RxPG News : Physiology

New genetic variants for COPD discovered in a groundbreaking study by SpiroMeta Consortium

Tue, 15 Dec 2009 04:59:12 PST

( from http://www.rxpgnews.com ) Scientists have discovered five genetic variants that are associated with the health of the human lung. The research by an international consortium of 96 scientists from 63 centres in Europe and Australia sheds new light on the molecular basis of lung diseases.

The research, part-funded by the Medical Research Council (MRC) and Asthma UK, is published today in Nature Genetics. It represents a significant advance because it is the first time that these five common genetic variations have been definitely linked with lung function.

The new findings provide hope for better treatment for lung diseases like Chronic Obstructive Pulmonary Disease (COPD) and asthma. In the past it has been difficult to develop new treatments because the molecular pathways that affect the health of the lung are not completely understood. It's hoped the new pathways discovered could in the future be targeted by drugs.

The ground-breaking research involved a genetic study of 2.5 million sites across the human genome involving samples from 20,000 people across the world. The consortium was led by Dr Martin Tobin from the University of Leicester and Professor Ian Hall from The University of Nottingham.

Lung function is commonly expressed using two measures recorded using a simple device called a spirometer. These measures are termed the FEV1 (or forced expiratory volume in 1 second) which is the volume of air that can be breathed out in 1 second, and the FVC (forced vital capacity) which is the total volume of air that can be breathed out. In chronic obstructive pulmonary disease (COPD), which encompasses chronic bronchitis and emphysema, narrowing of the airways causes a disproportionate reduction in FEV1. Cough, phlegm and shortness of breath are common symptoms of COPD. The simplest way to diagnose COPD is through spirometry, which is usually available in general practitioners' surgeries. Although there is no cure for COPD, stopping smoking and treatments can improve symptoms and reduce the impact of COPD on exercise and daily activities. Drug treatments include bronchodilators and, for exacerbations, may include short-term steroids. Patients with COPD are more susceptible to serious lung infections, so flu vaccination each winter is important.

The genetic determinants of COPD can be studied by investigating the genetic variants that affect the risk of developing COPD itself or by studying lung function itself, on which the diagnosis of COPD is based. Reduced lung function may also occur in patients with other airway diseases such as asthma.

Further research will be needed to study in detail the molecular alterations in the lung that result from the genetic variants identified, and to investigate whether these might be targeted by drugs. At this time there is no case for testing for common genetic variants that might predispose to COPD.

The scientists said: "This work is important because until now we have known very little about the genetic factors that determine an individual's lung function. By identifying the genes important in determining lung function, we can start to unravel the underlying mechanisms which control both lung development and lung damage. This will lead to a better understanding of diseases such as chronic obstructive pulmonary disease (COPD) and asthma. Crucially, it could open up new opportunities to manage and treat patients with lung conditions".

The authors added: "A large reduction in lung function occurs in chronic obstructive pulmonary disease (COPD), which affects around 1 in 10 adults above the age of 40 and is thought to be the fourth most common cause of death worldwide. Smoking is the major risk factor for development of COPD. Lung function and COPD cluster within families, indicating that variations in genes also predispose individuals to reduced lung function.

"The scientists of the SpiroMeta consortium compared genetic variants at each of 2.5 million sites across the human genome in over 20,000 individuals of European ancestry with their lung function measures. In five different locations in the human genome, genetic variants resulted in alterations in lung function. The scientists showed that these were real findings by checking the effects of the same variants in over 33,000 additional individuals. They also compared their results to those of a second consortium, CHARGE, which has published a paper in the same issue of the journal.

The scientists emphasise that they do not expect these findings to lead to immediately to genetic tests to predict who will develop lung disease. What is more important, they say, is that the findings will help understand the underlying causes of lung diseases and thus may indicate new ways of treating the condition.

"The research would not have been possible without the generous support of the participants of the contributing studies from the UK, Europe and Australia, to whom we offer our thanks."

Sticks and stones break bones, but this UH study may prevent it

Wed, 09 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) The best way to prevent a fracture is to stop bones from reaching the point where they are prone to breaking, but understanding the process of how bones form and mature has been challenging. Now researchers at the University of Houston department of health and human performance have created a process that grows real human bone in tissue culture, which can be used to investigate how bones form and grow.

We have manufactured a structure that has no synthetic components, said Mark Clarke, associate professor and principal investigator. It's all made by the two cell types bones start with inside the body. What you end up with is a piece of material that is identical to newly-formed, human, trabecular bone, including its mineral components, its histology and its growth factor content.

Being in a microgravity environment causes astronauts' bodies to lose more bone mineral than they can replace, which makes them vulnerable to fractures and breaks. Even when they return to Earth, the bone loss continues as their bodies slowly begin the process of replacing the bone mineral content.

The NASA-funded study, which included Clarke's collaborators at NASA-Johnson Space Center, Dr. Neal Pellis and Dr. Alamelu Sundaresan, used human osteoblasts and osteoclasts, the two major cell types involved in the formation of and breaking down of bone. The 3-dimensional bone constructs allowed for ideal conditions to investigate how bone forms and, more importantly, how bone is lost in environments such as space flight and conditions present in post-menopausal women and spinal cord patients.

Clarke has worked with NASA on other bone loss studies. He served as a principal investigator in a NASA study of micro-fabricated skin patches that collect sweat for analysis of biomarkers of bone loss, like calcium.

His research on bone formation also is proving to be market-ready, as a newly formed start-up company, OsteoSphere Inc., examines ways the breakthrough research can be used in a clinical setting for applications such as spinal fusions, facial reconstructions following bomb blasts or the re-growing of an individual bone outside of the patient,.

UH has now licensed the technology to OsteoSphere Inc. which is looking at ways to commercialize the technology in a clinical setting, including culturing an individual's own bone for subsequent transplantation back into the patient, developing other products for use in orthopedic reconstruction or using the technology as a screening tool for development of pharmaceuticals for combating bone loss or stimulating bone regeneration, Clarke said.

Think again about keeping little ones so squeaky clean

Tue, 08 Dec 2009 04:59:36 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- A new Northwestern University study suggests that American parents should ease up on antibacterial soap and perhaps allow their little ones a romp or two in the mud --- or at least a much better acquaintance with everyday germs.

The study is the first to look at how microbial exposures early in life affect inflammatory processes related to diseases associated with aging in adulthood.

Most provocatively, the Northwestern study suggests that exposure to infectious microbes early in life may actually protect individuals from cardiovascular diseases that can lead to death as an adult.

Contrary to assumptions related to earlier studies, our research suggests that ultra-clean, ultra-hygienic environments early in life may contribute to higher levels of inflammation as an adult, which in turn increases risks for a wide range of diseases, said Thomas McDade, lead author of the study, associate professor of anthropology in Northwestern's Weinberg College of Arts and Sciences and a faculty fellow at the Institute for Policy Research.

Relatively speaking, humans only recently have lived in such hyper-hygienic environments, he stressed.

The research suggests that inflammatory systems may need a higher level of exposure to common everyday bacteria and microbes to guide their development. In other words, inflammatory networks may need the same type of microbial exposures early in life that have been part of the human environment for all of our evolutionary history to function optimally in adulthood, said McDade, also a member of Northwestern's Cells to Society (C2S).

The Northwestern study is the first research on microbial effects on inflammatory systems in infancy that relate in later life to diseases associated with aging. Advancing the scientific literature on the developmental origins of disease, the study arguably is the most significant research on long-term effects of early environments on human physiological function and health in adulthood.

The research took advantage of a longitudinal study of Filipinos, following participants in utero through 22 years of age, to get a better understanding of how environments early in life affect production of C-reactive protein (CRP) production in adulthood.

Levels of the protein rise in the blood due to inflammation, an integral part of the immune system's fight against infection. CRP research mostly has centered on the protein as a predictor of heart disease, independent of lipids, cholesterol and blood pressure, though researchers still dispute that association. Researchers have been looking at excess body fat as a primary source of pro-inflammatory cytokines that produce CRP and behavioral factors related to diet, exercise and smoking. And the CRP research largely has been conducted in relatively affluent settings, such as in the United States, with low levels of infectious diseases.

The Northwestern researchers were interested in what CRP production looks like in the Philippines, a population with a high level of infectious diseases in early childhood compared to Western countries. Relative to Western countries, the Philippines also has relatively low rates of obesity and cardiovascular diseases, consistent with the Northwestern research findings.

Blood tests showed that C-reactive protein was at least 80 percent lower for study participants in the Philippines when they reached young adulthood, relative to their American counterparts, though the Filipinos suffered from many more infectious diseases as infants and toddlers. Filipino participants in their early 20s had average CRP concentrations of .2 milligrams per liter -- five to seven times lower than average CRP levels for Americans. CRP concentrations for Americans in their early 20s were on average around 1 to 1.5 milligram per liter.

Early Origins of Inflammation: Microbial Exposures in Infancy Predict Lower Levels of C-reactive Protein in Adulthood, will be published online December 9 in the journal

Women's soccer -- get fit while having fun

Fri, 02 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com )

Over a period of two years, 30 scientist lead by Associate Professor Peter Krustrup, University of Copenhagen, have investigated physiological, sociological and psychological aspects of women's soccer in comparison to running. 100 untrained adult premenopausal women have participated in the study.

The women (65 participated in the physiological study) were randomly divided into three groups: One soccer group, one running group and one control group. The soccer players and runners trained twice a week for one hour. After four and sixteen weeks, all the subjects went through extensive physiological tests. The same 65 subjects + another 35 women playing in soccer clubs were continually observed and interviewed to study the sociological and psychological effects of their training.

Many women find it difficult to fit in sport and exercise in their busy daily lives, and many state family and especially small children as the main reason for not finding the time.

The study reveals that contrary to common assumption, the flexibility of running as exercise form actually makes running harder to stick to for most women than soccer, which requires a fixed time and place.

What is really interesting is that the soccer players differed from the runners in their motivation. The runners were motivated by the idea of getting in shape and improving health. But the soccer players focused on the game itself and were motivated by the social interaction and by having fun with others. As it turns out, the soccer players got in better shape than the runners, and that combined with the social benefits makes soccer a great alternative to running, says Associate Professor Laila Ottesen and continues:

The women who played soccer have continued their soccer training as a group whereas few of the women in the running group continued running after the study. Actually, some of the women from the running group joined teams with the soccer group after the project finished.

When choosing a sport, women tend to favour cardiovascular training to strength training although the build-up of muscles and bone strength are vital to preserve health into old age.

While playing soccer, the women have high heart rates and perform many sprints, turns, kicks and tackles, making soccer an effective integration of both cardio and strength training, says project leader Peter Krustrup.

Our study shows that the 16 weeks of recreational women's soccer causes marked improvement in maximal oxygen uptake, muscle mass and physical performance, including the endurance, intermittent exercise and sprinting ability, explains Peter Krustrup, and continues

This makes soccer a very favourable choice of exercise training for women.

In the recent decade, we have seen a significant rise in women and girls playing soccer. It seems as though women are really beginning to take in soccer and make it a popular sport for women on their own terms. This is a very positive step forward, not only because of the improved physical fitness and health profile but also for the enjoyment of sports, Krustrup concludes.

The present results will be submitted online in the high-level international journal Scandinavian Journal of Medicine and Science in Sports next week (Bangsbo, Nielsen, Mohr, Randers, Krustrup, Brito, Nybo and Krustrup. Performance enhancements and muscular adaptations of a 16-week recreational football intervention for untrained women. Scand J Med Sci Sports, 2009).

In January 2010, the same journal will publish a supplementum describing multiple health effects of recreational football for various subject groups, including men, women, young and elderly. The supplementum includes one review and 13 original scientific papers.

The data will also be presented at the Scandinavian Congress of Medicine and Science in Sports 2010, Copenhagen, Denmark, 4-6 February 2010, and at the 3rd International Football Medicine Conference in Sun City, South Africa, 19-21 February 2010.

The project group currently includes collaborators from Switzerland, Norway and Italy, and major applications are currently being processed to include collaborators from England, Portugal, Belgium, Australia and Kenya.

Early identification of dementia increasingly difficult

Wed, 20 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) If grandma seems to forget things, will she end up demented? These days, memory loss is one of the very few symptoms that may signal which 70-year-olds risk developing dementia. This is shown in a doctoral thesis at the Sahlgrenska Academy at the University of Gothenburg, Sweden.

Several of the tests previously used to predict which elderly individuals risk developing dementia do not seem to work any longer. The thesis shows that memory loss is the only factor that can still be used to indicate who is at risk, although not among the very old.

The study compared nondemented 70-year-olds examined in the early 1970s with nondemented 70-year-olds examined in the year 2000. The results show that those who were examined in 2000 scored much higher on psychological tests than those examined 30 years earlier. This finding clearly indicates that such tests can no longer be used to predict future dementia.

'In the early 1970s, several different tests could be used to predict people's risks of developing dementia, but today it seems like psychiatric evaluation of the memory is the only useful test. In addition, it is more difficult to predict dementia the higher the person's level of education', says physician PhD Simona Sacuiu, the author of the thesis.

The follow-up of the 70-year-olds five years later showed that 5% had developed dementia. Those with memory problems showed an increased risk of developing dementia, although not everybody with poor memory developed dementia. Consequently, the link between forgetfulness and future dementia is more complex than commonly thought. Memory loss among elderly individuals may, but doesn't have to be, an early sign.

'In order to effectively detect dementia at an early stage, we need a useful tool that includes several types of tests, but the tests need continuous adjustments since the elderly of today perform much better at standardised psychological tests than previous generations', says PhD Sacuiu.

Examinations of a group of nondemented 85-year-olds show that the link between memory problems and dementia is not as clear in this age group. The 85-year-olds' ability to find words, to copy a geometric figure and to take quick decisions were some qualities that were evaluated in a psychiatric assessment. More than 300 individuals participated in the study, of which 17% had developed dementia three years later.

'We can't say that memory loss is the only meaningful sign of future dementia among 85-year-olds, since other symptoms, such as difficulties finding words or drawing a geometric figure, were needed for their risk of developing dementia to increase', says Sacuiu.

Navy grant to fund probe of squid and octopus camouflage

Wed, 20 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. -- Octopuses and squid are big brained species that use much of their mental powers to adjust their own appearances. This remarkable ability to camouflage on the fly has inspired the Office of Naval Research to award $7.5 million to Duke University and two collaborating institutions to learn more about how the animals do it.

Participating researchers plan to build an underwater version of the fictional Star Trek virtual reality holodeck. They will also go out on expeditions both to collect animals for study and to document their surroundings in unprecedented detail. They will even take their investigations down to the molecular level where the skin can change its own optical properties.

We need to know how the different animals we're going to look at actually see the world, said Sonke Johnsen, the Duke associate professor of biology who is principal investigator for this five-year Multidisciplinary University Research Initiative (MURI) study. What is the nature of their vision? How sharp is it, how quick does it respond to changes, and can they see colors?

Especially at the surface, where waves are moving and water quality is changing and the sun's positions are shifting, we need to measure how light fields around them change. We also want to see how they behave and change in different environments. That's where the holodeck will come in.

The cubical holodeck will be built by engineer and research oceanographer Jules Jaffe, one of two participating researchers at the University of California at San Diego's Scripps Institution of Oceanography. The aquarium-like chamber will be big enough to enclose the largest animals studied. Its walls will enable Duke and Scripps researchers to duplicate the changeable hues, lighting and optical conditions of the open ocean.

Cephalopods, the hundreds of different species classified as either octopuses or squids, are known to self-adjust skin colors and patterns in their effort to remain unnoticeable to predators or prey. Some can respond to the kinds of polarizing effects that humans need special sunglasses to discern. Some bioluminescent species even emit their own light, which they use to eliminate shadows that would give away their silhouettes.

We will be able to change the colors, resolution, speed and everything else so that we can step inside their visual world under laboratory conditions, Johnsen said. We will be able to show them natural scenes, but then also scenes that have been altered in different ways. The holodeck will be like a virtual reality machine for the ocean. In the world of marine biology we know of no other like it.

The other collaborator at Scripps will be Dariusz Stramski, a professor of oceanography who is a world expert on measuring rapidly changing light fields.

At the University of California at Santa Barbara, post-doctoral fellow Alison Sweeney, a former graduate student of Johnsen, will work with Daniel Morse, a professor of molecular genetics and biochemistry, to study proteins that can alter the animals' coloration. These pigments can self-assemble and disassemble, more or less under the control of their nervous systems, Johnsen said. And then those control how the animals look.

Meanwhile, a separate MURI led by the University of Texas at Austin will work toward goals so similar that some participants will be going on each other's research trips. In the case of the Duke-led group, that involves expeditions to islands off California and work on the Pacific island of Palau. The Texas group will head to the Florida Keys and the Gulf of Mexico. Collectively, the two efforts will receive about $15 million, Johnsen added.

So why is the military interested? Obviously, you can think that camouflage is a good thing to have, Johnsen said. You would like to be able to hide. But the work we do is at a basic, fundamental level. We won't do it with a particular application in mind. The military for ages has funded fairly basic research.

A second MURI award announced May 8 also has a Duke scientist as its principal investigator. Electrical and computer engineering professor David R. Smith is leading a study on transformation optical metamaterials funded by the U.S, Army Research Office. Smith's group works on metamaterials that can bend light to make an object appear invisible.

K-State professor awarded $1.48 million to study LASIK complictions

Fri, 01 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Gary Conrad, a university distinguished professor at Kansas State University's Division of Biology, has received a four-year grant renewal of $1.48 million from The National Eye Institute of the National Institutes of Health to study the cornea.

The NIH renewal will make Conrad's grant the longest continuously funded R01 grant in the state of Kansas at 41 years, said Jim Guikema, K-State associate vice president for research.

From the beginning, Conrad has been fascinated by the unique structure of the cornea.

Among all body tissues, the cornea is unique in being transparent, very highly innervated, free of blood vessels and yet composed of three layers of living cells, he said.

Conrad's research on embryonic development of the eye has led to knowledge that could possibly improve LASIK surgery. He and his research associates have identified a difference in the connective tissue of normal corneas compared to those that have been cut during LASIK.

LASIK, which stands for laser-assisted in situ keratomileusis, is a surgery using a laser to reshape the cornea as an alternative to wearing glasses or contact lens. During the procedure a thin-hinged flap is cut in the front of the cornea and peeled back out of the way to allow the laser to reshape the corneal connective tissue underneath the flap. When the laser is finished the flap is pulled back to its original position.

It was once believed that the flap would re-adhere permanently. However, the unique connective tissue of the cornea and a lack of blood vessels limit its ability to fully heal even years after the procedure, Conrad said. A trauma to the face, such as impact from an automobile air bag provides enough force to dislodge the flap, reopening the cornea, infecting it with dirt and debris, and causing instant loss of visual acuity.

After LASIK, differences in the structure of sugar molecules made the cornea prevent cut nerve ends from regenerating, as well as preventing the flap from re-adhering. However, the National Institutes of Health grant renewal will enable the lab group to test a possible solution that would strengthen the stromal flap and allow it to permanently bind back to the cornea after LASIK, Conrad said. It uses a combination of riboflavin and UVA light to permanently cross-link the connective tissue of the flap to the underlying corneal connective tissue. The treatment is currently in clinical trials in the U.S. for another eye dysfunction known as keratoconus.

The density of sensory nerve fibers that normally develop in our cornea is higher than anywhere else on the surface of our entire body, Conrad said. However, they regenerate extremely slowly if they are cut, so if we could get those nerves to regenerate, it would be a major medical advance.

Since the grant began in 1971, Conrad's lab group has discovered many properties of embryonic and adult corneas. He credits these accomplishments to the research professors, postdoctoral research associates, graduate students, research assistants and undergraduates in his lab who co-author many research publications that have made continuing grant funding possible.

His closest colleagues include his wife, Abigail Conrad, a K-State molecular, cellular, and developmental biologist; Yuntao Zhang, a K-State structural carbohydrate chemist; Peter Lwigale, a 2001 K-State doctoral graduate in biology and now an assistant professor at Rice University; Scott McCall, a K-State senior in biology and biochemistry and a 2008 Goldwater Scholar from Parker, Colo.; and Conrad's first doctoral student Gerald Hart, director of the department of biological chemistry at the Johns Hopkins University School of Medicine, Baltimore, Md.

Conrad is known for mentoring and encouraging undergraduates in his lab. As a result, Conrad has recommended McCall for a summer position in Hart's lab, researching structural chemistry.

Our molecular biology research is only as good as our K-State freshmen dishwashers and autoclavers, so we try to train them carefully, listen to their questions, and counsel them as our closest research colleagues, Conrad said. They teach us many things.

Risk of vibration-induced vascular injuries linked to vibration frequency differences

Sun, 19 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Speaking on April 19 at the Experimental Biology 2009 meeting in New Orleans, Dr. Kristine Krajnak, a team leader in the Engineering and Control Technologies Branch of the Health Effects Laboratory Division of NIOSH in Morgantown, West Virginia, describes results from the first study to directly link the different physical responses of tissue that occur with exposure to different vibration frequencies with biological mechanisms underlying the development of vascular dysfunction. Her presentation is part of the scientific program of The American Physiological Society.

The study, along with results of other studies conducted by NIOSH, supports the importance of reducing job-related exposure to vibration. Ongoing research is evaluating the effectiveness of anti-vibration devices, such as anti-vibration gloves and tools.

Higher frequency vibrations produced by an electric sander (greater than 100 Hz) are smoother than the slower vibrations of an electric hand drill (approximately 63 Hz) and therefore are less likely to cause users discomfort.

Don't let that fool you into not using protective devices that can reduce your exposure to vibration, she says. The new research study conducted at the National Institute for Occupational Safety and Health (NIOSH) suggests that exposure to high and low frequencies cause different physiological responses, but both may affect the risk of developing vibration-induced peripheral vascular dysfunction.

Of the 1.1 to 1.5 million U.S. workers exposed to hand transmitted vibration on a fairly regular basis, approximately half eventually develop some disorder such as Vibration White Finger, in which a single finger or sometimes the entire hand turns white and numb when exposed to the cold, due to restricted blood flow.

Workers also may experience reductions in tactile sensitivity, grip strength, and/or manual dexterity. Earlier studies have shown that risk goes up with frequency and duration of exposure, although NIOSH studies are underway to determine why certain people appear more susceptible to shorter exposure durations.

Dr. Krajnak's team looked at two aspects of vibration injury about which very little is known: the mechanisms of injury and the differences in response to frequency of vibration. The researchers used rats, since the tissues, nerves and arteries of rat-tails are similar to those in human fingers and the tails are known to respond to vibration in a way similar to that seen in fingers.

For four hours a day (the longest time a human can be exposed to workplace vibration according to U.S. and international standards) for 10 days, 15 rats (five in each group) were placed in a container where their tails were vibrated at either 63, 125 or 250 Hz. One control group of five rats accompanied them to the experimental area, to make sure any results seen were not related to noise or change of locale. A second control group stayed in their home cages, uninvolved in the activity.

After the last exposure, the scientists examined the tail arteries for changes. Neither control group had changes, suggesting the changes seen were directly related to the effects of vibration. The rats that experienced high frequency (125 and 250 Hz) vibration had higher levels of measures of oxidative stress, while rats that experienced the lower frequency (65 Hz) vibration showed higher levels of pro-inflammatory factors.

The changes seen following higher frequency vibration are associated with more immediate changes in the peripheral vascular system, such as those seen in workers with vibration injury, says Dr. Krajnak, but the changes following lower frequency vibration also can lead to vascular problems.

Jet lag disturbs sleep by upsetting internal clocks in 2 neural centers

Thu, 16 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Jet lag is the bane of many travelers, and similar fatigue can plague people who work in rotating shifts. Scientists know the problem results from disruption to the body's normal rhythms and are getting closer to a better understanding that might lead to more effective treatment.

New University of Washington research shows the disruption occurs in two separate but linked groups of neurons in a structure called the suprachiasmatic nucleus, below the hypothalamus at the base of the brain. One group is synchronized with deep sleep that results from physical fatigue and the other controls the dream state of rapid eye movement, or REM, sleep.

The ventral, or bottom, neurons receive light information directly from the eyes and govern rhythms in tune with periods of light and dark. The dorsal, or top, neurons do not receive direct light information and so govern rhythms as a more independent internal, or circadian, biological clock.

It turns out that some of the body's rhythms are more loyal to the ventral neurons and others are much more in tune with the dorsal neurons, said Horacio de la Iglesia, a UW associate professor of biology.

Normally the two neuron groups are synchronized with each other, but disruptions such as jet travel across time zones or shift work can throw the cycles out of kilter. Deep sleep is most closely tied to light-dark cycles and typically adjusts to a new schedule in a couple of days, but REM sleep is more tied to the light-insensitive dorsal neurons and can be out of sync for a week or more.

When we impose a 22-hour light-dark cycle on animals, the ventral center can catch up but the dorsal doesn't adapt and defaults to its own inner cycle, de la Iglesia said.

In the laboratory rats he uses for his research, that normal cycle is 25 hours. When the artificial 22-hour light-dark schedule was imposed, he found that the rats' deep sleep, largely governed by light but also a response to fatigue, quickly adapted to the 22-hour cycle, while their REM sleep continued to follow a 25-hour cycle. As a result, REM sleep did not occur in a normal progression following deep sleep.

We found that after exposing rats to a shift of the light-dark timing that simulates a trip from Paris to New York, REM sleep needed 6 to 8 days to catch up with non-REM, or deep, sleep, the sleep you usually experience in the first part of the night, de la Iglesia said.

The two types of sleep overlap immediately after the simulated jet lag occurs, he noted, and there is a greater likelihood of the animals entering REM sleep earlier than they should. That likely explains why it can take several days for travelers and shift workers to adapt to their new schedules, he said.

It also could explain why jet lag is associated with lower learning performance. We think the disruption of the normal circadian sequence of sleep states is very detrimental to learning, he said.

One of the problems is that you are doing things at times that your body isn't prepared to do them. One group of neurons tells your body it is Paris time and another says that it is New York time. You are internally desynchronized, said de la Iglesia.

He is lead author of a paper describing the work published online April 16 by

Two NYU Scientists Named Howard Hughes Medical Institute's early career scientists

Thu, 26 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Two researchers from NYU School of Medicine have been named Early Career Scientists by the Howard Hughes Medical Institute (HHMI). The honorees, Iannis Aifantis, Ph.D. associate professor of pathology, co-director of the Cancer Stem Cell Program at the NYU Cancer Institute and Jeremy S. Dasen Ph.D., assistant professor of physiology and neuroscience at NYU School of Medicine are among 50 of the nation's top scientists being honored by HHMI under this new initiative to establish, develop and grow unique research programs.

Dr. Aifantis, a cancer biologist investigating T-cell acute lymphocytic leukemia, a common form of leukemia in children and Dr. Dasen, a neuroscientist investigating the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control, will both receive a six-year appointment to the HHMI and funding to further explore their areas of research. HHMI will provide each NYU researcher with his full salary, benefits, and a research budget of $1.5 million over six-years.

The entire NYU Langone Medical Center community is proud of the groundbreaking work being conducted by Dr. Aifantis and Dr. Dasen and we congratulate them on their selection as HHMI Early Career Scientists, said Robert I. Grossman, M.D., Dean and CEO of NYU Langone Medical Center. These awards are recognition of the immense talent of these two scientists and the importance of the work that they are pursuing.

Dr. Aifantis has made majors strides towards understanding and developing new treatments for T-cell acute lymphocytic leukemia. He recently discovered a molecular door by which T cells, the soldiers of the immune system, slip into spinal fluid and the brain after they become malignant. Blocking this process could save thousands of lives each year. Aifantis is now testing hundreds of potential drugs that might prevent malignant T cells from reaching the nervous system. At the same time, he is learning what goes awry in blood stem cells that transform into leukemic T cells. Such insights may provide even more ways to combat deadly blood cancers.

Dr. Dasen's research focuses on deciphering the molecular code that helps developing motor neurons in the spinal cord connect with the muscles they control. Understanding this code, which relies on a large family of genes that produce proteins called Hox factors, may help scientists restore motor neuron function in people whose spinal cords have been damaged by trauma or disease. Dasen, has found that Hox proteins are not just present in motor neurons; they are pervasive throughout the nervous system. He plans to explore whether Hox proteins in interneurons and sensory neurons, which control motor neuron firing patterns and transmit feedback about muscle action, help assemble the complete circuits that control walking and running.

Children who are dissatisfied with their appearance often have problems with their peer group

Wed, 18 Mar 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Being satisfied with one's appearance is one of the most important prerequisites for a positive self image. However, in today's appearance culture it is the rule rather than the exception that children and young people are dissatisfied with their appearance.

Those children who are teased or subject to bullying are particularly critical of their appearance - and they tend to be this way over a long period. This is revealed in a new thesis in psychology from the University of Gothenburg, Sweden.

In her thesis Carolina Lunde has followed almost 1,000 children between the ages of 10 and 14. The aim has been to investigate the link between body image and peer group relationships.

An important conclusion is that both boys and girls become more dissatisfied with their body and their appearance during this age bracket - even though the girls were consistently more dissatisfied with their appearance than the boys.

The early teens can therefore be regarded as a high risk period for acquiring a negative body image. The children who weighed the most at 10 years old were particularly dissatisfied with their appearance. Furthermore, overweight children, primarily girls, were bullied and teased about their appearance considerably more often than the other children in the study.

Overweight children who are bullied can therefore be said to bear a double burden, which means that they are in the risk zone in terms of developing a negative body image.

As negative attitudes towards overweight people are formed when children are young, Carolina Lunde feels that it is important to try to counteract these prejudices at an early stage.

The fact that children and young people have a negative body image can have a number of serious psychological consequences. It increases the risk of developing eating disorders and depression. Exercising too much is also related to a negative body image. Being dissatisfied with one's appearance can also limit children and young people in their everyday lives.

They might focus to such an extent on their dissatisfaction with their appearance that they find it difficult to think of anything else. Avoiding situations that make them feel self-conscious and uncomfortable, getting changed for sports activities at school for example, is also common.

Carolina Lunde says that the title of the thesis What people tell you gets to you is a direct quotation from one of the young people who took part in one of the studies. The most dissatisfied young people indicated that their parents and their peer group frequently commented negatively about their appearance.

It might be the case that being bullied and teased about one's appearance during the early teens when the body is changing so much has a particularly negative impact on body image, observes Carolina Lunde.

Unexplained chest pain can be due to stress

Mon, 09 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Each year, many people seek emergency treatment for unexplained chest pains. A thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden, indicates several common factors among those affected, including stress at work, anxiety, depression and a sedentary lifestyle.

Chest pain is a common reason for patients to seek emergency treatment. A considerable number of patients are diagnosed with unexplained chest pain, which means that the pain cannot be linked to biomedical factors such as heart disease, or some other illness. The patient group is significant in size, with just over 20,000 patients seeking hospital treatment in 2006, and so far researchers have been unable to identify specific causes for unexplained chest pain.

Many suffer from recurring bouts of pain over several years, while the healthcare services are unable to find out what's causing it, says Registered nurse Annika Janson Fagring, the author of the thesis.

In her thesis, Annika Janson Fagring describes and analyses symptoms among patients with unexplained chest pain. The results show that most of them are middle-aged, and that over a third of those affected were born outside Sweden. The chest pain had a negative impact on the patients' daily life in the form of tiredness, anxiety and fear of death.

The main difference between women and men with unexplained chest pain is that men were more likely to perceive their lives and jobs as being stressful, while women tended more to suffer from symptoms of depressions and anxiety, says Annika Janson Fagring.

The patients, both men and women, experienced more symptoms of depression and anxiety, and work-related stress when compared with a reference group of people who were not suffering from heart disease. The male patients were more physically active in their spare time than the female patients, but compared with the reference group, both the men and the women with unexplained chest pain led a more sedentary lifestyle.

The thesis also looks at the development of symptoms and the prognosis for patients with unexplained chest pain over a period of time, compared with patients suffering from angina and patients who had suffered a heart attack. A register study revealed that from 1987 up until 2000, the number of patients with diagnosed unexplained chest pain increased, and then levelled out. The number of patients with angina increased up until 1994 and has since fallen, while the number of patients who have suffered heart attacks has fallen throughout the whole period examined.

There were fewer deaths among patients with unexplained chest pain a year after they became ill, compared with patients that became ill with angina or suffered heart attacks. Deaths among men a year after falling ill with unexplained chest pain were a third higher compared with men in the rest of the population, while women did not display any increased risk of death.

Annika Janson Fagring says that the thesis shows that it is important to improve knowledge and understanding of the symptoms experienced by patients with unexplained chest pain, in order to be able to offer more individualised care.

New study raises concerns about screen time among urban children with asthma

Wed, 04 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Urban children with asthma engage in an average of an hour more of screen time daily than the maximum amount American Academy of Pediatrics (AAP) recommends. This is the first study to examine screen time among children with asthma.

We know that both asthma and excessive screen time can be associated with other difficulties, including behavior problems, difficulty with attention, poor school performance and obesity, said Kelly M. Conn, M.P.H., of General Pediatrics at Golisano Children's Hospital at Strong and lead author of the study, which was published recently in Academic Pediatrics. (Academic Pediatrics changed its name from Ambulatory Pediatrics this year.) The study was conducted out of the University of Rochester Medical Center.

As a part of a larger study on how to more effectively treat asthma, Conn and her colleagues surveyed parents of urban children with asthma in Rochester, NY, to better understand their screen time viewing habits. Screen time includes TV watching and video tapes, playing video and computer games and using the Internet. The study found that 74 percent of the 226 children whose parents were surveyed exceeded more than two hours of screen time per day. On average, these children with asthma watched 3.4 hours daily.

Even though these findings are preliminary, a message for parents would be to remain aware of the amount of time your child is spending in front of screens and try to encourage your child to participate in a range of activities, Conn said. The types of programs children watch are also important; young children should watch shows meant for their age group, rather than watching PG-13 or R-rated movies, or playing Teen-rated games.

More than half of the parents interviewed knew that the AAP recommends a maximum of two hours of screen time per day and most parents who reported that their child had too much screen time were worried that this was the case. Though the AAP recommends that no child have a television in their bedroom, 77 percent of the children had a TV in their room and nearly half the children owned a hand-held video game system. The widespread presence and popularity of screen time activities in children's lives makes monitoring and setting limits for screen use very difficult. In addition, in an urban setting, safety concerns often limit a child's ability to engage in activities outside of the home.

Even though the goals of asthma therapy are to quell asthmatic symptoms and prevent limitations with activities, about 63 percent of children used screen time when their asthma symptoms physically limited their activities. Those children who used screens when they were having physically limiting symptoms used an average of 3.67 hours daily, which is more than half an hour extra daily than children who engaged in other non-physical activities such as resting, reading or coloring. Researchers suspect that some parents could have underestimated their child's screen time, which would demonstrate an even larger problem of excessive screen time and lack of other physical and mental activities than the study found.

The study did not have a control group of children without asthma. Children with asthma most likely watch a similar amount of screen time to all children, but children with asthma are more at risk for the health problems associated with too much screen time. In the study, children included were between 3- and 10-years-old. According to the Kaiser Family Foundation, on average children in this age range watch between two and four hours of screen time daily. So, while they may not spend more time on screens than children without asthma, the lost opportunities for physical and mental engagement may be even more detrimental to these vulnerable children.

It is not unreasonable or uncommon for children to watch TV or play a video game when they are not feeling well or when they need to slow down their activity. For all children, it is important for parents to be aware of how much screen time their children have and the types of programs they are watching, Conn said.

Conn suggests that parents of children with asthma can encourage a variety of alternate activities for their child, including reading, drawing and arts and crafts, or playing board games or puzzles. In addition, if a child is experiencing limitation of activity due to their asthma, parents should speak with their child's medical provider about ways to improve their asthma control. Many areas have organizations that were created to provide resources and support for families of children with asthma.

UT faculty members win American Heart Association awards for advancing research

Tue, 23 Dec 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Faculty members at The University of Texas Health Science Center at Houston (UTHSC-Houston) were honored for their work in the fight against heart disease at the 2008 American Heart Association's Scientific Sessions in New Orleans. Heart disease is the nation's No. 1 killer.

UT faculty members recognized were: Nobel Laureate Ferid Murad, M.D., Ph.D., director emeritus of The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of the UTHSC-Houston; John Holcomb, M.D., director of the Center for Translational Injury Research at the UTHSC-Houston; and Raffaella Lombardi, M.D., Ph.D., IMM postdoctoral fellow. The AHA scientific sessions were Nov. 8 -12.

Murad was named one of 13 Distinguished Scientists for 2008 by the American Heart Association. The prestigious award was created to honor researchers whose work has advanced the understanding of cardiovascular disease and stroke.

Murad found that nitroglycerin and several related heart drugs induce the formation of nitric oxide and that this gas acts to increase the diameter of blood vessels in the body, according to the American Heart Association. He shared the 1998 Nobel Prize in Physiology or Medicine with Robert Furchgott and Louis Ignarro for their major discoveries involving nitric oxide as a unique signaling molecule in the cardiovascular system.

Nitric oxide is one of the most important signaling molecules produced within our body. Dr. Murad's contributions to the field have revolutionized the concept of cell signaling by a gaseous molecule. Potential applications are far-reaching across multiple organ systems. Discovery of this pathway has allowed new therapeutic strategies to control blood pressure, correct conditions of endothelial dysfunction and even treat erectile dysfunction, said Nathan Bryan, Ph.D., assistant professor of molecular medicine at the IMM.

Murad completed his undergraduate work at DePauw University and received his M.D. and Ph.D. from Case Western Reserve University. He completed a medical residency at Massachusetts General Hospital and a fellowship at NIH in the Heart Institute.

Holcomb received the 2008 Lifetime Achievement Award in Trauma Resuscitation Science, which was established in 2003 to recognize leaders in this field. Holcomb's contributions to trauma medicine include increased hemorrhage control through dressings, tourniquets and intravenous methods, as well as trauma informatics and systems.

Each year the American Heart Association selects one surgeon to receive a Lifetime Achievement award for their contributions to the resuscitation of critically ill or injured patients. Dr. Holcomb, while serving in the U.S. Army (now retired) made significant contributions to the understanding and treatment of injured patients in war zones as well as civilian trauma. His contributions have led to a new paradigm in transfusion of patients sustaining blood loss. He well deserves this recognition, said Richard Andrassy, M.D., professor and chairman, the Denton A. Cooley, M.D., Chair in Surgery and the Jack H. Mayfield, M.D. Distinguished University Chair at The University of Texas Medical School at Houston.

Holcomb is past commander of the United States Army Institute of Surgical Research at the Brooke Army Medical Center in San Antonio. He finished his undergraduate work at Centenary College and received his degree of medicine at the University of Arkansas Medical School in Little Rock. He completed an internship and residency in general surgery at the William Beaumont Army Medical Center in El Paso.

Lombardi won the 2008 Louis N. and Arnold M. Katz Basic Science Research Award Prize for Young Investigators, which is given to the best scientific presentation at the annual scientific sessions of the American Heart Association.

Lombardi presented a manuscript describing the origin of the fat cells in the heart in a disease condition referred to as arrhythmogenic right ventricular cardiomyopathy, which is an important cause of sudden cardiac death in the young, especially athletes. In this disease, which is a genetic disorder, excessive fat cells replace cardiac myocytes in the heart, particularly the right side of the heart. She and her colleagues showed that fat cells originate from the stem cells in the heart that through a unique mechanism convert to fat cells in the presence of genetic mutations.

