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Week ending FRIDAY February 26---------------------News Archive / Current News
The Visible Embryo maintains a searchable database of artcles published since 2007

Good Parenting Triumphs Over Pre-Natal Stress

Stress Hormone in Womb Predicts Poorer Cognitive Development, but Loving Care Can “Undo” It.

A mother’s nurture may provide powerful protection against risks her baby faces in the womb, according to a new article published online today in the journal Biological Psychiatry. The research shows that fetuses exposed to high levels of stress hormone – shown to be a harbinger for babies’ poor cognitive development – can escape this fate if their mothers provide them sensitive care during infancy and toddler-hood.

The new study represents the first, direct human evidence that fetuses exposed to elevated levels of the stress hormone cortisol may have trouble paying attention or solving problems later on. But what may be more intriguing is the study’s second finding – that this negative link disappears almost entirely if the mother forges a secure connection with her baby.

“Our results shape the argument that fetal exposure to cortisol – which may in part be controlled by the mother’s stress level – and early caregiving experience combine to influence a child's neurodevelopment,” said study author Thomas O’Connor, Ph.D., professor of Psychiatry and of Psychology at the University of Rochester Medical Center, and director of the Wynne Center for Family Research. “If future studies confirm these findings, we'll need to not only engineer ways to reduce stress in pregnancy, but we’ll need to also promote sensitive caregiving by moms and dads.”

For the study, researchers recruited 125 women at an amniocentesis clinic in an urban maternity hospital, taking a sample of their amniotic fluid so that stress hormones in it could be measured. The mothers were at 17 weeks gestation on average; only mothers with normal, healthy pregnancies and subsequent deliveries were followed.

When their children reached 17 months of age, researchers administered a Bayley infant developmental scale test, which relies on puzzles, pretend play, and baby “memory” challenges to gauge youngsters’ cognitive development. They also observed the baby and mother using the Ainsworth “Strange Situation” test, which judges childrearing quality, categorizing mom-baby pairs as either showing secure or insecure attachment to each other (watch the YouTube video of a sample of this sort of test in action below).

With cortisol levels, relationship quality results, and cognition scores in hand, researchers analyzed how the first two measures might influence the third. Indeed, for children showing “insecure attachment” to their mothers, a high prenatal cortisol level was linked with shorter attention spans and weaker language and problem-solving skills. But interestingly, for kids who enjoyed secure relationships with their moms, any negative link between high prenatal cortisol exposure and kids’ cognitive development was eliminated.

“This is such refreshing news for mothers,” O’Connor said. “Pregnancy is an emotional experience for many women, and there is already so much for mothers to be careful of and concerned about. It’s a relief to learn that, by being good parents, they might ‘buffer’ their babies against potential setbacks.”

Study Spawns Future Questions

O’Connor goes on to note a couple important nuances of the study. The first is that the amniotic (in-utero) cortisol studied could result from two sources, and it’s hard to pinpoint which. It might, for instance, be passed along the placenta from an anxious mother to her unborn baby – or it could be created and excreted directly by a stressed fetus itself.

“While many large-scale studies have observed that prenatal stress may influence child development, our particular study sheds some light on the 'how',” O’Connor said. “Still, much more research is needed to better pinpoint the exact mechanisms behind a mother ‘transferring’ her stress to her unborn baby.”

This study plays into the much larger theory of “fetal programming,” which suggests that events in the womb may prime the developing child for long-term health and developmental outcomes. Past studies, for instance, have found a pregnant mother’s diet can sway a child’s long-term risk for heart disease, diabetes and obesity. Along with diet, prenatal stress has emerged as another large-looming factor in such programming.

“Our results support this emerging theory,” said London-based study co-author, Vivette Glover, Ph.D. “In neurology, the idea emerging is that unborn children sense their mothers’ stress hormone levels, programming them for greater watchfulness. We're trying to determine whether or not that sensitivity comes with greater anxiety during childhood, and if so, what we can do about it.”

The team’s next study will revisit these same children when they turn 6; at that point, researchers hope to give the group a battery of more definitive tests to see how the interplay between in-utero cortisol levels and sensitive parenting pans out in the long-term. Those tests would include imaging studies of the children’s brains, looking to see if the higher cortisol levels may be linked to anatomical changes.

