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Week Ending FRIDAY July 24, 2009---------------------------News Archive / Return to News Alerts


Possible Genetic Link to Cause of Pregnancy Loss & Disorders
Scientists at the University of Tennessee, Knoxville, and Lawrence Berkeley National Laboratory (LBNL) have published new findings about a cause of a condition at the root of genetic disorders such as Down Syndrome, pregnancy loss and infertility

Called aneuploidy, the condition is an abnormal number of chromosomes, and the research team found that if a mother’s egg cell has a mutation in just one copy of a gene, called Bub1, then she is less likely to have offspring that survive to birth.

The findings appear in the online early edition of the Proceedings of the National Academy of Sciences for the week of July 13.

Sundar Venkatachalam, an assistant professor of biochemistry and cellular and molecular biology at UT Knoxville, originally was studying the gene for a possible connection to colon cancer, when he found his lab mice showed strange fertility characteristics.

"Where you would normally expect a female to have eight to 10 pups, there were only one or two pups that survived to term in the litters of females that had one copy of Bub1," said Venkatachalam. "So this was unusual when we were looking for cancer effects, especially in this group of females."

Ordinarily, both copies of a gene in a chromosome must carry the same mutation in order for an organism to be adversely effected, but the drastic effects of a single mutation were unexpected.

Venkatachalam, working with pathologist Robert Donnell at the UT College of Veterinary Medicine and LBNL researcher Francesco Marchetti, also found that the harmful effects of this mutation increased with a mother’s age. As the female mice got older, there was eventually a complete loss of their ability to support a full-term pregnancy that lined up with an increase in aneuploidy. The same is true in humans: the chance of having an aneuploid pregnancy increases with the age of the mother.

For the past several years, scientists have used mice to study the genetic causes of aneuploidy. They’ve zeroed in on mutations in a handful of genes as the culprits, including Bub1.

The gene plays a role in a checkpoint that ensures that chromosomes are properly divided during meiosis, the cell division process that enables a stem cell to become an egg. This checkpoint hiccups when Bub1 is mutated, sometimes producing an egg with an extra chromosome or an egg with a missing chromosome.

The team linked the issue to females by mating both a male with one bad copy of the gene with a normal female and a female with a bad copy of the gene with a normal male. When the female carried the bad copy, there were fewer births.

Further research revealed this is because aneuploidy was generated in the egg and passed on to the single-cell zygote that forms when a sperm fertilizes an egg. And this led to the loss of the embryo.

"This work certainly points to Bub1 having a role in maternal age-induced fertility issues," said Venkatachalam. "Now that we know the gene seems to have this role, the next big question is why, and we hope to continue the research in that direction."

“Heterozygosity for a Bub1 mutation causes female-specific germ cell aneuploidy in mice” was published in the July 13-17, 2009 online early edition of the Proceedings of the National Academy of Sciences. Funding for the work came from UT Knoxville's Department of Biochemistry, Cellular and Molecular Biology and the U.S. Department of Energy.

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Injection Reverses Heart-Attack Damage
Growth factor enhances heart regeneration and improves heart function without need for cardiac stem cells - laying ground for reversing heart damage after heart attack and possibly spurring heart regeneration in children with congenital heart defects

Injured heart tissue normally can't regrow, but researchers at Children's Hospital Boston have now laid the groundwork for regenerating heart tissue after a heart attack, in patients with heart failure, or in children with congenital heart defects. In the July 24 issue of Cell, they show that a growth factor called neuregulin1 (NRG1), which is involved in the initial development of the heart and nervous system, can spur heart-muscle growth and recovery of cardiac function when injected systemically into animals after a heart attack.

After birth, heart-muscle cells (cardiomyocytes) normally withdraw from the cell cycle – meaning they stop dividing and proliferating. But the researchers, led by Bernhard Kühn, MD, and Kevin Bersell of the Department of Cardiology at Children's, were able to restart the cell cycle with NRG1, stimulating cardiomyocytes to divide and make copies of themselves -- even though they are not stem cells.

"Although many efforts have focused on stem-cell based strategies, our work suggests that stem cells aren't required and that stimulating differentiated cardiomyocytes to proliferate may be a viable alternative," says Kühn, the study's senior investigator and a practicing pediatric cardiologist at Children's since 2007.

When the team injected NRG1 into the peritoneal cavity of live mice after a heart attack, once daily for 12 weeks, heart regeneration was increased and pumping function (ejection fraction, assessed on echocardiograms) improved as compared with untreated controls. The NRG1-injected mice also lacked the left-ventricular dilation and cardiac hypertrophy that typify heart failure; both were seen in the controls.

When the researchers also stimulated production of a cellular receptor for NRG1, known as ErbB4, cardiomyocyte proliferation was further enhanced, demonstrating that NRG1 works by stimulating this receptor. They also identified the specific kinds of cardiomyocytes (mononucleated) that are most likely to respond to treatment.

In 2007, Kühn and colleagues first demonstrated that the heart has dormant regenerative capacities that can be reawakened. Kühn developed a sponge-like patch, soaked in a compound called periostin that is abundant in the developing fetal heart (and in injured skeletal muscle) but scarce in adult hearts. When the patch was placed over the site of cardiac injury in rats, it induced cardiomyocyte proliferation and improved heart function (Nature Medicine 2007; 13:962-9). Similar results were seen in larger animals, and periostin is now in preclinical development at Children's Hospital Boston for future application in human patients with heart failure.

The new work adds a second compound to the heart-regeneration toolbox, and reveals how both periostin and NRG-1 work at the cellular and molecular level, an essential step in predicting possible side effects. Both compounds ultimately act on the same cellular pathway, Kühn found.

"We applied periostin locally at the site of cardiac injury, but NRG1 works when given by systemic injection – a very promising result that suggests it may be feasible to use this in the clinic to treat heart failure," says Kühn, who won a first prize Young Investigator Award, from the American College of Cardiology in 2007.


Obesity Increases Pregnancy Complications
Obese women are much more likely to suffer from minor complications such as heart burn and chest infections during pregnancy

The Tommy’s Centre for Maternal and Fetal Health at the university is looking at obesity in pregnancy and how this can be addressed to improve both the health of mother and child.

Researchers studied the records of more than 650 pregnant women, of whom nearly half were overweight or obese at the beginning of their pregnancy.

Research found that obese mothers-to-be were nearly 10 times more likely to suffer from chest infections compared with pregnant women of a healthy weight.

They were more than twice as likely to suffer from headaches and heartburn and more than three times more likely to have carpal tunnel syndrome.

This occurs when an increase in fluid causes swelling in the wrist and can cause tingling, pain, numbness and lack of coordination in the hands.

