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In the current issue of the Journal of Medicinal Chemistry, they report insights that could potentially lead to the development of custom-tailored anti-cancer drugs.

What makes cancer cells so dangerous is that they proliferate much more rapidly than other cells. An important contribution to this capability is made by a particular group of proteins, the so-called kinases. And it's against the kinases that many cancer drugs in development today take aim. Another promising approach came to light a few years ago with the discovery that the proliferation of cancer cells could also be arrested through proteasome inhibition. Yet the first drug to employ this strategy caused a number of severe side-effects. Despite that, the drug is expected to generate revenues of more than a billion U.S. dollars this year.

In the search for alternatives, San Diego-based Nereus Pharmaceuticals homed in on a species of marine bacteria known as Salinispora tropica. These bacteria produce a small molecule that kills affected cells by disabling proteasomes, which serve as their waste processing plants. "In the life cycle of a cell, proteins are always being built up that will need to be demolished after they have done their work," explains TUM Professor Michael Groll, leader of the research team in Munich. "If this breakdown is blocked, the cells choke on their own waste."

After promising preclinical trials, the bacteria-produced Salinosporamide A (NPI-0052; Sal-A) has advanced into human clinical trials. "Over millions of years, the bacteria developed this substance into a perfect weapon," says Dr. Barbara Potts, vice president for chemical and oncological development at Nereus Pharmaceuticals. The ideal cancer drug would kill only cancer cells, while doing the least harm possible to healthy cells. The researchers took a closer look at the pathway for this reaction, in the hope that they might better understand the mechanism and the best approach to future generation analogues.

The research team of Barbara Potts and Michael Groll managed to produce crystals of proteasomes blocked by Salinosporamide A and determined, through X-ray crystallography, the precise arrangement of the atoms. It became clear why the bacterial poison is so effective: The molecule fits an opening in the proteasome like a key, and locks it up. A subsequent reaction transforms the molecule to a complex that can no longer be detached, in effect breaking off the key in the lock. Vital processes come to a halt.

Halogen-hydrocarbons are favored in industrial chemistry, because the halogen atom can be easily separated from other groups. It's just this trick that the Salinispora tropica bacterium employs in the case of Salinosporamide A. It uses a chloride as its so-called "leaving group" to trigger an internal reaction forming a ring-like bond. If the ring is closed, the lock is jammed.

The researchers next produced variants of Salinosporamide A and once again succeeded in crystallizing them and using X-ray techniques for structural analysis. By replacing the chlorine atom with fluorine, they were able to observe the progress of the reaction. After the key had been stuck in the lock for one hour of reaction time, the biochemists were still able to pull it out again. A few hours later, the fluorine was split off, and the lock was blocked.

"After the millions of years that have gone into the evolutionary development of this method in bacteria, it's unlikely that a better way to block the proteasome is even possible," Groll says. "Now that we know how the best possible reaction proceeds, we can alter it in targeted ways with the aim of developing tailored, effective proteasomal drugs that will have improved safety and efficacy."

The application, "Outbreaks Near Me," builds upon the mission and proven capability of HealthMap, an online resource that collects, filters, maps and disseminates information about emerging infectious diseases, and provides a new, contextualized view of a user's specific location – pinpointing outbreaks that have been reported in the vicinity of the user and offering the opportunity to search for additional outbreak information by location or disease.

Additional functionality of Outbreaks Near Me is the ability to set alerts that will notify a user on their device or by e-mail when new outbreaks are reported in their proximity, or if a user enters a new area of activity.

"We hope individuals will find the new app to be a useful source of outbreak information – locally, nationally, and globally," says HealthMap co-founder John Brownstein, PhD, assistant professor in the Children's Hospital Informatics Program (CHIP). "As people are equipped with more knowledge and awareness of infectious disease, the hope is that they will become more involved and proactive about public health."

The new application also features an option for users to submit an outbreak report. This will enable individuals in cities and countries around the world to interact with the HealthMap team and participate in the public health surveillance process. Users may take photos – of situations and scenarios of, and/or leading to, disease – with their iPhone and submit them to the HealthMap system for review and eventual posting as an alert on the worldwide map.

"This is grassroots, participatory epidemiology," says HealthMap co-founder Clark Freifeld, a PhD student at the MIT Media Lab and research software developer at CHIP. "In releasing this app we aim to empower citizens in the cause of public health, not only by providing ready access to real-time information, but also by encouraging them to contribute their own knowledge, expertise, and observations. In enabling participation in surveillance, we also expect to increase global coverage and identify outbreaks earlier."

HealthMap was founded in 2006 and mines the Internet – searching disparate data sources such as news reports, curated personal accounts, official alerts, blogs and chat rooms – to track and map infectious disease outbreaks. While the data have been shown to provide early information on new outbreaks, users are encouraged to interpret the data appropriately as it is drawn from both official and unofficial sources.

The HealthMap Web site (http://www.healthmap.org) averages 10,000 unique visits a day, including regular users from the World Health Organization, the CDC, and the European Centre for Disease Prevention and Control. During the peak of H1N1 swine flu this spring, visits to the site rose substantially, with as many as 150,000 visitors coming to the Web site to search for information.

Outbreaks Near Me was developed with support from Google.org and is available at no cost for download in the iTunes App Store. For more information on Outbreaks Near Me, visit: http://healthmap.org/iphone.php.

"Beauty," goes the old saying, "is in the eye of the beholder." But does the beholder have to be human? (Credit: iStockphoto)

Not necessarily, say scientists at Tel Aviv University. Amit Kagian, an M.Sc. graduate from the TAU School of Computer Sciences, has successfully "taught" a computer how to interpret attractiveness in women. But there's a more serious dimension to this issue that reaches beyond mere vanity. The discovery is a step towards developing artificial intelligence in computers. Other applications for the software could be in plastic and reconstructive surgery and computer visualization programs such as face recognition technologies.

From Mathematics to Aesthetics

"Until now, computers have been taught how to identify basic facial characteristics, such as the difference between a woman and a man, and even to detect facial expressions," says Kagian. "But our software lets a computer make an aesthetic judgment. Linked to sentiments and abstract thought processes, humans can make a judgment, but they usually don't understand how they arrived at their conclusions."

