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Week Ending FRIDAY May 15, 2009---------------------------News Archive

Vitamin D Insufficiency Linked to Bacterial Vaginosis in Pregnant Women
Bacterial vaginosis (BV) is the most common vaginal infection in US women of childbearing age, and is common in pregnant women. BV occurs when the normal balance of bacteria in the vagina is disrupted and replaced by an overgrowth of certain bacteria

Because having BV puts a woman at increased risk for a variety of complications, such as preterm delivery, there is great interest in understanding how it can be prevented.

Vitamin D may play a role in BV because it exerts influence over a number of aspects of the immune system. This hypothesis is circumstantially supported by the fact that BV is far more common in black than white women, and vitamin D status is substantially lower in black than white women.

This relation, however, has not been rigorously studied. To assess whether poor vitamin D status may play a role in predisposing a woman to BV, Bodnar and coworkers at the University of Pittsburgh and the Magee-Womens Research Institute studied 469 pregnant women. The results of their investigation are published in the June 2009 issue of the Journal of Nutrition.

This prospective epidemiologic study investigated the relation between vitamin D status and BV in 209 white and 260 black women at <16 wk of pregnancy with singleton gestations. Blood samples were taken, and serum analyzed for 25-hydroxyvitamin D [25(OH)D], a marker of vitamin D status. 25(OH)D levels below 80 nmol/L are typically considered insufficient. Pelvic examinations were performed, and Gram-stained vaginal smears were assessed to diagnose BV.

The data indicate that 41% of all enrolled women had BV, and that 93% had 25(OH)D levels indicative of vitamin D insufficiency.

Overall, women with BV had lower serum 25(OH)D concentrations than those without BV (P < 0.01). The prevalence of BV decreased as vitamin D concentration increased to 80 nmol/L (P < 0.001). Compared with 75 nmol/L, serum 25(OH)D concentrations of 20 nmol/L and 50 nmol/L were associated with 65% and 26% increases, respectively, in the likelihood of BV.

In summary, these findings suggest that vitamin D insufficiency is associated with BV in the first 4 months of pregnancy. Further, poor vitamin D status may contribute to the strong racial disparity in the prevalence of BV in US women. Controlled intervention trials will be needed to confirm this hypothesis.



ACLU versus Myriad Genetics - Landmark Case
The American Civil Liberties Union action in filing a lawsuit yesterday against Myriad Genetics is going to lead to one of the most important legal battles in the history of biotechnology, asserts Genetic Engineering & Biotechnology News (GEN). (www.genengnews.com)

The ACLU charged that the patenting of two human genes linked to breast and ovarian cancer will inhibit medical research. The organization also claims that the patents are invalid and unconstitutional.

“This is going to turn into one of the watershed events in the evolution of the bioindustry,” says John Sterling, Editor in Chief of GEN. “The pros and cons of patenting genes have been an ongoing, and often acrimonious series of debates, since the in re Chakrabarty decision in 1980.

But this particular case seems to have taken on a life of its own with over fifteen plaintiffs. For while the lawsuit specifically centers on the patentability of two cancer-related genes, the ACLU says it plans to challenge the entire concept of patenting genes. What we have here is one group, the ACLU and its allies, contending that gene patents stifle life science research and potentially harm the health of thousands of patients. On the other side are biotech companies who maintain that without gene patents research incentives are seriously diminished and innovation is smothered.”

Kenneth I. Berns, M.D., Ph.D., Editor in Chief of the peer reviewed journal, Genetic Testing and Molecular Biomarkers (http://www.liebertpub.com/gtmb), which is the official journal of the Genetic Alliance, says the “patenting of human genes is a bad idea and that healthcare in the U.S. would be enhanced if the ACLU suit prevails.” Dr. Berns is also Director of the University of Florida Genetics Institute in Gainesville.

William Warren, partner at the Sutherland law firm, thinks the ACLU, in this case, is barking up the wrong tree. “The ACLU unexpectedly based its invalidity challenge on claims to unpatentable subject matter,” he says. “The ACLU might have instead considered challenging the Myriad patents for obviousness.” Warren and Sutherland colleague, Lei Fang, Ph.D., M.D., have authored a legal article, which will be published in the June 1 issue of GEN entitled “Patentability of Genetic Sequences Limited.” It is now available online. (http://www.genengnews.com/news/bnitem.aspx?name=54504126&source=genwire)

For the specific details surrounding the lawsuit please see the article on the GEN website entitled “Myriad Genetics Comes under Legal Fire for Gene Patents” (www.genengnews.com/news/bnitem.aspx?name=54425046&source=genwire), which includes pertinent comments from both research and legal professionals.


Day care and Insensitive Parenting May Have Lasting Effects
Drawing on the large, longitudinal NICHD - supported study of early child care and youth development in the United States

A growing number of American children are enrolled in child care and questions remain about how these settings may affect them in both positive and negative ways.

A new study published in the May/June 2009 issue of the journal Child Development finds that early interpersonal experiences—center-based child care and parenting—may have independent and lasting developmental effects.

The study draws on the large, longitudinal Study of Early Child Care and Youth Development in the United States, which was carried out in collaboration with the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).

The NICHD study has followed about 1,000 children from 1 month through mid-adolescence to examine the effects of child care in children's first few years of life on later development. The researchers observed children in and out of their homes, and when the children were 15, they measured their levels of awakening cortisol—a stress-responsive hormone that follows a daily cycle (cortisol levels are usually high in the morning and decrease throughout the day).

Children who, during their first three years, (a) had mothers who were more insensitive and/or (b) spent more time in center-based child care - whether of high or low quality - were more likely to have the atypical pattern of lower levels of cortisol just after awakening when they were 15 years of age, which could indicate higher levels of early stress.

These findings held even after taking into consideration a number of background variables (including family income, the mothers' education, the child's gender, and the child's ethnicity), as well as observed parenting sensitivity at age 15. The associations were small in magnitude, and were not stronger for either boys or girls.

The study was supported by the National Institute of Child Health and Human Development, NICHD.

How UV Radiation Causes Cells to Die to Avoid Cancer Damage
Ultraviolet radiation from the sun can zap DNA, damage cells, and set the stage for the subsequent development of cancer. Scientists have now identified the built-in safety mechanism that forces some cells damaged by UV radiation to commit suicide so they do not perpetuate harmful mutations

Alberto R. Kornblihtt, a Howard Hughes Medical Institute international research scholar at the University of Buenos Aires and the National Research Council of Argentina, has found that UV radiation causes human cells to create proteins that trigger cell death. It’s a built-in safety pathway whose precise mechanism had never been seen before.

“It's better for the cell to die than to spread the mutations,” Kornblihtt says. The findings were published in the May 15, 2009 issue of the journal Cell.

All cells in the body rely on the same set of approximately 25,000 genes as the blueprint for the proteins they need to carry out their activities. They expand this limited repertoire through a mechanism called alternative splicing, which allows a cell to produce an assortment of different proteins from the same gene. They achieve this diversity by modifying messenger RNA (mRNA) molecules—the intermediary in the conversion from a gene to a protein.

