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Introns Nonsense DNA May Be More Important to Evolution of Genomes Than Thought

2009-12-15T05:57:00.000-08:00

The sequences of nonsense DNA that interrupt genes could be far more important to the evolution of genomes than previously thought, according to a recent Sciencereport by Indiana University Bloomington and University of New Hampshire biologists.

Their study of the model organismDaphnia pulex (water flea) is the first to demonstrate the colonization of a single lineage by "introns," as the interrupting sequences are known. The scientists say introns are inserted into the genome far more frequently than current models predict. The scientists also found what appear to be "hot spots" for intron insertion -- areas of the genome where repeated insertions are more likely to occur. And surprisingly, the vast majority of intron DNA sequences the scientists examined were of unknown origin.

"The thinking has been that these insertion events are very rare because they always have bad effects," said postdoctoral fellow Abraham Tucker, a lead author of the Science paper.

Graduate student Wenli Li, whose participation in the research overlaps her dissertation work, was the paper's co-lead author. Li said she was particularly interested in the notion of hot spots that make it more likely for separate lineages of Daphnia to gain introns in the same place (or the same general area) within the water fleas' genomes. Four of the 23 different kinds of introns the scientists found were not unique with respect to position. If introns were always inserted in random places within genes, the scientists would have expected zero introns to have identical insertion points.

"The most intriguing finding for me is the multiple instances of parallel intron gains, because this means that Daphnia is in an active phase of intron proliferation," Li said. "This makesDaphnia an extraordinary system to study intron evolution. In addition, we believe our work facilitates a more accurate estimate of intron gain rates, and directly challenges the assumption that parallel intron gains are rare in many prior analyses."

Whether or not Daphnia is typical of eukaryotes with respect to intron gain (and loss), IU Bloomington evolutionary biologist Michael Lynch, the project's principal investigator, agreed that the discovery of parallelism will surprise his colleagues.

"Remarkably, we have found many cases of parallel intron gains at essentially the same sites in independent genotypes," Lynch said. "This strongly argues against the common assumption that when two species share introns at the same site, it is always due to inheritance from a common ancestor."

A unique and important aspect of the scientists' work is that they focused on one species (Daphnia pulex). Past studies have looked at a few introns shared by vastly different species. In doing so, geneticists have almost certainly missed the ephemeral appearance of new introns, and therefore would come to the wrong conclusions about how introns are gained, why they are lost, and how frequently either occurs.

That many introns are not acquired from a common ancestor but are the result of separate insertion events, the scientists say, means that the rates of intron gain in any species' lineage could be considerably higher than currently estimated.

Even if the rates of intron gain and loss of introns in Daphnia pulex are unlike those found in humans, sunflowers, and mushrooms, the Science report suggests geneticists and genome biologists take another look at introns, some of which could have been the result of hot spot insertion events in separate lines.

"The immediate question will be whether our findings can readily be extended to other species," Lynch said. "We are, in fact, doing that now. In addition, there is need for some solid molecular work to test our hypothesis about the mechanism of intron origin."

Intron is short for "intragenic region," a segment of DNA embedded within the coding portion of a gene. Introns are common in eukaryotic organisms -- animals, plants, fungi, and protists. When genes are expressed, special machinery within the cell nucleus usually removes the introns, thereby producing a transcript of the gene that is devoid of nonsense. Some introns are very small (20 DNA base pairs or fewer). A few introns are shockingly long (nearly 500,000 base pairs) long. Within a gene region, the total length of introns may dwarf the actual coding regions. There's a gene on humans' 22nd chromosome that is so riddled with introns, only 10 percent of it actually contains coding DNA. The rest is comprised of introns.

Scientists have generally assumed introns are so deleterious, their insertion almost always spells doom for the cell lines within individual organisms that produce offspring. With the exception of alternative splicing, introns serve no apparent function and consume needless energy when cells must duplicate all of their DNA. More importantly, the insertion of a new intron in a bad place can interfere with the cellular machinery's expression of an important gene. Experts have taken all of this to mean intron insertions are extremely rare events.

Almost all of the introns the IU Bloomington biologists located possessed a sequence of indeterminate origin. Only one of the 24 identified sequences bore a resemblance to a specific DNA sequences associated either with the Daphnia genome or its parasites. The other 23 introns had sequences that appear to have been improvised by the machinery responsible for DNA synthesis. "Our molecular analyses have enabled us to reject a number of hypotheses for the mechanism of intron origins, while clearly indicating an entirely unexpected pathway -- emergence as accidents arising during the repair of double-strand breaks," Lynch said.

Abraham Tucker, now at Indiana University Bloomington, and paper co-author Way Sung were both graduate students of William Kelley Thomas at the University of New Hampshire's Hubbard Center for Genome Studies when they did the bioinformatic analysis of the Daphnia genome that led to the findings of this paper. Drawing on longtime collaborations between Lynch's lab and the Hubbard Center on the Daphniagenome project, the two were able to access all Daphniagenome sequences.

"It was a very intense analysis, but it was obvious within a few days that there was some very interesting data," says Thomas, who is Hubbard Professor in Genomics and director of the Hubbard Center for Genome Studies. "This was a wonderful collaborative project."

This research was funded with grants from the National Science Foundation.

Female Fruit Flies Can Be 'Too Attractive' to Males, Scientists Show

2009-12-15T05:56:00.000-08:00

Females can be too attractive to the opposite sex -- too attractive for their own good -- say biologists at UC Santa Barbara. They found that, among fruit flies, too much male attention directed toward attractive females leads to smaller families and, ultimately, to a reduced rate of population-wide adaptive evolution.

In an article published in the December 8 issue of Public Library of Science Biology, the authors described their experiments on the sex lives of fruit flies.

"Can females be too good looking?" asks William Rice, biology professor at UCSB. "Can there be disadvantages to being attractive? The answer is yes: If you are too attractive, you get too much male attention, and that interferes with your ability to function biologically."

The authors explain that the term "good looking," among fruit flies, refers to something, like a large body. From the perspective of a male fly, a desirable mate is a female that is larger and can therefore produce more offspring.

"These larger females are disproportionately courted and harassed by males attempting to obtain matings," said Tristan A. F. Long, the study's first author. "When these males are 'choosy' with their courtship, there may be negative consequences to the species' ability to adaptively evolve."

According to the scientists, too much mating is harmful to the females because seminal fluid from the male has toxic side effects. Too much courtship can also hinder the female's ability to forage effectively.

"When they court the females, the males sing to them; they do this by vibrating their wings," said Rice. "They dance and sing at the same time. This might sound romantic, and it would be if it only happened once. But males are doing it all the time. This courtship is unrelenting -- like mosquitoes on a warm summer night -- as the male fruit flies try to persuade females to mate. The males are so persistent that they get them to mate almost every day."

In many species, females are frequently subject to intense courtship "harassment" from males attempting to obtain additional matings, according to the researchers. These coercive activities can result in attractive females becoming less fit to reproduce -- a factor that has a major effect on the entire population.

"We found that when harmful courtship behaviors were directed predominantly toward larger females of greater fecundity potential -- and away from smaller females, of lesser fecundity potential -- this resulted in an overall reduction in the variation of lifetime reproductive success of females in the population," said Long.

The male-mediated, persistent courtship bias can have important consequences for the ability of a population to adaptively change over time. If, for example, a female acquires a mutation that increases metabolic efficiency, allowing her to grow larger, and produce more offspring over her lifetime, this mutation should rapidly spread through the population. However, if the males get in the way of the biological success of these more attractive females, the mutation won't spread through the population as well as it might if males courted females indiscriminately.

The experiments clearly showed that the evolutionary adaptation of fruit flies is hindered by this mating situation. "This change in the distribution of fitness represents a previously unappreciated aspect of sexual selection -- one with important implications for the ability of beneficial genetic variation to spread through the gene pool, and ultimately for a species' capacity to adaptively evolve," Long explained.

Long was a Natural Sciences and Engineering Research Council of Canada (NSERC) postdoctoral fellow at UCSB at the time that he carried out the experiments designed with Rice. Long is currently a postdoctoral fellow with the University of Toronto in the Department of Ecology and Evolutionary Biology. The other authors are Alison Pischedda, a graduate student, and Andrew D. Stewart, a postdoctoral fellow, both of UCSB.

Gaining Advantages From Childhood Experience

2009-12-13T05:16:00.000-08:00

It often seems that certain aspects of our personalities are influenced by events that occurred in our childhoods. A recent study by Dr. Akaysha Tang's research team from the University of New Mexico Psychology Department and collaborators at Rockefeller University examined how early life experience influences social skills and ability to handle stressful situations using a rat model. The study will be published on July 30th in the online, open-access journal PLoS ONE.

In this study, Dr. Tang and colleagues examined whether rats that experienced greater novelty by spending three minutes a day away from their familiar home environment during infancy had a greater ability to compete against other rats for exclusive access to chocolate reward compared to their siblings that stayed in the home environment during infancy. They found that novelty-exposed rats were able to "beat out" their competitors more often than their home-staying siblings. They also found that across repeated sessions of competition, novelty-exposed rats decreased their release of stress hormones into the bloodstream, suggesting that they adapted faster to the stressful situation.

These findings were made among rats that were 24 months of age—considered old age for a rat. Perhaps most remarkably, the differences in early experience were induced by approximately 60 minutes of cumulative differential treatment carried out during the first 3 weeks of life. This means that very brief exposures to a novel environment during infancy can have a life-long influence on social competitive ability and the stress response.

Another question asked by Dr. Tang and colleagues was whether the differences between siblings depended on the care received from their mothers during infancy. They measured how much mother rats licked and groomed their pups after the novelty exposure procedure and how consistently they provided this care from day to day. They discovered that the mother rats that delivered more care to their pups on average were inconsistent in their amount of care from day to day. This led to the surprising finding that the novelty-exposed rats with the most adaptive stress responses had mothers that gave highly consistent, but lesser amounts, of care.

In translating possible significance of these findings to the human species, although it is sometimes assumed that the overall amount of care from the mother is one of the most important influences on her children's development, this study by Dr. Tang and colleagues provides a different view—that the consistency of maternal care may be more important than the amount of maternal care and that other sources of influences, such as environmental novelty can play an important role in shaping a child's development.

If You're Feeling Helpless, It May Be Best To Be Alone

2009-12-13T05:13:00.000-08:00

If you're going to experience a period of helplessness, it's best to be alone. New research at the University of Haifa found that laboratory rats that were on their own when exposed to uncontrollable conditions, which create a feeling of helplessness, learned to avoid situations which create such feelings better than rats that were exposed to uncontrollable conditions in pairs.

The way laboratory rats react to uncontrollable situations in which their behaviors have no influence on subsequent events has been researched in the past. Results show that rats that are exposed to a situation in which they are powerless, for example, electric shocks that they can't possibly avoid, have a more difficult time learning how to avoid them in the future than rats that were never exposed to situations of helplessness -- a phenomenon known as "learned helplessness."

Researchers choose to experiment with rats because they are know as social animals and their brains work much the same way as human brains. However, most of the research done until now was done on rats exposed to uncontrollable conditions when they are alone.

In his doctoral dissertation, Dr. Qutaiba Agbaria, under the supervision of Dr. Richard Shuster, examined the differences in learned helplessness among rats that were exposed to uncontrollable conditions alone and in pairs. The researcher began with the hypothesis that rats would learn to be more adaptable in social situations, or in pairs, however, the research results revealed a very different picture. Rats that were exposed to uncontrollable conditions in pairs coped less well when they were no longer in uncontrollable situations than rats that were exposed to these situations alone.

The next phase of the research examined the influence of a rat that had never been exposed to an uncontrollable situation on a rat that had. These pairs of rats showed greater adaptability than pairs that had been exposed to helplessness as individuals or in pairs. In addition, the researchers did not find outstanding differences between the learning ability of these pairs of rats -- where one had been exposed to uncontrollable conditions and the other hadn't -- and pairs that were never exposed to uncontrollable conditions, which means that the effect of "learned helplessness" is effectively erased. "Now that we have see that "learned helplessness" can be "unlearned", we should continue to examine whether this change is a result of exposure to a rat that was not exposed to helplessness or rather that the social behavior between the two animals has another meaning," said Dr. Agbaria.

Social Scientists Build Case for 'Survival of the Kindest'

2009-12-12T02:19:00.000-08:00

Researchers at the University of California, Berkeley, are challenging long-held beliefs that human beings are wired to be selfish. In a wide range of studies, social scientists are amassing a growing body of evidence to show we are evolving to become more compassionate and collaborative in our quest to survive and thrive.

In contrast to "every man for himself" interpretations of Charles Darwin's theory of evolution by natural selection, Dacher Keltner, a UC Berkeley psychologist and author of "Born to be Good: The Science of a Meaningful Life," and his fellow social scientists are building the case that humans are successful as a species precisely because of our nurturing, altruistic and compassionate traits.

They call it "survival of the kindest."

"Because of our very vulnerable offspring, the fundamental task for human survival and gene replication is to take care of others," said Keltner, co-director of UC Berkeley's Greater Good Science Center. "Human beings have survived as a species because we have evolved the capacities to care for those in need and to cooperate. As Darwin long ago surmised, sympathy is our strongest instinct."

Empathy in our genes

Keltner's team is looking into how the human capacity to care and cooperate is wired into particular regions of the brain and nervous system. One recent study found compelling evidence that many of us are genetically predisposed to be empathetic.

The study, led by UC Berkeley graduate student Laura Saslow and Sarina Rodrigues of Oregon State University, found that people with a particular variation of the oxytocin gene receptor are more adept at reading the emotional state of others, and get less stressed out under tense circumstances.

Informally known as the "cuddle hormone," oxytocin is secreted into the bloodstream and the brain, where it promotes social interaction, nurturing and romantic love, among other functions.

"The tendency to be more empathetic may be influenced by a single gene," Rodrigues said.

The more you give, the more respect you get

While studies show that bonding and making social connections can make for a healthier, more meaningful life, the larger question some UC Berkeley researchers are asking is, "How do these traits ensure our survival and raise our status among our peers?"

One answer, according to UC Berkeley social psychologist and sociologist Robb Willer is that the more generous we are, the more respect and influence we wield. In one recent study, Willer and his team gave participants each a modest amount of cash and directed them to play games of varying complexity that would benefit the "public good." The results, published in the journal American Sociological Review, showed that participants who acted more generously received more gifts, respect and cooperation from their peers and wielded more influence over them.

"The findings suggest that anyone who acts only in his or her narrow self-interest will be shunned, disrespected, even hated," Willer said. "But those who behave generously with others are held in high esteem by their peers and thus rise in status."

"Given how much is to be gained through generosity, social scientists increasingly wonder less why people are ever generous and more why they are ever selfish," he added.

Cultivating the greater good

Such results validate the findings of such "positive psychology" pioneers as Martin Seligman, a professor at the University of Pennsylvania whose research in the early 1990s shifted away from mental illness and dysfunction, delving instead into the mysteries of human resilience and optimism.

While much of the positive psychology being studied around the nation is focused on personal fulfillment and happiness, UC Berkeley researchers have narrowed their investigation into how it contributes to the greater societal good.

One outcome is the campus's Greater Good Science Center, a West Coast magnet for research on gratitude, compassion, altruism, awe and positive parenting, whose benefactors include the Metanexus Institute, Tom and Ruth Ann Hornaday and the Quality of Life Foundation.

Christine Carter, executive director of the Greater Good Science Center, is creator of the "Science for Raising Happy Kids" Web site, whose goal, among other things, is to assist in and promote the rearing of "emotionally literate" children. Carter translates rigorous research into practical parenting advice. She says many parents are turning away from materialistic or competitive activities, and rethinking what will bring their families true happiness and well-being.

"I've found that parents who start consciously cultivating gratitude and generosity in their children quickly see how much happier and more resilient their children become," said Carter, author of "Raising Happiness: 10 Simple Steps for More Joyful Kids and Happier Parents" which will be in bookstores in February 2010. "What is often surprising to parents is how much happier they themselves also become."

The sympathetic touch

As for college-goers, UC Berkeley psychologist Rodolfo Mendoza-Denton has found that cross-racial and cross-ethnic friendships can improve the social and academic experience on campuses. In one set of findings, published in the Journal of Personality and Social Psychology, he found that the cortisol levels of both white and Latino students dropped as they got to know each over a series of one-on-one get-togethers. Cortisol is a hormone triggered by stress and anxiety.

Meanwhile, in their investigation of the neurobiological roots of positive emotions, Keltner and his team are zeroing in on the aforementioned oxytocin as well as the vagus nerve, a uniquely mammalian system that connects to all the body's organs and regulates heart rate and breathing.

Both the vagus nerve and oxytocin play a role in communicating and calming. In one UC Berkeley study, for example, two people separated by a barrier took turns trying to communicate emotions to one another by touching one other through a hole in the barrier. For the most part, participants were able to successfully communicate sympathy, love and gratitude and even assuage major anxiety.

Researchers were able to see from activity in the threat response region of the brain that many of the female participants grew anxious as they waited to be touched. However, as soon as they felt a sympathetic touch, the vagus nerve was activated and oxytocin was released, calming them immediately.

"Sympathy is indeed wired into our brains and bodies; and it spreads from one person to another through touch," Keltner said.

The same goes for smaller mammals. UC Berkeley psychologist Darlene Francis and Michael Meaney, a professor of biological psychiatry and neurology at McGill University, found that rat pups whose mothers licked, groomed and generally nurtured them showed reduced levels of stress hormones, including cortisol, and had generally more robust immune systems.

Overall, these and other findings at UC Berkeley challenge the assumption that nice guys finish last, and instead support the hypothesis that humans, if adequately nurtured and supported, tend to err on the side of compassion.

"This new science of altruism and the physiological underpinnings of compassion is finally catching up with Darwin's observations nearly 130 years ago, that sympathy is our strongest instinct," Keltner said.

Are Angry Women More Like Men?

2009-12-12T02:18:00.000-08:00

"Why is it that men can be bastards and women must wear pearls and smile?" wrote author Lynn Hecht Schafran. The answer, according to an article in the Journal of Vision, may lie in our interpretation of facial expressions.

In two studies, researchers asked subjects to identify the sex of a series of faces. In the first study, androgynous faces with lowered eyebrows and tight lips (angry expressions) were more likely to be identified as male, and faces with smiles and raised eyebrows (expressions of happiness and fear) were often labeled feminine.

The second study used male and female faces wearing expressions of happiness, anger, sadness, fear or a neutral expression. Overall, subjects were able to identify male faces more quickly than female faces, and female faces that expressed anger took the longest to identify.

"The present research shows that the association between anger and men and happiness and women is so strong that it can influence the decisions about the gender of another person when that person is viewed briefly," said Ursula Hess, PhD, from the Department of Psychology, University of Quebec at Montreal.

