Avian Flu Viruses Which Are Transmissible Between Humans Could Evolve in Nature

It might be possible for human-to-human airborne transmissible avian H5N1 influenza viruses to evolve in nature, new research has found.

Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green) [Credit: CDC/Courtesy of Cynthia Goldsmith; Jacqueline Katz; Sherif R. Zaki]

The findings, from research led by Professor Derek Smith and Dr Colin Russell at the University of Cambridge, were published June 22 in the journal Science.

Currently, avian H5N1 influenza, also known as bird flu, can be transmitted from birds to humans, but not (or only very rarely) from human to human. However, two recent papers by Herfst, Fouchier and colleagues in Science and Imai, Kawaoka and colleagues in Nature reveal that potentially with as few as five mutations (amino acid substitutions), or four mutations plus reassortment, avian H5N1 can become airborne transmissible between mammals, and thus potentially among humans. However, until now, it was not known whether these mutations might evolve in nature.

The Cambridge researchers first analysed all of the surveillance data available on avian H5N1 influenza viruses from the last 15 years, focusing on birds and humans. They discovered that two of the five mutations seen in the experimental viruses (from the Fouchier and Kawaoka labs) had occurred in numerous existing avian flu strains. Additionally, they found that a number of the viruses had both of the mutations.

Colin Russell, Royal Society University Research Fellow at the University of Cambridge, said: "Viruses that have two of these mutations are already common in birds, meaning that there are viruses that might have to acquire only three additional mutations in a human to become airborne transmissible. The next key question is 'is three a lot, or a little?' "

The scientists explored this key question using a mathematical model of how viruses replicate and evolve within a mammalian host and assessed the influence of various factors on whether the remaining three mutations could evolve in a single host or in a short chain of transmission between hosts

The factors that increased the likelihood of mutations evolving are:

1. Random mutation. The replication mechanisms of influenza viruses don't make perfect copies. On average, every time an influenza virus replicates itself it makes approximately one mutation somewhere in the genome of each new virus. In each infected human there will be billions of viruses, and thus with many viruses replicating, multiple mutations can accumulate within a single host.

2. Positive selection. If some of the remaining mutations help the avian virus to adapt to mammals, then those mutations will make the viruses more fit and thus will be positively selected and preferentially accumulate.

3. Long infection. The longer someone is infected and producing new viruses, the more time there is for mutations to accumulate.

4. Functionally equivalent substitutions. The sets of substitutions identified by Fouchier and Kawaoka are unlikely to be the only combinations of substitutions capable of producing an aerosol transmissible virus. The probability of emergence increases with the number of combinations.

5. Diversity in the within-bird virus population. Given all of the mutations there are likely to be within a host due to random mutation, it is possible that the viruses from a bird that infect a human might have a mutation that would not be detected by routine surveillance. For example, if 100 virus particles from a bird infect a human and one of those particles had a key mutation, it would increase the probability of the mutation reaching high levels within a host even though routine sequencing would not detect it.

6. Transmission between mammals. If mammals are capable of transmitting viruses that have some but not all of the necessary substitutions it could increase the probability of an airborne transmissible virus evolving.

The factors that decreased the likelihood of mutations evolving are:

1. An effective immune response. An effective immune response would shorten the length of an infection and thus decrease the time available to accumulate mutations.

2. Deleterious substitutions. If any of the substitutions necessary for airborne transmission were harmful to the virus it would, on average, slow the accumulation of mutations.

3. Order of acquiring mutations. It is not currently known if the mutations for airborne transmissibility need to be acquired in a specific order. If they do, it would, on average, slow the accumulation of mutations.

"With the information we have, it is impossible to say what the exact risk is of the virus becoming airborne transmissible among humans. However, the results suggest that the remaining three mutations could evolve in a single human host, making a virus evolving in nature a potentially serious threat," said Derek Smith, Professor of Infectious Disease Informatics at the University of Cambridge. "We now know that it is in the realm of possibility that these viruses can evolve in nature, and what needs to be done to assess the risk more accurately of these mutations evolving in nature."

The scientists recommend the following activities be considered high priority for estimating and ameliorating the risk of emergence of aerosol transmissible H5N1 viruses.

First, additional surveillance in regions where viruses with airborne transmission enabling substitutions have been observed and in regions connected to those regions by bird migration and trade. Also, increased surveillance for mutations that might have the same function as those found by the Fouchier and Kawaoka labs.

Second, related to surveillance, some targeted sequencing of H5N1 viruses should be done by "deep sequencing" where the lab sequences many viruses from an individual host to look for viruses that might have accumulated the critical mutations, even if those viruses are just a small proportion of the viruses within an animal.

Third, further investigations are needed to determine which substitutions and combinations of substitutions that are not the same as, but have the same function as, the substitutions identified by the Fouchier and Kawaoka labs are capable of making viruses airborne transmissible between mammals.

Fourth, further studies are needed to elucidate the changes in within-host fitness and between-host transmissibility associated with each airborne transmission enabling substitution and combination of substitutions.

Professor Smith added: "The situation is similar to assessing the risk of an earthquake or tsunami. We don't know exactly when and where, but by increasing monitoring and research -- some of which is already underway -- scientists and public health officials will be able to increase the accuracy with which the risk can be assessed and to minimise those risks."

The research was funded by multiple sources including the European Commission through framework 7 grants EMPERIE and ANTIGONE, the Royal Society, the Human Frontiers Science Program, the Wellcome Trust, and the National Institutes of Health.

Source: University of Cambridge [June 21, 2012]

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The Power of Suggestion: What We Expect Influences Our Behavior, for Better or Worse

A lucky rabbit foot. A glass of wine. A pill. What do these things all have in common? Their effects -- whether we do well on a test, whether we mingle at the cocktail party, whether we feel better -- all depend on the power of suggestion.

In a new article, psychological scientists Maryanne Garry and Robert Michael of Victoria University of Wellington, along with Irving Kirsch of Harvard Medical School and Plymouth University, delve into the phenomenon of suggestion, exploring the intriguing relationship between suggestion, cognition, and behavior. The article is published in the June issue of Current Directions in Psychological Science, a journal of the Association for Psychological Science.

Over their research careers, Garry and Kirsch have both studied the effects of suggestion on cognition and behavior. Kirsch focused mostly on suggestion in clinical psychology, while Garry, whose work is supported by the Marsden Fund of New Zealand, was interested in the effects of suggestion on human memory. When the two got to talking, "we realized that the effects of suggestion are wider and often more surprising than many people might otherwise think," says Garry.

Across many studies, research has shown that deliberate suggestion can influence how people perform on learning and memory tasks, which products they prefer, and how they respond to supplements and medicines, which accounts for the well-known placebo effect.

But what can explain the powerful and pervasive effect that suggestion has in our lives? The answer lies in our 'response expectancies,' or the ways in which we anticipate our responses in various situations. These expectancies set us up for automatic responses that actively influence how we get to the outcome we expect. Once we anticipate a specific outcome will occur, our subsequent thoughts and behaviors will actually help to bring that outcome to fruition.

So, if a normally shy person expects that a glass of wine or two will help him loosen up at a cocktail party, he will probably feel less inhibited, approach more people, and get involved in more conversations over the course of the party. Even though he may give credit to the wine, it is clear that his expectations of how the wine would make him feel played a major role.