The Katz Award is the most prestigious award given to young investigators in basic cardiovascular research by the American Heart Association, said Ali Marian, M.D., professor and director of the Center for Cardiovascular Genetic Research at the IMM. The work (of Lombardi) could lead to the development of new therapies aimed at preventing the cardiac stem cells from switching a muscle fate to a fat cell fate and therefore, prevention of this potentially deadly disease.

Lombardi received her medical degree and clinical training in internal medicine and cardiology at Federico II University of Naples, Italy. She joined Marian's research group in the IMM three years ago and earned a doctorate in clinical physiopathology and experimental medicine from Federico II University of Naples during this period.

Sweat it out: UH study examines ability of sweat patches to monitor bone loss

Wed, 01 Oct 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Some health assessments that are routinely carried out on Earth are not practical when the patients are free-floating astronauts on long space flights, such as missions to Mars or the Moon. A new, NASA-funded study from the University of Houston department of health and human performance will examine how well sweat patches the size of adhesive strips can detect levels of chemicals that may indicate bone loss.

Current assessments involve blood tests, urine analysis or bone density scans, all of which are time-consuming, inconvenient to the working astronauts or, in the case of bone density scans, require large equipment that's not practical on a space station, said Mark Clarke, associate professor and principal investigator. These patches are small, non-intrusive, and placed on the skin to collect a sweat sample. The sample is then analyzed for biomarkers of bone loss markers, such as calcium.

The three-year, $780,000 study will examine three types of sweat patches, each differing in the way the sweat is collected and extracted from the devices. One device collects the sweat between the skin and a plastic layer; another is a commercially used patch that absorbs the sweat and is then reconstituted with water. The third is called a Microfabricated Sweat Patch (MSP) built using micro-chip inspired-technology. Sweat is removed from the MSP using a mini-centrifuge. The technology was developed by Clarke and Daniel Feeback, a lead scientist with NASA's Life Science Directorate.

Our goal is to develop a micro-fabricated sweat patch that collects a sweat sample from the skin, performs a biomarker analysis and immediately provides a read-out to the user, said Clarke. The first phase of the study will determine if sweat can be used to monitor bone loss. Next, it will determine which patch technology most accurately measures the chemicals associated with bone loss.

The last phase of the study will look specifically at the MSP and will involve 60 people, from young college students to elderly men and women, to new Air Force recruits. Each will wear a series of patches during normal daily activities and then perform exercises at the UH Laboratory of Integrated Physiology. The patches then will be collected and the sweat analyzed. Changes in bone also will be monitored using bone mineral density scans performed in the department. Clarke expects this phase of the project to span at least eight months.

Being in a microgravity environment causes astronauts' bodies to lose more bone mineral than they can replace, which makes them vulnerable to fractures and breaks. Even when they return to Earth, the bone loss continues as their bodies slowly begin the process of replacing the bone mineral content. This is a critical concern, especially as the space program considers longer space missions to Mars or the Moon.

Clarke says the research has applications for those susceptible to bone loss, such as the elderly, post-menopausal women and adolescent girls

Typically, it takes up to six months to see if changes in your exercise and eating habits are helping to maintain or increase bone mineral density, Clarke said. Astronauts on long flights need this information quicker so that they can make adjustments to their exercise protocols, diet or drug treatments. Similarly, bone loss in women can be seen as early as the teen years, so this kind of fast and easy screening device can provide advance notice to fend off serious bone density issues later in their lives.

Better understanding of blood vessel constrictor needed to harness its power for patients

Thu, 18 Sep 2008 03:59:37 PST

( from http://www.rxpgnews.com ) To harness endothelin-1's power to constrict blood vessels and help patients manage high blood pressure or heart failure, scientists must learn more about how endothelin functions naturally and in disease states, says a Medical College of Georgia researcher.

Despite strong laboratory evidence that blocking endothelin-1 receptors would be an effective, targeted therapy for these two major health problems, the drugs failed patients, says Dr. Adviye Ergul, physiologist in the MCG Schools of Medicine and Graduate Studies.

These endothelin-1 receptors are logical targets for drugs to treat hypertension because of their key role in vasoconstriction, but the targets are moving and we don't know how one target plays off another, says Dr. Ergul, who discussed novel aspects of endothelin receptor interaction during the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

The current thinking in pharmacology is one hormone, one receptor equals boom: the effect. I think cells are much smarter, she says. This week, Dr. Ergul challenged colleagues across the country to consider emerging evidence that usual receptor communication is likely more complex than they thought and that disease may significantly alter communication.

Endothelin-1 receptors are known to interact: one way blood vessels keep a healthy tone, for example, is that a and b receptors on smooth muscle cells prompt constriction while b receptors on the lining of blood vessels work with nitric oxide to promote relaxation. Endothelin-1 receptors on the kidneys are a player as well, helping wring out excess water and salt. There is a delicate balance, says Dr. Ergul.

But there's apparently more to the relationships. She holds up a handful of recent journal articles which reflect mounting evidence that receptors actively work as teams of two or more. That teamwork could change their function. New technology enables scientists to literally watch receptors move closer together on a cell surface, clearly indicating that something is going on.

Numerous drugs have been developed that are antagonists that can block these receptors with the idea they can be used in hypertension and heart failure. In animal models, they worked well, she says. But in clinical trials they failed badly; a drug for heart failure actually worsened problems such as labored breathing and swelling in patients already having difficulty moving blood through their body.

The first antagonists blocked both known receptors: a and b; the next generation blocked one or the other but still didn't work. A notable exception is endothelin-1 antagonists that reduce excessive pressure and tissue buildup inside the blood vessels of patients with pulmonary hypertension. In addition to constricting blood vessels, endothelin-1 can help blood vessels grow bigger but too much can result in protein deposits that stiffen blood vessel walls.

Scientists have been scratching their heads over why blocking these receptors hasn't panned out; they've even looked for an atypical receptor that might explain it. But Dr. Ergul, an expert on endothelin-1's role in diabetes, believes the unexpected results are better explained by poorly understood relationships in normal and disease states. How receptors dimerize, how they get closer together on the cell surface, likely needs to affect our drug design, she says.

UGA researchers win $9.2 million stem cell grant from NIH

Mon, 04 Aug 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A research group led by Stephen Dalton, professor and Georgia Research Alliance Eminent Scholar of Molecular Biology at the University of Georgia, has been awarded $9.2 million as part of a major new research grant by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Dalton's group, headquartered in the department of biochemistry and molecular biology, will address the molecular underpinnings of the early steps that stem cells take in becoming specialized cell types. The scientists will also seek to identify the genetic and protein modification patterns that accompany this process of differentiation.

The new grant in UGA's Franklin College of Arts and Sciences is part of $27 million in funding awarded to the University of Wisconsin, UCLA and UGA that NIGMS has added to its ongoing effort to uncover the basic biology of human embryonic stem cells.

Our program will offer training for scientists seeking to gain expertise in the specialized techniques needed to work with embryonic stem cells and will serve as a source of reagents, technical support and methodology development, said Dalton, who is also a Georgia Cancer Coalition Distinguished Scholar and a member of UGA's developmental biology program.

The results of all three new programs are expected to deepen existing knowledge of the unique properties of stem cells and will be important to researchers trying to develop stem-cell-based therapies.

This program project grant is important for a number of reasons, said David Lee, UGA vice president for research. Certainly it highlights the expertise in stem cell biology and glycomics at the University of Georgia. But perhaps more important, it is cleverly designed to promote stem cell research throughout the Southeast. One of the core facilities funded by the grant is specifically tasked with developing new stem cell technologies that will be disseminated to researchers across the region via the new Southeast Stem Cell Consortium, which Professor Dalton chairs. We are extremely pleased by the leadership provided by Dr. Dalton in an area that offers so much promise for human health.

Dalton's position as a leader in stem-cell research has been solidified with the recent establishment of the Southeast Stem Cell Consortium. The consortium has strong interests in the basic biology of stem cells, their utility as a model for studying mammalian development and their potential as a cell source to develop therapies for degenerative disease and repair of chronic injury. Focus areas include diabetes, cardiovascular disease, spinal cord injury and neurodegenerative disease.

This is an innovative program that focuses on an understudied area of stem cell biology, said Marion Zatz, Ph.D., who oversees stem cell grants at the National Institute of General Medical Sciences of the National Institutes of Health. By looking at how proteins are modified by sugar molecules as stem cells differentiate, Dalton's team could help us understand how the many distinct cell types in our bodies are formed.

Dalton's research group at UGA focuses on the uses of stem cells in understanding diabetes and cardiovascular disease. One current project involves finding ways to use stem cells to repair the human heart.

The heart is an organ that doesn't repair itself, said Dalton. But we're studying a resident population of stem cells that have the capability of dividing and turning into cardiac cells. Theoretically, they could be used to help the heart repair itself after a heart attack.

The new programs join an NIGMS effort launched in 2003 to explore the basic molecular and genetic features of human embryonic stem cells. Prior to the latest awards, the initiative has included six exploratory centers, two multidisciplinary research programs and several independent research projects and supplements.

Special horseshoes measure acceleration in horses

Sun, 06 Jul 2008 03:59:37 PST

( from http://www.rxpgnews.com ) The most frequent injuries that horses suffer are derived from pressure exerted by riders, and knowing which forces are involved when horses move can prove highly informative when considering treatment for such injuries. A team of scientists from Wageningen University, led by Professor Johan van Leeuwen, has carried out studies both into the advantages of different rider techniques in reducing injury risk, and into the benefits of a method of equine rehabilitation. By using computer modelling and specialist horseshoes to measure acceleration, these investigations suggest that aqua-training rehabilitation is beneficial due to lower impact accelerations. However, rising trot may not be as advantageous as previously thought. Results will be presented on Monday 7th July at the Society for Experimental Biology's Annual Meeting in Marseille [Session A3].

Rehabilitation after equine joint and muscle injuries, including those of the back, shoulders and legs, now often involves 'aquatraining', whereby horses move in water-filled treadmills. Due to buoyancy, this treatment is currently thought to reduce weight-bearing forces, which can otherwise have detrimental effects on joints, but to date there has been a virtual absence of studies into the magnitude of these benefits. Professor van Leeuwen's team has used special horseshoes to measure accelerations of horses undergoing aquatraining, as well as walking normally, which provide a good indication of the impact forces involved. Our results, based on data from seven horses, show the accelerations are significantly lower during 'aquatic walking', he asserts. We will be carrying out further experiments to confirm these results, but at this stage, it appears that aquatraining may indeed be beneficial for rehabilitation after joint injury.

Professor van Leeuwen and his colleagues have also used specialised force gauges to measure the strain placed on the backs of horses through the saddle and stirrups. These measurements have been combined with the output of computer models to provide insight into the mechanisms that a rider can use to respond to the movements of a horse, and to prevent injury. We have given particular attention to the comparison of sitting and rising trot, as it is broadly accepted in the equestrian world that rising trot imposes less loading on the back of the horse, Professor van Leeuwen explains. However, our results have not been able to confirm the belief that rising trot is mechanically less demanding for the horse. Looking at back extension, which is most often related to back injuries, we found that the extension of the back is similar in rising and sitting trot.

Study identifies brain pathway that shuts down seizures

Sun, 08 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at the University of Iowa and the Veterans Affairs Iowa City Health Care System have uncovered a brain pathway that shuts down seizures.

The multidisciplinary team of scientists pieced together information from clinical observations made in the first half of the 20th century with knowledge from modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.

The link between low pH in the brain and seizure termination was first hinted at nearly 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures. Subsequent studies in the 1950s found that seizures themselves reduce brain pH. However, it was the modern discovery of an acid-activated ion channel (ASIC1a) in the brain that provided the key to the UI discovery, which is reported in Nature Neuroscience Advance Online Publication on June 8.

We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity, said Adam Ziemann, a student in the Medical Scientist Training Program at the UI and co-lead author of the study.

Specifically, the study shows that mice without the ASIC1a gene have more severe and longer seizures than mice with the gene. In addition, chemically blocking ASIC1a increases the severity and duration of seizures in mice with the gene. Conversely, increasing the expression of ASIC1a in mice protects the animals from severe seizures.

The team also showed that reducing the pH in slices of brain tissue expressing ASIC1a reduced seizure activity, but acid had no effect on seizures in tissue without the protein.

When the team measured pH in mouse brains, they showed that seizures lower the pH to levels that can activate ASIC1a channels. They also found that breathing carbon dioxide causes an additional rapid drop in brain pH, and that breathing 10 percent carbon dioxide was sufficient to protect mice with the ASIC1a protein from lethal seizures.

In seizures, ASIC1a appears to be activating inhibitory neurons, explained John Wemmie, M.D., Ph.D., senior study author and assistant professor of psychiatry in the UI Roy J. and Lucille A. Carver College of Medicine, and a staff physician and researcher at the VA Iowa City Health Care System. This is the first study to show that ASIC1a activation can have an inhibitory effect.

One of the most exciting aspects of the work is that it highlights the potent anti-epileptic effects of acid in the brain -- effects that have been recognized for nearly 100 years but until recently have been poorly understood -- and it identifies ASIC1a as a key player in mediating the anti-epileptic effect of low pH, Ziemann said.

We don't know yet, but presumably there might be examples where the seizures don't stop because of a deficit in this pathway, Wemmie added.

Seizures involve abnormal synchronous firing of groups of neurons, which can cause physical symptoms such as spasms or convulsions and, in the most serious cases, altered control of vital bodily functions, like breathing. Approximately 2 to 4 percent of people will have a seizure at some point in their lives. People who have epilepsy experience repeated seizure activity.

Although the vast majority of seizures are self-limiting and stop by themselves, seizures that don't stop can develop into a life-threatening condition called status epilepticus with a mortality rate of up to 20 percent.

The discovery helps explain why breathing carbon dioxide stops seizures, which might stimulate the use of carbon dioxide for stopping seizures, Wemmie said. However, although this work provides insight into how seizures normally stop and might help us learn more about how to terminate those seizures that don't stop, it will take more work to turn the finding into a new therapeutic approach. We will be working with colleagues in neurology and neurosurgery to try and translate the findings to treatments.

Ziemann noted that a particular strength of neuroscience research at the UI is the close interaction between faculty doing cutting-edge human studies and those pursuing basic science.

Toad research could leapfrog to new muscle model

Mon, 02 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A toad sits at a pond's edge eyeing a cricket on a blade of grass. In the blink of an eye, the toad snares the insect with its tongue. This deceptively simple, remarkably fast feeding action offers a new look at how muscles work.

This fresh perspective could lead to designing more efficient electric motors, better prostheses and new medical treatments for neuromuscular diseases like Parkinson's.

Science has long held that muscles behave largely like motors. Northern Arizona University researcher Kiisa Nishikawa suggests that muscle acts more like a spring.

Existing theories don't explain how muscles shorten rapidly, Nishikawa said. Muscles can only shorten to do work; they can't do work by lengthening. A spring also can only do work by shortening.

By example, Nishikawa explains that the jaw muscles in toads and chameleons shorten in the lower jaw, and the opening of the jaws causes the tongue to stretch by its own momentum.

When a toad or chameleon captures prey with its tongue, it exerts force over a distance. Figuring out how they do it has immense application to any device that actually moves.

A toad's jaw muscles can produce forces greater than 700 times the animal's weight. The best electric motor achieves about one-third of that force-to-weight ratio, Nishikawa noted.

Muscles also function as self-stabilizing springs.

They have built-in self-correcting mechanisms. Before the brain can even react, muscles are changing their elasticity adaptively, she said. Think of walking down a flight of steps and missing a step. Leg muscles instantly become less stiff to afford better shock absorption. It's an intrinsic property of muscle, Nishikawa said.

Tom Sugar and his colleagues Arizona State University have been inspired by biology in designing a robotic tendon. After meeting with Nishikawa about her work, Sugar said, We were amazed at the speed, energy storage and power of muscle. We learned how a frog tongue will store energy and release it in a powerful burst.

At ASU's Human Machine Integration Laboratory, Sugar and his team are building SPARKy (Spring Ankle with Regenerative Kinetics) that mimics biology by storing and releasing energy during the ankle gait cycle.

Energy is stored as the leg and body rolls over the ankle, and then this energy is released in a powerful burst to propel the user forward. By mimicking biology, we are able to build a very lightweight and functional device, Sugar said.

Putting motors and springs together in a smart way is something nature hit on about 600 million years ago (with the earliest vertebrates), Nishikawa said.

It's a notion that captured the interest of Discovery Channel Canada, which spent a day at NAU and a day at ASU taping for a segment of its Daily Planet show that will air in the fall.

The NAU researcher wants to know more about how the brain controls movement. About decade ago Nishikawa realized that how the brain and body work together to produce coordinated movement means understanding what muscles contribute to the whole process.

Understanding what the neurological part is and what the muscular part is can help establish cause and effect, she said.

Identifying these mechanisms at the molecular level might aid medical research in developing better treatments for sufferers of Parkinson's, whose low force output results in stiff movements.

Nishikawa's studies of the neuromuscular basis for extremely rapid movements in animals, such as the toad snaring prey with its tongue, could leapfrog to a new model of muscle function, changing the standard representation of muscle as a motor.

Genetic mutation linked to walking on all 4s

Sun, 01 Jun 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Barcelona, Spain: What are the genes implicated in upright walking of humans? The discovery of four families in which some members only walk on all fours (quadrupedality) may help us understand how humans, unlike other primates, are able to walk for long periods on only two legs, a scientist will tell the annual conference of the European Society of Human Genetics tomorrow (Monday 2 June).

The quadrupedal families in Turkey previously attracted attention in 2005, when they were discovered. Now the Turkish team reports that they have found the first gene implicated in quadrupedal locomotion in these families.

Professor Tayfun Ozcelik, of Bilkent University, Ankara, Turkey, and colleagues, studied four unrelated families where some members were affected by the rare quadrupedic condition, Unertan syndrome, which is also associated with imperfect articulation of speech, mental retardation, and defects in the cerebellum, a part of the brain involved in motor control. They found that the affected individuals in two families had mutations in the gene responsible for the expression of very low density lipoprotein receptor (VLDLR), a protein which is known to be critical to the proper functioning of the cerebellum during development.

Although the families lived in isolated villages 200-300 km apart and reported no ancestral relationships, the scientists expected to find a single genetic mutation implicated in the condition. They were surprised to find that this was not the case.

We carried out genome-wide screening on these families, said Professor Ozcelik, and found regions of DNA that were shared by all those family members who walk on all fours. However, we were surprised to find that genes on three different chromosomes are responsible for the condition in four different families.

In families A and D there were mutations in VLDLR on chromosome 9, and in family B the phenotype maps to chromosome 17 to a region that contains at least 157 genes, and we are still looking for the precise mutation. Neither region appears to be implicated for family C.

In all cases, the affected individuals were the offspring of consanguineous marriages, which suggests that if they had married outside the family they would not have had the condition. All of them had significant developmental delay in infancy. Whereas normal infants make the transition to walking on two legs in a relatively short period, said Professor Ozcelik, these individuals continued to move on their palms and feet and never walked upright. Although they can stand from a sitting position and maintain this upright position with flexed hips and knees, they virtually never initiate bipedal walking on their own.

It has been suggested in the past that lack of access to medical care exacerbated the effects of an under-developed cerebellum, and that this led to quadrupedality. Although it may be true that family B lacked proper medical care, families A and D had consistent access to good medical attention, and both families sought a correction of quadrupedality in their affected children, said Professor Ozcelik. Indeed, an unaffected member of family A is a physician, who has been actively involved in the medical interventions. In addition, the parents in family A also discouraged their affected children from walking on all fours, to no avail. We think that social factors are unlikely to be involved in the development of quadrupedal locomotion.

Mutations causing VLDLR deficiency are also found in Hutterites, a group of Anabaptists who live in colonies of North America. There, however, most of the affected individuals cannot walk at all. The neurological characteristics of the affected members of the Turkish families and the Hutterites seem similar, with the most striking difference being that the Turkish individuals are able to walk on all fours, said the scientists. They hypothesize that the Hutterites may be more profoundly affected due to the deficiency in VLDLR and a neighbouring gene, and therefore lack the motor skills even for quadrupedal locomotion.

Along with brain enlargement, speech, and the ability to make tools, upright walking has long been regarded as one of the key traits that have led to modern humans. Professor Ozcelik's team have opened a window on how mutations in VLDLR affect brain development and influence gait in humans.

It will be interesting to see if the VLDLR gene is involved in other types of cerebellar ataxias. In addition, we hope to identify the defective genes associated with quadrupedal locomotion in families B and C, he says.

How exercise changes structure and function of heart

Tue, 22 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) For the first time researchers are beginning to understand exactly how various forms of exercise impact the heart. Massachusetts General Hospital (MGH) investigators, in collaboration with the Harvard University Health Services, have found that 90 days of vigorous athletic training produces significant changes in cardiac structure and function and that the type of change varies with the type of exercise performed. Their study appears in the April Journal of Applied Physiology.

“Most of what we know about cardiac changes in athletes and other physically active people comes from ‘snapshots,’ taken at one specific point in time. What we did in this first-of-a-kind study was to follow athletes over several months to determine how the training process actually causes change to occur,” says Aaron Baggish, MD, a fellow in the MGH Cardiology Division and lead author of the study.

To investigate how exercise affects the heart over time, the MGH researchers enrolled two groups of Harvard University student athletes at the beginning of the fall 2006 semester. One group was comprised of endurance athletes – 20 male and 20 female rowers – and the other, strength athletes – 35 male football players. Student athletes were studied while participating their normal team training, with emphasis on how the heart adapts to a typical season of competitive athletics.

Echocardiography studies – ultrasound examination of the heart’s structure and function – were taken at the beginning and end of the 90-day study period. Participants followed the normal training regimens developed by their coaches and trainers, and weekly training activity was recorded. Endurance training included one- to three-hour sessions of on-water practice or use of indoor rowing equipment. The strength athletes took part in skill-focused drills, exercises designed to improve muscle strength and reaction time, and supervised weight training. Participants also were questioned confidentially about the use of steroids, and any who reported such use were excluded from the study.

At the end of the 90-day study period, both groups had significant overall increases in the size of their hearts. For endurance athletes, the left and right ventricles – the chambers that send blood into the aorta and to the lungs, respectively – expanded. In contrast, the heart muscle of the strength athletes tended to thicken, a phenomenon that appeared to be confined to the left ventricle. The most significant functional differences related to the relaxation of the heart muscle between beats – which increased in the endurance athletes but decreased in strength athletes, while still remaining within normal ranges.

“We were quite surprised by both the magnitude of changes over a relatively short period and by how great the differences were between the two groups of athletes,” Baggish says. “The functional differences raise questions about the potential impact of long-term training, which should be followed up in future studies.”

While this study looks at young athletes with healthy hearts, the information it provides may someday benefit heart disease patients. “The take-home message is that, just as not all heart disease is equal, not all exercise prescriptions are equal,” Baggish explains. “This should start us thinking about whether we should tailor the type of exercise patients should do to their specific type of heart disease. The concept will need to be studied in heart disease patients before we can make any definitive recommendations.”

Repeated methamphetamine use causes long-term adaptations in brains of mice, researchers find

Wed, 09 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Repeatedly stimulating the mouse brain with methamphetamine depresses important areas of the brain, and those changes can only be undone by re-introducing the drug, according to research at the University of Washington and other institutions. The study, which appears in the April 10 issue of the journal Neuron, provides one of the most in-depth views of the mechanisms of methamphetamine addiction, and suggests that withdrawal from the drug may not undo the changes the stimulant can cause in the brain.

The researchers set out to determine what sort of changes happen in the brain because of repeated use of the stimulant methamphetamine, and to better understand addiction-related behaviors like drug craving and relapse. Methamphetamine, also known as simply meth, is one of the most popular illegal drugs in the United States, and abuse of the drug can cause severe addiction.

Scientists have believed that abuse of drugs like meth can cause changes to the neurons in the brain and the synapses and terminals that control transmission of information in the brain. In this project, researchers focused on the mouse brain, and how it was affected by methamphetamine over 10 days, which is the mouse equivalent of chronic use in humans.

They found that the long administration and withdrawal of the drug depressed the neural terminals controlling the flow of signals between two areas of the brain, the cortex and striatum. Even a long period of withdrawal -- the equivalent of years in humans -- did not return the terminals to normal activity level. Re-introducing the drug, however, reversed the changes in the brain.

The areas affected by the drug are called pre-synaptic terminals, and are related to the flow of information from the cortex to the striatum. When a person sees something new in their environment, the scientists explained, she focuses attention on that item. At the neuron level, that process stimulates the release of dopamine, a chemical involved in transmitting signals in the brain. As the person sees the new item over and over again, the dopamine response drops, and synapses in the brain adapt to the no-longer-new item.

What happens with methamphetamine use is that the drug makes the nervous system release dopamine, which helps a user focus a lot of attention on a particular goal. Scientists believe that meth allows dopamine in the striatum to filter information coming from the cortex through the pre-synaptic terminals. The filtering of some of the terminals would help someone ignore other things and focus on that one goal or task.

After chronic use of methamphetamine, the filtering process eventually becomes a permanent depression in the activity of those terminals in the brain, the scientists found. And the only thing that can help the pre-synaptic terminals recover in mice, they found, was re-administering the drug.

What we found is that the repeated use of methamphetamine causes adaptations in the brain, and that only re-introducing the drug can reverse that, said Dr. Nigel Bamford, UW assistant professor of neurology and pediatrics and a physician at Seattle Children's Hospital. We think these changes in the brain may account for at least some of the physiological components of meth addiction.

If the mechanism turns out to be similar in people, Bamford said, this could have big effects on the treatment and management of methamphetamine addiction. One treatment for drug addiction is to give people smaller and smaller amounts of the drug to wean them from it and reduce the effects of withdrawal. Unfortunately, that method would not affect the adaptation of the neural terminals in the brain.

Now that we have some understanding of the mechanism through which meth addiction occurs, we may be able to develop other approaches to treating addiction, explained Bamford. We might be able to target some of the chemical receptors in the brain to reset the system and get rid of this depressed state in the pre-synaptic terminals.

Though scientists believe that other stimulants, like methylphenidate, may have similar effects on the brain, they caution against applying these findings to other situations. These synaptic changes may not occur in patients with underlying conditions that require treatment with stimulants, the scientists said.

U. Iowa study finds biological link between pain and fatigue

Mon, 07 Apr 2008 03:59:37 PST

( from http://www.rxpgnews.com ) A recent University of Iowa study reveals a biological link between pain and fatigue and may help explain why more women than men are diagnosed with chronic pain and fatigue conditions like fibromyalgia and chronic fatigue syndrome.

Working with mice, the researchers, led by Kathleen Sluka, Ph.D., professor in the Graduate Program in Physical Therapy and Rehabilitation Science in the UI Roy J. and Lucille A. Carver College of Medicine, found that a protein involved in muscle pain works in conjunction with the male hormone testosterone to protect against muscle fatigue.

Chronic pain and fatigue often occur together -- as many as three in four people with chronic, widespread musculoskeletal pain report having fatigue; and as many as 94 percent of people with chronic fatigue syndromes report muscle pain. Women make up the majority of patients with these conditions.

To probe the link between pain and fatigue, and the influence of sex, the UI team compared exercise-induced muscle fatigue in male and female mice with and without ASIC3 -- an acid-activated ion channel protein that the team has shown to be involved in musculoskeletal pain.

A task involving three one-hour runs produced different levels of fatigue in the different groups of mice as measured by the temporary loss of muscle strength caused by the exercise.

Male mice with ASIC3 were less fatigued by the task than female mice. However, male mice without the ASIC3 protein showed levels of fatigue that were similar to the female mice and were greater than for the normal males.

In addition, when female mice with ASIC3 were given testosterone, their muscles became as resistant to fatigue as the normal male mice. In contrast, the muscle strength of female mice without the protein was not boosted by testosterone.

The differences in fatigue between males and females depends on both the presence of testosterone and the activation of ASIC3 channels, which suggests that they are interacting somehow to protect against fatigue, Sluka said. These differences may help explain some of the underlying differences we see in chronic pain conditions that include fatigue with respect to the predominance of women over men.

The study, which was published in the Feb. 28 issue of the American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, indicates that muscle pain and fatigue are not independent conditions and may share a common pathway that is disrupted in chronic muscle pain conditions. The team plans to continue their studies and investigate whether pain enhances fatigue more in females than males.

Our long-term goal is to come up with better treatments for chronic musculoskeletal pain, Sluka said. But the fatigue that is typically associated with chronic widespread pain is also big clinical problem -- it leaves people unable to work or engage in social activities. If we could find a way to reduce fatigue, we could really improve quality of life for these patients.

Scientists identify new longevity genes

Wed, 12 Mar 2008 03:59:37 PST

( from http://www.rxpgnews.com ) Scientists at the University of Washington and other institutions have identified 25 genes regulating lifespan in two organisms separated by about 1.5 billion years in evolutionary change. At least 15 of those genes have very similar versions in humans, suggesting that scientists may be able to target those genes to help slow down the aging process and treat age-related conditions. The study will be published online by the journal Genome Research on March 13.

The two organisms used in this study, the single-celled budding yeast and the roundworm C. elegans, are commonly used models for aging research. Finding genes that are conserved between the two organisms is significant, researchers say, because the two species are so far apart on the evolutionary scale -- even farther apart than the tiny worms and humans. That, combined with the presence of similar human genes, is an indication that these genes could regulate human longevity as well.

Now that we know what many of these genes actually are, we have potential targets to go after in humans, said Brian Kennedy, UW associate professor of biochemistry and one of the senior authors of the study. We hope that in the future we could affect those targets and improve not just lifespan, but also the 'health span' or the period of a person's life when they can be healthy and not suffer from age-related illnesses.

Several of the genes that the scientists identified as being involved in aging are also connected to a key nutrient response pathway known as known as the Target of Rapamycin, or TOR. That finding gives more evidence to the theory that calorie intake and nutrient response affect lifespan by altering TOR activity. Previous studies have found that drastically restricting the caloric intake of organisms, an approach known as dietary restriction, can prolong their lifespan and reduce the incidence of age-related diseases. TOR inhibitors are being tested clinically in people for anti-cancer properties, and this work suggests they may also be useful against a variety of age-associated diseases.

What we'd like to eventually do is be able to mimic the effects of dietary restriction with a drug, explained Matt Kaeberlein, another senior author on the paper and a UW assistant professor of pathology. Most people don't want to cut their diet that drastically, just so they may live a little longer. But someday in the future, we may be able to accomplish the same thing with a pill.

These findings also give new insight into the genetic basis of aging, the scientists said, and provide some of the first quantitative evidence that genes regulating aging have been conserved during the process of evolution. Earlier evolutionary theories suggested that aging was not genetically controlled, since an organism does not get any advantage in natural selection by having a very long lifespan that goes far past their reproductive age.

To find these lifespan-controlling genes, the scientists took a genomic approach to comprehensively examine genes that affect aging in yeast and worms. Based on published reports, they first identified 276 genes in C. elegans that affected aging, and then searched for similar genetic sequences in the yeast genome. Of the 25 aging-related genes they found in both worms and yeast, only three had been previously thought to be conserved across many organisms.

Oregon study raises questions on synthetic progestins

Sun, 09 Mar 2008 04:59:37 PST

( from http://www.rxpgnews.com ) The widely used synthetic progestin medroxyprogesterone acetate (MPA) decreased endothelial function in premenopausal women in a study done at the University of Oregon. The finding, researchers said, raises concerns about long-term effects of MPA and possibly other synthetic hormones on vascular health in young women.

The vascular endothelium lines the inside of blood vessels. In recent years, it has been found to be a dynamic organ that serves an important role in the prevention of atherosclerosis.

The logical conclusion of this study is that over a long period of time it would not be good to have exposure to an agent that is reducing blood vessel flexibility, because it could be associated with the development of heart disease or related problems, said co-author Dr. Paul F. Kaplan, a long-time Eugene gynecologist and senior researcher in the UO's human physiology department. He stressed, however, that a longer, larger study is needed.

MPA is the progestin that was used in the Women's Health Initiative (WHI), including a clinical study on hormone-replacement therapy halted because of health concerns in postmenopausal women. MPA is the active ingredient of Provera, which is used to treat abnormal uterine bleeding, induce menstrual cycles and relieve symptoms of the menopause.

It's also a component in Depo/Provera, an injectible long-lasting contraceptive used by many young women. Millions of women use various hormone therapies with a variety of progestin types for contraception. In the U.S. alone, 80 percent of women have used oral contraceptives.

The UO study, appearing online ahead of regular publication by the journal Heart and Circulatory Physiology, is among the first to focus on the impact of MPA in premenopausal women. Fourteen women, 19-27 years old, took part in the study after passing thorough medical exams to screen out numerous health conditions.

The five-member UO team -- led by Jessica R. Meendering, a former UO doctoral student now a professor of exercise science at the University of Nebraska in Omaha -- studied the effects of the sex hormone estradiol by itself and in combination with MPA on endothelial function of the brachial artery. The health of the endothelium in this artery has been shown to be a telling proxy for the coronary arteries and a good predictor of cardiovascular risk.

When researchers gave an oral version of MPA to determine its impact, they found that it wiped out the positive effects on endothelial function that estradiol had provided. MPA reduced the function by reducing the brachial artery's ability to dilate -- grow bigger in diameter -- in response to the stress of changing blood flow, Kaplan said.

UO researchers also found that MPA had an effect on concentrations of endothelin-1, a peptide that promotes cell division and serves as a mediator of inflammation. It also acts as a constricting factor for blood vessels. When peptide levels rise, endothelin-1 is suspected to play a key role in many diseases of the airways, pulmonary circulation, inflammatory lung diseases and vasoconstriction of blood vessels. UO researchers saw levels decline with estradiol alone, but increase substantially with the addition of MPA, negating the benefits of the estrogen.

There is an overwhelming amount of evidence to suggest that estrogen is beneficial to arterial vascular health of women, Meendering said. Since the WHI found either no benefit or a slight increase in adverse cardiovascular events in postmenopausal women taking combination hormone-replacement therapy containing estrogen and MPA, many have questioned the vascular effects MPA and its use in postmenopausal women. This led our group to question how MPA affects the vasculature in young women.

We need to be taking the time to find out if different synthetic hormones have different effects on vascular health in young women, she said. It's not a big health concern right now, because there are no obvious short-term effects raising health concerns. But we don't know how these synthetic hormones taken by young women affect their long-term cardiovascular health. Maybe effects aren't being noticed while women are young, but maybe they are adding to the fact that rates of cardiovascular disease are so high in women.

Kaplan stressed that this project was a starting point of major basic science research, so this study does not say women should change what they are doing.

We can say that we saw vascular changes in the arteries of the arm that have been shown in previous studies involving coronary arteries, he added. This study does let us say that whatever changes we are seeing are important not just for the arm but probably for most of the major arteries in the body, and this is important for cardiac disease.

Genetic tags reveal secrets of memories' staying power in mice

Thu, 21 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A better understanding of how memory works is emerging from a newfound ability to link a learning experience in a mouse to consequent changes in the inner workings of its neurons. Researchers, supported in part by the National Institutes of Health's National Institute of Mental Health (NIMH), have developed a way to pinpoint the specific cellular components that sustain a specific memory in genetically-engineered mice.

Remarkably, this research demonstrates a way to untangle precisely which cells and connections are activated by a particular memory, said NIMH Director Thomas Insel, M.D. We are actually learning the molecular basis of learning and memory.

For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins triggered by the learning. Yet, it's been a mystery how these new proteins -- born deep inside a neuron -- end up becoming part of the specific connections in far-off neuronal extensions that encode that memory.

By tracing the destinations of such migrating proteins, the researchers located the neural connections, called synapses, holding a specific fear memory. In the process, they discovered these synapses are distinguished by telltale molecular tags that enable them to capture the memory-sustaining proteins.

Mark Mayford, Ph.D., and Naoki Matsuo, Ph.D., of the Scripps Research Institute, report on their findings in the February 22, 2008, issue of the journal Science.

The Scripps researchers have been applying their new technique in a series of studies that focus on progressively finer details of the molecular machinery of memory.

Inside neurons involved in a specific memory, we're tracing molecules activated by that learning to see how it ultimately changes neural connections, explained Mayford.

In a study published in the August 31, 2007, Science, Mayford and colleagues showed the same neurons activated by a learning experience are also activated when that memory is retrieved. The more neurons involved in the learning, the stronger the memory.

The researchers determined this by genetically engineering a strain of mice with traceable neurons in the brain's fear center, called the amygdala. Inserted genes caused activated neurons to glow red when the animals learned to fear situations where they received shocks, in a process known as fear conditioning -- and to glow green when the memory was later retrieved. The researchers then chemically prevented further expression of those neurons, so that resulting neural and behavioral changes could be confidently attributed to that learning experience at a later time. The study revealed which circuits and neurons were involved in the specific learning experience.

In the new study, Mayford and Matsuo adapted this approach to discover how fear learning works at a deeper level -- inside neurons of the brain's memory hub, called the hippocampus.

Evidence suggested that proteins called AMPA receptors strengthen memories by becoming part of the synapses encoding them. To identify these synapses, the researchers genetically engineered a strain of mice to express AMPA receptors traceable by a green glow. After fear conditioning had triggered new AMPA receptors deep in the neuron's nucleus, they chemically suppressed any further expression of the proteins. This allowed time for the receptors to migrate to their appointed synapses. Hours later, green fluorescence revealed the fate of the specific AMPA receptors born in response to the learning.

As expected, the newly synthesized AMPA receptors had traveled and become part of only certain hippocampus synapses -- presumably the ones holding the memory. Synaptic connections are made onto small nubs on the neuron called spines. These spines come in three different shapes called thin, stubby and mushroom. While little was known about the function of these differently shaped spines, the fact that they are altered in various forms of mental retardation, like Fragile-X syndrome, suggests a critical importance in mental function.

The researchers discovered the synapses that received the AMPA receptors with memory were limited to the mushroom type. The mushroom spines also figured prominently in the same neurons when the fear conditioning was reversed by repeatedly exposing the animals to the feared situation without getting shocked -- a procedure called extinction learning. This indicated that the same neurons activated when a fear is learned are also activated when it is lost. The surge in mushroom spine capture of the receptors appeared within hours of learning and was gone after a few days, but appeared to be critical for cementing the memory.

Immune deficiency and balance disorder result from single gene defect

Thu, 21 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A genetic defect that causes a severe immune deficiency in humans may also produce balance disorders, according to a new study by researchers at the University of Iowa, The Jackson Laboratory and East Carolina University.

The study, published online Feb. 21 in the Journal of Clinical Investigation, examined a specialized strain of Jackson Laboratory mice with a mutation that eliminates the production a protein called p22phox. Disruption of this protein causes a form of chronic granulomatous disease (CGD) -- a severe immune deficiency -- in humans.

The researchers found that mice without p22phox develop an immune deficiency that mimics human CGD. They also discovered that the gene defect produces a severe balance disorder in the mice caused by loss of gravity-sensing crystals in the inner ear.

The implication is that human patients with CGD caused by defects in this gene may also have balance disorders, said Botond Banfi, M.D., Ph.D., UI assistant professor of anatomy and cell biology and senior author of the study. If that is the case, this would be the first patient population where we could study the consequences of losing the sensation of gravity.

We hope that clinicians will test the balance capacity of those patients with this rare form of CGD Banfi added. Although it is hard to say what the consequences might be of not sensing gravity, these patients may be more prone to accidents like falling.