The study also found that obese women had a more than three-fold increased risk of suffering from a condition known as symphysis-pubis dysfunction.

The condition affects the pelvic joints and may cause walking difficulties if severe.

The study
The study, published in the British Journal of Obstetrics and Gynaecology, took into account factors such as age and smoking.

Costs of treating minor complications in obese women were estimated to be more than three times that of treating women of a healthy body weight.

Although symptoms such as heartburn are common and generally perceived to be benign, they can still have a major impact on the quality of life for pregnant women and can be linked to more serious conditions." says Dr Rebecca Reynolds, Tommy’s Centre for Maternal and Fetal Health

Obesity in pregnancy
Around a quarter of pregnant women giving birth are obese.

Obesity during pregnancy also increases the risk of more serious conditions such as gestational diabetes, pre-eclampsia and the need for a caesarean section.

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Genetic Toggle Switch Moves Closer to Possible Diabetes Cure
Scientists have identified a master regulator gene for early embryonic development of the pancreas and other organs, putting researchers closer to coaxing stem cells into pancreatic cells as a possible cure for type1 diabetes

Researchers at Cincinnati Children's Hospital Medical Center report their findings in the July 21 Developmental Cell.

Besides having important implications in diabetes research, the study offers new insights into congenital birth defects involving the pancreas and biliary system by concluding both organs share a common cellular ancestry in the early mouse embryo.

This discovery reverses a long standing belief that the biliary systems origin is connected to early embryonic formation of the liver, the researchers said. The pancreas regulates digestion and blood sugar, and the biliary system is vital for digestion. If the organs do not form properly during fetal development, it can be fatal.

The study reports that one gene, Sox17 (a transcription factor that controls which genes are turned on or off in a cell) is the key regulator for giving instruction to cells in early mouse embryos to become either a pancreatic cell or part of the biliary system.

The first author on the paper is Jason Spence, PhD, a research fellow in the lab of the study's senior investigator, James Wells, PhD, a researcher in the Division of Developmental Biology at Cincinnati Children's and associate professor of pediatrics at the University of Cincinnati College of Medicine.

We show that Sox17 acts like a toggle or binary switch that sets off a cascade of genetic events, said Dr. Wells. In normal embryonic development, when you have an undecided cell, if Sox17 goes one way the cell becomes part of the biliary system. If it goes the other way, the cell becomes part of the pancreas.

The finding advances ongoing research by Dr. Wells and his team to guide embryonic stem cells to become pancreatic beta cells, which scientists believe could be used to treat or cure type1 diabetes. The disease occurs when the immune system attacks insulin producing beta cells in the pancreas, usually destroying them beyond repair before the illness is diagnosed.

With this study showing us that turning one gene on or off in a mouse embryo instructs a cell to become pancreatic or biliary, now well see if that same gene, Sox17, can be used to direct an embryonic stem cell to become a biliary cell instead of a pancreatic cell. This might be used one day to replace a diseased pancreas or bile duct in people, said Dr. Wells.

The study explains that Sox17 initially works in conjunction with two other genes (the transcription factors Pdx1 and Hes1) to decide which organ fate ventral foregut progenitor cells will take. Researches demonstrated that Sox17s key role begins when the mouse embryo is 81/2 days old. If Sox17 toggles one way, with its expression repressed by its interaction with Hes1, then Pdx1 more or less takes over to prompt formation of the ventral pancreas. If Sox17 toggles the other way to increases its expression, the gene helps set off formation of the biliary system.

Dr. Wells and his colleagues are also using data from the current study to conduct experiments that should reveal what other genes are turned on or off along molecular cascade set into motion by Sox17.

Although Sox17 is the master switch, it triggers a molecular cascade of switches, and a defect in any of those can cause the whole thing to go wrong, resulting in congenital defects of the pancreas and biliary system, Dr. Wells said.

Jeffrey Whitsett, MD, executive director of the Cincinnati Children's Perinatal Institute and one of the current study's authors, said the research provides important clues for clinicians managing congenital birth defects of the pancreas and biliary system, which includes the bile ducts and gall bladder. Malformations in this region of the gastrointestinal tract can cause blockage of bile ducts or the intestines. One of the common defects is a condition called biliary atresia, in which the bile ducts are blocked, causing bile to accumulate, back up and leading to potential damage of the pancreas or liver.

Babies in neonatal intensive care frequently are born with medically challenging birth defects. The present studies help unravel the complex genetic systems controlling the formation of the gastrointestinal tract and provide the framework for future therapies of disease affecting the formation and function of the pancreas, liver, and bile ducts, Dr. Whitsett said.

THURSDAY July 23, 2009---------------------------News Archive / Return to News Alerts


Swine Flu Warning Issued to Pregnant Women
Health officials are warning pregnant women to be extra careful in the midst of the current swine flu pandemic after three pregnant patients in New South Wales are in intensive care after contracting the novel H1N1 influenza virus

Dr. Jeremy McAnulty from NSW Health says the outbreak may seem alarming, but is within the range of what was expected by health experts but expectant mothers are urged to take extra care and see a doctor immediately if they develop flu symptoms.

Apparently two other mothers with swine flu have given birth prematurely and one remains in intensive care.

Dr. McAnulty says there is a lack of immunity in the community to this particular strain of influenza which is why more people are affected - he says the outbreak is expected to continue throughout winter and is yet to peak.

Health experts advise those who are sick to stay at home, and carry out good hygiene practices particularly in public spaces - this involves washing hands regularly and discarding tissues in a bin after wiping or blowing the nose or sneezing.

As it now seems that it will be months before a vaccine becomes available such simple measures to protect against the virus are even more important.

The World Health Organization (WHO) has said the swine flu pandemic is "unstoppable" and immunisations would not be available for months.

Director General of WHO Dr. Margaret Chan has said despite media reports to the contrary, a vaccine would not be available for several months.

Dr. Chan says having a vaccine available is not the same as having a vaccine that has proven safe, and clinical trial data will not be available for another two to three months.

WHO director of vaccine research Marie-Paul Kieny had said that a swine flu vaccine should be available as early as September.

To date Australia is the worst-hit country in the Asia-Pacific region and in the midst of the southern hemisphere's traditional winter flu season, Australia cases have now topped 10,000 but experts warn that the real number could be much higher.

Australia with 10,387 confirmed swine flu cases now has more than 10% of the global total confirmed by the World Health Organization and Health Minister Nicola Roxon says the real number could be much higher, as mild cases are not being tested.

Ms Roxon says currently 123 people are hospitalised with swine flu and 58 of those are in intensive care - to date swine flu has been linked to the deaths of 20 Australians most of whom had underlying serious health issues - however there is some concern as in a few cases the disease has now started to severely affect otherwise healthy people.