In the first step of the study, 30 men and women were presented with 100 different faces of Caucasian women, roughly of the same age, and were asked to judge the beauty of each face. The subjects rated the images on a scale of 1 through 7 and did not explain why they chose certain scores. Kagian and his colleagues then went to the computer and processed and mapped the geometric shape of facial features mathematically.

Additional features such as face symmetry, smoothness of the skin and hair color were fed into the analysis as well. Based on human preferences, the machine "learned" the relation between facial features and attractiveness scores and was then put to the test on a fresh set of faces.

Says Kagian, "The computer produced impressive results -- its rankings were very similar to the rankings people gave." This is considered a remarkable achievement, believes Kagian, because it's as though the computer "learned" implicitly how to interpret beauty through processing previous data it had received.

Beauty is Golden

The notion that beauty can be boiled down to binary data and interpreted by a mathematical model is nothing new. More than 2,000 years ago the Greek mystic, philosopher and mathematician Pythagoras observed the connection between math, geometry and beauty. He reasoned that features of physical objects corresponding to the "golden ratio" were considered most attractive.

"I know that Plato connected the good to the beautiful," says Kagian. "Personally, I believe that some kind of universal correctness to beauty exists in nature, an aesthetic interpretation of the universal truth. But because each of us is trapped with our own human biases and personalized viewpoints, this may detract us from finding the ultimate formula to a complete understanding of beauty."

Kagian, who studied under the Adi Lautman multidisciplinary program for outstanding students at Tel Aviv University, says that a possible next step is to teach computers how to recognize "beauty" in men. This may be more difficult. Psychological research has shown that there is less agreement as to what defines "male beauty" among human subjects. And his own portrait, jokes Kagian, will not be part of the experiment.

"I would probably blow up the machine," he says.

Kagian published the findings in the scientific journal Vision Research. Co-authors on the work were Kagian's supervisors Prof. Eytan Ruppin and Prof. Gideon Dror.

Adapted from materials provided by Tel Aviv University.

Virtual peer Sam, designed to look around eight-years-old and is gender ambiguous, is projected on a large screen. A dollhouse with moveable furniture and figurines sits between the child with autism and Sam. Sam engages the child with autism in conversation and play while a researcher observes their interaction. (Credit: Northwestern University)

Justine Cassell, professor of communication studies and electrical engineering and computer science, recently presented a preliminary study on the work at a meeting of the American Association for the Advancement of Science.

"Children with high-functioning autism may be able to give you a lecture on a topic of great interest to them but they can't carry on a 'contingent' -- or two-way -- conversation," said Cassell, director of Northwestern's Center for Technology and Social Behavior.

Cassell and researcher Andrea Tartaro collected data from six children with high-functioning autism aged 7 to 11 as they engaged in play during an hour-long session with a real-life child, and with a virtual peer named Sam.

In an analysis of those interactions, they found that children with autism produced more and more "contingent" sentences when they spoke with the virtual peer, while their sentences did not become increasingly contingent when they were paired with the real-life children.

"Certainly we're not saying that virtual peers make the best playmates for children with autism," said Tartaro. "The overall goal is for the children with autism to generalize the skills they learn in practice sessions with virtual peers to meaningful interactions with real-world children."

Nor are Northwestern researchers saying they can teach "contingency" -- appropriate back and forth conversation -- in a single session. But their findings hold promise that virtual peers can be useful in helping children with autism develop communication and social skills.

And virtual peers have some distinct advantages over real-life children when it comes to practicing social skills. For starters, children with autism often like technology. "It interacts to us," said one child with autism upon first meeting a virtual peer.

What's more, said Cassell, virtual peers don't get tired or impatient. "We can program their conversation to elicit socially-skilled behavior, and we can vary the way that they look and behave so children with autism are exposed to different kinds of behavior."

Cassell and Tartaro's study is part of larger efforts taking place in the Articulab, the Northwestern University laboratory where Cassell and colleagues explore how people communicate with and through technology.

In the Articulab, Cassell, who was trained as a psychologist and linguist, and Tartaro are teaming up with psychologist Miri Arie to develop assessment and intervention procedures that they hope will give them a better understanding of peer behaviors of children with autism.

A major challenge for children with autism is learning the rules of social behavior that typically developing children seem to learn intuitively.

"Although children's play appears spontaneous and wild, it follows certain basic social rules," said Arie. "We hope virtual peers like Sam will allow children with autism to practice the rules behind joining a game, holding a conversation and maintaining social interaction. Then they can apply their newly acquired skills to real-life situations."

Adapted from materials provided by Northwestern University, via EurekAlert!, a service of AAAS.

Renewable energy sources, such as wind, could help society reduce emissions of carbon dioxide. (Credit: Photo by Bob Henson Copyright UCAR)

The authors, from the University of Colorado at Boulder, the National Center for Atmospheric Research (NCAR) in Boulder, and McGill University in Montreal, say the Intergovernmental Panel on Climate Change (IPCC) has significantly underestimated the technological challenges of reducing CO₂ emissions. The study, "Dangerous Assumptions," concludes that the IPCC is overly optimistic in assuming that, even without action by policymakers, society will develop and implement new technologies to dramatically reduce the growth of future emissions.

"In the end, there is no question whether technological innovation is necessary--it is," write the authors in the Nature commentary. "The question is, to what degree should policy focus explicitly on motivating such innovation" The IPCC plays a risky game in assuming that spontaneous advances in technological innovation will carry most of the burden of achieving future emissions reductions, rather than focusing on those conditions that are necessary and sufficient for those innovations to occur."

Recent changes in "carbon intensity"--CO₂ emissions per unit of energy consumed--already are higher than those predicted by the IPCC because of rapid economic development, says lead author Roger Pielke Jr. of the University of Colorado. In Asia, for instance, the demands of more energy-intensive economies are being met with conventional fossil-fuel technologies, a process expected to continue there for decades and eventually move into Africa.

In estimating the emissions reductions required for CO₂ concentration stabilization, the IPCC divides future emissions changes into those that will occur spontaneously (such as in the absence of climate policies) and those that are policy driven. This division hides the full challenge associated with stabilizing the amount of carbon dioxide in the atmosphere. The Nature commentary points out, for example, that to stabilize CO₂ levels at around 500 parts per million (compared to the present level of about 390 ppm), the IPCC scenarios assume that 57 to 96 percent of the total carbon removed from the energy supply over the coming century would occur spontaneously.