According to the report, the findings from this study as well as others lead to the idea that "the face is a complex social signaling system in which signals for emotion, behavioral intentions and sex all overlap."

Hess said that the same cues that make a face appear male -- a high forehead, a square jaw and thicker eyebrows -- have been linked to perceptions of dominance. Likewise, features that make a face appear female -- a rounded, baby face with large eyes -- have been linked to perceptions of the individual being approachable and warm.

"This difference in how the emotions and social traits of the two sexes are perceived could have significant implications for social interactions in a number of settings. Our research demonstrates that equivalent levels of anger are perceived as more intense when shown by men rather than women, and happiness as more intense when shown by women rather than men. It also suggests that it is less likely for men to be perceived as warm and caring and for women to be perceived as dominant."

First Evidence of Brain Rewiring in Children: Reading Remediation Positively Alters Brain Tissue

2009-12-11T05:43:00.001-08:00

Carnegie Mellon University scientists Timothy Keller and Marcel Just have uncovered the first evidence that intensive instruction to improve reading skills in young children causes the brain to physically rewire itself, creating new white matter that improves communication within the brain.

As the researchers report today in the journal Neuron, brain imaging of children between the ages of 8 and 10 showed that the quality of white matter -- the brain tissue that carries signals between areas of grey matter, where information is processed -- improved substantially after the children received 100 hours of remedial training. After the training, imaging indicated that the capability of the white matter to transmit signals efficiently had increased, and testing showed the children could read better.

"Showing that it's possible to rewire a brain's white matter has important implications for treating reading disabilities and other developmental disorders, including autism," said Just, the D.O. Hebb Professor of Psychology and director of Carnegie Mellon's Center for Cognitive Brain Imaging (CCBI).

Dr. Thomas R. Insel, director of the National Institute of Mental Health, agreed. "We have known that behavioral training can enhance brain function. The exciting breakthrough here is detecting changes in brain connectivity with behavioral treatment. This finding with reading deficits suggests an exciting new approach to be tested in the treatment of mental disorders, which increasingly appear to be due to problems in specific brain circuits," Insel said.

Keller and Just's study was designed to discover what physically changes in the brains of poor readers who make the transition to good reading. They scanned the brains of 72 children before and after they went through a six-month remedial instruction program. Using diffusion tensor imaging (DTI), a new brain imaging technique that tracks water movement in order to reveal the microscopic structure of white matter, Keller and Just found a brain change involving the white matter cabling that wires different parts of the brain together.

"Water molecules that are inside nerve fibers tend to move or diffuse parallel to the nerve fibers," explained Keller, a CCBI research scientist and author of the first developmental study of compromised white matter in autism. "To track the nerve fibers, the scanner senses areas in which many water molecules are moving along in the same direction and produces a road-map of the brain's wiring."

Previous DTI studies had shown that both children and adults with reading difficulty displayed areas of compromised white matter. This new study shows that 100 hours of intensive reading instruction improved children's reading skills and also increased the quality of the compromised white matter to normal levels. More precisely, the DTI imaging illustrated that the consistency of water diffusion had increased in this region, indicating an improvement in the integrity of the white matter tracts.

"The improved integrity essentially increases communication bandwidth between the two brain areas that the white matter connects, by a factor of 10," Just said. "This opens a new era of being able to see the brain wiring change when an effective instructional treatment is applied. It lets us see educational interventions from a new perspective."

Out of the 72 children, 47 were poor readers and 25 were reading at a normal level. The good readers and a group of 12 poor readers did not receive the remedial instruction, and their brain scans did not show any changes. "The lack of change in the control groups demonstrates that the change in the treated group cannot be attributed to naturally occurring maturation during the study," Keller said.

Keller and Just also found that the amount of change in diffusion among the treated group was directly related to the amount of increase in phonological decoding ability. The children who showed the most white matter change also showed the most improvement in reading ability, confirming the link between the brain tissue alteration and reading progress.

Additional analyses indicated that the change resulted from a decrease in the movement of water perpendicular to the main axes of the underlying white matter fibers, a finding consistent with increased myelin content in the region. Although the authors caution that further research will be necessary to uncover the precise mechanism for the change in white matter, some previous findings indicate a role for electrical activity along axons in promoting the formation of myelin around them, providing a plausible physiological basis for intensive practice and instruction increasing the efficiency of communication among brain areas.

"We're excited about these results," Just said. "The indication that behavioral intervention can improve both cognitive performance and the microstructure of white matter tracts is a breakthrough for treating and understanding development problems."

Battle of the Sexes: Ovaries Must Suppress Their Inner Male

2009-12-11T05:41:00.000-08:00

Is it a boy or a girl? Expecting parents may be accustomed to this question, but contrary to what they may think, the answer doesn't depend solely on their child's sex chromosomes.

Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany and the Medical Research Council's National Institute for Medical Research (NIMR) at Mill Hill, UK discovered that if a specific gene located on a non-sex chromosome is turned off, cells in the ovaries of adult female mice turn into cells typically found in testes. Their study, published in Cell, challenges the long-held assumption that the development of female traits is a default pathway. At the same time, it grants a valuable insight into how sex determination evolved.

In humans and most other mammals, an individual's sex is determined by its sex chromosomes: females have two X chromosomes, males have one X and one Y. Scientists had long assumed that the female pathway -- the development of ovaries and all the other traits that make a female -- was a kind of default: if it had a gene called Sry, which is located on the Y chromosome, an embryo would develop into a male, if not, then the result would be a female. But in adult animals it is the male pathway that needs to be actively suppressed, as Mathias Treier and his team at EMBL discovered.

A gene called Foxl2, which is located on an autosome -- a chromosome other than the sex chromosomes -- and therefore present in both sexes, was known to play an important role in the female pathway, but its precise function remained elusive. To elucidate the matter, Treier and colleagues ablated, or 'turned off', this gene in the ovaries of adult female mice.

"We were surprised by the results," says Treier, "We expected the mice to stop producing oocytes, but what happened was much more dramatic: somatic cells which support the developing egg took on the characteristics of the cells which usually support developing sperm, and the gender-specific hormone-producing cells also switched from a female to a male cell type."

Thus, the scientists discovered that Foxl2 plays a crucial role in keeping female mice female.

Teaming up with the group of Robin Lovell-Badge at the NIMR, they were able to decipher together the underlying molecular mechanism. They showed that FOXL2 and estrogen receptor act together by repressing a DNA element called TESCO that Lovell-Badge's group had previously identified to regulate expression of the testes-promoting gene Sox9. Sox9 was known to function in the embryo to make the early gonads become testes rather than ovaries, but the new studies suggest that it can perform the same task in the adult. FOXL2 is therefore critical to keep Sox9 turned off in ovaries throughout life.

"As most vertebrates have Foxl2, estrogen receptors and Sox9," Lovell-Badge explains, "this mechanism for maintaining female traits probably appeared early on in the evolution of vertebrates, while Sry and the mammalian Y chromosome are relatively new inventions."

These findings will have wide-ranging implications for reproductive medicine and may, for instance, help to treat sex differentiation disorders in children, for example where XY individuals develop as females or XX as males, and understand the masculinising effects of menopause on some women.

Why King Kong Failed to Impress: Humans, Apes Use Odor-Detecting Receptors Differently

2009-12-10T06:26:00.000-08:00

Humans have the same receptors for detecting odors related to sex as do other primates. But each species uses them in different ways, stemming from the way the genes for these receptors have evolved over time, according to Duke University researchers.

Varying sensitivity to these sex-steroid odors may play a role in mate selection -- and perhaps prevent cross-species couplings, the researchers speculate.

The researchers analyzed the sequences and functions of the gene for the odorant receptor OR7D4 in terms of perceiving two steroid molecules related to testosterone, androstenone and androstadienone. The study did not try to examine how the receptors and odor perception might relate to behavior.

"There's variation in sensitivity of the odorant receptor from this gene (all primates) have," said Hiroaki Matsunami, associate professor of molecular genetics and microbiology and neurobiology at Duke University Medical Center. "Maybe these molecules operate in the process of reproduction. The fact that there is variation fits with this theory. Reproduction demands that an animal avoid attraction to other species, so variation in the receptor's sensitivity to these odors may prevent any cross-species attraction."

The study was published online Dec. 3 in the Early Edition of the Proceedings of the National Academy of Sciences.

Animals rely on olfactory signals to make all sorts of decisions about other animals, particularly in reproduction, said Christine Drea, Ph.D., an associate professor of Biology at Duke who was not involved with this study. "Beyond identifying members of the same species, odors help identify kin or nonkin, members of the opposite sex, even whether individuals are fertile or genetically appropriate as mates. How they do so is still largely unknown," she said. "By deciphering evolutionary changes in receptor function across species, Dr. Matsunami and his colleagues have brought us another step closer to unraveling the mysteries of olfactory signaling."

The odorant receptor gene, which the paper traces back to the mongoose lemur, evolved differently within the various primate species. Human receptors were found to be most closely related to the chimps and bonobo monkeys, as opposed to gorillas and other primates.

The findings support the evidence that primates have a common ancestor, but we are very different now. "One of the differences is in how well we are able to sense odors, which is exemplified by changes in the function of this odor receptor," Matsunami said.

Ultimately, the work will aim at discerning how smelling these chemicals might affect human social and sexual behavior. "We will begin working with a collaborator to examine chimpanzee behavior with regard to odor perception," Matsunami said.

However, the sense of smell also can vary from animal to animal and person to person, because of combinations of a number of odor receptors.

"The sex-steroid related odors act as pheromones in pigs," Matsunami said. "Pigs that are ovulating and that are exposed to the pheromones assume a mating posture. It's debatable whether these chemicals act similarly in humans. But there is evidence that smelling these odors can affect the mood and physiological state of both men and women. We have a lot more studying to do, but this finding and others in the future will create a picture of how smell may relate to sexual reproduction."

Matsunami added that there are likely other receptors and receptor variants that may also play roles in how these two chemicals are perceived. Because there are about 400 specific smell receptors and humans can detect more than 10,000 different odors, different combinations of receptor genes and variants must be involved in perceiving each odor, Matsunami said.

First Evidence of Brain Rewiring in Children: Reading Remediation Positively Alters Brain Tissue

2009-12-10T06:23:00.000-08:00

Spices Halt Growth of Breast Stem Cells, Study Finds

2009-12-08T01:15:00.000-08:00

A new study finds that compounds derived from the spices turmeric and pepper could help prevent breast cancer by limiting the growth of stem cells, the small number of cells that fuel a tumor's growth.

Researchers at the University of Michigan Comprehensive Cancer Center have found that when the dietary compounds curcumin, which is derived from the Indian spice turmeric, and piperine, derived from black peppers, were applied to breast cells in culture, they decreased the number of stem cells while having no effect on normal differentiated cells.

"If we can limit the number of stem cells, we can limit the number of cells with potential to form tumors," says lead author Madhuri Kakarala, M.D., Ph.D., R.D., clinical lecturer in internal medicine at the U-M Medical School and a research investigator at the VA Ann Arbor Healthcare System.

Cancer stem cells are the small number of cells within a tumor that fuel the tumor's growth. Current chemotherapies do not work against these cells, which is why cancer recurs and spreads. Researchers believe that eliminating the cancer stem cells is key to controlling cancer. In addition, decreasing the number of normal stem cells -- unspecialized cells that can give rise to any type of cell in that organ -- can decrease the risk of cancer.

In this study, a solution of curcumin and piperine was applied to the cell cultures at the equivalent of about 20 times the potency of what could be consumed through diet. The compounds are available at this potency in a capsule form that could be taken by mouth. (Note: This work has not been tested in patients, and patients are not encouraged to add curcumin or piperine supplements to their diet at this time.)

The researchers applied a series of tests to the cells, looking at markers for breast stem cells and the effects of curcumin and piperine, both alone and combined, on the stem cell levels. They found that piperine enhanced the effects of curcumin, and that the compounds interrupted the self-renewal process that is the hallmark of cancer-initiating stem cells. At the same time, the compounds had no affect on cell differentiation, which is the normal process of cell development.

"This shows that these compounds are not toxic to normal breast tissue," Kakarala says. "Women at high risk of breast cancer right now can choose to take the drugs tamoxifen or raloxifene for prevention, but most women won't take these drugs because there is too much toxicity. The concept that dietary compounds can help is attractive, and curcumin and piperine appear to have very low toxicity."

Curcumin and piperine have been explored by other researchers as a potential cancer treatment. But this paper, published online in the journal Breast Cancer Research and Treatment, is the first to suggest these dietary compounds could prevent cancer by targeting stem cells.

In addition, tamoxifen or raloxifene are designed to affect estrogen, which is a factor in most, but not all breast cancers. In fact, the aggressive tumors that tend to occur more often in women with a family history or genetic susceptibility are typically not affected by estrogen. Because curcumin and piperine limit the self renewal of stem cells, they would impact cancers that are not estrogen sensitive as well as those that are.

Researchers are planning an initial Phase I clinical trial to determine what dose of curcumin or piperine can be tolerated in people. The trial is not expected to begin accruing participants until spring.

Breast cancer statistics: 194,280 Americans will be diagnosed with breast cancer this year and 40,610 will die from the disease, according to the American Cancer Society

Why Humans Outlive Apes: Human Genes Have Adapted to Inflammation, but We Are More Susceptible to Diseases of Aging

2009-12-08T01:14:00.000-08:00

In spite of their genetic similarity to humans, chimpanzees and great apes have maximum lifespans that rarely exceed 50 years. The difference, explains USC Davis School of Gerontology Professor Caleb Finch, is that as humans evolved genes that enabled them to better adjust to levels of infection and inflammation and to the high cholesterol levels of their meat rich diets.

In the December issue ofProceedings of the National Academy of Sciences (Early Edition), Finch reveals that these evolutionary genetic advantages, caused by slight differences in DNA sequencing and improvements in diet, make humans uniquely susceptible to diseases of aging such as cancer, heart disease and dementia when compared to other primates.

Finch, the ARCO & William F. Kieschnick Professor in the Neurobiology of Aging and a distinguished University Professor, argues that a major contributor to longevity for humans is the genes that adapt to higher exposure to inflammation.

"Over time, ingestion of red meat, particularly raw meat infected with parasites in the era before cooking, stimulates chronic inflammation that leads to some of the common diseases of aging," Finch said.

In addition to differences in diets between species of primates, humans evolved unique variants in a cholesterol transporting gene, apolipoprotein E, which also regulates inflammation and many aspects of aging in the brain and arteries.

ApoE3 is unique to humans and may be what Finch calls "a meat-adaptive gene" that has increased the human lifespan.

However, the minor allele, apoE4, when expressed in humans, can impair neuronal development, as well as shorten human lifespan by about four years and increase the risk of heart disease and Alzheimer disease by several-fold. ApoE4 carriers have higher totals of blood cholesterol, more oxidized blood lipids and early onset of coronary heart disease and Alzheimer's disease.

"The chimpanzee apoE functions more like the "good" apoE3, which contributes to low levels of heart disease and Alzheimer's," Finch said. Correspondingly, chimpanzees in captivity have unusually low levels of heart disease and Alzheimer-like changes during aging.

Finch hypothesizes that the expression of ApoE4 could be the result of the antagonistic pleiotropy theory of aging, in which genes selected to fight diseases in early life have adverse affects in later life.

"ApoeE may be a prototype for other genes that enabled the huge changes in human lifespan, as well as brain size, despite our very unape-like meat-rich diets," Finch said. "Drugs being developed to alter activities of apoE4 may also enhance lifespan of apoE4 carriers."

Scientists Rescue Visual Function in Rats Using Induced Pluripotent Stem Cells

2009-12-05T02:35:00.000-08:00

An international team of scientists has rescued visual function in laboratory rats with eye disease by using cells similar to stem cells. The research shows the potential for stem cell-based therapies to treat age-related macular degeneration in humans.

A team led by Dennis Clegg, of UC Santa Barbara, and Pete Coffey, of University College London (UCL), published their work in two papers, including one published the week of December 1 in the journal PloS One. The first paper was published in the October 27 issue of the journal Stem Cells.

The scientists worked with rats that have a mutation which causes a defect in retinal pigmented epithelial (RPE) cells and leads to photoreceptor death and subsequent blindness. Human RPE cells were derived from induced pluripotent stem cells -- embryonic stem cell-like cells that can be made from virtually any cell in the body, thus avoiding the controversy involved in using stem cells derived from embryos. Pluripotent means that the cells can become almost any cell in the body.

In experiments spearheaded by UCL's Amanda Carr, the team found that by surgically inserting stem cell-derived RPE into the retinas of the rats before photoreceptor degeneration, vision was retained. They found that the rats receiving the transplant tracked their visual focus in the direction of moving patterns more efficiently than control groups that did not receive a transplant.

"Although much work remains to be done, we believe our results underscore the potential for stem-cell based therapies in the treatment of age-related macular degeneration," said Sherry Hikita, an author on both papers and director of UCSB's Laboratory for Stem Cell Biology.

Dave Buchholz, first author of the article in Stem Cells, explained that by using induced stem cells that can be derived from patients, the scientists avoid immune rejection that might occur when using embryonic stem cells.

According to Buchholz, "RPE cells are essential for visual function. Without RPE, the rod and cone photoreceptors die, resulting in blindness. This is the basic progression in age-related macular degeneration. The hope is that by transplanting fresh RPE, derived from induced pluripotent stem cells, the photoreceptors will stay healthy, preventing vision loss."

Learning by Imagining: How Mental Imagery Training Aids Perceptual Learning

2009-12-05T02:31:00.000-08:00

Practice makes perfect. But imaginary practice? Elisa Tartaglia of the Laboratory of Psychophysics at Switzerland's Ecole Polytechnique Federale de Lausanne (EPFL) and team show that perceptual learning -- learning by repeated exposure to a stimulus -- can occur by mental imagery as much as by the real thing. The results, published in Current Biology, suggest that thinking about something over and over again could actually be as good as doing it.

"When trained, radiologists are able to detect anomalies on medical images which are extremely hard to detect for untrained people," Tartaglia says. "The results of our study would predict that mental imagery training, hence, repeatedly mentally visualizing the anomalies that one wants to detect, would be sufficient to become able to detect them."

In a series of experiments, the scientists asked some participants to practice identifying which line, the right or the left in a series of parallel lines, a central line was closest to and to identify it by pushing the correct button. In follow-up, "post-training" exercises, these participants improved their baseline performance significantly. But so did another set of volunteers who, instead of practicing with all three lines in training, were instead asked to imagine the bisecting line's proximity based on an audio tone. This group also improved their performance significantly in further testing, meaning that "imagery training" was sufficient for perceptual learning.

Some experts question the relevance of mental imagery in this kind of learning, which is generally assumed to be driven by stimulus processing -- synapses firing in response to a physical cue. Here, the researchers show that perceptual learning can also occur by mental imagery, i.e., in the absence of physical stimulation. The results help shine a light on what has been an ongoing puzzle in the field and suggest an overlap in how -- and possibly where -- mental imagery affects perceptual learning.

