SUNDAY - December 23, 2007-----------------------------------------------News Archive/Return to Today's News Alerts

New Studies Illuminate the Computational Power of Neurons

Scientists have found that individual neurons have more computational power and contribute more to behavior than previously thought.

The researchers used light to activate individual neurons in living mice and showed that even short bursts of activity in a few neurons can influence learning and decision making.

Karel Svoboda, Daniel Huber, and their colleagues at the Howard Hughes Medical Institute's Janelia Farm Research Campus and at Cold Spring Harbor Laboratory published their findings in two research articles in the journal Nature.

The researchers used light to study detailed aspects of how neurons function.

Svoboda used a new technique that relies on a light-sensing protein found in green algae called channelrhodopsin-2. Channelrhodopsin-2 is a protein that enables algae to migrate toward light. In previous work, the researchers had shown they could trigger nerve impulses by shining a laser on cells that contain channelrhodopsin-2. Only those neurons containing channelrhodopsin-2 fired when they were stimulated by light from a laser.

Using living, trained mice with implanted "windows" in their brains, the scientists watched the neurons in the mice respond to photostimulation. As part of the training exercise, the animals were placed in a chamber with two water ports. The animals learned to sip from one water port when they sensed photostimulation of their neurons, and to sip from the other port when they did not.

“The sparseness of stimulation required for detection was surprising, because we know that there is considerable ongoing activity in the brain,” he said. “The activity produced by the light impulses is just a tiny fraction of the total activity. These findings tell us that there are mechanisms in the brain that can read out very sparse subsets of activated neurons. So, the take-home message from these experiments is quite powerful: that very few neurons need to be activated with very few action potentials to drive perceptions and behavior.”

Svoboda believes the broader lesson is that stimulating neurons optically is a powerful way to study brain circuitry. “We can use these kinds of tools to figure out which neurons are connected to each other,” he said. “And we can also precisely manipulate particular neuronal populations and look at the effects on quantitative behaviors. That allows one to dissect how these circuits guide behavior.”

Published December 19, 2007 in the journal Nature
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Blind People 'See' Sunrise and Sunset

Some profoundly blind people can "see" after all - though not in the traditional way. Cells at the back of their eyes monitor light levels and use them to set the body's clock to either night or day.

This new information comes from experiments involving two blind people who lack the rods and cones needed for normal vision. Although neither person can see anything, they sense whether it is light or dark by detecting blue light.

The cells responsible are called retinal ganglion cells and are located in the outermost layer of cells lining the retina at the back of the eye. Retinal ganglion cells usually help to transmit visual information to the brain. Now it turns out that about 3 per cent of the ganglion cells respond to light and make melanopsin, a light-sensitive pigment. Normally, when we see, light penetrates this layer to reach rod and cone cells in the zone of the retina where light is focused to create sharp images.

"Retinal ganglion cells are fundamentally different to rods and cones," says Russell Foster of the Nuffield Laboratory of Ophthalmology at the University of Oxford, co-leader of the team whose results appear in Current Biology (vol 17, p 2122). "They're gauging the gross amount of light in the system, a bit like a photographer's light meter."

The light-sensing properties of these cells were first discovered in 2002 in rats by David Berson of Brown University in Rhode Island. Since then, experiments in mice engineered to have no rods and cones or melanopsin have proved that the ganglion cells are responsible for setting the animals' circadian clocks and respond most strongly to blue light. The latest experiments provide the most convincing evidence yet that the same cells do this job in humans.

Foster teamed up with Steven Lockley of the Brigham and Women's Hospital in Boston, and for 6.5 hours they shone light into the eyes of a 56-year-blind man who had no rods and cones. When they used blue light at night-time, they were able to delay his body clock cycle by 1.2 hours, proving that his ganglion cells were registering light. At the same time, blood levels of the "sleep hormone" melatonin fell by 60 per cent, the man's alertness sharpened and his brain activity increased, demonstrating that his body clock had been fooled into thinking it was daytime.

Nothing happened to the circadian cycle when green light from the centre of the visual light spectrum was shone in the man's eyes, showing they could only detect blue light. Further experiments involving an 87-year-old blind woman from England confirmed this.

The researchers say the results help to explain why blind people who have their eyes removed for cosmetic or health reasons suffer horrendous sleep disruption. Lockley recommends that doctors check to see whether blind people still have regular circadian clocks before doing such surgery. If their ganglion cells aren't functioning, they can set their clocks by taking nightly doses of melatonin.

Published December 18, 2007 in the journal Current Biology
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In Horse Breeding, Genes Aren't Always a Go

When it comes to success on the racetrack, nurture beats nature by a mile, new research suggests. A Scottish team has found that horse breeders who pay the highest stud fees to mate their mares with popular stallions--hoping to cash in on the bloodlines of a champion--won't necessary make out any better in the winner's circle.

It's a time-honored tradition in the Sport of Kings: Racehorses that ring up the biggest winnings on the track also command the highest fees when put out to stud. The rationale is understandable--the offspring of winners are likely to be winners themselves. But that's not what two evolutionary biologists found when they decided to see how well human breeders were succeeding at producing champion horses.