The study was supported by grants from the March of Dimes and the National Institute of Mental Health, part of the National Institutes of Health.

BPA in 'Safe' Plastics May Damage Female Babies

Yale scientists show how bisphenol A induces epigenetic changes in pregnant mice that cause hormonal imbalance in the later life of female progeny.

More evidence that "safe" plastics are not as safe as once presumed: New research published online in The FASEB Journal suggests that exposure to Bisphenol A (BPA) during pregnancy leads to epigenetic changes that may cause permanent reproduction problems for female offspring. BPA, a common component of plastics used to contain food, is a type of estrogen that is ubiquitous in the environment.

"Exposure to BPA may be harmful during pregnancy; this exposure may permanently affect the fetus," said Hugh S. Taylor, Ph.D., co-author of the study from Yale University School of Medicine in New Haven, Connecticut. "We need to better identify the effects of environmental contaminants on not just crude measures such as birth defects, but also their effect in causing more subtle developmental errors."

Taylor and colleagues made this discovery by exposing fetal mice to BPA during pregnancy and examining gene expression and DNA in the uteruses of female fetuses.

Results showed that BPA exposure permanently affected the uterus by decreasing regulation of gene expression. These epigenetic changes caused the mice to over-respond to estrogen throughout adulthood, long after the BPA exposure. This suggests that early exposure to BPA genetically "programmed" the uterus to be hyper-responsive to estrogen. Extreme estrogen sensitivity can lead to fertility problems, advanced puberty, altered mammary development and reproductive function, as well as a variety of hormone-related cancers.

BPA has been widely used in plastics and other materials. Examples include use in water bottles, baby bottles, epoxy resins used to coat food cans, and dental sealants.

"The BPA baby bottle scare may be only the tip of the iceberg." said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. "Remember how diethylstilbestrol (DES) caused birth defects and cancers in young women whose mothers were given such hormones during pregnancy. We'd better watch out for BPA, which seems to carry similar epigenetic risks across the generations. "

World First: Woman Delivers 2 Healthy Babies After Ovarian Transplant

For the first time, a woman has given birth to two children after her fertility was restored using transplants of ovarian tissue that had been removed and frozen during her cancer treatment and then restored once she was cured.

Following her ovarian transplant, Mrs Stinne Holm Bergholdt gave birth to a girl in February 2007 after receiving fertility treatment to help her become pregnant. But then, in 2008, she discovered she had conceived a second child naturally and gave birth to another girl in September 2008.

Her doctor, Professor Claus Yding Andersen, reports her case in Europe's leading reproductive medicine journal Human Reproduction. "This is the first time in the world that a woman has had two children from separate pregnancies as a result of transplanting frozen/thawed ovarian tissue," said Andersen.

So far, nine children have been born worldwide as a result of transplanting frozen/thawed ovarian tissue (including Mrs Bergholdt's two). Three have been born in Denmark after treatment carried out by Prof Andersen, who is Professor of Human Reproductive Physiology at the University Hospital of Copenhagen (Denmark). "Mrs Bergholdt gave birth to the first and the third babies and another woman delivered the second baby. This is the highest number of children born from one ovarian cryopreservation programme worldwide. It is interesting to note that nearly all of the nine pregnancies have occurred in Europe and so Europe is in the absolute forefront with this technology," he said.

Mrs Bergholdt, from Odense, Denmark, who is also one of the authors of the paper, was diagnosed with Ewing's sarcoma when she was 27 in 2004. Before she began chemotherapy, part of her right ovary was removed and frozen (her left ovary had been removed some years before because of a dermoid cyst, a type of benign ovarian tumour). Her cancer treatment was successful but, as expected, the drugs caused a menopause. In December 2005 six thin strips of ovarian tissue were transplanted back on to what remained of her right ovary. Her ovary began to function normally again and, after mild ovarian stimulation, she became pregnant and gave birth to her first daughter, Aviaja, in February 2007.

She breast-fed Aviaja until October 2007 and in January 2008 she returned to Prof Andersen's fertility clinic for additional IVF treatment so that she could conceive again. However, a pregnancy test revealed she was already pregnant naturally, and in September she gave birth to a healthy girl, Lucca.