New Therapy Targets for Amyloid Disease

2009-12-05T02:29:00.000-08:00

A major discovery is challenging accepted thinking about amyloids -- the fibrous protein deposits associated with diseases such as Alzheimer's and Parkinson's -- and may open up a potential new area for therapeutics.

It was believed that amyloid fibrils -- rope-like structures made up of proteins sometimes known as fibres -- are inert, but that there may be toxic phases during their formation which can damage cells and cause disease.

But in a paper published December 4 2009 in the Journal of Biological Chemistry, scientists at the University of Leeds have shown that amyloid fibres are in fact toxic -- and that the shorter the fibre, the more toxic it becomes.

"This is a major step forward in our understanding of amyloid fibrils which play a role in such a large number of diseases," said Professor Sheena Radford of the Astbury Centre for Structural Molecular Biology and the Faculty of Biological Sciences.

"We've revisited an old suspect with very surprising results. Whilst we've only looked in detail at three of the 30 or so proteins that form amyloid in human disease, our results show that the fibres they produce are indeed toxic to cells especially when they are fragmented into shorter fibres. "

Amyloid deposits can accumulate at many different sites in the body or can remain localised to one particular organ or tissue, causing a range of different diseases. Amyloid deposits can be seen in the brain, in diseases such as Parkinson's and Alzheimer's, whereas in other amyloid diseases deposits can be found elsewhere in the body, in the joints, liver and many other organs. Amyloid deposits are also closely linked to the development of Type II diabetes.

Professor Radford said: "Problems in the self-assembly process that results in the formation of amyloid are a natural consequence of longer life. In fact 85 per cent of all cases of disease caused by amyloid deposits are seen in those over the age of sixty or so."

The study was funded by the Wellcome Trust and the Biotechnology and Biological Sciences Research Council (BBSRC), supporting a team that included both cell biologists and biophysicists.

The next stage of this work is to look at a greater number of proteins that form amyloid fibres in order to consolidate these findings, says co-author and cell biologist Dr Eric Hewitt. "What we've discovered is fundamental and offers a whole new area for those working on therapeutics in this area. We anticipate that when we look at amyloid fibres formed from other proteins, they may well follow the same rules."

The team also hopes to discover why the shorter amyloid fibres are more toxic that their longer counterparts.

"It may be that because they're smaller it's easier for them to infiltrate cells," says Dr Hewitt. "We've observed them killing cells, but we're not sure yet exactly how they do it. Nor do we know whether these short fibres form naturally when amyloid fibres assemble or whether some molecular process makes them disassemble or fragment into shorter fibres.These are our next big challenges."

Newly Discovered Fat Molecule: An Undersea Killer With an Upside

2009-12-05T02:15:00.000-08:00

A chemical culprit responsible for the rapid, mysterious death of phytoplankton in the North Atlantic Ocean has been found by collaborating scientists at Rutgers University and the Woods Hole Oceanographic Institution (WHOI). This same chemical may hold unexpected promise in cancer research.

The team discovered a previously unknown lipid, or fatty compound, in a virus that has been attacking and killing Emiliania huxleyi, a phytoplankton that plays a major role in the global carbon cycle.

"Emiliania huxleyi is the rock star of phytoplankton," explains Kay Bidle, Rutgers assistant professor of marine science in the Institute of Marine and Coastal Sciences. "It blooms all over the oceans, and we can easily see it by satellite. We know that these blooms are frequently infected with viruses, and this virus is specific to this phytoplankton."

The lipids are the key ingredient in the virus that causes the phytoplankton to die," says WHOI scientist Benjamin Van Mooy. "We have a completely different lipid molecule that, as far as we know, is unknown to science."

E. huxleyi grows rapidly in the North Atlantic, "in these big blooms that you can actually see from outer space," Van Mooy says.

"But," adds Van Mooy, "they die just almost as quickly as they start out, and we're not sure why. They die after a few days."

Bidle and Assaf Vardi, a postdoctoral investigator in his laboratory and the study's lead author, had been examining the interaction between the virus and the dying phytoplankton and had developed ideas for how this process works. After Vardi heard lipid expert Van Mooy give a talk in Santa Fe, N.M., he suggested the collaboration between WHOI and Rutgers.

"I saw Ben's talk on marine microbes and lipids…[and] I ran after him," said Vardi. "We told him about our ideas" involving the virus's effect on the phytoplankton.

"They studied the viruses and I study lipids," Van Mooy said. "It seemed like a good mix."

Their paper is published in the Nov. 6 issue of Science., E. huxleyi performs photosynthesis -- "just like plants," says Van Mooy. "They suck up carbon dioxide." In doing so, they reduce the amount of CO2 released into the atmosphere. They form a calcium carbonate shell, also helping to regulate the carbon cycle.

If viruses are killing off phytoplankton, this can increase greenhouse emissions, Van Mooy suggests. "That's important because if viruses infect a whole bunch of cells, then they can't perform photosynthesis, they can't take up carbon dioxide."

In April 2008, Van Mooy's team visited the sites of E. huxleyiblooms during a research cruise between Woods Hole and Bermuda and collected samples for lipid analysis back in the laboratory.

They immediately recognized lipids that were just like those in virally infected E. huxleyi cells grown by the Rutgers team. Helen Fredricks, a research associate with Van Mooy, carried out the lipid analyses at WHOI. "Seeing this viral lipid appear during the course of infection was amazing, and then we found it in the ocean too. We were celebrating in the lab that day."

Adds Vardi: "Viruses are really important players in regulating phytoplankton blooms. We zoom into the bloom and try to understand the interaction between the viruses and host, which is this really important, cosmopolitan, bloom-forming species."

After isolating the viral lipids, the team found that the lipids alone were able to bring about the symptoms of viral infection in the phytoplankton. "The lipids themselves act just like the virus," says Van Mooy. "We can cause the phytoplankton to die by just giving the lipids."

This alone was enough to excite the team. "Now we have a biological marker that we can go out on a ship and look for and identify where this [infection of phytoplankton] is happening and learn how to study it better," Van Mooy says.

But there may be other, even farther-reaching implications. Both the virus and the newly found lipid deal their deadly blow by causing the upper-ocean plants to commit cellular suicide. As a major focus of their research at Rutgers, Bidle's lab has found that "programmed cell death" is an important process in the fate of marine phytoplankton and in the demise of blooms in the oceans. Bidle's group had previously found that successful infection of E. huxleyi induced, and actually required, the programmed cell death pathway.

But programmed cell death is not unique to phytoplankton. It is a common and healthy process in all kinds of cells, including human cells.

According to Vardi, "These lipids can induce programmed cell death in many organisms, including animals and plants. They also enrich in plasma membrane, and they are the port of the cell, where pathogens get in and out of the cell. This is important in viral diseases."

There is also a potential connection with cancer. If a healthy cell is stressed or damaged, usually it will kill itself with programmed cell death. But cancer cells have a defect: "They don't kill themselves," says Bidle.

"It's a critical aspect of cancer research, because cancer cells have figured out a way to turn off the programmed cell death pathway," he says. "In cancer studies, they try to figure out ways to reactivate those pathways."

The lipid may help shed light on why cancer cells are unable to commit suicide. Someday, the researchers say, it might suggest ways to correct that defect. Right now, the lipid is only known to be effective in algae, but in the future, the team is hoping to test the effectiveness of their molecule in experiments with cancer cells.

"There's a long way to go between here and curing cancer," Van Mooy says, "but the potential exists that this molecule could have therapeutic applications in the treatment of human disease, including cancer. Hopefully this paper will pique the interest of other investigators."

More immediately, scientists hope to learn more about the central role phytoplankton -- and viruses -- play in regulating climate. Bidle says this is a particularly interesting virus. "It appears that the virus has…borrowed, copied actually, the genes for this lipid from the host," he says. "Similar genes are still on the host, but the virus has figured out a way to take those genes and put them into its own genome, and alter them enough to make them more toxic."

"We find the biosynthetic pathway for this unique lipid encoded in the virus genome, not only in the host, and this has never been described before in any other virus," Vardi says. "We knew that [lipids] were important, but we were really intrigued about why the virus contained these genes. And what is the role of the pathway in the co-evolution of programmed cell death in the host and virus."

Van Mooy sees it as a struggle between two mighty forces. "The phytoplankton are at one end of the boxing ring and they're taking up carbon dioxide, and the viruses are at the other end, and they're out to kill them. And how that works out controls how much carbon dioxide is taken up.

"We're very interested in understanding what controls these phytoplankton," he says. "I didn't know that much about viruses until I started working on this project and the Rutgers researchers didn't know that much about lipids. So now we're both really onto something here. We're continuing to collaborate. "We have found other interesting lipids from these viruses," says Van Mooy.

"There are probably more out there. And who knows what kind of activities they may be involved with. They may hold a cure for a human disease or they may play unknown role in…phytoplankton.

Music and Speech Based on Human Biology, New Evidence Shows

2009-12-04T05:51:00.000-08:00

A pair of studies by Duke University neuroscientists shows powerful new evidence of a deep biological link between human music and speech.

The two new studies found that the musical scales most commonly used over the centuries are those that come closest to mimicking the physics of the human voice, and that we understand emotions expressed through music because the music mimics the way emotions are expressed in speech. Composers have long exploited the perception of minor chord music as sad and major chord music as happy, now the Duke team thinks they know why.

In a paper appearing in the Journal of the Acoustical Society of America(JASA), the Duke team, led by Dale Purves, a professor of neurobiology, found that sad or happy speech can be categorized in major and minor intervals, just as music can. So your mother was right: It's not only the words you say, but how you say them.

In a second paper appearing Dec. 3 in the online journal PLOS One, Kamraan Gill, another member of the team, found the most commonly used musical scales are also based on the physics of the vocal tones humans produce.

"There is a strong biological basis to the aesthetics of sound," Purves said. "Humans prefer tone combinations that are similar to those found in speech."

This evidence suggests the main biological reason we appreciate music is because it mimics speech, which has been critical to our evolutionary success, said Purves, who is also director of Duke's Neuroscience and Behavioral Disorders Program and executive director of the A*STaR Neuroscience Research Partnership at the Duke-NUS Graduate Medical School in Singapore.

To study the emotional content of music, the Duke team collected a database of major and minor melodies from about 1,000 classical music compositions and more that 6,000 folk songs and then analyzed their tonal qualities.

They also had 10 people speak a series of single words with 10 different vowel sounds in either excited or subdued voices, as well as short monologues.

The team then compared the tones that distinguished the major and minor melodies with the tones of speech uttered in the different emotional states. They found the sound spectra of the speech tones could be sorted the same way as the music, with excited speech exhibiting more major musical intervals and subdued speech more minor ones.

The tones in speech are a series of harmonic frequencies, whose relative power distinguishes the different vowels. Vowels are produced by the physics of air moving through the vocal cords; consonants are produced by other parts of the vocal tract.

In the PLOS One paper, the researchers argue the harmonic structure of vowel tones forms the basis of the musical scales we find most appealing. They show the popularity of musical scales can be predicted based on how well they match up with the series of harmonics characteristic of vowels in speech.

Although there are literally millions of scales that could be used to divide the octave, most human music is based on scales comprised of only five to seven tones. The researchers argue the preference for these particular tone collections is based on how closely they approximate the harmonic series of tones produced by humans.

Though they only worked with western music and spoken English, there is reason to believe these findings are more widely applicable. Most of the frequency ratios of the chromatic musical scale can be found in the speech of a variety of languages. Their analysis included speakers of Mandarin Chinese, said Duke neuroscience graduate student Daniel Bowling, who is the first author on the JASA paper, and this showed similar results.

"Our appreciation of music is a happy byproduct of the biological advantages of speech and our need to understand its emotional content," Purves said.

It would be hard to say whether singing or speech came first, but graduate student Dan Bowling supposes "emotional communication in both speech and music is rooted in earlier non-lingual vocalizations that expressed emotion."

Leptin Found To Control Appetite And Limb Development In Frogs

2009-12-04T05:47:00.000-08:00

Leptin, the hormone secreted by fat cells that plays an important role in food intake, has been described for the first time in a cold-blooded vertebrate, the South African clawed frog Xenopus.

As it does in humans and other mammals, leptin acts on the frog brain to suppress appetite. But the hormone also seems to play a role in the complex signaling that turns a finned tadpole into a four-legged frog, according to Robert Denver, an associate professor of biology at the University of Michigan.

Denver's team gave frogs a dose of leptin at various stages of development from tadpole to near adult and watched what happened. As in mice, the hormone is apparently a powerful appetite suppressant for these animals, causing them to give up eating even as their bodies waste away.

But the youngest tadpoles showed a different response to the hormone. Rather than going off their feed as the older frogs did, these tadpoles kept right on eating and quickly sprouted limbs.

Denver, who has studied the ability of frogs to speed up their metamorphosis in response to a drying pond, thinks that the tadpoles' feeding mechanism is stuck in the "on" position at the first stages of life, because they need to eat and grow as fast as possible to avoid being prey. For these tadpoles, the leptin signal isn't capable of turning the feeding behavior off, but it does apparently tell their bodies that they've had enough to eat now, and they can begin sprouting limbs.

"Leptin gets a lot of attention for its role in food intake, but it's clear that it does lots of other jobs," he said. The hormone is known to be part of a family of proteins called cytokines that includes pituitary growth hormone, and it has been found to increase cell proliferation in the brains of rats.

Leptin is also found in late-stage fetal humans, mice, and sheep, and appears to be linked to birth weight, but little is known about what role it might be playing overall in fetal growth and development.

Denver's study showed that there are receptors in the tadpole's waiting limbs that crank up cell division when leptin signals are received. "This hormone sets the stage for growth, both signaling to the brain that there are sufficient energy stores and perhaps directly promoting tissue growth and development." The timing of metamorphosis in frogs is central to their survival, Denver said. If tadpoles metamorphose too soon they are at a body size disadvantage with little fat reserves. They pay the cost of immediate survival by being more prone to drying out, to being eaten by predators and reaching sexual maturity at a later age. Denver speculates that leptin is probably important to gauge whether the tadpole has adequate energy reserves---in the form of body fat - to start metamorphosis at an appropriate time.

Finding leptin in the Xenopus genome was no small feat. The sequence for the "obese" gene that makes leptin is quite different between frogs and humans, so Denver's lab had some puzzles to solve to successfully clone the frog gene. But once they solved those issues and put the gene into E. coli bacteria to make quantities of leptin, the frog protein turned out to be functionally very similar to the human version, Denver notes.

"It would appear that leptin and its role as an energy balance indicator has been around a long time," Denver said. "Leptin's other roles in animal development are just beginning to be understood."

How a Brain Hormone Controls Insect Metamorphosis

2009-12-04T05:44:00.000-08:00

A team of University of Minnesota researchers have discovered how PTTH, a hormone produced by the brain, controls the metamorphosis of juvenile insects into adults.

The finding, published in the Dec. 4 issue of Science, will help scientists understand how insect body size is programmed in response to developmental and environmental cues and offers the opportunity to develop a new generation of more environmentally safe ways to control agricultural pests as well as insects that carry human pathogens.

Scientists have known for 100 years that a brain-derived neuropeptide known as PTTH controls metamorphosis and although its specific sequence was identified 20 years ago, the way it signaled endocrine tissue has remained elusive until now.

"Understanding the signaling pathway that controls metamorphosis has been a long-term goal for many insect physiologists," says lead author Michael O'Connor, professor of genetics, cell biology and development at the University of Minnesota's College of Biological Sciences, where he holds the Ordway Chair in Developmental Biology.

Although humans don't undergo metamorphosis, passage from childhood through puberty and development of adult sexual characteristics is also regulated by a brain-derived neuropeptide that is controlled by genetics, environment and nutrition. Understanding how this process works in insects sheds light on human development.

"In its overall design, insect metamorphosis is very much like passage through puberty," O'Connor says. "From a biological point of view, both puberty and metamorphosis accomplish the same goal -- to provide reproductive capacity for the species at the appropriate developmental time." The brain hormone becomes active when insects have reached a threshold body weight, which is also a trigger for human puberty.

Fruit flies and silk moths were used for the study; however, all insects that undergo complete metamorphosis appear to use this signaling system, O'Connor says. His next step is to learn how environmental and nutritional cues regulate the production of PTTH (prothoracicotropic hormone).

'Where Do I Know You From?' Recognition Shows Distinct Memory Processes

2009-12-03T05:27:00.000-08:00

New research from The University of Western Ontario suggests the sometimes eerie feeling experience when recognizing someone, yet failing to remember how or why, reveals important insight into how memory is wired in the human brain.

Western psychology graduate student Ben Bowles and psychology professor Stefan Köhler have found that this feeling of familiarity during recognition relies on a distinct brain mechanism and does not simply reflect a weak form of memory.

“Recognition based on familiarity can be contrasted with recognition when we spontaneously conjure up details about the episode in which we encountered the person before, such as where we met the person or when it happened,” explains Köhler.

The authors report that a rare form of brain surgery that can be highly effective for treatment of epilepsy can selectively impair the ability to assess familiarity.

“It is counterintuitive but makes a lot of sense from a theoretical perspective that familiarity can be affected, while the ability to recollect episodic detail is completely spared,” adds Köhler.

The research is based on Bowles’ Master’s thesis and was supported by a grant from the Canadian Institutes of Health Research (CIHR) to Dr. Köhler. It has important implications for understanding memory deficits in neurology, including in Alzheimer’s disease.

The study was conducted in collaboration with researchers at the London Health Sciences Centre, McGill University, and at the University of California. The research was published recently in the Proceedings of the National Academy of Sciences.

Abnormal Heartbeats Caused By Changes In Ion Channel Density

2009-12-03T05:26:00.000-08:00

Two independent studies have determined how changes in the density of different ion channels in the surface membrane of heart muscle cells can lead to life-threatening abnormal heartbeats, according to research to be published in the August 24 issue of the Journal of Clinical Investigation.

As Gail Robertson, at the University of Wisconsin — Madison, discusses in an accompanying commentary, these important studies provide new insight into the complex array of mechanisms controlling our heartbeat and how they can be perturbed.

The coordinated contraction of heart muscle cells that ensures a normal heartbeat is controlled by an electrical current that passes from one heart muscle cell to the next and along a special conduction system within the heart. A block in conduction of this electrical current disrupts the heartbeat and is the most common cause of pacemaker implantation. Many diseases that cause conduction block, including progressive familial heart block type I (PFHBI), are inherited. Olaf Pangs and colleagues, at Universität Hamburg, Germany, have now linked a mutation in the gene TRPM4 with PFHBI in 3 branches of a large South African Afrikaner pedigree with the disease. The TRPM4 gene is responsible for generating an ion channel that the authors found to be expressed at highest levels in a crucial region of the special conduction system within the human heart. Importantly, the PFHBI-associated mutation increased levels of the TRPM4 channel at the cell surface and blunted conduction of the electrical current.