Alastair Wilson and Andrew Rambaut of the University of Edinburgh, U.K., analyzed the race results and purses of nearly 4500 offspring of thoroughbreds foaled between 1922 and 2003.

Based on the lifetime earnings of those foals, they concluded that genetic links to previous champions had only a small effect on the amount of prize money - less than a 10% correlation. As they report online this week in Biology Letters, other factors, such as the farms where the horses were raised and the trainers employed to teach them how to race, exerted a considerably bigger influence - as much as a 90% correlation. "The best males are not necessarily those with the highest price tags," Wilson says. "People could potentially pay a lot of extra money to buy genes that are no better than average."

Evolutionary biologist David Coltman of the University of Alberta in Edmonton, Canada, agrees with the paper's conclusions. "It might be quite difficult to pick the right stud reliably based on genetics compared to the environmental effects," he says. Coltman adds that previous research had shown that stud fees correlate with the speed of the offspring, but the new findings indicate that the correlation doesn't necessarily translate into winning.

Published December 19, 2007 in the journal Science - Biology Letters
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SATURDAY - December 22, 2007--------------------------------------------News Archive/Return to Today's News Alerts

“Preschool for All” Would Help Nation, say 2008 Grawemeyer Award Winners

Making preschool available to all children age three and older in the United States would carry great benefits, say three Yale scholars who have won the 2008 University of Louisville Grawemeyer Award in Education.

The change would improve the school-readiness of the nation’s young children, fill a gap for working families, lower the high school dropout rate, reduce crime and boost the economy, award winners Edward Zigler, Walter Gilliam and Stephanie Jones, argue in their winning 2006 book, “A Vision for Universal Preschool Education.”

Forty U.S. states now fund pre-kindergarten programs, but the programs enroll fewer than 10 percent of all preschoolers, Zigler, Gilliam and Jones found.

Using research gathered over four decades, the winners set out specific actions that can be taken to develop good universal preschool systems. The book “stands alone in its field for its accessibility, clarity, timeliness and ability to combine a solid research background with practical recommendations,” said their award nomination.

Zigler, a Yale University professor emeritus of psychology who helped found the nation’s Head Start program, directs a child development and social policy center at Yale that carries his name.

Gilliam, a Yale psychologist, conducts research on the effects of preschool programs, while Stephanie Jones, now a Fordham University psychologist, studies the social and emotional aspects of early childhood and adolescence.


Details on all the 2008 Grawemeyer award winners or to download photos of the winners, see www.grawemeyer.org
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New Science Study Shows Institutionalized Children Fare Best in Foster Care

Newly published research in the journal Science confirms that institutionalized orphans placed into foster care have much better intellectual development than those who remain behind. The authors say the results have implications for countries "grappling with how best to care for abandoned, orphaned and maltreated young children."

A team of researchers including Nathan Fox, a professor of human development (College of Education) at the University of Maryland, has been studying a randomly chosen group of 136 abandoned children from six institutions in Bucharest, Romania for a number of years. The Bucharest Early Intervention Project (BEIP) tracked the children out to 54 months of age.

Also involved in the study are Charles Nelson of Harvard University ; Dr. Charles Zeanah and Anna Smyke of Tulane University , and Peter Marshall of Temple University. The research was supported by the MacArthur Foundation Research Network on "Early Experience and Brain Development."

Earlier evidence from the intervention project showed that young children who remain institutionalized suffered intellectual, emotional, psychiatric and brain development problems. Prof. Fox says, "They are deprived of typical social and emotional stimulation and interaction, as well as typical cognitive and language stimulation." Knowing this, the primary question researchers had was, is there a "best time" when intervention can help prevent these children from becoming psychologically deprived - when damage can be prevented. The Bucharest Early Intervention Project was designed to look at this issue of timing as it related to early deprivation.

The study accomplished this by randomly assigning children into two groups of children that were abandoned at or shortly after birth. "Children at the time of entry into the study ranged in age from 6-29 months of age," says Fox.

Half the children remained in the institution, the other half were placed into foster care. All children were the subject of follow-up assessments that included not only cognitive development, but also standardized intelligence tests. Timing related to the intervention was looked at closely. A third group of children - who were being reared by their biological families in Bucharest - served as a base group.

The study was conducted with the full approval of the Government of Romania and was conducted as a way to help guide that nation's child welfare policy. Before this study, there was a bias in the child welfare community towards institutionalized care. In fact, the BEIP had to create its own foster care program as part of the study because the government of Romania's foster care program was limited to "about one family." As part of the study's ethical guidelines, no child placed into foster care was returned to an institution.

The main findings from the study confirmed earlier results that "children reared in institutions showed greatly diminished intellectual performance relative to children reared in their families of origin." Further, children who were randomly assigned to foster care experienced "significant gains in cognitive function." Finally, on the importance of timing when pursuing intervention, Prof. Fox says, "the results show that the age point where things mattered was 24 months of age." The report adds that "there was a continuing 'cost' to children who remained in the institution over the course of the study.

Published December 21, 2007 in the journal Science
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Mutant Gene Identified as Villain in Hardening of the Arteries

A genetic mutation expands lesions in the aorta and promotes coronary atherosclerosis, more commonly known as hardening of the arteries, according to a study by Yale School of Medicine in Cell Metabolism.