Prof Andersen said: "This showed that the original transplanted ovarian strips had continued to work for more than four years and that Mrs Bergholdt still has the capacity to conceive and give birth to healthy children. It is an amazing fact that these ovarian strips have been working for so long and it provides information on how powerful this technique can be. She continues to have natural menstrual cycles and, at present, is using pregnancy-preventing measures to avoid becoming pregnant again.

Mrs Bergholdt, who is now 32, said: "When I found out I was pregnant for the first time I was of course very happy and excited – but also very afraid and sceptical since I found it very hard to believe that my body was really working again. My cancer had been diagnosed very late because the doctors didn't take my complaints seriously at that time and kept on telling me that nothing was wrong, so I also wondered if it was really true that I was completely recovered from it. But eventually I started to believe that the pregnancy was really happening and began to enjoy every aspect of it.

"The second time it was quite a surprise to find out I was pregnant since we hadn't been working on it – we thought we needed assistance like the first time. We had an appointment at the fertility outpatient clinic to talk about the possibility of a second baby, but it turned out that I was already pregnant – naturally. It was a very nice surprise to find out that my body was now functioning normally and that we were having a baby without having to go through the fertility treatment. It was indeed a miracle!"

Mrs Bergholdt said she and her husband had not decided yet whether they wanted more children. "The girls are still so small and need a lot of attention, but maybe in a couple of years we might think about it again."


WEDNESDAY February 24---------------------News Archive / Current News
The Visible Embryo maintains a searchable database of artcles published since 2007

Campus Child Care Needed ForStudent-Parents

Brent McBride, a professor of human development at Illinois, says the college drop-out rates of traditional undergraduates who are also full-time parents is a growing problem in the U.S.

The lack of affordable, high-quality on-campus day care programs that cater to undergraduate students who double as parents is a stealth issue that has the potential to harm both the student-parent and the child, says a University of Illinois expert in early childhood education.

According to Brent McBride, a professor of human development at Illinois, the college drop-out rates of traditional undergraduate students – college freshmen who have just transitioned from high school – who are also full-time parents is a growing problem in the U.S., one that’s further exacerbated by the lack of acceptable child care options for students pursuing a bachelor’s degree.

“The typical scenario is a young 18- to 20-year-old woman who’s away from home for the first time, separated from her familial support system, and may be in a difficult relationship with their partner,” McBride said. “It’s mostly a hidden issue, and that makes it that much worse for those student-parents, because it tends to make them feel that much more isolated. It’s just a difficult situation all around.”

Among the challenges student-parents face are a lack of money, a lack of support and understanding, and the mounting pressure of familial responsibilities.

Finding affordable child care is another big challenge student-parents face, but McBride, who also is the director of the university’s Child Development Laboratory, believes campus-based support programs, including affordable, high-quality campus day care, may provide the assistance that student-parents need to complete college while successfully raising a child.

With an on-campus day care center that’s welcoming of student-parents, “You take one big headache out of the equation,” McBride said.

“What we’ve found and what the literature supports is that traditional undergraduate students who are suddenly thrust into this role of parent aren’t prepared for all the responsibilities being a full-time parent entails,” he said. “They’ve been focused on social relationships and educational endeavors, but they haven’t thought about being a parent with a newborn baby. Having an on-campus day care program that welcomes and understands the demands on student-parents provides a support mechanism as well as a way for them to learn parenting skills.”

Affordable campus child care is also crucial to the success of student-parents from a personal developmental standpoint.

“The student-parents themselves are also at a very vulnerable stage of their own personal development,” McBride said. “They’re in that identity exploration phase where they’re transitioning to young adulthood, trying to figure out who they are, and are trying on different careers and roles for themselves.”

But with a baby in tow in addition to their full-time studies, student-parents often find themselves “tossed into an adult world with minimal preparation and minimal support for that change,” McBride said.

“Not only are they at risk for academic failure, they’re also severely at risk for personal problems because of that disruption of their own development,” he said. “That only amplifies the concern we have for these students.”

It should come as no surprise, then, McBride said, that student-parents are three times as likely as traditional undergraduates to drop out.

“If you’re a student-parent, you’re at greater risk of not succeeding at any type of institution of higher education simply because you’re a parent, and the hardships and hurdles are that much higher,” McBride said.