But it's not just deliberate suggestion that influences our thoughts and behaviors -- suggestions that are not deliberate can have the very same effects. As the authors point out, "simply observing people or otherwise making them feel special can be suggestive," a phenomenon termed the Hawthorne effect. As a result, people might work harder, or stick to a task for longer. And this case is more worrying, says Garry, "because although we might then give credit to some new drug or treatment, we don't realize that we are the ones who are actually wielding the influence."

It is for precisely this reason that the issue of unintentional suggestion has important implications for academic researchers. "In the scientific community, we need to be aware of -- and control for -- the suggestions we communicate to subjects," says Garry. The authors note that some recent failures to replicate previous research findings may ultimately be explained by such unintentional suggestion. "Recent research suggests that some of psychological science's most intriguing findings may be driven, at least in part, by suggestion and expectancies," Garry observes. "For example, a scientist who knows what the hypothesis of an experiment is might unwittingly lead subjects to produce the hypothesized effect -- for reasons that have nothing to do with the experiment itself."

And the unintended effects of suggestion aren't just restricted to the laboratory -- they cut across many real world domains, including the fields of medicine, education, and criminal justice. For example, converging evidence on eyewitness identification procedures demonstrates that the rate of false identifications is significantly higher when lineups are conducted by people who know who the suspect is than when the lineups are conducted by people who don't.

While research has provided clear evidence for the phenomenon of suggestion, there is still much more to learn about the underlying relationship between suggestion, cognition, and behavior. As the authors point out, researchers still don't know where the boundaries and limitations of these effects lie. "And, if a 'real' treatment and a 'suggestion' lead to a similar outcome, what differentiates between the two?" says Garry. Understanding these issues has important real world implications. "If we can harness the power of suggestion, we can improve people's lives."

Source: Association for Psychological Science [June 06, 2012]

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Statistical Model Attempting to Estimate Level of Alcohol Consumption That Is 'Optimal' for Health

Cutting the amount we drink to just over half a unit a day could save 4,600 lives a year in England, according to a modelling study by Oxford University researchers published in the journal BMJ Open.

Half a unit of alcohol is as little as a quarter of a glass of wine, or a quarter of a pint [Credit: © G.G. Lattek / Fotolia]

Scientists have carried out a complex analysis in an attempt to determine the "optimal" level of alcohol consumption that is associated with the lowest rates of chronic disease in the UK. They conclude that the intake of about one-half of a typical drink per day would result in the healthiest outcomes, and the authors conclude that the recommended alcohol intake for the UK should be reduced from the current advised level of drinking.

Half a unit of alcohol is as little as a quarter of a glass of wine, or a quarter of a pint. That's much lower than current government recommendations of between 3 to 4 units a day for men and 2-3 units for women.

The researchers set out to find the optimum daily amount of alcohol that would see fewest deaths across England from a whole range of diseases connected to drink. Previous studies have often looked at the separate effects of alcohol on heart disease, liver disease or cancers in isolation.

'Although there is good evidence that moderate alcohol consumption protects against heart disease, when all of the chronic disease risks are balanced against each other, the optimal consumption level is much lower than many people believe,' says lead author Dr Melanie Nichols of the BHF Health Promotion Research Group in the Department of Public Health at Oxford University.

The team used a mathematical model to assess what impact changing average alcohol consumption would have on deaths from 11 conditions known to be at least partially linked to drink.

These included coronary heart disease, stroke, high blood pressure, diabetes, cirrhosis of the liver, epilepsy, and five cancers. Over 170,000 people in England died from these 11 conditions in 2006, and ill health linked to alcohol is estimated to cost the NHS in England £3.3 billion every year.

The researchers used information from the 2006 General Household Survey on levels of alcohol consumption among adults in England. They combined this with the disease risks for differing levels of alcohol consumption as established in large analyses of published research.

They found that just over half a unit of alcohol a day was the optimal level of consumption among current drinkers.

They calculate this level of drinking would prevent around 4,579 premature deaths, or around 3% of all deaths from the 11 conditions.

The number of deaths from heart disease would increase by 843, but this would be more than offset by around 2,600 fewer cancer deaths and almost 3,000 fewer liver cirrhosis deaths.

'Moderating your alcohol consumption overall, and avoiding heavy-drinking episodes, is one of several things, alongside a healthy diet and regular physical activity, that you can do to reduce your risk of dying early of chronic diseases,' says Dr Nichols.

She adds: 'We are not telling people what to do, we are just giving them the best balanced information about the different health effects of alcohol consumption, so that they can make an informed decision about how much to drink.

'People who justify their drinking with the idea that it is good for heart disease should also consider how alcohol is increasing their risk of other chronic diseases. A couple of pints or a couple of glasses of wine per day is not a healthy option.'

Although this study in BMJ Open did not look at patterns of drinking, Dr Nichols says: 'Regardless of your average intake, if you want to have the best possible health, it is also very important to avoid episodes of heavy drinking ("binge drinking") as there is very clear evidence that this will increase your risks of many diseases, as well as your risk of injuries.'

Source: University of Oxford [June 06, 2012]

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To Quit Smoking, Try Eating More Veggies and Fruits

If you're trying to quit smoking, eating more fruits and vegetables may help you quit and stay tobacco-free for longer, according to a new study published online by University at Buffalo public health researchers.

If you're trying to quit smoking, eating more fruits and vegetables may help you quit and stay tobacco-free for longer [Credit: © taviphoto / Fotolia]

The paper, in the journal Nicotine and Tobacco Research, is the first longitudinal study on the relationship between fruit and vegetable consumption and smoking cessation.

The authors, from UB's School of Public Health and Health Professions, surveyed 1,000 smokers aged 25 and older from around the country, using random-digit dialing telephone interviews. They followed up with the respondents fourteen months later, asking them if they had abstained from tobacco use during the previous month.

"Other studies have taken a snapshot approach, asking smokers and nonsmokers about their diets," says Gary A. Giovino, PhD, chair of the Department of Community Health and Health Behavior at UB. "We knew from our previous work that people who were abstinent from cigarettes for less than six months consumed more fruits and vegetables than those who still smoked. What we didn't know was whether recent quitters increased their fruit and vegetable consumption or if smokers who ate more fruits and vegetables were more likely to quit."

The UB study found that smokers who consumed the most fruit and vegetables were three times more likely to be tobacco-free for at least 30 days at follow-up 14 months later than those consuming the lowest amount of fruits and vegetables. These findings persisted even when adjustments were made to take into account age, gender, race/ethnicity, education, household income and health orientation.

They also found that smokers with higher fruit and vegetable consumption smoked fewer cigarettes per day, waited longer to smoke their first cigarette of the day and scored lower on a common test of nicotine dependence.

"We may have identified a new tool that can help people quit smoking," says Jeffrey P. Haibach, MPH, first author on the paper and graduate research assistant in the UB Department of Community Health and Health Behavior. "Granted, this is just an observational study, but improving one's diet may facilitate quitting."

Several explanations are possible, such as less nicotine dependence for people who consume a lot of fruits and vegetables or the fact that higher fiber consumption from fruits and vegetables make people feel fuller.

"It is also possible that fruits and vegetables give people more of a feeling of satiety or fullness so that they feel less of a need to smoke, since smokers sometimes confuse hunger with an urge to smoke," explains Haibach.

And unlike some foods which are known to enhance the taste of tobacco, such as meats, caffeinated beverages and alcohol, fruits and vegetables do not enhance the taste of tobacco.

"Foods like fruit and vegetables may actually worsen the taste of cigarettes," says Haibach.