In their experiments, Kornblihtt and his colleagues—an international team of laboratories from the U.S., France, and Spain—bombarded human cells with a highly energetic form of UV radiation that is typically blocked by the ozone layer, called UV-C. They then looked inside the damaged cells for mRNA, which ferries the genetic message from gene to protein. By examining the sequence of nucleotide letters in the mRNA, Kornblihtt could see which genes or parts of genes were used to make proteins in the damaged cells—and if they had been alternatively spliced.

They compared mRNA sequences from the damaged cells to the mRNA in healthy cells to see which genes were alternatively spliced. Using special chips that analyzed the mRNA of about 500 genes, Kornblihtt found that 14 percent of the genes switched forms in response to UV-C. “We found that UV radiation causes changes in alternative splicing, but only in a certain subset of genes,” Kornblihtt says.

Manuel Muñoz, a graduate student in Kornblihtt’s lab who is first author of the Cell paper, decided to see if any of the genes that switched forms were important in apoptosis, the process that causes cells to commit suicide. Muñoz identified two genes, Bcl-X and caspase 9, that are known to be involved with apoptosis, or programmed cell death. Apoptosis culls unneeded cells during development and growth and protects organisms by killing defective cells. Defects in apoptosis can be harmful—leading to extended cell survival and the potential for the uncontrolled growth characteristic of cancer.

The Bcl-X and caspase-9 genes can produce two different proteins via alternative splicing. For each gene, one version prevents cell death, while the other version encourages it. Kornblihtt and Muñoz found that, in both cases, UV radiation triggered production of the protein that encourages cell death. “This finding was really striking,” Kornblihtt says.

The researchers then repeated the experiments in cells missing a key protein called p53. Normally, p53 triggers the cascade of events that lead to apoptosis in response to cellular damage. But even in cells lacking p53, UV radiation still caused apoptosis, with Bcl-X and caspase 9 helping the process along. “We demonstrated that the cell death mechanisms we found are independent of p53,” Kornblihtt says. “That’s an important finding because p53 is usually needed to cause apoptosis.”

To find out how UV damage induces cell death, Kornblihtt turned to his previous work studying alternative splicing, specifically a key enzyme called polymerase II. Polymerase II is like the Xerox machine of the cell. It reads DNA then makes mRNA copies, which are later processed to make proteins. Kornblihtt had previously shown that the speed that polymerase II moves along a strand of DNA determines whether an alternative splice of mRNA is made. If it moves quickly, the enzyme will skip over some segments of the DNA. But if it moves slowly, it will include those segments, leading to an alternative splice.

Kornblihtt and his colleagues looked to see if there were any obstacles in cells damaged by UV-C that might slow down polymerase II—and thereby induce alternative splicing. They fluorescently tagged the newly formed messenger RNA to measure polymerase II speed, and found that the enzyme slowed in response to UV radiation. This decrease in speed produced the alternative forms of Bcl-X and caspase 9 that then caused the cells to commit suicide.

Now the group plans to repeat the experiments with UV-A and UV-B, which are less energetic than UV-C but are more common causes of skin cell damage in people. Kornblihtt also wants to find out how UV-C causes polymerase II to slow down. “It’s clear that UV radiation indirectly affects the speed of polymerase II,” Kornblihtt says. “Although we don’t know exactly how this happens yet.”



THURSDAY May 14, 2009---------------------------News Archive

Embryo’s Heartbeat Drives Generation of New Blood Cells
During the early days of an embryo’s development, the heart begins to beat. It turns out that beating heart does more than circulate the embryo’s small existing blood supply. Howard Hughes Medical Institute investigators have found that the blood’s movement through the aorta triggers the production of new blood stem cells, which will give rise to all the red and white blood cells the organism needs to survive

The researchers have also discovered that this essential biomechanical signal can be mimicked with drugs. The findings could help clinicians expand the supply of blood stem cells needed to treat leukemia, autoimmune disorders, and other diseases.

“The biomechanical stress of early blood flow is needed for an organism to grow its initial supply of blood cells,” says George Daley, an HHMI investigator at Children’s Hospital Boston and senior author on one of the reports, published May 13, 2009, in Nature. The second report, with HHMI investigator Leonard Zon as senior author, was published May 13, 2009, in the journal Cell.

The two investigators homed in on the importance of flow for blood development from different angles.

“For a long time, I’ve had the idea that the initiation of the heartbeat in an embryo is crucial for the creation of blood stem cells,” says Daley, who hopes to grow blood stem cells from pluripotent stem cells in the laboratory so that they can be infused into patients to treat a range of diseases. He began investigating the idea with bioengineers at the Massachusetts Institute of Technology in 2001, and in early experiments Daley’s team noticed that streaming a fluid across embryonic stem cells growing in a bioreactor did spur the development of new blood cells.

Daley shelved that research for a time, but it took off again when he began collaborating with Guillermo García-Cardeña, from Brigham and Women’s Hospital in Boston. García-Cardeña invented a miniaturized cell-culturing system that can impose different degrees of fluid flow on cells. The system grows cells on a surface beneath a shallow inverted cone, which spins at different speeds to create different rates of fluid flow.

García-Cardeña’s team seeded the system with embryonic stem cells, and found that spinning fluid at a specific rate increased the production of blood stem cells. The system produced the most blood stem cells when the fluid force was equivalent to the force of blood flow in a developing mouse aorta when the heart begins beating, at about day ten and a half of embryonic development. “The cells are tuned to sense the right force,” says Daley.

Researchers had previously established that blood arises in two waves within mouse embryos. Early blood is produced in small quantities outside the embryo, in the yolk sac, while the later blood stem cells bud from the walls of the developing aorta. Daley’s work shows that when the embryo’s heart starts to beat, the frictional forces against the walls of the aorta trigger the production of blood stem cells.

Zon, also at Children’s Hospital Boston, approached the problem in a different way. Zon has been working to identify compounds that boost production of blood stem cells, with the ultimate goal of increasing the number of blood stem cells in bone marrow and umbilical cord blood, which are transfused into patients to rebuild their immune systems after cancer therapy.

To this end, Zon developed a system to quickly test thousands of drugs in zebrafish. This approach tags zebrafish embryos with a purple dye that appears only in new blood stem cells. Since zebrafish embryos are translucent, laboratory workers can watch new blood stem cells as they are generated. “You could never do this screen in any other animal, you have to do this in zebrafish,” says Zon. “We're literally looking at the aorta as blood stem cells are being born.”

In 2007, Zon and colleagues identified a compound, called prostaglandin E2, that increases the production of new blood stem cells. The drug screens also highlighted a class of compounds that increased blood flow, and showed that these compounds increased the production of blood stem cells. Until then, Zon says, “it was not known at all that blood flow is a signal that produces blood stem cells in embryos.”

Zon then worked with mutant zebrafish embryos missing a key heart protein. The hearts in these embryos never begin beating. “You never get circulation in these fish, and if you look in their aorta, you see very few blood stem cells. That confirmed to us that blood flow is truly required to make the blood stem cells,” Zon says.

With further experiments, Zon’s team found a group of drugs that enabled the fish without beating hearts to produce blood stem cells. These drugs all had something in common: they generated nitric oxide, a well-known molecule used by cells to talk to each other. Normal blood flow enhances the production of nitric oxide. “That's at least one of the critical signals that blood flow is triggering,” Zon says. But their experiments demonstrate that nitric oxide can actually supplant the need for flow.