The researchers found that mice engineered without the Akt1 gene and fed a high cholesterol diet had many more signs of aortic atherosclerosis compared to their littermates. And, surprisingly, their coronary lesions were similar to humans, say the scientists.

“About 20 percent of the mice died spontaneously, perhaps due to an acute heart attack,” said William Sessa, senior author of the study, professor of pharmacology, and director of Yale’s vascular biology and therapeutics program.

Atherosclerosis is a chronic inflammatory response in arterial walls, in large part due to deposits of lipoproteins - which are plasma proteins that carry cholesterol and triglycerides. The "hardening" or "furring" of the arteries is caused by plaque formation.

In the vascular wall, the Akt1 gene plays an important role in regulating the development of endothelial cells, which line the entire circulatory system, from the heart to the smallest capillary. Endothelial cells play an important role in regulating blood pressure, in blood clotting, in plaque formation in the arteries, and in formation of new blood vessels.

“The major finding of this study is that an absence of the Akt1 gene aggravates atherosclerotic lesions, promotes coronary atherosclerosis, and may be a model of acute coronary syndromes,” Sessa said. “Specific activation of Akt1 may provide a therapeutic approach to decrease formation of lesions in the arterial wall and promote plaque stabilization to prevent an acute heart attack.”

One concern, he said, is that specific drugs are being developed to inhibit Akt1 in cancer patients to reduce progression of tumors, and that these drugs may also promote hardening of the arteries.

Published December, 2007 in the journal Cell Metabolism
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FRIDAY - December 21, 2007------------------------------------------------News Archive/Return to Today's News Alerts

Some Temper Tantrums May be Associated with Clinical Problems in Preschool Children

Temper tantrums are common among preschool children 3 to 6 years of age.

Although these tantrums can range in duration and intensity, many parents worry whether tantrums are also symptoms of more serious problems. They may be right.

Dr. Andy Belden and colleagues from Washington University School of Medicine in St. Louis studied tantrum behaviors of 279 parent-child pairs. The researchers compared the tantrums of children previously diagnosed with depression and/or disruptive disorders, such as ADHD, with those of healthy children and found healthy children were less aggressive and, generally, had shorter tantrums.

The authors categorized the high-risk children according to five “tantrum styles:”

1) self-injurious behavior

2) consistent violent aggression towards others or objects

3) the inability to calm themselves without assistance

4) tantrums lasting for more than 25 minutes

5) an average of 5 tantrums a day, or 10-20 tantrums in a month

The first tantrum style was found most often in children with depression, and should be considered very serious. The other four may be indicators of emotional or behavioral problems.

The authors note that tantrums are commonly caused by hunger, fatigue, or illness, and are often considered normal among preschool children. However, Dr. Belden suggests that “preschoolers who consistently exhibit the behaviors outlined may be in need of a referral to a mental health professional for further evaluation.” This research may serve as a guideline for parents and caregivers to determine when assistance is needed for their child’s tantrums.

Published January, 2008 in The Journal of Pediatrics
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Bad PMS May Mean A Depressed Nervous System

For some women premenstrual syndrome (PMS) is a minor monthly annoyance, but for others, more severe symptoms seriously disrupt their lives.

A team of Japanese researchers led by Tamaki Matsumoto from the International Buddhist University in Osaka investigated whether the activity of the autonomic nervous system, which plays a vital role in equilibrium within the human body, changed during the menstrual cycle.

The team measured heart rate variability and hormone levels and used questionnaires to evaluate physical, emotional and behavioural symptoms accompanying 62 women's menstrual cycles.

Those with the most marked symptoms - known as premenstrual dysphoric disorder (PMDD) - had lower rates of nerve activity than the other groups during the entire menstrual cycle.

For women with PMDD, findings indicate that sympathovagal activity was altered even in the follicular phase, when the egg is still in the ovary.

Matsumoto asks: "Does this imply that women with lower autonomic function regardless of the menstrual cycle are vulnerable to more severe premenstrual disorders? At the moment, the underlying biomechanisms of PMS remain enigmatic."

PMS comprises a myriad of non-specific physical, emotional, behavioural, and cognitive symptoms that occur in the days prior to menstruation and is nearly omnipresent in women of reproductive age from all cultures and socio-economic levels.

The most prevalent symptoms include: irritability, mood lability, depression, anxiety, impulsivity, feelings of "loss of control," fatigue, decreased concentration, abdominal bloating, fluid retention, breast swelling, and general aches.

To be published January 15, 2007 in the journal BioPsychoSocial Medicine
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Infants Fine-Tune Their Visual and Auditory Skills in First Year of Life

Infants refine and narrow their ability to discriminate between things they see and hear in their first year. Offhand, a statement that might appear to suggest a decline in mental organization at a time when most other physical skills and functions are dramatically increasing.

But Lisa S. Scott, assistant professor of psychology at the University of Massachusetts Amherst, and her colleagues observe that between age 6 months and one year, infants undergo what is known as perceptual narrowing - an ability to give order to the overwhelming perceptual information they are receiving and refine it into more selective associations with their increasing experience.