While smoking rates in the U.S. continue to decline, Giovino notes, the rate of that decline has slowed during the past decade or so. "Nineteen percent of Americans still smoke cigarettes, but most of them want to quit," he says.

Haibach adds: "It's possible that an improved diet could be an important item to add to the list of measures to help smokers quit. We certainly need to continue efforts to encourage people to quit and help them succeed, including proven approaches like quitlines, policies such as tobacco tax increases and smoke-free laws, and effective media campaigns."

The UB researchers caution that more research is needed to determine if these findings replicate and if they do, to identify the mechanisms that explain how fruit and vegetable consumption may help smokers quit. They also see a need for research on other dietary components and smoking cessation.

Gregory G. Homish, PhD, assistant professor in the UB Department of Community Health and Health Behavior, also is a co-author.

Funding was provided by the Robert Wood Johnson Foundation and LegacyA®.

Source: University at Buffalo [June 06, 2012]

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1 Million Billion Billion Billion Billion Billion Billion: Number of Undiscovered Drugs

A new voyage into "chemical space" -- occupied not by stars and planets but substances that could become useful in everyday life -- has concluded that scientists have synthesized barely one tenth of 1 percent of the potential medicines that could be made. The report, in the journal ACS Chemical Neuroscience, estimates that the actual number of these so-called "small molecules" could be 1 novemdecillion (that's 1 with 60 zeroes), 1 million billion billion billion billion billion billion, which is more than some estimates of the number of stars in the universe.

A new voyage into "chemical space" -- occupied not by stars and planets but substances that could become useful in everyday life -- has concluded that scientists have synthesized barely one tenth of 1 percent of the potential medicines that could be made [Credit: Web]

Jean-Louis Reymond and Mahendra Awale explain that small molecules, which are able to cross cell walls and interact with biological molecules in the body, are prime targets for scientists who develop new medicines. Most existing medications are small molecules. The authors focused on the "chemical space" inhabited by all of the small molecules that could possibly exist according to the laws of physics and chemistry. 

Researchers have identified millions of these compounds -- the ACS' Chemical Abstracts Service database contains almost 67 million substances. Reymond and Awale estimate that the molecules synthesized and tested as potential drugs so far represent less than 0.1 percent of chemical space. To aid researchers looking for new ways to prevent and treat disease, they set out to find the best ways to search for new small molecules.

The authors discuss several ways of getting a handle on chemical space, including by the size, shape and makeup of molecules. They show how computers can help researchers efficiently narrow a search for a new drug candidate. Computer modeling of chemical interactions can help researchers find a handful of promising molecules to synthesize and test in the lab. "Small molecule drugs are essential to the success of modern medicine," the authors note, and suggest that their methods may be particularly useful for finding new pharmaceuticals that target the central nervous system.

Source: American Chemical Society [June 06, 2012]

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Air Pollution Linked to Chronic Heart Disease

Air pollution, a serious danger to the environment, is also a major health risk, associated with respiratory infections, lung cancer and heart disease. Now a Tel Aviv University researcher has concluded that not only does air pollution impact cardiac events such as heart attack and stroke, but it also causes repeated episodes over the long term.

Cardiac patients living in high pollution areas were found to be over 40 percent more likely to have a second heart attack when compared to patients living in low pollution areas, according to Dr. Yariv Gerber of TAU's School of Public Health at the Sackler Faculty of Medicine. "We know that like smoking cigarettes, pollution itself provokes the inflammatory system. If you are talking about long-term exposure and an inflammatory system that is irritated chronically, pollution may well be involved in the progression of atrial sclerosis that manifests in cardiac events," explains Dr. Gerber.

Done in collaboration with Prof. Yaacov Drory and funded by the Environmental and Health Fund in Jerusalem, the research was presented at the San Diego Epidemiological Meeting of the American Heart Association in March and the Annual Meeting of the Israeli Heart Society in April.

Risking recurrence

Air pollution has previously been acknowledged as a factor in heart attack risk, as well as other health risks. The goal of this study, says Dr. Gerber, was to quantify that association and determine the long-term effects of air pollution on myocardial infarction (MI) patients. Their study followed 1,120 first-time MI patients who had been admitted to one of eight hospitals in central Israel between 1992 and 1993, all of whom were under the age of 65 at the time of admittance. The patients were followed up until 2011, a period of 19 years.

Air quality was measured at 21 monitoring stations inareas where the patients lived, and analyzed by a group of researchers at the Technion in Haifa. After adjusting for other factors such as socio-economic status and disease severity, the researchers identified an association between pollution and negative clinical outcomes, including mortality and recurrent vascular events such as heart attack, stroke and heart failure.

Compared to patients who lived in areas with the lowest recorded levels of pollution, those in the most polluted environment were 43 percent more likely to have a second heart attack or suffer congestive heart failure and 46 percent more likely to suffer a stroke. The study also found that patients exposed to air pollution were 35 percent more likely to die in the almost 20 year period following their first heart attack than those who were exposed to lower levels of pollution.

According to Dr. Gerber, the true impact of air pollution might be even stronger than this study shows. "Our method of assessing exposure does have limitations. Because we are using data from monitoring stations, it's a crude estimate of exposure, which most likely leads to an underestimation of the association," he warns. He estimates that air pollution could have double the negative impact with more precise measurement.

Identifying vulnerable groups

The results of the study not only indicate a health benefit for a public policy that curtails air pollution caused by industrial emissions and second hand smoke, but also call for heightened awareness by clinicians. Doctors should be making their patients aware of the risks of remaining in high pollution areas, suggesting that they work to limit their exposure, Dr. Gerber suggests.

Another purpose of this study was to begin identifying populations that are vulnerable to MI and re-occurring MI. Establishing the connection between air pollution and long-term risk for patients with cardiovascular diseases was an important step towards that goal.

Source: American Friends of Tel Aviv University [June 05, 2012]

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Female Choice Key to Evolutionary Shift to Modern Family

It is a question that has puzzled evolutionary biologists for years: Why did we stop being promiscuous and decide to settle down to start families?

Sergey Gavrilets, professor of ecology and evolutionary biology at the University of Tennessee, Knoxville, may have found the answer, and it lies in the power of female choice. The study reveals how females chose their mates played a critical role in human evolution by leading to monogamous relationships, which laid the foundation for the institution of the modern family.

Using mathematical modeling, the associate director for scientific activities at the National Institute for Mathematical and Biological Synthesis (NIMBioS) at UT has discovered that the transformation may have occurred when early-hominid females started choosing males who were good providers.

Gavrilets' findings are published in the Proceedings of the National Academy of Sciences.

The "sexual revolution" entailed males first competing with other males for dominance, as a way to get matings. However, low-ranked males—and eventually all males except those with the highest societal stature—began supplying females with provisions in what is called "food-for-mating" to get a leg up on the competition. Females showed preference for the "provisioning" males, leading males' energy to be spent on providing for females and females becoming increasingly faithful. This spurred self-domestication and the modern family as we know it today.

"This change has confounded scientists for a long time because many species would be much better off evolutionarily if the effort spent on males competing for mates was redirected towards increasing female fertility or survivorship of their offspring," said Gavrilets.

The study demonstrates mathematically that the most commonly proposed theories for the transition to human pair bonding—or coupling—are not biologically feasible.

However, the study advances a new model showing that the transition to pair-bonding can occur when female choice and faithfulness, among other factors, are included. The result is an increased emphasis on males provisioning females over male competition for mating.