The latest tally from the WHO says 94,512 cases of A(H1N1) influenza have been reported, causing 429 deaths.

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New Design For Child Seat Belt Systems
The team of researchers from the Applus+ Chair has designed a load limiter that reduces the pressure on the chest area by absorbing part of the energy produced in a frontal impact. The system reduces the speed at which the child is thrown forward and back into the seat, a movement that leads to serious injury in many accidents

David Gallegos and Paco Liesa, researchers with the Technical University of Catalonia (UPC) Applus+ Automobile Safety Chair, have developed a textile load limiter for child seat belt systems, produced in accordance with the Isofix safety standard. The system absorbs part of the energy produced in a frontal collision, which reduces the risk of serious injury to the child, particularly in the chest area and neck.

The aim of the research project was to create a textile device that, when incorporated into the upper part of an existing seat belt system, would reduce by 50% the time during which the child is subjected to strong forces in the event of a frontal impact. The device reduces the acceleration produced in the same way as a load limiter installed in a standard seat belt system for adults.

The textile device consists of a series of folds sown into the upper part of the harness, which is the area that transmits the force of an impact to the anchoring points of the vehicle.

The decisive step in the design of new child retention systems was the development of a mechanism for extending the harness without increasing the risk of the child coming into contact with structural elements of the vehicle.

Despite its comparatively simple appearance, this new innovation is the product of a complex series of static and dynamic tests and electron microscopic analyses. The system is cheap to install, does not require additional components to be connected to the existing seat belt system, and does not affect the installation of a child seat or the way in which the child must be positioned.

Although systems of this type are widely available, 18% of child passengers in Barcelona and its area of influence do not travel with any type of child seat belt mechanism fitted. When three or more children are travelling in the same vehicle, this figure increases to 45%.

According to a preliminary study carried out by Applus+ Chair researchers, most new car models are fitted with the Isofix standard, which provides rigid attachment points between the chassis and the child seat that can be fixed easily to the child seat belt system. Therefore, research into new systems and mechanisms for increasing child car safety must take into account this anchoring standard.

An award-winning system
The project won the Mª Àngels Jiménez Barcelona Memorial Prize for Road Safety for the best university research project in this field, awarded by the Barcelona City Council, the Royal Automobile Club of Catalonia (RACC), AXA, and the Spanish Association for the Prevention of Traffic Accidents (PAT). The researchers were also finalists at the International Technical Conference on the Enhanced Safety of Vehicles, which holds an international competition between university research projects in the field of automobile safety.


Infants Who Breath Ultrafine Air Pollution Get Adult Asthma
Stephania Cormier, PhD, Associate Professor of Pharmacology at LSU Health Sciences Center New Orleans, has shown for the first time that early exposure to environmentally persistent free radicals (present in airborne ultrafine particulate matter) affects long-term lung function

She recently presented her latest research data at the 11th International Congress on Combustion By-Products and Their Health Effects at the Environmental Protection Agency Conference Center in Research Triangle Park, N.C.

Dr. Cormier, a 2006 National Institute of Environmental Health Sciences Outstanding New Environmental Scientist awardee, is conducting research to determine how inhalation exposure to environmental factors such as allergens, pollutants, and respiratory viruses during infancy leads to pulmonary inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma later in life.

Using protein profiling techniques, Dr. Cormier’s lab was able to determine that early exposure to these ultrafine pollutants caused genes to produce a number of proteins, including one associated with COPD and steroid-resistant asthma, and also caused proteins to misfold, rendering them dysfunctional. These genetic defects are linked to structural changes in the lung, airflow limitations, and permanent changes in immune responses.

“It is no surprise that elevations in airborne particulate matter (PM) are associated with increased hospital admissions for respiratory symptoms including asthma exacerbations,” notes Dr. Cormier. “What has come as a surprise is that early exposure to elevated levels of PM elicits long-term effects on lung function and lung development in children.”

These results could be especially important because the US Environmental Protection Agency does not currently regulate ultrafine PM emissions.

According to the National Institutes of Health, more than 12 million Americans are currently diagnosed with COPD and another 12 million probably have it and don’t know it. Asthma is now the most common chronic disorder of childhood, affecting an estimated 6.2 million US children under the age of 18.

“Glucocorticoid (steroid) treatment is the foundation of asthma treatment; however, while the majority of patients with asthma respond to glucocorticoid treatment there are a number of patients who do not,” says Dr. Cormier. “In cells, a protein called cofilin-1 appears to inhibit glucocorticoid function. We are currently testing whether cofilin-1 also does this in the body. If it does, then it is possible to envision the development of therapeutics aimed at inhibiting cofilin-1 for use in steroid-resistant asthmatics.”

Stop And Smell The Flowers To Soothe Stress
Feeling stressed? Then try savoring the scent of lemon, mango, lavender, or other fragrant plants

Scientists in Japan are reporting the first scientific evidence that inhaling certain fragrances alter gene activity and blood chemistry in ways that can reduce stress levels

Their study appears in ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.

In the new study, Akio Nakamura and colleagues note that people have inhaled the scent of certain plants since ancient times to help reduce stress, fight inflammation and depression, and induce sleep. Aromatherapy, the use of fragrant plant oils to improve mood and health, has become a popular form of alternative medicine today. And linalool is one of the most widely used substances to soothe away emotional stress. Until now, however, linalool's exact effects on the body have been a deep mystery.

The scientists exposed lab rats to stressful conditions while inhaling and not inhaling linalool. Linalool returned stress-elevated levels of neutrophils and lymphocytes — key parts of the immune system — to near-normal levels. Inhaling linalool also reduced the activity of more than 100 genes that go into overdrive in stressful situations. The findings could form the basis of new blood tests for identifying fragrances that can soothe stress, the researchers say.

WEDNESDAY July 22, 2009---------------------------News Archive / Return to News Alerts


New Weight Guidelines For Women Pregnant With Twins
Healthy, normal-weight women pregnant with twins should gain between 37 and 54 pounds, according to research from a Michigan State University professor who helped shape the recently released national guidelines on gestational weight gain

Barbara Luke, a professor in the College of Human Medicine’s Department of Obstetrics, Gynecology and Reproductive Biology and Department of Epidemiology, helped create the guidelines for the Institute of Medicine. Her research also found overweight women should gain between 31 and 50 pounds, while obese women should gain 25 to 42 pounds.

The parameters are based on a woman’s prepregnancy body mass index.

“This amount and pattern of weight gain has been shown to be associated with the best growth before birth and the healthiest mothers throughout pregnancy,” Luke said. “By setting weight gain goals based on a woman’s prepregnancy BMI, it will be possible to maintain a trajectory of fetal growth for twins that results in more optimal birth weight with lower neonatal morbidity.

