Archive for October, 2008

Activity and Aging

Indiana University researchers studied 730 highly active people, ages 20 to 93, to see how their physical and mental quality of life and rates of obesity-related diseases compare to the general population. Their study participants, United States Master Swimmers, reported swimming regularly for an average of 18.6 years. The percentage of Master Swimmers classified as obese (5.4 percent) and the prevalence of obesity-related diseases such as hypertension (6.5 percent), diabetes (1 percent) and coronary artery disease (1.3 percent), was significantly less than the general population. Their measures of physical and mental quality of life also were significantly better than the general public, with the typical decline in physical quality of life occurring later for them — around the age of 55. Jeanne Johnston, assistant professor in IU’s Department of Kinesiology, said research involving physical activity and obesity-related diseases typically begins by looking at sedentary people and uses this population to establish baseline data, rather than examining active people who could represent model behavior. “The low incidence of overweight and obesity as well as the self-reported diseases demonstrates that active engagement in physical activity improves both physical and mental health as well as the diseases people might have,” she said. Examining highly active people, Johnston and her colleagues wrote, might lead to a better understanding of the relationship between lifelong physical activity, successful aging, morbidity and quality of life.

Health of Caregivers

People taking care of more than one generation — such as their children and parents — engaged in fewer healthy behaviors, found a study by researchers from Indiana University and Arizona State University. As the U.S. population continues to age, more and more midlife adults find themselves similarly “sandwiched,” leading the research team to conclude that “encouraging healthy behaviors among caregivers has the potential to prevent significant illness and premature mortality.” The study involved 4,943 participants in a longitudinal study who reported the number of hours per week they spent caring for their children, parents and in-laws. The researchers looked at five health behaviors: checking food labels for health value when buying foods, using a seat belt, choosing foods based on health value, exercising regularly and cigarette smoking. Compared with people caring for a single generation, people in the sandwich generation were less likely to check food labels, wear seat belts or choose foods based on health values. They also smoked more cigarettes each day.

Dexterity Improved by Brain Stimulation

Applying electrical stimulation to the scalp and the underlying motor regions of the brain could make you more skilled at delicate tasks. Research published today in the open access journal BMC Neuroscience shows that a non-invasive brain-stimulation technique, transcranial direct current stimulation (tDCS), is able to improve the use of a person’s non-dominant hand.

Drs. Gottfried Schlaug and Bradley Vines from Beth Israel Deaconess Medical Center and Harvard Medical School, tested the effects of using tDCS over one side or both sides of the brain on sixteen healthy, right-handed volunteers, as well as testing the effect of simply pretending to carry out the procedure. The volunteers were not aware of which of the three procedures they were receiving. The test involved using the fingers of the left hand to key in a series of numbers displayed on a computer screen.

The results were striking; stimulating the brain over both the right and left motor regions (’dual hemisphere’ tDCS) resulted in a 24% improvement in the subjects’ scores. This was significantly better than stimulating the brain only over one motor region or using the sham treatment (16% and 12% improvements, respectively).

tDCS involves attaching electrodes to the scalp and passing a weak direct current through the scalp and skull to alter the excitability of the underlying brain tissue. The treatment has two principal modes depending on the direction in which the current runs between the two electrodes. Brain tissue that underlies the positive electrode (anode) becomes more excitable and the reverse is true for brain tissue that underlies the negative electrode (cathode). No relevant negative side effects have been reported with this type of non-invasive brain stimulation. It is not to be confused with electroconvulsive therapy, which uses currents around a thousand times higher.

According to Schlaug, “The results of our study are relevant to clinical research on motor recovery after stroke. They point to the possibility that stimulating both sides of the brain simultaneously, using the effects of the direct current to block unwanted effects of one motor region while using the opposite effects of the direct current treatment on the other motor region to enhance and facilitate the function of that motor region might catalyze motor recovery”.

Single MicroRNA Controls Forming of Heart Chambers

Scientists at the Gladstone Institute of Cardiovascular Disease (GICD) and the University of California San Francisco (UCSF) have identified a genetic factor critical to the formation of chambers in the developing heart. The discovery of the role of a microRNA called miR-138, could offer strategies for the treatment of congenital heart defects.The heart is one of the first and most important organs to develop. In fact, embryos cannot survive long with a functioning heart. In vertebrates (animals with backbones), special cells form a heart tube; that tube loops back on itself to form the atrium and ventricle and the canal and valve that separates them. This requires a complicated sequence of genes turning on and off. MicroRNAs are very small RNAs of 20 to 25 nucleotides that regulate numerous gene functions. Approximately 650 human miRNAs are known, but only a few have yet been studied to determine what they actually do in a cell.