While their friends and peers are attending class, studying and completing homework assignments, student-parents must do all that plus raise a child.

“The vast majority of their peers are traditional undergraduate students, so there’s no organization to support them, and no way for them to congregate and seek out others in their situation,” he said.

The faculty at a traditional college or university is also usually in the dark about a student’s parental responsibilities outside of class.

“How are student-parents supposed to complete group assignments if they have to take care of a child? Not being able to participate in normal undergraduate activities only serves to further isolate them, which in turn leaves them at greater risk of dropping out and not earning a degree.”

Faced with choice between raising a child or pursuing a degree, McBride says student-parents usually have no choice but to dropout and forgo what many educators and economists see as a key component to long-term economic stability and mobility.

“The lifelong trajectory of these students is, once they transition to parenthood, they don’t finish school,” he said. “And with the economy the way it is, this is a very vulnerable demographic. Their job prospects are really hamstrung.”

Having an on-campus day care center for undergraduate student-parents not only benefits the student who eventually graduates with a bachelor’s degree, it also benefits the child.

“It helps the student-parent, because it’s one less ball that they have to juggle,” McBride said. “Trying to balance school and parenting is a tough thing to balance, especially if you’re a young single parent. But day care also benefits the child in multiple ways.”

Research overwhelmingly suggests that high-quality child care has a significant positive impact on the development of young children’s language and pre-math skills, along with other soft skills such as self-control, sociability and cooperative play.

A campus-based day care center could also leverage university resources easier than a commercial day care center.

“If there’s a language delay, for example, we can tap into campus experts in that area,” McBride said. “If there’s dysfunctional parenting, we can step in and make referrals to campus resources to help with parenting.”

Campus-based day care facilities also offer better quality controls than profit-oriented child care programs. Research consistently indicates that as much as 40 to 60 percent of all child care in the United States has been deemed sub-standard – “so sub-standard that it’s harming the child rather than helping,” McBride said.

“For better or for worse, the quality of community-based child care programs is not always what we would want it to be,” he said. “Having federal dollars being poured into something that’s less than optimal from the child care perspective, that could actually be to the detriment of the child, is not a good investment of taxpayer dollars.”

A good investment is one that’s made in human capital, so marginalizing someone who is unable to complete a college degree simply because of a child care issue is, from a social justice perspective, a tragic mistake to make, McBride said.

“If a person has the human capital to go to college, we’ve got to help them cultivate that potential,” he said. “We need to encourage parents to be good parents, to be productive members of society and to be able to provide for their children. If you take away the opportunity for higher education, they’re not going to be able to provide. We don’t want to take away those opportunities. The consequences are just too great.”

To help low-income undergraduate student-parents complete their studies, the Child Development Laboratory at Illinois is now accepting undergraduate student-parents and their children into the Child Care Access Means Parents in School (CCAMPIS) program.

Funding for the program was provided by a grant from the U.S. Department of Education.

UCSF Launches Family-Oriented Web Portal, Family Survey, and Fourth Child Care Center

The University is launching the “My Family at UCSF” web portal to provide the UCSF community with resources and information on child, youth, and older adult services at UCSF and beyond.

The site acts as a centralized location for parents and others to find information, ranging from child care, health and nutrition and UC family policies, in a one-stop, easy-to-access web portal.

The web portal is a collaborative effort between the Chancellor’s Advisory Committee on Child Care, the Chancellor’s Advisory Committee on the Status of Women, Campus Life Services, and supportive friends and families at UCSF.

“The web portal provides a badly needed and overdue centralized site to coordinate resources and information regarding family life for our UCSF community,” says Diane Wara, MD, chair of the Chancellor’s Advisory Committee on Childcare and associate dean of Minority and Women’s Affairs at the UCSF School of Medicine. “For example, one can identify child care opportunities—including the new facility at Parnassus—lactation room locations throughout the UCSF campuses, or child nutrition suggestions by utilizing links available on the same page. Our thanks to the many individuals involved in its design.”

Coinciding with the launch of the web portal is a new survey that seeks input on family needs. With the goal of increasing the availability and access of family programs, services and events, UCSF is surveying the campus community to determine what support is valuable to families. Participants that include contact information (which will remain confidential) will be entered in a drawing for one of five $25 Safeway gift cards.