In addition to Banfi, the research team included Yoko Nakano, Ph.D., a UI postdoctoral fellow in Banfi's laboratory and lead author of the study; David Bergstrom, Ph.D., research scientist, and Chantal Longo-Guess, research assistant, both at The Jackson Laboratory; Sherri Jones, Ph.D., associate professor of communication sciences and disorders at East Carolina University; and William Nauseef, M.D., UI professor of internal medicine.

P22phox is emerging as a critical subunit of a family of enzymes that produce reactive oxygen species (ROS). For many years, ROS were simply thought of as destructive molecules that can kill infecting bacteria but also damage human cells. More recently, however, ROS have been shown to play an important role in many normal cell processes, including development and blood pressure regulation. The family of enzymes that produce ROS are called NADPH oxidases (Nox), and disruption of these enzymes has been implicated in a range of diseases, including cardiovascular and neurodegenerative diseases as well as immune deficiencies like CGD.

There are several forms of CGD caused by different genetic defects affecting the Nox complex of pathogen-fighting cells called phagocytes. CGD caused by lack of p22phox is one of the least common forms of the disease in humans. The mutant mouse, which was produced by The Jackson Laboratory's Neuromutagenesis Facility, represents the first animal model for this version of CGD and will be helpful in understanding the disease and developing potential treatments.

The study found that the mice without the p22phox protein were unable to produce ROS in phagocytes and were particularly susceptible to infection. For mice without the protein, infection with bacterial pneumonia was universally fatal. In contrast, normal mice had a 100 percent recovery rate from the same infection.

The mutant mice also had a severe balance disorder. Unlike normal mice that quickly learned how to walk on a rotating rod without falling off, the mutant mice always fell off within a few seconds. Additionally, the study showed that activity of nerve cells in the inner ear responsible for sending gravity signals to the brain was absent in the mutant mice.

Loss of p22phox affects two enzyme complexes: one in phagocytes that is responsible for the immune defect, and one in the inner ear, Banfi said. Since this is the first mouse model for defects in the p22phox subunit, this is the first time that its role in balance has been revealed.

Although inner ear cells looked normal in the mutant mice, the researchers discovered that otoconia -- tiny calcium carbonate crystals that are essential for sensing gravity -- do not form in the inner ears of these mice. Restoring the normal gene to the mutant mice rescued otoconial production and prevented the balance disorder. However, although the treatment did improve the mice's immune response, the partial restoration of gene expression was not sufficient to cure the immune deficiency completely.

This may mean that gene therapy, which would only partially restore expression of p22phox, would not completely cure CGD in humans, cautioned Banfi. We may have to look for alternatives and these mice will be ideal models to test new ideas for therapy.

The team was also able to track the location of the Nox complex during embryonic development of the inner ear by visualizing the location of p22phox. Interestingly, the complex does not reside in the same place that the otoconia form leading the researchers to propose a new mechanism by which the Nox complex controls production of the crystals.

Transparent fish to make human biology clearer

Wed, 06 Feb 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Zebrafish are genetically similar to humans and are good models for human biology and disease. Now, researchers at Children's Hospital Boston have created a zebrafish that is transparent throughout its life. The new fish allows scientists to directly view its internal organs, and observe processes like tumor metastasis and blood production after bone-marrow transplant in a living organism.

The fish, described in the February 7 issue of Cell Stem Cell, was created by Richard White, MD, PhD, a clinical fellow in the Stem Cell Program at Children's, with others in the laboratory of Leonard Zon, PhD.

The classic method for studying human diseases in animals is to allow the animal to get the disease, kill and dissect the animal, then ask, what happened? But in cancer and other fast-changing processes that traverse the body, this method is bound to miss something. It's like taking a photograph when you need a video, says White, also an instructor of medicine at the Dana-Farber Cancer Institute.

Zebrafish embryos have enabled researchers to study disease in live organisms, since they are transparent. But zebrafish adults are opaque. Everything after four weeks has been invisible to us, says White.

White's first experiment on the zebrafish examined how a cancer spreads. The process by which a tumor goes from being localized to widespread and ultimately fatal is the most vexing problem that oncologists face, says White. We don't know why cancer cells decide to move away from their primary site to other parts in the body.

White created a fluorescent melanoma tumor in the transparent fish's abdominal cavity. Viewing the fish under a microscope, White saw the cancer cells begin to spread within five days. He even saw individual cells metastasize, something that has not been observed, so readily and in real-time, in a living organism.

The spreading melanoma cells appeared to home to the skin after leaving the abdominal cavity. This told us that when tumor cells spread to other parts in the body, they don't do it randomly, says White. They know where to go.

White plans to study tumor cell homing, then look for ways to modify the tumor cells or cells of the host so that the spreading cells never find their new location.

The fish may also answer questions about stem cell transplants. While transplants of blood-forming stem cells help cancer patients rebuild healthy blood, some transplants don't take, for reasons that are unknown. Scientists have lacked a full understanding what steps blood stem cells must take to do their job, says White.

White showed the process is observable in the fish. He first irradiated a transparent fish's bone marrow, then transplanted fluorescent blood-forming stem cells from another zebrafish. By four weeks, the fluorescent stem cells had visibly migrated and grown in the fish's bone marrow, which is in the kidney. Even individual stem cells were visible, something researchers haven't easily observed in a living organism, White says.

By studying how the stem cells embed and build blood in the fish, scientists can look for ways to help patients rebuild their blood faster. Drugs and genes could be tested in the living fish, with direct observation of results, White says.

Anemia treatment may be a double-edged sword

Wed, 30 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Erythropoietin has so far been known to doctors as a hormone that boosts red-blood-cell production. Now, a mouse study led by Lois Smith, MD, PhD, an ophthalmologist at Children's Hospital Boston, shows it also keeps blood vessels alive and growing in the eye. The findings not only add a new function to the hormone, but also give doctors a reason to pause before prescribing it to patients with diseases affected by abnormal blood-vessel growth, such as retinopathy and cancer.

The study, published in the February issue of the Journal of Clinical Investigation (online January 24), also found that whether the hormone is a risk or benefit depends on the timing of administration.

Smith and first author Jing Chen, PhD, worked in mice with retinopathy, an eye disease that begins when healthy blood vessels nourishing the retina die. Numerous vessels then grow in, but they are deformed. Ultimately, the deformed vessels may pull the retina off the back of the eye, causing blindness.

The researchers measured erythropoietin produced in the retina as the disease progressed. Production was 3 to 10 times below normal during early-stage retinopathy, when healthy blood vessels died, and 12 to 33 times above normal during late-stage retinopathy, when deformed blood vessels grew into the retina. The researchers concluded that erythropoietin helps blood vessels survive and grow in the retina, with effects that may be healthy or harmful.

Next, the team examined whether giving erythropoietin could treat retinopathy. They injected erythropoietin into the bloodstream either early, as the mice lost healthy blood vessels, or later, when deformed blood vessels began to invade--then compared them with untreated mice.

Boosting erythropoietin early slowed the disease. The mice lost half as many healthy blood vessels, causing about 30 percent fewer deformed vessels to grow in. Raising erythropoietin levels later, when deformed blood vessels were present, appeared to accelerate the disease--slightly more deformed blood vessels grew in.

If similar effects are found in humans, and its use is properly timed, then giving erythropoietin early could slow loss of healthy blood vessels in retinopathy, says Smith. Right now, there is very little out there to treat blood vessel loss in patients with retinopathy. However, further studies on the restoration of normal levels of erythropoietin are needed to translate these results to patients.

In other diseases, like cancer, in which doctors need to slow blood vessel growth, the hormone could be blocked, although clinical trials would need to confirm this idea, she adds.

But given at the wrong time, erythropoietin may make blood vessels grow in an unhealthy way, says Smith. For example, because it boosts red blood cells, erythropoietin is often prescribed to premature babies and diabetic adults for anemia. Some of these patients also have retinopathy. Giving the hormone at the wrong time might help anemia, but worsen the eye disease.

We're not saying, 'don't do it.' We're saying, 'think about it,' says Smith. Physicians should look at the state of the eye before giving erythropoietin to patients with retinopathy. They should consider not giving it to patients with full-blown retinopathy, in which abnormal vessels are present, because our work suggests it may accelerate the disease. However, if a patient is early on in the disease, then our work suggests erythropoietin may be beneficial.

Cancer patients, who often take erythropoietin for anemia, face a similar potential risk, says Smith. Since erythropoietin has the potential to make blood vessels in tumors grow, it could make tumors worse, although a clinical trial is required to know if this is true in humans.

Overall, Smith says her mouse studies are a reason for doctors to think and researchers to investigate, not for patients to panic.

Breakdown of kidney's ability to clean its own filters likely causes disease

Tue, 29 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Jan. 29, 2008 -- The kidney actively cleans its most selective filter to keep it from clogging with blood proteins, scientists from Washington University School of Medicine in St. Louis reveal in a new study.

Researchers showed that breakdown of this self-cleaning feature can make kidneys more vulnerable to dysfunction and disease.

We speculate that defects of this clearance mechanism can leave things on the filter that can damage it, says senior author Andrey Shaw, M.D., Emil R. Unanue Professor of Immunobiology in Pathology and Immunology. This could include autoimmune antibodies that mistakenly target the body's own tissues like those that occur in the disease lupus.

The study appears in the Jan. 22 Proceedings of the National Academy of Sciences.

Despite extensive knowledge of the structure of the kidney, several scientific controversies linger over how the organ does its complicated and essential job of filtering wastes from the blood for disposal without simultaneously discarding too much water or key blood proteins in the urine. Understanding how these tricky tasks are accomplished is essential to developing new treatments for kidney disease and renal failure, which are among the top ten causes of death in the United States.

Like many mechanical filtering systems, the kidney passes the blood through a series of progressively finer screens. After passing through a structure known as the glomerular basement membrane (GBM), fluid and serum proteins must finally pass through the most selective filter of the kidney, which is comprised of specialized epithelial cells called podocytes. These cells form a web-like barrier to the passage of large serum proteins into the urine.

The kidney screens 150 to 200 liters of blood daily, and we were curious as to how the kidney keeps the filter from clogging up, says first author Shreeram Akilesh, an M.D./Ph.D. student. The two most common blood serum and plasma proteins are albumin, which helps regulate blood volume and convey a number of different substances around the body, and immunoglobin G (IgG), a type of immune system antibody. Because they're so common, we figured they would be among the most likely to get stuck on the filter, and set out to look for proteins that help clear them.

Researchers looked for proteins made in podocytes that could bind to albumin and IgG, reasoning that such proteins likely provide the handles the podocytes need to grab proteins and clear them from the filter.

A protein known as FcRn was high on the list of likely suspects. Akilesh had studied FcRn previously in the laboratory of coauthor Derry C. Roopenian, Ph.D., professor at the Jackson Laboratory in Bar Harbor, Maine. Prior research there and in other laboratories had revealed that FcRn binds to both IgG and albumin and is present in human podocytes.

After confirming that the FcRn protein also is made in mouse podocytes, scientists then asked if FcRn was responsible for clearing IgG antibody from the filter. To do this, they measured the retention of a radioactive tracer in the kidneys of normal mice and in mice where the gene for FcRn had been disabled. Mice lacking FcRn had difficulty clearing antibody from the kidney.

When researchers studied the mice lacking FcRn for longer periods of time, they saw evidence that antibodies were accumulating in the kidney.

In another experiment, researchers gave the mice injections of large quantities of protein to saturate the clearance system. They followed those injections with what would normally have been a harmlessly small dose of an antibody potentially toxic to the kidney. The mice developed kidney damage as a result. Researchers believe this was because they couldn't clear the toxic antibody from the GBM quickly enough.

This is the first clear demonstration that the filter system in the kidney isn't just a passive mechanical filter, it's actually involved in its own maintenance, says Akilesh. It also provides us with a nice mechanism for explaining how the normal function of this filter may be breaking down in ways that leads to kidney disease and damage.

To follow up, Shaw plans to look for other podocyte proteins involved in filter clearance.

Lungs' mast cells could provide new treatment target for asthma, other respiratory disease

Tue, 29 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Jan. 29, 2008) -- An enzyme released by mast cells in the lungs appears to play a key role in the tightening of airways that is a hallmark of asthma -- pointing to a potential new target for treatment against the illness.

Reporting in the online edition of Proceedings of the National Academy of Sciences, a team at Weill Cornell Medical College explains that during an immune response, mast cells release the enzyme -- called renin -- which in turn produces angiotensin, a potent constrictor of the smooth muscle that lines airways.

Mast cells are normally present in small numbers in all organs, and are best known for their role in allergy, shock, wound healing and defense against pathogens.

Back in 2005, our team was the first to discover that mast cells in the heart released renin locally, which elicited heart arrhythmias by triggering angiotensin production within the heart, explained co-senior author Dr. Roberto Levi, professor of pharmacology at Weill Cornell Medical College.

Now, we've expanded those findings to the lungs, where similar mechanisms appear to work locally to help trigger constriction in the airway, he says.

Renin is no stranger to medical research -- for decades, doctors have known that the enzyme is produced by the kidney in relatively large quantities for systemic use throughout the body. But the Weill Cornell team was the first to discover that mast cells also produced their own local supply of the enzyme, at a variety of body sites.

In the heart and now the lungs, this localized production of renin appears to have a profound effect on nearby tissues, says co-senior author Dr. Randi Silver, associate professor of physiology and biophysics at Weill Cornell.

More study is needed, of course, but our finding suggests that drugs that target renin might prove effective agents in dampening asthma or other respiratory diseases, she says. These types of 'renin inhibitors' are, in fact, currently being developed by the pharmaceutical industry right now.

The genesis of the new study came through the efforts of the study's lead author, Arul Veerappan, now a postdoctoral researcher in Dr. Silver's laboratory. He looked closely at rings of bronchial tissue from rodents, discovering that mast cells in these rings released renin along with other substances.

You ended up getting the same biochemical cascade that we had seen elsewhere -- newly produced renin bringing about a local rise in angiotensin in tissues, Veerappan says.

Research led by co-author Alicia Reid, also a postdoctoral associate in Dr. Silver's lab, led to another first. Using a technology Reid developed, the researchers confirmed for the first time that mast cells from human lung tissue release a form of renin that is nearly identical to renin found in human mast cells grown in culture or human kidney renin.

That's a big achievement, because it supports the notion that the mechanism we have discovered is not just a laboratory phenomenon -- it's actually occurring in the living human lung, Dr. Levi notes.

New research suggests that local renin production may also be crucial in diseases marked by tissue fibrosis (stiffening). In fact, Dr. Silver's lab is now looking at the role locally produced renin might play in a rare, deadly illness called idiopathic pulmonary fibrosis (IPF), where lung tissue becomes increasingly inflexible over time.

We're interested in any disease in which we can also detect local renin/angiotensin production because it appears to be linked to fibrosis, vasoconstriction, and now bronchoconstriction, Dr. Silver explains.

The goal of all this research: new treatment targets for a range of illnesses.

Of course, we already have antihypertensive medicines -- such as ACE inhibitors and angiotensin receptor blockers -- that focus on curbing angiotensin in a more systemic way, says Dr. Levi. But if we could find agents that dampen this renin-angiotensin cascade locally -- in the heart or the lung, for example -- that could prove to be a formidable new weapon against disease.

The pitter patter of little feet... climbing straight up a wall

Tue, 29 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Building upon several years of research into the gecko's uncanny ability to climb sheer walls, researchers at the University of California, Berkeley, have developed an adhesive that is the first to master the easy attach and easy release of the reptile's padded feet. The material could prove useful for a range of products, from climbing equipment to medical devices.

Unlike duct tape or glue, the new material is crafted from millions of tiny, hard, plastic fibers that establish grip; a mere square two centimeters on a side can support 400 grams (close to a pound). While tape sticks when it presses onto a surface, the new adhesive sticks as it slides on a surface and releases as it lifts -- this is the trick behind a gecko's speedy vertical escapes.

The new study appeared online Jan. 23, 2008, in the Journal of the Royal Society Interface.

There are other synthetic adhesives inspired by gecko feet and they adhere much like conventional tape. In contrast, the new adhesive brushes along a surface to develop traction. While ideal for hanging posters, the characteristic is even more important for any application that requires movement, such as climbing.

The gecko has a very sophisticated hierarchical structure of compliant toes, microfibers, nanofibers and nanoattachment plates that allows the foot to attach and release with very little effort, said co-author and Berkeley professor Ron Fearing, The gecko makes it look simple, but the animal needs to control the directions it is moving its toes--correct movement equates to little effort, he said.

The new material is also novel in that it gets stronger with use. In experiments, it tightened its hold as it was rubbed repeatedly against a glass plate. The extra strength is caused by the fibers bending over to make more contact, yet once released, the fibers returned to their original shape. The research team is exploring ways to permanently bend the fibers so that the grip strength is its strongest from the outset, no massaging required.

According to Fearing, the new material is the first to mimic the nature of the gecko's characteristic non-sticky by default feet. The Berkeley researchers, all engineers, have worked closely with biologists Robert Full, also at Berkeley, and Kellar Autumn of Lewis and Clark College in Portland, Ore., to uncover the key natural properties behind that unique foot, the secret to high mobility on sheer surfaces.

Fearing and his colleagues are part of an NSF-supported Nanoscale Interdisciplinary Research Team (NIRT) that was specifically tasked in 2003 with developing biologically-inspired synthetic gecko adhesives.

The results of this project are an impressive example of how teaming engineers with biologists results in a better understanding of the role of 'engineering' in nature, says Lynn Preston, the NSF officer who supported these NIRT researchers, and many other teams of engineers and biologists, through her leadership of NSF's Engineering Research Centers program. This is a perfect example of how to turn that understanding into products that are as sophisticated as those developed by 'Mother Nature'.

Researchers put the bite on mosquitoes

Wed, 16 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Few things sting like a mosquito's bite--especially if that bite carries a disease such as malaria, yellow fever, Dengue fever or West Nile virus. But if researchers from The University of Arizona in Tucson have their way, one day mosquito bites may prove deadly to the mosquitoes as well.

Our goal is to turn the female mosquito's blood meal into the last meal she ever eats, said project leader Roger L. Miesfeld, a professor of biochemistry and molecular biophysics in UA's College of Science and a member of BIO5 and the Arizona Cancer Center.

Other UA researchers involved with the project include Patricia Y. Scaraffia, Guanhong Tan, Jun Isoe, BIO5 member Vicki H. Wysocki, and the late Michael A. Wells.

These researchers have discovered that one particular mosquito species, Aedes aegypti, has a surprisingly complex metabolic pathway, one that requires its members to excrete toxic nitrogen after gorging on human blood. If the mosquitoes fail to do so, they'll also fail to lay eggs--and will likely sicken and die.

Scaraffia, a research assistant professor in UA's department of biochemistry and molecular biophysics, and the other members of the team published their findings in the January 15 issue of the Proceedings of the National Academy of Sciences. The research was funded by the National Institutes of Health.

Miesfeld and his colleagues are seeking a molecule that is harmless to humans, but will gum up the works of mosquito metabolism, forcing the mosquitoes to hang onto the nitrogen. Such a molecule would kill both the mosquitoes and their would-be progeny--thus slowing the spread of disease.

Once found, this molecule--and similar molecules aimed at other mosquito species--could be developed into an insecticide and sprayed in places where mosquitoes congregate, such as around water and on mosquito netting.

The researchers also envision developing an oral insecticide--a mosquito-slaying pill that members of a community with a high instance of, say, yellow fever or malaria might take to reduce the mosquito population. The pill wouldn't be a vaccine; if people who took it were later bitten by a disease-carrying mosquito, they would still become infected. However, the mosquito would ingest the insecticide along with the blood, causing her to bear fewer young and possibly die before she could bite anyone else.

The whole community would essentially become one big mosquito trap, Miesfeld said. Over time, mosquito populations and disease rates would both decline. It would be a group effort that in the long run could have a huge impact.

In a world where both mosquitoes and the diseases they carry are becoming increasingly resistant to known insecticides and medicines, finding new ways to fight them is crucial.

This would be one more weapon in our arsenal against diseases that kill millions of people a year, Miesfeld said.

UVa biomedical engineering study shows magnetic field can reduce swelling

Thu, 03 Jan 2008 04:59:37 PST

( from http://www.rxpgnews.com ) A recent study by University of Virginia researchers demonstrates that the use of an acute, localized static magnetic field of moderate strength can result in significant reduction of swelling when applied immediately after an inflammatory injury.

Thomas Skalak, professor and chair of biomedical engineering, and Cassandra Morris, a former Ph.D. student in biomedical engineering at U.Va., reported their findings in the November 2007 edition of the American Journal of Physiology.

In the study, the hind paws of anesthetized rats were treated with inflammatory agents in order to simulate tissue injury. Magnetic therapy was then applied to the paws. The research results indicate that magnets can significantly reduce swelling if applied immediately after tissue trauma.

Since muscle bruising and joint sprains are the most common injuries worldwide, this discovery has potentially significant implications. If an injury doesn't swell, it will heal faster - and the person will experience less pain and better mobility, says Skalak. This means that magnets might be used much the way ice packs and compression are now used for everyday sprains, bumps, and bruises, but with more beneficial results. The ready availability and low cost of this treatment could produce huge gains in worker productivity and quality of life.

Magnets have been touted for their healing properties since ancient Greece. Magnetic therapy is still widely used today as an alternative method for treating a number of conditions, from arthritis to depression, but there hasn't been scientific proof that magnets can heal.

Lack of regulation and widespread public acceptance have turned magnetic therapy into a $5 billion world market. Hopeful consumers buy bracelets, knee braces, shoe inserts, mattresses and other products that are embedded with magnets based on anecdotal evidence, hoping for a non-invasive and drug-free cure to what ails them.

The Federal Drug Administration regulates specific claims of medical efficacy, but in general static magnetic fields are viewed as safe, notes Skalak, who has been carefully studying magnets for a number of years in order to develop real scientific evidence about the effectiveness of magnetic therapy.

Skalak's lab leads the field in the area of microcirculation research - the study of blood flow through the body's tiniest blood vessels. With a five-year, $875,000 grant from the National Institutes of Health's National Center for Complementary and Alternative Medicine, Skalak and Morris set out to investigate the effect of magnetic therapy on microcirculation. Initially, they sought to examine a major claim made by companies that sell magnets: that magnets increase blood flow.

In their initial study, magnets of 70 milliTesla (mT) field strength - about 10 times the strength of the common refrigerator variety - were placed near the rats' blood vessels. Quantitative measurements of blood vessel diameter were taken both before and after exposure to the static magnetic fields - the force created by the magnets. Morris and Skalak found that the force had a significant effect: the vessels that had been dilated constricted, and the constricted vessels dilated, implying that the magnetic field could induce vessel relaxation in tissues with constrained blood supply, ultimately increasing blood flow.

Dilation of blood vessels is often a major cause of swelling at sites of trauma to soft tissues such as muscles or ligaments. The prior results on vessel constriction led Morris and Skalak to look closer at whether magnets, by limiting blood flow in such cases, would also reduce swelling.

Given the results of this latest study, Skalak envisions the magnets being particularly useful to high school, college and professional sports teams, as well as school nurses and retirement communities. He has plans to continue testing the effectiveness of magnets through clinical trials and testing in elite athletes. A key to the success of magnetic therapy for tissue swelling is careful engineering of the proper field strength at the tissue location, a challenge in which most currently available commercial magnet systems fall short. The new research should allow Skalak's biomedical engineering group to design field strengths that provide real benefit for specific injuries and parts of the body.

We now hope to implement a series of steps, including private investment partners and eventually a major corporate partner, to realize these very widespread applications that will make a positive difference for human health, says Skalak.

'Runner's high' may also strengthen hearts

Thu, 08 Nov 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Endorphins and other morphine-like substances known as opioids, which are released during exercise, don't just make you feel good -- they may also protect you from heart attacks, according to University of Iowa researchers.

It has long been known that the so-called runner's high is caused by natural opioids that are released during exercise. However, a UI study, which is published in the online edition of the American Journal of Physiology's Heart and Circulatory Physiology, suggests that these opioids may also be responsible for some of exercise's cardiovascular benefits.

Working with rats, UI researchers showed that blocking the receptors that bind morphine, endorphins and other opioids eliminates the cardiovascular benefits of exercise. Moreover, the UI team showed that exercise was associated with increased expression of several genes involved in opioid pathways that appear to be critical in protecting the heart.

This is the first evidence linking the natural opioids produced during exercise to the cardio-protective effects of exercise, said Eric Dickson, M.D., UI associate professor and head of emergency medicine in the Roy J. and Lucille A. Carver College of Medicine and the study's lead investigator. We have known for a long time that exercise is great for the heart. This study helps us better understand why.

Studies have shown that regular vigorous exercise reduces the risk of having a heart attack and improves survival rates following heart attack, even in people with cardiovascular disease. In addition, exercise also decreases the risk of atherosclerosis, stroke, osteoporosis and even depression. However, despite these proven health benefits, much less is understood about how exercise produces these benefits.

The UI study investigated the idea that the opioids produced by exercise might have a direct role in cardio-protection. The researchers compared rats that exercised with rats that did not. As expected, exercised rats sustained significantly less heart damage from a heart attack than non-exercised rats. The researchers then showed that blocking opioid receptors completely eliminated these cardio-protective effects in exercising rats, suggesting that opioids are responsible for some of the cardiac benefits of exercise.

The UI team also showed that exercise was associated with transient increases in expression of several opioid system genes in heart muscle, and changes in expression of other genes that are involved in inflammation and cell death. The researchers plan to investigate whether these altered gene expression patterns reveal specific cardio-protective pathways.

A better understanding of how exercise protects the heart may eventually allow scientists to harness these protective effects for patients with decreased mobility.

Hopefully this study will move us closer to developing therapies that mimic the benefits of exercise, Dickson said. It also serves as a reminder of how important it is to get out and exercise every day.

University of Iowa team discovers first moisture-sensing genes

Wed, 07 Nov 2007 04:59:37 PST

( from http://www.rxpgnews.com ) Researchers in the University of Iowa Roy J. and Lucille A. Carver College of Medicine have discovered the first two genes involved in moisture sensing (hygrosensation). The discovery also reveals a two-sensor hygrosensing system in fruit flies that may allow the flies to detect subtle changes in humidity -- an ability that is critical for the flies' survival. The results appear in the Nov. 8 issue of Nature.

Subtle variations in humidity influence reproductive behavior and geographic distribution in many animals, including insects, reptiles and birds. Because of their small size, insects, in particular, require a finely tuned ability to detect moisture levels in their environment in order to survive. However, the mechanisms and molecules involved in moisture sensing have remained a mystery.

Moisture sensing is a sensory modality, which up to this point no one has understood. This is the first study to identify genes that are involved, said Lei Liu, Ph.D., UI postdoctoral fellow in internal medicine and lead author of the study.

Liu and colleagues made their discovery by testing the idea that moisture sensing is a special form of mechanosensation -- the ability to detect physical forces like touch or movement. The researchers used various genetic techniques to study over 20 genes assumed to be involved in touch in fruit flies. Screening each gene mutation for its effect on the flies' ability to detect moisture, the researchers identified two genes that are required for normal moisture sensing. Furthermore, they found that one of the genes, nanchung, is involved in detecting dry air, while the other gene, water witch, is required for detecting moist air.

Both genes are members of the transient receptor potential (TRP) family of genes that code for ion channels. Nanchung, which means can't hear in Korean, has previously been shown to be involved in hearing. Water witch has no other known function and was named by Liu and colleagues for its role in sensing moist air. Disruption of either gene impaired the flies' hygrosensing ability.

The researchers also examined where the two genes are expressed in the fruit flies and determined that not only are two separate genes involved in hygrosensation, but also two types of neurons.

This work provides the first evidence for a sensory system coded by two types of sensory neurons, one responsible for detecting increased moisture and the other responsible for detecting decreased moisture, Liu said.

The researchers speculate that this two-sensor system may allow the flies to detect relative humidity with great sensitivity. Liu added that the two-sensor system might also be a model for other sensory processes where the ability to detect subtle environmental changes is important, such as temperature sensing.

The UI findings open the way to a better understanding of hygrosensation, they provide important clues for learning how mechanosensation works, and they may offer new insights into how sensory systems work in living creatures.

Hearing changes how we perceive gender

Wed, 24 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Think about the confused feelings that occur when you meet someone whose tone of voice doesn�t seem to quite fit with his or her gender.

A new study by neuroscientists from Northwestern University focuses on the brain�s processing of such sensory information about another�s gender to examine whether hearing fundamentally changes visual experience.

The study concludes that it does, weighing in with findings that contribute to provocative evidence about multi-sensory processing of our world that has been emerging in recent years.

�Auditory-Visual Cross-Modal Integration in Perception of Face Gender,� was published in a recent issue of Current Biology. The study�s co-authors are investigators at Northwestern�s Visual Perception, Cognition and Neuroscience Laboratory: lead author Eric Smith, graduate student, Marcia Grabowecky, research assistant professor of psychology, and Satoru Suzuki, associate professor of psychology.

�Researchers have long thought that one part of the brain does vision and another does auditory processing and that the two really don�t communicate with each other,� said Grabowecky.

�But emerging research suggests that rich information from different senses come together quickly and influence each other so that we don�t experience the world one sense at a time.�

The Northwestern study suggests that sensory interactions are happening at a very early level and tones of voices indeed fundamentally change visual processing.

�For our study, we used simple tones with no explicit gender information to get a window into how vision and audition work together to process gender information,� Grabowecky said. �Unlike stereotypical voices, the tones only hinted at male and female characteristics, and by coupling them with ambiguous faces, we were able to see how processing of various pitches affected vision very early in the sensory process.�

The study builds upon scarce scientific evidence supporting the idea that sounds can alter how masculine or feminine a person looks.

�Our vision can bias our experience of other senses, such as hearing,� said Smith. �We hear, for example, the ventriloquist�s voice coming from the dummy. In this study we wanted to see if hearing could change our visual experience.�

�We learn early on what auditory and visual characteristics accompany female and male voices, starting with our earliest experiences with our mothers and fathers,� said Grabowecky. �The question from the neuroscience perspective is when in the processing of perceptual information do auditory and visual senses interact with each other How does the brain do this�

To test whether a sound can influence perception of a face�s gender, the researchers digitally morphed male and female faces to create androgynous faces not easily categorized as male or female. Study participants were asked to look at the faces while listening to brief auditory tones, which fell within the fundamental speaking frequency range of either male or female voices.

In the initial stage of auditory processing, sounds are decomposed into basic frequency components, the lowest one called the fundamental frequency and higher ones called the harmonics. The fundamental frequency in the human voice typically falls between about 100 to 150 Hz for males and 160 to 300 Hz for females. Roughly speaking, the fundamental frequency determines the perceived pitch (lower for men and higher for women), and the harmonics add timbre (the quality of human voice).

In higher auditory brain areas, these frequencies are put back together to be coded as a human voice. The researchers took advantage of the fact that pure tones can be used to deliver individual frequency components that are registered in early auditory brain areas.

The findings showed that when an androgynous face was paired with a pure tone that fell within the female fundamental-frequency range, people were more likely to report that the ambiguous face was that of a female. But when the same face was paired with a pure tone in the male fundamental-frequency range, people were more likely to see a male face. (The bias did not occur when a face was paired with a pure tone that was too low or too high to be in the typical speaking range.)

�The strength of the study is that pure tones sound like beeps, and they primarily activate early stages of auditory processing,� Grabowecky said. �We think that the effect demonstrates a direct input from early auditory processing to visual perception.�

When people were forced to guess whether the tones were in the male range, the female range or outside of the typical speaking frequency range, their guesses were inaccurate and relative. In other words, when people heard a pair of pure tones, they tended to hear the higher tone to be feminine and the lower tone to be masculine regardless of the actual frequencies of the tones.

�Such relativity is not surprising, because our auditory experience depends on relative, rather than absolute, frequencies as most useful and entertaining auditory information, such as speech and music, is carried by how sound frequencies change over time,� Grabowecky said.

Absolute frequencies do not matter much, as we readily understand speech spoken by people with low and high voices and enjoy songs regardless of the keys in which they are played. In contrast, it is the �neglected� absolute-frequency information that influences visual perception of gender.

�A conscious impression of your voice is not what enhances your look of masculinity or femininity,� said Suzuki. �Sounds seem to influence visual gender in a much more fundamental way on the basis of their absolute frequencies processed in early auditory brain areas.�

The researchers focused on gender perception, because people have such a strong need to categorize people as male or female. �We all know the feeling of meeting a person who is very androgynous,� said Smith. �We simply need to know and will use any information at our disposal to identify a person�s gender. It is probably quite evolutionarily adaptive to be able to accurately tell males from females, as far as propagation of one�s genes is concerned.�

What is on the horizon?

�If sound can implicitly bias visual gender perception, then we need to consider whether other senses, such as smell, might yield similar effects,� said Smith. �Future studies might use masculine and feminine colognes, or even human pheromones to bias people to see androgynous faces as either male or female. With the possibility of other senses biasing the way that we see the world, our visual experience of gender might turn out to be much more than meets the eye.�

MSU researcher helps develop computer game for Ugandan children recovering from cerebral malaria

Tue, 23 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EAST LANSING, Mich. �The computer program Captain�s Log � originally used with individuals diagnosed with attention deficit hyperactivity disorder, brain injuries or learning disabilities � is being adapted to rehabilitate Ugandan children who are survivors of cerebral malaria.

Michael Boivin, a Michigan State University associate professor of neurology and ophthalmology and of psychiatry, and Bruno Giordani, a University of Michigan associate professor of psychiatry, are leading the project.

�So far as we know, this will be the first attempt to implement a cognitive rehabilitation training program in Uganda with children in the aftermath of brain injury,� Boivin said. �Such programs for children with special needs are readily available in America, and in other parts of the developed world, but not in Africa.�

Every 30 seconds a child in Africa dies from malaria - around 1 million every year, he said. Cerebral malaria is a severe form of malaria that affects the brain and is fatal in about 15 percent to 30 percent of the cases for hospitalized children.

�Our most recent follow-up evaluation of our cerebral malaria children indicates that 26 percent of them have persisting mild to moderate cognitive impairment, mostly in the area of attention and to some extent in visual-spatial working memory,� Boivin said.

The computer game is a comprehensive set of computerized cognitive training programs consisting of five modules including developmental, visual motor skills, conceptual skills, numeric concepts with memory skills and attention skills.

The research team is hoping that this intervention can help cerebral malaria-affected school-age Ugandan children improve their cognitive skills, leading to improvements for both activities of daily living and school-related learning and skill development.

�The program attempts to do so with the use of 33 multilevel brain-training exercises designed to help develop and remediate attention, concentration, memory, eye-hand coordination, basic numeric concepts, problem solving-reasoning skills, self-esteem and self-control,� Boivin said.

Originally developed in 1985, the program is used with children 6 years and older and adults and has been used in a variety of therapeutic, school and home settings in all 50 states, U.S. territories and 23

foreign countries. Also, the program has been adapted for use in a wide range of non-English speaking settings.

Boivin and Giordani have trained a Ugandan study team to help implement and evaluate the program.

�We trained our study team at Mulago Hospital in Uganda, and they helped us in testing the program,� Boivin said. �The onsite project research manager, Paul Bangirana, can now program and set up Captain's Log on his own.�

Endobronchial valve significantly improves emphysema

Mon, 22 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO, Oct. 22 � Emphysema patients whose lungs are implanted with a pencil eraser-sized, one-way endobronchial valve experience significantly improved measures of lung function and report better quality of life, University of Pittsburgh School of Medicine researcher Frank C. Sciurba, M.D., reported today at CHEST 2007, the annual meeting of the American College of Chest Physicians. Scientific sessions continue through Thursday, Oct. 25, at the McCormick Place Lakeside Center in Chicago.

�Normally, lungs easily expand and contract with breathing. But with emphysema, air sacs in the lungs lose elasticity and become hyper-inflated, resulting in decreased function and a feeling of breathlessness,� said Dr. Sciurba, principal investigator of the multi-center trial, known as the Endobronchial Valve for Emphysema Palliation Trial (VENT) and director of the Emphysema Research Center at the University of Pittsburgh. �Endobronchial valves can allow these over-distended, diseased portions of lung to deflate, improving overall function.�

The 31-center, two-year study ended in April 2006 and involved 321 patients in the United States. In the trial, emphysema patients were randomly assigned to either a treatment or control group. Lung function was re-evaluated at six months using a common clinical measure of the volume of air forcibly exhaled in one second (FEV-1) and a six-minute walk test, said Dr. Sciurba. Of the 220 patients who received valve implants, there was a 6.4 percent greater improvement in FEV-1, and a 5.7 percent improvement in distance walked, compared to controls, he said. For some important subsets of treated patients, the results were even more dramatic, Dr. Sciurba added.

�For example, patients who had a fissure completely separating the lobes of the lung and whose endobronchial valves were placed to exclude the entire diseased lobe had changes in FEV-1 of greater than 20 percent,� he said. �This is akin to the results achieved in unilateral lung-volume reduction surgery, without the risks of major surgery. Lessons learned in this trial can lead us to more effective targeting of regions in the lung that could provide an even greater response.�

Most patients required implantation of three to five valves to isolate the most damaged sections of their lungs. Computed tomography (CT) scanning confirmed significant reduction in size of the lung region where valves were placed, particularly among the subsets of patients with the most favorable responses.

Emphysema is the most common cause of respiratory-related death and the fourth most common cause of death overall in the United States. There are an estimated 1.8 million people in the U.S. who have emphysema, a disease heavily related to smoking.

Treated patients had a slightly higher risk of pneumonia. Most complications resolved within eight days of the procedure, and included shortness of breath, chest pain and low oxygen concentration in the bloodstream. Some patients who received valve treatment later had the valves removed for reasons including lack of efficacy or shifting of position. In nearly all cases, valves were easily removed up to a year following insertion.

Endobronchial valve data must be presented to the Food and Drug Administration and the Center for Medicare and Medicaid Services before the treatment becomes widely available to emphysema patients. Currently, the treatment is limited to those who took part in the clinical trial.

Spinal cord injury expert to be honored by research foundation

Thu, 18 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) NEW BRUNSWICK/PISCATAWAY, N.J. � Dr. Wise Young, the Richard H. Shindell Professor of Neuroscience at Rutgers University and founding director of Rutgers� W.M. Keck Center for Collaborative Neuroscience, is receiving the Melvyn H. Motolinsky Research Foundation�s 2007 Distinguished Service Award.

The award will be presented at the foundation�s annual meeting Oct. 28 at 2 p.m. in the Conference Center of the Clinical Academic Building at University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School in New Brunswick.

Dr. Clifton R. Lacy, president of the Motolinsky Foundation, associate professor of medicine at UMDNJ-Robert Wood Johnson Medical School and adjunct professor at Rutgers University Ernest Mario School of Pharmacy, said that Dr. Young was selected to receive the award because of his groundbreaking research in the treatment of spinal cord injury as well as his passionate support of stem cell research. �We also recognize the compassion and caring he shows for individuals with spinal cord injury and their families,� Lacy said.

Young is a world leader in the area of spinal cord injury and treatment. He is an outspoken advocate for stem cell research, a potential source of nerve cell regeneration therapies for damaged spinal cord tissue and other devastating conditions, such as Parkinson�s and Alzheimer�s diseases. Young is taking a leadership position at home and abroad in gathering support for stem cell research and has carried his strong advocacy to patients and politicians in the state and into the halls of Congress.

Young practices what he calls compassionate science, focusing on the needs of patients. He personally involves himself with people who have sustained these injuries and their families, holding regular open-house evenings at the Keck Center, where they are updated on the latest research findings and newest therapies.