“With twin pregnancies continuing to rise every year, these new guidelines will be very beneficial.”

The guidelines are important, Luke said, because while only 3 percent of live births involve twins, they do make up a disproportionate number of premature, low-birth-weight and growth-retarded births. Twins are seven times more likely to die before their first birthday.

To develop the guidelines, Luke and her team analyzed data from more than 2,300 pregnancies with twins from four sites across the nation. Maternal weight gain and fetal growth then were measured at three different points to develop models of optimal weight gain.

Luke’s research group took into account study site, maternal age, race and ethnicity, smoking and fertility treatments, among other factors.

“Dr. Luke and her colleagues should be congratulated on this significant contribution to the health of mothers and their twin infants,” said Richard Leach, chairperson of the Department of Obstetrics, Gynecology and Reproductive Biology in MSU’s College of Human Medicine.

“The inclusion of Dr. Luke’s career work into the prestigious Institute of Medicine’s guidelines speaks to her exceptional research.”

The Institute of Medicine developed the new guidelines, which last were revised 19 years ago, in response to several emerging factors: a higher proportion of women from racial/ethnic subgroups; the increase in prepregnancy BMI among all population groups; and women becoming pregnant at older ages and, as a result, being more likely to have chronic conditions before pregnancy.

“The 1990 report had general weight gain guidelines for twin pregnancies,” Luke said. “These newest guidelines are the first which are BMI-specific — they are the 25th to 75th percentile of BMI-specific weight gain associated with twin birth weights of 5 pounds 8 ounces or greater at full-term.”

The mean gain was 46 pounds, 42 pounds, and 35 pounds, respectively, for normal weight, overweight, and obese women.

For more information on the guidelines, visit http://www.nap.edu/catalog.php?record_id=12584

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Social Cognition May Be Well Developed By Age Of 6
Social cognition—the ability to think about the minds and mental states of others—is essential for human beings

In the last decade, a group of regions has been discovered in the human brain that are specifically used for social cognition. A new study in the July/August 2009 issue of the journal Child Development investigates these brain regions for the first time in human children. The study has implications for children with autism.

Researchers at Massachusetts Institute of Technology (MIT) and Yale University scanned the brains of 13 children ages 6 to 11 as they listened to children's stories. At the moment the plot of the stories revealed what a character wanted, believed, or knew, or presented the mental state of the character, the researchers observed increased activity in these specific brain regions. When the story turned to other topics—such as the physical world or the visual appearance of the characters—activity in these brain regions went back down.

On the whole, activity in the "social brain" of the children—the parts of their brains that are used for social cognition—looked very similar to the patterns previously observed in adults. But there was one intriguing difference: One of the brain regions, the right tempero-parietal junction, appeared to change its function between the ages of 6 and 11. At age 6, the brain region played a general role in thinking about people, but by age 11, this same brain region appeared to take on a more specialized role in thinking just about others' thoughts.

"What we found—a pattern of typical development—may offer clues as we study atypical social development, as happens in autism," according to Rebecca Saxe, the Fred and Carole Middleton Career Development Professor of cognitive neuroscience at MIT, who led the study.

"Children with autism appear to have specific difficulties thinking about other people's thoughts. Understanding how human brains typically learn to think about thoughts may let us detect what is going wrong in an autistic brain, and maybe even target interventions toward those neural systems, to improve chances for recovery."

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Screening for Childhood Depression Could Start By Age 7
New research indicates that screening children for symptoms of depression, the most common mental health disorder in the United States, can begin a lot earlier than previously thought, as early as the second grade

A University of Washington study that followed nearly 1,000 children from the second to the eighth grades also found five distinct patterns for the way symptoms of depression develop among adolescents.

"Some children are reporting that they don't have as many friends, feel lonelier and are more anxious than their peers," said James Mazza, a UW professor of educational psychology and lead author of the study. "They are telling us that they feel different from the typical happy- go-lucky second grader.

"We can start to build a profile of children's mental health in the second grade. This is important because children who are experiencing depression symptoms early on may be at greater risk for mental health concerns during adolescence, based on other research studies. We want to reassure parents that everyone, including children, may feel sad or depressed once in a while, but that doesn't mean they will go on to develop depression. We are trying to understand how depression starts and evolves in childhood so that we can develop interventions to help children," Mazza said.

The new study relied on annual self reports from the children as well as parental and teacher evaluations collected as part of the Raising Healthy Children study, a larger, long-term investigation looking at the development of healthy and problem behaviors among children at 10 suburban schools in the Pacific Northwest. The depression study used data from 511 boys and 440 girls, and 81 percent of the participants were white.

The study identified five patterns of depression symptoms, but 56 percent of the children showed no or very few symptoms of depression in the second grade.

The five patterns of depression symptoms the researchers found and the percentage of students in each group are:

• Low stables -- 26 percent. These children showed none or very few signs of depression in the second grade and their rates didn't change over time through the eighth grade.

• Low risers -- 30 percent. Children in this group also had no or few symptoms in the second grade, but the number went up by a small amount in subsequent years.

• Mild stables -- 24 percent. This group had few symptoms and then went up by a small amount in subsequent years.

• Moderate changers -- 11 percent. These children started out with a few more symptoms than the previous group and their number of symptoms rose through elementary school and then dropped in middle school.

• Moderate risers -- 9 percent. This group started off with a similar number of symptoms as the moderate changers, however their symptoms did not decrease in middle school.

The study identified different early depression risk factors for boys and girls. For boys, behavior and attention problems predicted membership in the different depression groups. For girls anxiety was an early risk factor. The research also reaffirmed previous findings showing gender differences in underlying depressive symptoms, with girls experiencing more symptoms than boys in the eighth grade

"Our children are our best resource in knowing what they are feeling inside. But it is also important to have multiple perspectives. Collecting assessments from parents, teachers and the child to identify children at early risk for depression is a good method for spotting those who may go on to have later mental health risks," Mazza said.


Nature Versus Nurture? Scientists Say Neither
It's easy to explain why we act a certain way by saying "it's in the genes," but a group of University of Iowa scientists say the world has relied on that simple explanation far too long.

In research to be published today in Child Development Perspectives, the UI team calls for tossing out the nature-nurture debate, which they say has prevailed for centuries in part out of convenience and intellectual laziness.

They support evolution -- but not the idea that genes are a one-way path to specific traits and behaviors. Instead, they argue that development involves a complex system in which genes and environmental factors constantly interact.

"You can't break it down and say there's a gene for being jealous, there's a gene for being depressed, there's a gene for being gay. Those types of statements are simplistic and misleading," said UI psychologist Mark Blumberg (right), a co-author of the paper. "There is no gene for any of those things. At most, one can say there's a system of which that gene and many others are a part that will produce those outcomes."