Daley, too, found that nitric oxide is crucial for development of blood stem cells. He used a drug to block nitric oxide production in pregnant mice, and found a marked decrease in blood stem cells in the embryos they carried.

“The lesson here may be that as we try to grow blood stem cells in the laboratory, any number of drugs that produce nitric oxide may be valuable,” Daley says.

Common Treatment to Delay Labor Decreases Preterm Infants’ Risk for Cerebral Palsy
Preterm infants born to mothers receiving intravenous magnesium sulfate, a common treatment to delay labor, are less likely to develop cerebral palsy (CP) than are preterm infants whose mothers do not receive it, reported researchers in a large National Institutes of Health (NIH) research network.1

The research was conducted by investigators in 20 participating research centers of the Maternal Fetal Medicine Units Network of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The 2,241 women in the study were at risk for preterm delivery between 24 and 31 weeks of gestation.

The researchers theorized that magnesium sulfate protects against CP because it can stabilize blood vessels, protect against damage from oxygen depletion, and protect against injury from swelling and inflammation.

CP refers to any one of a group of neurological disorders affecting control of body movement and muscle coordination. Although muscle movements are affected, CP is not caused by problems in muscles or nerves; there are abnormalities in the parts of the brain that control muscle movements that cause CP. Many people with CP suffer additional neurological disabilities, including mental retardation and epilepsy. In CP, the brain may be injured or develop abnormally during pregnancy, birth, or in early childhood; however, the causes of CP are not well understood.

For their primary calculation, the researchers grouped the proportions of infants with moderate and severe CP together with the proportion of infants who died. The researchers included the death rate in this primary calculation, because mortality among preterm infants is very high. The researchers found that a total of 11.3 percent of infants in the magnesium sulfate group had either moderate or severe CP, or had died at birth or were stillborn. In contrast, a total of 11.7 percent of the infants in the placebo group had moderate to severe CP or had died.

The results indicate that the risk of death occurring in the magnesium sulfate group (9.5 percent) did not differ significantly from those in the placebo group (8.5 percent). However, among the babies that did survive preterm births, moderate or severe CP occurred significantly less frequently in the magnesium sulfate group (1.9 percent vs. 3.5 percent). The study authors did not include mild CP in their analyses, as mild CP will often disappear with time.

These study results support the findings of an earlier National Institute of Neurological Disorders and Stroke study published in Pediatrics that reported that mothers of preterm infants who did not have CP were more likely to have received magnesium sulfate than were mothers of infants who had CP.2

The NIH study is the largest, most comprehensive study to date to analyze this inexpensive and commonly used treatment to reduce the occurrence of CP after preterm birth, according to the researchers. “This is a major advance,” said Catherine Y. Spong, MD, chief of NICHD’s Pregnancy and Perinatology Branch and an author of the study. “Our results show that obstetricians can use magnesium sulfate, which they have experience prescribing, to reduce the risk of a devastating condition - CP - in preterm infants.”

Researchers are continuing to examine the roles of genetics, environment, and traumatic events early in brain development that may lead to brain malformations and abnormalities that result in CP. The National Children’s Study, which is investigating how genetics and environmental influences before birth and in childhood impact health, will contribute to the body of research in CP and other health conditions.

Babies Increasingly Born to Unwed Mothers
By Rob Stein and Donna St. George, of the Washington Post
The number of babies being born out of wedlock has increased sharply in the United States, driven primarily by significant jumps in women in their 20s and 30s having children without getting married, according to a federal report released today


More than 1.7 million babies were born to unmarried women in 2007, a 26 percent rise from 2002 and more than double the number in 1980, according to the report from the National Center for Health Statistics. The increase reflected a 21 percent jump in the rates of unmarried women giving birth, which rose from 43.7 per 1,000 women in 2002 to 52.9 per 1,000 women.

That means that unmarried women accounted for 39.7 percent of all U.S. births in 2007 -- nearly four out of every 10 newborns -- up from 34 percent in 2002 and more than double the percentage in 1980.

"If you see 10 babies in the room, four them were born to women who were not married," said Stephanie J. Ventura, who led the analysis of birth certificate data nationwide. "It's been a huge increase -- a dramatic increase. It's quite striking."

Although the report did not examine the reasons for the increase, Ventura and other experts said the trend has been driven by a combination of factors, including the lessening of the social stigma associated with unmarried motherhood, an increase in couples delaying or forgoing marriage, and growing numbers of financially independent women and older and single women who decide to have children on their own after delaying childbearing.

"It's many factors," Ventura said. "Certainly the social disapproval factor has diminished. That's just not a factor that unmarried women once faced. And a lot of women are postponing marriage."

Some experts said the trend represents many positive changes for some women -- women are less likely to be shunned if they have children by themselves or to be forced to give their children up for adoption.

"We've seen a transformation of social norms," said Rosanna Hertz, a professor of sociology at Wellesley College. "Women can have children on their own and it's not going to destroy your employment and it's not going to mean that you'll be made a pariah by the community."

But others said that while the shift may represent some positive changes, the trend is disturbing because studies have shown that children generally tend to fare better when they grow up in stable households with two parents.

"We know that babies and children do best with committed, stable adult parents -- preferably married," said Sarah Brown of the National Campaign to Prevent Teen and Unplanned Pregnancy. "That tends to be the arrangement that produces the best outcome for children. I look at this and say, 'Maybe this trend is what young adults want or stumble into, but it's not in the best interest of children.'"

The trend has been indicated in previous reports, but the new analysis is the first to examine the dramatic social shift in detail, exploring differences in age and ethnicity as well as comparing the United States to other countries.

Although experts have been concerned about a recent uptick in births to older teens after years of decline, that is not the driving force in the overall trend but more likely a reflection of it, Ventura said.

Instead, much of the increase is due to significant increases in births among unmarried women in their 20s and 30s. Between 2002 and 2006, the rate at which unmarried women were having babies increased by 13 percent among women ages 20 to 24, by 21 percent for those ages 25 to 29, by 34 percent for women 30 to 34 and by 29 percent for those 35 to 39, the report found.

"Those are really big increases," Ventura said, noting that the increase among women in their 20s was the most important factor because they have the highest birth rate. "It's really what's happening for women in their 20s that is the dominant factor."

Compared to 1980, the rate of births among unmarried women more than doubled from 41 per 1,000 among women ages 20 to 24 to 80 per 1,000 in 2006, and nearly tripled for women ages 35 to 39 -- from 10 per 1,000 in 1980 to 27 per 1,000 in 2006, the report showed.

In 2007, 45 percent of women who gave birth in their 20s were unmarried. Sixty percent of those who had babies between 20 and 24 were single, up from 52 percent in 2002, and nearly one-third of those giving birth at ages 25 to 29 unmarried, up from one-fourth in 2002. Nearly one in five women who gave birth in their 30s were unmarried, compared with one in seven in 2002.