Researchers, led by Sarah Morton, an MD/PhD student at UCSF and GICD Director Deepak Srivastava MD, examined zebrafish, which are an ideal model system for understanding genetic functions. Zebrafish are small, reproduce fast, and are essentially transparent so that that events of heart formation can be studied while they are still alive. Yet many of their systems are quite similar to those of humans. For example, miR-138 is exactly the same in zebrafish and humans.

“What’s interesting is that a single microRNA is responsible for setting up the distinct patterning of a developing heart into separate chambers,” said Dr. Srivastava, senior author of the study. “Since many congenital heart defects involve abnormalities in the formation of the chambers, this is important information in finding ways of treating or avoiding those defects.”

The GICD scientists reported in today’s issue of the Proceedings of the National Academy of Sciences USA, that miR-138 is present in the zebrafish heart at specific times and in specific places in the developing heart. Furthermore, they showed that it is required to insure that the cardiac chambers develop properly. When the scientists used genetic engineering techniques to eliminate miR-138, cardiac function was disrupted, and the ventricles did not develop correctly, with the muscle precursor cells failing to mature properly.

“The miR-138 function was required during a discrete developmental window that occurred 24-34 hours after fertilization,” said Sarah Morton. The team also showed that the miRNA controlled development by regulating numerous factors that function jointly to define the chambers, including a key enzyme that makes retinoic acid.

Itching Stress

Current research suggests that stress may activate immune cells in your skin, resulting in inflammatory skin disease. The related report by Joachim et al., “Stress-induced Neurogenic Inflammation in Murine Skin Skews Dendritic Cells towards Maturation and Migration: Key role of ICAM-1/LFA-1 interactions,” appears in the November issue of The American Journal of Pathology.Skin provides the first level of defense to infection, serving not only as a physical barrier, but also as a site for white blood cells to attack invading bacteria and viruses. The immune cells in skin can over-react, however, resulting in inflammatory skin diseases such as atopic dermatitis and psoriasis.

Stress can trigger an outbreak in patients suffering from inflammatory skin conditions. This cross talk between stress perception, which involves the brain, and the skin is mediated the through the “brain-skin connection”. Yet, little is know about the means by which stress aggravates skin diseases.

Researchers lead by Dr. Petra Arck of Charité, University of Medicine Berlin and McMaster University in Canada, hypothesized that stress could exacerbate skin disease by increasing the number of immune cells in the skin. To test this hypothesis, they exposed mice to sound stress. Dr. Arck’s group found that this stress challenge resulted in higher numbers of mature white blood cells in the skin. Furthermore, blocking the function of two proteins that attract immune cells to the skin, LFA-1 and ICAM-1, prevented the stress-induced increase in white blood cells in the skin.

Taken together, these data suggest that stress activates immune cells, which in turn are central in initiating and perpetuating skin diseases. Fostered by the present observation, the goal of future studies in Dr. Arck’s group is to prevent stress-triggered outbreaks of skin diseases by recognizing individuals at risk and identifying immune cells suitable to be targeted in therapeutic interventions.

Blindsight Color

By manipulating the brain noninvasively in a new way with magnetic stimulation, researchers have shown that they can restore some experience of color where before there was no visual awareness whatsoever. They report their findings in the October 28th issue of Current Biology, a Cell Press publication.

The researchers made their discovery while studying a patient known as GY, who lacks vision in half of his visual field as a result of damage in one hemisphere of the primary visual cortex (a brain region also known as V1). That part of the brain had been considered absolutely essential for visual awareness, a notion that is challenged by the current findings, according to Juha Silvanto of the University of Essex.

“The implication is that even though [lesions in this part of the brain] abolish visual awareness, it can be restored,” Silvanto said. “The neural processes that make V1 critical may be taken over by other brain regions—not automatically, but you can make it happen.”

