turning face down, the geckos in the study often used their tails to maneuver in mid-air like a skydiver steering toward a targeted drop zone. In wind tunnel tests, geckos could actually hover in the air stream and, using their tails, steer toward a solid perch.

"Why go into this Superman posture?" Full asked. "We found that it allowed them to use their tails to turn or control yaw and pitch. In the wild, this might allow a gecko escaping a predator to just go off the end of a branch and maneuver to another place."

Pitch refers to a head-down versus tail-down position, while yaw is a rotation to the left or right around a vertical axis.

Jusufi is now observing geckos in the wild to determine how these aerobatic skills serve them in the forest.

"We believe these animals are using their tails instead of their bodies to simplify control," he said. "Geckos reorient mainly around one axis, whereas air-righting maneuvers in mammals involve several axes and appear to require far more coordination."

"This discovery is another example of how basic research leads to unexpected applications - new climbing and gliding robots, highly maneuverable unmanned aerial vehicles and even energy-efficient control in space vehicles," said Full, who directs UC Berkeley's new Center for Interdisciplinary Bio-inspiration in Education and Research (CiBER). CiBER's goal is to discover principles that will inspire engineers from academia and industry to develop new materials and design novel robots, but also to seek feedback from engineering successes and failures to suggest new biological hypotheses.

Jusufi and Full are continuing their study of how the gecko uses its tail, and they plan to look at other lizards to determine how widespread this behavior is.

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