The UI team believes genes are expressed at every point in development and are affected all along the way by a gamut of environmental factors -- everything from proteins and chemicals to the socioeconomic status of a family. These ideas are unified by a perspective called developmental systems theory.

"The nature-nurture debate has a pervasive influence on our lives, affecting the framework of research in child development, biology, neuroscience, personality and dozens of other fields," said lead author and UI psychologist John Spencer (left).

"People have tried for centuries to shift the debate one way or the other, and it's just been a pendulum swinging back and forth. We're taking the radical position that the smarter thing is to just say 'neither' -- to throw out the debate as it has been historically framed and embrace the alternative perspective provided by developmental systems theory."

The UI researchers illustrate the inadequacies of the debate by examining recent studies of imprinting, spatial cognition and language development that support the nature point of view.

Imprinting is a rapid form of learning in which animals develop preferences through brief exposure to things early in life. Nativists (researchers who align themselves with the 'nature' perspective) attribute the quick learning to a genetic predisposition, pointing to examples like ducklings following their mother's call as soon as they hatch. But research has shown that embryonic ducks, while still in the egg, are exposed to sounds from their embryonic siblings as well as sounds that they themselves make.

When these so-called 'talking eggs' are deprived of these embryonic experiences, they do not show a preference for their mother's call upon hatching. Clearly, Blumberg said, to say that imprinting in ducks is innate does not come close to capturing the elegance and complexity of the real process.

UI researchers also raised issues with studies proposing that children and animals have a built-in sense of direction as they move through the world around them and thus exhibit an innate reliance on geometric cues.

In a 2007 experiment, fish reared in a circular tank were placed in a rectangular tank to see if they would know where to find food when it was hidden in the diagonally opposite corners. They did -- which was presented as evidence of an innate ability to use geometry -- but the UI team pointed out that each fish had eight to 12 days of experience in the rectangular tank prior to the experiment and could have learned the behavior then.

"Researchers sometimes claim we're hard-wired for things, but when you peel through the layers of the experiments, the details matter and suddenly the evidence doesn't seem so compelling," Spencer said. "The problem is that it's much more complicated to explain why the evidence is on shaky ground, and often the one-liner wins out over the 10-minute explanation."

The challenge young children face when they encounter a new word has also been used to bolster nativist claims. When children are told a new word and shown a visual scene that contains unfamiliar objects, there are an infinite number of possible meanings for the word. But children are very good at figuring out which object in the scene the new word refers to. Given this amazing ability, researchers have suggested that kids have an innate ability to consider only some of the possible meanings of the word.

But in 2007, researchers at Indiana University placed cameras on children's foreheads to examine, from the child's perspective, how they found the correct referent for the word. They learned that a child's view of the nearby world -- which is limited by her small size and short arms -- is much more focused than originally thought. With few possibilities in sight, it's easy to figure out which object matches up with a novel word.

"When people say there's an innate constraint, they're making suppositions about what came before the behavior in question," Spencer said. "Instead of acknowledging that at 12 months a lot of development has already happened and we don't exactly know what came before this particular behavior, researchers take the easy way out and conclude that there must be inborn constraints. That's the predicament scientists have gotten themselves into."

UI psychologist Larissa Samuelson (left), a co-author of the paper, points to the "shape bias" as evidence that word learning is a cascading developmental process -- not an ability that's there from the beginning. Babies and toddlers learn to recognize solid objects with standard shapes -- things like ball, car, or book -- and those easy-to-distinguish objects typically become their first words.

"Language is so complex that people can't imagine how kids could do it so well without it somehow being innate," Samuelson said. "But if we steer clear of the nature-nurture debate and consider it from a developmental systems perspective, we can see how pieces of knowledge -- which may not even seem related to language -- build over time. It gets us closer to understanding the full complexity of language learning."

The UI authors realize their paper is raising eyebrows -- it has spurred several responses from other researchers that will be published in the same issue of the journal. And they understand that getting scientific peers to buy into their ideas will be a challenge -- after all, the debate dates back to Aristotle and Plato, and many scientists are passionately rooted on one side or the other.

"This is one attempt at getting the ideas out there and starting a dialog, continuing to educate the public and the scientific community, especially the younger generation of researchers," Blumberg said. "We know we don't have a sound bite that's as clean and simple and sexy as saying 'it's genetic.' But we're working on it."

TUESDAY July 21, 2009---------------------------News Archive / Return to News Alerts


How The Body Keeps A Pregnancy
For decades, scientists assumed that the ovary alone produced steroid hormones during pregnancy. In a new study in mice, however, researchers demonstrate that once an embryo attaches to the uterine wall, the uterus itself actually synthesizes the estrogen needed to sustain the pregnancy.

This is the first time that the uterus has been identified as an endocrine organ, said University of Illinois veterinary biosciences professor Indrani Bagchi, who led the study with doctoral student Amrita Das. Their findings appear this week in the Proceedings of the National Academy of Science.

“It’s the local estrogen that’s critical in maintaining the growth of blood vessels within the uterus,” Das said. After an embryo implants, the researchers found, this locally produced estrogen acts in concert with progesterone secreted from the ovaries to spur the differentiation of uterine stromal cells, a process called decidualization, and promotes the growth of blood vessels that support the development of the embryo.

The researchers discovered that during decidualization, mouse uterine stromal cells increase their expression of P450 aromatase, a key enzyme that acts with other enzymes to convert androgens to estrogen.

Even in pregnant mice that have had their ovaries removed, the production of uterine estrogen is able to support the growth and differentiation of the tissue and blood vessels needed to sustain the pregnancy.

Progesterone supplementation is required, however, indicating that local estrogen alone is not sufficient to maintain pregnancy.

Blocking the activity of the aromatase with an inhibitor also blocked decidualization, the researchers found, another indication that a successful pregnancy relies on estrogen production in uterine cells.

There are advantages to producing the appropriate amount of estrogen right where it is needed, rather than relying on the ovaries, Bagchi said.

“During pregnancy, the ovaries would need to secrete a high level of estrogen to ensure that the right amount of estrogen is present in the uterus to support decidualization,” she said. “You can imagine that if the estrogen level goes high systemically, it could have a deleterious effect on pregnancy itself by antagonizing the progesterone action.”

The findings may also be helpful to the study of endometriosis, said molecular and integrative physiology professor Milan Bagchi, an author on the study. This disorder involves the growth of endometrial tissue, which is normally shed during menstruation, at sites outside the uterus, such as the peritoneal cavity and ovaries, producing painful lesions. Endometriosis is spurred, in part, by unusually high levels of estrogen secreted from endometrial tissue growing at these extrauterine sites, he said.