A noninherited cause of an abnormal heartbeat is low levels of potassium (K+) in the blood, which can trigger life-threatening changes to the heartbeat. Shetuan Zhang and colleagues, at Queen's University, Ontario, have now determined in rabbits that low levels of potassium in the blood cause decreased levels of the IKr ion channel at the surface of rabbit heart muscle cells. Specifically, low levels of potassium caused increased internalization and degradation of the channels. Similarly, low levels of potassium in culture medium decreased levels of the human counterpart, HERG, in cell lines. These data provide insight into how a drop in levels of potassium in the blood can cause sudden cardiac death.

Second Pathway to Feeling Your Heartbeat, Study Reveals

2009-12-03T05:24:00.000-08:00

A new study suggests that the inner sense of our cardiovascular state, our "interoceptive awareness" of the heart pounding, relies on two independent pathways, contrary to what had been asserted by prominent researchers.

The University of Iowa study was published online this week in the journal Nature Neuroscience by researchers in the department of neurology in the Roy J. and Lucille A. Carver College of Medicine and the graduate programs in neuroscience and psychology.

The researchers found that, in addition to a pathway involving the insular cortex of the brain -- the target of most recent research on interoception -- an additional pathway contributing to feeling your own heartbeat exists. The second pathway goes from fibers in the skin to most likely the somatosensory cortex, a part of the brain involved in mapping the outside of the body and the sense of posture.

The UI team also confirmed the widely held belief by researchers that the insula and anterior cingulate cortex (ACC) regions of the brain are important, but not necessary, for a person to feel his or her own heartbeat. The insula helps with such higher-order functions as self-awareness, while the ACC is believed to regulate heart rate.

"What's shown in this study is there are probably two pathways that can participate in the conscious representation of these sensations," said David Rudrauf, Ph.D., assistant professor of neurology and radiology and director of the laboratory of brain imaging and cognitive neuroscience. Rudrauf is lead author of the study along with Sahib Khalsa, M.D., Ph.D., who received medical and doctoral degrees from the UI and is currently working on his psychiatry residency at UCLA.

Daniel Tranel, Ph.D., a professor of neurology and psychology and director of the postdoctoral residency program in clinical neuropsychology, and Justin Feinstein, a graduate student in clinical neuropsychology, are co-authors on the study, titled "The pathways of interoceptive awareness."

The UI researchers studied an extremely rare neurological patient named "Roger" who has virtually complete bilateral insula and ACC damage, but who has the bilateral primary somatosensory cortex intact. They also studied 11 healthy age-matched male comparison participants.

Roger has been studied in the UI laboratory for 15 years. His brain damage occurred in 1980 following an episode of herpes simplex encephalitis. With Roger, Rudrauf and his colleagues wanted to see if the regions of the brain he's missing are really necessary to feel your own heartbeat.

The researchers injected the participants with a synthetic form of adrenaline to get their hearts to shoot up about 25 beats a minute. They then had the participants turn a dial to track their moment-to-moment experience of the intensity of their heartbeat sensations.

As it turned out, Roger felt his own heartbeat just like the healthy comparison participants in a dose-response fashion.

"It was a delayed reaction, but he was still feeling it," Feinstein said.

This development suggested that the insula and ACC were not necessary, strictly speaking, for interoceptive awareness of heartbeat sensations.

The researchers suspected that Roger was feeling his heartbeat because his brain was using a different pathway, relying on the impact of the heartbeat on the chest wall and pulsations in blood vessels stretching the skin. So they applied a topical lidocaine anesthetic to the location on the skin where participants reported feeling the maximal heartbeat sensation.

They then repeated the injection procedure to increase each participant's heart rate. Roger again demonstrated heart rate increases identical to the healthy comparison participants. However, under anesthetic, he reported that he no longer felt his heartbeat. Conversely, the healthy comparison participants' ability to feel their heartbeats was unaffected by the anesthetic.

"There are two pathways. One conveys the heartbeat signal from the surface of the chest wall and blood vessels pulsating under the skin, to the somatosensory cortex, so whenever you feel your heart pounding it's stimulating that pathway," Feinstein said. "Roger is able to feel his heart beating because that area of his brain -- the somatosensory cortex -- is still there. When you get rid of that sensation by anesthetizing the skin, you need areas such as the insular cortex in order to feel the heart pulsing from deep within. That's what is missing in Roger and that's where the healthy person is able to feel it."

As emphasized by Rudrauf, interoceptive awareness, including the awareness of our cardiovascular states, is key in emotion, feeling and the sense of self. The pathways revealed by this study could be involved in everything from the pounding of the heart during a state of panic to the feeling of a "broken heart" during a state of grief.

Long-Term Physical Activity Has an Anti-Aging Effect at the Cellular Level

2009-12-03T05:22:00.000-08:00

Intensive exercise prevented shortening of telomeres, a protective effect against aging of the cardiovascular system, according to research reported in Circulation: Journal of the American Heart Association.

Researchers measured the length of telomeres -- the DNA that bookends the chromosomes and protects the ends from damage -- in blood samples from two groups of professional athletes and two groups who were healthy nonsmokers, but not regular exercisers.

The telomere shortening mechanism limits cells to a fixed number of divisions and can be regarded as a "biological clock." Gradual shortening of telomeres through cell divisions leads to aging on the cellular level and may limit lifetimes. When the telomeres become critically short the cell undergoes death. The 2009 Nobel Prize in Physiology or Medicine was awarded to researchers who discovered the nature of telomeres and how chromosomes are protected by telomeres and the enzyme telomerase.

"The most significant finding of this study is that physical exercise of the professional athletes leads to activation of the important enzyme telomerase and stabilizes the telomere," said Ulrich Laufs, M.D., the study's lead author and professor of clinical and experimental medicine in the department of internal medicine at Saarland University in Homburg, Germany.

"This is direct evidence of an anti-aging effect of physical exercise. Physical exercise could prevent the aging of the cardiovascular system, reflecting this molecular principle."

Essentially, the longer telomere of athletes is an efficient telomere. The body's cells are constantly growing and dividing and eventually dying off, a process controlled by the chromosomes within each cell. These chromosomal "end caps" -- which have been likened to the tips of shoelaces, preventing them from fraying -- become shorter with each cell division, and when they're gone, the cell dies. Short telomeres limit the number of cell divisions, Laufs said. In addition, the animal studies of Laufs and colleagues show that the regulation of telomere stabilizing proteins by exercise exerts important cellular functions beyond the regulation of telomere length itself by protecting from cellular deterioration and programmed cell death.

In the clinical study, researchers analyzed 32 professional runners, average age 20, from the German National Team of Track and Field. Their average running distance was about 73 kilometers (km), a little over 45 miles, per week.

Researchers compared the young professional athletes with middle-aged athletes with a history of continuous endurance exercise since their youth. Their average age was 51 and their average distance was about 80 km, or almost 50 miles, per week.

The two groups were evaluated against untrained athletes who were healthy nonsmokers, but who did not exercise regularly. They were matched for age with the professional athletes.

The fitness level of the athletes was superior to the untrained individuals. The athletes had a slower resting heart rate, lower blood pressure and body mass index, and a more favorable cholesterol profile, researchers said.

Long-term exercise training activates telomerase and reduces telomere shortening in human leukocytes. The age-dependent telomere loss was lower in the master athletes who had performed endurance exercising for several decades.

"Our data improves the molecular understanding of the protective effects of exercise on the vessel wall and underlines the potency of physical training in reducing the impact of age-related disease," Laufs said.

Arthritis Treatment: Just Keep Moving, Ladies

2009-12-02T05:46:00.000-08:00

Women in their 70s who keep active could be dodging painful arthritis symptoms, according to research published today in Arthritis Research & Therapy. The study is the first to show that the more you exercise, the better your chances of preventing the onset of stiff and painful joints.

Kristiann Heesch and colleagues at the University of Queensland, Australia examined data on middle-aged (48-55) and older (72-79) women collected using surveys over three years as part of the Australian Longitudinal Study on Women's Health. Excluding women who reported arthritis symptoms at the beginning of the study, the authors looked at those who began reporting stiff or painful joints 'often' and how much exercise they undertook.

The results suggest that for women in the older age bracket, doing a little over an hour of moderate physical activity each week will lessen your chances of developing frequent arthritis symptoms in the next three years. Pushing that up to 2 ½ hours per week is even more likely to prevent arthritis symptoms appearing. These results were not seen for the middle-aged group.

A debilitating health problem which is more likely to strike as we get older and affects more women than men, arthritis is almost as common as cardiovascular disease in Australia, affecting 17% of the population. By 2020 this figure is set to approach US levels, where arthritis is the most prevalent chronic condition for middle aged and older people, affecting over a fifth of the population. Exercising into old age could ensure movement without stiffness and pain for longer, and could reduce the burden of arthritis on the healthcare system.

Childhood Physical Abuse Linked To Arthritis, Study Finds

2009-12-02T05:45:00.000-08:00

Adults who had experienced physical abuse as children have 56 per cent higher odds of osteoarthritis compared to those who have not been abused, according to a new study by University of Toronto researchers.

University of Toronto researchers investigated the relationship between self-reported childhood physical abuse and a diagnosis of osteoarthritis (OA). After analyzing representative data from the 2005 Canadian Community Health Survey, the researchers determined a significant association between childhood physical abuse and osteoarthritis in adulthood.

The study is published in the November issue of the journalArthritis Care & Research.

Osteoarthritis is an often debilitating chronic condition that affects millions of adults. "We found that 10.2 per cent of those with osteoarthritis reported they had been physically abused as children in comparison to 6.5 per cent of those without osteoarthritis," says lead author Esme Fuller-Thomson of U of T's Factor-Inwentash Faculty of Social Work and Department of Family and Community Medicine. "This study provides further support for the need to investigate the possible role that childhood abuse plays in the development of chronic illness."

Co-author Sarah Brennenstuhl, a doctoral student at the University of Toronto, stated that, "We were surprised that the significant association between childhood physical abuse and osteoarthritis persisted even after controlling for major potentially confounding factors such as obesity, physical activity levels as well as age, gender, income and race."

According to Fuller-Thomson, one important avenue for future research is to investigate the pathways through which arthritis may develop as a consequence of childhood physical abuse.

Too Much Physical Activity May Lead to Arthritis, Study Suggests

2009-12-02T05:44:00.000-08:00

Middle-aged men and women who engage in high levels of physical activity may be unknowingly causing damage to their knees and increasing their risk for osteoarthritis, according to a new study presented at the annual meeting of the Radiological Society of North America (RSNA).

"Our data suggest that people with higher physical activity levels may be at greater risk for developing knee abnormalities and, thus, at higher risk for developing osteoarthritis," said Christoph Stehling, M.D., research fellow in the Department of Radiology and Biomedical Imaging at the University of California, San Francisco (UCSF) and radiology resident in the Department of Clinical Radiology, University of Muenster, Germany.

Osteoarthritis is a degenerative joint disease that causes pain, swelling and stiffness. According to the Centers for Disease Control and Prevention, osteoarthritis is the most common form of arthritis and affects an estimated 27 million American adults.

The UCSF study involved 236 asymptomatic participants who had not reported previous knee pain and were enrolled in the National Institutes of Health Osteoarthritis Initiative. Study participants included 136 women and 100 men, age 45 to 55, within a healthy weight range. The participants were separated into low-, middle-, and high-activity groups based on their responses to the Physical Activity Scale for the Elderly (PASE) questionnaire. PASE is a standard test that scores an older individual's physical activity level, based on the type of activity and the time spent doing it. Several factors contribute to the final PASE score, but a person whose activity level is classified as high typically might engage in several hours of walking, sports or other types of exercise per week, as well as yard work and other household chores.

Subsequent MRI analysis by two musculoskeletal radiologists indicated a relationship between physical activity levels and frequency and severity of knee damage. Specific knee abnormalities identified included meniscal lesions, cartilage lesions, bone marrow edema and ligament lesions. Abnormalities were associated solely with activity levels and were not age or gender specific.

"The prevalence of the knee abnormalities increased with the level of physical activity," Dr. Stehling said. "In addition, cartilage defects diagnosed in active people were more severe."

The findings also indicated that some activities carry a greater risk of knee damage over time.

"This study and previous studies by our group suggest that high-impact, weight-bearing physical activity, such as running and jumping, may be worse for cartilage health," Dr. Stehling said. "Conversely, low-impact activities, such as swimming and cycling, may protect diseased cartilage and prevent healthy cartilage from developing disease."

Dr. Stehling noted that there is a need for prospective studies to evaluate the influence of low-impact versus high-impact physical activity on disease progression.

Infections Are Common in ICUs Worldwide, Study Finds

2009-12-02T05:42:00.000-08:00

An international study that examined the extent of infections in nearly 1,300 intensive care units (ICUs) in 75 countries found that about 50 percent of the patients were considered infected, with infection associated with an increased risk of death in the hospital, according to a study in the December 2 issue of JAMA.

"Infection and related sepsis are the leading cause of death in noncardiac ICUs, with mortality rates that reach 60 percent and account for approximately 40 percent of total ICU expenditures," the authors write. International data related to the prevalence, risk factors, microorganisms causing the infections and outcomes of infection are necessary to increase awareness of the impact of infection, and to help in the development of local and international guidelines for diagnosis and treatment and guide resource allocation, according to background information in the article. However, little information is available about the global epidemiology of infections in ICUs.

Jean-Louis Vincent, M.D., Ph.D., of Erasme Hospital, Université libre de Bruxelles, Belgium, and colleagues conducted a study to provide an indication of the extent and patterns of infection in ICUs around the world. The Extended Prevalence of Infection in Intensive Care (EPIC II) study was a 1-day study (May 8, 2007), in which data including demographic, physiologic, bacteriological, therapeutic, and outcomes were collected on this day for 14,414 patients in 1,265 participating ICUs from 75 countries. Analyses focused on the data from 13,796 adult (18 years or older) patients.

The researchers found that on the day of the study, 51 percent of the patients (7,087) were classified as infected and 71 percent were receiving antibiotics (as prophylaxis or treatment). The lungs were the most common site of infection, accounting for 64 percent of infections, followed by the abdomen and bloodstream. "Seventy percent of infected patients had positive microbial isolates: 47 percent of the positive isolates were gram-positive, 62 percent gram-negative, and 19 percent fungal."

The authors also found a relationship between the number of days spent in the ICU before the study day and the rate of infection: the infection rate increased from 32 percent for patients with an ICU stay of 0 or 1 day before the day of the study to more than 70 percent for patients with an ICU stay of more than 7 days before the day of the study. Infected patients had longer ICU and hospital lengths of stay than those not infected. The ICU mortality rate of infected patients was more than twice that of noninfected patients (25 percent vs. 11 percent), as was the hospital mortality rate (33 percent vs. 15 percent).

In examining infection rates in different areas of the world, Central and South America had the highest infection rate (60 percent) and Africa had the lowest (46 percent). Also, infection rates were related to health care expenditure, with higher rates of infection reported in countries that had a lower proportion of gross domestic product devoted to health care.

"The EPIC II study demonstrates that infections remain a common problem in ICU patients," the authors write. "These important data provide a picture of patterns of infection around the world, which can enhance understanding of global and regional differences and provide pointers to help optimize infection prophylaxis and management."

Editorial: Antibiotic Usage and Resistance -- Gaining or Losing Ground on Infections in Critically Ill Patients?

In an accompanying editorial, Steven M. Opal, M.D., of Warren Alpert Medical School of Brown University, Providence, R.I., and Thierry Calandra, M.D., Ph.D., of Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland, offer suggestions regarding antibiotic usage in ICUs.

"Limiting use of antibiotics to patients with clear evidence of infection rather than colonization is essential, and discontinuation of antibiotics when their possible benefits have been obtained is also critical. New initiatives such as the use of biomarkers to aid clinicians in the decision to discontinue unnecessary antibiotic therapy should be encouraged. Immunotherapies and reduced reliance on invasive diagnostic and hemodynamic monitoring techniques might also be useful in the future. Development of novel classes of antimicrobial agents is sadly lacking and needs to be a major research priority. New drugs are needed to replace the increasingly obsolete classes of antibiotics that currently exist. A 'postantibiotic era' is difficult to contemplate but might become a reality unless the threat of progressive antibiotic resistance is taken seriously."

Protein Engineering Advancing Alzheimer’s Research

2009-11-30T22:32:00.000-08:00

No one has yet found a cure or a way to prevent people from developing Alzheimer's disease. Researchers from the Swedish University of Agricultural Sciences, among others, are breaking new ground in biotechnology to find new tools that can help provide new solutions. A protein constructed by these researchers has yielded experimental results that are promising when it comes to stopping the disease. And for the first time, using protein engineering, it seems they have successfully created the oligomer that is believed to trigger the disorder.

Alzheimer's disease is the most common form of dementia. In the 60-64 age group, one percent have the disorder, and among people age 85 and older, 25 percent are affected. At present there is no cure for Alzheimer's. Those who develop it grow gradually worse, and the disease leads to death, often after several years of sickness. Besides the tragedy entailed when people contract Alzheimer's disease, the healthcare involved consumes huge resources.

Symptoms of Alzheimer's disease begin with loss of memory. The disorder is caused by damage to the nerves in the brain. This damage is caused by so-called oligomers of the peptide Aß, which is also found in amyloid plaques, a kind of precipitate, that accumulate in the brain.

At the Swedish University of Agricultural Sciences (SLU) in Uppsala, Sweden, Professor Torleif Härd of the Department of Molecular Biology is directing a research project that is developing new biotechnological tools that could be used to in research and as potential therapies. They are deploying protein engineering, and experiments have yielded highly promising results.

One of the strategies for finding an answer to how Alzheimer's disease could be prevented is based on the idea of adding a protein to the blood, to bind to the Aß peptide there. In this way the Aß peptide becomes harmless, and the disease might be prevented.

The research team has studied how an artificial so-called Affibody protein entirely encases the Aß peptide, thereby preventing the formation of toxic forms.

"Nothing like this has ever been done before, and the results have attracted a great deal of attention," says Torleif Härd. "Our success in also determining the structure of this complex constituted a breakthrough, because it paved the way for new ideas for further research."

Now the SLU scientists, working with teams from the Royal Institute of Technology (KTH) in Stockholm and Affibody AB, are seeking to alter the characteristics of the Affibody protein so it won't be broken down when it enters the blood. The strategy is also being tested in flies, and the preliminary results indicate that the strategy works.