In the portion of his visual field controlled by the damaged part of the brain, GY has a condition called blindsight. This phenomenon can occur when people do not consciously see as a consequence of a V1 lesion. However, when forced to guess which way a moving object they “observed” was traveling, for instance, they get it right most of the time. In other words, despite the fact that they do not experience vision, they nonetheless continue to detect things around them.

In the new study, the researchers applied a method called transcranial magnetic stimulation (TMS) to GY’s primary visual cortex. By stimulating both the normal and the damaged hemispheres of the brain, the method can induce visions of flashes of light (or phosphenes) in the blind fields of people like GY.

This method has previously been used in a general way to stimulate entire brain regions. In the new study, Silvanto’s team developed a more targeted method to activate particular neurons with TMS by taking advantage of a trend that had been seen before: TMS preferentially activates those neurons that were less active to begin with.

They asked GY to look at a screen in the color red for a time; this adapts the brain to the color red, leaving the neurons responsible for the experience of red to become less active. They then applied TMS to GY’s damaged and intact visual processing centers. The result: he saw the color red.

“This was the first time this patient [consciously] experienced a colored visual percept in his blind field,” Silvanto said.

“In summary,” the researchers wrote, “our results show that in the absence of V1, color perception may be possible via the intact hemisphere.”

The more targeted TMS method the team developed is also an important technical advance for cognitive neuroscience, Silvanto added. “Now we can target the stimulation at specific populations of neurons,” he said. “It makes the resolution of the technique much higher.”

Perceiving Moving Objects Bias

A universal bias in the way people perceive moving objects means that tennis referees are more likely to make mistakes when they call balls “out” than when they call them “in,” according to a new report in the October 28th issue of Current Biology, a Cell Press publication. Because recent rule changes allow professional tennis players to challenge the refs’ calls, athletes could exploit the new findings to their advantage, according to researchers at the University of California, Davis.

Like all visual illusions, the new discovery provides visual neuroscientists with a window on how the brain processes information, explained David Whitney.

“The visual system faces a big challenge when trying to code the locations of objects so that we can perceive them,” Whitney said. “Consider one of the difficulties: every time we move our eyes, the image on our retina moves. Even if our coffee cup is actually stationary on our desk, we move our eyes and head while reaching to pick it up so the image of the cup will move on our retina. This is a problem because the visual system is sluggish—it takes a hundred or more milliseconds for us to become aware of an image that strikes our retina. So, by the time we perceive an object like the coffee cup in one location, it will have already changed location as we move toward it. Our perception lags behind reality. The visual system has mechanisms that help alleviate this problem of living in the past, but these mechanisms are not perfect and occasionally result in visual illusions—like the misperception of tennis ball location we discovered.”

Similar kinds of perceptual biases in the visual system had been documented before, but rarely in real-world situations. People consistently misperceive moving objects as shifted in the direction of their motion, so that at any moment they appear to be farther along their path than they are. Whitney said he realized it might be possible to study this in the context of tennis when he saw a referee call overturned by a player’s challenge during a Wimbledon match.

On a tennis court, a ball could physically bounce in the court but be called out, or a ball could physically bounce out of the court but be called in. If tennis referees were bias-free, they would be equally likely to make each of these two kinds of errors. But because objects generally appear to be shifted in the direction of their motion, referees should incorrectly judge balls as being out more often.

Whitney’s team confirmed that prediction. In a review of more than 4,000 randomly selected Wimbledon tennis points, the researchers uncovered 83 incorrect calls. Of those, 70 of the errors were of the type predicted.

Further study of the phenomenon in the laboratory confirmed that the refs’ mistakes are not the result of poor refereeing. Rather, the errors are a general artifact of the way the human brain processes visual information about motion.

Indeed, the researchers said, tennis players and audience members surely make the same mistakes that refs do. The new findings suggest, however, that players could maximize their opportunity to challenge calls by focusing on balls that are called “out,” since they are more likely to be incorrect.

The report also suggests that every shot in professional tennis should perhaps be reviewed by instant replay. “If that proves prohibitively time-consuming, the rules allowing players to challenge referee judgments should be scrutinized at least, in light of the current findings,” they wrote. “If all else fails,” they added, “perhaps professional tennis venues should follow the French, and universalize the clay court,” where skid marks on the clay reduce reliance on the referees’ motion perception.