"According to the IPCC report, the majority of the emission reductions required to stabilize CO₂ concentrations are assumed to occur automatically," says Pielke. "Not only is this reduction unlikely to happen under current policies, but we are moving in the opposite direction right now. We believe these kinds of assumptions in the analysis blind us to reality and could potentially distort our ability to develop effective policies."

Stabilization of atmospheric concentrations of CO₂ and other greenhouse gases was the primary objective of the 1992 United Nations Framework Convention on Climate Change approved by almost all countries, including the United States, notes co-author Tom Wigley of NCAR.

"Stabilization is a more daunting challenge than many realize and requires a radical 'decarbonization' of energy systems," Wigley says. "Global energy demand is projected to grow rapidly, and these huge new demands must be met by largely carbon-neutral energy sources--sources that either do not use fossil fuels or that capture and store any emitted CO₂."

Unlike the IPCC assumptions of large future "spontaneous" technological innovations, the Nature commentary authors began with a set of "frozen technology" scenarios as baselines--scenarios in which energy technologies are assumed to stay at present levels.

"With a frozen technology approach, the full scope of the carbon-neutral technology challenge is placed into clear view," says co-author Christopher Green of McGill University.

"In the end, our message should be viewed optimistically rather than pessimistically," Pielke notes, "because it is only with a clear-eyed view of the mitigation challenge that we can ever hope to adopt effective policies. We hope that our analysis is one step toward such a clear-eyed view."

The University Corporation for Atmospheric Research operates the National Center for Atmospheric Research under primary sponsorship by the National Science Foundation.

Adapted from materials provided by National Center for Atmospheric Research/University Corporation for Atmospheric Research.

Diabetes is not exclusively a man’s disease. Males and females of all ages can suffer from diabetes. Diabetes is not a disease that anyone can afford to ignore. It will not go away, and while it can be treated, it cannot be cured.

There are two types of diabetes. Type 1, or diabetes mellitus, is insulin-dependent diabetes and is frequently called ‘juvenile diabetes’ because it occurs at a young age and is usually caused by a viral attack on the body. Most experts believe that the body’s immune system is already weak when this occurs. The result is the destruction of beta cells in the pancreas. The pancreas is no longer able to manufacture insulin. Without insulin the body is unable to utilize glucose, the main food source for the body.

Type 2 diabetes is non-insulin dependent diabetes and often occurs in older individuals with a family history of diabetes. Type 2 is different from Type 1 in that the pancreas does produce insulin, but for reasons not fully understood the insulin is not effective. Some of the common symptoms are poor vision, fatigue, and unusual thirst, frequent urination, slow healing of wounds and tingling or numbness in the feet. Type 2 diabetes has been linked to poor diets.

The National Institute of Health says that there are twenty to twenty-five million people with diabetes related problems. As many as five million people have undetected Type II diabetes. Diabetes can be diagnosed with a simple urine test.

Whether Type 1 or Type 2, the resulting high glucose level in the blood causes the blood to become thick or ‘sticky’ and this causes blood clots or thrombosis that damage blood vessels. Individuals who suffer from diabetes are at higher risk for kidney disease, arteriosclerosis, blindness, heart disease, nerve diseases, and are at greater risk for infections than the general population.

Because diabetes can cause problems related to the nerves and blood vessels it can cause neuropathy, a condition which causes nerve damage throughout the body. Erectile dysfunction, as a result of neuropathy is common in more than half of men who have been diagnosed with diabetes. Nerve damage does not allow proper communication to achieve an erection, and narrow blood vessel damage does not allow healthy circulation of blood in and out of the penis. The emotional response to engage in intercourse is there, but nerve damage and blood vessel constriction do not allow the proper physical response. This type of problem, diabetes related erectile dysfunction, does not respond as well to drugs such as Viagra as non diabetes related erectile dysfunction.

A diabetic male who is experiencing erectile dysfunction should speak to his health professional. This will determine if the problem is entirely related to diabetes.

Other ways to help with the diabetes related problems include:

• Controlling blood sugar
• Avoid all forms of tobacco
• Reduce or avoid alcohol consumption
• Seek treatment for cardiovascular risk
• Seek counseling if diabetes and erectile dysfunction are causing depression

Diabetes, if neglected, can lead to serious health issues besides erectile dysfunction. Proper diet and a healthy lifestyle can greatly reduce the consequences of diabetes and if treatment is started early and is persistent, the risk of erectile dysfunction and other health problems will be greatly reduced. If you believe you have symptoms of diabetes see your health care professional immediately.

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Changing dendritic spines on a neuron -- evidence of brain rewiring. (Credit: Image courtesy of University of Rochester Medical Center)

The work ties together several research threads that touch upon the health benefits of exercise. While those benefits are broadly recognized, how the gains accrue at a molecular level has been largely unknown. The new research gives scientists a way to produce changes in the brain that mirror those brought about by exercise, by reducing the effect of the nogo receptor.

The find comes as a surprise, because for much of the last decade, the nogo receptor has been a prime target of researchers trying to coax nerves in the spinal cord to grow again. They named the protein after its ability to stop neurons from growing. Its action in the brain has not been a hot topic of study.

The find by neuroscientists at the University of Rochester Medical Center casts the nogo receptor in a new light. Instead of serving as a target for efforts at regrowing spinal nerve fibers -- indeed, the Rochester team showed last year that the molecule doesn't control that process -- the molecule suddenly has much broader implications for learning and memory.

"One of the central questions in neuroscience is -- what is the molecular and cellular basis of learning?" said Roman Giger, Ph.D., associate professor in the Department of Biomedical Genetics, who led the study. "The nogo receptor seems to play a role."

The receptor is a promiscuous molecule that hooks up with several other molecules which prevent the growth of neurons in the spinal cord. For most of this decade, scientists have worked to target the molecule, thinking that if they could block it, they could possibly regenerate nerves, repairing spinal cord damage in a way that is impossible today.

But that road has proved difficult. Last year in the same journal, the Rochester team led by Giger showed that while the nogo receptor does play a role in preventing spinal nerves from growing, it does not control the process outright. While nogo receptor activation can transiently stunt the growth of neurons, it is not required for chronic outgrowth inhibition of injured nerve cells.