The rates increased for all races, but they remained highest and rose fastest for Hispanics and blacks. There were 106 births to every 1,000 unmarried Hispanic women, 72 per 1,000 blacks, 32 per 1,000 whites and 26 per 1,000 Asians, the report showed.

The rate of babies being born to unmarried women in the United States is starting to look more like that of some European countries, the report showed. For example, the percentage of babies born to unmarried women is about 66 percent in Iceland, about 55 percent in Sweden, about 50 percent in France and about 44 percent in the United Kingdom.

In many of those countries couples are living together instead of getting married, which is also the case in the United States, Ventura noted. Previous research indicates about 40 percent of births to unmarried women occur in households where couples are cohabitating, she said.

"We're seeing a big drop in emphasis on marriage," Hertz said. "There are more people living together without being married -- look at Brad and Angelina."


Brain Chemical Reduces Anxiety, Increases Survival of New Cells
Animal study suggests potential new treatment for anxiety disorders and depression

New research on a brain chemical involved in development sheds light on why some individuals may be predisposed to anxiety. It also strengthens understanding of cellular processes that may be common to anxiety and depression, and suggests how lifestyle changes may help overcome both.

The animal study, in the May 13 issue of The Journal of Neuroscience, shows an important role for fibroblast growth factor 2 (FGF2), a chemical important in brain development, in anxiety. The findings advance understanding of cellular mechanisms involved in anxiety and illuminate the role of neurogenesis, or cell birth and integration in the adult brain, in this process. Together, these findings may offer new drug targets for the treatment of anxiety and potentially for depression as well.

According to the National Institute of Mental Health, approximately 40 million Americans adults have anxiety disorders, and 14.8 million suffer from major depression. These disorders often co-occur: people with anxiety frequently also have depression, and research suggests that the two disorders may share common causes. Previous human studies led by the senior author, Huda Akil, PhD, at the University of Michigan and her collaborators in the Pritzker Consortium, showed that people with severe depression had low levels of FGF2 and other related chemicals. However, it was unclear whether reductions in FGF2 were the cause or effect of the disease.

This new study, led by Javier Perez, PhD, also at the University of Michigan, examined FGF2 levels in rats selectively bred for high or low anxiety for over 19 generations. Consistent with the human depression studies, the researchers found lower FGF2 levels in rats bred for high anxiety compared to those bred for low anxiety.

The study also suggests that environmental enrichment reduces anxiety by altering FGF2. Other researchers have shown that anxiety behaviors in rats can be modified by making changes to their environment, perhaps akin to lifestyle changes for people. Perez and colleagues found that giving the high-anxiety rats a series of new toys reduced anxiety behaviors and increased their levels of FGF2. Furthermore, they found that FGF2 treatment alone reduced anxiety behaviors in the high-anxiety rats.

“We have discovered that FGF2 has two important new roles: it’s a genetic vulnerability factor for anxiety and a mediator for how the environment affects different individuals. This is surprising, as FGF2 and related molecules are known primarily for organizing the brain during development and repairing it after injury,” Perez said.

Finally, the findings suggest that part of FGF2’s role in reducing anxiety may be due to its ability to increase the survival of new cells in a brain region called the hippocampus. Previous research has suggested that depression decreases the production and incorporation of new brain cells, a process called neurogenesis. Although the researchers found that high-anxiety rats produced the same number of new brain cells as low-anxiety rats, they found decreased survival of new brain cells in high-anxiety rats compared to low-anxiety rats. However, FGF2 treatment and environmental enrichment each restored brain cell survival.

“This discovery may pave the way for new, more specific treatments for anxiety that will not be based on sedation — like currently prescribed drugs — but will instead fight the real cause of the disease,” said Pier Vincenzo Piazza, MD, PhD, Director of the Neurocentre Magendie an INSERM/University of Bordeaux institution in France, an expert on the role of neurogenesis in addiction and anxiety who was not involved in the current study.

The research was supported by the National Institute of Mental Health, National Institute on Drug Abuse, Office of Naval Research, and The Pritzker Neuropsychiatric Disorders Research Fund.



WEDNESDAY May 13, 2009---------------------------News Archive

Folic Acid Supplements Before Birth Reduce Preemie Risk
Taking folic acid supplements for at least a year before conception is associated with reduction in the risk of premature birth, according to a study by Radek Bukowski (from the University of Texas Medical Branch, United States of America) and colleagues, published in this week's PLoS Medicine

Although most pregnancies last about 40 weeks, many babies (for example around 12% in the United States) are born before 37 completed weeks of pregnancy. Babies born prematurely are less likely to survive than full-term babies and are more likely to have breathing difficulties and learning or developmental disabilities.

Currently, there are no effective methods of prevention or treatment of premature (preterm) birth, but previous studies have suggested that lower concentrations of folate (folic acid) are associated with shorter duration of pregnancy. Bukowski and colleagues therefore tested this idea, by analyzing data collected from a cohort of nearly 35,000 pregnant women.

The results of this study showed that taking folate supplements for at least one year before conception was associated with a 70% reduction in spontaneous premature birth between 20 and 28 weeks (a reduction from 0.27% to 0.04%), and a 50% reduction between 28 and 32 weeks (reduction from 0.38% to 0.18%), as compared to the rate of preterm birth when mothers did not take additional folate supplementation.

Folate supplementation for less than a year before conception was not linked to a reduction in the risk of premature birth in this study, and folate supplementation was not associated with any other complications of pregnancy.

In a related commentary also published in this week's PLoS Medicine, Nicholas Fisk from the University of Brisbane, Australia, and colleagues (who were not involved in the original study) say "Methodologically, the study has several strengths... It is based on a huge dataset, with prospective recording of dietary supplements and potential confounders, and gestational age determined accurately on first trimester ultrasound. Those born preterm because of intervention were appropriately censored."

Nevertheless, Nicholas Fisk and colleagues also point out limitations to the study – for example, this was a secondary analysis of a Down syndrome screening study, so information on folic acid dose, formulation (with or without other supplements), and daily compliance is incomplete.

The study design was observational, so the presence of other factors, such as healthier behaviors on the part of women who take folate supplements, may explain the findings. Further evidence as to whether folic acid prevents spontaneous preterm birth will require a randomized controlled trial.

Molecular Structure of The Color of Hair and Eyes
Scientists have long known that members of the phenoloxidase family are involved in skin and hair coloring. When they are mutated, they can cause albinism – the loss of coloring in skin and hair. Produced over abundantly, they are associated with the deadly skin cancer melanoma

In an elegant structural study, a team of Baylor College of Medicine (www.bcm.edu) and German researchers explain how hemocyanin, an oxygen-carrying large protein complex which can be turned into phenoloxidase, is activated – a finding that could lead to a better understanding of both ends of the skin and hair color spectrum. A report of their work appears in the current issue of the journal Structure.

When Dr. Yao Cong, a postdoctoral researcher in the laboratory of Dr. Wah Chiu (http://www.bcm.edu/biochem/?PMID=3715), displays the computer representation of hemocyanin, it glows like a four-part jewel on the computer screen (see Figure 1). Chiu is professor of biochemistry and molecular biology at BCM and director of the National Center for Macromolecular Imaging (http://ncmi.bcm.tmc.edu/ncmi/).