New Pesticide Health Effects

Even though the U. S. Environmental Protection Agency (EPA) has given final approval for use of a new pesticide, regulators in California and other states are taking a closer look at the substance’s potential adverse health effects before allowing the chemical to be used, according to an article scheduled for the Oct. 27 issue of Chemical & Engineering News, ACS’ weekly newsmagazine.

In the article, C&EN Associate Editor Britt E. Erickson notes that EPA first considered approving the pesticide, methyl iodide, in 2006 as a replacement for methyl bromide —which is now being phased out because of environmental concerns that it may damage the ozone layer. Although methyl iodide appears unlikely to have that effect, it is toxic to nerve cells and may carry a risk of thyroid damage, cancer, and other adverse health effects.

At least one environmental group and some scientists opposed EPA’s approval of the pesticide, alleging that EPA had been secretive during the review process, failing to fully consider the chemical’s health effects, and they pointed to an apparent conflict of interest involving the pesticide’s manufacturer. States like California and Florida had their own concerns about the pesticide’s safety and decided to do their own risk assessments before allowing use of methyl iodide. Florida finished its assessment and approved the use of methyl iodide last July, but not before requiring additional safety measures beyond those required by EPA. California’s assessment is still ongoing, the article notes.

African Sleeping Sickness

Scientists in the United Kingdom and Russia are reporting identification of a long-sought chink in the armor of the parasite that causes African sleeping sickness, a parasitic disease that kills at least 50,000 people each year. Their study appears in the current edition of ACS Chemical Biology, a monthly journal.

In the study, Michael Ferguson and colleagues cite an “urgent” need for new treatments for the disease, which is spread by the tsetse fly and also affects cattle — a precious possession that represents a bank account on four feet to impoverished people in sub-Sahara Africa. Current treatments for African sleeping sickness, Ferguson says, are not only difficult to administer, but also expensive and toxic.

Their research identified the first compound to impede a key step in an essential biochemical pathway in the sleeping sickness parasite. Blocking this pathway disrupts the production of a key glycolipid that anchors protective proteins to the surface of the parasite. The analysis also revealed notable differences between pathways of parasitic and human cells, which could reveal insight into possible therapeutic targets.

Non Invasive Disease Diagnosis

Scientists are reporting development of a device that could serve as the electronic “reader” for a coming generation of “wellness cards,” specimen holders used to diagnose disease from a drop of a patient’s saliva or blood. The research, done by scientists in Utah, Iowa, Arizona, and Minnesota, is presented in two papers scheduled for the November 1 issue of ACS’ Analytical Chemistry, a semi-monthly journal.

In those studies, Marc Porter and colleagues describe using the same technology at the heart of miniaturized hard disk drives to create the new rapid-screening sensor. Using a phenomenon known as giant magnetoresistance (GMR), the device can detect samples on much smaller areas compared to older technologies, the papers note.

As a test, Porter demonstrated the GMR sensor could detect as few as 800 magnetic beads with microscopic dimensions. “Several laboratories have begun to transition GMRs from the data storage domain to that of the bioanalytical sciences,” the paper states. “We believe that, by leveraging advances made in the magnetic recording industry (for example portable digital music players), a robust, field-deployable, assay device capable of sensing single-binding events is just over the horizon.”

Soy Flatulance

Soybeans may drop off the list of musical fruit. Scientists in Singapore are reporting victory over some consumers’ No. 1 complaint about soy products — the “flatulence factor” caused by indigestible sugars found in soy. In a study scheduled for the November 12 issue of ACS’ bi-weekly Journal of Agricultural and Food Chemistry, they describe a method for significantly reducing the amount of flatulence-causing carbohydrates in soy yogurt while raising the levels of healthy antioxidants known as isoflavones.

In the study, Dejian Huang and colleagues note that soy yogurt has a global market share of only 1.9 percent, even though it has a number of health advantages over dairy-based yogurt. That’s partly because of the flatulence-causing compounds in soy. “It would be desirable to remove the flatulence-causing raffinose and stachyose from the soy yogurt to improve consumers’ preferences. The objective of this study was to develop a new soy yogurt enriched with isoflavones with reduced levels of flatulence-causing oligosaccharides,” the scientists said.