Giger's team has found that in some areas of the brain, such as the hippocampus, the nogo receptor is at least 10 times more prevalent than in the spinal cord.

In the brain, Giger's team found that the nogo receptor wields broad influence over a process known as neuroplasticity, which describes how our brain cells change and adapt constantly to meet our needs. It can be thought of simply as the brain's ability to rewire itself on the fly to meet the demands of an organism. The process explains why people are able to recover many of their abilities even after a traumatic brain injury or a stroke: Other brain cells pick up the work for the ones that have died.

Giger's team found that the nogo receptor plays an important role in changing the brain in two ways.

First, the molecule plays a completely unexpected role manipulating the strength of signals between brain cells in the synapses. A team led by Peter Shrager, Ph.D., professor of Neurobiology and Anatomy, made sophisticated measurements of the strengths of the signals as they passed from cell to cell in mice. They found that mutant mice with fewer nogo receptors than normal had stronger brain signaling, what scientists call "long-term potentiation.

The molecule also affected tiny structures known as dendritic spines, crucial connections that are extensions of the neuron and help cells "talk" to other cells. Mice with lots of the nogo receptor had a different mix of dendritic spines than normal mice. In the hippocampus, the mutant mice had fewer mushroom-shaped dendritic spines and more stubby and thin spines than the other mice. Scientists don't yet know the ramifications of the change, but they say it's firm evidence that the nogo receptor has effects on the anatomic structure of the brain. Creation and removal of dendritic spines is an important form of brain rewiring.

The team attributes much of the effects of the nogo receptor to its ability to strongly bind to a growth factor known as FGF2 (fibroblast growth factor 2), which in the brain and other parts of the central nervous system nourishes neurons, allowing them to branch out and grow new sprouts. When the nogo receptor is present in abundance, it binds to FGF2 molecules, and as a result neurons no longer branch and sprout as they otherwise would.

Altogether, the findings show that the nogo receptor has a broad impact on processes in the brain that underlie learning and memory, said Giger.

"It's known that changes in synaptic strength can lead to rewiring of the nervous system in such a way that we can compensate for mild to moderate injuries," said Giger, who is a scientist in the Center for Neural Development and Disease. "Enhancing synaptic plasticity can partially counter the effects of an injury like stroke, or traumatic brain injury. Really, the process happens routinely in many stroke patients -- it's what makes rehabilitation after stroke possible."

Much of the same type of rewiring also happens as a result of exercise. Scientists have shown that exercise improves the brain's neuroplasticity, boosting the brain's ability to sprout new structures and send crisp signals, which in turn helps people recover from injuries to the central nervous system. And recently, researchers at the Karolinska Institute in Stockholm showed that exercise reduces the abundance of the nogo receptor in the brain. Giger's work provides a molecular framework that brings the disparate findings together.

The findings could also explain something that has puzzled scientists, said Giger. Mice with damaged spinal cords that have been treated with compounds designed to knock out the nogo receptor seem to improve a bit, even though scientists have never been able to demonstrate nerve regrowth in those mice. It may be that their improvement instead is coming through the signal-boosting effect in the synapses.

While it's tempting to think that knocking down the nogo receptor is a simple process that would help people under all circumstances by boosting their brain power, Giger points out that the molecule is not only found at synapses but also along axons, where scientists believe it plays an important role limiting the sprouting of nerve fibers. Any effort to reduce the nogo receptor will have to be studied thoroughly to watch for other effects.

The findings are in the March 12 issue of the Journal of Neuroscience. While Giger headed the project, much of the research was done in equal part by the two first authors, Research Assistant Professor Hakjoo Lee, Ph.D., and graduate student Stephen Raiker. Other authors include former graduate student Karthik Venkatesh, Ph.D., now at the University of Michigan; former Professor Hermes Yeh, Ph.D., now at Dartmouth; technician Rebecca Geary; graduate student Laurie Robak; and Yu Zhang, Ph.D., now a research assistant professor in the Department of Neurosurgery.

The work was funded by the National Institute of Neurological Disorders and Stroke, the New York State Spinal Cord Injury Research Program, and the Dr. Miriam and Sheldon G. Adelson Research Medical Foundation's Adelson Program in Neural Repair and Rehabilitation.

Adapted from materials provided by University of Rochester Medical Center.

Age on the brain. An experimental drug, S18986, seems to counteract numerous symptoms of aging in rats. Animals given the drug daily for four months were active, with better memories and less inflammation in their brains. Dopamine-producing neurons in the forebrain of an 18-month-old drugged rat (top) are far more active than those in a normal rat of the same age. (Credit: Image courtesy of Rockefeller University)

The drug, temporarily designated S18986, interacts with AMPA (short for α- Amino-3-hydroxy-5- methylisoxazole-4- propionic acid, or ampakine) receptors in the brain. These receptors transmit excitatory signals in the brain, and

researchers were interested in experimental AMPA-receptor drugs (such as S18986) for their neuroprotective abilities and for the way they temporarily boost memory. But rather than investigating the compound’s short-term effects, Alfred E. Mirsky Professor Bruce McEwen and his lab members made a far longer commitment: The scientists studied the drug’s impacts on middle-aged to elderly rats and found that, when administered daily over four consecutive months, it appeared to improve memory and slow brain aging.

“Nobody had ever looked at the long-term effects of these ampakines on the aging brain,” says McEwen, head of Rockefeller’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology. Short-term studies, he notes, had shown that the drug appears to improve aspects of memory, likely by temporarily ramping up AMPA receptors in the hippocampus — the brain’s memory and learning center. But McEwen, research assistant Erik Bloss and postdocs Elizabeth Waters and Richard Hunter found that, over the course of four months, S18986 changed the entire profile of the older rodents’ brains.

When compared to control animals that had received only sugar water, the drugged rats were not only more active and better at memory tests, but their brains showed physical signs of slowed aging. Neurons in the forebrain that produce acetylcholine, a neurotransmitter known to play a role in learning and memory, had 37 percent less decline. Dopamine-producing neurons, which are responsible for sustaining activity and motivation levels, slowed their decline by 43 percent. Levels of inflammation in the brain were also significantly lower. “Every marker we chose to look at seemed to indicate there was some preservation of function during aging with chronic treatment,” Hunter says. The drug appears to slow aging’s effects throughout the entire brain.