If you are a member of the UCSF community and wish to take the online survey click here.

“We request that everyone with family needs complete the campus survey distributed,” Wara says. “Your thoughts and needs will be considered as we move forward with UCSF child, youth and adult services at UCSF.”

The results will be used by the Chancellor’s Advisory Committee on Child Care, helping them develop short- and long-term plans to provide more child care, youth programs, parent education and elder care.

The new “My Family” aims to help UCSF employees strike a work-life balance by providing information such as youth fitness programs, child care referrals, and health information.

“It is very exciting to have a centralized site where we can efficiently find essential information and resources about work-family life at UCSF,” says Elizabeth Ozer, faculty co-chair of the Chancellor’s Advisory Committee On the Status of Women (CACSW).

Features of the “My Family at UCSF” web portal include a “Spotlight” story, links to web resources, a child/family-focused calendar, news articles, and partner sites. Currently in the Spotlight is an article about the new Kirkham Child Development Center, the newest UCSF Child Care Center that opened on the Parnassus campus in January.

“Additionally, CACSW applauds the hard work and dedication that went into opening a new child care facility. Both initiatives reflect the campus’ ongoing commitment to support UCSF families,” adds Cathy Garzio, CACSW staff co-chair.

The Kirkham Child Development Center is now taking applications for ten open spots; application information can be found in the Spotlight article.

“This web portal is for everyone at UCSF, and includes a wide range of resources that we feel will meet the needs of our diverse families,” says Tracey Gearlds, director of Programs and Services at Campus Life Services. “Supporting families at our university is a priority for us.”

UCSF now operates four campus child care centers including: Kirkham Child Development Center (72 children 24 mths to 5 years), Marilyn Reed Lucia Child Care Study Center (currently being remodeled for 24 infants 3 months to 2 years), University Child Care Center At Laurel Heights (111 children - 3 months to five years), and University Child Care at Mission Bay (80 children - 3 months to five years).


TUESDAY February 23---------------------News Archive / Current News
The Visible Embryo maintains a searchable database of artcles published since 2007

Evolution of Neural Circuitry

James Rilling entered the University of Wisconsin in Madison as a pre-med major, following in the footsteps of three older brothers who are physicians. But an evolutionary biology class changed his plans.

"I thought the course was so powerful," says Rilling, associate professor of anthropology and the founder of Emory's Laboratory for Darwinian Neuroscience. "All societies have had a need to understand their origins. But they've made up myths to explain it, while evolutionary biology is trying to get at the true story."

Encouraged by his parents to pursue his passion, Rilling left the pre-med track to study the essence of human nature. "It's like the space program," he says. "We believe that we should be trying to understand the universe around us. I feel the same way about exploring the brain to learn who we are and how we got here."

The Milwaukee native came to Emory as a graduate student, drawn by the anthropology department's emphasis on human biology. "It's a definite strength," Rilling says, citing the department's access to Yerkes National Primate Research Center, and the quality of the faculty.

For his dissertation, Rilling used functional magnetic resonance imaging (fMRI) to compare the neuroanatomy of humans and 10 other primate species at Yerkes. The 1998 study was the first in-depth look at whether the human brain is merely a scaled-up version of the brains of other primates.

"We found that human temporal lobes are larger than you would expect for a primate of our brain size," Rilling says. "We've done subsequent work that shows this larger size is likely due to the evolution of language pathways in humans."

The study also found that the human prefrontal cortex is more convoluted than expected. "One of the things that causes these cortical folds is when strongly connected areas of cortex get pulled together. That could be the neural basis for our ability to integrate lots of different types of information," Rilling says, explaining that the prefrontal cortex is involved in functions like planning, decision-making, emotional regulation and working memory.

Rilling's Laboratory for Darwinian Neuroscience is a leader in the use of non-invasive imaging technology to compare the neuroanatomy of living primates.

Much previous work has focused on the gray matter of brains. Rilling's group is the only one in the world using diffusion tensor imaging (DTI) to compare the white matter connections of monkeys, humans and our closest relative, chimpanzees. White matter contains the fiber tracts that connect and "wire" the brain.