Another strategy involves using protein engineering to stabilize the toxic oligomers that are the cause of nerve cell death and memory loss. Oligomers are a stage halfway between the Aß peptide and amyloid plaques. In the laboratory environment they survive only about 15 minutes, making it impossible to study them. If these oligomers can be stopped, it should be possible to prevent Alzheimer's disease from breaking out. To find out more about the structure and mechanism of these oligomers, scientists need to stabilize them in order to examine them, and this is something the scientists in the project have managed to do: they have create a stable oligomer with the same toxic properties as before.

"We are now busy determining the 3D structure of the oligomer. This is important if we are to be able to further study the molecular mechanisms, and it may lead on to drug development," says Torleif Härd. In collaboration with MIVAC Development AB, they are also investigating the possibility of directly developing a vaccine against the disease.

It Takes Two to Infect: Structural Biologists Shed Light on Mechanism of Invasion Protein

2009-11-30T22:28:00.000-08:00

Bacteria are quite creative when infecting the human organism. They invade cells, migrate through the body, avoid an immune response and misuse processes of the host cell for their own purposes. To this end, every bacterium employs its own strategy.

In collaboration with a British research group, structural biologists from the Helmholtz Centre for Infection Research in Braunschweig, Germany, and the University of Bielefeld, Germany, have now elucidated one mechanism of Listeria bacteria.

Two so-called invasion proteins are crucial for infection. Each binds a specific receptor on the surface of human cells, which stimulates the host cell to take up the pathogen. Normally, these receptor molecules exert a different function, for example the regulation of cell growth and wound healing. The group's results have now been published in the current issue of the Journal of Molecular Biology.

Spoiled meat is one of the sources for Listeria infections leading to listeriosis. Pregnant women, newborns and immune compromised people are susceptible for a severe progression of this disease. Firstly, the pathogen breaches the intestinal barrier and thus enters the body. The key for further spreading is the invasion protein internalin B that is located on the bacterial surface. On human cells, internalin B activates a receptor molecule called "Met," thereby signaling the host cell to take up the pathogen. Inside the cell, Listeria uses the host cell's nutrients and is somehow sheltered from an immune response.

Until now, the researchers did not know how the bacterial invasion protein activates the human receptor. To solve this question, the structural biologists from the HZI first analysed the crystal structures of the single internalin B molecule and of its complex bound to human Met. "In X-Ray structural analysis we noticed that in protein crystals two internalin B molecules align characteristically," says Hartmut Niemann, assistant professor at the University of Bielefeld. Professor Dirk Heinz, head of the structural biologists at the HZI, explains: "This gave rise to the idea of a dimer -- two congregated internalin B molecules -- playing a pivotal role in the activation of the Met receptor."

Minor changes in the internalin B molecule confirmed their hypothesis: inhibiting the congregation of two internalin B molecules prevented the activation of Met. On the other hand, strengthening the interaction resulted in particularly strong receptor activation.

These results may lead to the development of new protein drugs in the future. "Met plays a major role in the body, for example during wound healing," says Heinz. "Thanks to the extraordinary ability of the internalin B dimer to strongly activate Met, therapeutics for improved wound healing may result someday."

Brain Scan Study Shows Cocaine Abusers Can Control Cravings

2009-11-30T22:26:00.000-08:00

When asked to inhibit their response to a "cocaine-cues" video, active cocaine abusers were, on average, able to suppress activity in brain regions linked to drug craving, according to a new study at the U.S. Department of Energy's Brookhaven National Laboratory. The results, to be published in an upcoming issue of NeuroImage, suggest that clinical interventions designed to strengthen these inhibitory responses could help cocaine abusers stop using drugs and avoid relapse.

"Exposure to drugs or stimuli associated with using drugs is one of the most common factors leading to relapse in drug-addicted individuals," said Nora Volkow, Director of the National Institute on Drug Abuse and lead author on the paper.

"We know from previous studies that drug cues can trigger dramatic changes in the brain that are linked to a strong craving response," added co-author Gene-Jack Wang, Chair of Brookhaven's medical department. "This study provides the first evidence that cocaine abusers retain some ability to cognitively inhibit their craving responses to drug-related cues."

Added Volkow, "Our findings provide enormous hope because they imply that cognitive interventions might be developed to maximize cocaine abusers' success in blocking the drug-craving response to help them avoid relapse."

The scientists used a brain-scanning technique called positron emission tomography (PET) and a radioactively "tagged" form of glucose -- the brain's main fuel -- to measure brain activity in 24 active cocaine abusers during three different conditions:

while subjects simply lay in the scanner with eyes open;
while subjects watched a "cocaine-cues" video with scenes simulating the purchase, preparation, and smoking of crack cocaine; and
while subjects watched the video but were told to try to inhibit their craving response.

Scans were performed in random order and on separate days.In each scan, the PET camera tracked the radioactive signal from the tagged glucose as it was taken up by various regions of the brain. A stronger signal indicates higher metabolic activity in a particular brain region where more glucose is being used. This technique allows scientists to accurately monitor which brain regions are most active and how that activity changes with time or in response to different situations.

The scientists also monitored the research subjects’ heart rate and blood pressure and asked them to describe their level of craving during the scans. Compared with the baseline condition, the cocaine-cues video triggered increases in brain activity in several brain regions associated with drug craving, as well as increases in research subjects’ self-reports of craving.

When the research subjects were asked to inhibit their response to the video, and those scans were compared with the no-inhibition condition, metabolic activity decreased dramatically in brain regions involved in experiencing and anticipating rewards, and in a part of the brain that plays a role in assigning value, or salience, to different stimuli. During inhibition, research subjects also reported lower levels of craving compared with the no-inhibition video condition.

The researchers say the findings have significant clinical implications: “Many current drug treatment programs help addicted individuals predict when and where they might be exposed to drug cues so that they can avoid such situations,” Volkow said. “While this is a very useful strategy, in real-word situations, cues may come up in unexpected ways. Our findings suggest that a clinical strategy that trains cocaine abusers to exert greater cognitive control could help them selectively inhibit the craving response whenever and wherever drug cues are encountered — whether expectedly or unexpectedly.”

Because inhibitory control is crucial for regulating emotions and desires, the findings from this study could have implications for other disorders involving loss of behavioral control, such as gambling and obesity.

This study was supported by the intramural program from the National Institutes of Health Intramural Research Program at the National Institute on Alcohol Abuse and Alcoholism. Brookhaven Lab’s infrastructure for PET imaging and radiotracer development also receive support from the DOE Office of Science.

Birth Control Pill for Men? Scientists Find a Hormonal on-and-Off Switch for Male Fertility

2009-11-30T22:25:00.000-08:00

A new research report published in the December 2009 print issue of The FASEB Journal could one day give men similar type of control over their fertility that women have had since the 1960s. That's because scientists have found how and where androgenic hormones work in the testis to control normal sperm production and male fertility. This opens a promising avenue for the development of "the pill" for men.

The discovery also offers hope to those who cannot have children because of low sperm counts. Although the research was conducted in mice, a similar effect is likely to obtain in other mammals, such as humans.

"This study provides a new opportunity to identify how androgens control sperm production, which could provide new insight for the development of new treatments for male infertility and perhaps new male contraceptives," said Michelle Welsh, Ph.D., co-author of the study, from the Centre for Reproductive Biology at The Queen's Medical Research Institute in Edinburgh, UK.

To make this discovery, Welsh and colleagues performed studies in two groups of mice. The first group of mice was normal, but the second group of mice was missing a gene from the peritubular myoid cells in the testis. This gene that was missing codes for the androgen hormone receptor, and when missing, sperm production was significantly decreased when compared to the normal group. The result was infertility.

"Although 'the pill' arguably has been liberating for women since its development in the 1960s, a similar birth control drug for men has been elusive," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Not only does this research pinpoint androgenic hormones and their cellular receptors as prime targets for the development of new birth control drugs, but it promises to speed the development of new agents to boost sperm production."

Small Hairy Balls Hide Foul-Tasting Healthful Enzymes

2009-11-29T22:30:00.001-08:00

Dutch researcher Saskia Lindhoud has discovered a new way to package enzymes by causing charged polymers to form a 'ball of hair' around them. Her approach significantly increases the utility of the enzymes. For example, healthy enzymes with a foul taste can be packaged in such a way that they are released in the stomach without being tasted.

Enzymes are molecules that can trigger specific chemical reactions. They are responsible for the taste of beer, the effectiveness of detergents and the digestion of food in our guts. However, the optimal use of enzymes requires that they do not trigger the chemical reactions too early or too late. Moreover, enzymes are quite sensitive to changes in their environment such as temperature fluctuations and changes in the salt concentration or pH. Enzymes can be protected from such influences by means of a packaging. Lindhoud discovered a new way of doing this well.

Hairy balls

Lindhoud used polyelectrolyte complex micelles for the packaging. These consist of at least two types of molecules that have an opposite charge and of which at least one type has a charged and an uncharged block (diblock copolymer). If these molecules are mixed together then the oppositely charged parts of the molecules form a complex because opposite charges attract. The uncharged parts of the molecules prefer not to be located in the core and stick outwards. This results in the automatic formation of balls with hairs on the outside.

As enzymes are also charged they can be packaged into these hairy balls. Yet unfortunately, particles that consist of just enzymes and diblock copolymers are not very robust. Lindhoud therefore substituted a part of the enzymes with a polymer of the same charge. This improved the stability and robustness of the particles. Moreover, Lindhoud discovered that the enzymes preferred not to be located in the core of the particle but on the boundary of this instead. Adding polymers with the same charge increased the surface of this boundary.

The advantage of enzymes packaged using Lindhoud's approach is the ease with which these can be unpackaged again. This is essential for the effective use of enzymes in industrial applications. Lindhoud's research could therefore do more than improve detergents; it could enable new applications of enzymes. One such possible application is the specific delivery of medicines. Saskia Lindhoud carried out her research with a TOP grant from the NWO Division for the Chemical Sciences. She is now a postdoctoral researcher at the University of Bath.

RNA Network Seen in Live Bacterial Cells for First Time

2009-11-29T22:28:00.000-08:00

Scientists who study RNA have faced a formidable roadblock: trying to examine RNA's movements in a living cell when they can't see the RNA. Now, a new technology has given scientists the first look ever at RNA in a live bacteria cell -- a sight that could offer new information about how the molecule moves and works.

Interest in RNA, which plays a key role in manufacturing proteins, has increased in recent years, due in large part to its potential in new drug therapies. RNA localization and movement in bacterial cell are poorly understood. The problem has been finding a way to mark RNA in a living cell so that scientists can track it, says Natasha Broude, a research associate professor at Boston University's Department of Biomedical Engineering.

"You can label any protein within the cell and watch what it is doing," says Broude, a senior researcher on the new study, published in a recent issue of the Proceedings of the National Academy of Sciences. "For RNA it was much more difficult because RNA is more mobile and less stable than both proteins and DNA."

Before now, scientists used green fluorescent protein (GFP) to label RNA in a cell. But proteins were also tagged with GFP and their fluorescence was so bright, it drowned out the glow from the RNA. "The initial idea was to do something to allow us to decrease background fluorescence," Broude says.

In 2007, Broude and her colleagues developed a system to persuade a cell to synthesize protein in two fragments rather than a whole, which made the protein inactive. They then modified an RNA molecule, adding a small tail of RNA sequence that works like a handle, grabbing the fragments and pulling them together, which makes the protein active -- and glow bright green. The scientists can then follow the RNA as it moves through the cell.

"In our case, the protein becomes fluorescent because it binds to RNA," Broude says. "If there is no RNA, we don't see this protein."

In this new work, the team modified this system to allow for the controlled synthesis of RNA -- allowing the researchers to track RNA as soon as it appears in the cell. For the study, they used live Eschericha coli cells, the simplest bacteria model, and a nonfunctional RNA. To monitor the RNA and capture images as it moved through the cell, the team used a sophisticated microscope and detection system developed by colleague Amit Meller, a co-author of the study and associate professor of biological engineering at Boston University. Meller's system made it possible to watch RNA in whole cells with high resolution. Their observations are not only the first of their kind, they also contradict previously held theories about RNA localization, which held that RNA was evenly distributed throughout the cell.

"The first thing we saw is that RNA is localized along mostly the periphery of the cell," Broude says. One possibility for this could be that the middle of the bacterial cell, which is occupied by DNA, is less accessible to the RNA.

The researchers also noted that the RNA appeared to form helical structures resembling those seen in proteins involved in producing the cell's cytoskeleton, which is involved in DNA replication, cell division and other important processes. "They are necessary structural elements which rule all changes in bacterial life," Broude says. "But we need to learn more before we can say anything about the RNA helical structure's function."

With this new technology in place, Broude and her colleagues can learn more about the RNA network they've observed, examine the localization and movement of other types of RNA in live bacterial cells and, ultimately, mammalian cells.

Other study authors included Maria Valencia-Burton, research associate in biomedical engineering, Ankita Shah, undergraduate student, Jason Sutin, graduate student, Azra Borogovac, undergraduate student, and Charles Cantor, professor and director of biomedical engineering, all at Boston University, and Ron McCullough with Sequenom, Inc.

First-Ever Blueprint of 'Minimal Cell' Is More Complex Than Expected

2009-11-29T22:25:00.000-08:00

What are the bare essentials of life, the indispensable ingredients required to produce a cell that can survive on its own? Can we describe the molecular anatomy of a cell, and understand how an entire organism functions as a system? These are just some of the questions that scientists in a partnership between the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, and the Centre de Regulacio Genòmica (CRG) in Barcelona, Spain, set out to address.

In three papers published back-to-back in Science, they provide the first comprehensive picture of a minimal cell, based on an extensive quantitative study of the biology of the bacterium that causes atypical pneumonia, Mycoplasma pneumoniae. The study uncovers fascinating novelties relevant to bacterial biology and shows that even the simplest of cells is more complex than expected.

Mycoplasma pneumoniae is a small, single-cell bacterium that causes atypical pneumonia in humans. It is also one of the smallest prokaryotes -- organisms whose cells have no nucleus -- that don't depend on a host's cellular machinery to reproduce. This is why the six research groups which set out to characterize a minimal cell in a project headed by scientists Peer Bork, Anne-Claude Gavin and Luis Serrano chose M. pneumoniae as a model: it is complex enough to survive on its own, but small and, theoretically, simple enough to represent a minimal cell -- and to enable a global analysis.

A network of research groups at EMBL's Structural and Computational Biology Unit and CRG's EMBL-CRG Systems Biology Partnership Unit approached the bacterium at three different levels. One team of scientists described M. pneumoniae's transcriptome, identifying all the RNA molecules, or transcripts, produced from its DNA, under various environmental conditions. Another defined all the metabolic reactions that occurred in it, collectively known as its metabolome, under the same conditions. A third team identified every multi-protein complex the bacterium produced, thus characterising its proteome organisation.

"At all three levels, we found M. pneumoniae was more complex than we expected," says Luis Serrano, co-initiator of the project at EMBL and now head of the Systems Biology Department at CRG.

When studying both its proteome and its metabolome, the scientists found many molecules were multifunctional, with metabolic enzymes catalyzing multiple reactions, and other proteins each taking part in more than one protein complex. They also found that M. pneumoniae couples biological processes in space and time, with the pieces of cellular machinery involved in two consecutive steps in a biological process often being assembled together.

Remarkably, the regulation of this bacterium's transcriptome is much more similar to that of eukaryotes -- organisms whose cells have a nucleus -- than previously thought. As in eukaryotes, a large proportion of the transcripts produced fromM. pneumoniae's DNA are not translated into proteins. And although its genes are arranged in groups as is typical of bacteria, M. pneumoniae doesn't always transcribe all the genes in a group together, but can selectively express or repress individual genes within each group.

Unlike that of other, larger, bacteria, M. pneumoniae's metabolism doesn't appear to be geared towards multiplying as quickly as possible, perhaps because of its pathogenic lifestyle. Another surprise was the fact that, although it has a very small genome, this bacterium is incredibly flexible and readily adjusts its metabolism to drastic changes in environmental conditions. This adaptability and its underlying regulatory mechanisms mean M. pneumoniae has the potential to evolve quickly, and all the above are features it also shares with other, more evolved organisms.

"The key lies in these shared features," explains Anne-Claude Gavin, an EMBL group leader who headed the study of the bacterium's proteome: "Those are the things that not even the simplest organism can do without and that have remained untouched by millions of years of evolution -- the bare essentials of life".

This study required a wide range of expertise, to understand M. pneumoniae's molecular organisation at such different scales and integrate all the resulting information into a comprehensive picture of how the whole organism functions as a system -- an approach called systems biology.

"Within EMBL's Structural and Computational Biology Unit we have a unique combination of methods, and we pooled them all together for this project," says Peer Bork, joint head of the unit, co-initiator of the project, and responsible for the computational analysis. "In partnership with the CRG group we thus could build a complete overall picture based on detailed studies at very different levels." Bork was recently awarded the Royal Society and Académie des Sciences Microsoft Award for the advancement of science using computational methods. Serrano was recently awarded a European Research Council Senior grant.

New Synthetic Molecules Trigger Immune Response To HIV And Prostate Cancer

2009-11-08T06:48:00.000-08:00

Researchers at Yale University have developed synthetic molecules capable of enhancing the body's immune response to HIV and HIV-infected cells, as well as to prostate cancer cells. Their findings, published online in theJournal of the American Chemical Society, could lead to novel therapeutic approaches for these diseases.

The molecules -- called "antibody-recruiting molecule targeting HIV" (ARM-H) and "antibody-recruiting molecule targeting prostate cancer" (ARM-P) -- work by binding simultaneously to an antibody already present in the bloodstream and to proteins on HIV, HIV-infected cells or cancer cells. By coating these pathogens in antibodies, the molecules flag them as a threat and trigger the body's own immune response. In the case of ARM-H, by binding to proteins on the outside of the virus, they also prevent healthy human cells from being infected.

"Instead of trying to kill the pathogens directly, these molecules manipulate our immune system to do something it wouldn't ordinarily do," said David Spiegel, Ph.D., M.D., assistant professor of chemistry and the corresponding author of both papers.

Because both HIV and cancer have methods for evading the body's immune system, treatments and vaccinations for the two diseases have proven difficult. Current treatment options for HIV and prostate cancer -- including antiviral drugs, radiation and chemotherapy -- involve severe side effects and are often ineffective against advanced cases. While there are some antibody drugs available, they are difficult to produce in large quantities and are costly. They also must be injected and are accompanied by severe side effects of their own.

By contrast, the ARM-H and ARM-P molecules, which the team has begun testing in mice, are structurally simple, inexpensive to produce, and could in theory be taken in pill form, Spiegel said. And because they are unlikely to target essential biological processes in the body, the side effects could be smaller, he noted.

"This is an entirely new approach to treating these two diseases, which are extraordinarily important in terms of their impact on human health," Spiegel said.