Dopamine is a motivation- and movement-related neurotransmitter in the brain, and its presence is necessary for maintaining normal activity levels — it’s the chemical that helps you get up off the couch and socialize or exercise. A severe loss of dopamine production causes Parkinson’s disease, “so this drug has the potential, perhaps, to block the progression of the disease,” Hunter says.

Not only that, but it could be helpful for much less severe conditions, too. As people age, it’s often harder for them to feel motivated to socialize or even eat, leading to depression and making latent conditions worse. “So maybe this drug isn’t going to be the one that prevents Parkinson’s,” Waters says, “but maybe it’s going to improve the quality of life as you age, so that up until the very end of your life you can sustain that quality and sustain a higher activity level.”

With such a variety of impacts on neurotransmitters, S18986 holds enormous potential. But so far, it’s only potential. The researchers hope to dig deeper to find out precisely how the drug works. “There’s a lot to be done,” Hunter says, “and this shows that there’s broad potential for these compounds.”

Reference: Experimental Neurology 210(1):109–117 (March, 2008)

Adapted from materials provided by Rockefeller University.

Each human nose encounters hundreds of thousands of scents in its daily travels perched front and center on our face. Some of these smells are nearly identical, so how do we learn to tell the critical ones apart? Something bad has to happen. Then the nose becomes a very quick learner. (Credit: iStockphoto/Stacey Newman)

Something bad has to happen. Then the nose becomes a very quick learner.

New research from Northwestern University's Feinberg School of Medicine shows a single negative experience linked to an odor rapidly teaches us to identify that odor and discriminate it from similar ones.

"It's evolutionary," said Wen Li, lead author of the study and a postdoctoral fellow at the Cognitive Neurology and Alzheimer's Disease Center at the Feinberg School. "This helps us to have a very sensitive ability to detect something that is important to our survival from an ocean of environmental information. It warns us that it's dangerous and we have to pay attention to it."

In the study, subjects were exposed to a pair of grassy smells which were nearly identical in their chemical makeup and perceptually indistinguishable. The subjects received an electrical shock when they were exposed to one scent, but not when they were exposed to the other similar one.

After being shocked, the subjects learned to discriminate between the two similar smells. This illustrates the tremendous power of the human sense of smell to learn from emotional experience. Odors that once were impossible to tell apart became easy to identify when followed by an aversive event.

Li and her colleagues also found specific changes in how odor information is stored in "primitive" olfactory regions of the brain, enhancing perceptual sensitivity for smells that have a high biological relevance.

The study will be published March 28 in the journal Science.

Motorcyclist with safety helmet. The motorcyclist fatality rate has increased in states that repealed their universal helmet laws during the past decade. (Credit: iStockphoto/Joshua Blake)

Lilliard Richardson, professor in the MU Truman School of Public Affairs, and David J. Houston, associate professor at the University of Tennessee, Knoxville, compared the changes in helmet laws across all 50 states and the District of Columbia from 1975 through 2004. In states where repeals of universal coverage were instituted, the fatality rate increased an average of 12.2 percent. Conversely, in states with universal helmet laws, the fatality rate was 11.1 percent lower than in states with no helmet mandates.

“Previous studies have been limited to certain states and fail to distinguish the states with partial coverage from those with no legislation,” Richardson said. “Our focus was not limited to a single state or a single change. We looked at effects in states that went from universal helmet laws to partial laws and states that went from partial laws to no laws, and states which kept their laws in place. We highlighted repeals of laws in six states by using separate variables to distinguish the effects of universal and partial coverage. We included controls for temperature, precipitation, per capita alcohol consumption, income, age, population density and other traffic safety policies.”

Experts have estimated that an additional 615 motorcyclist fatalities occurred in the six states that repealed motorcycle helmet laws from 1997 to 2004, Richardson said. The researchers also found that fatality numbers in states with partial laws were not statistically different from those with no helmet laws.

“The federal government has pressured states to adopt universal helmet laws, but the trend has been toward more state control of helmet laws,” Richardson said. “The National Highway Traffic Safety Administration promotes the effectiveness of helmet laws for getting motorcyclists to wear helmets, but there is no strategy for encouraging states to maintain or adopt universal coverage laws. This does not bode well for the future of universal helmet laws and motorcycle safety in the United States.”

Currently, several states are considering modifying their helmet laws.

“Advocates in many states are pushing to repeal state universal helmet laws or impose partial mandates that require only young riders to wear helmets,” Richardson said. “Many assume that wearing

helmets becomes a habit for riders like wearing a seatbelt is for drivers and that having a law in place isn’t necessary. This is a misconception. When laws aren’t in place and enforced, the evidence shows that a majority of riders do not wear helmets.”

The study, “Motorcycle Safety and the Repeal of Universal Helmet Laws,” was published in the American Journal of Public Health.

Adapted from materials provided by University of Missouri-Columbia.

Couple in Hawaii. Satisfactory sexual intercourse for couples lasts from 3 to 13 minutes, contrary to popular fantasy about the need for hours of sexual activity, according to a survey of U.S. and Canadian sex therapists. (Credit: iStockphoto/Justin Horrocks)

Penn State Erie researchers Eric Corty and Jenay Guardiani conducted a survey of 50 full members of the Society for Sex Therapy and Research, which include psychologists, physicians, social workers, marriage/family therapists and nurses who have collectively seen thousands of patients over several decades.

Thirty-four, or 68 percent, of the group responded and rated a range of time amounts for sexual intercourse, from penetration of the vagina by the penis until ejaculation, that they considered adequate, desirable, too short and too long.

The average therapists' responses defined the ranges of intercourse activity times: "adequate," from 3-7 minutes; "desirable," from 7-13 minutes; "too short" from 1-2 minutes; and "too long" from 10-30 minutes.

"A man's or woman's interpretation of his or her sexual functioning as well as the partner's relies on personal beliefs developed in part from society's messages, formal and informal," the researchers said. ""Unfortunately, today's popular culture has reinforced stereotypes about sexual activity. Many men and women seem to believe the fantasy model of large penises, rock-hard erections and all-night-long intercourse. "

Past research has found that a large percentage of men and women, who responded, wanted sex to last 30 minutes or longer.

"This seems a situation ripe for disappointment and dissatisfaction," said lead author Eric Corty, associate professor of psychology. "With this survey, we hope to dispel such fantasies and encourage men and women with realistic data about acceptable sexual intercourse, thus preventing sexual disappointments and dysfunctions."