"The study reveals that female choice played a crucial role in human evolution," said Gavrilets.

According to Gavrilets, the transition to coupling has opened the path to intensified male parental investment, which was a breakthrough adaptation with multiple anatomical, behavioral and physiological consequences for early hominids and for all of their descendants. It shifted the dynamic away from males competing with each other for sex to males competing with each other to see who is a better provider to get better mates.

"Pair bonding laid the foundation for a later emergence of the institution of the modern family," said Gavrilets.

Source: University of Tennessee [May 30, 2012]

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16th-Century Korean Mummy Provides Clue to Hepatitis B Virus Genetic Code

The discovery of a mummified Korean child with relatively preserved organs enabled an Israeli-South Korean scientific team to conduct a genetic analysis on a liver biopsy which revealed a unique hepatitis B virus (HBV) genotype C2 sequence common in Southeast Asia.

The ancient Korean mummy of a child provides clues to the hepatitis B virus genome [Credit: Seoul National Univesity]

Additional analysis of the ancient HBV genomes may be used as a model to study the evolution of chronic hepatitis B and help understand the spread of the virus, possibly from Africa to East-Asia. It also may shed further light on the migratory pathway of hepatitis B in the Far East from China and Japan to Korea as well as to other regions in Asia and Australia where it is a major cause of cirrhosis and liver cancer.

The reconstruction of the ancient hepatitis B virus genetic code is the oldest full viral genome described in the scientific literature to date. It was reported in the May 21 edition of the scientific journal Hepathology by a research team from the Hebrew University of Jerusalem's Koret School of Veterinary Medicine, the Robert H. Smith Faculty of Agriculture, Food and Environment; the Hebrew University's Faculty of Medicine, the Hadassah Medical Center's Liver Unit; Dankook University and Seoul National University in South Korea.

Carbon 14 tests of the clothing of the mummy suggests that the boy lived around the 16th century during the Korean Joseon Dynasty. The viral DNA sequences recovered from the liver biopsy enabled the scientists to map the entire ancient hepatitis B viral genome.

Using modern-day molecular genetic techniques, the researchers compared the ancient DNA sequences with contemporary viral genomes disclosing distinct differences. The changes in the genetic code are believed to result from spontaneous mutations and possibly environmental pressures during the virus evolutionary process. Based on the observed mutations rates over time, the analysis suggests that the reconstructed mummy's hepatitis B virus DNA had its origin between 3,000 to 100,000 years ago.

The hepatitis B virus is transmitted through the contact with infected body fluids , i.e. from carrier mothers to their babies, through sexual contact and intravenous drug abuse. According to the World Health Organization, there are over 400 million carriers of the virus worldwide, predominantly in Africa, China and South Korea, where up to 15 percent of the population are cariers of the virus. In recent years, universal immunization of newborns against hepatitis B in Israel and in South Korea has lead to a massive decline in the incidence of infection.

The findings are the result of a collaborative effort between Dr. Gila Kahila Bar-Gal of the Hebrew University of Jerusalem's Koret School of Veterinary Medicine; Prof. Daniel Shouval of the Hadassah Medical Center's Liver Unit and Hebrew University; Dr. Myeung Ju Kim of Dankook University, Seok Ju Seon Memorial Museum; Dr. Dong Hoon Shin of Seoul National University, College of Medicine ; Prof Mark Spigelman of the Hebrew University's Dept. of Parasitology and Dr. Paul R. Grant of University College of London,Dept. of Virology.

Source: Hebrew University of Jerusalem [May 29, 2012]

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Nanoparticles Seen as Artificial Atoms

In the growth of crystals, do nanoparticles act as "artificial atoms" forming molecular-type building blocks that can assemble into complex structures? This is the contention of a major but controversial theory to explain nanocrystal growth. A study by researchers at the U.S. Department of Energy (DOE)'s Lawrence Berkeley National Laboratory (Berkeley Lab) may resolve the controversy and point the way to energy devices of the future.

These are sequential color TEM images showing the growth of Pt3Fe nanorods over time, displayed as minutes:seconds. At the far right, twisty nanoparticle chains straighten and stretch into nanorods [Credit:  Haimei Zheng]

Led by Haimei Zheng, a staff scientist in Berkeley Lab's Materials Sciences Division, the researchers used a combination of transmission electron microscopy and advanced liquid cell handling techniques to carry out real-time observations of the growth of nanorods from nanoparticles of platinum and iron. Their observations support the theory of nanoparticles acting like artificial atoms during crystal growth.

"We observed that as nanoparticles become attached they initially form winding polycrystalline chains," Zheng says. "These chains eventually align and attach end-to-end to form nanowires that straighten and stretch into single crystal nanorods with length-to-thickness ratios up to 40:1. This nanocrystal growth process, whereby nanoparticle chains as well as nanoparticles serve as the fundamental building blocks for nanorods, is both smart and efficient."

Zheng is the corresponding author of a paper describing this research in the journal Science. The paper is titled "Real-Time Imaging of Pt3Fe Nanorod Growth in Solution." Co-authors are Hong-Gang Liao, Likun Cui and Stephen Whitelam.

If the near limitless potential of nanotechnology is to even be approached, scientists will need a much better understanding of how nano-sized particles can assemble into hierarchical structures of ever-increasing organization and complexity. Such understanding comes from tracking nanoparticle growth trajectories and determining the forces that guide these trajectories.

Through the use of transmission electron microscopy and liquid observation cells, scientists at Berkeley Lab and elsewhere have made significant progress in observing nanoparticle growth trajectories, including the oriented attachment of nanoparticles -- the chemical phenomenon that starts the growth of nanocrystals in solution. However, these observations have typically been limited to the first few minutes of crystal growth. In their study, Zheng and her colleagues were able to extend the time of observation from minutes to hours.

"The key to studying the growth of colloidal nanocrystals with different shapes and architectures is to maintain the liquid in the viewing window long enough to allow complete reactions," Zheng says. "We dissolved molecular precursors of platinum and iron in an organic solvent and used capillary pressure to draw the growth solution into a silicon-nitride liquid cell that we sealed with epoxy. The sealing of the cell was especially important as it helped keep the liquid from turning viscous over time. Previously, we'd often see the liquids become viscous and this would prevent the nanoparticle interactions that drive crystal growth from taking place."

Zheng and her colleagues chose to study the growth of platinum iron nanorods because of the electrocatalytic material's promising potential for use in next generation energy conversion and storage devices. They were able to observe these nanoparticles assemble into nanorod crystals using powerful transmission electron microscopes at Berkeley Lab's National Center for Electron Microscopy, including TEAM 0.5 (Transmission Electron Aberration-corrected Microscope), which can produce images with half‑angstrom resolution -- less than the diameter of a single hydrogen atom.

"From what we observed only single nanoparticles exist at the beginning of crystal growth, but, as growth proceeds, small chains of nanoparticles become dominant until, ultimately, only long chains of nanoparticles can be seen," Zheng says. "Our observations provide a link between the world of single molecules and hierarchical nanostructures, paving the way for the rational design of nanomaterials with controlled properties."

Source: DOE/Lawrence Berkeley National Laboratory [May 24, 2012]

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Drug Destroys Human Cancer Stem Cells but Not Healthy Ones

A team of scientists at McMaster University has discovered a drug, thioridazine, successfully kills cancer stem cells in the human while avoiding the toxic side-effects of conventional cancer treatments.