At the Keck Center, Young assembled a team of researchers who collaborate with more than 100 laboratories worldwide in the search for cures to spinal cord injuries and brain injuries and disorders. He recently embarked on an initiative to set up a clinical network of more than a dozen spinal trauma centers in China capable of performing state-of-the-art clinical trials.

�I am truly honored to be amongst such eminent recipients of the Distinguished Service Award as Mason Gross, Denton Cooley and Clifton Lacy,� Young said. �To me, this award is not just an honor but recognition that scientists do science not just for its own sake but for the people who will benefit from that science.�

Immune cells promote blood vessel formation in mouse endometriosis

Thu, 18 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A discovery in mice of immune cells that promote the formation of new blood vessels could lead to new treatments for endometriosis, a painful condition associated with infertility that affects up to 15 percent of women of reproductive age.

The formation of new blood vessels, or angiogenesis, is known to encourage the growth of tumors and endometriosis lesions. A team led by Ofer Fainaru, MD, PhD, a research associate in the Vascular Biology Program at Children's Hospital Boston and Harvard Medical School, found that dendritic cells�highly specialized immune cells�help trigger angiogenesis in a mouse model of endometriosis. Their findings were published online last month in the FASEB journal. Judah Folkman, MD, director of Children�s Vacular Biology Program, who helped found the field of angiogenesis, was the paper�s senior author.

Endometriosis occurs when endometrium, a tissue normally found in the inner lining of the uterus, grows elsewhere in the body�most commonly in the abdominal cavity. The misplaced endometrial tissue begins as small lesions, or masses, but once blood vessels are recruited, the lesions grow larger and respond to female hormones, resulting in inflammation, cyclic pelvic pain, and infertility.

In the mouse model, the researchers observed that dendritic cells infiltrate endometriosis lesions, and near the sites where they invade, new blood vessels form. Injecting mice with excess dendritic cells caused their lesions to gain more blood vessels and to grow larger.

The researchers also found that dendritic cells have a strikingly similar effect on intra-abdominal tumors.

When the researchers grew dendritic cells together with endothelial cells�the cells that line blood vessel walls�the endothelial cells migrated towards the dendritic cells. The team hypothesizes that dendritic cells, after embedding in a new lesion or tumor, act like foremen on a building team: they call in, direct and support endothelial cells that build the new blood vessels.

We believe that targeting dendritic cells may prove to be a promising strategy for treating conditions dependent on angiogenesis, such as endometriosis and cancer, says Fainaru. But first, the team must demonstrate that dendritic cells are essential�that without these cells in mice, new blood vessels do not form.

Our next step would be to look for specific dendritic cell inhibitors that could have the potential to block angiogenesis in these conditions, says Fainaru.

The team hopes to develop cell-specific therapy for angiogenesis-dependent diseases that will be more effective and less toxic than current treatments. Currently, the most effective treatment for endometriosis is surgically removing the lesions, but this does not prevent them from growing back�as large and symptomatic as before. If dendritic cells are indeed ringmasters and not sideliners in new blood vessel growth, locally knocking them out just after an initial surgery, or altering them in some way, could render the lesions tiny and harmless.

Similarly, potential dendritic-cell inhibitors, when added to other agents that stop new blood vessels from forming, could enhance doctors� ability to choke off growing tumors, Fainaru adds.

Massive microRNA scan uncovers leads to treating muscle degeneration

Wed, 17 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers have discovered the first microRNAs � tiny bits of code that regulate gene activity � linked to each of 10 major degenerative muscular disorders, opening doors to new treatments and a better biological understanding of these debilitating, poorly understood, often untreatable diseases. The study, to be published online this week by the Proceedings of the National Academy of Sciences, was led by Iris Eisenberg, PhD, of the Program in Genomics at Children�s Hospital Boston. Louis Kunkel, PhD, director of the Program in Genomics and an investigator with the Howard Hughes Medical Institute, was senior investigator.

The disorders include the muscular dystrophies (Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophies, Miyoshi myopathy, and fascioscapulohumeral muscular dystrophy); the congenital myopathies (nemaline myopathy); and the inflammatory myopathies (polymyositis, dermatomyositis, and inclusion body myositis). While past studies have linked them with an increasing number of genes, it's still largely unknown how these genes cause muscle weakness and wasting, and, more importantly, how to translate the discoveries into treatments.

For instance, most muscular dystrophies begin with a known mutation in a �master gene,� leading to damaged or absent proteins in muscle cells. In Duchenne and Becker muscular dystrophies, the absent protein is dystrophin, as Kunkel himself discovered in 1987. Its absence causes muscle tissue to weaken and rupture, and the tissue becomes progressively nonfunctional through inflammatory attacks and other damaging events that aren�t fully understood.

�The initial mutations do not explain why patients are losing their muscle so fast,� says Eisenberg. �There are still many unknown genes involved in these processes, as well as in the inflammatory processes taking place in the damaged muscle tissue.�

She and Kunkel believe microRNAs may help provide the missing genetic links. Their team analyzed muscle tissue from patients with each of the ten muscular disorders, discovering that 185 microRNAs are either too abundant or too scarce in wasting muscle, compared with healthy muscle.

Discovered in humans only in the past decade, microRNAs are already known to regulate major processes in the body. Therefore, Eisenberg believes microRNAs may be involved in orchestrating the tissue death, inflammatory response and other major degenerative processes in the affected muscle tissue. The researchers used bioinformatics to uncover a list of genes the microRNAs may act on, and now plan to find which microRNAs and genes actually underlie these processes.

The findings raise the possibility of slowing muscle loss by targeting the microRNAs that control these �cascades� of damaging events. This approach is more efficient than targeting individual genes.

The team also defined the abnormal microRNA �signatures� that correspond to each of the ten wasting diseases. They hope these will shed light on the genes and disease mechanisms involved in the most poorly understood and least treatable of the degenerative disorders, such as inclusion body myositis.

�At this point, it�s very theoretical, but it�s possible,� says Eisenberg.

Testosterone turns male juncos into blustery hunks -- and bad dads

Mon, 15 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- The ability to ramp up testosterone production appears to drive male dark-eyed juncos to find and win mates, but it comes with an evolutionary cost. Big fluctuations in testosterone may also cause males to lose interest in parenting their own young, scientists have learned.

In the December issue of The American Naturalist (now online), Indiana University Bloomington, University of Virginia and University of Southern Mississippi researchers report the results of the first study to examine, in the wild, the way in which natural changes in testosterone levels determine how a male spends his time.

It's a new take on the subject. IUB biologist Ellen Ketterson and other researchers had thought it might be the total amount of testosterone in a male bird that determines his tendency toward aggression and monogamy. The latest findings suggest it's a bit more complicated. It's how much and how quickly his testosterone levels can rise and fall that determines whether he's the kind to stick around and feed his young. Males whose testosterone levels were more stable were more likely to invest more time and energy in parenting.

This study is one of the first to show for a songbird living in the field under natural conditions that individual variation in the hormone testosterone maps onto variation in aggression and parental behavior, said Ketterson, senior author of the study. Our data also suggest that there is more than one way to be successful at reproduction. Some males may seek mates at the expense of parental behavior, but other males are doing the opposite. They are being more parental at the expense of aggression. And apparently both ways of being in the world work.

Ketterson, lead author Joel McGlothlin (University of Virginia) and Jodie Jawor (University of Southern Mississippi) see the male Junco's plight as a classic trade-off in evolutionary biology: males have a certain amount of energy and time they can invest in attracting mates and sticking around to parent offspring. Under certain circumstances it may be beneficial for male birds to love 'em and leave 'em, maximizing the number of female partners during a mating season. Under other circumstances, it may be in the male junco's best interests to mate with only one female and stick around until the chick is old enough to fend for itself.

The results are exciting because they show us how animals that make different choices might differ from each other on a physiological level. On an evolutionary level, they suggest that there may often be more than one right choice, depending on the circumstances, Virginia's McGlothlin said.

Is testosterone calling all the shots It is surely more complicated than that, Ketterson said. The link between testosterone and aggressive and sexual behavior is probably more direct than the link between testosterone and parental behavior. The latter needs much more study.

Diversity in the behavior of male dark-eyed junco is more of a continuum than a dichotomy of Don Juans and Mr. Moms.

One of the interesting things is that all males stick around and help, Ketterson said. If they have higher testosterone they help less. If they have lower testosterone they help more.

The situation presents an interesting evolutionary question. Why wouldn't one of the behaviors win out over the other

Variation in behavior may persist because the environment varies, Ketterson said. In cold, wet years, or years when lots of predators are attacking young in the nest, good fathers may be more successful at leaving offspring. When food is plentiful and predators are few, males that focus on mating may be more successful. The balance between the two is probably dynamic.

Another possibility, McGlothlin explained, is that male quality is why males divide up their time differently.

There are only so many eggs out there to fertilize, so every male can't be successful getting extra-pair fertilizations, McGlothlin said. High-quality males -- those who have more energy to invest -- ought to spend more of it on trying to attract mates. These males may be less likely to survive, but they are more likely to be successful at getting extra-pair fertilizations. The low-quality males don't have as much energy to invest, so they play it safe.

Ketterson, McGlothlin and Jawor studied a natural population of Carolina dark-eyed juncos (Junco hyemalis carolinensis). The birds' behavior is well known -- thanks to the work of IU Bloomington biologist (emeritus) Val Nolan, who is married to Ketterson. Male birds were observed extensively in and around nests, and were at times captured and catalogued. During the male birds' brief captivity, the scientists measured circulating testosterone levels, then injected the birds with gonadotropin-releasing hormone (GnRH) to determine the degree to which each male could produce testosterone in response.

Males that were capable of producing more testosterone in response to the injections not only demonstrated more aggressive behavior, but were also observed to spend less time parenting.

The next essential step is to relate variation in testosterone to actual measures of fitness, namely lifespan and offspring actually produced, Ketterson said. Is it true that individuals who resolve the trade-off in different ways have equal fitness Can a good parent be just as successful in an evolutionary sense as a good mater

Marines land at UO, leave with plans to wear Oregon-made training suits

Wed, 10 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EUGENE, Ore. -- (Oct. 10, 2007) -- A few came. They ran. They left. As a result of their August visit the U.S. Marine Corp begins training in 2008 in new running suits chosen after tests of competing products in the University of Oregon's environmental chamber.

The experience was enough to make both the University of Oregon and Beaverton-based InSport Inc. proud. UO researchers were unaware that it was InSport's training clothes that they had recommended until the company announced Oct. 2 that it had won a $14 million contract to produce the suits for the Marine Corps, said John Halliwill, a professor of human physiology and co-director of the UO's Exercise and Environmental Physiology Laboratories.

The Marine Corps cold-called us and asked us to run tests for them and to report back to them, Halliwill said. We weren't supposed to know who the suits came from, and, to be honest if someone had mentioned InSport to me last summer I wouldn't have known who they were talking about. But I do now.

Halliwill and lab co-director Christopher Minson led the testing, in which 29 Marines (22 men and seven women) jogged on a treadmill for 30 minutes at 6 mph and at a 2 percent incline on four separate occasions. The climate in the lab was manipulated to mimic two common training periods: either cool and humid early mornings (45 degrees Fahrenheit and 70-80 percent relative humidity) or warm and humid late mornings (55 degrees and 40-65 percent relative humidity).

The UO's state-of-the-art environmental chamber is a 12-foot-square room capable of simulating altitude up to 18,000 feet, holding temperature constant at a set point between 14 degrees and 122 degrees Fahrenheit, and controlling humidity anywhere from 10 percent to 95 percent. The chamber was installed in 2005, built with a $250,000 grant from the U.S. Department of Defense and a $150,000 gift from Dave and Nancy Petrone of San Mateo, Calif. It can be switched from one extreme environment to another in 30 minutes, and the system allows researchers to monitor minute vascular and respiratory changes of subjects both at rest and when exercising.

The Marines had a specific need to see how the suits performed during typical winter conditions at U.S. Marine bases such as Quantico and Camp Pendelton, but testing had to be completed during the summer so that the suits could be deployed in time for winter, Halliwill said. We have the ability to create weather on demand, practically any climate or weather condition we want with the flip of a switch, so we were able to give them Base Quantico in winter even though it was August in Oregon.”

Each Marine was weighed immediately before and after each running session. Hearts were monitored throughout the sessions, and each subject was asked every five minutes about skin moisture, comfort and difficulty they perceived while in one of the jogging suits. Subjects each day took a two-hour break and then repeated the procedure a second time.

Researchers recorded heart rates, pre-exercise weight of the suits, changes in body weight in each run, moisture retained in suits and underwear and the moisture transferred into the environment.

Dealing with cooler temperatures is not difficult in terms of clothing, Minson said. What is difficult is moisture management. Even on relatively dry days, moisture from sweating can build up under a suit that does not ventilate well. This leads to less heat loss and less comfort. Most importantly, the excess moisture in clothes can lead to very rapid heat loss when exercise is stopped, which can be uncomfortable at best, but can be dangerous in certain circumstances. Moisture management is one of the areas where the material by InSport really stood out.

In the end, the Marines reported more comfort and a preference for Design 2, which turned out to be InSport's product, over Design 1, and, the researchers concluded in their report: In our view, and we believe supported by the data, Design 2 is superior to Design 1 and should be considered for adoption by the Marine Corps.

The recommended product, according to participating Marines, generated less friction. Researchers noted that neither design was tested for wind- or water-proofness, which usually are important to people during their exercise regimens. There were few significant differences between the suits in the tested environments, but Design 2 weighed less before exercise, retained less moisture and allowed for better moisture transfer to the environment than the other product.

Appendix isn't useless at all: It's a safe house for bacteria

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) DURHAM, N.C. � Long denigrated as vestigial or useless, the appendix now appears to have a reason to be � as a �safe house� for the beneficial bacteria living in the human gut.

Drawing upon a series of observations and experiments, Duke University Medical Center investigators postulate that the beneficial bacteria in the appendix that aid digestion can ride out a bout of diarrhea that completely evacuates the intestines and emerge afterwards to repopulate the gut. Their theory appears online in the Journal of Theoretical Biology.

�While there is no smoking gun, the abundance of circumstantial evidence makes a strong case for the role of the appendix as a place where the good bacteria can live safe and undisturbed until they are needed,� said William Parker, Ph.D., assistant professor of experimental surgery, who conducted the analysis in collaboration with R. Randal Bollinger, M.D., Ph.D., Duke professor emeritus in general surgery.

The appendix is a slender two- to four-inch pouch located near the juncture of the large and small intestines. While its exact function in humans has been debated by physicians, it is known that there is immune system tissue in the appendix.

The gut is populated with different microbes that help the digestive system break down the foods we eat. In return, the gut provides nourishment and safety to the bacteria. Parker now believes that the immune system cells found in the appendix are there to protect, rather than harm, the good bacteria.

For the past ten years, Parker has been studying the interplay of these bacteria in the bowels, and in the process has documented the existence in the bowel of what is known as a biofilm. This thin and delicate layer is an amalgamation of microbes, mucous and immune system molecules living together atop of the lining the intestines.

�Our studies have indicated that the immune system protects and nourishes the colonies of microbes living in the biofilm,� Parkers explained. �By protecting these good microbes, the harmful microbes have no place to locate. We have also shown that biofilms are most pronounced in the appendix and their prevalence decreases moving away from it.�

This new function of the appendix might be envisioned if conditions in the absence of modern health care and sanitation are considered, Parker said.

�Diseases causing severe diarrhea are endemic in countries without modern health and sanitation practices, which often results in the entire contents of the bowels, including the biofilms, being flushed from the body,� Parker said. He added that the appendix�s location and position is such that it is expected to be relatively difficult for anything to enter it as the contents of the bowels are emptied.

�Once the bowel contents have left the body, the good bacteria hidden away in the appendix can emerge and repopulate the lining of the intestine before more harmful bacteria can take up residence,� Parker continued. �In industrialized societies with modern medical care and sanitation practices, the maintenance of a reserve of beneficial bacteria may not be necessary. This is consistent with the observation that removing the appendix in modern societies has no discernable negative effects.�

Several decades ago, scientists suggested that people in industrialized societies might have such a high rate of appendicitis because of the so-called �hygiene hypothesis,� Parker said. This hypothesis posits that people in hygienic societies have higher rates of allergy and perhaps autoimmune disease because they -- and hence their immune systems -- have not been as challenged during everyday life by the host of parasites or other disease-causing organisms commonly found in the environment. So when these immune systems are challenged, they can over-react.

�This over-reactive immune system may lead to the inflammation associated with appendicitis and could lead to the obstruction of the intestines that causes acute appendicitis,� Parker said. �Thus, our modern health care and sanitation practices may account not only for the lack of a need for an appendix in our society, but also for much of the problems caused by the appendix in our society.�

Parker conducted a deductive study because direct examination the appendix�s function would be difficult. Other than humans, the only mammals known to have appendices are rabbits, opossums and wombats, and their appendices are markedly different than the human appendix.

Parker�s overall research into the existence and function of biofilms is supported by the National Institutes of Health. Other Duke members of the team were Andrew Barbas, Errol Bush, and Shu Lin.

New thoracic imaging approach can pinpoint underlying venous problems

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CINCINNATI� University of Cincinnati (UC) radiologists have developed a new technique for capturing images of chest veins that eases diagnosis of venous diseases.

Multi-detector computed tomography (CT) scanners are traditionally used to create three-dimensional images of arteries, the vessels which carry oxygen-rich blood away from the heart and distribute blood throughout the body. Veins, smaller vessels that return blood to the heart, are more difficult to accurately image.

Developed by Cristopher Meyer, MD and Achala Vagal, MD, the new protocol allows radiologists to compensate for the extra time it takes contrast solution to reach the veins so useful images can be produced using the CT scanner.

�We found that the rapid-imaging scanners were almost too fast for venous studies,� explains Vagal, a UC assistant professor and radiologist at University Hospital. �By the time the contrast reached the patient�s veins, there were too many artifacts to make any meaningful conclusions about possible disease�for example, blood clots.�

�Venous disease is rare and can be difficult to pinpoint,� she adds. �This new protocol uses the same imaging equipment in a novel way that allows us to acquire better venous images and make good clinical decisions.�

Vagal presented guidelines for this thoracic imaging protocol at the North American Society of Cardiovascular Imaging�s 35th Annual Meeting and Scientific Sessions in Washington, D.C., on Oct. 8.

For this new imaging technique, the CT technologist prepares two syringes of contrast: The first includes 140 cubic centimeters (CC) of undiluted contrast; the second contains a diluted mixture of 100 CC of contrast and 10 CC of saline solution.

�The key to getting accurate clinical images of the veins is in the timing,� Vagal says.

Both syringes are given consecutively at a rate of four CC per second, with a 60-second delay between the final injection and initiation of the CT scan.

�Previously, there was so much dense contrast in the veins that all you could see on the CT scan were streaks that didn�t tell you anything about possible venous disease,� explains Vagal. �Delaying the scan gave us enough time for both the arteries and the veins to be opacified, which resulted in the crisp images that allowed us to make better clinical determinations.�

Vagal is affiliated with the Neuroscience Institute at UC and University Hospital, a center of excellence that focuses on the main diseases of the brain and nerves such as stroke, brain tumors, brain trauma, Parkinson�s and Alzheimer�s disease, epilepsy, ALS and multiple sclerosis.

Evil genes made me do it

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) While there have been numerous medical studies investigating the physiological and biochemical basis for behavioral disorders such as antisocial personality disorder and borderline personality disorder, there have been virtually no comprehensive studies aimed at providing a physiological explanation of malignant narcissism�a term that characterizes individuals who exhibit malevolent behavior but are still able to function effectively in society.

Inspired both by the dearth of scientific literature on the subject and by her sister�s Machiavellian personality, Barbara Oakley, Associate Professor of Bioengineering at Oakland University in Michigan, set out to conduct an investigation of the physiology of this particular disorder and the impact it has had on human society. The result is Evil Genes: Why Rome Fell, Hitler Rose, Enron Failed, and My Sister Stole My Mother�s Boyfriend (Prometheus Books $28.95), which Harvard professor Steven Pinker praises as �a fascinating scientific and personal exploration of the roots of evil, filled with human insight and telling detail.�

Evil Genes is the first book to tie together the cutting edge neuroscientific and genetic results that explain human evil, showing that some deceitful, manipulative, and even sadistic behavior appears to be programmed genetically. Unlike other popular books about human evil, Evil Genes goes far beyond �explaining� psychopathic behavior using old-fashioned psychological theories or religious dogma. Instead, it centers on what neuroscience and genetics are revealing about not only psychopathy, but also the more subtly devious behavior of seemingly ordinary people. Oakley follows clues from the diary of her late sister�who actually did steal her mother�s boyfriend�and takes the reader inside the heads of malevolent people you know, perhaps all too well, but could never understand�until now.

Starting with psychology as a frame of reference, Oakley uses cutting-edge images of the working brain to provide startling support for the idea that �evil� people act the way they do mainly as the result of certain dysfunctions, some of which have a genetic basis. But there are unexpected fringe benefits to Evil Genes. We may not like them�but we literally can�t live without them. The recent dramatic findings presented in Evil Genes illuminate not only the eerily similar behavior of dictators far afield, such as Hitler, Mao, and Milosevic, but aspects of politics at home, as well as business, religion, and everyday life. As Terrance Deacon, Professor of Biological Anthropology and Neuroscience at UC Berkeley, says, �shining this light on some of the most problematic figures of our era�challenges our assumptions about the roots of terrorism, genocide, crime, corruption�and even the sinister sides of politics, business, and religion.�

In fact, history has been shaped by the strange confluence of genes and environment that science is just now beginning to understand. Oakley links the latest findings of molecular research to a wide array of seemingly unrelated historical and current phenomena, from the harems of the Ottomans and the chummy jokes of �Uncle Joe� Stalin, to the remarkable memory of investor Warren Buffett.

William A. Wulf, President Emeritus, National Academy of Engineering, says, �Oakley deftly moves through psychology, functional brain imagery, and molecular biology to weave a compelling and provocative case for a genetic base for evil. 'Scientific non-fiction' and 'page turner' aren�t two phrases I�d expect in the same sentence, but for the remarkable Evil Genes, they fit.�

Evil Genes is a tour-de-force of popular science writing that brilliantly melds scientific research with intriguing family history and puts both a human and scientific face to evil.

Barbara Oakley, PhD, �a female Indiana Jones,� is one of the few women to hold a doctorate in systems engineering. She chronicled her adventures on Soviet fishing boats in the Bering Sea in Hair of the Dog: Tales From Aboard a Russian Trawler. She also served as a radio operator in Antarctica and rose from private to captain in the U.S. Army. Now an associate professor of engineering at Oakland University in Michigan, Oakley is a recent vice president of the IEEE Engineering in Medicine and Biology Society. Her work has appeared in numerous publications.

Study links chemical to inhibited milk synthesis, secretion in humans

Mon, 08 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CINCINNATI�University of Cincinnati (UC) researchers have identified the neurotransmitter serotonin as the chemical responsible for inhibiting milk production and secretion in human mammary glands.

As growing demand outstrips milk supplies in some parts of the world, the finding could aid development of therapeutics or technologies that would increase milk production and yields from other mammals.

Results of the human study, led by Nelson Horseman, PhD, UC professor of molecular and cellular physiology, appear in the Oct. 8�12, 2007, early edition of Proceedings of the National Academy of Sciences (PNAS).

�Knowing the chemical responsible for inhibiting milk production could help us to improve milk yields in other mammals,� Horseman says.

In lactating mammals, milk synthesis and secretion gradually slows to a stop when mammary glands become full. Once mammary glands are emptied, milk production begins again.

For decades, scientists have been trying to pinpoint the cause of inhibited milk production. In the 1970s, researchers in Scotland and New Zealand determined that a chemical had to regulate milk synthesis and secretion. A UC-led rodent study in 2004 identified the chemical as serotonin.

Serotonin is a naturally occurring neurotransmitter made in the brain and intestinal tract. When produced in the intestinal tract, the chemical is stored in blood platelets and released at wound sites to promote clotting and healing. Low levels of serotonin in the brain have been linked to depression and other mood disorders.

Horseman and his team now report that serotonin is also produced in human mammary glands�building up as the mammary gland fills with milk, inhibiting further milk synthesis and secretion.

�If we can understand how to stop or reduce serotonin production in the mammary gland, we can reverse its actions,� Horseman says.

The investigator was recently issued a patent for specific drugs known to inhibit serotonin production. Inhibiting this chemical in the mammary gland, he says, has been shown to increase milk yields by up to 15 percent.

Improved milk yields, says Horseman, could help ease milk shortages in some parts of the world caused by drought and increased demand.

�Demand for milk has increased in Asia and prices for milk have gone up across the world,� says Horseman.

A United States Department of Agriculture (USDA) 2001�2005 summary of 30 American cities showed that, over a five-year period, the average price of whole milk rose by 11 percent.

�Farmers currently use a growth hormone to improve milk yields,� says Horseman. �Use of that hormone has declined in recent years at the request of consumers, but milk shortages are getting worse. Finding ways to increase yield in a way that�s acceptable to consumers is important.�

In March 2007, the USDA awarded Horseman and colleagues a $350,000 grant to further study milk synthesis and secretion in cows.

The UC team is partnering with researchers in the University of Arizona�s animal science program to study cows and cow mammary tissue.

Although the rodent and human cells they have studied have many similarities, cow cells appear to have some unique differences. For example, Horseman�s team has identified one receptor for serotonin in the mammary gland of humans and rodents, and at least three in cows.

�We hope that by gaining a better understanding of how serotonin works in cows, we can find ways to inhibit its synthesis without the use of drugs or growth hormones,� says Horseman. �Our ultimate goal would be to increase milk yield in a way that�s effective without side effects.�

Treatment blocks pain without disrupting other functions

Wed, 03 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A combination of two drugs can selectively block pain-sensing neurons in rats without impairing movement or other sensations such as touch, according to a new study by National Institutes of Health (NIH)-supported investigators. The finding suggests an improved way to treat pain from childbirth and surgical procedures. It may also lead to new treatments to help the millions of Americans who suffer from chronic pain.

The study used a combination of capsaicin � the substance that makes chili peppers hot � and a drug called QX-314. This combination exploits a characteristic unique to pain-sensing neurons, also called nociceptors, in order to block their activity without impairing signals from other cells. In contrast, most pain relievers used for surgical procedures block activity in all types of neurons. This can cause numbness, paralysis and other nervous system disturbances.

The Holy Grail in pain science is to eliminate pathologic pain without impairing thinking, alertness, coordination, or other vital functions of the nervous system. This finding shows that a specific combination of two molecules can block only pain-related neurons. It holds the promise of major future breakthroughs for the millions of persons who suffer with disabling pain, says Story C. Landis, Ph.D., director of the National Institute of Neurological Disorders and Stroke (NINDS) at the NIH, which funds the investigators' research along with the National Institute of Dental and Craniofacial Research (NIDCR) and the National Institute of General Medical Sciences (NIGMS). NINDS and NIDCR are co-chairs of the NIH Pain Consortium. The study appears in the October 4, 2007, issue of Nature.*

Lidocaine, the most commonly used local anesthetic, relieves pain by blocking electric currents in all nerve cells. Although it is a lidocaine derivative, QX-314 alone cannot get through cell membranes to block their electrical activity.

That's where capsaicin comes in. It opens large pores called TRPV1 channels � found only within the cell membrane of pain-sensing neurons. With these channels propped open by capsaicin, QX-314 can pass through and selectively block the cells� activity.

The research team, led by Clifford J. Woolf, M.D., Ph.D., of Massachusetts General Hospital and Harvard Medical School and Bruce Bean, Ph.D., at Harvard Medical School, tested the combination of capsaicin and QX-314 in neurons isolated in Petri dishes and found that it blocked pain-sensing neurons without affecting other nerve cells. They then injected the drugs into the paws of rats and found that the treated animals could tolerate much more heat than usual. They also injected the two drugs near the sciatic nerve that runs down the hind leg. The treated rats did not show any signs of pain, and five of the six animals continued to move and behave normally. This showed that the drugs could block pain without impairing motor neurons that control movement.

The drug combination took half an hour to fully block pain in the rats. However, once it began, the pain relief lasted for several hours.

Current nerve blocks cause paralysis and total numbness, Dr. Woolf says. This new strategy could profoundly change pain treatment in the perioperative setting.

The treatment tested in this study is unique in that it uses a type of ion channel (TRPV1 channels) as an avenue to deliver medication. Ion channels are pores in the cell membrane that control the flow of electrically charged ions in and out of cells. I'm not aware of any other strategy that uses a channel within cells to deliver a drug to a select set of cells, Dr. Woolf says. The strategy builds on research done since the 1970's, largely supported by NIH, that shows how electrical signaling in the nervous system results from expression of dozens of different types of ion channels. Some of these ion channels are found only in specific types of neurons.

This project is a nice illustration of how research trying to understand very basic biological principles can have practical applications, says Dr. Bean.This type of treatment has great potential to improve pain treatment during childbirth, dental procedures, and surgery, the researchers say. Surgical pain is the obvious first application for this type of treatment, Dr. Woolf says. However, similar therapies might eventually be useful for treating chronic pain, he adds. Chronic pain continues for weeks, months, or even years and can cause severe problems, and is often resistant to standard medical treatments.

While the researchers focused on finding a treatment for pain, this strategy might also be useful for treating itch from eczema, poison ivy rashes, and other conditions, Dr. Woolf says. Like pain sensations, itch signals come from nociceptors. One problem with the combination treatment is that the capsaicin can cause unpleasant burning sensations until the QX-314 takes effect, Dr. Woolf says. Administering the QX-314 ten minutes before the capsaicin minimized this problem in rats. The investigators are now looking for ways to open the TRPV1 channels without the burning sensations, perhaps by finding an alternative to capsaicin. They also hope to find ways of prolonging the pain relief. Eventually, they might be able to develop pills that will stop pain signals without requiring injections, Dr. Woolf adds.

UAB wins $5.7M neurofibromatosis grant

Tue, 02 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BIRMINGHAM, Ala. � A team of UAB geneticists, doctors and biostatisticians has received $5.7 million from the U.S. Department of Defense to study and test new treatments for neurofibromatosis, or NF.

UAB is the lead research center in a nine-institution group called the NF Consortium. The coalition formed more than two years ago to design and manage multiple clinical trials held across the nation looking at new and more effective therapeutic options for adults and children diagnosed with NF.

The $5.7 million award will be shared among the NF Consortium members, with UAB�s research team serving as the operations center and distribution point for the government funds.

Bruce Korf, M.D., Ph.D., chair of the UAB Department of Genetics and an internationally recognized expert in neurofibromatosis type 1, said the goal of the consortium is to streamline and improve the way clinical trials are performed for this disease, and to break down past barriers to discovering and testing cutting-edge NF treatments.

�We expect results from the NF Consortium studies to provide a wider range of therapeutic options for patients with the goal of reducing the rates of tumor growth, and improving quality of life,� Korf said.

�By monitoring not only the clinical outcomes, but the effects of therapies on molecular targets, it will be possible to better understand NF as a disease,� he said.

The other eight participating institutions are Children�s Hospital Boston, Children�s Hospital of Philadelphia, Children�s National Medical Center in Washington, D.C., Cincinnati Children�s Hospital Medical Center, Washington University in St. Louis, the University of Chicago, the University of Utah in Salt Lake City, and the National Cancer Institute in Bethesda, Md.

Often diagnosed in childhood, NF is a hereditary condition that causes tumors to grow on nerve tissue that affects many bodily systems. As the tumors grow, they can press on vital areas and lead to deformities, high blood pressure, scoliosis, speech impairment, early or delayed puberty, blindness and other medical problems. About 10 percent of NF type 1 cases lead to cancer.

The recent $5.7 million grant is in addition to $2.9 million awarded two years ago to start the NF Consortium. The recent award will be used to put the group�s scientific plans into action, said Jeannette Y. Lee, Ph.D., a biostatistician and professor in the UAB School of Medicine. Lee directs the NF Consortium operations center and serves as the grant�s overall principal investigator.

Lee said three clinical trials will be the focus of the consortium�s first studies. These include:

Scientists say sabercat bit like a pussycat

Mon, 01 Oct 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In public imagination, the sabre-toothed cat Smilodon ranks alongside Tyrannosaurus rex as the ultimate killing machine. Powerfully built, with upper canines like knives, Smilodon was a fearsome predator of Ice-Age America's lost giants.

For more than 150 years, scientists have debated how this iconic predator used its ferocious fangs to kill its prey. Now a new Australian study, published today in the US Proceedings of the National Academy of Science, hopes to lay the arguments to rest. And the results will put in dent in Smilodon's reputation.

Scientists from the University of New South Wales and University of Newcastle have used a computer-based technique called Finite Element Analysis (FEA) to test the bite force and feeding mechanics of the fearsome predator.

FEA, normally used in the analysis of trains, planes and cars, allowed the team to reverse engineer designs to find out what sort of forces a structure like a sabrecat skull was able to handle.

Skulls are much more complex then most man-made structures, and to apply the technique to a fossil big cat required some tricks engineers usually have to handle, says the University of Newcastle's Colin McHenry, lead author on the paper.

Historically there have been a number of interpretations about how Smilodon killed, says UNSW palaeontologist Dr Steve Wroe. Early researchers thought it had a weak bite. More recently, people have suggested that the bite was strong.

Using the skull of a modern-day lion for comparison, the team determined that Smilodon had a relatively weak bite - about one third as powerful as a lion of similar size. For all its reputation, Smilodon had a wimpy bite says Dr Wroe. It bit like a moggy.

In a range of digital crash-tests, the team found that under most conditions, the sabre-tooth skull performed very poorly compared to that of the lion. This would have seriously limited the big toothed fossil cat cat to a very specific range of killing behaviours.

Although its bite was weak, this is not to imply Smilodon was not was a formidable predator. Anything but, says Dr Wroe. Smilodon was an awesome beast -- and what it lacked in bite force it more than made up for elsewhere.

The sabrecat had an immensely powerful body; perfect for wrestling large prey to the ground, and our models show that it needed to do this before trying a bite, explains Mr McHenry. Killing was more likely applied to the prey's throat, because it is easier to restrain the prey this way. Once the bite was done the prey would have died almost instantly.

Dr Wroe describes the lion as a better all rounder in the hunting stakes. Smilodon was massively over-engineered for the purposes of taking small prey, but a ruthlessly efficient hunter of big game.

The team is now applying their techniques to inform medical research involving dentists, surgeons and safety scientists.

Discovery supports theory of Alzheimer's disease as form of diabetes

Wed, 26 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Insulin, it turns out, may be as important for the mind as it is for the body. Research in the last few years has raised the possibility that Alzheimer�s memory loss could be due to a novel third form of diabetes.

Now scientists at Northwestern University have discovered why brain insulin signaling -- crucial for memory formation -- would stop working in Alzheimer�s disease. They have shown that a toxic protein found in the brains of individuals with Alzheimer�s removes insulin receptors from nerve cells, rendering those neurons insulin resistant. (The protein, known to attack memory-forming synapses, is called an ADDL for �amyloid �-derived diffusible ligand.�)

With other research showing that levels of brain insulin and its related receptors are lower in individuals with Alzheimer�s disease, the Northwestern study sheds light on the emerging idea of Alzheimer�s being a �type 3� diabetes.

The new findings, published online by the FASEB Journal, could help researchers determine which aspects of existing drugs now used to treat diabetic patients may protect neurons from ADDLs and improve insulin signaling in individuals with Alzheimer�s. (The FASEB Journal is a publication of the Federation of American Societies for Experimental Biology.)

In the brain, insulin and insulin receptors are vital to learning and memory. When insulin binds to a receptor at a synapse, it turns on a mechanism necessary for nerve cells to survive and memories to form. That Alzheimer�s disease may in part be caused by insulin resistance in the brain has scientists asking how that process gets initiated.

�We found the binding of ADDLs to synapses somehow prevents insulin receptors from accumulating at the synapses where they are needed,� said William L. Klein, professor of neurobiology and physiology in the Weinberg College of Arts and Sciences, who led the research team. �Instead, they are piling up where they are made, in the cell body, near the nucleus. Insulin cannot reach receptors there. This finding is the first molecular evidence as to why nerve cells should become insulin resistant in Alzheimer�s disease.�

ADDLS are small, soluble aggregated proteins. The clinical data strongly support a theory in which ADDLs accumulate at the beginning of Alzheimer�s disease and block memory function by a process predicted to be reversible.

In earlier research, Klein and colleagues found that ADDLs bind very specifically at synapses, initiating deterioration of synapse function and causing changes in synapse composition and shape. Now Klein and his team have shown that the molecules that make memories at synapses -- insulin receptors -- are being removed by ADDLs from the surface membrane of nerve cells.

�We think this is a major factor in the memory deficiencies caused by ADDLs in Alzheimer�s brains,� said Klein, a member of Northwestern�s Cognitive Neurology and Alzheimer's Disease Center. �We�re dealing with a fundamental new connection between two fields, diabetes and Alzheimer�s disease, and the implication is for therapeutics. We want to find ways to make those insulin receptors themselves resistant to the impact of ADDLs. And that might not be so difficult.�

Using mature cultures of hippocampal neurons, Klein and his team studied synapses that have been implicated in learning and memory mechanisms. The extremely differentiated neurons can be investigated at the molecular level. The researchers studied the synapses and their insulin receptors before and after ADDLs were introduced.

They discovered the toxic protein causes a rapid and significant loss of insulin receptors from the surface of neurons specifically on dendrites to which ADDLs are bound. ADDL binding clearly damages the trafficking of the insulin receptors, preventing them from getting to the synapses. The researchers measured the neuronal response to insulin and found that it was greatly inhibited by ADDLs.

�In addition to finding that neurons with ADDL binding showed a virtual absence of insulin receptors on their dendrites, we also found that dendrites with an abundance of insulin receptors showed no ADDL binding,� said co-author Fernanda G. De Felice, a visiting scientist from Federal University of Rio de Janeiro who is working in Klein�s lab. �These factors suggest that insulin resistance in the brains of those with Alzheimer�s is a response to ADDLs.�

�With proper research and development the drug arsenal for type 2 diabetes, in which individuals become insulin resistant, may be translated to Alzheimer�s treatment,� said Klein. �I think such drugs could supercede currently available Alzheimer�s drugs.�

Pathway to cell death redefined in landmark study

Thu, 20 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 20 -- A new study led by investigators from the University of Pittsburgh School of Medicine demonstrates that the process of necrosis, long thought to be a chaotic, irreversible pathway to cell death, may actually be triggered as part of a regulated response to stress by a powerful protein, SRP-6, that can potentially halt necrosis in its path. Further, the research team realized that this protein might be harnessed to direct some cells -- those in cancerous tumors, for instance -- to die, while saving others, such as degenerating neural cells responsible for Alzheimer�s and Parkinson�s diseases. The work appears on the Sept. 21 cover of the journal Cell.

This remarkable molecular trigger, SRP-6, is a serine protease inhibitor or serpin, and targets the cell�s digestive center, the lysosome. The authors report that the family of intracellular serpins may help cells survive in the face of stressors by protecting against lysosomal injury and its cellular consequences.