Corty and Guardiani, then-undergraduate student and now a University graduate, are publishing their findings in the May issue of the Journal of Sexual Medicine, but the article is currently available online.

The survey's research also has implications for treatment of people with existing sexual problems.

"If a patient is concerned about how long intercourse should last, these data can help shift the patient away from a concern about physical disorders and to be initially treated with counseling, instead of medicine," Corty noted.

Adapted from materials provided by Penn State.

New research suggests that a woman's waistline may have less to do with rigorous exercise and abstaining from sweets than it does with the genes of her parents. (Credit: iStockphoto/Alexander Novikov)

A woman's waistline may have less to do with rigorous exercise and abstaining from sweets than it does with the genes of her parents, according to a new study by Prof. Gregory Livshits from the Sackler Faculty of Medicine at Tel Aviv University and colleagues from King's College in London. Dr. Livshits and his colleagues have found a scientific link between the lean body mass of a woman and her genes. They've determined that thinness -- like your smile or the color of your eyes -- is an inheritable trait.

Bad News First, Then the Good

Prof. Livshits, whose findings were published in the Journal of Clinical Endocrinology and Metabolism (2007), says, "The bad news is that many of our physical features, including our weight, are dependent on our genes. The good news is that women still have an opportunity to go against their genetic constitution and do something about it."

Until now, scientists were not sure to what extent environmental influences and genetics played a role in a woman's body size. When controlling for the variance of age, the differences in womens' body sizes can be predicted in the genes more than 50 percent of the time, the researchers found.

Prof. Livshits conducted his study on more than 3,000 middle-aged women in the United Kingdom who belonged to either an identical or fraternal twin pair. He measured their "total lean mass," one of the three major components of body weight, and compared it to markers in their genes.

A Slim Chance?

Additional collaborative research between the two teams, which builds on the past study, is to be published in the next few months. It may help pave the way for a "skinny gene test," which one day may help women trying to lose weight understand what kind of battle they can expect.

Those without the lean genes, however, will always find it harder to stay slim, predicts Prof. Livshits. But before your diet falls by the wayside, consider Prof. Livshits' contention that genetics can be overcome.

Curb Your Enthusiasm

It's important to not have high expectations, he warns. "Women need to know that what they can do about their body weight -- especially when they age -- is relatively little, and they will do it only with much difficulty."

Very few studies to date have been able to associate a body's lean mass with genetics. The topic is a specialty at the Tel Aviv University lab, one of the top labs in the world to study the genetics of aging of body composition. This area includes the study of bone, fat and lean mass as it develops in a person over time.

Research on body composition components -- their growth, degradation and genes -- is part of Prof. Livshits' ongoing work on aging and health. Issues such as weight gain are complex, he says, especially when age is factored in.

So don't get too jealous of your friend's dress size. It may be mostly out of your hands -- and in your DNA.

Adapted from materials provided by Tel Aviv University.

House flies can have a role in spreading Salmonellato poultry. (Credit: Photo by Stephen Ausmus)

Agricultural Research Service (ARS) microbiologist Peter S. Holt and entomologist Christopher J. Geden found that the common housefly, Musca domestica, readily picks up bacteria from its surroundings. When the chickens eat the flies, the bacteria get inside the birds. Holt works in the Egg Safety and Quality Research Unit at the ARS Richard B. Russell Research Center in Athens, Ga., while Geden is at the ARS Center for Medical, Agricultural and Veterinary Entomology in Gainesville, Fla.

ARS is the U.S. Department of Agriculture's chief scientific research agency.

In three experiments, Holt placed chickens in individual, adjacent laying cages. Geden delivered fly pupae just 48 hours short of hatching as flies; this timing ensures the flies aren't exposed to any microbe prior to emergence. The fly pupae were placed in an open box in the bird room. Three days later, hens were orally infected with Salmonella.

The researchers detected the bacteria in and on 45 to 50 percent of the flies within the first 48 hours of the flies' hatching.

Next, uninfected hens were exposed to the newly infected flies. Just being around the flies didn't cause healthy birds to become infected, but eating infected flies did. This showed that simple physical contact may not be the primary method of transfer of Salmonella bacteria to different surfaces in a poultry house. But, according to the researchers, a hen's eating of contaminated flies does seem to be the primary mechanism of transmission of Salmonella from flies to birds.

According to Holt, this shows that flies in poultry houses are not only a nuisance, but also a threat to the safety of poultry products.

Adapted from materials provided by US Department of Agriculture.

Hand X-Ray. (Credit: Image courtesy of American Association of Neurological Surgeons)

An estimated 260,000 carpal tunnel surgeries are performed annually in the United States, and of those, more than 35,000 were performed in 2006 by neurosurgeons, according to AANS statistics. A neurosurgeon’s primary role in the treatment of carpal tunnel syndrome is diagnosis, interpretation of test results, and when necessary, surgery. There are frequently other medical professionals involved in the treatment process, such as physical therapists.

Carpal tunnel syndrome most often occurs when the median nerve in the wrist becomes inflamed, caused by a combination of thickened ligaments over the nerve and repetitive movements. “Carpal tunnel syndrome is most prevalent in women ages 40 to 60, and also tends to affect people more frequently who use their hands excessively, such as pianists, concert violinists, hairdressers, computer operators, manual laborers, artists, sculptors, dentists, and even neurosurgeons,” says James R. Bean, MD, AANS president-elect.

Any repetitive motions that cause significant swelling, thickening or irritation of membranes around the tendons in the carpal tunnel can result in pressure on the median nerve, disrupting transmission of sensations from the hand up to the arm and to the central nervous system.

Diseases or conditions that may increase your chances of developing carpal tunnel syndrome include pregnancy, diabetes, menopause, broken or dislocated bones in the wrist, and obesity. Additional causes include repetitive and forceful grasping with the hands, bending of the wrist, and arthritis.

It is important to seek medical advice when you first notice persistent symptoms. Do not wait for your pain to become intolerable. Before your doctor can recommend a course of treatment, he or she will perform a thorough evaluation, including a medical history, physical examination and diagnostic tests. Your doctor will ask about the extent to which your symptoms affect daily living. Sometimes a case turns out to be tendonitis and not carpal tunnel, but only a doctor can make a proper diagnosis.