For example, in one study, 6-month-old infants were able to differentiate between two human faces as easily as two monkey faces. But 9-month-olds could only differentiate between two human faces. However, if infants are familiarized with monkey faces from age 6 months to 9 months, they maintain their ability to tell the difference between two monkey faces - and the two human faces. Their experience has influenced their ability to place the faces into familiar categories.

Scott and her colleagues, Olivier Pascalis of the University of Sheffield in England, and Charles A. Nelson of Harvard Medical School and Children’s Hospital in Boston, say this process also takes place in other perceptual systems. In one test examining speech, 6-month-old infants could discriminate one sound from another from virtually every language, but by 9 months, this ability declines – unless the child receives experience with such sounds.

Scott says the research suggests that infants aren’t undergoing a developmental regression, but rather a move toward greater efficiency in perceiving and processing “salient rather than less salient environmental input.”

During development the human brain goes through a series of changes that are never again replicated throughout the lifespan, Scott says. “During this time the brain is sensitive and responsive to the surrounding environment. A dominant theme of this research is to understand how both typical and atypical experience influences the course of development and the organization of the brain.

She says her research examines “how we fine-tune our brains in an ever-changing world and how specific early experiences influence later abilities.

Published August 22, 2007 in the Current Directions in Psychological Science, a journal of the Association for Psychological Science
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THURSDAY - December 20, 2007--------------------------------------------News Archive/Return to Today's News Alerts

UC Irvine Scientists Find New Way to Sort Stem Cells

UC Irvine scientists have found a new way to sort stem cells that should be quicker, easier and more cost-effective than current methods. The technique could in the future expedite therapies for people with conditions ranging from brain and spinal cord damage to Alzheimer’s and Parkinson’s diseases.

The method uses electrodes on a tiny, inch-long glass slide to sort cells by their electric charges and has been used in cancer research. The stem cell field suffers from a lack of tools for identifying and sorting cells. This important discovery could add a new tool to current sorting methods, which generally require expensive, bulky equipment.

“For therapeutic purposes, we want stem cells to turn into specific cell types once they have been transplanted. The trick to doing this is identifying beforehand which cells will become the desired cell type, such as a neuron,” said Lisa Flanagan, lead author of the study and a stem cell biologist at UCI. “We have discovered a new, potentially better way to do this by focusing on the electric properties of the cells.”

Currently, stem cells most often are separated using a machine called a fluorescence-activated cell sorter (FACS). FACS machines, which use lasers to detect the light scattering and fluorescent characteristics of the cells, can weigh hundreds of pounds and cost $500,000 or more. The UCI-designed dielectrophoresis device is just a fraction of the size and cost. The two devices could be used to complement each other to create ultra pure stem cell populations.

With the goal of identifying future neurons, UCI engineers built a tiny device using a glass slide to perform the dielectrophoresis. First, scientists place unsorted mouse stem cells on one side of the device. The cells then float in sugar water through a tiny channel past electrodes set to a particular frequency. At a certain frequency, stem cells destined to become neurons will stick to the electrodes while other cells pass by. The cells that stick then can be removed and grouped together, potentially for use in a therapy.

“Once the mold is created, these sorts of devices can cost just pennies to make,” said Ed Monuki, senior author and UCI developmental biologist. “You could have many for every member of your lab and it wouldn’t be prohibitively expensive.”

Published December 20, 2007 in the journal Stem Cells
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Certain Diseases, Birth Defects May be Linked to Failure of Protein Recycling System

A group of signaling proteins known as Wnt - which help build the human body's skin, bone, muscle and other tissues - depend on a complex delivery and recycling system to ensure they are transported to tissue-building cell sites, according to a study at Cincinnati Children's Hospital Medical Center.

When the recycling system - the Retromer Complex - fails, the delivery of these signaling proteins stops. This important finding provides new insight into what may be a mechanism behind cancer, heart disease or birth defects related to Wnt proteins.

"We know secreted Wnt proteins play essential roles in many biological processes, including the development of diseases, but very little is known about the mechanisms by which Wnt processing and secretion are regulated," said Xinhua Lin, Ph.D., a researcher in the Division of Development Biology at Cincinnati Children's and senior author of the study.

In their study, the researchers proposed a delivery cycle model where Wnt initially enters the Trans-Golgi Network and binds with the Wls cargo receptor, which then transports Wnt to targeted cell surfaces.

Once the Wls cargo receptor has delivered the Wnt proteins, one of two things occurs, depending on whether the Retromer Complex is functioning normally.

Functioning normally, the Retromer Complex retrieves the spent Wls protein for return to the Trans-Golgi.

When the Retromer Complex breaks down, the Wls cargo receptor is absorbed into the cell's lysosome, where it is digested and destroyed.

To be published January 15, 2007 in the journal Developmental Cell
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Humour 'Comes From Testosterone'

Men are naturally more comedic than women because of the male hormone testosterone, an expert claims.

Men make more gags than women and their jokes tend to be more aggressive, Professor Sam Shuster, of Norfolk and Norwich University Hospital, says.

Research suggests men are more likely to use humour aggressively by making others the butt of the joke. Professor Shuster believes humour develops from aggression caused by male hormones. He documented the reaction of over 400 individuals to his unicycling antics through the streets of Newcastle upon Tyne.

Almost half of people responded verbally - more being men. Very few of the women made comic or snide remarks, while 75% of the men attempted comedy - mostly shouting out "Lost your wheel?", for example.