The researchers grew soybeans in the presence of a fungus that produced enzymes capable of degrading the undesired sugars. “We have demonstrated for the first time that germinated black soybeans under fungal stress can be fermented into a soy yogurt which features a low amount of flatulence-causing oligosaccharides but with a significant level of isoflavones,” says Huang.

Blood Brain Barrier Building

Construction of the brain’s border fence is supervised by Wnt/b-catenin signaling, report Liebner et al. in The Journal of Cell Biology.

Like many a modern nation, the brain requires tight border security to maintain levels of nutrients and keep out toxic substances. The blood–brain barrier (BBB) is a virtually impermeable network of tight junctions between endothelial cells that prevents paracellular flow of materials. Because Wnt/b-catenin signaling is a major pathway regulating other aspects of brain development, the authors examined its potential role in constructing the BBB.

In brain endothelial cells, Wnt signaling was active during the time of maximum vascular development, but not after the BBB matured. Activation of the Wnt signaling pathway in vivo and in vitro promoted BBB development, and inactivation prevented it. In vitro increasing Wnt signaling also strengthened junctions between non-brain endothelial cells.

This suggests that Wnt signaling might be tweaked to mend the BBBs in patients where it has failed—such as in stroke—or to temporarily open the BBB to deliver drugs that would normally be shut out.

New Strategy to Treat Common Infection

Researchers at Georgetown University Medical Center (GUMC) have successfully tested a genetic strategy designed to improve treatment of human infections caused by the yeast Candida albicans, ranging from diaper rash, vaginitis, oral infections (or thrush which is common in HIV/AIDS patients), as well as invasive, blood-borne and life-threatening diseases.Their findings confirm that inhibiting a key protein could provide a new drug target against the yeast, which inhabits the mucous membranes of most humans. The research was presented today at the 48th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy/46th Annual Meeting of the Infectious Diseases Society of America (ICAAC/IDSA) in Washington, DC.

“This is a genetically intelligent approach to target identification and drug design,” says the study’s lead author, Richard Calderone, PhD, professor and chair of the department of microbiology and immunology and co-director of the PhD program in the global infectious disease program at GUMC.

Candida infections are often treatable, however, in patients that are immunocompromised following cancer chemotherapy, bone marrow transplantation, or surgery, diagnosis is often delayed, postponing therapy,” he says. “Also when drug-resistant yeast pathogens cause the infection, clinical management of the patient becomes a problem.”

Candida invasive, blood-borne infections are the fourth most common hospital-acquired infection in the United States, costing the healthcare system about $1.8 billion each year, Calderone says.

“More drug resistance is being seen clinically, so there is significant room for improvement in the therapies used today,” he says

This study continues research in which Calderone and his colleagues identified a protein, the product of the Ssk1 gene that Candida needs to infect its host. To date, this protein has not been found in humans or in animals, which means it could be “targeted” with a novel drug without producing toxicity because such an agent should only attack the fungus.

The researchers found that if the Ssk1 gene is deleted from Candida albicans, the “triazole” drugs that are now used to treat these diseases are much more effective in the laboratory. “This allows the triazole drugs to do their job,” Calderone says. “We propose that this finding might lead to other, possibly more effective, treatment options.”

In this study, the researchers used a gene microarray analysis to further understand what knocking out the Ssk1 gene does to the organism, and they discovered that the gene is critical to the pathogenic nature of the fungi.

What this means is that an Ssk1 inhibitor might work in synergy with a triazole or perhaps as an effective stand-alone drug to treat Candida infections, the researchers say. If it works in Candida, it may have broader activity in other pathogens because Ssk1p is found in other fungi.

“Using the genome of the organism to find genes to target is a logical approach to drug design,” he says. The researchers are now working with other groups to find the right agent to target the Ssk1protein.

Beckwith Wiedemann Syndrome Mechanism

Researchers from Uppsala University have discovered a mechanism that silences several genes in a chromosome domain.  The findings, published in today’s on-line issue of Molecular Cell, have implications in understanding the human disorder Beckwith-Wiedemann syndrome.

In mammals the cells contain two copies of each chromosome, one inherited from the mother and one from the father.  The genes on the chromosomes can either be active or inactive.  If a gene is active on the maternal chromosome, the corresponding gene is usually active also on paternal chromosome.  However, in some domains of the chromosome the activity is shut down on one of the chromosomes but not on the other.  The genes in these domains cannot be activated the normal way but are completely silenced.  The present study shows for the first time how this silencing of several genes on a chromosome is accomplished.