�For years, we believed that cell death related to a catastrophic insult such as a stroke or heart attack that deprives tissue of oxygen couldn�t really be treated, so we focused on strategies to prevent further damage by restoring blood flow as quickly as possible with clot busters and surgery,� said Gary A. Silverman, M.D., Ph.D., chief of newborn medicine in the department of pediatrics at the Pitt School of Medicine and the study�s senior author. �But our research indicates that necrosis can be interrupted and possibly repaired, even after the injury process is well underway. This insight has exciting implications for the management of heart disease, stroke and neurological illnesses.�

Representing more than five years of study, the Cell publication is the result of a chance observation made by primary author Cliff J. Luke, Ph.D., assistant professor of pediatrics at Pitt and an investigator at the university-affiliated Magee-Womens Research Institute. Drs. Luke, Silverman and colleagues have been studying how a certain class of proteins called proteases, when uncontrolled, can kill cells. In the process, they discovered that another group of proteins, the serpins, might block, or inhibit, these destructive proteases and protect cells from injury. SRP-6 is among a vast family of pro-survival serpins, which are key regulatory molecules in many complex biologic processes, including blood cell coagulation, inflammation, tumor growth and cell death. Although previous research has shown that bloodstream serpins, including antithrombin and alpha-1 antitrypsin, control protein degradation, little is known about the role of serpins that function within cells, especially in a living organism.

Enter serendipity. When collecting specimens of a microscopic worm called Caenorhabditis elegans in water, rather than in a saline solution as is more common, Dr. Luke noticed that an extraordinarily large number of the animals were dying. �My worm yield was way down,� he said. When he examined the dying worms, he determined that they were genetic �knock-outs� that had been modified to be deficient in SRP-6. The normal worms were just fine.

A frequently studied animal model because of its 1,000-cell structure, transparency and easily visible development, C. elegans is a primitive organism whose complete genetic code has been sequenced and is well known to scientists. The worm typically lives in soil, flourishes in water and exists to eat bacteria and reproduce. The investigators were using a �reverse genetic� approach in which they hoped, by studying the relatively limited intracellular serpin repertoire of C. elegans, they could gain insights that might be applicable to serpin function in higher organisms, including humans.

�Serpin proteins are critical,� said Dr. Silverman, a neonatologist and a senior investigator at the Magee-Womens Research Institute. �For example, we know that in patients who have a certain type of skin cancer, those whose tumors express a lot of intracellular serpins don�t do as well. Now we know that SRP-6 is a crucial pro-survival mechanism that can protect cells from injury, initiate repair after injury, or, if absent, lead to a cascade of cell death.�

With further investigation, it may be possible to use this knowledge to deprive cancer cells of their serpin protectors and target them for death. Alternatively, physicians might be able to boost serpin activity to stop cells from dying � for example, intestinal cells affected by the bacterial infection necrotizing enterocolitis (NEC), a major cause of death and illness in fragile, premature infants.

�We still treat NEC the same way we did 30 years ago, with supportive care, antibiotics and surgery to remove dead portions of intestine,� said Dr. Silverman. �We can�t stop the mucosal lining from dying. But with these worms as models, we can do drug screens to search for compounds that can block necrosis.�

Drs. Silverman, Luke and colleagues have dramatically illustrated the devastating consequences of cellular stress in C. elegans when the crucial protector SRP-6 is missing. A cascade of cell necrosis begins in SRP-6-deficient animals exposed to a number of different stressors, including water, heat and lack of oxygen. In the case of water exposure, the SRP-6 knock-outs move a bit but soon become immobile. Finally, the worms� organs are violently expelled through their bodily openings, resulting in what the authors refer to as a �grim fate.�

�Animals with normal genetic sequences are fine in water, but the knock-out animals usually die rapidly,� said Dr. Luke, explaining that this observation led him to realize the importance of SRP-6 in protecting the lysosome, an internal cell structure enclosed in its own protective membrane that acts as the cell�s garbage disposal. Powerful enzymes within the lysosome digest old, worn out proteins, carbohydrates, lipids, DNA, RNA, other damaged cell structures and even invading bacteria and viruses. But if the lysosome becomes damaged and leaky, these enzymes can turn against the cell and possibly overcome the serpin defense � useful if the cell is part of a cancerous tumor.

The investigators determined that SRP-6 staves off necrosis by protecting the lysosome membrane from damage caused by the calpain family of cysteine proteases and by neutralizing other cysteine proteases released from injured cellular structures called organelles as they are being digested by the lysosome. As part of their study, Drs. Silverman, Luke and colleagues labeled enzymes within the lysosomes of SRP-6-deficient animals with a fluorescent biomarker to observe how these enzymes reacted after an injury to the critical structure.

�The lysosomes popped, released their contents into the cell and these digestive enzymes began to activate, making the whole animal fluoresce,� said Dr. Silverman. �Again, this experiment showed the importance of SRP-6 in management of the necrosis pathway.�

�There are a lot of diseases associated with cell necrosis, such as stroke, neurodegenerative diseases and NEC, and now we know that the pathway to necrosis is much more systematic than we once thought it was,� said Dr. Luke. �With further study, we may be able to identify targets of intervention to halt the necrotic progression in some of these diseases and possibly even prevent them.�

Velociraptor had feathers

Thu, 20 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A new look at some old bones have shown that velociraptor, the dinosaur made famous in the movie Jurassic Park, had feathers. A paper describing the discovery, made by paleontologists at the American Museum of Natural History and the Field Museum of Natural History, appears in the Sept. 21 issue of the journal Science.

Scientists have known for years that many dinosaurs had feathers. Now the presence of feathers has been documented in velociraptor, one of the most iconic of dinosaurs and a close relative of birds.

The fossil specimen that the group examined was a velociraptor forearm unearthed in Mongolia in 1998. They found on it clear indications of quill knobs�places where the quills of secondary feathers, the flight or wing feathers of modern birds, were anchored to the bone with ligaments. Quill knobs are also found in many living bird species and are most evident in birds that are strong flyers. Those that primarily soar or that have lost the ability to fly entirely, however, were shown in the study to typically lack signs of quill knobs.

�A lack of quill knobs does not necessarily mean that a dinosaur did not have feathers,� said Alan Turner, lead author on the study and a graduate student of paleontology at the American Museum of Natural History and at Columbia University in New York. �Finding quill knobs on velociraptor, though, means that it definitely had feathers. This is something we'd long suspected, but no one had been able to prove.�

Previous signs of feathers on dinosaurs had been restricted to fossils found in a particular kind of lake sediment that favored preservation of small-bodied animals.

The velociraptor in the current study stood about three feet tall, was about five feet long, and weighed about 30 pounds. Combined with its relatively short forelimbs compared to a modern bird, this indicated it lacked volant, or flight, abilities. The authors suggest that perhaps an ancestor of velociraptor lost the ability to fly, but retained its feathers. In velociraptor, the feathers may have been useful for display, to shield nests, for temperature control, or to help it maneuver while running.

�The more that we learn about these animals the more we find that there is basically no difference between birds and their closely related dinosaur ancestors like velociraptor,� said Mark Norell, a Curator in the Division of Paleontology at the American Museum of Natural History and co-author on the study. �Both have wishbones, brooded their nests, possess hollow bones, and were covered in feathers. If animals like velociraptor were alive today our first impression would be that they were just very unusual looking birds�.

Species still have more viable offspring if they can choose their best mate

Tue, 18 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Athens, Ga. -- When it comes to picking a mate, Crosby, Stills, Nash and Young had an answer: �If you can�t be with the one you love, love the one you�re with.� As it turns out, that may be a cardinal rule in the animal kingdom, too.

New research that crosses several species boundaries shows that when animals must choose less-than-preferred (to them) mates, females and males apparently have ways to compensate that increase the chance their offspring will survive. The study, just published in the Proceedings of the National Academy of Sciences, adds weight to the Compensation Hypothesis, a proposal that has given insight into how individuals can pass on their genes even under less than ideal circumstances.

�It�s always better for offspring if parents can mate with preferred partners, but it�s becoming clear that when parents can�t have that preferred partner, they have ways of making up for it,� said Patricia Adair Gowaty, a Distinguished Research Professor of Ecology and Genetics at the University of Georgia and lead author of the study. �When female �choosers� were in enforced pairs with males they did not prefer, they laid more eggs. Similarly, when males are paired with females they do not prefer, they ejaculate more sperm. This compensation seems to be a way of making the best of a bad job.�

Co-authors of the paper were Wyatt Anderson, Alumni Foundation Distinguished Professor of Genetics, and Yong-Kyu Kim, an assistant research scientist in Anderson�s lab, both at UGA; Cynthia K. Bluhm of the Delta Waterfowl and Wetlands Research Station in Canada; Lee C. Drickamer of Northern Arizona University; and Allen J. Moore of Centre for Ecology and Conservation at the University of Exeter in the United Kingdom.

One of the new study�s strongest arguments for the Compensation Hypothesis is that it includes experimental results in Tanzanian cockroaches, fruit flies, pipefish, wild mallards and feral house mice. When each species faced experimental constraints on free expression of their mate preferences, individuals found ways around the predicament that could improve the chances that offspring could survive and perhaps even flourish.

�Just how an individual finds its best mate isn�t really known,� said Gowaty, �though there�s some evidence that he or she may be somehow sensing the advantage of the potential mate�s immune system in relation to the chooser�s own.� She points out that many factors are probably at work, including behavioral cues and what potential resources a mate may bring.

While the strategies for dealing with nonpreferred mates can help offspring, advantages for the mating pairs themselves are less clear. In experimental situations, for example, females mated to non-preferred males didn�t live as long as females mated to their preferred choice.

One interesting aspect of the study is its implication that all individuals in a species have a flexible response to such problems as constraints on expression of their mating preferences. If that�s true, it hints that compensation may evolve�which could add an unexpected wrinkle to the story of natural selection.

�How compensation evolves is crucial,� Anderson said.

The issues at stake are, in fact, even broader.

�The study also has implications for conservation because it suggests that the best way to keep species alive may be, if possible, to let individuals choose their own mates,� said Gowaty.

The Compensation Hypothesis is Gowaty�s work and was first published only four years ago, though she has been working on it for more than a decade.

Just how�and if�the hypothesis works in humans remains unknown, since studying the subject remains practically (and ethically) improbable. Still, the idea remains a deep part of popular culture.

When Mick Jagger sings �You can�t always get what you want,� most of us nod. And then we start to plot a way around the problem.

New research seeks to enhance quality and security of wireless telemedicine

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A team of researchers led by Fei Hu, assistant professor of computer engineering at Rochester Institute of Technology, is working to advance the integration of radio frequency identification technology, also known as RFID, into cardiac sensor networks, a new wireless technology for telemedicine delivery. The team will also work to enhance the security of the systems used in the process, thereby reducing the possibility of identity theft and cyber-terrorism. The effort is being supported by a $400,000 grant from the National Science Foundation�s Cyber Trust Program. Hu, the principal investigator, will collaborate with Yang Xiao, professor of computer science at the University of Alabama.

�Telemedicine technology can greatly increase the quality of medical care while also decreasing health care costs,� notes Hu. �Through this project we hope to increase the integration of RFID into existing cardiac sensor networks, ensure the overall security of the system and promote the implementation of the technology in nursing homes and adult care facilities across the country.�

�This research will advance an important technology development, while also enhancing RIT�s skills and capabilities in the area of computer engineering and design,� adds Andreas Savakis, chair of RIT�s Department of Computer Engineering.

The United States� growing nursing home and long-term care populations are putting a severe strain on the national health care system, in part due to the costs of medical care and doctor visits to these facilities. Cardiac sensor networks use wireless sensors to remotely monitor a patient�s heart beating pattern and blood pressure and transfer this information to doctors and hospitals off site. According to Hu, they are seen as a major avenue for increasing the quality of diagnosis and reducing the need for medical supervision.

Furthermore, the integration of RFID tags on medication bottles into this system will allow doctors to know immediately what medications a person is taking and reduce the chance of negative drug reactions or accidental over doses, adds Hu.

One of the major roadblocks in the further development of the system has been concern over the security of wireless networks used in telemedicine delivery. Hu and Xiao will research the use of anti-interference technology to reduce radio distortion of these networks and design and test new RFID security schemes that will decrease the chance of information being stolen. They will also look to assist the overall implementation and integration of RFID to further the development of this technology in telemedicine systems.

�There are well known security challenges associated with cardiac sensor networks and RFID,� Hu notes. �It is my hope this research will assist in better protecting these systems and allow greater numbers of doctors and patients to take advantage of the benefits of telemedicine.�

Women prescribed drugs linked to birth defects not often advised to use birth control

Mon, 17 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 17 � Although prescription medications that may increase the risk of birth defects are commonly used by women in their childbearing years, only about half receive contraceptive counseling from their health care providers, according to a large-scale study from the University of Pittsburgh School of Medicine reported in the Sept. 18 issue of the Annals of Internal Medicine.

�We found that over the course of a year, one in six women of reproductive age filled a prescription for a medication labeled by the Food and Drug Administration as increasing the risk of fetal abnormalities,� said Eleanor Bimla Schwarz, M.D., assistant professor in the departments of medicine and obstetrics, gynecology and reproductive medicine at the University of Pittsburgh School of Medicine and first study author. �Unfortunately, many women filling prescriptions that can increase risk of birth defects remain at risk of pregnancy.�

Half of pregnancies in the United States are unintended, according to national estimates. While regular use of contraception can prevent unplanned pregnancies, women filling prescriptions that can increase the risk of birth defects are no more likely to use contraception than other women, the study authors note.

For this investigation, Dr. Schwarz and colleagues studied patient data related to all prescriptions filled by 488,175 reproductive-aged women enrolled with a large managed health care plan during 2001. Prescriptions involved drugs considered safe for use in pregnancy and those labeled as posing a fetal risk.

The researchers examined use of contraception and results of pregnancy tests. When they compared medications labeled as increasing the risk of birth defects to safer medications, the researchers found little difference in rates of contraceptive counseling, use of contraception or subsequent pregnancy test results.

�Many women � and perhaps their physicians � may be unaware of the risks associated with the use of some medications, the chance that women may become pregnant, or both,� said Dr. Schwarz, who also is an assistant investigator at the Pitt-affiliated Magee-Womens Research Institute. �The scary thing is that we know women in other primary care health care settings are even less likely to get information about birth control.�

While about half of the women in this study had received contraceptive counseling, other studies have shown that nationwide, only about 20 percent of women are advised to use birth control when they receive potentially dangerous medications.

�While efforts are needed to ensure that women get information about birth control and the risk of medication-induced birth defects, it also is important to realize that different birth control methods are not equally effective,� she said. �Women who were using the most effective methods of contraception, such as the intrauterine device or IUD, were least likely to have a positive pregnancy test after filling a prescription for a potentially dangerous medication.�

The researchers found that internists and family practitioners prescribed the largest proportion (48 percent) of riskier medications to women of childbearing age. Psychiatrists prescribed 15 percent of these drugs; dermatologists, 12 percent; obstetrician/gynecologists, 6 percent; and pediatricians, 3 percent, according to the study.

�Women should not avoid using prescription medications, but clinicians need to remember that sometimes birth control is needed until a woman is ready to have a healthy pregnancy and a healthy baby,� Dr. Schwarz added.

Researchers discover correlation between GERD and obesity in females

Fri, 14 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A group of scientists recently discovered an association between being overweightand a disease called gastro-esophageal reflux disease (GERD) in women.

This discovery was published in the Sept. 14 issue of the World Journal of Gastroenterology by a research group led by Dr. Corazziari from the University La Sapienza of Rome. Dr. Corazziari has been a leader in the field of gastroenterology for a long time and published over 200 research articles and 20 professional books. He and his fellow researchers (with Dr. Piretta being the first author of this article) discovered that, in comparison to average population, overweight and obesity are risk factors for GERD in women and not so much in men.

GERD is a disease with chronic symptoms or mucosal damage produced by the abnormal reflux of gastric contents into the esophagus. Heartburn (burning discomfort behind the breastbone) is the major symptom of GERD because the gastric acid gets into esophagus.

It is known that fatty foods can produce a prolonged inhibitory effect on the lower esophageal sphincter (LES), thus increase the possibility of gastro-esophageal reflux (GER). Gastric distention following a copious meal also relaxes LER and increases the possibility of GER too.

Had these mechanisms play big roles in the patients studied by Dr Corazziari, then the overweight male patients (not just female) should also have a significant higher possibility of GERD than general population.

Since oestrogen can also inhibit the LES, Dr. Corazziari suggests that concentration of this hormone may be a possible explanation of increased GERD prevalence in obese females.

Nicotine may accelerate atherosclerosis, may be as dangerous as tar

Wed, 12 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) NEW YORK (Sept. 10, 2007) -- It's well known that smoking cigarettes increases risk for a host of serious health problems from cancer to heart disease. Now a new study from Weill Cornell Medical College in New York City looks at how they do their dirty work by contributing to atherosclerosis, or hardening of the arteries. The evidence points to nicotine, the addictive chemical in cigarettes.

By comparing reduced-nicotine cigarettes like Quest 3 and Eclipse with regular cigarettes, researchers discovered that the extent of cigarette-smoke induced atherosclerosis in mice correlated with the levels of nicotine -- the higher the nicotine, the more disease.

Right now, the general consensus is that the problem with cigarettes is tar and that nicotine is safe. That's why you can buy nicotine gum or patches to help you stop smoking. Our study presents new evidence that nicotine may not be safe at all, especially for your heart, says Dr. Daniel F. Catanzaro, principal investigator of the study, recently published in the journal Cardiovascular Toxicology. Dr. Catanzaro is associate research professor of physiology and biophysics in the Departments of Medicine and Cardiothoracic Surgery at Weill Cornell Medical College.

Previous studies have suggested that nicotine in cigarettes can hurt the heart by activating the sympathetic nervous system and increasing the heart rate -- potentially leading to fatal arrhythmias. (Nicotine also affects most organ systems -- including the gastrointestinal tract, the skin and the central nervous system.)

The new Weill Cornell study looked at two so-called potentially reduced exposure products (PREPs) -- Eclipse and Quest. Eclipse cigarettes work by heating inhaled air to activate its contents without burning the tobacco. Quest cigarettes are made with tobacco that is genetically-modified to have lower nicotine. Eclipse and Quest 3 have nicotine yields of 0.2 and 0.05 mg per cigarette, respectively. This compares to the two regular cigarettes studied -- 2R4F and Quest 1, with nicotine yields of 1 and 0.6 mg per cigarette, respectively. Eclipse and Quest cigarettes are marketed with the implication that they may be less harmful or addictive than conventional cigarettes. Quest cigarettes purportedly provide smokers the opportunity to taper their nicotine consumption by progressively moving to lower nicotine cigarettes. 2R4F is a research cigarette supplied by the University of Kentucky.

The study found that mice exposed to smoke from low-nicotine cigarettes had significantly smaller atherosclerotic lesions, compared to those exposed to regular cigarettes but still larger than lesions in control mice not exposed to cigarette smoke, which showed the least evidence of atherosclerosis. The accelerating effects of smoking on lesions was seen early, within weeks of smoke exposure.

While our study seems to suggest that low-nicotine cigarettes are safer, we also know that smokers adjust their smoking habits to maintain their level of nicotine. In other words, if you switch to a low-nicotine product, you will probably increase the number of cigarettes you smoke, or change the way you smoke to get more nicotine out of each cigarette. The best thing to do is quit, says Dr. Catanzaro.

Although Quest 1, Quest 3 and 2R4F cigarettes all have the same tar yield (10 mg/cigarette), mice exposed to smoke from the high-nicotine 2R4F and Quest 1 cigarettes developed larger lesions than did mice exposed to smoke from Quest 3, which has the lowest nicotine content of all the products tested. According to the Weill Cornell investigators, this finding points to the special role of nicotine in promoting arteriosclerosis.

Researchers also found that iPF2alphaV, a marker for oxidative stress that has been linked with atherosclerosis in humans, increased proportionately with the level of nicotine. This finding may indicate that nicotine promotes atherosclerosis, in part, by blocking production of nitric oxide, a chemical that mediates the protective functions of the lining of blood vessels.

These findings are preliminary. Going forward we will want to look at whether doping cigarettes with extra nicotine increases their atherogenic potential; whether blockers of nicotine reduce atherosclerosis; and if oral administration of nicotine has the same effects, says Dr. Catanzaro.

About 20 percent of Americans smoke. Cigarette smoke is linked to risk for cancer, chronic lung disease (emphysema and chronic bronchitis), cardiovascular disease (atherosclerosis, thrombosis and vascular dysfunction), stroke and cataracts as well as poor wound healing.

MIT: Leveraging learning for artificial respiration

Tue, 11 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CAMBRIDGE, MA- MIT researchers have found that the body's innate ability to adapt to recurring stimuli could be leveraged to design more effective and less costly artificial respirators. The new approach could minimize the need for the induced sedation or paralysis currently necessary for some patients on mechanical ventilation.

Nonassociative learning, or our innate ability to adapt to recurring stimuli, is the focus of work to be described in the September 12 issue of PLoS ONE, the online, open-access journal from the Public Library of Science.

Specifically, Chi-Sang Poon, a research scientist at the Harvard-MIT Division of Health Sciences and Technology (HST), and colleagues examined rats under mechanical ventilation to see how they applied different forms of nonassociative learning to adapt to the rhythm imposed by the respirator.

Existing respirators do not consider the adaptive nature of breathing in their design. Some ignore the patient's natural rhythm and pump air in and out of the lungs on set intervals. As a result, doctors often must sedate or paralyze patients to prevent them from fighting an unfamiliar rhythm. Other respirator designs rely entirely on the patient to trigger the airflow. These systems, however, are costly and tend to be unreliable for weak patients such as newborns or those in critical care.

The MIT research suggests, however, that if a doctor takes the patient's natural breathing rhythm into account and sets the ventilator's rhythm in that same range, the patient will adapt and synchronize with the ventilator. This new approach could minimize the need for induced sedation or paralysis.

�We have intrinsic nonassociative learning capabilities, called habituation and desensitization, that [can] make up for changes in the spontaneous rhythm due to artificial lung inflation,� says Poon.

In tests of rats under artificial respiration, Poon found that, if using a suitable rhythm, rats adapted to the mechanical ventilation. He also found that this learning capability enabled mice to adapt to an artificial rhythm even when the mechanical respirators applied constant air pressure. The rats effectively �tuned out� this extra pressure, filtering it out as background noise. When Poon disabled the neural pathways involved in nonassociative learning, the rats' ability to adapt was either eliminated or compromised.

Though nonassociative learning is familiar and commonly applied to smelling roses and adjusting to sunlight after emerging from a dark movie theater, it is not usually applied in a clinical environment. Because of their focus on stabilizing patients, clinicians often discount the power of learning. Many ventilators are designed as if the patient were never in the equation,� says Poon. �But it turns out, our vital functions can learn to adapt in order to survive.�

Low vitamin D during pregnancy linked to pre-eclampsia

Fri, 07 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) PITTSBURGH, Sept. 7 � Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia, according to a study from the University of Pittsburgh Schools of the Health Sciences reported this week in the Journal of Clinical Endocrinology and Metabolism.

A serious complication of pregnancy marked by soaring blood pressure and swelling of the hands and feet, preeclampsia is the leading cause of premature delivery and maternal and fetal illness and death worldwide, conservatively projected to contribute to 76,000 deaths each year. Preeclampsia, also known as toxemia, affects up to 7 percent of first pregnancies, and health care costs associated with preeclampsia are estimated at $7 billion a year in the United States alone, according to the Preeclampsia Foundation.

�Our results showed that maternal vitamin D deficiency early in pregnancy is a strong, independent risk factor for preeclampsia,� said Lisa M. Bodnar, Ph.D., M.P.H., R.D., assistant professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH) and lead author of the study. �Women who developed preeclampsia had vitamin D concentrations that were significantly lower early in pregnancy compared to women whose pregnancies were normal. And even though vitamin D deficiency was common in both groups, the deficiency was more prevalent among those who went on to develop preeclampsia.�

For this investigation, Dr. Bodnar and her colleagues evaluated data and banked blood samples taken from women and newborns between 1997 and 2001 at Magee-Womens Hospital of the University of Pittsburgh Medical Center (UPMC) and affiliated private obstetrician practices. Data were analyzed for 1,198 women enrolled in the Pregnancy Exposures and Preeclampsia Prevention Study, a prospective survey designed to examine factors that may predispose women to preeclampsia. Out of this group, 55 cases of preeclampsia and 220 controls were selected for further study.

Samples of maternal blood were taken prior to 22 weeks pregnancy and again just before delivery. Samples of newborn umbilical cord blood also were tested for 25 hydroxyvitamin D, an indicator of vitamin D status.

�Low vitamin D early in pregnancy was associated with a five-fold increase in the odds of preeclampsia,� said Dr. Bodnar, who also is an assistant investigator at the university-affiliated Magee-Womens Research Institute (MWRI). �Data showed this increase risk persisted even after adjusting for other known risk factors such as race, ethnicity and pre-pregnancy body weight. Also troubling was the fact that many of the women reported taking prenatal vitamins, which typically contain 200 to 400 International Units of vitamin D,� she said.

�Even a small decline in vitamin D concentration more than doubled the risk of preeclampsia,� noted James M. Roberts, M.D., senior author of the study and MWRI founding director. �And since newborn�s vitamin D stores are completely reliant on vitamin D from the mother, low vitamin levels also were observed in the umbilical cord blood of newborns from mothers with preeclampsia.�

A vitamin closely associated with bone health, vitamin D deficiency early in life is associated with rickets � a disorder thought to have been eradicated in the United States more than 50 years ago � as well as increased risk for type 1 diabetes, asthma and schizophrenia.

In the developing world, preeclampsia accounts for up to 80 percent of maternal deaths. And while treatment is more available in developed countries, preeclampsia remains the leading cause of maternal death. Infants born to mothers with preeclampsia have a risk of mortality five times greater than those born to women with normal pregnancies. In the United States alone, nearly 15 percent of preterm deliveries are a result of preeclampsia.

Specific brain protein required for nerve cell connections to form and function

Wed, 05 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHAPEL HILL � Neurons, or nerve cells, communicate with each other through contact points called synapses. When these connections are damaged, communication breaks down, causing the messages that would normally help our feet push our bike pedals or our mind locate our car keys to fall short.

Now scientists at the University of North Carolina at Chapel Hill School of Medicine have shown that a protein called neurexin is required for these nerve cell connections to form and function correctly.

The discovery, made in Drosophila fruit flies may lead to advances in understanding autism spectrum disorders, as recently, human neurexins have been identified as a genetic risk factor for autism.

This finding now gives us the opportunity to see what job neurexin performs within the cell, so that we can gain a better insight into what can go wrong in the nervous system when neurexin function is lost� said Dr. Manzoor Bhat, associate professor of cell and molecular physiology in the UNC School of Medicine and senior author of the study.

The study, published online September 6, 2007, in the journal Neuron, is the first to successfully demonstrate in a Drosophila model the consequences that mutating this important protein may have on synapses.

The research was supported in part by grants from the National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health and funds from the state of North Carolina.

During the last decade, scientists have learned that neurexins are integral to the transmission of chemical signals within the nervous system. Neurexins interact with binding partners called neuroligins to link neighboring nerve cells together so that signals can be sent and received correctly.

Previous attempts to study these proteins in animal models have been challenging. In vertebrates such as mice, three different genes code for the production of certain neurexin proteins. Deleting just one of these genes causes no adverse effects in mouse models, while removing all three is fatal. But fruit flies have only one gene for neurexin, and when Bhat and colleagues deleted the gene, the flies survived � barely.

Knocking out neurexin basically resulted in a fly with defective nervous system� said Bhat, also a member of the UNC Neuroscience Center and the UNC Neurodevelopmental Disorders Research Center.

First of all, the mutated fruit flies had trouble moving around. When the researchers examined the synapses in these flies, they found that half of them were gone. The synapses that remained were deformed, causing them to send out less chemical signals. The researchers, led by Jingjun Li, a graduate student in neurobiology in the UNC School of Medicine, concluded that neurexin is required for the growth of synapses, for the maintenance of their structure and for their function.

Currently, Bhat and other scientists are working to identify the proteins that neurexin binds to, how they interact, and what sequence of events ultimately results in the organization of synapses within nerve cells. The hope is that such studies in Drosophila will one day clarify the role neurexin plays in learning and memory, ultimately leading to a better understanding of how defects in this protein can lead to human disorders such as autism, Bhat said.

Mice stressed in simulated weightlessness show organ atrophy

Mon, 03 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) New Brunswick, N.J. � A ground-based, experimental model used to simulate astronaut weightlessness in space has provided Rutgers scientists an opportunity to study the effects of stress on immune organs.

Earlier collaborative research with Japanese scientists employing this model implicated the protein osteopontin (OPN) in bone mineral loss associated with simulated weightlessness in mice. This research was made possible by the creation at Rutgers of a mouse unable to make OPN (a �knock-out� mouse). Studies with this Rutgers mouse have demonstrated that OPN likely plays a role in a variety of human problems including cancer metastasis, multiple sclerosis and other autoimmune diseases, osteoporosis and certain inflammatory responses.

The new study, which also simulated weightlessness, demonstrated that OPN is required for the atrophy of immune organs brought on by the stress resulting from hindlimb unloading � a technique employed to simulate weightless conditions by lifting the animal�s body weight off its hind legs. Results are presented Sept. 3 online in the Proceedings of the National Academy of Sciences (PNAS) and in the Sept. 11 print issue.

�The bone loss seen in astronauts or bedridden patients is not a stress issue,� explained David Denhardt, a professor in the Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey. �They are experiencing a loss of weight bearing on the bones, and the loss of bone mineral is a direct result of this load reduction.�

The presence of OPN, a feature common to both the bone loss and the organ atrophy, is produced by two different causes � weightlessness and stress � coincidentally related to the same laboratory conditions.

OPN is the continuing focus of Denhardt�s research interests. His long-term goal is to develop an OPN antibody � a monoclonal or target-specific antibody � that will inhibit OPN function in lab mice, and ultimately, in humans. This antibody could prove useful in treating the many destructive diseases associated with OPN.

Denhardt�s graduate student Kathryn Wang, a co-author on the PNAS paper, had previously conducted experiments in which the mouse was positioned in such a way as to produce hind limb unloading. This simulated weightless condition produced OPN-dependent bone loss in the hind limbs and provided a potential testing ground for possible OPN antibodies. The specialized equipment for that experiment was supplied by another co-author on the paper, Yufang Shi, a professor in the Department of Molecular Genetics, Microbiology and Immunology at Robert Wood Johnson Medical School�University of Medicine and Dentistry of New Jersey.

Shi, an authority on stress, suggested that along with the bone loss studies, the Rutgers researchers should look at the spleen and thymus � the organs responsible for most of the animal�s immune cells. If stress affects the spleen and thymus so that they atrophy, the immune system becomes impaired. People under severe stress often get sick.

The Rutgers scientists took their colleague�s advice and compared the OPN-deficient knock-out mice to normal mice, with some dramatic results.

�To our astonishment and surprise, the OPN-deficient animals responded differently to the stress than the normal controls,� Denhardt said. �We had no basis to expect this, but the spleen and thymus of the OPN-deficient animals remained normal whereas there was atrophy of the spleen and thymus in the normal controls. This was a novel and totally unexpected result for which we have no explanation at this time. The next phase of our research will ask what exactly is going on.�

The stressed normal mice also displayed elevated levels of corticosterone � a hormone known to induce apoptosis (programmed cell death), a process evident in the spleen and thymus of these mice and a possible mechanism underlying the atrophy.

Denhardt said that their results indicate that OPN needs to be present for these stress related symptoms to occur, pointing to a whole new physiological realm in which the culprit osteopontin is causing problems.

High and mighty: first common height gene identified by researchers behind 'obesity gene' finding

Sun, 02 Sep 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Whilst we all know that tall parents are more likely to have tall children, scientists have been unable to identify any common genes that make people taller than others. Now, however, scientists have identified the first gene, known as HMGA2, a common variant of which directly influences height.

The difference in height between a person carrying two copies of the variant and a person carrying no copies is just under 1cm in height, so does not on its own explain the range of heights across the population. However, the researchers believe the findings may prove important.

Previous studies have suggested that, unlike conditions such as obesity, which is caused by a mix of genetic and environmental factors � so called nature and nurture � 90% of normal variation in human height is due to genetic factors rather than, for example, diet. However, other than very rare gene variants that affect height in only a small number of people, no common gene variants have until now been identified.

The research was led by Dr Tim Frayling from the Peninsula Medical School, Exeter, Professor Mark McCarthy from the University of Oxford and Dr Joel Hirschhorn from the Broad Institute of Harvard and MIT in Cambridge, US. Dr Frayling and Professor McCarthy were also part of a Wellcome Trust-funded study team that discovered the first common gene linked to obesity in April this year.

Using data from the Wellcome Trust Case Control Consortium, the largest study ever undertaken into the genetics underlying common diseases, and the Diabetes Genetics Initiative, in the US, the researchers conducted a genome-wide study of DNA samples from 5,000 people. The findings � that variations in the gene HMGA2 make some people taller than others � are published online today in the journal Nature Genetics.

Each of us carries two copies of each gene, one from our mother and one from our father. However, each copy can be a variant, or allele � in the case of the HMGA2 gene, a tall version and a short version. The researchers found that as many as 25% of white Europeans carried two tall versions of this particular gene, making them approximately 1cm taller than the 25% of people who carry two short versions.

Height is a typical 'polygenic trait' � in other words, many genes contribute towards making us taller or shorter, explains Dr Frayling. Clearly, our results do not explain why one person will be 6'5 and another only 4'10. This is just the first of many that will be found � possibly as many as several hundred.

The exact role that HMGA2 has in growth is unclear, but the researchers believe it is most likely in increased cell production. This may have implications for the development of cancer as tumours occur due to unregulated cell growth. Previous studies have shown an association between height and certain cancers: taller people are statistically more likely to be at risk from cancers, including those found in the prostate, bladder and lung.

There appears to be a definite correlation between height and some diseases, explains Dr Mike Weedon, lead author on the study. For example, there are associations between shortness and slightly increased risks of conditions such as heart disease. Similarly, tall people are more at risk from certain cancers and possibly osteoporosis.

Dr Frayling believes that the study has major implications for helping scientists understand how common variations in DNA in the human the genome actually affect us, especially in relation to growth and development.

Even though improved nutrition means that each generation is getting successively taller, variation in height within a population is almost entirely influenced by our genes, says Dr Frayling. This fact, coupled with the ease of measuring height, means that height can act as a model trait, allowing us to explore in detail the influence that the genome actually has on our general make-up, not just disease risk.

In addition to being a textbook example of a complex trait, height is a common reason children are referred to specialists. Although short stature by itself typically does not signify cause for concern, delayed growth can sometimes reflect a more serious underlying medical condition.

�By defining the genes that normally affect stature, we might someday be able to better reassure parents that their child�s height is within the range predicted by their genes, rather than a consequence of disease,� said Dr Hirschhorn from the Broad Institute of Harvard and MIT.

Flies prefer fizzy drinks

Wed, 29 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) While you may not catch a fly sipping Perrier, the insect has specialized taste cells for carbonated water that probably encourage it to binge on food with growing microorganisms. Yeast and bacteria both produce carbon dioxide (CO2) when they feast, and CO2 dissolves readily in water to produce seltzer or soda water.

This is one of the first, if not the only taste sensation discovered in animals beyond the five that humans taste - sweet, sour, bitter, salty and umami, or savory.

This was unexpected, because fruit flies also smell CO2 and they avoid it, said neurobiologist Kristin Scott, assistant professor of molecular and cell biology at UC Berkeley. One way that we like to think of it is that flies seek the right amount of rottenness - if fruit is only half rotten, producing a little CO2, it's good; if too rotten, it gives off a lot of CO2 and is bad tasting. They seek a balance.

Scott and her UC Berkeley colleagues, graduate students Walter Fischler, technician Priscilla Kong and postdoctoral fellow Sunanda Marella - all in the Department of Molecular and Cell Biology and the Helen Wills Neuroscience Institute - report their discovery in the Aug. 30 issue of Nature.

Mammals have five known types of taste receptors, though there may be more to discover, Scott said. Flies may have five distinct receptors also, but not the same ones mammals have. While Scott has shown that fruit flies can detect sweet and bitter compounds, and now carbonation, she has discounted their ability to taste umami and said that their ability to taste sour compounds is questionable. She and her lab continue to investigate other unknown taste modalities in fruit flies, which could be any of a number of tastes, such as salt or alcohol.

The discovery came when Fischler, frustrated that he could not find a chemical that stimulated an unknown type of fruit fly taste cell he had isolated, tested the cells' reaction to a drop of Samuel Adams beer. Surprised by a positive response, he tried to narrow down the taste preference to one of the many chemicals in beer. Flat beer and dry yeast, for example, did not work. That's when he discovered the leftover bottle of Calistoga mineral water.

As he was searching for beer components to test, he said, I opened the refrigerator and looked in, when a light bulb went on. Calistoga would be a great way of testing CO2.

The rest is history. Dry ice - frozen CO2 - produced a strong response, while high levels of gaseous CO2 produced a weak response in the taste cells. Sodium bicarbonate in a basic solution that does not contain CO2 bubbles did not work; bicarbonate in a solution with CO2 bubbles did. The liquid in which yeast grow, though not the yeast themselves, also elicited a response from the taste cell. These and a few other genetic tests narrowed the taste trigger down to dissolved carbon dioxide.

The preference for carbonation is weak compared with that for sweetness, Scott noted, implying that seltzer enhances taste or makes other tastes more acceptable. This makes sense because CO2 has no nutritional value, but is a byproduct of organisms - yeast and bacteria - that do provide nutrients, she said.

The newly discovered taste sensors for carbonation reside on their own structures, called taste pegs, on the tongue of the fly. While a fruit fly's four other taste cells are perched on the tip of bristles that cover the entire body, the carbonated water taste cells are clustered around the margins of the sponge-like tip of the proboscis, at the base of taste bristles.

Scott investigates taste cells, which are a type of nerve cell, and is characterizing the cells and genes associated with different tastes. So far, she and her laboratory colleagues have identified the sweet and bitter cells and some of the gustatory receptor genes that detect sweet and bitter compounds in fruit flies.

Fischler now is trying to isolate the actual receptor in the CO2-sensing nerve cell that grabs the CO2 molecule and sends a signal to the fly brain that there is carbonation in the food. It will then be possible to see if others, including humans, also have carbonation receptors on taste cells.

There may be many more taste modalities in humans than the five known today, said Scott. Even if CO2 is a taste unique to fruit flies, it's discovery suggests that other animals may have taste receptors tuned to important chemicals in their environment, she said, either to avoid them, as is the case with bitter chemicals, or seek them out, as is the case with sugars and CO2.

Thus, taste modalities may differ according to nutritional needs, she and her colleagues wrote. Alternatively, CO2 may be an unappreciated taste modality in many organisms.

Gene triggers obsessive compulsive disorder-like syndrome in mice

Wed, 22 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Using genetic engineering, researchers have created an obsessive-compulsive disorder (OCD) - like set of behaviors in mice and reversed them with antidepressants and genetic targeting of a key brain circuit. The study, by National Institutes of Health (NIH) -funded researchers, suggests new strategies for treating the disorder.

Researchers bred mice without a specific gene, and found defects in a brain circuit previously implicated in OCD. Much like people with a form of OCD, the mice engaged in compulsive grooming, which led to bald patches with open sores on their heads. They also exhibited anxiety-like behaviors. When the missing gene was reinserted into the circuit, both the behaviors and the defects were largely prevented.

The gene, SAPAP3, makes a protein that helps brain cells communicate via the glutamate chemical messenger system.