Often the men's comments were mocking and intended as a put-down. Young men in cars were particularly aggressive - they lowered their windows and shouted abusively. This type of behaviour decreased among older men however, who tended to offer more admiring comments, much like the women.

Initial aggressive intent seems to become channelled into a more subtle and sophisticated joke, so the aggression is hidden by wit, claims Professor Shuster.

Dr Nick Neave is a psychologist at the University of Northumbria who has been studying the physical, behavioural, and psychological effects of testosterone. He suggests men might respond aggressively because they see the other unicycling man as a threat, attracting female attention away from themselves.

"This would be particularly challenging for young males entering the breeding market and thus it does not surprise me that their responses were the more threatening."

Published December 22, 2007 in the BMJ - British Medical Journal, Christmas Issue
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WEDNESDAY - December 19, 2007------------------------------------------News Archive/Return to Today's News Alerts

Cancer And Arthritis Therapy Promising Treatment For Diabetes

An antibody used to treat certain cancers and rheumatoid arthritis appears to greatly delay type 1 diabetes in mice, Yale School of Medicine researchers report.

"Even better, the beneficial effects of the antibody continue to be observed long after the antibody is no longer administered," the researchers said.

The antibody, rituximab (anti-CD20), depletes B cells. Experimental evidence in mutant mice indicates that B cells play a role in autoimmune diseases by interacting with T cells of the immune system. It is T cells that destroy insulin-producing cells directly in the pancreas, leading to type 1 diabetes.

"Our paper shows, for the first time, that after successful B cell depletion, regulatory cells emerge that can continue to suppress the inflammatory and autoimmune response even after the B cells return," said Li Wen, senior research scientist in the division of endocrinology. "Even more strikingly, we found that these regulatory cells include both B and T cells."

To determine if B cell depletion would work as a therapy for type 1 diabetes, Wen and her colleague at Yale, Mark Shlomchik, M.D., professor of laboratory medicine and immunobiology, developed a mouse model. They engineered mice that were predisposed to diabetes and had the human version of CD20, the molecule rituximab targets, on the surface of their B cells.

The researchers tested a mouse version of the drug to deplete B cells in mice either before diabetes onset, or within days of diagnosis with diabetes. The drug treatment significantly delayed diabetes onset in pre-diabetic mice. This translated to a 10- to 15-week delay in developing diabetes compared to mice given a "sham" treatment. The equivalent period for humans would be approximately 10 to 15 years. Of the 14 mice that already had diabetes, five stopped needing insulin for two to five months while all the sham-treated mice remained diabetic.

"These studies suggest that B cells can have dual roles in diabetes and possibly other autoimmune diseases. The B cells might promote disease initially, but after being reconstituted following initial depletion with rituximab, they actually block further disease," Shlomchik added.

"This means that multiple rounds of medication to deplete the B cells might not be necessary or even advisable."

Published December 14, 2007 in the Journal of Clinical Investigation
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Twin Study Gives Insight Into Brain’s Organization

A new study of twins indicates the genetic foundation for the brain’s ability to recognize faces and places is much stronger than for other objects, such as words. The results are some of the first evidence demonstrating the role of genetics in assigning function to specific regions of the brain.

“We are social animals who have specialized circuitry for faces and places,” says Arthur W. Toga, PhD, director of the Laboratory of NeuroImaging at UCLA School of Medicine. “Some people are better at recognizing faces and places, and this study provides evidence that it is partially determined by genetics.”

Using a functional magnetic resonance imaging (fMRI) scanner, Thad Polk, PhD, Joonkoo Park, and Mason Smith of the University of Michigan, along with Denise Park, PhD, at the University of Illinois at Urbana-Champaign, measured activity in the visual cortex of 24 sets of fraternal and identical twins. The twins watched several series of images: sets of people’s faces, houses, letters strung together, and chairs, as well as scrambled images that served as a baseline measurement.

Previous research had identified distinct regions in the visual cortex where different categories of information are processed, a sort of division of labor in the brain that handles information about people, as opposed to another area which stores information related to cars - for example.

Polk’s analysis of brain activity patterns from the twins suggests how the organization of these independent regions is shaped. By showing greater similarity in the brain activity of identical twins than their fraternal counterparts when processing faces and places, the results indicate a genetic basis for these functions. Activity in response to words, Polk suggests, may be shaped to a greater degree by one’s experiences and environment.

“Face and place recognition are older than reading on an evolutionary scale, they are shared with other species, and they provide a clearer adaptive advantage,” says Polk. “It is therefore plausible that genetics would shape the cortical response to faces and places, but not orthographic stimuli.”

Published December 19, 2007 by the Journal of Neuroscience.
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An Ambulance For Muscle Damage

It doesn't take much to injure a muscle. Sometimes a sudden, movement can do the job. Unfortunately, damaged muscles are not as efficient at repair as other tissues such as bone.

Researchers of the European Molecular Biology Laboratory's Mouse Biology Unit [EMBL], Italy, and the Harefield Heart Science Centre of Imperial College London, have now discovered a molecular signal that helps muscle regenerate and protects it from atrophy. The naturally occurring protein is a promising candidate for new strategies in treating muscle damage and wasting.