HIV is a global pandemic that affects 33 million people worldwide, while prostate cancer is the second leading cause of cancer-related death among American men, with one out of every six American men expected to develop the disease.

Funding for this research was provided by the National Institutes of Health.

Higher Incidence Of Thyroid Cancer In Volcanic Area Of Sicily

2009-11-08T06:45:00.000-08:00

People living in volcanic areas may be at a higher risk for thyroid cancer, according to a new study published online November 5 in the Journal of the National Cancer Institute.

The increasing incidence of thyroid cancer has been attributed to more sensitive screening, but recent evidence indicates that this may not be the only cause. Various environmental factors, such as those associated with volcanoes, have not been excluded as risk factors.

To study this, Gabriella Pellegriti, M.D., Ph.D., of the endocrinology division, University of Catania Medical School, Garibaldi-Nesima Hospital in Italy, and colleagues collected incidence [newly diagnosed cases] of thyroid cancers in Sicily from January 1, 2002 through December 31, 2004 to compare the cancer rates of residents living in the volcanic area of Mt. Etna of Catania with those in the rest of Sicily.

The researchers found that residents of the Catania province had a more than two times higher incidence of papillary thyroid cancer, but not follicular or medullary thyroid cancers, than elsewhere on the island. Also, papillary tumors from patients in Catania more frequently carried the BRAF V600E gene mutation, which has been associated with more aggressive thyroid cancer.

The authors point out that a volcanic environment -- which can produce toxic compounds that are suspended particulate matter and gases and elements that may pollute the water -- may increase the incidence of thyroid cancer; however, the mechanism by which it affects risk is unknown.

"The striking increase in papillary thyroid cancer incidence that was associated with the Etna volcanic environment leads us to suggest that residents of other volcanic areas…could be at increased risk for thyroid cancer and, possibly, of other cancers," the authors write. "Although specific risk factors for thyroid cancer in this volcanic environment are still unknown, identification of these factors could help to better understand the cause(s) of the increasing thyroid cancer incidence in Europe and North America and perhaps to develop prevention measures."

Women Have More Diverse Hand Bacteria Than Men

2009-11-07T05:35:00.000-08:00

A new University of Colorado at Boulder study indicates that not only do human hands harbor far higher numbers of bacteria species than previously believed, women have a significantly greater diversity of microbes on their palms than men.

The results have implications for better understanding human bacteria and should help establish a "healthy baseline" to detect microbial community differences on individuals that are associated with a wide variety of human diseases, said CU-Boulder Assistant Professor Noah Fierer, lead study author. A paper on the subject by the CU-Boulder researchers was published online Nov. 3 in the Proceedings of the National Academy of Sciences.

Using powerful gene sequencing techniques, the team found a typical hand in the new study had roughly 150 different species of bacteria living on it, said Fierer of CU-Boulder's ecology and evolutionary biology department. While the researchers detected and identified more than 4,700 different bacteria species across 102 human hands in the study, only five species were shared among all 51 participants.

"The sheer number of bacteria species detected on the hands of the study participants was a big surprise, and so was the greater diversity of bacteria we found on the hands of women," said Fierer. The study also showed that the diversity of bacteria on individual hands was not significantly affected by regular hand washing, he said.

The 332,000 gene sequences obtained by the CU team were nearly 100 times greater than those obtained from other studies of skin bacteria also obtained by sampling the entire DNA of microbe communities, known as "metagenomics." The new CU-Boulder study also confirms that standard skin culturing of human skin bacteria, a technique used by many labs, dramatically underestimates the full extent of microbial diversity, Fierer said.

Co-authors on the PNAS study included Micah Hamady of CU-Boulder's computer science department, Christian Lauber of CU-Boulder's Cooperative Institute for Research in Environmental Sciences and CU-Boulder chemistry and biochemistry Assistant Professor Rob Knight. The study was funded primarily by the National Institutes of Health and the National Science Foundation.

Fierer speculated that skin pH may play a role in the higher bacterial diversity on women's hands, since men generally have more acidic skin, and other research has shown microbes are less diverse in more acidic environments. The findings also could be due to differences in sweat and oil gland production between men and women, the frequency of moisturizer or cosmetics applications, skin thickness or hormone production, he said.

The right and left palms of the same individual shared an average of only 17 percent of the same bacteria types, said Knight. Study volunteers, all CU undergraduates, shared an average of only 13 percent of bacteria species with each other, he said.

Although the composition of bacterial communities on dominant and non-dominant hands of subjects was significantly different, diversity levels were similar, Fierer said. The differences found between dominant and non-dominant hands were likely due to environmental conditions like oil production, salinity, moisture or variable environmental surfaces touched by either hand of an individual, he said.

While some groups of bacteria were less abundant following hand washing, others were more abundant, said Knight, who stressed that regular hand washing with anti-bacterial soap is beneficial. "The vast majority of bacteria are non-pathogenic, and some bacteria even protect against the spread of pathogens," Knight said. "From a public health standpoint, regular hand washing has a very positive effect."

"Although hand washing altered community composition, overall levels of bacterial diversity were unrelated to the time since the last hand washing," wrote the researchers in PNAS. "Either the bacterial colonies rapidly re-establish after hand washing, or washing (as practiced by the students included in this study) does not remove the majority of bacteria taxa found on the skin surface."

The CU-Boulder team used the metagenomic survey to simultaneously analyze all of the bacteria on a given palm surface, said Knight. In simple terms, the effort involved isolating and amplifying tiny bits of microbial DNA, then building complementary DNA strands with a high-powered sequencing machine that allowed the team to identify different families, genera and species of bacteria from the sample.

Knight recently received a $1.1 million NIH grant to develop new computational tools to better understand the composition and dynamics of microbial communities. He has been developing novel methods to tag DNA samples with error-correcting "barcodes" to obtain more accurate sequencing data.

The richness of bacteria types on the palm was three times higher than that found on the forearm and elbow, according to the researchers. The total diversity of hand bacteria appears to match or exceed levels of bacteria colonizing other parts of the body, including the esophagus, the mouth and lower intestine, Fierer said.

"I view humans as 'continents' of microscopic ecological zones with the kind of diversity comparable to deep oceans or tropical jungles," Fierer said. "Today we have the ability to answer large-scale questions about these complex microbial communities and their implications for human health that we weren't even asking six months or a year ago."

Hormone That Affects Finger Length Key To Social Behavior

2009-11-07T05:33:00.000-08:00

Research at the universities of Liverpool and Oxford into the finger length of primate species has revealed that cooperative behavior is linked to exposure to hormone levels in the womb.

The hormones, called androgens, are important in the development of masculine characteristics such as aggression and strength. It is also thought that prenatal androgens affect finger length during development in the womb. High levels of androgens, such as testosterone, increase the length of the fourth finger in comparison to the second finger. Scientists used finger ratios as an indicator of the levels of exposure to the hormone and compared this data with social behaviour in primate groups.

The team found that Old World monkeys, such as baboons and rhesus macaques, have a longer fourth finger in comparison to the second finger, which suggests that they have been exposed to high levels of prenatal androgens. These species tend to be highly competitive and promiscuous, which suggests that exposure to a lot of androgens before birth could be linked to the expression of this behaviour.

Other species, such as gibbons and many New World species, have digit ratios that suggest low levels of prenatal androgen exposure. These species were monogamous and less competitive than Old World monkeys.

The results show that Great Apes, such as orangutans and chimpanzees, expressed a different finger ratio. The analysis suggests that early androgen exposure is lower in this groups compared to Old World monkeys. Lower androgen levels could help explain why Great Apes show high levels of male cooperation and tolerance.

Emma Nelson, from the University of Liverpool's School of Archaeology, Classics and Egyptology, explains: "It is thought that prenatal androgens affect the genes responsible for the development of fingers, toes and the reproductive system. High androgen levels from a foetus or mother during pregnancy, may alter gene function and lead to subtle changes in relative digit length and the functioning of the reproductive system. Finger ratios do not change very much after birth and appear to tell us something about how very early androgens affect adult behaviour, particularly behaviour linked to mating and reproduction."

Dr Susanne Shultz, from the Institute of Cognitive and Evolutionary Anthropology at the University of Oxford, said: "Humans are unique in that they live in large multi-male, multi-female groups, but maintain strong bonds and show high levels of group cooperation in both males and females. In most other species males are competitive rather than co-operative. Research from finger ratios may help us understand more clearly the development of human sociality and its evolutionary origins."

This research, published in the American Journal of Physical Anthropology, is supported by the British Academy Centenary Research Project, Lucy to Language -- a multi-disciplinary project that aims to understand the complexities of human social evolution

Map Of Human Bacterial Diversity Shows Wide Interpersonal Differences

2009-11-07T05:30:00.000-08:00

A University of Colorado at Boulder team has developed the first atlas of bacterial diversity across the human body, charting wide variations in microbe populations that live in different regions of the human body and which aid us in physiological functions that contribute to our health.

The study showed humans carry "personalized" communities of bacteria around that vary widely from our foreheads and feet to our noses and navels, said CU-Boulder's Rob Knight, senior author on the paper published in the Nov. 6 issue ofScience Express. The researchers found unexpectedly wide variability in bacterial communities from person to person in the study, which included nine healthy volunteers and which targeted 27 specific sites on the body.

"This is the most complete view we have yet of the microbial side of ourselves, one that our group and others will be adding to over the coming years," said Knight an assistant professor in CU-Boulder's chemistry and biochemistry department. "The goal is to find out what is normal for a healthy person, which will provide a baseline for further studies to look at people with diseased states. One of the biggest surprises was how much variation there was from person to person in a healthy group of subjects."

Co-authors on the Science Express study, the online version of the journal Science, included CU-Boulder's Elizabeth Costello, Christian Lauber, Micah Hamady and Noah Fierer, as well as Jeffrey Gordon from the Washington University School of Medicine in St. Louis.

There are an estimated 100 trillion microbes residing on and within each human being that are thought to collectively endow us with the essential traits we rely on for a variety of functions, including the proper development of our immune systems, efficient digestion of key foods and resistance to invasion by lurking microbial pathogens.

The CU-Boulder team looked high and low, analyzing microbial communities in places such as hair on the head, ear canals, nostrils, mouth, lower intestine, and 18 different skin sites ranging from foreheads and armpits, forearms, palms, index fingers, navels, the back of the knees and the soles of the feet. The team used the latest generation of massively parallel DNA sequencers and new computational tools developed at CU-Boulder.

The study subjects were sampled four times each over a three-month period, typically after showering an hour or two earlier. Microbial DNA was then isolated directly from swabs used for sampling each body site, eliminating the standard culturing step. Specific bacterial RNA genes present in the DNA were then amplified using a technique known as PCR and the genes were then sequenced with high-capacity DNA sequencers, said Knight.

The specific bacterial RNA genes amplified from each sample, which were obtained from each body site of each individual, were "tagged" during the PCR step with a sample-specific DNA barcode developed by Knight's group. This allowed the team to pool hundreds of samples together prior to a single sequencing "run," reducing the cost and increasing the speed of the work.

Specific skin sites, as well as hair, nostril and ear canal sites, had the highest levels of variability within individuals over time and were roughly on a par with the human lower intestine, according to the study. The highest diversity skin sites were the forearms, palm, index finger, back of the knee and sole of the foot. The armpits and soles of the feet showed some similarities, perhaps because they are from dark and moist environments, said Fierer.

The mouth cavity showed the least variation in diversity both within individuals and between people, according to the study. The team also found the skin "head group" -- which included forehead, external nose, external ear and hair -- was dominated by one type of bacteria, while sites on the trunk and legs were dominated by a different group.

"We have an immense number of questions to answer," said Fierer, an assistant professor in CU-Boulder's ecology and evolutionary biology department who was a co-author on the study. "Why do healthy people have such different microbial communities? Do we each have distinct microbial signatures at birth, or do they evolve as we age? And how much do they matter? We just don't know yet."

Costello, the first author on the paper who recently accepted a postdoctoral position at Stanford University, likened the analysis of human bacterial communities to charting the growth of newborns. "Just as babies are tracked for weight and height as they grow to see where they fall in relation to normal ranges, we'd like to be able to find out if there are normal ranges of microbial communities for humans that could be tracked over time."

In an intriguing microbial community "transplant" experiment, the team disinfected the forearms and foreheads of some test subjects, then "inoculated" both sites with bacterial communities harvested from the tongue. The tongue bacteria persisted longer on the forearms than foreheads, suggesting some bacterial populations more strongly prefer sebaceous, or oily sites.

"As some others have speculated, it may be that drier areas of the skin like forearms make generally more hospitable landing pads for bacteria," Costello said. The team did not find any significant difference in how easily a person's forehead or forearm could be colonized by his or her own "transplanted" microbes as opposed to those of other people.

"These patterns suggest that the search for microbial factors associated with disease, although difficult to ascertain due to the high intrinsic levels of variability among healthy individuals, may be achieved using broad profiling techniques such as those employed here," the authors wrote in Science Express.

Previous microbial studies of healthy individuals have generally focused on individual body habitats including the lower intestine, skin and mouth. The new study builds on a 2008 CU study on hand bacteria indicating that while more than 4,200 species of bacteria resided on 102 human hands, only about five species were shared by all 51 participants. The 2008 study also showed women had a greater diversity of bacteria on their palms than men.

Knight, also a faculty member in CU-Boulder's computer science department and who is a member of the university's Colorado Initiative in Molecular Biotechnology, said understanding the variation in human microbial communities holds promise for future clinical research.

"If we can better understand this variation, we may be able to begin searching for genetic biomarkers for disease," he said. The CU-Boulder researchers said it might someday be possible to identify sites on the human body that would be amenable to microbial community transplants with either natural or engineered microbial systems that would be beneficial to the health of the host.

The research was funded by the Howard Hughes Medical Institute, the National Institutes of Health, the Bill and Melinda Gates Foundation and the Crohn's and Colitis Foundation of America.

Babies' Language Learning Starts From The Womb

2009-11-06T06:10:00.000-08:00

From their very first days, newborns' cries already bear the mark of the language their parents speak, reveals a new study published online on November 5th in Current Biology, a Cell Press publication. The findings suggest that infants begin picking up elements of what will be their first language in the womb, and certainly long before their first babble or coo.

"The dramatic finding of this study is that not only are human neonates capable of producing different cry melodies, but they prefer to produce those melody patterns that are typical for the ambient language they have heard during their fetal life, within the last trimester of gestation," said Kathleen Wermke of the University of Würzburg in Germany. "Contrary to orthodox interpretations, these data support the importance of human infants' crying for seeding language development."

Human fetuses are able to memorize sounds from the external world by the last trimester of pregnancy, with a particular sensitivity to melody contour in both music and language, earlier studies showed. Newborns prefer their mother's voice over other voices and perceive the emotional content of messages conveyed via intonation contours in maternal speech (a.k.a. "motherese"). Their perceptual preference for the surrounding language and their ability to distinguish between different languages and pitch changes are based primarily on melody.

Although prenatal exposure to native language was known to influence newborns' perception, scientists had thought that the surrounding language affected sound production much later, the researchers said. It now appears that isn't so.

Wermke's team recorded and analyzed the cries of 60 healthy newborns, 30 born into French-speaking families and 30 born into German-speaking families, when they were three to five days old. That analysis revealed clear differences in the shape of the newborns' cry melodies, based on their mother tongue.

Specifically, French newborns tend to cry with a rising melody contour, whereas German newborns seem to prefer a falling melody contour in their crying. Those patterns are consistent with characteristic differences between the two languages, Wermke said.

The new data show an extremely early impact of native language, the researchers say. Earlier studies of vocal imitation had shown that infants can match vowel sounds presented to them by adult speakers, but only from 12 weeks on. That skill depends on vocal control that just isn't physically possible much earlier, the researchers explain.

"Imitation of melody contour, in contrast, is merely predicated upon well-coordinated respiratory-laryngeal mechanisms and is not constrained by articulatory immaturity," they write. "Newborns are probably highly motivated to imitate their mother's behavior in order to attract her and hence to foster bonding. Because melody contour may be the only aspect of their mother's speech that newborns are able to imitate, this might explain why we found melody contour imitation at that early age."

The researchers include Birgit Mampe, University of Wurzburg, Wurzburg, Germany; Angela D. Friederici, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Anne Christophe, Ecole Normale Superieure/CNRS, Paris, France; and Kathleen Wermke, University of Wurzburg, Wurzburg, Germany.

Domestic Horse Genome Sequenced

2009-11-06T06:08:00.000-08:00

An international team of researchers has decoded the genome of the domestic horse Equus caballus, revealing a genome structure with remarkable similarities to humans and more than one million genetic differences across a variety of horse breeds. In addition to shedding light on a key part of the mammalian branch of the evolutionary tree, the work also provides a critical starting point for mapping disease genes in horses.

"Horses and humans suffer from similar illnesses, so identifying the genetic culprits in horses promises to deepen our knowledge of disease in both organisms," said senior author Kerstin Lindblad-Toh, scientific director of vertebrate genome biology at the Broad Institute of MIT and Harvard and a professor of comparative genomics at Uppsala University in Sweden. "The horse genome sequence is a key enabling resource toward this goal."

For centuries, horses have been close human companions. The animals were first domesticated 4,000 to 6,000 years ago and were harnessed primarily for power and transportation. Over time, as machines have become the chief sources of agricultural and industrial muscle, those roles have shifted to mainly sports and recreational activities.

Predating this coexistence, humans and horses share an evolutionary history that has implications for the health of both species. Like other mammals, the two species share much of the same DNA. Moreover, horses suffer from more than 90 hereditary diseases that show similarities to those in humans. Recognizing the need for genomic tools to foster biomedical research on horses as well as humans, a research consortium led by scientists at the Broad Institute of MIT and Harvard launched a project three years ago to decode the horse's genetic blueprint. The effort was based on a ten-year collaboration among an international group of scientists to exploit genomic technologies for the benefit of equine health known as the Horse Genome Project.

"We are especially grateful to our collaborators in the horse genetics community who participated in this project," said Lindblad-Toh. "We really could not have done this work without them."

To generate a high-quality genome sequence, the researchers analyzed DNA from an adult female Thoroughbred named Twilight. The horse's DNA was decoded using conventional capillary DNA sequencing technology (known as Sanger sequencing) to reveal a genome that is roughly 2.7 billion letters, or nucleotides, in size -- slightly larger than the genome of the domestic dog, and smaller than both the human and cow genomes.

A remarkable feature of the horse genome is the small number of chromosomal rearrangements that have occurred in horses relative to humans. During the course of evolution, parts of chromosomes can get shuffled to other locations in the genome, or they can remain in their original ancestral order, like beads on a string -- a situation known as "synteny." More than half of the horse chromosomes show synteny with a single human chromosome. This is in contrast to dogs, where the figure is less than one-third.