Except during pregnancy, “a normal cycling uterus does not make estrogen,” he said. High estrogen levels block the activity of progesterone and can cause the non-cancerous growth of tissue seen in endometriosis.

This study was supported by the National Institutes of Health (NIH) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development at the NIH as part of the Specialized Cooperative Centers Program in Reproduction and Infertility Research.

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A Child's IQ Can Be Affected by Mom's Exposure to Pollution
Prenatal exposure to environmental pollutants known as polycyclic aromatic hydrocarbons (PAHs) can adversely affect a child's intelligence quotient or IQ, according to new research by the the Columbia Center for Children's Environmental Health (CCCEH) at the Mailman School of Public Health

PAHs are chemicals released into the air from the burning of coal, diesel, oil and gas, or other organic substances such as tobacco. In urban areas motor vehicles are a major source of PAHs. The study findings are published in the August 2009 issue of Pediatrics.

The study, funded by the National Institute of Environmental Health Sciences (NIEHS), a component of the National Institutes of Health, the U.S. Environmental Protection Agency and several private foundations, found that children exposed to high levels of PAHs in New York City had full scale and verbal IQ scores that were 4.31 and 4.67 points lower, respectively than those of less exposed children. High PAH levels were defined as above the median of 2.26 nanograms per cubic meter (ng/m3).

"These findings are of concern because these decreases in IQ could be educationally meaningful in terms of school performance," says Frederica Perera, DrPH, professor of Environmental Health Sciences and director of the CCCEH at Columbia University Mailman School of Public Health and study lead author. "The good news is that we have seen a decline in air pollution exposure in our cohort since 1998, testifying to the importance of policies to reduce traffic congestion and other sources of fossil fuel combustion byproducts."

The study included children who were born to non-smoking Black and Dominican American women age 18 to 35 who resided in Washington Heights, Harlem or the South Bronx in New York. The children were followed from in utero to 5 years of age. The mothers wore personal air monitors during pregnancy to measure exposure to PAHs and they responded to questionnaires.

At 5 years of age, 249 children were given an intelligence test known as the Wechsler Preschool and Primary Scale of the Intelligence, which provides verbal, performance and full-scale IQ scores. The researchers developed models to calculate the associations between prenatal PAH exposure and IQ. They accounted for other factors such as second-hand smoke exposure, lead, mother's education and the quality of the home caretaking environment. Study participants exposed to air pollution levels below the average were designated as having "low exposure," while those exposed to pollution levels above the average were identified as "high exposure." A total of 140 children were classified as having high PAH exposure.

"The decrease in full-scale IQ score among the more exposed children is similar to that seen with low-level lead exposure," noted Dr. Perera. "This finding is of concern because IQ is an important predictor of future academic performance, and PAHs are widespread in urban environments and throughout the world. Fortunately, airborne PAH concentrations can be reduced through currently available controls, alternative energy sources and policy interventions."


Babies Understand Dog-Speak
New research shows babies have a handle on the meaning of different dog barks – despite little or no previous exposure to dogs.

Infants just 6 months old can match the sounds of an angry snarl and a friendly yap to photos of dogs displaying threatening and welcoming body language.

The new findings come on the heels of a study from the same Brigham Young University lab showing that infants can detect mood swings in Beethoven’s music.

Though the mix of dogs and babies sounds silly, experiments of this kind help us understand how babies learn so rapidly. Long before they master speech, babies recognize and respond to the tone of what’s going on around them.

“Emotion is one of the first things babies pick up on in their social world,” said BYU psychology professor Ross Flom, lead author of the study.

Flom and two BYU students report their latest “amazing baby” findings in the journal Developmental Psychology.

“We chose dogs because they are highly communicative creatures both in their posture and the nature of their bark,” Flom said.

In the experiment, the babies first saw two different pictures of the same dog, one in an aggressive posture and the other in a friendly stance. Then the researchers played – in random order – sound clips of a friendly and an aggressive dog bark.

“They only had one trial because we didn’t want them to learn it on the fly and figure it out,” Flom said.

While the recordings played, the 6-month-old babies spent most of their time staring at the appropriate picture. Older babies usually made the connection instantly with their very first glance.

Study co-authors Dan Hyde and Heather Whipple Stephenson conducted the experiments as undergrads and don’t recall any babies getting upset.

“Many of them enjoyed it,” said Hyde. “Others just looked.”

“Infants are pretty cooperative subjects,” Stephenson added.

The mentored research experience helped Hyde and Stephenson secure spots at prestigious grad schools. Hyde is currently at Harvard working toward a Ph.D. in developmental psychology. Fellow co-author Heather Whipple Stephenson recently completed a master’s degree in educational psychology at the University of Minnesota.

“With this study, my favorite part was watching a somewhat zany idea grow into a legitimate research project,” Stephenson said.

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Stink Bombs and Pregnancy?
Scientists at the University of Leicester are investigating how the stuff of stink bombs and flatulence could play a critical role in the human reproductive system

Hydrogen sulphide –partially responsible for the foul odour of stink bombs- is also a toxic gas and has been used for chemical warfare.

But research at the University of Leicester is now looking at beneficial effects it has in the body- and the potentially critical role the chemical might have in term and pre-term births.

Dr. Ray Carson of the Department of Medical and Social Care Education at the University of Leicester presented his research at the First International Conference on Hydrogen Sulphide in Biology and Medicine in Shanghai, China.

He said: "Evidence has been gathering over the last ten years that the gas hydrogen sulphide has a signalling role in the body. Hydrogen sulphide has been shown to relax smooth muscle in the body and it may have a role in inflammation."

"For the past decade, I have studied the role of hydrogen sulphide in the female reproductive tract. So far, hydrogen sulphide has been shown to relax the uterus and it can be produced by the placenta, uterine tissue and the amniotic sac."

Dr Carson's interest is in the initiation of term labour, premature labour and pre-eclampsia, which are still poorly understood.

He said: "It is possible that research on hydrogen sulphide could provide some insight into these areas."

Dr Carson recently joined the University of Leicester and is continuing research into hydrogen sulphide in collaboration with Prof. Justin Konje in the Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine.

A recent publication in the field reported that mice that lack a key enzyme that produces hydrogen sulphide had high blood pressure, so it seems certain that interest in hydrogen sulphide will continue to grow.

MONDAY July 20, 2009---------------------------News Archive / Return to News Alerts


Stem Cells Can Be Harvested From The Placenta
Placental stem cells may soon multiply the number of children who can be cured of blood disorders thanks to a research team at Children’s Hospital & Research Center Oakland

In the 07/09 issue of Experimental Biology and Medicine, Children’s researchers demonstrate that stem cells in human placentas can become blood-manufacturing cells and that they can be harvested. The team was led by principal investigator Frans Kuypers, PhD, senior scientist and Vladimir Serikov, MD, PhD, assistant staff scientist.