A crucial regulator of muscle function and repair is a signalling molecule called calcineurin. Activated by injury and the corresponding rise in calcium levels, calcineurin flips on transcription factors that control everything from immune responses to heart development to muscle cell differentiation. The two halves of the protein, CnA and CnB, come in several forms.

Scientists discovered a new version of CnA, known as CnAβ1, nearly 20 years ago, but they knew little about its function. Nadia Rosenthal, head of EMBL's Mouse Biology Unit, and her team have now found a naturally occurring version of calcineurin, called CnAß1, that is permanently active and uncouples the protein's activity from injury signals.

The researchers show that, with CnAβ1, undifferentiated muscle cells divide more quickly and are less likely to specialize. Calcineurin usually exerts its influence by activating the NFAT transcription factors. CnAβ1, however, activates a different signaling pathway and blocks the transcription factor FoxO.

"This system allows flexible reaction to muscle injury," says Rosenthal. "Permanently active CnAß1 is expressed only in proliferating stem cells and regenerating muscles, suggesting it as something like an ambulance man that is called only in response to muscle damage."

To test the effects of permanent CnAß1 expression Enrique Lara-Pezzi from Rosenthal's lab overexpessed CnAß1 in muscle cells, and observed increased proliferation of muscle stem cells. Switching off the protein had the opposite effect; stem cells stopped dividing and differentiated into muscle cells instead.

In the mice that received an injection of a muscle-destroying poison, boosting CnAß1 levels caused an increase in the number of active muscle stem cells and a thickening of regenerating muscle fibers. CnAß1 also trimmed the number of macrophages at the injury site and limited accumulation of fresh extracellular matrix.

"Supplementary CnAß1 also reduces the formation of scars in damaged muscle, helps speed up the resolution of inflammation and protects muscle cells from atrophy under starvation," says Rosenthal. "These effects make CnAß1 a promising candidate for new therapeutic approaches against muscle wasting."

Thus CnAβ1 helps muscle heal by encouraging cell division, calming inflammation, and limiting scarring, leaving more room for new muscle cells. The next question, the scientists say, is whether the variant is important for other fast-dividing cells, such as stem cells and tumor cells.

Published December 17, 2007 in the Journal of Cell Biology
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TUESDAY - December 18, 2007----------------------------------------------News Archive/Return to Today's News Alerts

In Skin & Scales, Pigment Shows the Path of Evolution

When waves of people left Africa roughly 50,000 years ago and spread across Europe and Asia, they developed lighter skin color to adapt to lower levels of sunlight.

Now researchers at the Stanford University School of Medicine have found the gene responsible for that change, adding that it also explains how groups of light-colored fish evolved from darker fish.

David Kingsley, PhD, professor of developmental biology and senior author of the study, said evolutionary biologists have long debated exactly how evolution progresses. Some argue that many mutations accumulate like tiny drops of dye added to paint that, after thousands of drops, accumulate into a noticeable color change. Others think mutations occur in important genes like a large dollop of pigment, changing the color in one fell swoop.

Kingsley’s findings add support to the genetic dollop theory.

This is the third time Kingsley has found a single gene repeated in different populations, but producing similar evolutionary change. Each of these findings came about through studying a finger-length fish called the threespine stickleback.

Humans and sticklebacks share many similarities. Both migrated out of their ancestral environments into new locals a few thousand generations ago. Both emigrant populations adapted traits, such as skin color changes, to live successfully in their new locations.

Some of the originally oceanic fish ended up in lakes or streams where the original darker color might have helped them hide from predators. Others wound their way into new homes where losing the darker color was an advantage.

Kingsley's group compared the DNA of lighter fish and darker fish and found each population had mutations in a gene called Kit ligand.

Collecting DNA from people with a variety of skin colors, the team began to look for alterations in the Kit ligand gene. Sure enough, people with lighter skin had an altered form of the gene. The Kit ligand gene isn’t alone in controlling a person’s skin color, but it does account for about 20 percent of the differences in pigmentation between people of African and northern European descent.

“It is the same genetic mechanism between organisms that are very different from each other,” Kingsley said. Kit ligand gene is now known to make a protein that plays a role in maintaining the melanocyte skin cells that control pigmentation.

Published December 14, 2007 in the journal Cell
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Most Faby-Food Manufacturers Using Toxic Chemical in Packaging

The Washington-based Environmental Working Group (EWG) says that cans containing liquid infant formula and sold in North America, contain the toxic chemical Bisphenol A (BPA).

BPA is a chemical that mimics the hormone estrogen and is especially toxic to children.

Two separate panels sponsored by the U.S. National Institutes of Health (NIH) have both expressed concerns within the last year about infant exposure to BPA.

One of the panels was made up of 38 international BPA experts who expressed grave concerns that human exposures are at or above the levels that cause harm in animal studies.

The other panel concluded that there was "some concern" that infant exposure could harm brain development and adversely affect behaviour; they advise parents to avoid infant exposure to the chemical until serious outstanding questions about BPA's potential harm are cleared up.

A survey by EWG has revealed that all the major manufacturers of liquid infant formula sold in North America use cans lined with bisphenol A, and most manufacturers of powdered formula also acknowledge using the chemical in their packaging.