Another intriguing result to emerge from the horse genome analysis pertains to chromosomes and something called the "centromere." If you imagine chromosomes as X-shaped, centromeres are the central constrictions where the arms of the 'X' come together.

More than just a nexus, centromeres ensure that cells inherit copies of each chromosome during cellular division. Despite this essential role, relatively little is known about them. It is clear that they contain highly repetitive DNA sequences, but what is less clear is which comes first, the centromere or its repeats.

Lindblad-Toh and her colleagues, including Elena Giulotto of Pavia University in Italy, were surprised to uncover a region on horse chromosome 11 that contains a developing centromere, already functional, but frozen in a young state. Analyses of this budding centromere revealed no repetitive DNA, suggesting that centromeres appear first and their repeats appear later

"We don't know a lot about centromeres, particularly because they have proven so difficult to analyze by DNA sequencing," said first author Claire Wade, a former researcher at the Broad Institute and the Center for Human Genetic Research at Massachusetts General Hospital who is now a professor at the University of Sydney in Australia. "This result helps address some important questions about how centromeres evolve."

In addition to sequencing the genome of a Thoroughbred horse, the researchers also examined DNA from a variety of other horse breeds, including the American quarter horse, Andalusian, Arabian, Belgian draft horse, Hanoverian, Hakkaido, Icelandic horse, Norwegian fjord horse, and Standardbred breeds. The team surveyed the extent of genetic variation both within and across breeds to create a catalog of more than one million single-letter genetic differences (called "single nucleotide polymorphisms" or SNPs).

In a first proof-of-principle of the power of trait mapping in horses, the researchers harnessed the SNP catalog to localize the candidate mutation in the Leopard Complex or "Appaloosa spotting," in which horses' coats are mottled with striking patches of white, either with or without colored spots. Horses carrying this trait often suffer from a form of night blindness, a disorder that also afflicts humans. The researchers narrowed the list of genetic suspects in horses to 42 associated SNPs, including two candidate mutations residing near a gene involved in pigmentation.

"This demonstrates the utility of the horse for disease gene mapping," said Wade. "By making these resources freely available to the scientific community, we hope that many new results will flow from them in the coming years."

The research was funded by the National Human Genome Research Institute as well as the Dorothy Russell Havemeyer Foundation, the Volkswagen Foundation, the Morris Animal Foundation and the Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale.

Gene Therapy Technique Slows Brain Disease ALD Featured In Movie 'Lorenzo's Oil'

2009-11-06T06:06:00.000-08:00

A strategy that combines gene therapy with blood stem cell therapy may be a useful tool for treating a fatal brain disease, French researchers have found.

These findings appear in the 6 November 2009 issue of the journalScience, which is published by AAAS, the nonprofit science society.

In a pilot study of two patients monitored for two years, an international team of researchers slowed the onset of the debilitating brain disease X-linked adrenoleukodystrophy (ALD) using a lentiviral vector to introduce a therapeutic gene into patient's blood cells. Although studies with larger cohorts of patients are needed, these results suggest that gene therapy with lentiviral vectors, which are derived from disabled versions of human immunodeficiency virus (HIV), could potentially become instrumental in treating a broad range of human disorders.

"This is the first time we were able to successfully use an HIV-derived lentivirus vector for gene therapy in humans, and also the first time that a very severe brain disease has been treated with efficacy by gene therapy. We've demonstrated that this HIV-derived lentivirus vector works as was hoped for so many years," said coauthor Patrick Aubourg, professor of pediatrics at University Paris-Descartes and head of a research unit at Inserm-University Paris Descartes.

Featured in the movie "Lorenzo's Oil," ALD is a severe hereditary condition caused by a deficiency of a protein called ALD that is involved in fatty acid degradation. Sufferers steadily lose their myelin sheath, the protective layer that coats nerve fibers in the brain. Without myelin the nerves lose function, leading to increasing physical and mental disability in patients. X-linked ALD, the most common form of the disease, affects boys starting at age 6-8 years of age and death usually occurs before the patients reach adolescence.

Bone marrow transplants typically slow progression of the disease because the donor marrow includes cells that develop into myelin-producing cells. However, finding a matching bone marrow donor can be a challenging and lengthy process, and the procedure carries considerable risks.

Genetically correcting the blood stem cells in the patients' own bone marrow may prove to be a valuable alternative approach when no matched donors are available.

In most gene therapy studies, a working gene is inserted into the genome to replace a dysfunctional, disease-causing gene. A carrier molecule called a vector is used to deliver the therapeutic gene into the patient's cells. Vectors are typically the backbones of viruses that have been genetically altered to carry normal human DNA. Scientists have recently turned to vectors based on the lentivirus genus of retroviruses, which includes HIV. Lentiviral vectors are a type of retrovirus that can infect both dividing and nondividing cells, and are thought to provide long-term and stable gene expression, unlike other retroviruses.

"The HIV-derived lentivirus vector allows expression of the therapeutic gene in principle for life, because the therapeutic gene is inserted in the chromosomes -- the genome. Therefore, cells that derive from the initially corrected cells, stem cells in particular, will continue to express the therapeutic gene forever," said Aubourg.

In the study, blood stem cells were removed from the patients and genetically corrected in the lab, using a lentiviral vector to introduce a working copy of the ALD gene into the cells. The modified cells were then infused back into the patients' after they had received a treatment that destroyed their bone marrow. Two years later, healthy ALD proteins were still detectable in both patients' blood cells. Encouragingly, both patients showed neurological improvement and a delay in disease progression comparable to that seen with bone marrow transplants.

The healthy ALD protein was expressed in about 15 percent of blood cells, yet surprisingly this low level was sufficient to slow brain disease in ALD. "This percentage of correction will not be sufficient for all diseases," warns Aubourg. "There is a lot of work to be done to make this gene therapy vector more powerful, less complicated, and less expensive. This is only the beginning," he said.

Gene therapy is not without serious risks. Like other retrovirus vectors, the HIV-derived lentivirus vector is tasked with inserting the therapeutic gene in the chromosomes of the patients' cells. In a worst case scenario, this action could disturb the biology of the cells and patients could end up with leukemia; this outcome has occurred in past gene therapy trials. "The HIV-derived lentivirus vector basically has this same risk, although the design of the vector makes patients less prone to this side effect," said Aubourg.

This research was funded by INSERM (National Institute of Health and Research Medical), Assistance Publique des Hôpitaux de Paris, PHRC programs, the Deutsche Forchungsgemeinschaft and the German Ministry of Education and Research, the European Leukodystrophy Association, the Association Française contre les Myopathies, the Stop ALD Foundation and University Paris-Descartes.

Related Press Briefing in France: A press conference related to the forthcoming Science paper, "Hematopoietic Stem Cell Gene Therapy with a Lentiviral Vector in X-linked Adrenoleukodystrophy," by Dr. Nathalie Cartier and colleagues is planned for 2:00 p.m. in Paris on Wednesday, 4 November

'Spoonful Of Sugar' Makes The Worms' Life Span Go Down

2009-11-05T05:13:00.000-08:00

If worms are any indication, all the sugar in your diet could spell much more than obesity and type 2 diabetes. Researchers reporting in the November issue of Cell Metabolism, a Cell Press publication, say it might also be taking years off your life.

By adding just a small amount of glucose to C. elegans usual fare of straight bacteria, they found the worms lose about 20 percent of their usual life span. They trace the effect to insulin signals, which can block other life-extending molecular players.

Although the findings are in worms, Cynthia Kenyon of the University of California, San Francisco, says there are known to be many similarities between worms and people in the insulin signaling pathways. (As an aside, Kenyon says she read up on low-carb diets and changed her eating habits immediately -- cutting out essentially all starches and desserts -- after making the initial discovery in worms. The discovery was made several years ago, but had not been reported in a peer-reviewed journal until now.)

"In the early 90s, we discovered mutations that could double the normal life span of worms," Kenyon said. Those mutations effected insulin signals. Specifically, a mutation in a gene known as daf-2 slowed aging and doubled life span. That longer life depended on another "FOXO transcription factor" called DAF-16 and the heat shock factor HSF-1.

Now, the researchers show that those same players are also involved in numbering the days of worms who are fed on glucose. In fact, glucose makes no difference to the life span of worms that lack DAF-16 or HSF-1, they show. Glucose also completely prevents the life-extending benefits that would otherwise come with mutations in the daf-2 gene.

Ultimately, worms fed a steady diet containing glucose show a reduction in aquaporin channels that transport glycerol, one of the ingredients in the process by which the body produces its own glucose. "If there is not enough glucose, the body makes it with glycerol," Kenyon explained. That glycerol has to first get where it needs to go, which it does via the aquaporin channels.

Further studies are needed to see if these same effects of sugar can be seen in mice, or even people. But there is reason to think they may.

"Although we do not fully understand the mechanism by which glucose shortens the life span of C. elegans, the fact that the two mammalian aquaporin glycerol-transporting channels are downregulated by insulin raises the possibility that glucose may have a life-span-shortening effect in humans, and, conversely, that a diet with a low glycemic index may extend human life span," the researchers write. Kenyon also points to recent studies that have linked particular FOXO variants to longevity in several human populations, making the pathway the first with clear effects on human aging.

She says the findings may also have implications for drugs now in development for the treatment of diabetes, which are meant to block glucose production by inhibiting glycerol channels. The new findings "raise a flag" that glycerol channels might be doing something else, she says, and that drugs designed to block them might have a downside.

The researchers include Seung-Jae Lee, University of California, San Francisco, CA, Pohang University of Science and Technology, Pohang, Kyungbuk, South Korea; Coleen T. Murphy, University of California, San Francisco, CA; and Cynthia Kenyon, University of California, San Francisco, CA

'Spoonful Of Sugar' Makes The Worms' Life Span Go Down

2009-11-05T05:11:00.000-08:00

Phytochemicals In Plant-based Foods Could Help Battle Obesity, Disease

2009-11-05T05:07:00.000-08:00

The cheeseburger and French fries might look tempting, but eating a serving of broccoli or leafy greens first could help people battle metabolic processes that lead to obesity and heart disease, a new University of Florida study shows.

Eating more plant-based foods, which are rich in substances called phytochemicals, seems to prevent oxidative stress in the body, a process associated with obesity and the onset of disease, according to findings published online in advance of the print edition of the Journal of Human Nutrition and Dietetics.

To get enough of these protective phytochemicals, researchers suggest eating plant-based foods such as leafy greens, fruits, vegetables, nuts and legumes at the start of a meal. Using what is known as a phytochemical index, which compares the number of calories consumed from plant-based foods compared with the overall number of daily calories, could also help people make sure they remember to get enough phytochemicals during their regular meals and snacks, said Heather K. Vincent, Ph.D., the lead author of the paper.

"We need to find a way to encourage people to pull back on fat and eat more foods rich in micronutrients and trace minerals from fruits, vegetables, whole grains and soy," said Vincent, an assistant professor in the UF Orthopaedics and Sports Medicine Institute. "Fill your plate with colorful, low-calorie, varied-texture foods derived from plants first. By slowly eating phytochemical-rich foods such as salads with olive oil or fresh-cut fruits before the actual meal, you will likely reduce the overall portion size, fat content and energy intake. In this way, you're ensuring that you get the variety of protective, disease-fighting phytochemicals you need and controlling caloric intake."

The researchers studied a group of 54 young adults, analyzing their dietary patterns over a three-day period, repeating the same measurement eight weeks later. The participants were broken into two groups: normal weight and overweight-obese.

Although the adults in the two groups consumed about the same amount of calories, overweight-obese adults consumed fewer plant-based foods and subsequently fewer protective trace minerals and phytochemicals and more saturated fats. They also had higher levels of oxidative stress and inflammation than their normal-weight peers, Vincent said. These processes are related to the onset of obesity, heart disease, diabetes and joint disease, she added.

"Diets low in plant-based foods affect health over the course of a long period of time," Vincent said. "This is related to annual weight gain, low levels of inflammation and oxidative stress. Those are the onset processes of disease that debilitate people later in life."

Oxidative stress occurs when the body produces too many damaging free radicals and lacks enough antioxidants or phytochemicals to counteract them. Because of excess fat tissue and certain enzymes that are more active in overweight people, being obese can actually trigger the production of more free radicals, too.

Because many phytochemicals have antioxidant properties, they can help combat free radicals, Vincent said. Phytochemicals include substances such as allin from garlic, lycopene from tomatoes, isoflavones from soy, beta carotene from orange squashes and anythocyanins from red wine, among others.

"People who are obese need more fruits, vegetables, legumes and wholesome unrefined grains," she said. "In comparison to a normal-weight person, an obese person is always going to be behind the eight ball because there are so many adverse metabolic processes going on."

Instead of making drastic changes, people could substitute one or two choices a day with phytochemical-rich foods to make a difference in their diets, Vincent said. For example, substituting a cup of steeped plain tea instead of coffee or reaching for an orange instead of a granola bar could increase a person's phytochemical intake for the day without even changing the feeling of fullness. Over time, replacing more pre-packaged snacks with fresh produce or low-sugar grains could become a habit that fights obesity and disease, Vincent said.

"We always want to encourage people to go back to the whole sources of food, the nonprocessed foods if we can help it," Vincent said. "That would be the bottom line for anyone, regardless of age and body size, keep going back to the purer plant-based foods. Remember to eat the good quality food first."

Currently, there are no recommendations for how much of these plant compounds people should be getting each day, says Susanne Talcott, Ph.D., an assistant professor of food science and nutrition at Texas A&M University. Using the phytochemical index could be a good way to come up with these recommendations, she said.

Like Vincent, Talcott also cautions people to try and stick to the whole sources of foods and be wary of processed foods that promise benefits from added plant compounds.

"Consumers should stick with what we have known for decades and eat fresh or frozen fruits and vegetables," she said. "Stick with those kinds of foods rather than reaching out for a tropical wonder pill or juice."

No Pain, No Gain: Mastering A Skill Makes Us Stressed In The Moment, Happy Long Term

2009-11-04T06:18:00.000-08:00

No pain, no gain applies to happiness, too, according to new research published online in the Journal of Happiness Studies. People who work hard at improving a skill or ability, such as mastering a math problem or learning to drive, may experience stress in the moment, but experience greater happiness on a daily basis and longer term, the study suggests.

"No pain, no gain is the rule when it comes to gaining happiness from increasing our competence at something," said Ryan Howell, assistant professor of psychology at San Francisco State University. "People often give up their goals because they are stressful, but we found that there is benefit at the end of the day from learning to do something well. And what's striking is that you don't have to reach your goal to see the benefits to your happiness and well-being."

Contrary to previous research, the study found that people who engage in behaviors that increase competency, for example at work, school or the gym, experience decreased happiness in the moment, lower levels of enjoyment and higher levels of momentary stress. Despite the negative effects felt on an hourly basis, participants reported that these same activities made them feel happy and satisfied when they looked back on their day as a whole. This surprising find suggests that in the process of becoming proficient at something, individuals may need to endure temporary stress to reap the happiness benefits associated with increased competency.

The study examined whether people who spend time on activities that fulfill certain psychological needs, believed to be necessary for growth and well-being, experience greater happiness. In addition to the need to be competent, the study focused on the need to feel connected to others and to be autonomous or self-directed, and it examined how fulfilling these three needs affects a person's happiness moment by moment within a day.

For two days, participants reported how they spent each hour, the enjoyment and stress experienced in that hour, and whether the activity met their need for competency, connectedness to others or autonomy. A second group of participants completed a similar survey, but reported on the day as a whole.

While behaviors that increase competency were associated with decreased happiness in the moment, people who spent time on activities that met the need for autonomy or feeling connected to others experienced increased happiness both an hourly and daily basis. The greatest increase in momentary happiness was experienced by participants who engaged in something that met their need for autonomy -- any behavior that a person feels they have chosen, rather than ought to do, and that helps them further their interests and goals.

The authors suggest that shifting the balance of needs met in a day could help people find ways to cope with short term stress in the workplace. "Our results suggest that you can decrease the momentary stress associated with improving your skill or ability by ensuring you are also meeting the need for autonomy and connectedness, for example performing the activity alongside other people or making sure it is something you have chosen to do and is true to who you are," Howell said.

Relating these momentary gains in happiness to people's long term life satisfaction, the study found that those who are already satisfied with their life in the long term stand to gain most from the momentary happiness that is derived from feeling connected to others and a sense of autonomy.

"Like a wine connoisseur whose experience means they can appreciate a fine wine more than a novice, people who are already satisfied with their life may have learned how to glean the satisfaction of these needs from their daily activities," Howell said.

Angry Faces: Facial Structure Linked To Aggressive Tendencies

2009-11-04T06:15:00.000-08:00

Angry words and gestures are not the only way to get a sense of how temperamental a person is. According to new findings in Psychological Science, a quick glance at someone's facial structure may be enough for us to predict their tendency towards aggression.

Facial width-to-height ratio (WHR) is determined by measuring the distance between the right and left cheeks and the distance from the upper lip to the mid-brow. During childhood, boys and girls have similar facial structures, but during puberty, males develop a greater WHR than females. Previous research has suggested that males with a larger WHR act more aggressively than those with a smaller WHR. For example, studies have shown that hockey players with greater WHR earn more penalty minutes per game than players with lower WHR.

Psychologists Justin M. Carré, Cheryl M. McCormick, and Catherine J. Mondloch of Brock University conducted an experiment to see if it is possible to predict another person's propensity for aggressive behavior simply by looking at their photograph. Volunteers viewed photographs of faces of men for whom aggressive behavior was previously assessed in the lab. The volunteers rated how aggressive they thought each person was on a scale of one to seven after viewing each face for either 2000 milliseconds or 39 milliseconds.

The photographs were very revealing: Volunteers' estimates of aggression correlated highly with the actual aggressive behavior of the faces viewed, even if they saw the picture for only 39 milliseconds. Even more interestingly, the volunteers' estimates were also highly correlated with WHR of the faces -- the greater the WHR, the higher the aggressive rating, suggesting that we may use this aspect of facial structure to judge potential aggression in others. These findings indicate that subtle differences in face shape may affect personality judgments, which may, in turn, guide how we respond to certain individuals.

TV Exposure May Be Associated With Aggressive Behavior In Young Children

2009-11-04T06:12:00.000-08:00

Three-year-old children who are exposed to more TV appear to be at an increased risk for exhibiting aggressive behavior, according to a report in the November issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

"Early childhood aggression can be problematic for parents, teachers and childhood peers and sometimes is predictive of more serious behavior problems to come, such as juvenile delinquency, adulthood violence and criminal behavior," according to background information in the article. Various predictive factors for childhood aggression have been studied. These include parents' discipline style, neighborhood safety and media exposure. "After music, television is the medium children aged 0 to 3 years are exposed to the most." Although the American Academy of Pediatrics recommends no screen media for children younger than age 2, studies have found consistent use of television in that age group.