"We've discovered a difference in both the size and the trajectory of the fiber tract that runs between Wernicke's area in the left temporal lobe and Broca's area in the left inferior frontal cortex," Rilling says. Broca's area is involved in speech production and Wernicke's in understanding language. In humans, the pathway that connects the two areas is much more massive, and projects beyond Wernicke's area down to the ventral part of the temporal lobe.

"There's something special going on in the human brain with that pathway," Rilling says. "It's organized differently than in other primates."

The lab is also exploring the neural basis of human cognition and behavior. One of its studies showed that reciprocation in humans is tied to activation of a reward pathway in the brain. "The magnitude of that reaction correlated to how likely the person was to cooperate in the future," Rilling says.

When you cooperate and someone else fails to reciprocate, activation is found in the anterior insula, a brain region known to track visceral responses of the body.

Why are some people more cooperative than others? How does the brain change with age? What promotes social bonding and attachment? These are just a few of the many research questions the lab is tackling.

"We want to start to understand individual human differences in social behavior, at both the genetic and neurological levels," Rilling says. He adds that he's particularly interested in understanding why some men are more nurturing as fathers than others.

"It's important to have someone besides the mother involved in a child's care. I think one way that we could improve childhood development is to have more committed dads," says Rilling, who is married to a psychiatrist and hopes to one day become a father.

Progesterone Reduces Traumatic Brain Injury

Researchers at 17 medical centers across the country soon will begin using the hormone progesterone to treat patients who experience traumatic brain injury (TBI).

The treatment is part of a randomized, double-blind Phase III clinical trial that will enroll approximately 1,140 people over a three- to six-year period beginning in March, 2010. The trial is funded by a grant to Emory University from the National Institutes of Health.

The clinical trial is led by David Wright, MD, associate professor of emergency medicine at Emory University School of Medicine. Atlanta's Grady Memorial Hospital will serve as the lead center, with faculty from Emory School of Medicine and Morehouse School of Medicine.

Wright will discuss progress in clinical trials using progesterone for TBI at the American Association for the Advancement of Science (AAAS) Annual Meeting in San Diego. His presentation takes place in a panel discussion about traumatic brain injury at 1:30 p.m. PST, Friday, Feb. 19, 2010.

Emory researchers concluded in an earlier three-year clinical trial conducted in 100 patients that giving progesterone to trauma victims shortly after a brain injury appears to be safe and may reduce the risk of death and long-term disability. That clinical trial was called ProTECT I (Progesterone for Traumatic brain injury – Experimental Clinical Treatment). The current trial is named ProTECT III.

The earlier trial found evidence that progesterone is safe for use in patients suffering from traumatic brain injuries. Results also showed a 50 percent reduction in mortality in those patients treated with progesterone. The treatment improved functional outcomes and reduced disability in patients with moderate brain injury.

Progesterone is naturally present in small but measurable amounts in the brains of males and females. Human brain tissue is loaded with progesterone receptors. Laboratory studies suggest that progesterone is critical for the normal development of neurons in the brain and exerts protective effects on damaged brain tissue.

Donald G. Stein, PhD, Asa G. Candler Professor of Emergency Medicine, Emory School of Medicine, and director of Emory's Department of Emergency Medicine Brain Research Laboratory, pioneered discoveries regarding the effect of progesterone following traumatic brain injury – first discovering the neuro-protective properties of progesterone in the laboratory more than 25 years ago.

Every 15 seconds, someone in the United States sustains a significant traumatic brain injury. Approximately 2 million adults and children in the United States suffer from traumatic brain injuries each year - leading to 50,000 deaths and 80,000 new cases of long-term disability, according to the Centers for Disease Control and Prevention. Despite the enormity of the problem, scientists have failed to identify effective medications to improve outcomes following a traumatic brain injury.

"No new treatment for severe TBI has been approved in over 30 years," says Wright. "With such promising success in laboratory testing and in our previous clinical trial, we hope to conclude in this national trial that progesterone–along with standard medical trauma care–works better than standard medical care alone in reducing brain damage caused from a TBI."

The trial will be conducted through the Neurological Emergencies Treatment Trial (NETT) network coordinated by the University of Michigan. Data analysis will occur at the Medical University of South Carolina.