“Yes the stem cells are there; yes they are viable; and yes, we can get them out,” declared Dr. Kuypers.

These Stem Cells Save the Lives of Kids With Blood Disorders
Stem cells harvested from umbilical cord blood have already cured hundreds of children with bone marrow-related disorders, including sickle cell disease, thalassemia and leukemia. But upstream from that cord river is a whole placenta lake, filled with many times more stem cells. Harvesting them would mean many more children could be helped.

The placenta is the organ inside a pregnant woman that supplies her fetus with oxygen and food. It also collects fetal waste and disposes of it through the maternal kidneys. After birth, the placenta is expelled and discarded.

Implanting placental stem cells in special laboratory mice, the team showed these stem cells not only thrived, they “made human blood in the mouse.”

What’s next is demonstrating that placental stem cells, like those found in cord blood, will do the same in a human.

Children’s Hospital a Pioneer of Cord Blood Stem Cell Research
Since 1997, using cord blood stem cells, researchers and clinicians at Children’s Hospital, among the pioneers in this work, have cured more than 100 children with bone marrow-related disorders, including sickle cell disease, thalassemia and leukemia.

This new research could dramatically increase the numbers of children and adults who could be treated and cured with such stem cells.

Stem Cells Don't Know the Difference Between 'Self' & 'Not-Self’
The importance of stem cells is that they are relatively immunologically naïve. Their "naïveté" helps them swiftly and safely take up their new job of making blood cells, including white blood cells, one of the immune system's armies. Instead of attacking host cells, the new white blood cells adopt them, becoming part of their host's new immune system. When successfully transplanted, cord blood stem cells take up residence in a patient’s bone marrow, replacing blood-manufacturing cells damaged or destroyed by disease.

“The more stem cells, the bigger the chance of success,” said Dr. Kuypers. “Some day we will be able to serve more kids and adults with this important resource.”

Genetic Match Needed - But Threshold is Lower
Of course, there still needs to be a genetic match between donor stem cells from cord or placental blood, and the cells of the person receiving them, but the threshold is lower, than for bone marrow cells, for example.

Someone ill with sickle cell disease, who needs their blood-making ability restarted, may need to match a bone marrow donor on six markers. But only four of those markers need to match for a good chance at a successful cord blood transplant. Dr. Kuypers is hopeful the same will be proved true of a placental stem cell transplant.

Gathering Placental Stem Cells on a Large Scale is Best Way to Help Kids
Dr. Kuypers believes that harvesting placental stem cells on a large scale is the best and perhaps the only way to feasibly develop their use.

“We’re looking for partnerships with industry to get placenta-derived stem cells in large quantities into the clinic,” said Dr. Kuypers.

That’s why the team also developed a patent-pending process for freezing placentas that allows them to later be defrosted without damaging the stem cells, allowing harvesting of healthy stem cells when they are needed.

This approach makes it possible to gather, ship and store placentas in a systematic way. For example, the placenta of a baby delivered in Fresno could be frozen there and information about the blood entered in a database accessible across the country. Then the placenta could be shipped to a large-scale storage facility in, for instance, Denver.

Once a transplant team, in say, Seattle, searches the database and finds a match, the frozen placenta could be shipped to them, where the stem cell transplant was to be performed. Then the needed stem cells could be extracted from the placenta on site, using a technique developed by Children’s team.

One day, thanks to research at Children’s Hospital Oakland, unneeded placentas like these, and the potentially life-saving stem cells they contain, may give countless sick children another chance at life.

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The Fancier the Cortex, the Smarter the Brain?
Why are some people smarter than others?

In a new article in Current Directions in Psychological Science, a journal of the Association for Psychological Science, Eduardo Mercado III from the University at Buffalo, The State University of New York, describes how certain aspects of brain structure and function help determine how easily we learn new things, and how learning capacity contributes to individual differences in intelligence.

Cognitive plasticity is the capacity to learn and improve cognitive skills such as solving problems and remembering events. Mercado argues that the structural basis of cognitive plasticity is the cortical module. Cortical modules are vertical columns of interconnected neuronal cells. Across different areas of the cerebral cortex, these columns vary in the number and diversity of neurons they contain. Identifying how cortical modules help us learn cognitive skills may help explain why variations in this capacity occur — that is, why people learn skills at different rates and why our ability to learn new skills changes as we age.

Studies examining a number of different species have shown that, on average, a larger cortex predicts greater intellectual capacity. The source of this correlation is unclear, but Mercado believes that a "more expansive cortex provides more space within which a larger quantity and greater diversity of cortical modules can be distributed." In other words, Mercado notes that when it comes to intellectual potential, it is not the absolute or even relative size that is important, but how many cortical modules (with various types of neurons) are available. These features of cortical organization and function determine how effectively our brain distinguishes events. This ability to differentiate events may be what enables us to learn cognitive skills.

One implication of this proposal is that experience can be as important as genetics in determining intellectual capacity. Specifically, structural changes of cortical modules generated by development and learning experiences may also contribute to individual differences in intelligence. As these networks of neurons develop over time, their diversity increases, leading to further increases in cognitive plasticity.

This research has important implications for improving educational techniques and can potentially lead to new methods for rehabilitating patients suffering from brain damage. In addition, understanding how cortical modules function may lead to new ways of increasing intelligence. However, Mercado cautions that "new technologies for increasing cognitive plasticity have ethical implications far beyond those raised by doping in sports." He concludes, "The phrase 'changing your mind' may soon take on a whole new meaning."


New Breast Pumping Approach Helps Preemies' Moms
Mothers of premature infants shouldn’t rely solely on breast pumps to establish and maintain their breast milk supply, researchers at Lucile Packard Children’s Hospital and the Stanford University School of Medicine have found. Moms already have a simple, safe and free tool for assisting breast milk production: their own hands

In the study, 67 new mothers of premature infants learned how to combine an electric breast pump with hand-expression techniques to extract milk. Unlike prior research showing poor milk production in preemies’ moms, the subjects who used both hands and pump established plentiful milk supplies. By the end of the eight-week study, their average milk production exceeded the amount needed to feed a healthy 3-month-old, even though none of the women studied could nurse when their babies were born. The findings could have implications for women who have full-term infants, too.

“When I saw the data, I realized, oh, my gosh, this is impressive,” said Jane Morton, MD, who led the study. Morton was the director of the breast-feeding medicine program at Packard Children’s when the study, which appeared online July 2 in the Journal of Perinatology, was conducted.