"The unusual aspect of our finding is the way this human-ready drug actually kills cancer stem cells; by changing them into cells that are non-cancerous," said Mick Bhatia, the principal investigator for the study and scientific director of McMaster's Stem Cell and Cancer Research Institute in the Michael G. DeGroote School of Medicine.

Unlike chemotherapy and radiation, thioridazine appears to have no effect on normal stem cells.

The research, published May 24 in the science journal Cell, holds the promise of a new strategy and discovery pipeline for the development of anticancer drugs in the treatment of various cancers. The research team has identified another dozen drugs that have good potential for the same response.

For 15 years, some researchers have believed stem cells are the source of many cancers. In 1997, Canadian researchers first identified cancer stem cells in certain types of leukemia. Cancer stem cells have since been identified in blood, breast, brain, lung, gastrointestinal, prostate and ovarian cancer.

To test more than a dozen different compounds, McMaster researchers pioneered a fully automated robotic system to identify several drugs, including thioridazine.

"Now we can test thousands of compounds, eventually defining a candidate drug that has little effect on normal stem cells but kills the cells that start the tumor," said Bhatia.

The next step is to test thioridazine in clinical trials, focusing on patients with acute myeloid leukemia whose disease has relapsed after chemotherapy. Bhatia wants to find out if the drug can put their cancer into remission, and by targeting the root of the cancer (cancer stem cells) prevent the cancer from coming back. Researchers at McMaster have already designed how these trials would be done.

Bhatia's team found thioridazine works through the dopamine receptor on the surface of the cancer cells in both leukemia and breast cancer patients. This means it may be possible to use it as a biomarker that would allow early detection and treatment of breast cancer and early signs of leukemia progression, he said.

The research team's next step is to investigate the effectiveness of the drug in other types of cancer. In addition, the team will explore several drugs identified along with thioridazine. In the future, thousands of other compounds will be analyzed with McMaster robotic stem cell screening system in partnership with collaborations that include academic groups as well as industry.

"The goal for all of the partners is the same -- to find unique drugs to change the way we tackle and treat cancer," he said.

The research was supported by grants from the Canadian Institute of Health Research (CIHR), the Canadian Cancer Society Research Institute (CCSRI) and the Ontario Ministry of Economic Development and Innovation (MEDI)'s Ontario Consortium of Regenerating inducing Therapeutics (OCRiT).

Source: McMaster University [May 24, 2012]

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Stressed Men Are More Social

Freiburg researchers have refuted the common belief that stress always causes aggressive behavior. A team of researchers led by the psychologists and neuroscientists Prof. Markus Heinrichs and Dr. Bernadette von Dawans at the University of Freiburg, Germany, examined in a study how men react in stressful situations -- and have refuted a nearly 100-year-old doctrine with their results.

According to this doctrine, humans and most animal species show the "fight-or-flight" response to stress. Only since the late 1990s have some scientists begun to argue that women show an alternate "tend-and-befriend" response to stress -- in other words, a protective ("tend") and friendship-offering ("befriend") reaction. Men, in contrast, were still assumed to become aggressive under stress. Von Dawans refuted this assumption, saying: "Apparently men also show social approach behavior as a direct consequence of stress."

With this study, the research team experimentally investigated male social behavior under stress for the first time. The results are published in the  journal Psychological Science. The economists Prof. Ernst Fehr of the University of Zurich, Switzerland, and Prof. Urs Fischbacher of the University of Konstanz, Germany, as well as the psychologist Prof. Clemens Kirschbaum from the Technical University of Dresden, Germany, also participated in the study. Last year, Heinrichs and von Dawans already developed a standardized procedure for inducing stress in groups using a public speaking task. The researchers examined the implications of this stressor for social behavior using specially designed social interaction games.. These games allowed them to measure positive social behavior -- for example, trust or sharing -- and negative social behavior -- for example, punishment.

In the study, subjects who were under stress showed significantly more positive social behavior than control subjects who were not in a stressful situation. Negative social behavior, on the other hand, was not affected by stress. For Markus Heinrichs, this has far-reaching consequences for our understanding of the social significance of stress: "From previous studies in our laboratory, we already knew that positive social contact with a trusted individual before a stressful situation reduces the stress response. Apparently, this coping strategy is anchored so strongly that people can also change their stress responses during or immediately after the stress through positive social behavior."

Source: Albert-Ludwigs-Universität Freiburg [May 21, 2012]

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Genetic Discovery Will Revolutionize Understanding Of Gene Expression

Over the past decade, research in the field of epigenetics has revealed that chemically modified bases are abundant components of the human genome and has forced us to abandon the notion we've had since high school genetics that DNA consists of only four bases.

Over the past decade, research in the field of epigenetics has revealed that chemically modified bases are abundant components of the human genome and has forced us to abandon the notion we've had since high school genetics that DNA consists of only four bases. Now, researchers have made a discovery that once again forces us to rewrite our textbooks. This time, however, the findings pertain to RNA, which like DNA carries information about our genes and how they are expressed. The researchers have identified a novel base modification in RNA which they say will revolutionize our understanding of gene expression [Credit: © Attila Németh / Fotolia]

Now, researchers at Weill Cornell Medical College have made a discovery that once again forces us to rewrite our textbooks. This time, however, the findings pertain to RNA, which like DNA carries information about our genes and how they are expressed. The researchers have identified a novel base modification in RNA which they say will revolutionize our understanding of gene expression.

Their report, published in the journal Cell, shows that messenger RNA (mRNA), long thought to be a simple blueprint for protein production, is often chemically modified by addition of a methyl group to one of its bases, adenine. Although mRNA was thought to contain only four nucleobases, their discovery shows that a fifth base, N6-methyladenosine (m6A), pervades the transcriptome. The researchers found that up to 20 percent of human mRNA is routinely methylated. Over 5,000 different mRNA molecules contain m6A, which means that this modification is likely to have widespread effects on how genes are expressed.

"This finding rewrites fundamental concepts of the composition of mRNA because, for 50 years, no one thought mRNA contained internal modifications that control function," says the study's senior investigator, Dr. Samie R. Jaffrey, an associate professor of pharmacology at Weill Cornell Medical College.

"We know that DNA and proteins are routinely modified by chemical switches that have profound effects on their function in both health and disease. But biologists believed mRNA was simply an intermediate between DNA and protein," he says. "Now we know mRNA is much more complex, and defects in RNA methylation can lead to disease."

Indeed, as part of the study, the researchers demonstrated that the obesity risk gene, FTO (fat mass and obesity-associated), encodes an enzyme capable of reversing this modification, converting m6A residues in mRNA back to regular adenosine. Humans with FTO mutations have an overactive FTO enzyme, which results in low levels of m6A and causes abnormalities in food intake and metabolism that lead to obesity.

The researchers uncovered links between m6A and other diseases as well.

"We found that m6A is present in many mRNAs encoded by genes linked to human diseases, including cancer as well as several brain disorders, such as autism, Alzheimer's disease, and schizophrenia," says the study's lead investigator, Dr. Kate Meyer, a postdoctoral researcher in Dr. Jaffrey's laboratory. 

"Methylation in RNA is a reversible modification that appears to be a central step in a wide variety of biological pathways and physiological processes," she says.

The first time that m6A was detected in mRNA was in 1975, but at the time scientists were unsure whether this finding was a result of contamination by other RNA molecules, Dr. Jaffrey says. Over 90 percent of RNA is either transfer RNA (tRNA) or ribosomal RNA (rRNA), cellular workhorses that are routinely modified.