Exception from Informed Consent (EFIC)

As part of the trial, patients who are enrolled in the study may be provided the progesterone hormone without consent of family members or next-of-kin, in large part because success of the drug is highly dependent on its being administered to the patient as quickly as possible after sustaining a brain injury.

According to Wright, researchers normally get permission (consent) before a person participates in a clinical study. If that person is unconscious, such as in a traumatic brain injury (TBI), they will be unable to consent for themselves. In these cases researchers will ask for permission from a person's legal guardian (usually next of kin). However, since TBI must be treated quickly, there might not be enough time to locate and talk to someone about the study before the medication is started.

"In ProTECT III, a person might very well be enrolled in the study without a legal guardian's or family member's consent," explains Wright. "The U.S. Food and Drug Administration (FDA) has, in fact, created a set of special rules, called "Exception from Informed Consent" (EFIC). These rules allow research studies in certain emergency situations to be conducted without consent."

EFIC applies only when all of the following apply: A. The person is in a life-threatening situation; B. Current treatments are unproven or unsatisfactory; C. The study might provide direct benefit to the person; D. It is not possible to obtain informed consent from: 1) the person because of his or her medical condition or 2) the person's guardian because there is a very short amount of time required to treat the medical condition.


MONDAY February 22---------------------News Archive / Current News
The Visible Embryo maintains a searchable database of artcles published since 2007

How Nerve Cells Grow

Max Planck Institute researcher decodes a molecular process that controls the growth of nerve cells.

Brain researcher Hiroshi Kawabe has discovered the workings of a process that had been completely overlooked until now, and that allows nerve cells in the brain to grow and form complex networks.

The study, which has now been published in the journal Neuron, shows that an enzyme which usually controls the destruction of protein components has an unexpected function in nerve cells: it controls the structure of the cytoskeleton and thus ensures that nerve cells can form the tree-like extensions that are necessary for signal transmission in the brain. (Neuron, February 11, 2010)

Fig.: In the brain of mice, which cannot produce Nedd4-1, the extensions of nerve cells are shorter and of much simpler construction (example top) than in the brain of normal mice (example bottom). Image: Hiroshi Kawabe

In order to be able to receive signals from other cells, nerve cells form complex extensions called dendrites (from the Greek ‘dendron’ meaning tree).

The growth of dendrites in the human brain takes place mainly during late embryonic and infantile brain development. During this phase, dendrites, with a total length of many hundred kilometres, grow from the 100 billion nerve cells in our brain. The result is a highly-complex network of nerve cells that controls all bodily functions - from breathing to complicated learning processes.

In order that this incredible growth phase of brain development does not lead to chaos, the growth of the dendrites must be accurately controlled. In fact, a large number of signal processes control the direction and the speed of dendrite growth by influencing the structure of the cytoskeleton, which is inside the growing dendrite and responsible for its shape and extension.

Hiroshi Kawabe has now discovered exactly how the growth of the cytoskeleton is controlled during the dendrite development.

Using specially bred genetically engineered mice, the Japanese guest scientist conducting research at the Max Planck Institute for Experimental Medicine, discovered that the Nedd4-1 enzyme is essential for regular dendrite growth.

Nedd4-1 is an enzyme that usually controls the degradation of protein components in cells by combining them with another protein called ubiquitin. The cell identifies these ubiquitinated molecules as "waste" and degrades them. In some cases, however, the ubiquitination does not lead to the degradation of the marked protein but changes its function instead.

Nedd4-1 prevents degradation of the cytoskeleton

Hiroshi Kawabe has now shown that the Nedd4-1 enzyme ubiquitinates a signal protein called Rap2, preventing it from initiating the dismemberment of the cytoskeleton and collapse of the dendrites.

"As long as Nedd4-1 is active, the nerve cell dendrites can grow normally," reports Kawabe. "In its absence, the dendrite growth comes to a standstill and previously formed dendrites collapse, with dramatic consequences for the function of nerve cell networks in the brain."

There are, however, probably a number of parallel operating signal paths which control dendrite growth. This explains why nerve cells can also form dendrites without Nedd4-1 - although significantly fewer - and shorter - in number. The Nedd4/Rap2/TNIK mechanism would then be only one of several that can partially compensate for each other.