The main purpose of conservative treatment is to reduce or eliminate repetitive injury to the median nerve. In some cases, carpal tunnel syndrome can be treated by immobilizing the wrist in a splint to minimize or stop pressure on the nerves. If that does not work, patients are sometimes prescribed anti-inflammatory medications or cortisone injections in the wrist to reduce swelling. Your doctor may suggest specific types of hand and wrist exercises, which may be helpful. Treatment for carpal tunnel syndrome may include rest, the use of a wrist splint during sleep, or physical therapy. Conservative treatment methods may continue for up to eight weeks.

If conservative treatment methods do not provide sufficient relief, your doctor may perform diagnostic studies to determine if surgery is an effective option. These diagnostic tests include x-rays and electromyogram and nerve conduction studies. X-rays can help determine if any abnormalities in bones of the wrist may be contributing factors. Electromyogram and nerve conduction studies can reveal significant compression on the median nerve in the carpal tunnel.

If patients suffer from severe pain that cannot be relieved through rest, rehabilitation or nonsurgical treatment, there are several surgical procedures that can be performed to relieve pressure on the median nerve. The most common procedure is called a carpal tunnel release, which can be performed using an open incision or with endoscopic techniques. The open incision procedure or carpal tunnel release, involves the neurosurgeon making an incision in the wrist or palm and then releasing the ligament that is compressing and placing pressure on the median nerve. The endoscopic carpal tunnel release procedure involves making a smaller incision and using a miniaturized camera to assist the neurosurgeon in viewing the carpal tunnel.

Risks of carpal tunnel surgery are minimal. The majority of individuals recover completely. “The results of surgery are usually excellent, with most patients receiving nearly full relief of their symptoms. The earlier you get diagnosis and treatment, generally the better the outcome,” states Dr. Bean.

Adapted from materials provided by American Association of Neurological Surgeons, via Newswise.

Kelly Shimoda for The New York Times

FLEX, POSE, SMILE Melvin Cooper, 64, entered his first bodybuilding contests last year

UNTIL nine years ago, Dr. Neal Grossman didn’t make a habit of parading around his bedroom in his skivvies and admiring his physique in the mirror. Nor did he ever imagine that his oldest son, then a teenager, would take one look at his father midflex and cry out, “Dad, put your clothes back on!”

Enlarge This Image

Jessica Kourkounis for The New York Times

Ed Cole, 72, also entered his first bodybuilding contests last year.

But now that Dr. Grossman, a 60-year-old Baltimore dentist, is a competitive amateur bodybuilder, an extra ounce of flab makes the difference between a sizable trophy and going home empty-handed. “The minute you start winning, that’s all the validation people need to accept what you do as legitimate and something to be appreciated,” said Dr. Grossman, who is 5-foot-2 and a chiseled 121 pounds.

He is one of a small but growing number of 60- and 70-year-old bodybuilders stripping down to Speedos, slathering on bronzer, and strutting their stuff onstage in natural, or drug-free, competitions. The season for amateur and pro-level events begins this month.

Last year, the World Natural Sports Organization, one of about a dozen bodybuilding groups devoted to drug-free contests, had 44 competitors older than 60, up from two in 2000, said Jeffrey Kippel, a founder.

Many bodybuilding contestants are not tested and steroids use is rampant. But most natural bodybuilding contests require participants to complete urinalysis and polygraph tests before events.

In the last five years, the number of men and women in their 60’s and 70’s competing in United States Bodybuilding Federation shows has doubled to 16, said Brian Washington, the commissioner of the federation, another drug-free group. Those figures will not put senior softball leagues out of business any time soon, but in an age in which athletes are publicly flogged for using steroids and human growth hormones, it is heartening to find a cohort of older Americans hellbent on getting cut the old-fashioned way. Or so they say.

Skeptics believe that natural bodybuilders may not be entirely drug-free.

Still, the oldest age group of natural bodybuilders has drawn enough interest that last year the Fame World Tour, a series of physique competitions sanctioned by Mr. Kippel’s organization, hired Scott Hults, a retired Naval officer-turned-bodybuilder to be in charge of promotions for the 60-plus division.

“Age is a statistic, not a burden and there is no reason a man or woman can’t get into and maintain the best shape of their lives at any age,” said Mr. Hults, 64, who has competed in 26 shows since 2005 and last year won an age-group title.

Some older bodybuilders were weight lifters or wrestlers in their youth; others are fitness buffs who want to test their mettle; still others are retirees who refuse to go gently anywhere.

Although it is harder to build muscle later in life — 18 to 35 are considered the prime muscle-building years — it is possible, said Jose Antonio, the vice president of the National Strength and Conditioning Association.

Take Ed Cole, who entered his first bodybuilding contest last year at age 71. After retiring in 1992, Mr. Cole, who is 5-5, ballooned to 195 pounds. In 2000, he resolved to start weight training, which he had not done since he was a gymnast in his youth. He spent 90 minutes a day hoisting weights in the fitness center he built in his basement, and by 2004, he was 50 pounds lighter, and a certified personal trainer to boot.

He overhauled his diet, too. But after roughly seven years of diligent eating “for nutrition only,” he was ready to grease up his muscles and join the brawny and drug-free. To this day, he said, nothing stronger than magnesium has passed his lips.

Older bodybuilders tend to be disciplined purists. Younger competitors might want to push the envelope and beef up as much as possible, said Dr. Antonio, who has a Ph.D in muscle physiology. “Older individuals just want to improve their physique.”

Mr. Hults said: “Maybe if I had started bodybuilding in my 20’s instead of my 60’s, I might have used steroids. But since I did get into the game later in life, it made sense for me to go the natural route. I’m glad I did. I have been able to achieve much on my own, without illegal muscle enhancements. That in itself is very satisfying.”

But he does acknowledge knowing several senior athletes now on steroids, human growth hormone or testosterone replacement therapy.

For the most part, the senior bodybuilders say they take great pride that their amped-up pectorals are strictly the result of diet, exercise and vitamins and supplements.

Know how a whiff of certain odors can take you back in time, either to a great memory or bad one? It turns out emotion plays an even bigger role with the nose, and that your sense of smell actually can sharpen when something bad happens.

Northwestern University researchers proved the surprising connection by giving volunteers electric shocks while they sniffed novel odors.