But Dr. Jaffrey says he has always been interested in the idea that mRNA may be modified - "DNA, proteins, other forms of RNA are modified, so why not mRNA?" he says - so he and investigators in his laboratory developed a technique to help them uncover methylation in mRNA taken from both mouse and human samples.

They used two different antibodies that recognize and bind to m6A in mRNA in order to selectively isolate the mRNAs that contain m6A. By subjecting these mRNAs to next-generation sequencing, they were able to identify the sequence of each individual mRNA they had isolated. Co-authors Dr. Christopher Mason and Dr. Olivier Elemento, assistant professors from the Department of Physiology and Biophysics and Computational Genomics in Computational Biomedicine at Weill Cornell Medical College, then developed computational algorithms to reveal the identity of each of these methylated mRNAs.

The Weill Cornell researchers don't know how the thousands of m6As they detected in humans work to control the function of mRNAs, but they do note that the m6As are located near "stop codons" in mRNA sequences. These areas signal the end of translation of the mRNA, suggesting that m6A might influence ribosomal function. "But we really don't know yet," says Dr. Mason, a co-lead investigator on the study. "It may allow other proteins to bind to mRNA, or subject these mRNAs to a whole new regulatory pathway. Our bioinformatics analyses are providing several hints about the possible impact of methylation on RNA function."

Indeed, in their study, the investigators have already found that m6A sites frequently occur in regions of mRNA that are highly conserved across several species of vertebrates. "This shows that m6A sites are not just important for humans, but rather are maintained under selection across hundreds of millions of years of evolution, and thus are likely of critical importance for all animals," Dr. Mason says.

"This is the first demonstration of an epitranscriptomic modification - alterations in RNA function that are not due to changes in the underlying sequence," he adds.

"These findings are very, very exciting, and amazing, really, when you consider that mRNA has been around for so long and that nobody realized, in all this time, that they were being regulated in this way," Dr. Jaffrey says. "It was right under our noses."

In addition to investigating how m6A regulates mRNAs within cells, the researchers are now focused on identifying the enzymes and pathways that control mRNA methylation.

Their study already demonstrates that FTO is capable of reversing adenosine methylation and suggests that it acts on a large proportion of cellular mRNA. "FTO mutations are estimated to occur in one billion people worldwide and are a leading cause of obesity and type 2 diabetes. Our studies link m6A levels in mRNA to these major health problems and identify for the first time the mRNAs which are potentially targeted by FTO," Dr. Meyer says.

The investigators are currently working to understand how defective regulation of m6A in patients with FTO mutations causes obesity and metabolic disorders, and they are also developing tests to rapidly identify compounds that inhibit FTO activity. These compounds are expected to inhibit the overactive FTO found in humans, potentially leading to novel therapeutics for diabetes and obesity.

Source: Medical News Today {May 19, 2012]

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Emotionally Intelligent People Are Less Good at Spotting Liars

People who rate themselves as having high emotional intelligence (EI) tend to overestimate their ability to detect deception in others. This is the finding of a paper published in the journal Legal and Criminological Psychology on18 May 2012.

Professor Stephen Porter, director of the Centre for the Advancement of Psychological Science and Law at University of British Columbia, Canada, along with colleagues Dr. Leanne ten Brinke and Alysha Baker used a standard questionnaire to measure the EI of 116 participants.

These participants were then asked to view 20 videos from around the world of people pleading for the safe return of a missing family member. In half the videos the person making the plea was responsible for the missing person's disappearance or murder.

The participants were asked to judge whether the pleas were honest or deceptive, say how much confidence they had in their judgements, report the cues they had used to make those judgements and rate their emotional response to each plea.

Professor Porter found that higher EI was associated with overconfidence in assessing the sincerity of the pleas and sympathetic feelings towards people in the videos who turned out to be responsible for the disappearance.

Although EI, in general, was not associated with being better or worse at discriminating between truths and lies, people with a higher ability to perceive and express emotion (a component of EI) were not so good at spotting when people were telling lies.

Professor Porter says: "Taken together, these findings suggest that features of emotional intelligence, and the decision-making processes they lead to, may have the paradoxical effect of impairing people's ability to detect deceit.

"This finding is important because EI is a well-accepted concept and is used in a variety of domains, including the workplace."

Source: British Psychological Society (BPS) [May 18, 2012]

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How Exercise Affects the Brain

Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth's David Bucci thinks there is much more going on.

Exercise clears the mind. It gets the blood pumping and more oxygen is delivered to the brain. This is familiar territory, but Dartmouth's David Bucci thinks there is much more going on [Credit: Web]

"In the last several years there have been data suggesting that neurobiological changes are happening -- [there are] very brain-specific mechanisms at work here," says Bucci, an associate professor in the Department of Psychological and Brain Sciences.

From his studies, Bucci and his collaborators have revealed important new findings:

• The effects of exercise are different on memory as well as on the brain, depending on whether the exerciser is an adolescent or an adult.

• A gene has been identified which seems to mediate the degree to which exercise has a beneficial effect. This has implications for the potential use of exercise as an intervention for mental illness.

Bucci began his pursuit of the link between exercise and memory with attention deficit hyperactivity disorder (ADHD), one of the most common childhood psychological disorders. Bucci is concerned that the treatment of choice seems to be medication.

"The notion of pumping children full of psycho-stimulants at an early age is troublesome," Bucci cautions. "We frankly don't know the long-term effects of administering drugs at an early age -- drugs that affect the brain -- so looking for alternative therapies is clearly important."

Anecdotal evidence from colleagues at the University of Vermont started Bucci down the track of ADHD. Based on observations of ADHD children in Vermont summer camps, athletes or team sports players were found to respond better to behavioral interventions than more sedentary children. While systematic empirical data is lacking, this association of exercise with a reduction of characteristic ADHD behaviors was persuasive enough for Bucci.

Coupled with his interest in learning and memory and their underlying brain functions, Bucci and teams of graduate and undergraduate students embarked upon a project of scientific inquiry, investigating the potential connection between exercise and brain function. They published papers documenting their results, with the most recent now available in the online version of the journal Neuroscience.

Bucci is quick to point out that "the teams of both graduate and undergraduates are responsible for all this work, certainly not just me." Michael Hopkins, a graduate student at the time, is first author on the papers.

Early on, laboratory rats that exhibit ADHD-like behavior demonstrated that exercise was able to reduce the extent of these behaviors. The researchers also found that exercise was more beneficial for female rats than males, similar to how it differentially affects male and female children with ADHD.

Moving forward, they investigated a mechanism through which exercise seems to improve learning and memory. This is "brain derived neurotrophic factor" (BDNF) and it is involved in growth of the developing brain. The degree of BDNF expression in exercising rats correlated positively with improved memory, and exercising as an adolescent had longer lasting effects compared to the same duration of exercise, but done as an adult.

"The implication is that exercising during development, as your brain is growing, is changing the brain in concert with normal developmental changes, resulting in your having more permanent wiring of the brain in support of things like learning and memory," says Bucci. "It seems important to [exercise] early in life."

Bucci's latest paper was a move to take the studies of exercise and memory in rats and apply them to humans. The subjects in this new study were Dartmouth undergraduates and individuals recruited from the Hanover community.