Because BPA is tasteless the chemical is widely used to make the epoxy linings on the insides of food and beverage cans and it is also used in polycarbonate plastic baby bottles and water bottles.

Many new parents are already aware that the toxic chemical leaches from plastic baby bottles and have switched to BPA-free bottles for their infants.

The EWG says they should have access to BPA-free formula as well.

Previous formula tests carried out by EWG and the Food and Drug Administration (FDA) have shown that BPA leaches from the plastic lining of metal cans into liquid formula, exposing formula-fed babies to potentially harmful concentrations that are higher than levels leaching from the bottles.

BPA levels in powdered formula sold in the United States have not yet been tested, but this formula is diluted with water before being fed to babies, and therefore poses less risk to babies.

Published October & November, 2007 by the Environmental Working Group (EWG).
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Bacteria That Cause Urinary Tract Infections Invade Bladder Cells

Scientists at Washington University School of Medicine in St. Louis have found definitive proof that some of the bacteria that plague women with urinary tract infections (UTIs) are entrenched inside human bladder cells.

The finding confirms a controversial revision of scientists' model of how bacteria cause UTIs. Previously, most researchers assumed that the bacteria responsible for infections get into the bladder but do not invade the individual cells that line the interior of the bladder.

Understanding what bacteria do in the bladder is critical to developing better diagnoses and treatments for UTIs, Hultgren says. The bacterium Escherchia coli is thought to be responsible for 80 percent to 90 percent of UTIs, which occur mainly in women and are one of the most common bacterial infections in the United States. Scientists estimate that more than half of all women will experience a UTI in their lifetimes, and recurrent UTIs will affect 20 percent to 40 percent of those patients.

"Recurrence is one of the biggest problems of UTIs," says Hultgren. "Even though we have treatments that eliminate the acute symptoms, the fact that the disease keeps recurring in so many women tells me that we need to develop better treatments."

Scientists also thought that if the bacteria were getting into bladder cells, they would replicate and spread rapidly, sometimes leading to sepsis. But after Hultgren first discovered that bacteria are able to invade bladder cells in 1998, he later found evidence in his animal model that bacteria could establish residence inside those cells. He showed that this process involved several behavioral changes that allow the bacteria to form cooperative communities known as biofilms. By working together, bacteria in biofilms build themselves into structures that are more firmly anchored in infected cells and are more resistant to immune system assaults and antibiotic treatments.

Hultgren's experiments had previously suggested that some bacteria progress to a filament-like shape when exiting out of the biofilm. Rosen was able to identify bacteria with this filamentous morphology in 41 percent of samples from patients with symptomatic UTIs.

"What we're learning about how bacteria behave in the bladder may also have application to other chronic, treatment-resistant infections such as sinus infections and ear infections," he says.

"We're increasingly starting to realize that biofilm formation is generally an important strategy bacteria use to evade host responses and antibiotic therapies. Attacking biofilms is going to be a really important approach as we enter a new era of fighting infectious diseases."

Published December 14, 2007 in the journal PLoS - Public Library of Science Medicine
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MONDAY - December 17, 2007----------------------------------------------News Archive/Return to Today's News Alerts

Simple Diet Changes May Boost Fertility

Ovulation problems - in which women ovulate irregularly or not at all - account for 18% to 30% of all infertility cases, says Dr. Jorge Chavarro, a research fellow at the Harvard School of Public Health's department of nutrition. Doctors often prescribe fertility drugs as treatment, but the medication can raise the risk of conceiving twins or higher-order multiples.

His study should open some eyes in the field of reproductive medicine, says Dr. Fady Sharara, a Virginia fertility doctor who has studied fertility and body mass index and has long supported the value of a healthful diet for fertility.

Few studies have specifically examined diet and infertility. These findings were culled from the long-running Nurses' Health Study II, an epidemiology study of registered nurses launched at Brigham and Women's Hospital in 1989. For the fertility analysis, the researchers analyzed data collected from 17,544 women who had no history of infertility over eight years as they tried to become pregnant or became pregnant. They surveyed the women on their diets, exercise habits, weight and many other health factors.

“In general, the study's findings point to factors that can disrupt the delicate balance of hormones needed for reproduction. For example, women with a disorder called polycystic ovary syndrome frequently experience ovulatory infertility due to insulin sensitivity and high testosterone levels. They are more likely to get pregnant after they lose weight or are treated with medications to improve insulin sensitivity.

One recommendation in "The Fertility Diet," is for women to avoid refined carbohydrates - white bread, potatoes and sugared sodas - which quickly raise blood sugar and insulin and disrupt the balance of hormones. In the Nurses' Health Study II, women who had the highest glycemic load - a measure of the amount of carbohydrates in the diet and how quickly carbohydrates are turned into blood sugar -- were 92% more likely to have had ovulatory infertility than women with the lowest glycemic load.

A strong correlation was found with the amount of trans fats women consumed. Eating a modest amount of trans fat - just 2% of calories - in place of healthier fats and carbohydrates would raise the risk of infertility by 73% to 131%. Previous research has shown that trans fats, unhealthy fats that increase the risk for cardiovascular disease, can affect how quickly insulin is cleared from the body.