�Since this is the first study to directly link OCD-like behaviors to abnormalities in the glutamate system in a specific brain circuit, it may lead to new targets for drug development,� explained Guoping Feng, Ph.D., Duke University, whose study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute of Mental Health, and the National Institute of Environmental Health Sciences (NIEHS). �An imbalance in SAPAP3 gene-related circuitry could help explain OCD.�

Feng, Jeffrey Welch, Ph.D., Jing Lu, Ph.D., William Wetsel, Ph.D., Nicole Calakos, M.D., Ph.D., and colleagues report on their discovery in the August 23, 2007, issue of Nature.

�This serendipitous discovery illustrates how pursuit of basic science questions can provide important insights with promising clinical implications into poorly understood diseases,� said NINDS director Story C. Landis, Ph.D.

�Ultimately, the challenge will be to translate what we learn from this stunning new genetic animal model into help for the 2.2 million American adults haunted by unwanted thoughts and repetitive behaviors,� added NIMH director Thomas R. Insel, M.D., who conducted clinical studies on OCD earlier in his career.

Previous studies of OCD had implicated a circuit in which the striatum, which straddles the middle of the brain, processes decisions by the cortex, the executive hub at the front of the brain. But exactly how circuit communications might go awry remained a mystery, and glutamate was not a prime suspect.

Nor were Feng and colleagues initially interested in OCD. Rather, they sought to understand the function of the protein made by the SAPAP3 gene, which is involved in glutamate-mediated communications in the cortex-striatum circuit. To find out how it worked, they used genetic engineering to generate SAPAP3 knockout mice.

The mice seemed normal at first, but after four to six months, all developed telltale bald patches of raw flesh on their faces, caused by compulsive scratching. Videotapes confirmed that the sores were self-inflicted � grooming behavior gone amok.

�We were surprised by the magnitude of this phenomenon,� recalled Feng. �The parallels with OCD were pretty striking.�

In a series of behavioral tests, his team determined that the SAPAP3 knockout mice also showed anxiety-like behaviors, often associated with OCD. They were slower to venture into � and quicker to exit � risky environments. And like their human counterparts, the animals responded to treatment with a serotonin selective reuptake inhibitor (fluoxetine), which reduced both the excessive grooming and anxiety-like behaviors.

SAPAP3 is the only member of a glutamate-regulating family of proteins that is present in large amounts in the striatum. It is part of the machinery at the receiving end of the connections between brain cells, where the neurotransmitter binds to receptors, triggering increased activity among the cells.

The researchers found that lack of SAPAP3 genes dampened the increased activity usually caused by glutamate and stunted the development and functioning of circuit connections.

When the researchers injected the striatum of seven-day-old knockout mice with a probe containing the SAPAP3 gene, it protected them from developing the OCD and anxiety-like behaviors 4 to 6 months later and corrected the circuit dysfunction. This confirmed that the absence of the SAPAP3 gene in the striatum was indeed responsible for the OCD-like effects.

The findings suggest that anxiety-related behavior may stem from the striatum, which serves as a pivotal link between the cortex and emotion hubs. The researchers note that recent genetic studies of OCD have hinted at involvement of glutamate-related mechanisms.

Feng�s team is also looking beyond the SAPAP3 gene to other related genes in the circuit that could lead to similar behavioral problems. They are exploring how the SAPAP3 gene affects neural communications and how it works at the molecular level � with an eye to possible applications in drug development. Collaborating clinical investigators are exploring whether specific variants of the SAPAP3 gene in humans may be related to OCD spectrum disorders, such as trichotillomania, or obsessive hair pulling � a human syndrome also characterized by bald patches on the head.

Elephantnose fish 'see' with their chin

Tue, 21 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Originating in Central Africa, Peters' elephantnose fish (Gnathonemus petersii), finds its bearings by means of weak electrical fields. Scientists from the University of Bonn have now been able to show how well this works. In complete darkness the animals can even distinguish the material of objects at a distance or dead organisms from living ones. The results have now been published in the Journal of Experimental Biology.

The fish, which is as long as a cigar, hovers with its head inclined, close to the gravel-covered bed. While it swims forward slowly, its trunk-like elongated chin sweeps steadily from right to left, always at a distance of a few millimetres from the bottom. This way the fish behaves like treasure hunters searching for buried gold coins on the beach with their metal detector. Basically, this is precisely what the fish is doing. Hidden in the sediment there are large numbers of dead nematocera larvae waiting for it, its favourite food.

Zoologists from the University of Bonn have hidden the larvae there. 'We wanted to see whether it can find them and if the answer is yes, then down to what depth,' Professor Gerhard von der Emde explains. 'It', that is the African Peters' elephantnose fish. Yet its characteristically shaped chin does not work like a particularly sensitive nose. Instead, it contains more than 500 electric sensors with which it senses its surroundings. With this sense the animal has conquered the night. During the day it hides, only under cover of darkness does it goes searching for food.

The chin of Peters' elephantnose fish is basically its eye. In its tail is the corresponding torch. Via mutated muscle cells it produces regular electrical pulses of a few volts with it. 80 times per second the fish switches this little battery on and off for the blink of an eye. 'At the same time it measures the electrical field which builds up around it via sensors in the skin,' explains Professor von der Emde. Nearby objects distort the field, so that the fish obtains an image of its surroundings, which is a surprisingly complex one.

Professor von der Emde and his team have tested what the animals can perceive with their electric sense. For this they set up a small cube and a pyramid in an aquarium, for example. Whenever the fish swam to the pyramid, they were rewarded with a nematocera larva. Their eyes were no use to these agile fish, because the experiments took place with infrared lighting, so that only the researchers could see anything, using their special cameras. They were flabbergasted themselves by their results. In nine out of ten cases the fish swam straight towards the pyramid through the pitch black darkness. Even when the researchers used wire models instead of solid objects, the fish could not be fooled. They were even able to handle discontinuous contours. 'For example, we removed the vertical edges of a cube, i.e. we embedded two wire squares on top of each other in a gel that was permeable for electrical fields,' Professor von der Emde says. 'The fish still perceived it as a cube, so they supplied the contours very much like humans would.' Furthermore, they seem to calculate the volume of objects in water. 'A cube has a larger volume than a pyramid of the same height,' Gerhard von der Emde explains. 'If we decreased the size of the cube so much that its volume became smaller than that of the pyramid, the fish often changed their minds and swam to the cube.' So, the Peters' elephantnose fish can also internalise abstract concepts: 'Always swim to the less voluminous of two objects, irrespective of their absolute size.'

As in Starship Enterprise

What Bones, the ship's doctor of the Enterprise does, the little fish from Africa has been doing for a long time, viz. distinguishing living from dying or dead organisms without touching them. 'With its electric sense, it measures their capacitative properties, i.e. their ability to store charges,' Prof. von der Emde explains. 'Dead plants or animals cannot do that.' The electrical field image even tells it what material the object in question is made of. The image of metal is very bright, by contrast non-conductors weaken the electrical field around the fish. And it can even measure distances to a precision of several millimetres. In order to do so, it uses the fact that the electrical image becomes increasingly 'blurred'. From the degree of fuzziness it thus calculates the distance.

There is a reason for this brain power. The cerebellum of Peters' elephantnose fish is hugely enlarged. In comparison with their body length the animals have a larger brain than humans. 'They are really intelligent,' the zoologist says fondly, 'that's why it is so much fun working with them.' At one point he tried to train electric fish from South America. 'That was a flop,' he reminisces, 'the fish are beautiful, but definitely too stupid for complex tasks.'

Scientists tackle mystery mountain illness

Tue, 21 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Experts at the University are studying an illness known as HAPE (high altitude pulmonary oedema), which causes fluid to build up in the lungs can and can occur from as low as 2,500 metres, affecting people of all age groups and fitness levels.

Little is known about the condition and there is no way of predicting who is likely to be affected although studies have suggested a genetic link. It is thought that around one in 50 people who travel to high altitudes suffer from HAPE.

The database, which is being run in collaboration with researchers from America, Austria, Bolivia, and Britain, aims to encourage registration from previous sufferers of HAPE. It will facilitate research that could potentially identify people susceptible to the condition. Genetic studies using the database may also provide greater understanding of what happens in HAPE sufferers' lungs.

Dr Kenneth Baillie, co-ordinator of the database and a researcher at the University of Edinburgh, said: �There is no way of predicting who is likely to suffer from HAPE, as it can affect anyone even if you are young, healthy and active. Because it occurs from 2,500 metres, it can affect skiers as well as mountaineers. Treatment options are very limited and sufferers need to descend from high altitude and see a doctor straight away.

�A major problem is that sufferers may not know that they have HAPE until it is too late. Once the symptoms start to appear � which may include breathlessness at rest and blueness of the lips � sufferers may not realise the severity of the illness and the urgency of reducing altitude and seeking medical treatment. It may also be that sufferers are not in a position to go down a mountain in time, whether this is due to how ill they are, weather conditions or how high up they are. This all reinforces how important it is to find out who may be susceptible in advance so that they can either try to prevent the onset of the illness or not put themselves in a potentially life-threatening situation.�

Use of the database will be open to researchers worldwide, although details of individual members will be not be given out without their consent.

HAPE is the most common form of altitude sickness and can kill within hours if untreated. As the illness progresses, it can cause drowsiness and lack of coordination, leading to a coma and death. As cases are not registered, nobody knows exactly how many people have died as a result of the condition.

The main treatment is descent, but this is often impossible as a sufferer may need to be carried for miles on a stretcher, only to descend a few hundred feet. Other treatments include breathing oxygen and two drugs, dexamethasone and nifepidine, which may not be available when somebody becomes ill.

Blood vessels inside the lungs constrict in response to low oxygen to such an extent that fluid is forced from the capillaries (narrow tubes through which blood cells pass), leading to flooding of the lung�s air sacs.

Risk factors include rapid ascent, physical exertion and a previous history of the condition. By understanding who is most at risk, potential sufferers could take precautions such as climbing much more slowly or taking drugs to prevent the onset of the condition.

Understanding hypertension in African Americans proves elusive

Thu, 16 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Exercise cannot reduce a sodium-retaining hormone in African Americans known to potentially cause hypertension, found Michael D. Brown, Ph.D., the senior author of a study in the September issue of Experimental Physiology. Brown is an associate professor of kinesiology at Temple Universityï¿½s College of Health Professions.

The hormone, aldosterone, influences the kidneyï¿½s regulation of blood pressure, but too much of it can contribute to the development of hypertension because it causes the kidney to retain salt. Aldosterone, released by the adrenal glands on top of the kidneys, plays a role in the complex system used by the body to regulate blood pressure.

ï¿½Although the results are discouraging for African Americans and hypertension, itï¿½ll point us in other directions that may have more potential and could be the key to reducing hypertension,ï¿½ said Brown, who has a background in exercise physiology.

Many African Americans develop the salt-sensitive form of hypertension. Approximately 40 percent of African Americans have hypertension ï¿½ the highest rate of any racial or ethnic group in the United States ï¿½ but there is little data about what makes them more susceptible to this condition, Brown said.

This study is based on the premise that the prevalence of blood pressure sensitivity to salt is extremely high is African Americans. Alterations in aldosterone regulation may play a role because aldosterone causes the kidney to retain salt. Brown said he wanted to find out if exercise could lower the levels.

In the study, he found that the level of aldosterone was related to how the two racial groups distributed body fat. Caucasians generally stored fat in the abdomen area, whereas African Americans had fat distributed throughout the body in a layer under the skin. The six-month study involving 35 Caucasians and African Americans with hypertension found that aerobic exercise training program reduced aldosterone levels in Caucasians by 32 percent, but levels for African Americans were reduced by only 8 percent. Total body fat was reduced only in Caucasians, which might be a clue to the drop in aldosterone.

ï¿½The kidneys help to regulate blood pressure by changing the levels of salt and water in our body. Sometimes the kidneys reset at a higher blood pressure level if it has retained too much salt,ï¿½ Brown said.

While the study showed exercise did not lower aldosterone in African Americans, exercise still has many other benefits for this population, Brown said.

ï¿½Exercise has the capacity to affect so many things. Itï¿½s a way for the body to correct itself,ï¿½ he added.

Brown will continue his research in this area with a $3.5 million National Institutes of Health grant awarded earlier this year. In September, Brown will recruit African Americans with hypertension for a study on how exercise can improve the blood vessel condition. The study will also take an in-depth look at how genes can contribute to hypertension.

ï¿½Solving the cause of hypertension is similar to solving a big puzzle. Each piece of the puzzle represents a contributing factor to hypertension. Each of these pieces, or possible causes of hypertension, needs to be studied in a systematic way,ï¿½ Brown said.

New Joslin research identifies sirtuin protein instrumental in fat production and metabolism

Wed, 15 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON--August 15, 2007--A new Joslin Diabetes Center-led study has identified a protein found in fat cells that may play a major role in how fat is produced and stored, offering a new target for treatments to prevent obesity and reduce the risk for type 2 diabetes. This latest research appears in the August 2007 issue of Cell Metabolism.

The study examined the role of a protein called Sirt2, a member of the sirtuin family of seven cellular proteins. These proteins have recently been shown to be important in the control of aging and metabolism. Previous studies have focused on one member of this family, Sirt1, which is activated by high doses of resveratrol, a substance found in red grapes, which can prevent diabetes from developing and also prolong life. This finding generated tremendous attention, leading biotechnology and pharmaceutical companies to begin developing drugs and supplements to harness this effect. Joslin researchers have focused on other sirtuin proteins to find out what role they might play in fat and glucose metabolism and fat development.

This led to the discovery that Sirt2 is the most abundant of the sirtuins in fat cells, expressed in quantities five to ten times higher than other sirtuin proteins. We wanted to find out what would happen to the behavior of fat cells--in terms of metabolism or growth--if we changed the levels of Sirt2, said lead investigator C. Ronald Kahn, M.D., an internationally recognized researcher who is head of the Joslin section on Obesity and Hormone Action and the Mary K. Iacocca Professor of Medicine at Harvard Medical School.

When a person gains weight, cells in connective tissue known as pre-adipocytes differentiate and fill with fat and form adipocytes, which are able to store fat as a potential energy source when food is not available. However, too much fat storage leads to obesity and obesity-related diseases, including type 2 diabetes.

Using genetically altered cells from mice, the Joslin researchers were able to manipulate Sirt2 levels in adipocytes. They found that increasing Sirt2 levels in the cell would block the cell's ability to undergo differentiation and store fat, while reducing Sirt2 would promote adiopogenesis, or fat production. They then went on to pinpoint exactly how Sirt2 produced these effects by interacting with and modifying one of the key transcription factors, or molecular switches, regulating fat differentiation and function, a molecule called FoxO1. FoxO1 is also an important target of insulin action in fat where it helps control the aging process.

Thus, when Sirt2 levels in pre-adipocytes are low, more fat cells develop, while when Sirt2 levels are high, this process is blocked. So, to reduce the amount of fat in the body and help people stay thin, we need to find an activator of Sirt2, said Kahn.

The discovery of Sirt2's role in fat production gives researchers a new avenue to pursue in preventing and treating obesity. Since most of the diabetes epidemic is driven by obesity, Sirt2 may also play a role in preventing type 2 diabetes from developing and in treating people who have already developed the disease, said Kahn.

This is an important goal since more than 60 percent of Americans are now overweight or obese, and obesity is a major factor driving the current epidemic of type 2 diabetes, which now affects more than 20 million people in the U.S. alone.

The next step in the research process will be to create an animal model to validate the results. Once they are confirmed, biotechnology companies can try to develop drugs that would activate Sirt2 in fat cells and provide another tool for combating obesity and diabetes.

Older climbers face uphill battle on Mount Everest

Tue, 14 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In this era of not surrendering to age, some claim that 60 is the new 40. But new research shows that 60 year olds cannot keep up with 40 year olds on Mount Everest and suffer a sharply higher chance of dying if they do reach the summit.

The study shows that among 2,211 climbers during the spring seasons from 1990 through 2005, the overall chances of reaching Everest's summit were nearly 31 percent, but they dropped to 13 percent for climbers in their 60s. The overall chances of dying on the mountain were 1.5 percent, but they more than tripled to 5 percent for climbers 60 and older.

The researchers did not find any gender differences.

Before we did this analysis, we didn't know whether age would be important. Younger climbers have a physical advantage but probably have less experience than older climbers, said Raymond Huey, a University of Washington biology professor. We used to refer to this advantage of age as the Kareem Abdul-Jabbar effect. As he got older, his physical skills declined but he was so smart and experienced that he was able to compensate and still play professional basketball at the highest levels.

Unfortunately for older climbers, that effect does not apply on the world's highest mountain, said Huey, lead author of a paper describing the research published online Aug. 15 in the Royal Society journal Biology Letters. The Royal Society is the United Kingdom's national science academy.

Other authors are Richard Salisbury, a database analyst and mountaineering historian in Ann Arbor, Mich., and statisticians Jane-Ling Wang and Meng Mao at the University of California, Davis.

The findings run counter to the notion published in a medical journal in 2000 that people in their 60s could safely climb peaks of about 26,300 feet. Mount Everest is about 29,030 feet.

I think they were overstating the safety factor. I think it's much more risky, Huey said.

Huey suspects there are two possible reasons why fewer climbers older than 40 reach the summit and successfully make it down again declining physical capacities and a higher degree of caution that causes them to stop short of their goal of reaching the summit.

By the time you are 50 or 60, you've probably been banged up once or twice. You know it hurts, and you've seen consequences of losing fingers or toes to frostbite, Huey said. So older climbers are probably more cautious, but I can't determine whether it's greater caution, reduced fitness or a combination of the two that explains the lower success rate for older climbers.

The research, funded by the National Science Foundation, consisted of a statistical analysis of climbers since 1990, looking at the influence of age and gender on success and death rates. Much of the data come from Elizabeth Hawley, who chronicled climbing expeditions in the Himalayas and for four decades conducted interviews that provided a large historical archive of mountaineering information.

The analysis found virtually no difference between men and women on Everest there are many fewer women climbers, but their rates of reaching the summit and of dying are very similar to those for men.

But age differences were stark. Those at least 60 years old who started up the mountain had a death rate at least three times higher than younger climbers. For those who actually reached the summit, 25 percent died before completing the descent, compared with 2.2 percent for younger climbers. However, because the sample of older climbers is relatively small, the actual difference could be exaggerated or understated, Huey said.

Many more people in general are trying to climb Everest than, say, 30 years ago there are reports that just this spring more than 600 people reached the summit. The first two climbers to scale Everest, Edmund Hillary and Tenzing Norgay, were 33 and 39 when they succeeded in 1953. For many years, only about 20 percent of the climbers were older than 40, and those older than 60 were very rare. But the scientists found that in recent years nearly half of all climbers are at least 40, and one of every 30 is at least 60 years old. Until now, these older climbers had no way of knowing about how age correlates with their chances of success and death.

Huey believes it is likely more older climbers are now attempting to climb Everest because guided expeditions are readily available and because many older climbers have sufficient disposable income to pay for those guided trips.

Older people are usually healthier now than they were 50 years ago, he said. Many fewer people smoke and health care is better, so increasingly older people are participating in a variety of sports.

But, as the researchers concluded in their paper, On Everest, youth and vigor trump age and experience.

Risk of common vaginal infection linked to preterm birth appears higher for blacks

Sat, 11 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) BOSTON, Aug. 11 Risk of a common vaginal infection linked to preterm birth appears to escalate when even one partner is African-American, according to a University of Pittsburgh School of Medicine study presented today at the 34th annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology in Boston.

When a pregnant woman has bacterial vaginosis, her risk of preterm birth goes up, said Hyagriv Simhan, M.D., M.S.C.R., assistant professor of obstetrics, gynecology and reproductive sciences at the University of Pittsburgh School of Medicine. And now we can say that gauging risk for bacterial vaginosis is not as simple as just looking at the woman. We also should consider her partner.

Bacterial vaginosis (BV) is a common gynecological infection that affects up to 50 percent of women in some populations. BV is characterized by an increase in vaginal alkalinity and an overgrowth of abnormal bacteria. Among the infections more prominent symptoms is a milky, foul-smelling discharge.

For years, clinicians have thought of BV infection as a minor problem, but in addition to increasing the risk for preterm birth, other studies have shown that women who have BV also are more likely to get herpes and other sexually transmitted diseases, including HIV, said Dr. Simhan, a maternal-fetal medicine specialist at the Magee-Womens Hospital of the University of Pittsburgh Medical Center.

For this observational study, Dr. Simhan and his colleagues considered 325 women who were in their first trimester of pregnancy. Among these women, 129 (39.7 percent) were white female/white male partnerships, 35 (10.8 percent) were white female/black male couples, 12 (3.7 percent) were black female/white male couples, and 149 (45.9 percent) were black female/black male partnerships.

Generally, BV was less common among white women compared to black women in the group. But notably, partner race also showed an influence on BV risk, Dr. Simhan said. Our results showed that when one partner is black whether male or female risk of BV goes up two-fold.

BV infection is commonly treated with a range of antibiotics. However, in some cases treatment fails and infections become resistant. Even women whose infection clears frequently can become re-infected later.

We found that paternal race is an independent risk factor for BV during pregnancy, and that this is at least as important a risk factor as maternal race, continued Dr. Simhan. Studies on the contribution of BV to adverse pregnancy outcomes should consider paternal race as an important factor.

A recent study from the U.S. Centers for Disease Control and Prevention found that preterm birth contributed to more than a third of infant deaths twice as many as previously thought, making it the leading cause of infant deaths yet the underlying causes of premature birth are not well understood.

Reasons for the observed variance in BV rates among racial groups also are not well understood, Dr. Simhan said.

There could be genetic differences that relate to why infection rates are different, and maybe some differences in nutritional status that could play a part. But we dont even know the differences in normal vaginal flora among racial groups, he said. More study is definitely needed. What we can say now is that its just not as simple as treating the woman.

Gene predicts better outcome as cortex normalizes in teens with ADHD

Mon, 06 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Brain areas that control attention were thinnest in children with attention deficit hyperactivity disorder (ADHD) who carried a particular version of a gene in a study by the National Institutes of Healths (NIH) National Institute of Mental Health (NIMH). However, the areas, on the right side of the brains outer mantle, or cortex, normalized in thickness during the teen years in these children, coinciding with clinical improvement. Although this particular gene version increased risk for ADHD, it also predicted better clinical outcomes and higher IQ than two other common versions of the same gene in youth with ADHD.

Since this gene version had similar structural effects in healthy children as in children with the disorder, our findings suggest that ADHD is at the far end of a continuum of normal traits, said Philip Shaw, M.D., NIMH Child Psychiatry Branch, who led the research. ADHD likely stems from interactions between several such genes and non-genetic factors.

Shaw, Judith Rapoport M.D., and colleagues report on their magnetic resonance imaging (MRI) study in the August 2007 Archives of General Psychiatry.

This study provides us with a first glimpse of how variation in a specific gene influences both brain development and clinical prognosis in ADHD, said NIMH Director Thomas R. Insel, M.D.

When the NIMH researchers first reported last year that normalization of right cortex thickening was associated with better clinical outcomes in ADHD, there were few hints of a genetic connection. Yet evidence from several previous studies led them to suspect involvement of an ADHD-implicated version of a gene that codes for a receptor protein that binds to the brain chemical messenger dopamine.

This version of the dopamine D4 receptor gene, called the 7-repeat variant, accounts for about 30 percent of the genetic risk for ADHD, making it by far the strongest candidate gene implicated in the disorder. Its called the 7-repeat because it contains the same repeating sequence in its genetic code seven times. Everyone inherits two copies of the D4 receptor gene, one from each parent, so some people have two copies of the same version while others may carry two different versions.

For the current study, the researchers scanned and determined the D4 gene types of 105 children with ADHD and 103 healthy controls and re-scanned them through their teen years.

They found that nearly one-fourth of youth with ADHD and in about one-sixth of the healthy controls had at least one copy of the 7-repeat version. Nearly two thirds of the ADHD youth and three-fourths of the healthy controls had the most common 4-repeat version; fewer than one-tenth in each group had a 2-repeat version.

While the 7-repeat version was linked to thinner attention-controlling cortex in both ADHD and healthy subjects, it appeared to confer advantage only among youth with ADHD. For example, participants with ADHD who lacked at least one copy of this 7-repeat variant had significantly lower IQs, and more than half of them still had pronounced ADHD symptoms when followed-up about six years later, compared to only 21 percent of those with at least one copy of the 7-repeat variant. There was also a trend toward better overall functioning among those with at least one copy of the 7-repeat variant at follow-up.

The MRI scans revealed that 7-repeat carriers with ADHD started out with the thinnest cortex areas important for controlling attention (right orbitofrontal and posterior parieto-occipital). The next thinnest were children with ADHD who did not have the 7-repeat version, followed by healthy children with the 7-repeat. Healthy children lacking the 7-repeat had the thickest cortex, but this did not appear to affect their IQ. However, the researchers note that other studies have found correlations between cortex thickness and certain measures of memory and intelligence.

In 7-repeat carriers with ADHD, the attention-controlling areas thickened to normal by age 16 (see time-lapse image below). Gene variants of two other dopamine system components showed few such anatomic correlates, confirming that the findings were specific to the D4 receptor gene.

Some genes have a good side, even though theyre linked to disorder, said Shaw, who noted that other traits linked to the 7-repeat version, such as novelty seeking and impulsiveness, might confer advantage in some settings. Evidence suggests that the 7-repeat may be a relatively new variant that may have been favored through evolution because such traits proved adaptive for survival.

The researchers are following up with studies on the relationship between cortex thickness and cognitive features of ADHD, such as working memory and the ability to inhibit responses.

Why nectar-feeding bats need a 'power drink' to fly

Sun, 05 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Nectar-feeding bats burn sugar faster than any other mammal on Earth and three times faster than even top-class athletes ecologists have discovered. The findings, published online in the British Ecological Society's journal Functional Ecology, illustrate that because they live life on an energetic knife edge, these bats are very vulnerable to any changes in their environment that interrupt their fuel supply for even a short period.

Working with a captive breeding colony in Germany, Dr Christian Voigt of the Leibniz Institute for Zoo and Wildlife Research in Berlin and Professor John Speakman of the University of Aberdeen fed long-tongued bats (Glossophaga soricina) sugar labelled with non-radioactive carbon-13 and then measured the amount of carbon-13 in the bats exhaled breath.

We found that nectar-feeding bats made use of the sugar they were drinking for their metabolism within minutes after drinking it, and after less than half an hour they were fuelling 100% their metabolism from this source. For comparison, the highest rates reported in humans are for athletes who can fuel up to 30% of their metabolism directly from power drinks, they say.

The reason these bats live on such an energetic knife edge is down to the food source they live on and the way they get around. They feed on floral nectars that contain simple sugars such as sucrose, glucose and fructose, but which are produced in only very small amounts by flowering plants. These sugars are rapidly absorbed and digested, and by metabolising them directly rather than converting them to fat or glycogen and then using them up later the bats get the maximum energy they can from the sugars. This is important because they hover like humming birds, and this kind of flight uses up a great deal of energy.

According to Voigt and Speakman: All animals need energy to power their metabolism. Ultimately this energy comes from food, but usually only a small fraction of the energy being used comes directly from the food. Normally, most of the food is converted into storage and this is drawn on later to fuel metabolism. Small nectar-feeding bats have among the highest metabolic costs among mammals, and mostly eat a diet low in fat and protein but rich in sugars. Metabolising these sugars immediately they are consumed saves the costs of converting them to and from storage.

In a second experiment, Voigt and Speakman measured how fast the bats used their meagre fat stores. We found the bats depleted almost 60% of their fat stores each day, but even this phenomenal rate was still barely enough to sustain their metabolism when nectar was absent. This underlines how accurately these bats must balance their energy requirements every day and how vulnerable they are to ecological perturbations that might interrupt their fuel supply for even a short period, they say.

Nectar-feeding bats live in south and central America and are among the smallest of all living mammals, weighing less than 10g. They feed at night and can ingest up to 150% of their body weight as nectar.

Scientists find why red beans and rice can be nauseating

Wed, 01 Aug 2007 03:59:37 PST

( from http://www.rxpgnews.com ) People cry foul when fowl is undercooked, but what about red beans and rice

Scientists have discovered how lectins, a family of proteins believed to be a natural insecticide that is abundant in undercooked legumes and grains, can make you feel temporarily miserable.

Its known that it can be a toxin, Dr. Paul L. McNeil, cell biologist at the Medical College of Georgia, says of the lectin protein thats commonly found in vegetables. Lectins, which bind strongly to carbohydrates that decorate cell surfaces, have a particular affinity for the heavy-carbohydrate coats of epithelial cells that line the gastrointestinal tract.

Researchers have long known that ingesting too much undercooked lectin can cause nausea, diarrhea and vomiting. What they didnt know was how lectin caused food poisoning.

Work published Aug. 1 in PloS One shows lectins disable GI tract cells, which are constantly bombarded while digesting food, from repairing tears in cells walls from all the activity. Repair normally occurs in seconds: internal membranes move up to patch the tear, the cell recovers and the one-cell layer lining of the GI tract remains intact.

If those individual cells cannot repair tears, they die, says Dr. McNeil. That means you have gaps in the integrity of the surface area of the epithelium and you are exposing the nasty internal world of your GI tract to your blood supply.

The epithelial lining is a continuous, natural barrier between digesting food in the GI tract and the blood supply. When intact, it allows only good stuff like nutrients to pass through.

Your body senses that lack of barrier function and tells you to eliminate the entire contents of the GI tract, says Dr. McNeil, noting that lectins apparent role as a natural insecticide and as a source of food poisoning are related. If you get vomiting and diarrhea you are going to eliminate the entire contents of your gastrointestinal tract, right And, you are not going to eat red beans again the next day, right That is probably the point if they are natural insecticides. Alcohol will do the same thing. When you drink too much alcohol, you can destroy the lining of your stomach.

But the scientist who first identified how injured cells patch themselves says lectin blocks this repair mechanism better than anything else hes seen. Interestingly, he and his colleagues showed in PloS Biology in 2006 how roughage which includes beans help people stay regular by causing more cell tears, which enables more mucus to escape from cells, essentially greasing the GI tract.

That same research team, which includes Dr. Katsuya Miyake, MCG cell biologist, and Dr. Toru Tanaka, pharmacologist at Josai University in Japan, has now shown lectin is also very good at blocking mucus expulsion from cells.

In fact, they discovered lectins role in stopping cell-patching and mucus release while researching roughage. The multipurpose lectin is a powerful stain the team used to look at mucus released by cells after tearing. They found if they used too much lectin there was no patching or mucus, just cell death.

Biologically its interesting because it might tell us more about the mechanism of repair, says Dr. McNeil, who wants to learn more about how lectin interferes with repair. We know the mechanism involves surface binding because you can add lectin and the cells cant repair. You take the same culture of cells, wash the lectin away, injure other cells in the culture and they repair fine. We also know its a very rapid, surface-initiated inhibition.

In addition to the immediate discomfort undercooked beans and rice can cause, long term concerns ingestion of lectin has also been linked to colorectal cancer and celiac disease, a common problem in which individuals are sensitive to gluten, a mixture of proteins derived from wheat flour that includes lectins. The small intestine of the celiac sufferer is unable to properly absorb nutrients after gluten ingestion.

Oddly, in a laboratory dish, safe from mechanical stresses that cause surface tears, lectin can make cells divide, which is quite the opposite of making cells sick, Dr. McNeil says. A recent Science paper implicated lectin in diabetes as well.

Its possible that this bioactive property of lectin that binds to our cells could have long-term consequences taken even in small amounts, he says, noting that thorough cooking destroys most but not all lectin. Maybe the bloating and gas is telling us something about lectin when its just a minor irritation.

He notes lectin is easily among the top-10 causes of food poisoning but is unlikely to be lethal because the body is so good at sensing the break in the GI barrier and eliminating the problem.

Learning a second language -- Is it all in your head?

Wed, 25 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, Ill. --- Think you haven't got the aptitude to learn a foreign language New research led by Northwestern University neuroscientists suggests that the problem, quite literally, could be in your head.

Our study links brain anatomy to the ability to learn a second language in adulthood, said neuroscientist Patrick Wong, assistant professor of communication sciences and disorders at Northwestern and lead author of a study appearing online today (July 25) in Cerebral Cortex.

Based on the size of Heschl's Gyrus (HG), a brain structure that typically accounts for no more than 0.2 percent of entire brain volume, the researchers found they could predict -- even before exposing study participants to an invented language -- which participants would be more successful in learning 18 words in the pseudo language.

Wong and his colleagues measured the size of HG, a finger-shaped structure in both the right and left side of the brain, using a method developed by co-authors Virginia Penhune and Robert Zatorre (Montreal Neurological Institute). Zatorre and Penhune are well known for research on human speech and music processing and the brain.

We found that the size of left HG, but not right HG, made the difference, said Northwestern's Catherine Warrier, a primary author of the article titled Volume of Left Heschl's Gyrus and Linguistic Pitch. Anil K. Roy (Northwestern), Abdulmalek Sadehh (West Virginia University) and Todd Parish (Northwestern) also are co-authors.

The study is the first to consider the predictive value of a specific brain structure on linguistic learning even before training has begun. Specifically, the researchers measured the size of study participants' right and left Heschl's Gyrus on MRI brains scans, including calculations of the volume of gray and white matter.

Studies in the past have looked at the connection between brain structure and a participant's ability to identify individual speech sounds in isolation rather than learning speech sounds in a linguistic context. Others have looked at the connection between existing language proficiency and brain structure.

While our study demonstrates a link between biology and linguistics, we do not argue that biology is destiny when it comes to learning a second language, Wong emphasized. Adults with smaller volumes of left HG gray matter need not despair that they can never learn another language.

We are already testing different learning strategies for participants whom we predict will be less successful to see if altering the training paradigm results in more successful learning, Wong added.

According to Warrier, Northwestern research professor of communication sciences and disorders, the researchers were surprised to find the HG important in second language learning. The HG, which contains the primary region of the auditory cortex, is typically associated with handling the basic building blocks of sound -- whether the pitch of a sound is going up or down, where sounds come from, and how loud a sound is -- and not associated with speech per se, she said.

The 17 research participants aged 18 to 26 who had their brain scans taken prior to participating in the pseudo second language training were previously participants in two related studies published by Wong and his research team.

The three studies have identified behavioral, neurophysiologic and, with the current study, neuroanatomic factors which, when combined, can better predict second language learning success than can each single factor alone.

In a behavioral study, Wong's group found that musical training started at an early age contributed to more successful spoken foreign language learning. The study participants with musical experience also were found to be better at identifying pitch patterns before training.

In a neurophysiologic study -- again with the same participants -- Wong's team used functional magnetic resonance imaging to observe what parts of brain were activated when participants listened to different pitch tones. They found that the more successful second language learners were those who showed activation in the auditory cortex (where HG resides).

The participants all were native American English speakers with no knowledge of tone languages. In tone languages (spoken by half the worlds population), the meaning of a word can change when delivered in a different pitch tone. In Mandarin, for example, the word mi in a level tone means to squint, in a rising tone means to bewilder and in a falling and then rising tone means rice.

For the study reported in Cerebral Cortex, Wong's 17 participants entered a sound booth after having their brains were scanned. There they were trained to learn six one-syllable sounds (pesh, dree, ner, vece, nuck and fute). The sounds were originally produced by a speaker of American English and then re-synthesized at three different pitch tones, resulting in 18 different pseudo words.

The participants were repeatedly shown the 18 pseudo words and a black and white picture representing each word's meaning. Pesh, for example, at one pitch meant glass, at another pitch meant pencil, and at a third meant table. Dree, depending upon pitch, meant arm, cow, or telephone.

As a group - and sometimes in fewer than two or three sessions the nine participants predicted on the basis of left HG size to be more successful learners achieved an average of 97 percent accuracy in identifying the pseudo words. The less successful participants averaged 63 percent accuracy and sometimes required as many as 18 training sessions to correctly identify the words.

Whats important is that we are looking at the brain in a new way that may allow us to understand brain functions more comprehensively and that could help us more effectively teach foreign languages and possibly other skills, said Wong.

Discoverer of Sly Syndrome finds way of delivering medicine to fight rare genetic disorder

Wed, 25 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) ST. LOUIS -- The scientist who discovered Sly Syndrome nearly four decades ago and a team of colleagues at Saint Louis University are a step closer to finding an approach to treat the rare genetic disease. Sly Syndrome causes bone defects, mental retardation, vision and hearing problems, heart disease and premature death.

They found that a potentially life-saving enzyme can be induced to cross the blood-brain barrier, a structure which protects the brain from foreign substances, if it is given with the hormone epinephrine.

Ever since William S. Sly, M.D., chairman of the department of biochemistry and molecular biology at Saint Louis University, discovered the rare genetic disease in 1969, he and his colleagues have conducted research to learn more about how to treat it. He says their recent findings have significance beyond treating the extremely rare disease that bears his name.

There are at most 100 living cases of Sly Syndrome. Nonetheless, this disease is a model for all the diseases in this group, some of which are much more common, Sly says.

Lysosomal storage diseases affect 1 in 7,000 live births, and 90 percent of those with the diseases have brain involvement. What we find with Sly Syndrome has some importance for all those diseases as well. It is potentially a big finding and an important first step.

The discovery potentially points to a new way to get big molecules, such as certain medications, across the blood-brain barrier. It is reported in the Proceedings of the National Academy of Sciences Online Early Edition the week of July 16.

SLU researchers found that the right amount of epinephrine probably works by stimulating transport by vesicles blister-like wrappers that carry substances across the blood-brain barrier so that the enzyme missing in patients who have Sly Syndrome can get into the brain.

Those who have Sly Syndrome lack the enzyme called beta-glucuronidase. Without this enzyme, protein-sugar molecules accumulate in the brain and other organs in the body. By replacing the missing enzyme, doctors believe they can treat the genetic disease. The problem, though, was slipping the enzyme past the blood-brain barrier to where it needs to do its work.

This is a disease that is simply made for testing drug delivery vehicles. If you can get the enzyme into the brain, the vehicle that delivered it could work to deliver other chemicals, too, says William A. Banks, M.D., professor of geriatrics and pharmacological and physiological sciences at Saint Louis University, and a leading researcher on the blood-brain barrier.

Sly Syndrome, which occurs in fewer than one in 100,000 births, is a progressive disorder that ranges in severity from mild to deadly. It is among a group of genetic diseases call mucopolysaccharidoses.

Some children who have this group of diseases are doomed to an early death because they dont make a certain enzyme, Banks says.

Enzyme replacement therapy or putting the missing enzyme into the bodies of those who have Sly Syndrome holds promise in treating the physical problems of the disease.

In the case of Sly Syndrome, the missing enzyme is more than 1,000 larger than a sugar molecule and so huge it cant get across the blood-brain barrier, which prevents it from reaching the brain.

Scientists used a mouse model to figure out how to get the enzyme into the brain. They knew that injections of the missing enzyme into the brains of baby mice reached their target, but similar injections into mature mice did not. As the mice grew older, the transporter that brought the enzyme past the protective blood-brain barrier was lost.

We found that the right amount of epinephrine allowed the enzyme to pass into the brain of older mice, which means we reinduced the way to get the enzyme where it is needed, Banks says.

Epinephrine is a drug that treats cardiac arrest and is given to open the airways of asthma patients who have difficulty breathing. Discovering epinephrine as the transportation key to unlock the blood-brain barrier for the missing enzyme was a shot in the dark, Banks says.