Bucci says that, "the really interesting finding was that, depending on the person's genotype for that trophic factor [BDNF], they either did or did not reap the benefits of exercise on learning and memory. This could mean that you may be able to predict which ADHD child, if we genotype them and look at their DNA, would respond to exercise as a treatment and which ones wouldn't."

Bucci concludes that the notion that exercise is good for health including mental health is not a huge surprise. "The interesting question in terms of mental health and cognitive function is how exercise affects mental function and the brain." This is the question Bucci, his colleagues, and students continue to pursue.

Author: Joseph Blumberg | Source: Dartmouth College [May 18, 2013]

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Are character traits determined genetically?

Genes play a greater role in forming character traits -- such as self-control, decision making or sociability -- than was previously thought, new research suggests.

Genes play a greater role in forming character traits -- such as self-control, decision making or sociability -- than was previously thought, new research suggests [Credit: Web]

A study of more than 800 sets of twins found that genetics were more influential in shaping key traits than a person's home environment and surroundings.

Psychologists at the University of Edinburgh who carried out the study, say that genetically influenced characteristics could well be the key to how successful a person is in life.

The study of twins in the US -- most aged 50 and over- used a series of questions to test how they perceived themselves and others. Questions included "Are you influenced by people with strong opinions?" and "Are you disappointed about your achievements in life?"

The results were then measured according to the Ryff Psychological Well-Being Scale which assesses and standardizes these characteristics.

By tracking their answers, the research team found that identical twins -- whose DNA is [presumed to be] exactly the same -- were twice as likely to share traits compared with non-identical twins.

Psychologists say the findings are significant because the stronger the genetic link, the more likely it is that these character traits are carried through a family.

Professor Timothy Bates, of the University of Edinburgh's School of Philosophy, Psychology and Language Sciences, said that the genetic influence was strongest on a person's sense of self-control.

Researchers found that genes affected a person's sense of purpose, how well they get on with people and their ability to continue learning and developing.

Professor Bates added: "Ever since the ancient Greeks, people have debated the nature of a good life and the nature of a virtuous life. Why do some people seem to manage their lives, have good relationships and cooperate to achieve their goals while others do not? Previously, the role of family and the environment around the home often dominated people's ideas about what affected psychological well-being. However, this work highlights a much more powerful influence from genetics."

The study, which builds on previous research that found that happiness is underpinned by genes, is published online in the Journal of Personality.

Source: University of Edinburgh [May 16, 2013]

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In the Genes, but Which Ones? Studies That Linked Specific Genes to Intelligence Were Largely Wrong, Experts Say

For decades, scientists have understood that there is a genetic component to intelligence, but a new Harvard study has found both that most of the genes thought to be linked to the trait are probably not in fact related to it, and identifying intelligence's specific genetic roots may still be a long way off.

For decades, scientists have understood that there is a genetic component to intelligence, but a new study has found both that most of the genes thought to be linked to the trait are probably not in fact related to it, and identifying intelligence's specific genetic roots may still be a long way off [Credit: Web]

Led by David I. Laibson '88, the Robert I. Goldman Professor of Economics, and Christopher F. Chabris '88, Ph.D. '99, assistant professor of psychology at Union College in Schenectady, N.Y., a team of researchers examined a dozen genes using large data sets that included both intelligence testing and genetic data. As reported in a forthcoming article in the journal Psychological Science, they found that in nearly every case, the hypothesized genetic pathway failed to replicate. In other words, intelligence could not be linked to the specific genes that were tested.

"It is only in the past 10 or 15 years that we have had the technology for people to do studies that involved picking a particular genetic variant and investigating whether people who score higher on intelligence tests tend to have that genetic variant," said Chabris. "In all of our tests we only found one gene that appeared to be associated with intelligence, and it was a very small effect. This does not mean intelligence does not have a genetic component, it means it's a lot harder to find the particular genes, or the particular genetic variants, that influence the differences in intelligence."

To get at the question of how genes influence intelligence, researchers first needed data, and plenty of it.

Though it had long been understood, based on studies of twins, that intelligence was a heritable trait, it wasn't until relatively recently that the technology emerged to allow scientists to directly probe DNA in a search for genes that affected intelligence.

The problem, Chabris said, was that early technology for assaying genes was very expensive, meaning that such studies were typically limited to, at most, several hundred subjects, who would take IQ tests and provide DNA samples for testing.

As part of their study, Chabris and his colleagues relied on several pre-existing data sets -- a massive study of Wisconsin high school graduates that began in the 1950s, the Framingham Heart Study, and an ongoing survey of all twins born in Sweden -- to expand that subject pool from a few hundred to many thousands.

"What we want to emphasize is that we are not saying the people who did earlier research in this area were foolish or wrong," Chabris said. "They were using the best technology they had available. At the time it was believed that individual genes would have a much larger effect -- they were expecting to find genes that might each account for several IQ points."

To identify genes that might play a role in intelligence, previous researchers used the "candidate gene approach," which requires identifying a gene that is already linked with a known biological function -- such as Alzheimer's disease or the production of a specific neurotransmitter. If people who scored high on intelligence tests shared a particular variant of that gene, it was believed, that demonstrated the gene's role in intelligence.

"These were reasonable hypotheses," said study co-author Daniel J. Benjamin '99, Ph.D. '06, assistant professor of economics at Cornell University. "But in retrospect, either the findings were false positives or the effects of the genes are much, much smaller than anyone had anticipated."

Chabris, however, emphasized that the results don't point to the idea that the dozen genes examined in the study play no role in intelligence, but rather suggest that intelligence may be tied to many genes and the ways in which they interact.

"As is the case with other traits, like height, there are probably thousands of genes and their variants that are associated with intelligence," he said. "And there may be other genetic effects beyond the single gene effects -- there could be interactions between genes, there could be interactions between genes and the environment. What our results show is that the way researchers have been looking for genes that may be related to intelligence -- the candidate gene method -- is fairly likely to result in false positives, so other methods should be used."

Author: Peter Reuell | Source: Harvard University [February 24, 2012]

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A walk in the park gives mental boost to people with depression

A walk in the park may have psychological benefits for people suffering from depression. In one of the first studies to examine the effect of nature walks on cognition and mood in people with major depression, researchers in Canada and the U.S. have found promising evidence that a walk in the park may provide some cognitive benefits.

The study was led by Marc Berman, a post-doctoral fellow at Baycrest's Rotman Research Institute in Toronto, with partners from the University of Michigan and Stanford University. It is published online this week, ahead of print publication, in the Journal of Affective Disorders.

"Our study showed that participants with clinical depression demonstrated improved memory performance after a walk in nature, compared to a walk in a busy urban environment," said Dr. Berman, who cautioned that such walks are not a replacement for existing and well-validated treatments for clinical depression, such as psychotherapy and drug treatment.

"Walking in nature may act to supplement or enhance existing treatments for clinical depression, but more research is needed to understand just how effective nature walks can be to help improve psychological functioning," he said.

Dr. Berman's research is part of a cognitive science field known as Attention Restoration Theory (ART) which proposes that people concentrate better after spending time in nature or looking at scenes of nature. The reason, according to ART, is that people interacting with peaceful nature settings aren't bombarded with external distractions that relentlessly tax their working memory and attention systems. In nature settings, the brain can relax and enter a state of contemplativeness that helps to restore or refresh those cognitive capacities.