Jennifer A. Manganello, Ph.D., M.P.H., of University at Albany, State University of New York, Rensselaer, and Catherine A. Taylor, Ph.D., M.S.W., M.P.H., of Tulane University School of Public Health and Tropical Medicine, New Orleans, analyzed data from 3,128 mothers of children born from 1998 to 2000 in 20 large U.S. cities to examine associations of child television exposure and household television use with aggressive behavior in children. Parents were interviewed at the time of the child's birth and at one and three years. At three years, they were asked to report time the child spent watching TV directly as well as household TV use on a typical day. Aggression also was assessed at 3 years of age using a 15-item aggressive subscale for 2- and 3-year-old children. Demographic information and other risk factors for aggression were also noted.

About two-thirds (65 percent) of mothers reported that their 3-year-old child watched more than two hours of television per day. On average, children were exposed to an additional 5.2 hours of household TV use per day.

Direct child TV exposure and household TV use were both significantly associated with childhood aggression, after accounting for other factors such as parent, family, neighborhood and demographic characteristics. "One explanation that could link both child and household TV measures with aggression involves the parenting environment," the authors write. Households with higher rates of TV use may have fewer restrictions on children's viewing habits such as exposure to unregulated television content. Increased household television use may also affect daily routines such as eating and communication patterns and may decrease time spent on other activities.

"Current American Academy of Pediatrics recommendations mainly suggest limitations for direct child exposure to TV and other media; however, our findings suggest that additional household TV use may also be an important predictor of negative childhood outcomes, such as early childhood aggression," the authors conclude. "Future research in this area should consider inclusion of both of these TV variables along with additional parent-child interaction assessments, observational assessments when possible, quality and/or content of TV programs and longitudinal analyses."

Short Heels Make Elite Sprinters Super Speedy: Longer Toes, Unique Ankle Structure Aid Sprinters

2009-11-04T06:02:00.000-08:00

Longer toes and a unique ankle structure provide sprinters with the burst of acceleration that separates them from other runners, according to biomechanists.

"At the start of a sprint the only way a runner can speed up is through the reaction force that results from the action of leg muscles pushing on the ground," said Stephen Piazza, associate professor of kinesiology, Penn State. "Long toes provide sprinters the advantage of maintaining maximum contact with the ground just a little bit longer than other runners."

Piazza and his colleague Sabrina S. M. Lee, former Penn State graduate student now a post-doctoral fellow at Simon Fraser University, Vancouver, Canada, studied the muscle architecture of the foot and ankle to look at the differences between sprinters and non-sprinters.

They matched 12 collegiate sprinters with 12 non-athletes of the same height. They measured the distance between the heel and the end of the toes and used ultrasound imaging to measure the sliding of the Achilles tendon during ankle motion, from which the leverage of the tendon can be calculated.

"What we found was that the lever arms (distance between the tendon and center of rotation of the ankle) were significantly shorter -- about 25 percent shorter -- in sprinters," said Piazza, whose findings appeared recently in the Journal of Experimental Biology. "This difference might be explained by a tradeoff between leverage and muscle force-generating capacity."

Because the lever arms are shorter, the muscles shorten less for the same joint rotation. If muscles shorten less, they shorten more slowly, which helps them to produce greater force that more than compensates for the reduced leverage.

While there is little published work on foot shapes and sprinting, previous work on animals suggests that ostriches, greyhounds and cheetahs have feet built for sprinting.

To understand the kind of human foot that would produce a similar sprinting advantage, the researchers developed a simple computer model that could analyze the physiological data they had collected earlier.

"We wanted to see how much acceleration we could get out of the model when we changed the tendon lever arm and the length of the toes," said Piazza. "What we found is that when the Achilles tendon lever arm is the shortest and the toes are longest, we get the greatest acceleration."

Piazza cites other recent research suggesting that shorter toes in modern humans could be an evolutionary adaptation for efficient distance running.

"Maybe our ancestors with longer toes were better sprinters. Or maybe longer toes were selected for at a time when navigating in trees was more important and our toes became shorter as endurance running became more important for our survival," he added.

The Penn State researcher cautions that while the study could be a piece of the puzzle in determining who could potentially be a good sprinter, other physiological components such as body type, cardiovascular physiology and muscle fiber types should also be taken into account.

It is also unclear whether sprinting ability is congenital or whether training can influence the shape of bones in the foot.

"It is not too far-fetched to think that training can help accentuate the shape of the bone," said Piazza. "But if sprinters' skeletal characteristics were shown to be immutable, it would support the coaches' adage that sprinters are born and not made."

Moderate Amounts Of Protein Per Meal Found Best For Building Muscle

2009-11-01T07:01:00.000-08:00

For thousands of years, people have believed that eating large amounts of protein made it easier to build bigger, stronger muscles. Take Milo of Croton, the winner of five consecutive Olympic wrestling championships in the sixth century BC: If ancient writers are to be believed, he built his crushing strength in part by conNo modern athlete would go to such extremes, but Milo's legacy survives in the high-protein diets of bodybuilders and the meat-heavy training tables of today's college football teams. A recent study by University of Texas Medical Branch at Galveston metabolism researchers, however, provides evidence that strongly contradicts this ancient tradition. It also suggests practical ways to both improve normal American eating patterns and reduce muscle loss in the elderly.
The study's results, obtained by measuring muscle synthesis rates in volunteers who consumed different amounts of lean beef, show that only about the first 30 grams (just over one ounce) of dietary protein consumed in a meal actually produce muscle.
"We knew from previous work that consuming 30 grams of protein -- or the equivalent of approximately 4 ounces of chicken, fish, dairy, soy, or, in this case, lean beef -- increased the rate of muscle protein synthesis by 50 percent in young and older adults," said associate professor Douglas Paddon-Jones, senior author of a paper on the study published in the September issue of the Journal of the American Dietetic Association. "We asked if 4 ounces of beef gives you a 50 percent increase, would 12 ounces, containing 90 grams of protein, give you a further increase?"
The UTMB researchers tested this possibility by feeding 17 young and 17 elderly volunteers identical 4- or 12-ounce portions of lean beef. Using blood samples and thigh muscle biopsies, they then determined the subjects' muscle protein synthesis rates following each of the meals.
"In young and old adults, we saw that 12 ounces gave exactly the same increase in muscle protein synthesis as 4 ounces," Paddon-Jones says. "This suggests that at around 30 grams of protein per meal, maybe a little less, muscle protein synthesis hits an upper ceiling. I think this has a lot of application for how we design meals and make menu recommendations for both young and older adults."
The results of the study, Paddon-Jones points out, seem to show that a more effective pattern of protein consumption is likely to differ dramatically from most Americans' daily eating habits.
"Usually, we eat very little protein at breakfast, eat a bit more at lunch and then consume a large amount at night. When was the last time you had just 4 ounces of anything during dinner at a restaurant?" Paddon-Jones said. "So we're not taking enough protein on board for efficient muscle-building during the day, and at night we're taking in more than we can use. Most of the excess is oxidized and could end up as glucose or fat."
A more efficient eating strategy for making muscle and controlling total caloric intake would be to shift some of extra protein consumed at dinner to lunch and breakfast.
"You don't have to eat massive amounts of protein to maximize muscle synthesis, you just have to be a little more clever with how you apportion it," Paddon-Jones said. "For breakfast consider including additional high quality proteins. Throw in an egg, a glass of milk, yogurt or add a handful of nuts to get to 30 grams of protein, do something similar to get to 30 for lunch, and then eat a smaller amount of protein for dinner. Do this, and over the course of the day you likely spend much more time synthesizing muscle protein."
Other authors of the paper include postdoctoral fellow T. Brock Symons, associate professor Melinda Sheffield Moore and University of Arkansas professor Robert R. Wolfe. The study was supported by funding from the National Cattlemen's Beef Association Checkoff Program and UTMB's National Institutes of Health Claude D. Pepper Older Americans Independence Center.suming 20 pounds of meat every day.

Chewing Gum Can Reduce Calorie Intake, Increase Energy Expenditure, Nutritionist Finds

2009-10-31T06:59:00.000-07:00

A nutrition professor at the University of Rhode Island studying the effects of chewing sugar-free gum on weight management has found that it can help to reduce calorie intake and increase energy expenditure.

Kathleen Melanson, URI associate professor of nutrition and food sciences, compared gum chewing to non-gum chewing in healthy adult volunteers who came to her lab for two standardized tests in random order. When study subjects chewed gum for a total of one hour in the morning (three 20-minute gum-chewing sessions), they consumed 67 fewer calories at lunch and did not compensate by eating more later in the day. Male participants also reported feeling significantly less hungry after chewing gum. Melanson also found that when her subjects chewed gum before and after eating, they expended about 5 percent more energy than when they did not chew gum. In addition, her subjects reported feeling more energetic after chewing gum.

"Based on these results, gum chewing integrates energy expenditure and energy intake, and that's what energy balance is about," Melanson said. According to the URI researcher, nerves in the muscles of the jaw are stimulated by the motion of chewing and send signals to the appetite section of the brain that is linked to satiety, which may explain why the act of chewing might help to reduce hunger.

Melanson said that she expected that chewing would increase the amount of energy her subjects expended. "However, what makes the energy expenditure data particularly interesting is that this study simulated real-life gum chewing, with the subjects chewing at their own relaxed, natural pace and for realistic time periods," she said.

In her study, 35 male and female subjects made two visits to the URI Energy Metabolism Lab after having fasted over night. During one visit, they chewed gum for 20 minutes before consuming a breakfast shake and twice more during the three hours before lunch. During both visits, participants remained as still as possible as measurements were conducted of their resting metabolism rates and blood glucose levels at regular intervals before and after breakfast and lunch. They also conducted periodic self-assessments of their feelings of hunger, energy and other factors during both visits.

"This was a short term study, so the next step is to do a longer study and to use subjects who need to lose weight," said Melanson. "But based on these initial results, one could hypothesize that gum chewing may be a useful adjunct to a weight management program."

The study was supported by a $25,000 research award from the Wrigley Science Institute that was presented during the 2007 annual meeting of The Obesity Society.

3 Vegetables That Fight Against Stomach Fat

2009-10-30T06:17:00.000-07:00

A unique way that a few specific vegetables can actually stimulate the burning of abdominal fat...

article by Mike Geary, Certified Personal Trainer, Certified Nutrition Specialist

I bet you didn't know that there is a specific class of vegetables that contain very specific phytonutrients that actually help to fight against stubborn belly fat.

Let me explain what these unique vegetables are and why they help to burn stomach fat...

Chemicals that force your body to hold onto belly fat

Something you may have never heard about is that certain chemicals in our food supply and our environment, such as pesticides, herbicides, and certain petrochemicals from air and water pollution, household cleaners, cosmetics, etc can react with your body and make your body store excess abdominal fat.

These chemicals are known as xenoestrogens.

Xenoestrogens are chemicals that you are exposed to (and are hard to avoid in the modern world) that have an estrogenic effect in your body. Excess exposure to these can cause hormone balance disruptions for both men and women. So these can wreak havoc in the body for both guys and gals.

These estrogenic chemicals that we are exposed to on a daily basis can stimulate your body to store belly fat, along with many other problems (including cancer risks in the long term).

So here's where this specific class of vegetables comes in handy...

One of those cool tricks that I teach my clients that hire me for nutritional counseling is the use of cruciferous vegetables to help fight against stomach fat.

Cruciferous vegetables such as broccoli, cauliflower, brussels sprouts, kale, cabbage, etc. contain very specific and unique phytonutrients such as indole-3-carbinol (I3C) that help to fight against these estrogenic compounds...

And by fighting against these belly fat stimulating estrogenic chemicals, this is just 1 more step in helping you to win the battle against abdominal fat!

So there you go... just another excuse to do what mom always told you and eat more broccoli!

I've really learned to like brussells sprouts in the last year too... Melt a little grass-fed cheese on them and some garlic and they're great!

Pumpkin Skin May Scare Away Germs

2009-10-29T08:51:00.000-07:00

The skin of that pumpkin you carve into a Jack-o'-Lantern to scare away ghosts and goblins on Halloween contains a substance that could put a scare into microbes that cause millions of cases of yeast infections in adults and infants each year. That's the conclusion of a new study.

In the study, Kyung-Soo Hahm, Yoonkyung Park and colleagues note that some disease-causing microbes are becoming resistant to existing antibiotics. As a result, scientists worldwide are searching for new antibiotics. Past studies hinted that pumpkin, long used as folk medicine in some countries, might have antibiotic effects.

The scientists extracted proteins from pumpkin rinds to see if the proteins inhibit the growth of microbes, including Candida albicans (C. albicans). That fungus causes vaginal yeast infections, diaper rash in infants, and other health problems. One protein had powerful effects in inhibiting the growth of C. albicans, in cell culture experiments, with no obvious toxic effects. The pumpkin protein could be developed into a natural medicine for fighting yeast infections in humans, the report suggests. The protein also blocked the growth of several fungi that attack important plant crops and could be useful as an agricultural fungicide, they add.

Deadly Stomach Infection Rising In Community Settings

2009-10-28T05:57:00.000-07:00

Clostridium difficile is a serious bacteria that can cause symptoms ranging from diarrhea to life-threatening inflammation of the colon. These findings were presented October 26 at the 2009 American College of Gastroenterology (Clostridium difficile, often called C. difficile or "C. diff," is a bacterium that is resistant to some antibiotics and is most often contracted by the elderly in hospitals and nursing homes.

"Recent reports have shown increasing incidence and severity ofC. difficile infection -- especially in the older population," says Darrell Pardi, M.D., Mayo Clinic gastroenterologist and senior author on the study. "Our study examines why the cases are on the rise and who is getting the infection."

In this population-based study, researchers studied 385 cases of C. difficile bacterial infection from 1991-2005 to determine how many cases were hospital-acquired versus community-acquired infections. Of the cases, 192 were hospital-acquired and 35 were residents of nursing homes. Of these hospital-acquired cases, the median age of infection was 72 years; in contrast, 158 cases were community-acquired and the median age was 50 years. Thirty-five percent of the hospital infections had a severe illness compared to 22 percent of community infections who had a severe illness.

The patients with community-acquired infection were also less likely than the hospital-acquired group to have been exposed to antibiotics before their infection. Thus, many of the community-acquired infections lacked the traditional risk factors for infection, namely recent hospitalization and exposure to antibiotics.

There were no differences between community- and hospital-acquired infections in terms of what patients were treated with (primarily metronidazole), response rates, or recurrence rates after treatment.

"We are seeing more cases of C. difficile in the community, but they tend to be less severe and in a younger population," says Dr. Pardi. "The growing incidence of C. difficile infection in both inpatient and outpatient settings could be linked to the increasing usage of antibiotics and to the possibility that C. difficile may be getting resistant to some of our newer antibiotics."

There are hundreds of kinds of bacteria found normally in the intestines. Many play beneficial roles in the body. When a patient takes an antibiotic to treat an infection, it often destroys beneficial bacteria as well as the bacteria that are causing the illness. Without enough healthy bacteria, dangerous pathogens such as C. difficile can quickly grow out of control. Once it takes hold, C. difficile can produce two virulent toxins that attack the lining of the intestine.

"Doctors have gotten better at spotting C. difficile in hospitals and nursing homes; however, now doctors and patients need to be more aware that you can get this infection as an outpatient and that a case of diarrhea or abdominal cramps at home could become serious," says Dr. Pardi.

According to the Centers for Disease Control and Prevention, each year in the United States, C. difficile is responsible for tens of thousands of diarrhea cases and at least 5,000 deaths.

Children Can Complete Treatment For Peanut Allergies And Achieve Long-term Tolerance, Studies Suggest

2009-10-27T06:49:00.000-07:00

It appears these children have lost their allergies," says Wesley Burks, MD, Chief of the Division of Pediatric Allergy and Immunology at Duke. "This gives other parents and children hope that we'll soon have a safe, effective treatment that will halt allergies to certain foods."

Long-term tolerance in children with peanut allergies was documented for the first time by the presence of key immunologic changes, according to researchers at Duke and Arkansas Children's Hospital who presented their findings at the American Academy of Asthma and Immunology meeting in Washington, DC March 15.

This procedure is not currently recommended for patients as it has not been fully tested, and it should never be attempted without full medical supervision.

Tests of several immunologic indicators suggest the body builds tolerance quickly.

"At the start of the study, these participants couldn't tolerate one-sixth of a peanut," Burks said. "Six months into it, they were ingesting 13 to 15 peanuts before they had a reaction."

About four million Americans have food allergies, and allergies to tree nuts and peanuts are the most common. Life-threatening reactions can occur from exposure to even a trace amount of peanuts, and nearly half of the 150 deaths attributed to food allergies each year are caused by peanut allergies.

Duke and Arkansas Children's Hospital began enrolling patients in studies five years ago to determine if incremental doses of peanut protein could change how the body's immune system responds to its presence. The doses start as small as 1/1000 of a peanut. Eight to 10 months later, the children are ingesting the equivalent of up to 15 peanuts per day. The children stay on that daily therapy for several years and are monitored closely.

Nine of the 33 children participating in the study have been on maintenance therapy for more than 2.5 years. After a series of food challenges, four of those children were taken off the treatment and continue to eat peanuts. Some have been off treatment for more than a year. Doctors keep tabs on any potential changes in their immune system via skin, blood and immune studies.

One of the tests used in the study looks at immunoglobulin E (IgE), a protein the body makes in response to peanut allergens. "If you have it, you're likely allergic, if you don't, you aren't," explained Burks. Children in this study generally started with IgE levels greater than 25. "At the end of the study, their peanut IgEs were less than 2 and have remained that way since we stopped the treatment," he said.

Because the pool of children now off treatment is so small, Burks says it's hard to say whether these children simply outgrew their allergies or if the therapy did something to enhance that outcome. The next step is a blinded study in which children on treatment are compared to a control group. First year results were presented at the meeting by Stacie M. Jones, MD, a pediatric allergist at Arkansas Children's Hospital. So far, the oral immune therapy appears to be working.

"We see initial desensitization effects of the treatment are real," Burks says. "Those children are now able to eat up to 15 peanuts with no reaction, but the children not on treatment have symptoms early on in the study."

Despite the news, Burks insists this research is still ongoing and cautions parents and professionals against trying any version on their own. "In my clinic, I would do the same things I've always done. Once diagnosed with a food allergy, I would recommend they avoid the food. We have to wait for the studies to show the treatment is safe, and to see desensitization start to work. We also want to know the therapy works long term."

FDA Approves Twynsta (telmisartan/amlodipine) for Hypertension

2009-10-27T06:44:00.000-07:00

FDA Approves New Use for Micardis in Cardiovascular Risk Reduction and Twynsta as New Combination Treatment for High Blood Pressure Ridgefield, CT, October 19, 2009 - Boehringer Ingelheim Pharmaceuticals, Inc. announced today that the U.S. Food...