The research group, led by Chandrasekhar Kanduri, has studied a domain with several silenced genes on chromosome 7 in the mouse.  The corresponding domain with silenced genes is located on the human chromosome 11.  When part of this domain is transcribed a long RNA molecule, Kcnq1ot1-RNA, is formed.  This RNA does not give rise to any protein, instead it mediates the silencing of eight to ten genes in a much larger area on the chromosome.  Based on their findings the researchers have suggested a model for how this is accomplished.  The Kcnq1ot1-RNA binds to the DNA in the domain and recruits specific enzymes that chemically modify DNA-binding proteins.  This modification makes the DNA inaccessible for transcription and thereby the genes cannot be activated.  In addition, the Kcnq1ot1-RNA targets the silenced domain to a specific area in the cell nucleus.  There it is protected during cell division and the genes will stay silenced also in the daughter cells.

– We show for the first time how a long RNA molecule can establish and maintain silencing of multiple genes in a large domain on the chromosome, says Chandrasekhar Kanduri.  The popular belief is that it is only a gene located in the same area as where the long RNA molecule is transcribed from that can be silenced.

This mechanism is important for understanding the genetic disorder Beckwith-Wiedemann Syndrome.  In this condition silencing of the chromosome 11 domain does not function properly and both copies of the genes in the domain become inactive, instead of just one.  Less protein is produced from the genes, leading to the excess growth characteristics associated with the syndrome: enlargement of organs in the foetus and an increased risk for tumours in the affected organs.

Drinking Your Vegetables

Making vegetable juice a daily habit could be a small step that can lead to big changes in meeting daily vegetable recommendations, according to a new study being presented by researchers from the University of California-Davis this week at the American Dietetic Association annual conference1.

With seven out of 10 adults falling short of the daily recommended vegetable intake as put forth by the U.S. Dietary Guidelines, researchers studied whether drinking vegetable juice could be a simple behavior change to help boost the intake of this critical food group2.  And it was.

The study looked at three groups of healthy men and women.  All three groups received dietary counseling on ways to get more vegetables, but only two of the groups were instructed to consume at least one serving of vegetable juice, in the form of V8® 100% vegetable juice each day.  Of those two groups, one drank one 8-ounce glass of vegetable juice every day and the other drank two 8-ounce glasses of vegetable juice every day as part of a balanced eating plan.

The study found that those who received dietary counseling and consumed vegetable juice were far more likely to meet the daily vegetable recommendations, about two and a half cups (five servings), than those who received counseling alone.  Specifically, more than half of the participants who drank one serving of V8 100% vegetable juice met the recommendations, as did all of those who drank two 8-ounce glasses of V8 100% vegetable juice each day.  Of those who did not drink any vegetable juice, less than a quarter got enough vegetables.

Researchers concluded that changing dietary behavior is much more effective when dietary advice is complemented with tangible, real, easy and convenient solutions.

“What we found in this study is that drinking vegetable juice seemed to address some of the key barriers to vegetable consumption such as convenience, portability and taste, so individuals were more likely to meet their daily recommendations,” said Carl Keen, PhD, study author and distinguished Professor of Nutrition & Internal Medicine at University of California, Davis.  “Furthermore, vegetable juice drinkers reported that they actually enjoyed drinking their vegetables, which is critical to adopting dietary practices for the long-term.”

In fact, after six weeks of the study, vegetable drinkers reported they felt “more satisfied” with the ease of getting vegetables into their diet, and that V8 100% vegetable juice provided an important additional source of vitamins and minerals.

Experts Agree

A growing body of science indicates vegetables are important to promoting good health, including helping to reduce risk factors for heart disease, diabetes and achieving a healthy weight.  According to Produce For Better Health, all forms count.

“The best type of vegetable is one that you will actually consume, so it’s important to provide people with a variety of great tasting options and ways to include them in their diet,” said Elizabeth Pivonka, PhD, RD, Produce for Better Health Foundation.  “That’s why we encourage people to explore all types of vegetables, such as 100% juice, fresh, frozen or canned, to get at least one serving of vegetables at each meal occasion throughout the day.”