High doses of epinephrine can destroy the blood-brain barrier and let everything into the brain, which is toxic, Banks says. We tested three things. One didnt work at all. One worked partially and epinephrine worked incredibly well.

The finding changes how scientists look at getting medications through the blood-brain barrier, he says, and could have implications for treating other diseases such as Alzheimers disease and obesity.

Instead of viewing the blood-brain barrier as an obstacle to fight, researchers should consider it something to finesse, using its special features to help in drug delivery, Banks adds.

The field has approached the problem as if you have a Volkswagen that can get across the street and you put your cargo on it so the cargo can get there too. Weve found that trying to transport the cargo changes the Volkswagen and the Volkswagen can no longer get across.

Monell researchers find metabolic defect in liver that can lead to obesity

Tue, 24 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Philadelphia (July 24, 2007) -- Researchers at the Monell Chemical Senses Center have identified a genetically-transmitted metabolic defect that can lead to obesity in some individuals. The defect involves decreased production of liver enzymes needed to burn fat and may help to explain why some people become obese while others remain thin.

The global obesity epidemic is thought to be caused in part by the increased availability and intake of high calorie foods rich in fat and carbohydrates. These foods promote weight gain in humans and other animals, leading to a diet-induced obesity. The propensity to gain weight and become obese when consuming a high-fat diet is at least partially controlled by genes.

Results of this study help explain the interaction between genes and diet that underlies diet-induced obesity, comments senior author Mark Friedman. They also point to a way to identify individuals at risk for dietary obesity, perhaps even during childhood before the development of unhealthy eating habits.

The current study, published in the August issue of Metabolism, demonstrates that genetic susceptibility to diet-induced obesity is due to a reduced capacity to burn fat.

Fat is one of the fuels that the bodys cells burn to provide energy. This process, known as fat oxidation, takes place inside mitochondria, the cells power plants for generating energy.

If the ability to oxidize fat is impaired, the bodys capacity to make energy is reduced. This leads to increased hunger and overeating, as the body tries to increase the amount of energy available to meet its needs.

When the diet is low in fat, a reduced ability to burn fat has relatively little impact on energy production. However, if fat oxidation is impaired and the diet is high in fat, a greater proportion of calories cannot be used and food intake increases to cover the energy deficit. Because fat fuels are stored in fat tissue when theyre not oxidized, the increased food intake causes weight gain.

To determine whether preexisting differences in fat oxidation might contribute to individual susceptibility to diet-induced obesity, Friedman and lead author Hong Ji used rats that differ in their genetic predisposition to gain weight and become obese when fed a high-fat diet.

The closely-related strains weigh the same and eat the same amount of calories when fed a low-fat diet. However, when switched to a high-fat diet, the strain that is obesity-prone overeats and becomes obese, while the obesity-resistant strain does not.

The researchers found that even when eating a low-fat diet and still lean, the obesity-prone rats were less able to burn fat than were the obesity-resistant rats. This intrinsic deficit in fat oxidation was associated with a decrease in the capacity to make two liver enzymes. One, CD36, is responsible for transferring fat fuels into liver cells, while the second enzyme, acyl-coenzyme A dehydrogenase, begins the oxidation process in mitochondria.

When fed a high-fat diet, the obesity-prone rats overate and became obese, gaining 36% more weight than resistant animals. Fat oxidation was further compromised due to a decreased ability to make CPT1A, the liver enzyme responsible for transporting fat into mitochondria.

The inherited propensity to gain weight when eating a high-fat diet appears to be due to a preexisting limit on the ability to burn fat in the liver. This defect persists during the development of obesity and is then further compounded by additional deficits in the fat oxidizing machinery, comments Friedman.

Other studies in Friedmans laboratory have demonstrated that a decrease in fat oxidation and energy production in the liver generates a signal that stimulates eating. Experiments in his and other laboratories have also found that treatments that increase fat oxidation reduce food intake and cause weight loss in obese rodents.

With this in mind, Friedman notes, The present findings point to fat oxidation in the liver as a target for the development of drugs that suppress appetite and promote weight loss in obese individuals.

Future studies will guide development of such interventions by examining more closely the function and activity of the target enzymes.

Study sheds light on why humans walk on two legs

Mon, 23 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Studying chimpanzees trained to use treadmills, a team of anthropologists has gathered new evidence suggesting our earliest apelike ancestors started walking on two legs because it required less energy than getting around on all fours.

The research will appear in the July 24 print edition of the Proceedings of the National Academy of Sciences.

When our earliest ancestors started walking on two legs, they took the first steps toward becoming human, said lead researcher Michael Sockol of UC Davis. Our findings help answer why.

This is the first time anyone has succeeded in studying energetics and biomechanics in adult chimps, said Sockol, who worked for two years to find an animal trainer willing to coax adult chimps to walk on two legs and to knucklewalk on all fours on the sort of treadmill found in most gyms. The five chimps also wore face masks used to help the researchers measure oxygen consumption.

While the chimps worked out, the scientists collected metabolic, kinematic and kinetic data that allowed them to calculate which method of locomotion used less energy and why. The team gathered the same information for four adult humans walking on a treadmill.

The researchers found that human walking used about 75 percent less energy and burned 75 percent fewer calories than quadrupedal and bipedal walking in chimpanzees. They also found that for some but not all of the chimps, walking on two legs was no more costly than knucklewalking.

We were prepared to find that all of the chimps used more energy walking on two legs -- but that finding wouldn't have been as interesting, Sockol said. What we found was much more telling. For three chimps, bipedalism was more expensive, but for the other two chimps, this wasn't the case. One expended about the same energy walking on two legs as on four. The other used less energy walking upright.

These two chimps had different gaits and anatomy than their knucklewalking peers. And when the researchers examined the early hominid fossil record, they found evidence of these traits skeletal characteristics of the hip and hind limb that allow for greater extension of the hind limb -- in some early bipeds.

Taken together, the findings provide support for the hypothesis that anatomical differences affecting gait existed among our earliest apelike ancestors, and that these differences provided the genetic variation natural selection could act on when changes in the environment gave bipeds an advantage over quadrupeds.

Fossil and molecular evidence suggests the earliest ancestors of the human family lived in forested areas in equatorial Africa in the late Miocene era some 8 to 10 million years ago, when changes in climate may have increased the distance between food patches. That would have forced early hominids to travel longer distances on the ground and favored those who could cover more ground using less energy.

This isn't the complete answer, Sockol said. But it's a good piece of a puzzle humans have always wondered about: How and why did we become human And why do we alone walk on two legs

Enzyme eliminated by cancer cells holds promise for cancer treatment

Wed, 18 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An enzyme that cancer cells eliminate, apparently so they can keep proliferating, may hold clues to more targeted, effective cancer treatment, scientists say.

In a high-stakes tit for tat, protein kinase G enables healthy cells to stay on task to proliferate, differentiate then provide a useful function. Cancer somehow reduces or eliminates PKG and cells get stuck proliferating.

The bottom line is, in normal tissue, you can see PKG being expressed; but tumors or cell lines that correlate with those tissues dont have nearly as much, says Dr. Darren Browning, cancer researcher at the Medical College of Georgia.

Cell lines used for all types of research appear to support his hypothesis. Many are actually cancer cells because of their proclivity to keep producing; Dr. Browning and others have shown PKG is lost in these cells. You split them once or twice and they kind of lose their character, he says.

The same appears true for tumors in people, says Dr. Browning, whose lab has found dramatic differences in PKG levels in tumors compared to even nearby, healthy tissue removed in surgery to ensure a cancer-free margin.

The findings made him wonder if the change in PKG level was just an artifact or was critical to cancer survival. A lot of proteins are lost by cancer cells, so we asked, What happens if we put PKG back into the cancer cells

He took metastatic colon cancer cells, created a system for reintroducing PKG, then put the cells into mice without an immune system. He admits he was disappointed that the PKG-enhanced cells grew but became very interested in how they grew.

Cancer cells without PKG created hard, solid tumors that spread. PKG-enhanced cells created a soft, non-invasive tumor that literally fell apart on contact and seemed to grow in little islands. After consultation with pathologists and others, he realized the PKG-enhanced cells were congregating around the few blood vessels. We know that cancer cells, particularly colon cancer cells, are very aggressive at bringing blood vessels into the tumor, he says. Cells poor at recruiting blood vessels dont grow well, which seems to be the case for PKG-enhanced colon cancer cells.

Now he wants to know how PKG nullifies aggressive metastatic cancer cells. We think PKG inhibits cancer by getting rid of a cancer-promoting gene called beta-catenin, which slows growth and blocks the tumors ability to recruit blood vessels that are needed to grow bigger, says Dr. Browning, who recently received a $720,000 American Cancer Society grant to pursue his hypothesis. His proposal was ranked number one by the ACS Cell Structure and Metastasis Study Section.

Hes already shown that PKG can reduce vascular endothelial growth factor, or VEGF; anti-VEGF drugs are the focus of numerous anti-cancer trials underway in the country because of VEGFs critical role in development of new blood vessels. Maybe by activating PKG or increasing PKG expression in tumors, we are going to reduce the amount of VEGF they produce, he says. We dont know whether PKG has a role in going from normal tissue to the initiation of a tumor, but we think its important to the tumor both in terms of angiogenesis and blocking metastasis. He points to one of his studies in which colon cancers spread to the lungs a common path for metastatic colon cancer was completely blocked by PKG expression.

A big part of the magic of PKG may be its impact on a gene called beta-catenin, which enables many stem cells, including those in the skin, bone marrow and colon, to proliferate throughout life. Little pits called crypts in the wall of the colon contain Wnt hormone which stimulate nearby stem cells, causing an increase in beta-catenin. The net effect is the colon makes new cells to replace cells lost to the ongoing grind of absorbing water and minerals from food and forming and eliminating waste.

As cells start moving out of the crypt, away from the Wnt hormone, beta-catenin levels go down so cells should stop dividing and start maturing. Essentially all colon cancers have an aberration in this beta-catenin system that prevents normal degradation and allows cell to keep proliferating.

In the normal cells that line the colon, you dont see very much beta-catenin. We think PKG in these cells keeps it that way to keep the cells from continuing to proliferate and spread, says Dr. Browning, who has already shown that in the test tube at least, adding PKG lowers beta-catenin levels. Interestingly, beta-catenin also is known to regulate VEGF expression in colon cancer.

In a nutshell, the first and most important genetic lesions leading to colon cancer cause increased beta-catenin levels, says Dr. Browning. We found PKG can knock down beta-catenin levels by up to 80 percent in some colon cancer cells and we think that is part of the mechanism by which PKG is able to block tumor angiogenesis and metastasis.

Hes excited by the implications and is involved in extensive collaborations to understand how PKG regulates beta-catenin and how it might be used in cancer therapies.

Evidence of PKGs effectiveness in fighting colon cancer in humans may already be available. Colon and rectal cancer is the third most common cancer in men and women in the United States but its rare in developing countries where residents eat less processed food and ingest more bacteria. Some of these bacteria make a protein, STa, which appears to prevent and even kill colon cancer cells. Dr. Browning believes that PKG is responsible for STas anti-cancer effects.

Evidence found for novel brain cell communication

Mon, 16 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An article published today, July 16, 2007, in Proceedings of the National Academy of Sciences provides strong evidence for a novel type of communication between nerve cells in the brain. The findings may have relevance for the prevention and treatment of epilepsy, and possibly in the exploration of other aspects of brain functions, from creative thought processes to mental illnesses such as schizophrenia.

The work was performed jointly by scientists at SUNY Downstate Medical Center in Brooklyn, New York; Colorado State University in Fort Collins, Colorado; Mount Sinai School of Medicine in Manhattan, New York; and the University of Newcastle in the United Kingdom. The lead author was Dr. Farid Hamzei-Sichani, an MD/PhD student at Downstate Medical Center, working in the laboratory of Roger Traub, MD, professor of physiology and pharmacology and of neurology at SUNY Downstate.

Epilepsy a group of disorders characterized by the recurrent occurrence of spontaneous seizures affects roughly one-half of one percent of the U.S. population, and a higher percentage still in developing countries. In approximately one-third of patients, seizures are not properly controlled by available treatments. Problems can arise in the ability of patients to function at home and in society.

Epileptic seizures are customarily regarded to reflect an imbalance between the ability of nerve cells to excite one another, on the one hand, and to inhibit one another, on the other hand. The excitation and inhibition take place because the activity of nerve cells leads to the release of particular chemicals called neurotransmitters at specialized junctions that are called chemical synapses. The neurotransmitters diffuse across a tiny space between the nerve cells, and then bind to proteins (called receptors) on other nerve cells. Binding of a neurotransmitter to a receptor in turn causes excitation or inhibition in the other nerve cells.

This is the classic means of communication between nerve cells, and lies at the base of most of current understanding of how the brain processes information and controls muscles in the body.* A seizure is presumed to occur when there is too much chemical synaptic excitation, and/or not enough inhibition.

There is, however, another means for nerve cells to communicate with one another, called gap junctions. Gap junctions allow electric current to flow directly from one cell to another, without involving the release and diffusion of transmitter chemicals, and may be thought of as short circuits linking or cutting across the pathways through which cells normally communicate.

Gap junctions are found in many parts of the body, such as the heart. Gap junctions between nerve cells have been most studied in older vertebrates (such as fish) and in invertebrates (such as leeches and crabs); additionally, gap junctions in mammals have been studied that exist between nerve cells that produce inhibition that is, between cells that are not primarily involved in epileptic seizures. Gap junctions between excitatory cells in the mammalian brain have not traditionally been part of the thinking of neuroscientists.

One source of the idea that gap junctions were vitally important in epilepsy came from observations of brain waves that are recorded just before a seizure begins: these waves can occur at very high frequencies, 100 times per second or even more. That observation, and other experiments performed in Europe starting 10 years ago, led one of the authors of the PNAS article (Roger Traub, at SUNY Downstate) to propose a novel hypothesis: that excitatory nerve cells the cells most critical in the generation of epileptic seizures are also coupled together by gap junctions; that is, gap junctions are not confined to the cells that produce inhibition. Furthermore, gap junctions between excitatory cells were predicted to occur at an unexpected place: the axons of the cells (the axon is the part of the cell that allows propagation of a signal over long distances).

Such an hypothesis was naturally controversial. Scientists wanted to see these proposed gap junctions. But the gap junctions are tiny, and seeing them requires the use of an electron microscope, an instrument able to resolve structural details that are smaller than the wavelength of visible light details on the scale of tens of Angstroms (an Angstrom is roughly the diameter of a hydrogen atom). Application of the electron microscope to examine tiny structures in nerve cells is a special interest of Dr. Patrick Hof of the Mount Sinai School of Medicine, another of the PNAS authors. Furthermore, in the study of gap junctions, use of the electron microscope is often joined with chemical (antibody) techniques that allow one to determine which proteins are present within the junctions. Such techniques were pioneered by Dr. John Rash of Colorado State University, and applied by Dr. Naomi Kamasawa in Dr. Rashs laboratory: both are also authors of the PNAS article.

The PNAS article by Hamzei-Sichani et al. provides the first electron microscopic evidence (or ultrastructural evidence) for gap junctions on the axons of excitatory nerve cells in the mammalian brain. Gap junctions at this site, on axons, would be expected to act as short circuits for nerve signals and to produce cross-talk. The new data raise the provocative question as to whether cross-talk is an aspect of normal brain function.

What are the implications for epilepsy First, more needs to be learned about the distribution of gap junctions what nerve cells have them, where on the cells are they located, and how are they controlled (i.e. can the gap junctions be opened or closed by chemical signals) Second, more needs to be learned about exactly how gap junctions contribute to the very fast brain waves that can presage a seizure. And finally, it needs to be determined if attenuating or preventing these very fast brain waves can prevent seizures. As is virtually always the case in biomedicine, each discovery creates the need for more experiments.

What is clearly the case, however, is that a whole new direction is opening up in understanding the origins of epilepsy, and in conceiving of new approaches to treatment and prevention.

* The classic model of how brain cells communicate was put forth in 1943 by Warren McCulloch and Walter Pitts, at the time the first digital computers were being envisaged, and the McCulloch-Pitts model suggested that brain cells communicate in a binary fashion, represented by a 1 for firing and a 0 for not firing, much as a modern computer functions.

While it is common to say that a mammalian brain functions like a computer, this is a somewhat faulty idea, in part because the observation from the Traub lab suggests that gap junctions cause short circuiting as part of the brains normal functions. (A real computer could not function if it short circuited.) It is possible that these short circuits in the mammalian brain generally enhance brain function and adaptation to the environment, such as by permitting creative thinking, the combining of isolated facts into new ideas.

Additionally, Dr. Jeremy Coplan, a professor of psychiatry at SUNY Downstate - has proposed that excessive firing of these circuits along gap junctions may play a role in psychosis and mania.

Bak protein sets stressed cells on suicide path, researchers show

Thu, 12 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) When a cell is seriously stressed, say by a heart attack, stroke or cancer, a protein called Bak just may set it up for suicide, researchers have found.

In a deadly double whammy, Bak helps chop the finger-like filament shape of the cells powerhouse, or mitochondrion, into vulnerable little spheres. Another protein Bax then pokes countless holes in those spheres, spilling their pro-death contents into the cell.

We found out Bak has a distinct function in regulation of the mitochondrial morphology, says Dr. Zheng Dong, cell biologist at the Medical College of Georgia and the Veterans Affairs Medical Center in Augusta and corresponding author on a paper published this week in Proceedings of the National Academy of Sciences. Bax, on the other hand, is not involved in morphological regulation but needs to be there to puncture holes.

One has to break up, kind of soften, the mitochondria for injury, and the other one actually punches the holes to kill it, says Craig Brooks, MCG graduate student and the papers first author.

Bak and Bax have similar structures and scientists have long suspected they play major, similar roles in programmed cell death, or apoptosis. These two proteins are very important for mitochondrial injury and subsequent apoptosis, says Dr. Dong.

To stress cells, they blocked oxygen supplies and used the common chemotherapeutic agent cisplatin, then documented that filamentous mitochondria became fragmented very early and quickly in apoptosis. Ironically they also found the deadly fragmentation results from Baks interaction with mitochondria-shaping proteins called mitofusins, which help mitochondria keep their filamentous shape in non-stressed cells. Dr. Dong suspects Bak may also play a role in mitofusin regulation in normal, non-stressful conditions.

In fact, the researchers suspect Bak, Bax and the contents they spill into the cell all have roles in keeping a cell functioning until a stressor kicks in.

They probably are both kept in check normally in the cell by other proteins, and when something happens that overwhelms the cell, it activates Bak and Bax to start cell death, says Mr. Brooks. Some of the same proteins, cytochrome c is the big one, are needed for daily mitochondrial function like making energy, but if they are released from the mitochondria, they activate a cell killing or apoptotic pathway, says Dr. Dhong, referencing the contents that spill from punctured mitochondria.

Looking at kidney cells and neurons in a Bak deficient mouse, they also showed that Bak and Bax need each other to successfully spawn cell suicide. If you have Bak but not Bax, the mitochondria still fragment but they dont die; if you have Bax but not Bak, you still have punctures in the mitochondria but with low efficiency, says Mr. Brooks.

Now they want to know exactly how Bak interacts with mitofusins, how the interaction is regulated and how it affects mitochondrial morphology, physiology and pathology. Their long-term goal for better understanding the cell suicide mechanism is developing drugs to block it in the case of a stroke, for example, or induce it to kill cancer.

Scleroderma outlook improves as survival increases

Thu, 12 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Washington, D.C. -- Individuals with scleroderma are living significantly longer today, compared with 30 years ago, and the physicians who treat this rare disease of connective tissue hope the newer drugs now on the market may extend lives even further.

Scleroderma, a rare autoimmune disorder of unknown origin, results when collagen builds up in the bodys connective tissue and causes thickening of the skin. In the chronic and often progressive systemic form, scleroderma causes stiff joints and hardening of the internal organs and blood vessels.

In the July issue of the journal Annals of the Rheumatic Diseases, Georgetown University Medical Center professor Virginia Steen, M.D., studied 2,000 patients with scleroderma (also known as systemic sclerosis) treated between 1972 and 2001 at the University of Pittsburgh and found that 10-year survival steadily improved over those years by 12 percent-- from 54 percent to 66 percent.

This is really good progress, which we hope to improve upon, said Steen, a leading expert on the disorder who has helped make Georgetown University Hospital a national treatment center for scleroderma. In the 1980s, while at the University of Pittsburgh, she developed a natural history database of scleroderma patients and this database has continued to evolve into the largest in the United States.

The reason overall mortality has dropped, Steen says, is partly because a class of medications, angiotensin converting enzyme (ACE) inhibitors became available which dramatically improved the treatment of renal crisis. Renal crisis used to be almost always fatal and now it is a very treatable complication of scleroderma, she said. Now pulmonary arterial hypertension and pulmonary fibrosis, a condition that is traditionally the second-most frequent cause of death, is responsible for most of the mortality, but these conditions may be increasingly treatable, she said. Patients may develop either disorder, or both.

Before, it was kidney and then lung disorders that affected most of our patients, and now that we have successfully treated the kidneys, mortality due to lung disease has become the issue, Steen said. We are working on ways to use the newer medications to help treat these disorders, hoping to further improve overall survival.

While all scleroderma-related disorders are believed to affect as many as 900,000 people in the United States, only between 40,000 and 165,000 are diagnosed with systemic scleroderma, according to the National Institutes of Health (NIH). Like all scleroderma disorders, systemic scleroderma affects more women than men, and varies in severity.

In this study, Steen collaborated with co-author Thomas Medsger, M.D., professor of medicine at the University of Pittsburgh to study patients with systemic scleroderma enrolled in the registry. They studied patients evaluated at the University of Pittsburgh between 1972 and 2001, dividing them into five-year time periods, depending on when they were seen.

They found survival improved in each of the five-year periods, and that the frequency of death due to renal crisis significantly decreased over the 30 years, from 42 percent to 6 percent. But the proportion of patients who died from pulmonary fibrosis increased from 6 percent to 33 percent, Steen said. The frequency of pulmonary hypertension also increased, but there was no change in gastrointestinal and heart-related deaths.

Use of ACE inhibitors made all the difference in saving patients from renal failure, and now it is important that physicians use drugs now available to treat lung disorders and researchers continue to search for new therapies, Steen said.

More muscle for the argument to give up smoking

Mon, 09 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers at The University of Nottingham have got more bad news for smokers. Not only does it cause cancer, heart attacks and strokes but smokers will also lose more muscle mass in old age than a non-smoker. The effect of this predisposes smokers to an accelerated decline in physical function and loss of independence.

Research has already established that smokers tend to have a lower muscle mass than non-smokers but no one has been able to explain why.

Now, Michael Rennie, a Professor of Clinical Physiology, and Dr Philip Atherton, a Research Fellow, both from the universityï¿½s School of Graduate Entry Medicine and Health at Derby, have, with collaborators in Denmark and the USA, discovered that smoking impairs the day to day upkeep of muscle. Their research shows that smoking is likely to speed up a condition known as sarcopenia ï¿½ the loss of muscle mass with ageing which is linked to poor balance, gait speed, falls, and fractures.

16 people took part in the study which was part funded by the Biotechnology and Biological Sciences Research Council. The men and woman in their mid sixties were selected because of their similar lifestyles in terms of alcohol consumption and physical activity. They were all considered to be healthy, with no symptoms of lung disease. They were studied in two equal groups: heavy smokers, who had smoked at least a pack of 20 cigarettes a day for at least 20 years: and non-smokers.

To measure the synthesis of muscle protein they were given an intravenous infusion of blood with a tagged amino acid (one of the building blocks of protein). Samples of muscle were taken from their thighs before and after the infusion to follow how much had ï¿½stuckï¿½ in muscle protein. This measured the rate of synthesis of muscle protein which contributes to the daily maintenance of the muscle mass. The researchers found that it was substantially less in smokers than non-smokers.

During extensive studies, carried out in collaboration with Washington University, St Louis and Copenhagen University, Professor Rennie and Dr Atherton discovered that the amounts of myostatin, a muscle growth inhibitor and MAFbx enzyme, which breaks down muscle protein, were higher in smokers than non-smokers.

Dr Philip Atherton said: ï¿½From our tests, we can conclude that smoking slows the muscle protein synthesis machinery ï¿½ probably impairing day to day upkeep of muscle. We are all well aware of the ill affects of smoking on the lungs but our study reveals yet another cause of ill-health associated with smoking. Hopefully the UK smoking ban will encourage people to quit while they are still young, helping them to keep in good health in later lifeï¿½.

First all-African produced genetically engineered maize is resistant to maize streak virus

Sun, 08 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Maize streak viruses (MSV), geminiviruses that can destroy most of a maize crop, are endemic to sub-Saharan Africa and adjacent Indian Ocean islands where they are transmitted by leafhoppers in the genus Cicadulina. Maize can supply 50% of the caloric intake in sub-Saharan Africa but, in certain years, a farmers entire crop can be wiped out. Now, scientists at the University of Cape Town, South Africa, along with colleagues at the South African seed company, PANNAR Pty Ltd, have developed a resistant variety of maize that they hope will help alleviate food shortages as well as promote the reputation of genetically engineered (GE) foods in Africa. Dr. Dionne Shepherd of the University of Cape Town will be presenting the results of her recent work and that of coauthors B. Owor, R. Edema, A. Varsani, D.P. Martin, J.A. Thomson and E.P. Rybicki, at the annual meeting of the American Society of Plant Biologists in Chicago (July 8, 11:20 AM) in a major symposium on Plant Biology in Sub-Saharan Africa organized by Debby Delmer of UC Davis.

Maize, which originated in Mexico, was carried to Africa in the 1500s and eventually displaced native food crops such as sorghum and millet. Maize streak virus, an endemic pathogen of native African grasses, was then carried to maize plants by viruliferous leafhoppers. African scientists have been working for more than a quarter century on developing resistant varieties of maize by selecting and crossing varieties with various degrees of resistance to the virus.

However, resistance requires multiple genes located on different chromosomes, so the process is not straightforward. The group at the University of Cape Town took the opposite approach. They mutated a viral gene that encodes a protein that the virus needs to replicate itself and inserted it into maize plants. When the virus infects one of these transgenic maize plants, the mutated protein, which is expressed at a high level, prevents the virus from replicating and killing the plant. The transgenic maize variety has proven consistently resistant to MSV and the trait can be reliably passed on to the next generation and in crosses to other varieties. Field trials are scheduled to begin soon, not only to test the effectiveness of the technology in the field but also to ensure that the GE maize variety has no unintended effects on beneficial organisms that may feed on it. The resistant maize will also be tested to ensure that the viral protein is digestible and non-allergenic. The MSV-resistant maize is the first GE crop developed and tested solely by Africans.

This group of scientists also surveyed 389 Ugandan MSV isolates to assess the diversity and genetic characteristics of this destructive pathogen. They found that the most prevalent strain of this virus is a product of recombination of different viral genotypes, thus identifying an important source of new pathogenic variants and illustrating the constantly changing evolutionary battle between plants and pathogens. MSV was first sequenced in 1984 and found to contain a genome of only 2700 DNA bases in a circle of single-stranded DNA. When it infects susceptible plants, they produce deformed cobs and are often severely dwarfed. As the name of the virus suggests, the leaves are marked with parallel, yellow-white streaks.

The timing of infection, the maize genotype, and prevailing climatic conditions can all influence the extent of damage wreaked by this viral pathogen. Young plants cannot survive the infection but older plants are better able to contain the infection, resulting in smaller losses of grain. However, drought can have a devastating effect on maize fields over a wide geographical area. Under warm and wet conditions, a long-bodied morph of the leafhopper C. mbila emerges, but this form only travels short distances of 10 meters or less, thus limiting its damage to crops. Under drought conditions, a stronger, short-bodied morph that can fly great distances spreads the disease over large areas, thus exacerbating the effects of the drought itself.

Disease caused by similar geminiviruses, Wheat dwarf virus (WDV) and various sugarcane streak viruses, also affect other crops, including barley, wheat, oats, sugarcane, and millet. Thus, the technology developed for MSV could potentially be adapted to develop resistance in these other crops. Virologist Edward Rybicki and microbiologist Jennifer Thomson are hopeful that this years field trials will demonstrate not only the effectiveness of this technology in producing resistance to a destructive pathogen but also the safety of GE foods. Part of the objective is to provide seed that will be sold at a minimal profit to subsistence farmers, thus removing the objection that GE technology is principally profit-driven.

A gene that protects from kidney disease

Sun, 08 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Researchers from the European Molecular Biology Laboratory (EMBL) and the University of Michigan have discovered a gene that protects us against a serious kidney disease. In the current online issue of Nature Genetics they report that mutations in the gene cause nephronopthisis (NPHP) in humans and mice. NPHP is a disease marked by kidney degeneration during childhood that leads to kidney failure requiring organ transplantation. The insights might help develop effective, noninvasive therapies.

The kidneys are the organs that help our body dispose of potentially harmful waste. Diseases that affect this fundamental function are very serious but so far only poorly understood. NPHP is such a disease; it causes the kidneys to degenerate and shrink starting early on in childhood often leading to renal failure before the age of 30. So far, kidney transplantation in early age has been the only way to save patients suffering from NPHP. With a new mouse model Mathias Treier and his group at EMBL have shed new light on the molecular mechanisms underlying NPHP opening up novel ways to treat the disease.

Our mice show striking similarities with NPHP patients, says Mathias Treier, group leader at EMBL. Very early on in their lives their kidney cells start to die and the mice develop all the characteristic disease symptoms. It is the first time that a mouse model reveals increased cell death as the mechanism underpinning kidney degeneration in NPHP. The genetic cause is a mutation in a gene called GLIS2.

GLIS2 normally prevents cell death in the adult kidney. It does so by shutting down genes that initiate cell death and that are only required during the development of the organ. A mutation interfering with GLIS2 function reactivates these harmful genes the result being that large numbers of kidney cells die. The organ shrinks and changes in its architecture occur which affect normal kidney function.

To find out if GLIS2 has the same effect in humans Friedhelm Hildebrandt and his team at the University of Michigan carried out a genetic screen of patients suffering from NPHP. They found that like the mouse model some patients carried mutations in the same GLIS2 gene, confirming that GLIS2 is a crucial player in NPHP also in humans.

This is an excellent example of how combining basic research with clinical studies can help uncovering mechanisms of human disease, says Henriette Uhlenhaut who carried out the research in Treiers lab. The next step will be to translate the insights gained into new therapeutic approaches to develop alternatives to kidney transplantations. With GLIS2 we have already identified one promising candidate drug target and our mouse model will help us find many others.

Rapid evolution of defense genes in plants may produce hybrid incompatibility

Sun, 08 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) One of the basic tenets of evolution is speciation in which populations of the same species become so genetically and morphologically variable that they can be classified as two different species. Individuals of these species may be capable of mating, but they may not produce offspring, and if offspring are produced, they will be sterile or so defective that they die before they are able to reproduce. Although speciation has been observed and studied since Darwin and Wallace first proposed their theory, the complex molecular mechanisms responsible are not yet fully known. One of these molecular mechanisms, hybrid necrosis, was studied by Dr. Detlef Weigel and his colleagues at the Max Planck Institute for Developmental Biology in Germany. Dr. Kirsten Bomblies will present their results at the Presidents symposium at the annual meeting of the American Society of Plant Biologists (July 11, 2PM). Bomblies and Weigel observed hybrid necrosis in crosses of thale cress, Arabidopsis thaliana, a member of the mustard family, and found that it is associated with plant genes that respond to pathogen attack.

Plants must frequently cope with environmental stresses such as heat, cold, high acidity or salinity, or attack by pathogens such as viruses or insect predators. Such stresses mobilize defense genes that initiate physiological responses that help the plants to survive. One such response is programmed cell death, which occurs in response to invasion by viruses or bacteria. The cells invaded by the pathogens are quickly marked by the plant for death so that the microbe cannot use them to replicate and spread to the rest of the plant. These types of genes have been shown to evolve rapidly, giving plants the capability to adapt to changing conditions and pathogens. Bomblies and Weigel found that the same type of gene is involved in hybrid incompatibility in Arabidopsis. Because these genes evolve so rapidly, there are likely to be different forms present in the population, and when two of these are joined in a hybrid, they can cause fatal defects in the hybrid offspring.

A biological species is defined as a population of individuals that can interbreed among each other freely, but not with members of other species. What finally establishes two populations as different species is that gene flow between them stops. However, this does not happen suddenly. Rather, it is a gradual process in which one barrier after another is raised between two species, including inviable embryos and defective and sterile adults, as well as genetic incompatibilities that prevent even the formation of an embryo. The hybrid incompatibility identified by Bomblies and Weigel is an example of the kind of genetic incompatibility that can result in speciation.

Because plant reproduction often requires an outside agent like a pollinator or the wind, which spreads pollen far from the parent plant, the offspring can be hybrids between parents from two different populations or even from two different although closely related species. Such hybrid offspring can be successful but may also be prevented or defective because some of the parents genes are not compatible. In their survey of 900 first generation hybrid offspring among 293 strains of thale cress, Bomblies and Detlef found that 2% of the offspring were severely defective. They call this phenomenon hybrid necrosis or hybrid weakness, and identified the gene responsible for the incompatibility as a disease resistance gene that has different forms in the two parents.

Some of the molecular mechanisms that prevent hybridization between species are well-known in both animals and plants. There are a number of gene flow barriers in plants that are similar to those of animalsamong them are ecological factors such as reproductive season, morphological differences, and hybrid sterility. However, hybrid necrosis produced by autoimmune responses due to pathogen resistance genes has not been observed in animals and may represent a molecular pathway to speciation unique to plants. Knowledge of these mechanisms is important not only in the study of the evolutionary history of plants but can also provide tools for ensuring the safety of genetically engineered crops. If incompatibility genes can be bred into a GE crop, it might be possible to prevent the formation of superweeds and to lessen the probability that harmful genes can be spread to other species.

Research suggests fitness reduces inflammation

Fri, 06 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Although a number of studies have suggested that regular exercise reduces inflammation a condition that is predictive of cardiovascular and other diseases, such as diabetes it is still not clear whether there is a definitive link. And if such a link exists, the nature of the relationship is by no means fully understood.

A recent study by kinesiology and community health researchers at the University of Illinois provides new evidence that may help explain some of the underlying biological mechanisms that take place as the result of regular exercise.

According to the researchers, that knowledge could potentially lead to a better understanding of the relationship between exercise and inflammation.

The objective of their research was to examine the independent effect of parasympathetic tone in this case, determined by assessing heart-rate recovery after exercise on circulating levels of C-reactive protein (CRP). Parasympathetic tone and its inverse function sympathetic tone are components of the autonomic nervous system. CRP, which is secreted by the liver, circulates in the bloodstream and is a biomarker for inflammation in the body.

The sympathetic nervous system speeds things up, and the parasympathetic slows things down, said Victoria J. Vieira, a predoctoral fellow in kinesiology and community health and in nutritional sciences, and the primary author and designer of the study, published in a recent issue of the Journal of the American Geriatrics Society. So when youre exercising, your sympathetic nervous system will be on, increasing your heart rate, your respiration, etc. Once you stop, your body always tries to get back to homeostasis. So the parasympathetic nervous system kicks in to get everything back down to baseline levels.

Co-author and kinesiology and community health professor Jeffrey A. Woods said cardiologists are already routinely gauging CRP levels in much the same way they look at lipids panels to assess cholesterol levels.

Certainly, thats being done in the cardiovascular disease realm, but I think (it may be effectively used as a monitor) for other diseases, such as Alzheimers, diabetes and metabolic syndrome, he said.

Woods said the main question motivating the current research was, What factors are related to CRP in the elderly

Weve known that as people age, their CRP levels go up, Vieira said. Thats one of the reasons why older individuals are more prone to develop inflammation-related diseases such as diabetes and heart disease. So we just wanted to look at whats predicting those levels of CRP in an average older population that is relatively healthy.

Perhaps the most notable result of the study, according to the researchers, relates to heart-rate recovery following exercise.

The quicker the individuals were able to get back to their resting heart rate after a strenuous exercise test was inversely related to their CRP, Vieira said. In other words, individuals who had better parasympathetic tone had lower levels of inflammation.

And the reason were excited about this is that exercise is a great way to improve parasympathetic tone. When you exercise that is the sympathetic/parasympathetic communication your sympathetic goes up, and when you stop exercising, your parasympathetic kicks in to bring you back to normal. An untrained person will take a while to get their heart rate back down to resting. A trained persons heart rate will come back down very quickly.

The cross-sectional study focused on baseline test results from 132 sedentary, independently living individuals aged 60 to 83 (47 males; 85 females) who had been recruited to participate in the Immune Function Intervention Trial (ImFIT), a randomized longitudinal trial designed by Woods and funded by the National Institute on Aging to examine the relationship between exercise and immune function.

Participants included only individuals who did not take medications that included corticosteroids, which could interfere with immune measurements. Smokers and/or those with severe arthritis, a history of cancer or inflammatory disease, chronic obstructive pulmonary disorder, uncontrolled diabetes mellitus, congestive heart failure, recent illness or vaccination, or a positive stress test were excluded.

The physical fitness of subjects was assessed through a battery of tests that measured such variables as fatigue, blood pressure, oxygen intake and carbon dioxide elimination and heart-rate recovery in conjunction with exercise on a walking treadmill. Tests also were administered to determine the subjects levels of physical activity, physical fitness, emotional stress and body composition (bone density and body fat). Blood samples also were drawn to measure CRP levels.

The major criterion we were looking at was their fitness level, Vieira said. A strength of our study is that we have very good data on their fitness levels.

And while other studies have explored the relationship between exercise and inflammation, another unique aspect of the U. of I. research, Vieira said, is that no other studies have adjusted for fitness and body fat percentages simultaneously to really get at that question, Is exercise independently reducing CRP levels, or is it modulated through a decrease in adiposity (body fat)

Because the study was cross-sectional meaning the researchers essentially took a snapshot of the participants reactions and measurements at a single, fixed point only Vieira said it was important to note that we cant say anything about cause and effect relationships.

However, Woods said, it gives you some idea of what factors are related, and then you test those in a more rigorous manner.

Vieira said the research certainly suggests that fitness may be associated with a decrease in inflammation even independent of body fat and several things, and the mechanism may involve a parasympathetic anti-inflammatory reflex.

We know inflammation is bad. We know it increases as we age, with stress and other things, she said. So if we can decrease that to protect ourselves somehow by just adopting a physically active lifestyle, thats definitely an advantage.

And while the study confirms the conclusions of previous research by others indicating that high body fat is related to high inflammation and high fitness to low inflammation, the unique part of this paper is that controlling for those, we also show that high parasympathetic tone is related to low inflammation, Woods said.

And its even independent of their fitness level, Vieira interjected.

Fitness, fatness and parasympathetic tone appear to be important, Woods said, summing up the findings. And at least according to our results, parasympathetic tone might even be more important than those other factors.

Illinois researchers presenting at ASPB Annual Meeting in Chicago, July 7-11

Fri, 06 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Leading scientists at research institutions in Chicago and across Illinois will be presenting research findings at the American Society of Plant Biologists (ASPB) annual Plant Biology meeting in Chicago (July 7-11). ASPBs meeting will be held as a Joint Congress in conjunction with the annual meetings of the American Fern Society (AFS), the American Society of Plant Taxonomists (ASPT), and the Botanical Society of America (BSA).