"It is very large and composed of 24 molecules," Cong said. In fact, it consists of four hexamers, each with six monomers (Movie 1 and Figure).

Just getting this far required using single particle electron cryomicroscopy (cryo-EM) to produce three dimensional density maps of the molecule at sub-nanometer resolution.
"Cryo-EM is becoming a structural tool that can be used for understanding structural mechanism of large protein, which has translational and biotechnological application as demonstrated in this study," said Chiu, a senior author.

"There are some critical structural features are very well resolved in our maps," said Cong. "which could not be captured using other techniques."

She and her colleagues used the detergent SDS, which is usually used as denaturant to degrade protein, to activate hemocyanin. At certain high concentrations, instead of destroyomg the complex, it turns hemocyanin into an enzymatically active phenoloxidase.
Each monomer of the protein particle has three domains.

"It is very interesting," said Cong. "One domain is more flexible than the other two domains because it has much less interaction with neighboring subunits as compared with the other two domains."

Upon activation, there is an overall conformational change of the complex (Movie 2). The most obvious is formation of two bridges in the previously vacant middle of the protein, which strengthens the interaction between the two halves of the complex.

"Zoom into the active site," said Cong. The intrinsically flexible domain twists away from the other two domains, dragging away a blocking residue and exposes the entrance to the active site (Movie 3). This movement is then stabilized by enhanced interhexamer interactions."

"This is all about interaction," said Cong. "A single change in the local domain of a subunit can result in conformation changes in the entire complex and make it work cooperatively. This is really a molecular machine."

Using hemocyanin as a model system, scientists can learn about the activation mechanism of other phenoloxidase enzymes in the same family, opening the door to new understanding of both melanoma and albinism, she said.

"If you know the mechanism of activating the protein, you could mutate it to enhance the interaction or inhibit it – depending on what you want to accomplish," she said.

Not only does this research have implications for human disease, it could also play a role in agriculture, where enzymes in this protein family are responsible for fruit and vegetables turning brown as they age.

Imaging Technique Reveals Structural Changes of Tourette's
Toddlers with autism appear more likely to have an enlarged amygdala, a brain area associated with functions such as the processing of faces and emotion, a study by University of North Carolina at Chapel Hill School of Medicine researchers has found

In addition, this brain abnormality appears to be associated with the ability to share attention with others, a fundamental ability thought to predict later social and language function in children with autism.

These findings are published in the May 2009 issue of Archives of General Psychiatry. Lead author of the article is Matthew W. Mosconi, Ph.D. of the UNC Neurodevelopmental Disorders Research Center. Joseph Piven, M.D., director of both the Neurodevelopmental Disorders Research Center and the Carolina Institute for Developmental Disabilities at UNC, is the study’s senior and corresponding author.

“Autism is a complex neurodevelopmental disorder likely involving multiple brain systems,” Piven said. “Converging evidence from magnetic resonance imaging, head circumference and postmortem studies suggests that brain volume enlargement is a characteristic feature of autism, with its onset most likely occurring in the latter part of the first year of life.” Based both on its function and studies of changes in its structure, the amygdala has been identified as a brain area potentially associated with autism.

Mosconi, Piven and colleagues conducted a magnetic resonance imaging study involving 50 autistic children and 33 control children. Participating children underwent brain scans along with testing of certain behavioral features of autism at ages 2 and 4. This included a measure of joint attention, which involves following another person’s gaze to initiate a shared experience.

Compared to control children, those children with autism were more likely to have amygdala enlargement both at age 2 and age 4. “These findings suggest that, consistent with a previous report of head circumference growth rates in autism and studies of amygdala volume in childhood, amygdala growth trajectories are accelerated before age 2 years in autism and remain enlarged during early childhood,” the authors write. “Moreover, amygdala enlargement in 2-year-old children with autism is disproportionate to overall brain enlargement and remains disproportionate at age 4 years.”

Among children with autism, amygdala volume was associated with an increase in joint attention ability at age 4. This suggests that alterations to this brain structure may be associated with a core deficit of autism, the authors note.

“The amygdala plays a critical role in early-stage processing of facial expression and in alerting cortical areas to the emotional significance of an event,” the authors write. “Amygdala disturbances early in development, therefore, disrupt the appropriate assignment of emotional significance to faces and social interaction.” Continued follow-up of research participants, now under way, will help determine whether amygdala growth rates continue at the same rate or undergo another period of accelerated growth or a period of decelerated growth in autistic children after age 4.

The study was funded by grants from the National Institutes of Health.


Neutralizing Tumor Growth in Embryonic Stem Cell Therapy
Researchers at the Hebrew University of Jerusalem have discovered a method to potentially eliminate the tumor-risk factor in utilizing human embryonic stem cells. Their work paves the way for further progress in the promising field of stem cell therapy

Prof. Nissim Benvenisty (seated, center) with students and team members of the Stem Cell Unit and the Embryonic Stem Cell Bank, established at the Faculty of Science with the support of the Legacy Heritage Fund

Human embryonic stem cells are theoretically capable of differentiation to all cells of the mature human body (and are hence defined as "pluripotent"). This ability, along with the ability to remain undifferentiated indefinitely in culture, make regenerative medicine using human embryonic stem cells a potentially unprecedented tool for the treatment of various diseases, including diabetes, Parkinson’s disease and heart failure.

A major drawback to the use of stem cells, however, remains the demonstrated tendency of such cells to grow into a specific kind of tumor, called teratoma, when they are implanted in laboratory experiments into mice. It is assumed that this tumorigenic feature will be manifested upon transplantation to human patients as well. The development of tumors from embryonic stem cells is especially puzzling given that these cells start out as completely normal cells.

A team of researchers at the Stem Cell Unit in the Department of Genetics at the Silberman Institute of Life Sciences at the Hebrew University has been working on various approaches to deal with this problem.

In their latest project, the researchers analyzed the genetic basis of tumor formation from human embryonic stem cells and identified a key gene that is involved in this unique tumorigenicity. This gene, called survivin, is expressed in most cancers and in early stage embryos, but it is almost completely absent from mature normal tissues.

The survivin gene is especially highly expressed in undifferentiated human embryonic stem cells and in their derived tumors. By neutralizing the activity of survivin in the undifferentiated cells as well as in the tumors, the researchers were able to initiate programmed cell death (apoptosis) in those cells.

This inhibition of this gene just before or after transplantation of the cells could minimize the chances of tumor formation, but the researchers caution that a combination of strategies may be needed to address the major safety concerns regarding tumor formation by human embryonic stem cells.

A report on this latest project of the Hebrew University stem cell researchers appeared in the online edition of Nature Biotechnology. The researchers are headed by Nissim Benvenisty, who is the Herbert Cohn Professor of Cancer Research, and Ph.D. student Barak Blum. Others working on the project are Ph.D. student Ori Bar-Nur and laboratory technician Tamar Golan-Lev.


TUESDAY May 12, 2009---------------------------News Archive

Equality of the Sexes? Not Always When it Comes to Biology
MUHC researchers demonstrate that estrogen renders the innate immune system of women more powerful than that of men.