Kawabe's discovery provides important new insight into the mechanisms which control the development of the brain. Scientists have long been aware that Nedd4-1 is one of the most prevalent ubiquitination enzymes in nerve cells and is produced with great frequency in the developmental phase when nerve cells grow and form their dendrites.

As Kawabe points out, the function of Nedd4-1 has already been investigated in dozens of studies. "But very little work has been carried out on its role in nerve cell development, which would have been the obvious thing to do. What is surprising is that no-one has investigated this before," says the Japanese biochemist. "

Losing “Guardian Angel” Gene May Trigger Premature Birth

Some cases of premature birth may be caused by mutations in a gene that normally helps protect the body from genetic instability, according to new research from the Division of Reproductive Sciences, Perinatal Institute at Cincinnati Children’s Hospital Medical Center.

The study, recently published in the Journal of Clinical Investigation, reports that more than 50 percent of the pregnancies in genetically engineered mice lacking the protein p53 ended in premature birth and high rates of neonatal death.

“Preterm birth and prematurity are problems that pose huge long-term social and economic liabilities, and there is an urgent need for research with new approaches to combat this public health concern,” said Sudhansu K. Dey, PhD, director of the Division of Reproductive Sciences at Cincinnati Children’s and the study’s senior investigator.

Premature birth is responsible for 30 percent of all neonatal deaths and is a significant cause of long-term disability. However, the genetic and physiological reasons for preterm births remain poorly understood.

In the new study, scientists analyzed the role of Trp53, a tumor-suppressing gene that expresses the p53 protein. Trp53 is sometimes called “the guardian angel gene” because it plays an important role in preserving genetic stability and preventing mutation.

Dey and his team developed a mouse model in which the Trp53 gene was deleted in the uterus, thus removing uterine p53’s roles from the pregnancy process.

The team observed that female mice had normal ovulation, fertilization and embryo implantation. However, without p53, decidual cells surrounding the implanted embryos were prompted to undergo premature senescence and terminal differentiation. This, in turn, led to increased activation of the COX2 enzyme, which is known to trigger early muscle contractions and premature birth.

The researchers say finding this connection between the loss of Trp53 gene and premature birth is striking, because COX2 activity can be inhibited by the drug celecoxib. Dey says future prematurity studies should focus more closely on p53 and the reproductive processes it helps control.

Calcineurin Critical Enzyme to Normal Heart Growth

Scientists are reporting the first-ever data to show that the enzyme calcineurin is critical in controlling normal development and function of heart cells, and that loss of the protein leads to heart problems and death in genetically modified mice.

Published Feb. 26 in the Journal of Biological Chemistry as the paper of the week, and posted online Feb. 19, the research was led by scientists at Cincinnati Children's Hospital Medical Center and the Howard Hughes Medical Institute.

The study demonstrates that calcineurin in hearts of mice is directly linked to proper cardiac muscle contraction, rhythm and maintenance of heart activity. The near total absence of calcineurin in mice leads to heart arrhythmia, failure and death, according to the research team.

Scientists knew previously that calcineurin is important to heart function, but the extent of its role had not been defined prior to the current study. Although the research involved mice, it offers important insights for future studies that could lead to new approaches in diagnosis and treatment of heart patients, said Marjorie Maillet, Ph.D., the study's first author.

"We found that when you eliminate calcineurin, a pool of genes that regulates calcium in the heart went awry. This leads to defects in the growth and proliferation of heart cells, heart disease, arrhythmia, loss of contractility and heart failure and disease," said Dr. Maillet.

Calcium is also important to cardiac growth and the contraction of heart muscle. Previous studies have linked abnormalities in calcium handling to cardiac disease, especially in adults. In mice genetically bred for calcineurin deficiency, the researchers saw that this deficiency causes a dramatic reduction in the expression of genes that coordinately regulate calcium-handling and contraction.

The scientists also report a newly identified "feed-forward" mechanism, in which the direct activation of calcineurin by calcium augments the expression of genes that regulate calcium-handling proteins in the heart.

Funding support for the study came from the National Institutes of Health, the Howard Hughes Medical Institute, the Ohio Valley Affiliate of the American Heart Association and a collaborative research grant in cardiovascular disease from the Fondation Leducq.















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