This Joint Congress will include several hundred exhibits, scientific sessions and events. Attendees from all of these societies will participate in each others events. Such cross-pollination of ideas and debate will inform and catalyze development across over 40 different plant science research areas.Presenters include scientists from the University of Chicago, the University of Illinois and Southern Illinois University. Their findings will include information on improved plant genome measurement technologies, plant cell-to-cell signaling, and plant reproduction, physiology and metabolism.

Five important studies that will be presented at the meetings were conducted by University of Chicago researchers in conjunction with research partners from other national and international labs. Three of these Chicago-based studies focus on new and innovative plant genome technologies. The first study was managed by Justin Borevitz of University of Chicagos Ecology and Evolution Department. Borevitz and several colleagues created a presentation based on their paper entitled Detecting Circadian Clock Regulated Transcription using Genome Tilting s. Their work will be presented by Sam Hazen on July 8th. Borevitz also will join Xu Zhang and Jake Byrnes, two more of his co-researchers who are also from Chicago, to present on July 8th their findings from their Survey of splicing variation and allele specific expression in natural accessions of Arabidopsis thaliana using SNP-tilting array. Rick Williams, also a University of Chicago Ecology and Evolution lab researcher, completed research with several local and nationally-based colleagues on another application using tilting arrays. Their paper which will be presented on July 8th is called Deletion and Duplication Detection in Arabidopsis using Tilting s. Williams can be reached at

Cell-to-cell and long-distance plant signaling are the key topics of the work done by University of Chicagos Karen Deak and Jocelyn Malamy. This presentation slated for July 8th is based on their paper Long Distance Signals Regulate Lateral Root Emergence in Arabidopsis thaliana. Deak can be reached at

Kiera von Bessar of the University of Chicagos Department of Molecular Genetics and Cell Biology teamed with other pollen biology experts to prepare a presentation for July 9th on Arabidopsis reproduction. The Arabidopsis plant is well-represented in this group of studies because it is of particular interest and usefulness to plant scientists due to its quick growth and reproduction cycles and simple genome.

The University of Illinois also will post five research studies from various plant science labs at the Joint Congress. Two of these University of Illinois-based studies, are extensively described in separate news releases, Elevated CO2 in Atmosphere Weakens Defenses of Soybeans to Herbivores and Ilinois-based Study of Energy Crops Finds Miscanthus More Productive than Switchgrass. These news releases can be requested from Katie Engen at

A presentation from University of Illinois researchers is based on a paper about secondary metabolism co-authored by Sanjeewa G. Rupashinge and Mary A. Schuler. They will present their three-dimensional model of plant structures used for metabolism on July 10th. Mary Schuler can be reached at

Robert Coates of University of Illinois Department of Chemistry joined Aldwin Anterola, Erin Shanle, Katayoun Mansouri, Scott Schuette, Romina Vidal-Russell and Karen Renzaglia all of Southern Illinois Universitys Department of Plant Biology to explore plant development and physiology. On July 10th this group will share their findings on the science behind using moss bryophytes to better understand plant evolution. Anterola can be reached at

Faulty cell membrane repair causes heart disease

Tue, 03 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) During vigorous exercise, heart muscle cells take a beating. In fact, some of those cells rupture, and if not for a repair process capable of resealing cell membranes, those cells would die and cause heart damage (cardiomyopathy).

Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine have discovered a specific repair mechanism in heart muscle and identified a protein called dysferlin that is critical for resealing heart muscle cell membranes.

The study, led by UI researcher and Howard Hughes Medical Institute investigator Kevin Campbell, Ph.D., also shows that loss of dysferlin causes cardiomyopathy in mice. Furthermore, heart damage in these mice is exaggerated by vigorous exercise or by inherent muscle weakness caused by a muscular dystrophy defect. The results are published in the July 1 issue of the Journal of Clinical Investigation.

Active tissues, like a beating heart or contracting muscle, need mechanisms to repair the inevitable cell membrane tears caused by physical stress and strain. In 2003, Campbell and his colleagues identified dysferlin as a key protein in this vital repair mechanism in skeletal muscle. In humans, dysferlin deficiency -- which leads to faulty muscle membrane repair -- causes three types of muscular dystrophy.

The new study expands knowledge of dysferlin function, showing that dysferlin-mediated membrane repair is also important in heart muscle cells and suggests that inadequate membrane repair can also lead to cardiomyopathy.

If we could boost this repair mechanism, it might be possible to slow cardiac and skeletal muscle damage in muscular dystrophy patients, said Campbell who also holds the Roy J. Carver Biomedical Research Chair in Molecular Physiology and is head of the department and a UI professor of neurology.

The UI team initially found that young mice that lacked dysferlin showed no heart damage, which is consistent with what is seen in humans with dysferlin mutations. However, a case study describing late-onset cardiomyopathy in a Japanese patient with a dysferlin deficiency prompted the UI team to look at the mice as they aged.

They found that the mice started to develop cardiomyopathy at about one year of age (middle aged for a mouse). The team also found that exercise exaggerated the stress-induced injury in these mice, suggesting that inadequate membrane repair led to cardiomyopathy.

The research team also bred mice that lacked both dysferlin and the protein dystrophin, which is missing in patients with Duchenne muscular dystrophy. These double knockout mice had early onset cardiomyopathy, which was much more severe than in mice with either of the single mutations. The results suggest that dysferlin might provide some protection against heart damage in Duchenne patients, at least at a young age, by delaying the onset of cardiomyopathy.

We hope these findings will stimulate clinicians to look at the cardiac health of muscular dystrophy patients and the overall muscle health of patients with cardiomyopathy, Campbell said.

Chronically sleep deprived? You can't make up for lost sleep

Mon, 02 Jul 2007 03:59:37 PST

( from http://www.rxpgnews.com ) EVANSTON, IL -- Weve all experienced that occasional all-too-short night of sleep -- staying out too late at a party on a weeknight, studying into the wee hours for a morning exam or being kept up during the night with a sick child. Our bodies try to catch up by making us sleep more and/or more deeply the following night.

It is well established that following an acute period of sleep loss, the body responds this way in order to maintain a homeostatic balance between sleep and wakefulness. Very little is known, however, about the health consequences of chronic partial sleep loss -- losing a little bit of sleep over a period of days, months or even years.

Now sleep researchers at Northwestern University have discovered that when animals are partially sleep deprived over consecutive days they no longer attempt to catch up on sleep, despite an accumulating sleep deficit. Their study is the first to show that repeated partial sleep loss negatively affects an animals ability to compensate for lost sleep. The body responds differently to chronic sleep loss than it does to acute sleep loss.

The results, which shed light on a problem prevalent in industrialized nations with 24/7 societies such as the United States, where Americans get nearly an hour less sleep a night than they did 40 years ago, were published online recently by the Proceedings of the National Academy of Sciences (PNAS).

We now know that chronic lack of sleep has an effect on how an animal sleeps, said Fred W. Turek, professor of neurobiology and physiology and director of Northwesterns Center for Sleep and Circadian Biology and an author of the paper. The animals are getting by on less sleep but they do not try and catch up. The ability to compensate for lost sleep is itself lost, which is damaging both physically and mentally.

In the study, the researchers kept animals awake for 20 hours per day followed by a four-hour sleep opportunity, over five consecutive days. The team monitored brain wave and muscle activity patterns in order to precisely quantify sleep-wake patterns.

After the first day of sleep loss, animals compensated by increasing their intensity, or depth, of sleep, which is indicative of a homeostatic response. However, on the subsequent days of sleep loss, the animals failed to generate this compensatory response and did not sleep any more deeply or any longer than they did under non-sleep deprived conditions (baseline measurements). At the end of the study, the animals were given three full days to sleep as much as they wanted. Amazingly, they recovered virtually none of the sleep that was lost during the five-day sleep deprivation period.

The findings support what other scientists have discovered in recent experimental studies in humans. Chronic partial sleep loss of even two to three hours per night was found to have detrimental effects on the body, leading to impairments in cognitive performance, as well as cardiovascular, immune and endocrine functions. Sleep-restricted people also reported not feeling sleepy even though their performance on tasks declined.

The Northwestern teams results suggest that animals may undergo a change in their need for sleep, or in their sleep homeostat, in situations where normal sleep time is prohibited or where sleep could be detrimental for survival. An extreme but realistic example of this, says Turek, would be how animals respond to catastrophic environmental conditions, such as Hurricane Katrina. No matter how sleep deprived an animal or human may be, it would not be adaptive for the sleep homeostat to kick in and to make the animal fall sleep when it is in the midst of a flood or forest fire. Therefore, the body undergoes some change that allows it to counter its homeostatic need for sleep and to stay awake to avoid danger.

Turek and his team propose that this change in the sleep regulatory system is reflective of an allostatic response. In the short term, allostatic responses are adaptive, but when sustained on a chronic basis, such as in their study, an allostatic load will develop and lead to negative health outcomes. The allostatic load resulting from the accumulating sleep debt loops back to the sleep regulatory system itself and alters it.

Even though animals and humans may be able to adapt their sleep system to deal with repeated sleep restriction conditions, there could be negative consequences when this pattern is maintained over a long period of time, said Turek. This brings us back to the idea that repeated partial sleep restriction in humans has been linked to metabolic dysfunction and cardiovascular disease.

Our lab is very interested in the interactions between sleep loss and metabolic function, said Aaron D. Laposky, research assistant professor at the Center for Sleep and Circadian Biology and an author of the paper. As Americans have been getting less sleep per night, there has been a parallel trend for body mass index to significantly increase. We believe that when partial sleep loss occurs repeatedly over a long period of time, individuals are predisposed to alterations in the function of many physiological systems.

Key to male infertility

Fri, 29 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) A factor in immune cells regulates human semen and seems to determine whether a man will be fertile, according to a new study.

Yousef Al-Abed, PhD, and his colleagues at The Feinstein Institute for Medical Research have isolated an immune substance called macrophage migration inhibitory factor (MIF) in semen samples from infertile and reproductively healthy men. MIF is key to helping sperm mature, which is necessary for its union with an egg. The finding could lead to a diagnostic test to determine fertility status.

The study appears in the latest issue of Molecular Medicine. The semen samples were collected from men three to five days after a period of sexual abstinence. The scientists had no idea when analyzing levels of MIF whether the sample came from any of the 68 men who had problems conceiving or from the 27 healthy controls. The findings have a Goldilocks kind of quality: Those with infertility problems had MIF levels that were either too high or too low. Those who had no problems conceiving had levels that were just right.

When the scientists added MIF into lab dishes filled with healthy sperm, it decreased the count and impaired their motility.

If MIF has a role in infertility, Dr. Al-Abed and his colleagues are wondering whether it might just work as a form of male contraception. In the meantime, the scientists have a patent on an assay that can be used to analyze MIF levels to help determine whether a man will have problems conceiving. About 15 percent of couples attempting to get pregnant for the first time have problems conceiving. About 40 percent of infertility problems are due to disorders in the male.

MIF is a key player of the immune system. MIF was identified 40 years ago but it was only recently that scientists discovered its role as a pro-inflammatory substance. MIF has now been linked to many autoimmune and inflammatory diseases - such as diabetes and sepsis - and Al-Abed, an organic chemist by training, has been trying to identify and design small molecules that would block MIF activity.

The Feinstein researchers recently identified a critical area on the MIF protein surface that is crucial for the inflammatory response. Such a substance designed to target this area could be used to treat a variety of conditions, including septic shock, sepsis, rheumatoid arthritis and diabetes. The team designed a specific inhibitor called ISO-1 to fit into this pro-inflammatory site. In an animal model of sepsis, ISO-1 abolishes MIFs potent inflammatory abilities and the animals respond dramatically. They lived through the once-fatal sepsis.

In patients in the throes of sepsis - an over-reactive and potentially fatal immune response to a bacterial infection - MIF concentrations are 10 to 20 times higher than normal. If MIF goes down, the chance that patients will survive sepsis is increased dramatically. The idea is to suppress inflammation so that cells stop producing MIF, said Dr. Al-Abed.

Every year, 215,000 Americans die of sepsis, a systemic inflammatory reaction to infection. Another 500,000 survive the infection, and scientists are still trying to figure out why these patients survive and others dont. There are no treatments for this massive all-out war on the body. Those who survive often face serious cardiovascular problems. Scientists examining cardiac function during sepsis have identified macrophage migration inhibitory factor (MIF) as a key factor in heart damage. And antibodies targeted to MIF, so-called anti-MIF antibodies, significantly improves cardiac performance during septic shock.

MIF levels are also two times higher in autoimmune diseases like rheumatoid arthritis and diabetes. In the laboratory, Al-Abed and his colleagues found that having MIF on board in high amounts in animals prone to diabetes set the disease process in motion weeks earlier than expected. The team is now trying to design a clinical study to look at MIF levels in type 1, or juvenile, diabetes.

One thing has become clear about the MIF molecule: It needs a network. To act as a pro-inflammatory soldier, it relies on other substances to help. MIF on its own is not toxic, Dr. Al-Abed said. They are now trying to figure out what substances MIF partners with to do its dirty work.

Natural signal holds promise for psoriasis, age-related skin damage

Thu, 28 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) The body may hold a secret to normalizing skin cell growth that is over zealous in psoriasis and non-melanoma skin cancers and too slow in aging and sun-damaged skin, researchers say.

Phosphatidylglycerol, a natural body lipid or fat, appears to signal cells to normalize growth and maturation or differentiation. When we apply it to skin cells, we see the normalization ability, says Dr. Wendy B. Bollag, cell physiologist at the Medical College of Georgia.

Her research, published online in The Journal of Investigative Dermatology, helps piece together the signaling pathway that prompts skin cells to stop multiplying and start differentiating.

Perhaps most importantly it shows that bypassing that pathway one researchers suspect becomes dysfunctional in diseases like psoriasis and giving the signal itself restores normal differentiation of skin cells or keratinocytes.

The findings prompted Dr. Bollag and John Edwards, CEO of Apeliotus Technologies of Atlanta, to seek National Institutes of Health funding for yearlong study in animal models of mild psoriasis to see if it works, with human trials as the goal. Proof of principle is the first phase. If in vivo data looks promising, well put together a study we can take into the clinic, says Dr. Bollag. She and Apeliotus received an NIH Small Business Technology Transfer grant, which supports small businesses collaborating with U.S. research institutions to develop technologies and methodologies with commercial potential.

A Georgia Research Alliance Industry Partnership Grant will allow parallel studies in animal models of chronological aging and photoaging from too much sun exposure, Dr. Bollag says.

MCG and Apeliotus will work with Avanti® Polar Lipids, Inc., of Alabaster, Ala., which has a chicken-egg derived phosphatidylglycerol used primarily for lipid research. Avanti is developing different phosphatidylglycerol ointments or salves for the new studies. Dr. Bollag notes that the lipid, already used as drug-delivery mechanism in humans, has been ingested at higher doses, so she believes lower doses applied externally will be safe.

Glycerol, a precursor of phosphatidylglycerol, also is available commercially and used in many skin care products because its long been known to help skin retain moisture, so it looks and feels better. We think that, yes, its a water attractor, but we think it also has this additional role as a precursor for an important lipid signal in the skin, says Dr. Bollag. Naturally occurring glycerol is an important precursor for many things such as fat, phospholipids, various sugars and metabolic pathways in the body. Glycerol levels go up when you exercise, because you are using fats as fuel.

Shes shown that the channel, aquaporin-3, delivers glycerol to phospholipase D, resulting in the skin cell differentiation signal, phosphatidylglycerol. This is serving as a signal, like an elevator operator who says, This way for normal keratinocyte differentiation, says Dr. Bollag. Thats good because without it, you get abnormal differentiation in skin diseases like psoriasis, non-melanoma skin cancer, some of the dermatitises; in a lot of these conditions, the cells proliferate too much and dont differentiate properly. We think maybe in psoriasis, the phospholipase D and aquaporin-3 become disconnected so now they cant produce phosphatidylglycerol. If you only put glycerol on it, it may not help.

But it looks as though the signal does.

Her newest research, done in mouse skin cells in culture, showed that aquaporin-3 manipulation impacted phosphatidylglycerol generation. The glycerol was coming through aquaporin. If we blocked it, we stopped glycerol from coming through and we also blocked phosphatidylglycerol. Then we started manipulating the various players. We did some over expression of aquaporin and showed it promoted differentiated status of the keratinocytes.

Then we wondered what would happen if we actually gave phosphatidylglycerol itself, so we bypassed the whole aquaporin-phospholipase D system and we saw some interesting results.

Phosphatidylglycerol inhibited growth of rapidly growing skin cells and increased growth in slow-growing cells. MCG has a patent pending on the ability of phosphatidylglycerol to normalize skin cell function.

The key is cells are supposed to proliferate in this one layer, she says of the basal layer, where a skin cell divides, with one staying to divide again and the other expressing different genes, proteins and functions as it moves toward the surface. Without phosphatidylglycerol, cells can proliferate too much and differentiate improperly, Dr. Bollag explains.

Right before cells reach the layer that we actually see, called the cornified layer, they spit out lipids they synthesize to make the water permeability barrier then they basically die. But they leave behind these hard shells that give skin its mechanical strength. When you get older, you dont turn it over as well, Dr. Bollag says, explaining why despite ongoing cell turnover old skin looks, well, old.

As its name implies, aquaporin also transports water, but interestingly, researchers have learned its a lot better at delivering glycerol. Phospholipids are the fats that comprise most of the plasma membranes that encase cells. Skin cells secrete extra lipids to help provide the water permeability barrier that keeps organs and fluids inside where they belong as well as the mechanical barrier that protects the body from invaders. That would just kill a normal cell, but the skin can survive that, she says, plopping her elbow down on a table. Temperature regulation and sensation are two other major skin functions.

Type 1 diabetes and heart disease -- Heavier may mean healthier

Sat, 23 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO, June 23 -- Researchers at the University of Pittsburgh Schools of the Health Sciences studying links between an early sign of heart disease called coronary artery calcification and body fat have found that, paradoxically, more fat may have some advantages, at least for people particularly women who have type 1 diabetes. Cardiovascular complications, including heart disease, are a leading cause of death for people with diabetes, who tend to suffer cardiovascular disease decades earlier than non-diabetics.

Gaining weight may reflect good or better treatment with insulin therapy, which may partly explain why participants who gained weight over time had lower mortality rates, said Trevor Orchard, M.D., professor of epidemiology at the University of Pittsburgh Graduate School of Public Health (GSPH), who is presenting the findings during the 67th annual meeting of the American Diabetes Association. Scientific sessions take place June 22-26 at the McCormick Place Convention Center, Chicago.

For this particular report, Dr. Orchard and his colleagues focused on 315 patients with type 1 diabetes participating in the Pittsburgh Epidemiology of Diabetes Complications Study, an 18-year prospective study of childhood onset type 1 diabetes, which began in 1986. As part of the study, the patients recently received a special computed tomography scan (CT) to assess coronary artery calcification.

The participants mean age was 42, and mean duration of diabetes was 34 years. In addition to the CT scan, patients were evaluated for fat underneath the skin and in the abdominal region, body mass index (BMI) and waist circumference. Although investigators noted a positive association for all measures of fatness and having any coronary artery calcification, in the two-thirds of patients who had calcification, the relationship reversed so that people with more fat had less severe calcification.

This association also varied by gender. Women with less fat under the skin had more evidence of coronary artery calcification than those with more fat. Thinner men also had more evidence of coronary artery calcification than men with a higher BMI.

What it comes down to is a kind of double-edged relationship, said Baqiyyah Conway, M.P.H., lead author of the abstract, adding that these associations of less severe artery calcification with greater fat persisted even when controlling for standard cardiovascular disease risk factors such as increased levels of LDL, or bad cholesterol, triglycerides, high blood pressure and lower levels of HDL, or good cholesterol. Controlling for kidney disease, another common complication of diabetes, weakened the association in men but not in women.

This is not a firm recommendation to people with type 1 diabetes to put on weight, but it does raise the possibility that weight recommendations in type 1 diabetes may be somewhat different than those for the general population, and emphasizes the complex relationship between body fat and cardiovascular risk in diabetes, said Dr. Orchard, who also is professor of medicine and pediatrics at the University of Pittsburgh School of Medicine.

Study suggests other causes for childhood brain aneurysms

Wed, 13 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CINCINNATIA new University of Cincinnati (UC) study questions the commonly held scientific belief that childhood brain aneurysms are caused by trauma, infection or underlying vascular malformations.

In a retrospective review of 53 Ohio children with intracranial (brain) arterial aneurysms, Todd Abruzzo, MD, found that the most common type of aneurysm among all age groups appeared to occur spontaneouslywith no related trauma or infection, recognizable clinical warnings signs or underlying medical causes, such as vascular malformations.

Researchers say this data suggests unknown genetic factors, environmental exposures or an interaction of the two may predispose certain children to aneurysm development.

An aneurysm occurs when a blood vessel weakens and stretches, forming a bulge in the vessel wall that can rupture and hemorrhage. Intracranial arterial aneurysmsuncommon in pediatric patientsare bulges that develop in the arteries that carry blood to the brain.

In addition, Abruzzo reports that 75 percent of the patients whose aneurysms developed spontaneously had no risk factors for vascular disease, which in adults include smoking and high blood pressure.

This is very significant because it provides insight into the mechanisms of aneurysm formation, says Abruzzo, an assistant professor of radiology, neurosurgery and biomedical engineering at UC and interventional neuroradiologist at University Hospital and Cincinnati Childrens Hospital Medical Center. Most cerebrovascular specialists believe that aneurysms arise from mechanical fatigue of the arterial wallresulting from wear and tear caused by a lifetime of excessive blood pressure and flow on thin-walled cerebral arteries.

But our study suggests thatunlike the adult diseasechildhood aneurysms may be driven by unique predisposing factors that we have not yet identified. It could have much less to do with underlying conditions commonly thought to contribute to their development, he explains.

Abruzzo will present this research, believed to be one of the largest reported case series of pediatric intracranial arterial aneurysms in the United States, at 3 p.m. Wednesday, June 13, at the American Society of Neuroradiologys annual meeting in Chicago.

For the study, the neuroradiology team reviewed epidemiological, anatomical, pathological and clinical characteristics of the 53 patientsall under age 19at Cincinnatis University Hospital, Cincinnati Childrens Hospital and Columbus Childrens Hospital from January 1993 to November 2006. Most of these patients had developed intracranial hemorrhage, which occurs when intracranial aneurysm ruptures.

It turns out the aneurysms not only occurred in different places in children compared to adults, but there also appeared to be a difference in the way the disease develops, says Abruzzo. These differences merit further investigation to give neuroradiologists the knowledge they need to develop ongoing treatment and strategies for monitoring this at-risk population.

Drug slows and may halt Parkinson's disease

Sun, 10 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO --- Northwestern University researchers have discovered a drug that slows and may even halt the progression of Parkinsons disease. The drug rejuvenates aging dopamine cells, whose death in the brain causes the symptoms of this devastating and widespread disease.

D. James Surmeier, the Nathan Smith Davis Professor and chair of physiology at Northwestern Universitys Feinberg School of Medicine, and his team of researchers have found that isradipine, a drug widely used for hypertension and stroke, restores stressed-out dopamine neurons to their vigorous younger selves. The study is described in a feature article in the international journal Nature, which will be published on-line June 10.

Dopamine is a critical chemical messenger in the brain that affects a persons ability to direct his movements. In Parkinsons disease, the neurons that release dopamine die, causing movement to become more and more difficult.

Ultimately, a person loses the ability to walk, talk or pick up a glass of water. The illness is the second most common neurodegenenerative disease in the country, affecting about 1 million people. The incidence of Parkinsons disease increases with age, soaring after age 60.

Our hope is that this drug will protect dopamine neurons, so that if you began taking it early enough, you wont get Parkinsons disease, even if you were at risk. said Surmeier, who heads the Morris K. Udall Center of Excellence for Parkinsons Disease Research at Northwestern. It would be like taking a baby aspirin everyday to protect your heart.

Isradipine may also significantly benefit people who already have Parkinsons disease. In animal models of the disease, Surmeiers team found the drug protected dopamine neurons from toxins that would normally kill them by restoring the neurons to a younger state in which they are less vulnerable.

The principal therapy for Parkinsons disease patients currently is L-DOPA, which is converted in the brain to dopamine. Although L-DOPA relieves many symptoms of the disease in its early stages, the drug becomes less effective over time. As the disease progresses, higher doses of L-DOPA are required to help patients, leading to unwanted side-effects that include involuntary movements. The hope is that by slowing the death of dopamine neurons, isradipine could significantly extend the time in which L-DOPA works effectively.

If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance, Surmeier said.

The work by Surmeiers group is particularly exciting because nothing is known to prevent or slow the progression of Parkinsons disease.

There has not been a major advance in the pharmacological management of Parkinsons disease for 30 years, Surmeier said.

Surmeier, who has researched Parkinsons disease for 20 years, had long been frustrated because it wasnt known how or why dopamine cells die in the disease. It didnt seem like we were making much progress in spite of intense study on several fronts, he said.

Because hes a physiologist, Surmeier decided to investigate whether the electrical activity of dopamine neurons might provide a clue to their vulnerability. All neurons in the brain use electrical signals to do their job, much like digital computers.

First, Surmeier observed that dopamine neurons are non-stop workers called pacemakers. They generate regular electrical signals seven days a week, 24 hours a day, just like pacemaker cells in the heart. This was already known. But then he probed more deeply and discovered something very strange about these dopamine neurons.

Most pacemaking neurons use sodium ions (like those found in table salt) to produce electrical signals. But Surmeier found that adult dopamine neurons use calcium instead.

Sodium is a mild mannered ion that does its job without causing a whit of trouble to the cell. Calcium ions, however, are wild and rambunctious. Remember when Marlon Brando rode into town with his motorcycle gang in The Wild One Those guys were like calcium ions.

The reliance upon calcium was a red flag to us, Surmeier said. Calcium ions need to be chaperoned by the cell almost as soon as they enter to keep them from causing trouble, he noted. The cell has to sequester them or keep pumping them out. This takes a lot of energy.

Its a little like having a room full of two year olds you have to watch like a hawk so they dont get into trouble, Surmeier said. Thats really going to stress you. With three boys under age eleven, he can relate to the stressed dopamine neuron.

Surmeier theorized that the non-stop stress on the dopamine neurons explains why they are more vulnerable to toxins and die at a more rapid rate as we age.

But these findings still didnt offer him a new therapy.

Then, serendipity struck when he was working on a different problem. He discovered that young dopamine neurons and adult ones have an entirely different way of operating.

When the neurons are young, Surmeier found they actually use sodium ions to do their work. But as the neurons age, they become more and more dependent on the troublesome calcium and stop using sodium. This calcium dependence and the stress it causes the neurons --is what makes them more vulnerable to death.

What would happen, Surmeier wondered, if he simply blocked the calciums route into the adult neuron cells Would the neurons revert to their youthful behavior and start using sodium again

The cells had put away their old childhood tools in the closet. The question was if we stopped them from behaving like adults would they go into the closet and get them out again Surmeier asked. Sure enough, they did.

When he gave the mice isradipine, it blocked the calcium from entering the dopamine neuron. At first, the dopamine neurons became silent. But within a few hours, they had reverted to their childhood ways, once again using sodium to get their work done.

This lowers the cells stress level and makes them much more resistant to any other insult thats going to come along down the road. They start acting like theyre youngsters again, Surmeier said.

The next step will be launching a clinical study.

This animal study suggests that calcium channel blockers, drugs currently used to reduce blood pressure, might someday be used to slow the steady progression of Parkinson's disease, said Walter J. Koroshetz, M.D., deputy director of the NINDS.

Drug slows and may halt Parkinson's disease

Sun, 10 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) CHICAGO -- Northwestern University researchers have discovered a drug that slows and may even halt the progression of Parkinsons disease. The drug rejuvenates aging dopamine cells, whose death in the brain causes the symptoms of this devastating and widespread disease.

D. James Surmeier, the Nathan Smith Davis Professor and chair of physiology at Northwestern Universitys Feinberg School of Medicine, and his team of researchers have found that isradipine, a drug widely used for hypertension and stroke, restores stressed-out dopamine neurons to their vigorous younger selves. The study is described in a feature article in the international journal Nature, which will be published on-line June 10.

Dopamine is a critical chemical messenger in the brain that affects a persons ability to direct his movements. In Parkinsons disease, the neurons that release dopamine die, causing movement to become more and more difficult.

Ultimately, a person loses the ability to walk, talk or pick up a glass of water. The illness is the second most common neurodegenenerative disease in the country, affecting about 1 million people. The incidence of Parkinsons disease increases with age, soaring after age 60.

Our hope is that this drug will protect dopamine neurons, so that if you began taking it early enough, you wont get Parkinsons disease, even if you were at risk. said Surmeier, who heads the Morris K. Udall Center of Excellence for Parkinsons Disease Research at Northwestern. It would be like taking a baby aspirin everyday to protect your heart.

Isradipine may also significantly benefit people who already have Parkinsons disease. In animal models of the disease, Surmeiers team found the drug protected dopamine neurons from toxins that would normally kill them by restoring the neurons to a younger state in which they are less vulnerable.

The principal therapy for Parkinsons disease patients currently is L-DOPA, which is converted in the brain to dopamine. Although L-DOPA relieves many symptoms of the disease in its early stages, the drug becomes less effective over time. As the disease progresses, higher doses of L-DOPA are required to help patients, leading to unwanted side-effects that include involuntary movements. The hope is that by slowing the death of dopamine neurons, isradipine could significantly extend the time in which L-DOPA works effectively.

If we could double or triple the therapeutic window for L-DOPA, it would be a huge advance, Surmeier said.

The work by Surmeiers group is particularly exciting because nothing is known to prevent or slow the progression of Parkinsons disease.

There has not been a major advance in the pharmacological management of Parkinsons disease for 30 years, Surmeier said.

Surmeier, who has researched Parkinsons disease for 20 years, had long been frustrated because it wasnt known how or why dopamine cells die in the disease. It didnt seem like we were making much progress in spite of intense study on several fronts, he said.

Because hes a physiologist, Surmeier decided to investigate whether the electrical activity of dopamine neurons might provide a clue to their vulnerability. All neurons in the brain use electrical signals to do their job, much like digital computers.

First, Surmeier observed that dopamine neurons are non-stop workers called pacemakers. They generate regular electrical signals seven days a week, 24 hours a day, just like pacemaker cells in the heart. This was already known. But then he probed more deeply and discovered something very strange about these dopamine neurons.

Most pacemaking neurons use sodium ions (like those found in table salt) to produce electrical signals. But Surmeier found that adult dopamine neurons use calcium instead.

Sodium is a mild mannered ion that does its job without causing a whit of trouble to the cell. Calcium ions, however, are wild and rambunctious. Remember when Marlon Brando rode into town with his motorcycle gang in The Wild One Those guys were like calcium ions.

The reliance upon calcium was a red flag to us, Surmeier said. Calcium ions need to be chaperoned by the cell almost as soon as they enter to keep them from causing trouble, he noted. The cell has to sequester them or keep pumping them out. This takes a lot of energy.

Its a little like having a room full of two year olds you have to watch like a hawk so they dont get into trouble, Surmeier said. Thats really going to stress you. With three boys under age eleven, he can relate to the stressed dopamine neuron.

Surmeier theorized that the non-stop stress on the dopamine neurons explains why they are more vulnerable to toxins and die at a more rapid rate as we age.

But these findings still didnt offer him a new therapy.

Then, serendipity struck when he was working on a different problem. He discovered that young dopamine neurons and adult ones have an entirely different way of operating.

When the neurons are young, Surmeier found they actually use sodium ions to do their work. But as the neurons age, they become more and more dependent on the troublesome calcium and stop using sodium. This calcium dependence and the stress it causes the neurons --is what makes them more vulnerable to death.

What would happen, Surmeier wondered, if he simply blocked the calciums route into the adult neuron cells Would the neurons revert to their youthful behavior and start using sodium again

The cells had put away their old childhood tools in the closet. The question was if we stopped them from behaving like adults would they go into the closet and get them out again Surmeier asked. Sure enough, they did.

When he gave the mice isradipine, it blocked the calcium from entering the dopamine neuron. At first, the dopamine neurons became silent. But within a few hours, they had reverted to their childhood ways, once again using sodium to get their work done.

This lowers the cells stress level and makes them much more resistant to any other insult thats going to come along down the road. They start acting like theyre youngsters again, Surmeier said.

The next step will be launching a clinical study.

This animal study suggests that calcium channel blockers, drugs currently used to reduce blood pressure, might someday be used to slow the steady progression of Parkinson's disease, said Walter J. Koroshetz, M.D., deputy director of the NINDS.

Synthetic amylin curbs tendency to binge eat

Fri, 08 Jun 2007 15:59:37 PST

( from http://www.rxpgnews.com ) The synthetic form of a hormone previously found to produce a feeling of fullness when eating and reduce body weight, also may help curb binge eating and the desire to eat high-fat foods and sweets. The findings on fast food consumption and binge eating tendencies are based on a 6-week research study of 88 obese individuals.

"Satiety hormones are commonly thought to control food intake by signaling to the brain when we are full," said Christian Weyer, M.D., the study's senior author and executive director of clinical research at Amylin Pharmaceuticals, Inc., in San Diego, Calif. "The findings of our clinical study further suggest that satiety hormones such as amylin can exert multiple effects on human eating behavior, such as reduced intake of highly-palatable foods and reduced binge eating tendency."

The study was carried out in 10 U.S. research sites and was reported by Steven R. Smith of the Pennington Biomedical Research Center in Baton Rouge, La.; John E. Blundell of the University of Leeds, United Kingdom; and Colleen Burns, Cinzia Ellero, Brock E. Schroeder, Nicole C. Kesty, Kim Chen, Amy E. Halseth, Cameron W. Lush and Christian Weyer, all of Amylin Pharmaceuticals.

Agonized death throes probable cause of open-mouthed, head-back pose of many dino fossils

Fri, 08 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) Berkeley -- The peculiar pose of many fossilized dinosaurs, with wide-open mouth, head thrown back and recurved tail, likely results from the agonized death throes typical of brain damage and asphyxiation, according to two paleontologists.

A classic example of the posture, which has puzzled paleontologists for ages, is the 150 million-year-old Archaeopteryx, the first-known example of a feathered dinosaur and the proposed link between dinosaurs and present-day birds.

Virtually all articulated specimens of Archaeopteryx are in this posture, exhibiting a classic pose of head thrown back, jaws open, back and tail reflexed backward and limbs contracted, said Kevin Padian, professor of integrative biology and curator in the Museum of Paleontology at the University of California, Berkeley. He and Cynthia Marshall Faux of the Museum of the Rockies published their findings in the March issue of the quarterly journal Paleobiology, which appeared this week.

Dinosaurs and their relatives, ranging from the flying pterosaurs to Tyrannosaurus rex, as well as many early mammals, have been found exhibiting this posture. The explanation usually given by paleontologists is that the dinosaurs died in water and the currents drifted the bones into that position, or that rigor mortis or drying muscles, tendons and ligaments contorted the limbs.

I'm reading this in the literature and thinking, This doesn't make any sense to me as a veterinarian,' said lead author Faux (pronounced fox), a veterinarian-turned-paleontologist who also is a curatorial affiliate with Yale University's Peabody Museum. Paleontologists aren't around sick and dying animals the way a veterinarian is, where you see this posture all the time in disease processes, in strychnine cases, in animals hit by a car or in some sort of extremis.

Faux and Padian argue in Paleobiology that the dinosaurs died in this posture as a result of damage to the central nervous system. In fact, the posture is well known to neurologists as opisthotonus and is due to damage to the brain's cerebellum. In humans and animals, cerebellar damage can result from suffocation, meningitis, tetanus or poisoning, and typically accompanies a long, slow death.

Some animals found in this posture may have suffocated in an ash fall during a volcanic eruption, consistent with the fact that many fossils are found in ash deposits, Faux and Padian said. But many other possibilities exist, including disease, brain trauma, severe bleeding, thiamine deficiency or poisoning.

This puts a whole new light on the mode of death of these animals, and interpretation of the places they died in, Padian said. This explanation gives us clues to interpreting a great many fossil horizons we didn't understand before and tells us something dinosaurs experienced while dying, not after dying.

Also, because the posture has been seen only in dinosaurs, pterosaurs and mammals, which are known or suspected to have had high metabolic rates, it appears to be a good indicator that the animal was warm blooded. Animals with lower metabolic rates, such as crocodiles and lizards, use less oxygen and so might have been less traumatically affected by hypoxia during death throes, Padian said.

Padian acknowledged that many dinosaur fossils show signs that the animal died in water and the current tugged the body into an arched position, but currents cannot explain all the characteristics of an opisthotonic pose. By studying a large number of fully articulated fossil skeletons, he and Faux were able to distinguish animals that underwent post-mortem water transport, a non-biological or abiotic process, from those with the classic dead-bird posture, which they interpret to be the result of biological processes.

Faux, who also works as a disaster veterinarian from her home in Lewiston, Idaho, set out to test other post-mortem processes - rigor mortis, which is the temporary stiffening of muscles after death; and the drying of muscles, tendons and ligaments - that some paleontologists credit with creating the opisthotonic posture. She obtained badly injured birds -owls, falcons and red-tailed hawks - that had been euthanized at a raptor recovery center and watched them for 8-10 hours, checking periodically to see if they moved during the process.

In horses and smaller animals, rigor mortis sets in within a couple of hours, so I just looked to see if they were moving or not, Faux said. And they weren't moving. They were staying in whatever position I'd left them in. I thought, 'If birds aren't doing it, and I'd never observed a horse doing it, then why would dinosaurs be doing it'

The idea that drying causes muscles or tendons to contract asymmetrically also didn't make sense, she said, based on her veterinary experience and an experiment she conducted with two euthanized red-tailed hawks, which she dried for two months set them in Styrofoam peanuts to dr. Most joints have counterbalancing muscles that dry the same way, she said, so there was no reason to expect that the muscles would turn a joint during drying. She found no post-mortem movement. She also pinned beef tendons as they dried, and though they shrank a bit, they did not shrink enough even to dislodge the pins. Given these observations, it is hard to imagine how shrinking tendons or muscles could drag a heavy creature into a different position, the researchers noted.

Padian pointed out, too, that all opisthotonic dinosaurs are very well preserved, meaning they evidently did not sit out in the open for long, or scavengers would have quickly scattered the bones. So, he wondered, how could they have been exposed long enough to dry out

The only explanation that makes sense, they concluded, is central nervous system damage. The cerebellum is responsible for fine muscle movement, controlling, for example, the body's antigravity muscles that keep the head upright. Once the cerebellum ceases to modulate the behavior of the antigravity muscles, Faux said, the muscles pull at full force, tipping the head and tail back, contracting the limbs and opening the mouth.

Padian and Faux urge reanalysis of many fossil finds, referring, for example, to a mass death uncovered in Nebraska in the early 20th century. They argue that cerebellar dysfunction explains the opisthotonic posture of the numerous camel-like fossils better than does the common explanation - that the animals died in a stream and were washed into an eddy or backwater.

The authors also point to a fossil of Allosaurus, a T rex-like animal, that displayed bone lesions suggestive of a bacterial infection that also can lead to meningitis, a disease that can produce opithotonus. The authors point out that their explanation of the opisthotonic posture in dinosaurs and other animals provides a way to assess the role played by microbes in evolution, whether through disease or through other processes such as algal blooms - so-called red tides - that can suffocate aquatic animals.

This example and others suggest that reevaluation may be in order for an untold number of paleoenvironments whose story has been at least partly explained on the basis of the death positions of many of their fossil vertebrates, the authors write in their Paleobiology paper.