When it comes to immunity, men may not have been dealt an equal hand. The latest study by Dr. Maya Saleh, of the Research Institute of the McGill University Health Centre and McGill University, shows that women have a more powerful immune system than men. In fact, the production of estrogen by females could have a beneficial effect on the innate inflammatory response against bacterial pathogens. These surprising results will be published today in the Proceedings of the National Academy of Sciences.

More specifically, estrogen naturally produced in women seems to block the production of an enzyme called Caspase-12, which itself blocks the inflammatory process. The presence of estrogen would therefore have a beneficial effect on innate immunity, which represents the body's first line of defence against pathogenic organisms. "These results demonstrate that women have a more powerful inflammatory response than men," said Dr. Saleh.

This study was conducted on mice that lack the Caspase-12 gene, meaning that the mice were extremely resistant to infection. The human Caspase-12 gene was implanted in a group of male and female mice, yet only the males became more prone to infection. "We were very surprised by these results, and we determined that the estrogen produced by the female mice blocked the expression of the human Caspase-12 gene," explained Dr. Saleh. "We were also able to locate where the estrogen receptor binds on the gene in order to block its expression, which indicates that the hormone exerts direct action in this case."

Since these experiments were conducted using a human gene, the researchers consider these results to be applicable to humans. This feature of the female innate immune system might have evolved to better protect women's reproductive role.

The positive effect of natural estrogen on our resistence to infection is also exhibited with synthetic hormones such as 17-beta-estradiol. This finding might therefore open the door to new therapeutic applications that reinforce the immune system, but a question remains: will men be amenable to the idea of being treated with an exclusively female hormone?

Study Reveals Conflict between Doctors, Midwives over Homebirth
Two Oregon State University researchers have uncovered a pattern of distrust – and sometimes outright antagonism – among physicians at hospitals and midwives who are transporting their homebirth clients to the hospital because of complications

Oregon State University assistant professor Melissa Cheyney and doctoral student Courtney Everson said their work revealed an ongoing conflict between physicians and midwives, similar to that found in other studies of the dynamics between the two groups across the country.

The pair recently examined birth records in Oregon’s Jackson County from 1998 through 2003, a period when that county saw higher-than-expected rates of prematurity and low birth weight in some populations. The researchers wanted to assess whether those rates were linked to midwife-attended homebirths.

The findings revealed that assisted homebirths did not appear to be contributing to the lower-than-average health outcomes and, in fact, that the homebirths documented all had successful outcomes. But even more importantly to Cheyney, discussions with doctors and midwives uncovered a deep mistrust between the two groups of birthing providers, with doctors expressing the firm belief that only hospital births are safe, while midwives felt marginalized, mocked and put on the defensive when in contact with physicians.

“We’ve been getting insight into their world view, and it’s been quite illuminating,” Cheyney said.
Cheyney, who is a practicing midwife in addition to being an assistant professor of medical anthropology and reproductive biology, said she was surprised that physicians, when presented with scientifically conducted research that indicates homebirths do not increase infant mortality rates, still refuse to believe that births outside of the hospital are safe.

“Medicine is a social construct, and it’s heavily politicized,” she said.

She is working with Lane County obstetrician Dr. Paul Qualtere-Burcher to draft guidelines that would help midwives and their clients decide when they need to seek medical help, based in large part on Cheyney’s research, and another that would ask physicians to recognize midwives as legitimate caregivers.

Qualtere-Burcher said creating an open channel of communication isn’t easy.

“I do get some pushback from physician friends who say that I’m too open and too supportive,” he said. “My answer, to quote (President) Obama, is that dialogue is always a good idea.”

Qualtere-Burcher said he believes that if midwives felt more comfortable contacting physicians with medical questions or concerns, there would be a greater chance that women would get medical help when they needed it.

“Treat (midwives) with respect, as colleagues, and they’ll not be afraid to call,” he said.

While Qualtere-Burcher believes it would be wonderful, but Utopian, for all midwives to agree to seek medical assistance under the guidelines they’re proposing, and for all physicians to learn to deal more collegially with midwives, he hopes that if a small group on each side agrees to the plan, it will provide more evidence that a stronger relationship between physicians and midwives will lead to better outcomes for mothers and infants.

Last year the American Medical Association passed Resolution 205, which states: “the safest setting for labor, delivery and the immediate post-partum period is in the hospital, or a birthing center within a hospital complex…” The resolution was passed in direct response to media attention on home births, the AMA stated.

What is interesting, Cheyney points out, is that 99 percent of American births occur in the hospital, but the United States has one of the highest infant mortality rates of any developed country, with 6.3 deaths per 1,000 babies born. Meanwhile, the Netherlands, where a third of deliveries occur in the home with the assistance of midwives, has a lower rate of 4.73 deaths per 1,000.

One of the biggest problems Cheyney sees is that physicians only come into contact with midwives when something has gone wrong with the homebirth, and the patient has been transported to the hospital for care. There are a number of reasons why this interaction often is tension-filled and unpleasant for both sides, she says.

First is the assumption that homebirth must be dangerous, because the patient they’re seeing has had to be transported to the hospital. Secondly, the physician is now taking on the risk of caring for a patient who is unknown to them, and who has a medical chart provided by a midwife which may not include the kind of information the physician is used to receiving.

And because the midwife is often feeling defensive and upset, Cheyney said, the contact between her and the physician can often be tense and unproductive. Meanwhile, the patient, whose intention was not to have a hospital birth, is already feeling upset at the change in birth plan, and is now watching her care provider come into conflict with the stranger who is about to deliver her baby.

“It’s an extremely tension-fraught encounter,” Cheyney said, “and something needs to be done to address it.” As homebirths increase in popularity, she added, these encounters are bound to increase and a plan needs to be in place so that doctors and midwives know what protocol to follow.
“We’re having a meeting in early May to propose a draft for a model of collaborative care that might be the first of its kind,” in the United States, Cheyney said.

Cheyney is also pushing to get hospitals and the state records division to better track homebirths. The department of vital records had no way to indicate whether a birth occurred at home until 2008, and without being able to pull data, Cheyney said it’s hard to explore the nature of home birth in Oregon. She’s also working on education programs for midwives in rural areas, including a cultural competency piece as demographics in Oregon continue to change.
The research was funded by Oregon State University's Department of Anthropology Summer Writing Fellowship, the Center for the Study of Women and Society, and the Stanton Women’s Health Fellowship.

Toddlers with Autism More Likely to have Enlarged Amygdala
Toddlers with autism appear more likely to have an enlarged amygdala, a brain area associated with functions such as the processing of faces and emotion, a study by University of North Carolina at Chapel Hill School of Medicine researchers has found

In addition, this brain abnormality appears to be associated with the ability to share attention with others, a fundamental ability thought to predict later social and language function in children with autism.

These findings are published in the May 2009 issue of Archives of General Psychiatry. Lead author of the article is Matthew W. Mosconi, Ph.D. of the UNC Neurodevelopmental Disorders Research Center. Joseph Piven, M.D., director of both the Neurodevelopmental Disorders Research Center and the Carolina Institute for Developmental Disabilities at UNC, is the study’s senior and corresponding author.