Other Observations and Suggestions:

One serving a day of a low- or nonfat dairy product increased the risk of ovulatory infertility by 11%. But adding one serving per day of a full-fat dairy product, particularly whole milk, decreased it by 22%.

One or two servings a day of whole milk or other full-fat dairy foods. The idea is to balance the ratio of male to female hormones - not pack on pounds which disrupt the balance of hormones needed for reproduction.

Take a multivitamin. Though American women of childbearing age are advised to consume 400 micrograms of folic acid per day to prevent neural tube birth defects, the nurses study found that ovulation and conception improve with consumption of at least 700 micrograms per day.

Women who regularly took an iron supplement of at least 40 milligrams a day were 40% less likely to have trouble getting pregnant. But this was only true of women who got the iron from fruits, vegetables, beans and supplements. Those who consumed iron from mostly meat, which contains a different form of iron than that found in other food sources, weren't protected from ovulatory infertility. Previous research suggests that a woman's eggs and the embryo need iron to function properly.

"It's incredible that some of the simplest interventions - simple in theory at least - may in fact be the most effective," says Adamson, a reproductive endocrinologist in San Jose. "It's really important for women to understand that there are a lot of things they do to ensure the best reproductive outcome for themselves."

Published November, 2007 in the journal Obstetrics & Gynecology
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Losses of Long-Established Genes Contributed to Human Evolution

Scientists at the University of California, Santa Cruz, have carried out the first systematic computational analysis to identify long-established genes that were lost during the millions of years of evolution leading to the human species.

"This is the first study designed to search the entire genome for recent loss of genes that do not have any near-duplicate copies elsewhere in the genome. These are likely to be the more important gene losses," said David Haussler, professor of biomolecular engineering at UCSC.

To find gene losses, Zhu employed a software program called TransMap that Diekhans had developed. The program begins by comparing mouse and human genomes, then moves on to compare the complete genomes of the human, chimpanzee, rhesus monkey, mouse, rat, dog, and opossum - searching for genes having changes significant enough to render them nonfunctional sometime during the 75 million years.

One previously unknown loss, the gene for acyltransferase-3 (ACYL3), particularly caught their attention. Multiple copies of the ACYL3 gene are encoded in the fly and worm genomes.

"This is an ancient protein that exists throughout the whole tree of life," said Zhu. "In the mammalian clade there is only one copy left, and somewhere along primate evolution, that copy was lost."

"In our analysis, we found that this gene contains a nonsense mutation in human and chimp, and it appears to still be functional in rhesus," added Sanborn. The researchers also found that the mutation is not present in the orangutan, so the gene is probably still functional in that species. To further narrow down the timing of the loss, the researchers looked to see if the gene is still active in the gorilla.

"On the evolutionary tree leading to human, on the branch between chimp and orangutan, sits gorilla," Sanborn explained.

After sequencing the corresponding region in a DNA sample from a gorilla, he found the gene intact, without the mutation, meaning the loss likely occurred in the primate lineage after the speciation of the gorilla and before that of the chimpanzee.

"A highlight of our research was that we were able to find a list of these orphan losses," said Zhu. "Some of them have been functional for more than 300 million years, and they were the last copies left in the human genome."

While the copies of these genes remaining in the human genome appear to be nonfunctional, functional copies of all of them exist in the mouse genome.

"It would be interesting to find out what was the biological effect of these losses. Once their function is well characterized in species that still have active copies, we could maybe speculate about their effects on human evolution" said Zhu.

Published December 14, 2007 issue of the PLoS Computational Biology.
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Bacteria In Cows' Milk May Cause Crohn's Disease

Scientists at the University of Liverpool have found how a bacterium, known to cause illness in cattle, may cause Crohn's disease in humans.

Crohn's is a condition that affects one in 800 people in the UK and causes chronic intestinal inflammation, leading to pain, bleeding and diarrhoea.

The team found that a bacterium called Mycobacterium paratuberculosis releases a molecule which prevents a type of white blood cell from killing E.coli bacteria found in the body. Large numbers of E.coli ae found in Crohn's tissue.

The Mycobacteria may make their way into the body's system via cows' milk and other dairy products. In cattle it can cause an illness called Johne's disease - a wasting, diarrhoeal condition. Until now, however, it was unclear how this bacterium could trigger intestinal inflammation in humans.

"These Mycobacteria release a complex molecule containing a sugar, called mannose. This molecule prevents a type of white blood cells, called macrophages, from killing internalised E.Coli" says Jon Rhodes, PhD, from the University of Liverpool's School of Clinical Sciences.

People with Crohn's disease have increased numbers of a 'sticky' type of E.coli and a weakened ability to fight off the intestinal bacteria. The Mycobacterial molecule's suppressive effect on macrophage white blood cells suggests it is the mechanism weakening the body's defence against the bacteria.

Professor Rhodes added: "We also found that this bacterium is a likely trigger for a circulating antibody protein (ASCA) that is found in about two thirds of patients with Crohn's disease, suggesting that these people may have been infected by the Mycobacterium."

The team is beginning clinical trials to assess whether an antibiotic combination can be used to target the bacteria contained in white blood cells as a possible treatment for Crohn's disease.

Published December 14, 2007 in the journal Gastroenterology
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