The discovery, reported in Friday's edition of the journal Science, helps explain how our senses can steer us clear of danger. More intriguing, it could shed light on disorders such as post-traumatic stress syndrome.

"This is an incredibly unique study," said Dr. David Zald, a Vanderbilt University neuroscientist who studies how the brain handles sensory and emotional learning. "We're talking about a change in our perceptual abilities based on emotional learning."

Scientists long have known of a strong link between the sense of smell and emotion. A certain perfume or scent of baking pie, for instance, can raise memories of a long-dead loved one. Conversely, a whiff of diesel fuel might trigger a flashback for a soldier suffering PTSD.

Could an emotionally charged situation make that initial cue be perceived more strongly in the first place?

The research team recruited 12 healthy young adults to find out.

Volunteers repeatedly smelled sets of laboratory chemicals with odors distinctly different from ones in everyday life. An "oily grassy" smell is the best description that lead researcher Wen Li, a Northwestern postdoctoral fellow in neuroscience, could give.

Two of the bottles in a set contained the same substance and the third had a mirror image of it, meaning its odor normally would be indistinguishable. By chance, the volunteers correctly guessed the odd odor about one-third of the time.

Then Li gave the volunteers mild electric shocks while they smelled just the odd chemical. In later smell tests, they could correctly pick out the odd odor 70 percent of the time.

MRI scans showed the improvement was more than coincidence. There were changes in how the brain's main olfactory region stored the odor information, essentially better imprinting the shock-linked scent so it could be distinguished more quickly from a similar odor.

In other words, the brain seems to have a mechanism to sniff out threats.

That almost is certainly a survival trait evolved to help humans rapidly and subconsciously pick a dangerous odor from the sea of scents constantly surrounding us, Li said. Today, that might mean someone who has been through a kitchen fire can tell immediately if a whiff of smoke has that greasy undertone or simply comes from the fireplace.

But the MRI scans found the brain's emotional regions did not better discriminate among the different odors, Li noted. That discrepancy between brain regions is where anxiety disorders may come in. If someone's olfactory region does not distinguish a dangerous odor signal from a similar one, the brain's emotional fight-or-flight region can overreact.

Researchers say that is a theory not yet tested.

For now, Northwestern neuroscientist Jay Gottfried, the study's senior author, says the work illuminates a sense that society too often gives short shrift.

"People really dismiss the sense of smell," said Gottfried, who researches "how the brain can put together perceptions of hundreds of thousands of different smells. ... Work like this really says that the human sense of smell has much more capacity than people usually give it credit."

AP Photo: A sound level indicator of the Sonicu system hangs from the ceiling of the neonatal...

INDIANAPOLIS - Warning lights hover over the snoozing patients in Riley Hospital for Children's neonatal intensive care unit, ready to flash whenever sound levels creep beyond normal conversation.

As decibels rise, the colors on the new monitoring system change from green to yellow to red, hushing chatty parents or doctors so the babies get the rest they need to develop.

Noise louder than roughly the level of conversation can cause premature or sick babies' hearts to beat too fast or too slowly, said Dr. William Engle, a neonatologist at Riley. And interfering with babies' vital signs or sleep can slow development and healing because their bodies do most of that work while they sleep.

"The function of babies is to grow and develop, and in between they eat," he said.

Preemies also need quiet so they can learn their mother's voice and their brains can figure out how to process sound, things that normally happen in the last trimester before birth.

"It's definitely a great idea," Dr. Bob White, a neonatologist at South Bend's Memorial Hospital, said of the monitoring system in Riley's neonatal intensive care unit, or NICU.

White, who is not involved in creating or distributing the system, helped write national noise standards for NICUs that have been adopted by the American Institute of Architects and are used in most hospital design.

Inventor Chris Smith hopes doctors around the country agree with White. He has sold his Sonicu system to several Indiana hospitals and wants to expand nationally.

Smith, 43, had no training as a sound engineer and no plans to become an entrepreneur when his son Sean was born five weeks premature in 2000. But he noticed Sean flinch in response to bright light in the NICU of St. Vincent Indianapolis Hospital, and he wound up designing a system to soften the unit's lighting.

Then the nurses asked him what he could do about sound.

"That's really when I realized that there was no good way out there to measure sound, other than your standard, hand-held meter," he said.

Babies born too soon lose the muffling effect of the womb before their ears can filter sound, White said.

"The sounds ... come from all different directions and all different sources, and they're often associated with unpleasant sensations for the baby," White said.

NICUs are rife with noise pollution created by employees, equipment and excited family members.

"There's no good way for the nurses or doctors to walk up to a parent, tap them on the shoulder and say, 'You're being too loud,'" Smith said. "That's confrontational."

The former car mechanic filled hours of spare time in the evenings and on weekends researching sound standards and building a system.

Smith, who tinkered in radio and TV electronics in high school, hired an acoustical engineer to help. They created a ceiling-mounted system of microphones that picked up sound and funneled data back to a large control panel.

"There was a lot of wiring, a lot of labor, a lot of programming," he said.

St. Vincent paid around $100,000 for the system, which it installed about five years ago. Smith had no interest in shopping his invention to other hospitals because the work took so much time.

Then Riley Hospital, also in Indianapolis, called a few months later.

"They basically said, 'I want that,'" he said.

The latest version of Sonicu can feed a stream of both sound and light data digitally to a computer. It offers the cone-shaped warning lights and can quickly dim the lighting in a room that gets too noisy. It also can make lighting mimic the sun by brightening toward noon and then fading, which also helps babies sleep well.

White, the neonatologist who helped write the national standards, said he knows of no other NICU monitoring system that sophisticated.

Smith has sold systems to a handful of Indiana hospitals, so far to good reviews. He said the systems can cost anywhere from $40,000 to $400,000, depending on each hospital's needs.

The monitors have taught hospital staff to limit the number of groups making rounds at the same time because having more than one group in a room raises noise levels dramatically.

Most NICUs are filled with noise that can't be helped, White said. Fans in the heating and ventilation system have to operate almost constantly, and the monitors need to beep.

The Sonicu system reins in the main noise maker that can be controlled.

"People think, 'Oh gosh, I didn't realize, I'll go over here so I won't have to talk so loud,'" White said. "It really is something that addresses the human factors that we do have some control over."