“Autism is a complex neurodevelopmental disorder likely involving multiple brain systems,” Piven said. “Converging evidence from magnetic resonance imaging, head circumference and postmortem studies suggests that brain volume enlargement is a characteristic feature of autism, with its onset most likely occurring in the latter part of the first year of life.” Based both on its function and studies of changes in its structure, the amygdala has been identified as a brain area potentially associated with autism.

Mosconi, Piven and colleagues conducted a magnetic resonance imaging study involving 50 autistic children and 33 control children. Participating children underwent brain scans along with testing of certain behavioral features of autism at ages 2 and 4. This included a measure of joint attention, which involves following another person’s gaze to initiate a shared experience.

Compared to control children, those children with autism were more likely to have amygdala enlargement both at age 2 and age 4. “These findings suggest that, consistent with a previous report of head circumference growth rates in autism and studies of amygdala volume in childhood, amygdala growth trajectories are accelerated before age 2 years in autism and remain enlarged during early childhood,” the authors write. “Moreover, amygdala enlargement in 2-year-old children with autism is disproportionate to overall brain enlargement and remains disproportionate at age 4 years.”

Among children with autism, amygdala volume was associated with an increase in joint attention ability at age 4. This suggests that alterations to this brain structure may be associated with a core deficit of autism, the authors note.

“The amygdala plays a critical role in early-stage processing of facial expression and in alerting cortical areas to the emotional significance of an event,” the authors write. “Amygdala disturbances early in development, therefore, disrupt the appropriate assignment of emotional significance to faces and social interaction.” Continued follow-up of research participants, now under way, will help determine whether amygdala growth rates continue at the same rate or undergo another period of accelerated growth or a period of decelerated growth in autistic children after age 4.

The study was funded by grants from the National Institutes of Health.


New Tissue Scaffold Regrows Cartilage and Bone
MIT engineers have built a new tissue scaffold that can stimulate bone and cartilage growth when transplanted into the knees and other joints

The scaffold could offer a potential new treatment for sports injuries and other cartilage damage, such as arthritis, says Lorna Gibson, the Matoula S. Salapatas Professor of Materials Science and Engineering and co-leader of the research team with Professor William Bonfield of Cambridge University.

"If someone had a damaged region in the cartilage, you could remove the cartilage and the bone below it and put our scaffold in the hole," said Gibson. The researchers describe their scaffold in a recent series of articles in the Journal of Biomedical Materials Research.

The technology has been licensed to Orthomimetics, a British company launched by one of Gibson's collaborators, Andrew Lynn of Cambridge University. The company recently received approval to start clinical trials in Europe.

The scaffold has two layers, one that mimics bone and one that mimics cartilage. When implanted into a joint, the scaffold can stimulate mesenchymal stem cells in the bone marrow to produce new bone and cartilage. The technology is currently limited to small defects, using scaffolds roughly 8 mm in diameter.

The researchers demonstrated the scaffold's effectiveness in a 16-week study involving goats. In that study, the scaffold successfully stimulated bone and cartilage growth after being implanted in the goats' knees.

The project, a collaboration enabled by the Cambridge-MIT Institute, began when the team decided to build a scaffold for bone growth. They started with an existing method to produce a skin scaffold, made of collagen (from bovine tendon) and glycosaminoglycan, a long polysaccharide chain. To mimic the structure of bone, they developed a technique to mineralize the collagen scaffold by adding sources of calcium and phosphate.

Once that was done, the team decided to try to create a two-layer scaffold to regenerate both bone and cartilage (known as an osteochondral scaffold). Their method produces two layers with a gradual transition between the bone and cartilage layers.

"We tried to design it so it's similar to the transition in the body. That's one of the unique things about it," said Gibson.

There are currently a few different ways to treat cartilage injuries, including stimulating the bone marrow to release stem cells by drilling a hole through the cartilage into the bone; transplanting cartilage and the underlying bone from another, less highly loaded part of the joint; or removing cartilage cells from the body, stimulating them to grow in the lab and re-implanting them.

The new scaffold could offer a more effective, less expensive, easier and less painful substitute for those therapies, said Gibson.

MIT collaborators on the project are Professor Ioannis Yannas, of mechanical engineering and biological engineering; Myron Spector of the Harvard-MIT Division of Health Sciences and Technology (HST); Biraja Kanungo, a graduate student in materials science and engineering; recent MIT PhD recipients Brendan Harley (now at the University of Illinois) and Scott Vickers; and Zachary Wissner-Gross, a graduate student in HST. Dr. Hu-Ping Hsu of Harvard Medical School also worked on the project.

Cambridge University researchers involved in the project are Professor William Bonfield, Andrew Lynn, now CEO of Orthomimetics, Dr. Neil Rushton, Serena Best and Ruth Cameron.

The research was funded by the Cambridge-MIT Institute, the Whitaker-MIT Health Science Fund, Universities UK, Cambridge Commonwealth Trust and St. John's College Cambridge.


MONDAY May 11, 2009---------------------------News Archive

Estrogen Controls How the Brain Processes Sound
Scientists at the University of Rochester have discovered that the hormone estrogen plays a pivotal role in how the brain processes sounds.

The findings, published in today's issue of The Journal of Neuroscience, show for the first time that a sex hormone can directly affect auditory function, and point toward the possibility that estrogen controls other types of sensory processing as well. Understanding how estrogen changes the brain's response to sound, say the authors, might open the door to new ways of treating hearing deficiencies.

"We've discovered estrogen doing something totally unexpected," says Raphael Pinaud, assistant professor of brain and cognitive sciences at the University of Rochester and lead author of the study. "We show that estrogen plays a central role in how the brain extracts and interprets auditory information. It does this on a scale of milliseconds in neurons, as opposed to days, months or even years in which estrogen is more commonly known to affect an organism."

Previous studies have hinted at a connection between estrogen and hearing in women who have low estrogen, such as often occurs after menopause, says Pinaud. No one understood, however, that estrogen was playing such a direct role in determining auditory functions in the brain, he says. "Now it is clear that estrogen is a key molecule carrying brain signals, and that the right balance of hormone levels in men and women is important for reasons beyond its role as a sex hormone," says Pinaud.

Pinaud, along with Liisa Tremere, a research assistant professor of brain and cognitive sciences, and Jin Jeong, a postdoctoral fellow in Pinaud's laboratory, demonstrated that increasing estrogen levels in brain regions that process auditory information caused heightened sensitivity of sound-processing neurons, which encoded more complex and subtle features of the sound stimulus. Perhaps more surprising, says Pinaud, is that by blocking either the actions of estrogen directly, or preventing brain cells from producing estrogen within auditory centers, the signaling that is necessary for the brain to process sounds essentially shuts down. Pinaud's team also shows that estrogen is required to activate genes that instruct the brain to lay down memories of those sounds.

"It turns out that estrogen plays a dual role," says Pinaud. "It modulates the gain of auditory neurons instantaneously, and it initiates cellular processes that activate genes that are involved in learning and memory formation."

Pinaud and his group stumbled upon these findings while investigating how estrogen may help change neuronal circuits to form memories of familiar songs in a type of bird typically used to understand the biology of vocal communication. "Based on our findings we must now see estrogen as a central regulator of hearing," he says. "It both determines how carefully a sound must be processed, and activates intracellular processes that occur deep within the cell to form memories of sound experiences."