“We were worried about mothers of preterm babies establishing any milk supply, much less an average-or-better supply,” said William Rhine, MD, a neonatologist at Packard Children’s and the study’s senior author. The findings contradict widely held assumptions that premature delivery lessens the hormone signals needed to establish breast-feeding.

The women in the study had given birth at least 10 weeks early. Their fragile infants could not nurse for several weeks, so the mothers initially faced the challenge of establishing milk flow using only the suction of a pump. Although the women were given top-of-the-line electric breast pumps and lots of instruction and encouragement, Morton soon noticed that the first few subjects enrolled in the study were expressing only a fraction of their colostrum (the body’s precursor to milk).

That’s when she decided to break out the hand-expression expertise she’d garnered early in her 37-year career, before breast pumps were widely available. She began showing the subjects how to supplement electric pumping with hand expression, directing them to use this technique as often as possible until their milk came in. Once milk came in, mothers came to Packard Children’s for regular, monitored pumping sessions. They were instructed how to use their hands, while pumping, to massage and compress areas of the breasts that felt firm. (The study techniques are demonstrated online at http://newborns.stanford.edu/Breastfeeding/index.html.)

The women tracked how often they pumped and used hand expression, and recorded how much milk they produced.

The study’s most important finding was that women who expressed colostrum using hand expression at least six times daily during their infants’ first three days of life had the most milk later on. By the end of the study, these women were producing 45 percent more milk than women who used hand expression fewer than twice a day during the first three postpartum days. Both groups used the electric pump with the same frequency.

“What you do in those first three days makes an enormous difference,” Morton said, explaining that immediately after birth, the body is looking for signals about how much milk to produce. “Early on, it’s not just how frequently you nurse but also how effectively you nurse.” Hand expression helped women empty their breasts, sending a strong stimulus for future milk production.

Surprisingly, the hand-expression technique worked well even in women at risk for breast-feeding problems. Earlier studies showed that women who are overweight or obese, deliver by cesarean, have no prior breast-feeding experience, deliver twins or conceive via in vitro fertilization are at greater risk for under-production. However, in the current study, these risk factors did not predispose women to low milk volume. Fifteen women did not complete the study for reasons including death of their infant, transfer of the infant to another hospital, maternal health problems or decision to discontinue pumping.

The study will have implications not just for preemies’ moms but also for women who give birth to full-term infants, Morton said. “If you have a baby who doesn’t latch on and nurse effectively at first, this is a risk-free, cost-free, simple-to-learn way to express your colostrum, which can be fed to your baby,” she said. Hand expression without a pump may be sufficient to help some women with slightly preterm infants ensure they produce enough milk in the future, she added.

And for mothers who notice a decrease in their milk supply after returning to work, hands-on pumping could make electric pumping more effective. A low milk supply is the most common reason moms discontinue breast-feeding in the first year, according to recent studies. “There’s no reason to think that these same principles of milk production and pumping physiology shouldn’t also apply to full-term mothers,” said Rhine, who is also a professor of pediatrics at the School of Medicine. “They’ll probably be able to get more milk sooner and in higher volumes by using these same tricks of the trade.”

The study was funded by grants from the National Institutes of Health and by Medela, Inc. Medical Research in Switzerland, a manufacturer of breast pumps.

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Discovery of New Mechanism Controlling Neuron Migration
Understanding how neurons migrate to their proper place during brain development will offer insights into how malfunctions in the machinery cause epilepsy and mental retardation

The molecular machinery that helps brain cells migrate to their correct place in the developing brain has been identified by scientists at St. Jude Children’s Research Hospital. The finding offers new insight into the forces that drive brain organization in developing fetuses and children during their first years. Disruption of this brain-patterning machinery can cause epilepsy and mental retardation and understanding its function could give new insight into such disorders.

Led by David Solecki, Ph.D., an assistant member in the St. Jude Department of Developmental Neurobiology, the researchers published their findings in the July 16 issue of the journal Neuron.

In the experiments, the researchers sought to understand the biological machinery powering a process called glial-guided neuronal migration. Glial cells in the brain support and guide neurons, which make up the brain’s wiring. During brain development, neurons are born in germinal zones at some distance from where they must ultimately land in order to form brain structures and integrate into the brain’s circuitry.

Glial cells produce very thin fibers, and neurons in essence walk a tightrope along these fibers in moving from these germinal zones to their final position,” Solecki said. In earlier work, Solecki and his colleagues identified a control molecule called Par6 alpha that regulates this migration. Other researchers had produced evidence that a molecular motor called Myosin II might power the migration. Myosins are proteins that use chemical energy to create contractions by moving along filamental proteins called actins—like a train moves along a railroad track.

The researchers used a technique of microscopic time-lapse imaging to establish that Myosin II and actin made up the machinery of neuronal migration. Working with cultures of migrating neurons, the investigators used fluorescent dyes to label Myosin II and actin proteins, as well as key cell structures. The scientists then illuminated the cultures with rapid-fire pulses of laser light measured in thousandths of a second, taking an image with each flash. The result was a series of micromovies that revealed how the Myosin II and actin proteins and cell structures behaved during migration.

These micromovies showed that the Myosin II-actin machinery powers neuronal migration. As part of a step-wise migration process, the machinery pulls the internal cell structures of the neuron forward during migration to allow those structures to build the scaffolding that enables the neuron to move the main cell body forward. The researchers demonstrated that both Myosin II and actin are necessary for the process, because they could completely shut it down by using drugs that inhibited either molecule.

“No one had actually looked in living cells to see the configuration of actin in migrating neurons to show how it positions the machinery that will eventually elicit movement of the cell,” Solecki said. “We also found that contraction of Myosin II in the leading portion of a neuron powers movement.”

Critical to the researchers’ success was the development of a computer analysis technique for the massive number of time-lapse images, Solecki said. The analysis program was developed by study co-authors Ryan Kerekes, Ph.D., and Shaun Gleason, Ph.D., of Oak Ridge National Laboratories in Tennessee.

“Our time-lapse microscopy could image hundreds of cells in a single afternoon, but analyzing that mass of data by hand would have taken months,” Solecki said. “However, the automated analysis enabled those data to be analyzed in a matter of hours. Also, the automated analysis was free of the kind of natural bias that can occur when humans analyze such images.”

In further experiments, the researchers also showed that Par6 alpha regulates Myosin II motor activity, shedding light on how the machinery is regulated. Additional studies will explore that regulation mechanism further.

Basic understanding of the migration machinery could have important clinical implications.

“If we more clearly understand how neurons migrate in neural development, we will have a better framework to explain the basis of neuronal migration defects in children,” Solecki said. “Also, cell migrations may contribute towards the spread of brain tumors in children. If we can understand how normal neurons migrate, we might be able to dissect the machinery of the migration of brain tumor cells.”

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