In a research paper he published in 2008 in Psychological Science, Dr. Berman showed that adults who were not diagnosed with any illness received a mental boost after an hour-long walk in a woodland park – improving their performance on memory and attention tests by 20 percent – compared to an hour-long stroll in a noisy urban environment. The findings were reported by The Wall Street Journal, The Boston Globe, The New York Times, and in the Pulitzer Prize finalist book by Nicholas Carr, The Shallows: What the internet is doing to our brains.

In this latest study, Dr. Berman and his research team explored whether a nature walk would provide similar cognitive benefits, and also improve mood for people with clinical depression. Given that individuals with depression are characterized by high levels of rumination and negative thinking, the researchers were skeptical at the outset of the study that a solitary walk in the park would provide any benefit at all and may end up worsening memory and exacerbating depressed mood.

For the study, 20 individuals were recruited from the University of Michigan and surrounding Ann Arbor area; all had a diagnosis of clinical depression. The 12 females and eight males (average age 26) participated in a two-part experiment that involved walking in a quiet nature setting and in a noisy urban setting.

Prior to the walks, participants completed baseline testing to determine their cognitive and mood status. Before beginning a walk, the participants were asked to think about an unresolved, painful autobiographical experience. They were then randomly assigned to go for an hour-long walk in the Ann Arbor Arboretum (woodland park) or traffic heavy portions of downtown Ann Arbor. They followed a prescribed route and wore a GPS watch to ensure compliance.

After completing their walk, they completed a series of mental tests to measure their attention and short-term/working memory and were re-asssessed for mood. A week later the participants repeated the entire procedure, walking in the location that was not visited in the first session.

Participants exhibited a 16 percent increase in attention and working memory after the nature walk relative to the urban walk. Interestingly, interacting with nature did not alleviate depressive mood to any noticeable degree over urban walks, as negative mood decreased and positive mood increased after both walks to a significant and equal extent. Dr. Berman says this suggests that separate brain mechanisms may underlie the cognitive and mood changes of interacting with nature. 

Source: Baycrest Centre for Geriatric Care [May 14, 2012]

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Powerful Function of Single Protein That Controls Neurotransmission Discovered

Scientists at Weill Cornell Medical College have discovered that the single protein -- alpha 2 delta -- exerts a spigot-like function, controlling the volume of neurotransmitters and other chemicals that flow between the synapses of brain neurons. The study, published online in Nature, shows how brain cells talk to each other through these signals, relaying thoughts, feelings and action, and this powerful molecule plays a crucial role in regulating effective communication.

In the study, the investigators also suggest how the widely used pain drug Lyrica might work. The alpha 2 delta protein is the target of this drug and the new work suggests an approach to how other drugs could be developed that effectively twist particular neurotransmitter spigots on and off to treat neurological disorders. The research findings surprised the research team, which includes scientists from University College London.

"We are amazed that any single protein has such power," says the study's lead investigator Dr. Timothy A. Ryan, professor of Biochemistry and associate professor of Biochemistry in Anesthesiology at Weill Cornell Medical College. "It is indeed rare to identify a biological molecule's function that is so potent, that seems to be controlling the effectiveness of neurotransmission."

The researchers found that alpha 2 delta determines how many calcium channels will be present at the synaptic junction between neurons. The transmission of chemical signals is triggered at the synapse by the entry of calcium into these channels, so the volume and speed of neurotransmission depends on the availability of these channels.

Researchers discovered that taking away alpha 2 delta from brain cells prevented calcium channels from getting to the synapse. "But if you add more alpha 2 delta, you can triple the number of channels at synapses," Dr. Ryan says. "This change in abundance was tightly linked to how well synapses carry out their function, which is to release neurotransmitters."

Before this study, it was known that Lyrica, which is used for neuropathic pain, seizures and fibromyalgia, binds to alpha 2 delta, but little was understood about how this protein works to control synapses.

Lifting up the Hood

Dr. Ryan is building what he calls a "shop manual" of neurological function, much of which centers on synaptic neurotransmission. In 2007 and 2008, he discovered crucial clues to how neurons repackage the chemicals used to signal across synapses. In 2011, Dr. Ryan discovered that distinct neurons differently tune the speed by which they package these chemicals. And in a recent study published April 29 in Nature Neuroscience, he described, for the first time, the molecular mechanisms at the synapse that control the release of dopamine, a crucial neurotransmitter.

"We are looking under the hood of these machines for the first time," he says. "Many neurological diseases are considered to arise from pathologies of synaptic function. The synapse is so complex; at least a few thousand genes control how they work. Repairing them through treatment requires that we understand how they work."

Dr. Ryan and his team often use two tools to conduct these studies -- they pin fluorescent tags on to molecules involved in synaptic function, and use ultra sensitive microscopy technology to watch these molecules up close and in real-time.

The researchers used the same toolkit to examine the function of calcium channels, which triggers neurotransmission. "At all synapses, the secretion of a neurotransmitter is driven by the arrival of an electric impulse, initiated by another neuron," Dr. Ryan says. When this impulse arrives at the nerve terminal it triggers the opening of calcium channels. The calcium that rushes in is the key trigger that drives a synapse to secrete its neurotransmitter.

"We have known for the past half century that calcium is a key controller of neurotransmission," he says. "Any small change in calcium influx has a big impact on neurotransmission."

Protein Acts like a Shipping Label

But the number of calcium channels at the synapse is not static. Neurons constantly replace worn out channels, and to do this, they build the channels in the neuron's cell body and then package them up and ship them to the nerve terminal. In some cases, that is a very long journey -- as much as a few feet, such as the distance between the brain and the base of the spinal cord or the length of a leg.

In the study, researchers tagged fluorescent proteins onto a gene that encodes protein that makes a calcium channel and delivered it to neurons. They then watched the progress of the newly formed channels as they made their way, from day four to day seven, from the bodies of neurons to the synapse.

They also manipulated the levels of alpha 2 delta, a suspected calcium channel partner, and discovered that when the protein was increased, more calcium channels were moved to the synapse. Less alpha 2 delta reduced the flow. "We discovered that alpha 2 delta made the decision of how many calcium channels should be shipped the length of the neuron to the synapse," Dr. Ryan says. "It's like the channels couldn't be transported without an alpha 2 delta shipping label."

The research team found however that alpha 2 delta must work in at least two steps. When they impaired a piece of alpha 2 delta that resembles proteins that are involved in how cells bind to each other, they found that this broken alpha 2 delta could still help get calcium channels shipped down to synapses. But once there, they no longer helped drive neurotransmitter release. "This means that not only does alpha 2 delta help to get calcium channels shipped out, but it also implies that something at the synapse has to sign-off on receiving the calcium channels, putting them in the right place for them to do their job," Dr. Ryan says.

The researchers suggest that Lyrica might work by interfering with this final step since the piece of alpha 2 delta they "broke" that prevents the signing-off resembles parts of proteins that allows them to stick to each other in a kind of handshake.

These findings suggest that future therapies designed to manipulate neurotransmission could try to target this handshaking process, Dr. Ryan says. To do this will require that researchers identify the missing partner in the handshake.

"We hope these exciting findings are providing a new direction in how to make better drugs to control communication between brain cells," Dr. Ryan says.

The study was funded by the National Institutes of Mental Health and the Welcome Trust. Co-authors of the study include Dr. Michael B. Hoppa from Weill Cornell Medical College, and Dr. Beatrice Lana, Dr. Wojciech Margas, and Dr. Annette C. Dolphin from University College London.

Source: NewYork-Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College [May 13, 2012]

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