Pinaud and his team will continue their work investigating how neurons adapt their functionality when encountering new sensory information and how these changes may ultimately enable the formation of memories. They also will continue exploring the specific mechanisms by which estrogen might impact these processes.

"While we are currently conducting further experiments to confirm it, we believe that our findings extrapolate to other sensory systems and vertebrate species," says Pinaud. "If this is the case, we are on the way to showing that estrogen is a key molecule for processing information from all the senses."

When Your Brain Doesn't Know What Your Body Is Doing
As anyone with a busy schedule can attest, intending to do something and actually doing it are two different things

But your brain doesn't make such neat distinctions, according to a new study. Researchers have found that when you wave at someone, for example, the intention to move your hand creates the feeling of it having moved, not the physical motion itself. The discovery sheds new light on how the brain tracks what the body does.

Although neuroscience has revealed much about how the brain processes experiences, the origin of intention has remained a mystery. Past studies linked it to the posterior parietal cortex and the premotor cortex, two regions of the brain also associated with motion and awareness of movement, but each region's role and how they work together remained unclear.

Neuroscientist Angela Sirigu of the Centre de Neuroscience Cognitive in Bron, France, became intrigued by the posterior parietal's role in willed actions when working with patients who had injured that part of their brains. The patients couldn't define when they began to want to move, says Sirigu, because they couldn't monitor their own intention.

Sirigu joined researchers at the University of Lyon in France and neurosurgeon Carmine Mottolese of Lyon's Hôpital Pierre Wertheimer to take advantage of a common operating room practice. As part of their preparation for surgery, neurosurgeons sometimes electrically stimulate the brains of their patients, who are awake under local anesthetic, to map the brain and minimize surgical complications. During brain tumor surgery on seven patients, Mottolese stimulated their frontal, parietal, and temporal brain regions, and Sirigu's team asked the patients to describe what they felt.

After stimulation of the parietal cortex, patients reported "wanting" to move their arms, legs, lips, or chest but didn't actually move them. When Mottolese stimulated the same region more intensely, patients believed that they had moved the body parts they'd intended to move even though they hadn't. Stimulating the premotor cortex, on the other hand, resulted in real movements, but the patients were never conscious of their motions.

The results, reported in May 8th issue of Science, suggest that "we need intention to be aware of what we are doing," says Sirigu. The brain's intention and its prediction of what will result from carrying out that intention create our experience of having moved, she says.

"I think this study is extremely exciting," says Patrick Haggard, a cognitive neuroscientist at University College London in the United Kingdom. "It's quite encouraging to think that there could be a neuroscience of volition," he says. "And this idea of volition is about as central to our nature as it gets."

Iron Deficiency in Womb May Delay Auditory Nervous System in Preemies
Iron plays a large role in brain development in the womb, and new University of Rochester Medical Center research shows an iron deficiency may delay the development of auditory nervous system in preemies

This delay could affect babies ability to process sound which is critical for later language development in early childhood.

The study evaluated 80 infants over 18 months, testing their cord blood for iron levels and using a non-invasive tool -- auditory brainstem-evoked response (ABR) -- to measure the maturity of the brain's auditory nervous system soon after birth. The study found that the brains of infants with low iron levels in their cord blood had abnormal maturation of auditory system compared to infants with normal cord iron levels.

"Sound isn't transmitted as well through the immature auditory pathway in the brains of premature babies who are deficient in iron as compared to premature babies who have enough iron," said Sanjiv Amin, M.D., associate professor of Pediatrics at the University of Rochester Medical Center and author of the abstract presented today at the Pediatric Academic Society meeting in Baltimore. "We suspect that if the auditory neural system is affected during developmental phase, then other parts of the brain could also be affected in the presence of iron deficiency."

As many as 20 to 30 percent of pregnant women with lower socio-economic status are iron deficient. Iron deficiency in pregnant woman can cause anemia, a condition in which there are not enough red blood cells to carry oxygen around the body. Anemia can cause a range of problems in pregnancy from exhaustion to preterm labor and low birth weight. But physicians didn't know that an iron deficiency in a fetus may also delay auditory neural maturation. which could lead to language problems.

"We are concerned by these findings because of its potential implications for language development," Amin said. "More study is needed to fully understand what this delay in maturation means. This finding at least underscores an already understood need to monitor iron levels in pregnant women."

Does Mom Know When Enough is Enough?
As the childhood obesity epidemic in the United States continues, researchers are examining whether early parent and child behaviors contribute to the problem

A study from the Department of Nutritional Sciences, Rutgers University, published in the May/June 2009 issue of the Journal of Nutrition Education and Behavior reports that mothers who miss signs of satiety in their infants tend to overfeed them, leading to excess weight gains during the 6 month to 1 year period.

Ninety-six low-income black and Hispanic mothers, who chose to formula feed exclusively, were enrolled in the study. Data was collected during an initial interview and three home visits at 3, 6, and 12 months. During the home visits, feedings were observed, the mothers were interviewed, and the child's weight was measured. Feeding diaries were also checked for omissions or clarifications.

A number of characteristics that predicted infant weight gain from birth to 3 months were included in the analysis. These were birth weight, gender, race/ethnicity, maternal age, education, country of origin, body mass index (BMI) before pregnancy, and weight gain during pregnancy. For the 3 to 6 month period, birth weight, maternal BMI, infant weight gain from birth to 3 months, infant length gain from birth to 3 months, the estimated number of feeds per day, the month that solid food was introduced, and the mothers' sensitivity to the infants' signals at 3 months were included. And, finally, for the 6 to 12 month period, birth weight, maternal BMI, infant weight gain from 3 to 6 months, infant length gain from 3 to 6 months, maternal sensitivity to infant signals at 6 months, and the estimated number of feeds/day at 6 months were entered as the independent variables.

None of these variables served to predict infant weight gain over the first 3 months, or similarly, from 3 to 6 months. However, the number of feeds per day at 6 months approached significance in predicting weight gain from 6 to 12 months, and maternal sensitivity to the infants' signals reached predictive significance, but in a negative direction—indicating that mothers who were less sensitive to satiety cues had infants who gained more weight.

Writing in the article, John Worobey, PhD; Maria Islas Lopez, MA; and Daniel J. Hoffman, PhD, state, "More frequent feedings, particularly with formula, are an easy culprit on which to assign blame. But maternal sensitivity to the infant's feeding state, as reflected by the Feeding Scale scores, suggests that an unwillingness to slow the pace of feeding or terminate the feeding when the infant shows satiation cues may be overriding the infant's ability to self-regulate its intake."

However, the researchers warn that, "To use this knowledge to better inform low-income/educated mothers, indeed, mothers of any background who have settled on a feeding method, could pose a daunting challenge. Feeding an infant is a primal behavior, and to suggest to a new mother that she is feeding her infant too often, too much, or worse yet, is not very good at reading her infant's signals, would require an extremely skilled nurse or social worker. Giving counsel after watching a mother feed her infant might be seen as threatening, or at the very least meddling, and just pointing it out could be construed as an accusation of 'poor mothering.'"















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