The Visible Embryo News Archive

A protein discovered in fruit fly eyes has brought a Johns Hopkins team closer to understanding how the human heart and other organs automatically “right size” themselves, a piece of information that may hold clues to controlling cancer.

The protein, named Kibra, is linked to a relay of chemical signals responsible for shaping and sizing tissue growth by coordinating control of cell proliferation and death, according to research published Feb. 16 in Developmental Cell by teams at Johns Hopkins and Florida State University.

In a series of experiments, the scientists manipulated Kibra’s role in a signaling network called the Hippo pathway, which consists of several proteins working together as a braking system. Counterparts of the components in the Hippo pathway in flies are found in most animals, suggesting that this pathway may act as a “global regulator” of organ size control, according to Duojia Pan, Ph.D., a professor of molecular biology and genetics at Johns Hopkins University School of Medicine and an investigator of the Howard Hughes Medical Institute.

“People have always been curious about what makes a hippopotamus grow so much bigger than a mouse,” says Pan, “as well as how our two hands, which develop independently, get to very similar sizes. Our studies show that Kibra regulates Hippo, which keeps organs characteristically sized, preventing my heart or your liver from becoming as hefty as those befitting a large African amphibious mammal,” he adds, referring to the signaling pathway’s name.

Pan's team identified the gene they named Hippo in 2003, showing that an abnormal copy of it led to an unusually large eye in a developing fruit fly. Two years later, the team established that Hippo lies in the middle of a signaling cascade: Its “stop growing” message is relayed along a molecular pathway of biochemically linked proteins, which limits the expression of genes that otherwise promote cell division and cell survival. In 2007, they showed that by manipulating the pathway in a mouse liver, the organ grew to five times its normal size and became cancerous.

The new experiments, Pan says, moved the investigation “slowly and methodically upstream” to find Hippo’s trigger, where, he believes, “the key to size-control lies.” The Hippo-Kibra link could be a key to understanding and treating cancer, Pan adds, because cancer is literally a disease of uncontrolled growth.

The Johns Hopkins and Florida State teams discovered Kibra by studying ovarian cells from adult flies and by using a gene-controlling technique called RNA interference (RNAi) to systematically turn off each of the approximately 14,000 genes in the fly genome, one at a time, in cultured fly cells. They then analyzed the function of Kibra in the developing fly larvae.

Each of the specialized discs that develop into a fly’s eyes starts out with approximately 30 to 40 cells and then grows by about a thousand-fold in the larval stage before stopping, making larvae the ideal place to catch the right-sizing process in action, Pan says. These studies told them that the Hippo pathway was not active in the absence Kibra.

Further studies on human cells measured the activity of the Hippo pathway while manipulating human Kibra and showed that like its fruit fly counterpart, human Kibra acts as a tumor suppressor protein that regulates Hippo signaling.

“The discovery of Kibra moves us an important step closer to identifying the initial signal that triggers Hippo’s activation,” Pan says. “We’re making progress along the Hippo pathway, heading toward the cell surface, and believe we will find that elusive signal en route.”

The name Kibra, a shortened combination of the words kidney and brain, is based on earlier evidence that Kibra is prominently expressed in those two organs. Kibra’s role in memory performance in humans has already garnered interest.

Authors of the paper, in addition to Pan, are Jianzhong Yu, Stephen Klusza and Wu-Min Deng of Florida State University; and Yonggang Zheng and Jixin Dong of Johns Hopkins.

This research was supported by grants from the National Institutes of Health.

Prenatal Advice Inconsistent in Weight Counseling

A new study from UCSF shows that prenatal health care professionals are concerned about patients’ excessive weight gain during pregnancy but have difficulty providing effective counseling.

Excessive weight gain during pregnancy is associated with short and long term adverse health for mothers and children, and is increasing in the United States. Health care providers agree that weight gain is an important topic with pregnant women, yet researchers identified inconsistent counseling among clinicians and barriers - including insufficient training, concern about the sensitivity of the topic and the perception that counseling is ineffective - that prevent them from talking to patients.

Their findings will be reported in the April 2010 issue of the Journal of Women’s Health.

“Clinicians in the study raised concerns about shaming or stressing pregnant women, and often wait for patients to raise the question of proper weight gain. Many providers – especially physicians – also said they lacked education in weight management issues,” said Naomi E. Stotland, MD, lead author of the study and assistant professor in the UCSF Department of Obstetrics, Gynecology, and Reproductive Sciences.

New Pregnancy Weight Guidelines
Guidelines for pregnancy weight gain, based on woman's BMI (body mass index) before becoming pregnant with single baby:
Underweight:	Gain 28-40 pounds
Normal weight:	Gain 25-35 pounds
Overweight:	Gain 15-25 pounds
Obese:	Gain 11-20 pounds
Guidelines for weight gain during pregnancy with twins, based on the mother's prepregnancy BMI:
Normal weight:	Gain 37-54 pounds
Overweight:	Gain 31-50 pounds
Obese:	Gain 25-42 pounds
Underweight: No weight gain guidelines are available because of insufficient data.

The Institute of Medicine’s (IOM) guidelines for weight gain during pregnancy are widely accepted by professional medical organizations. However, several providers said they did not proactively share the ranges with patients. Another clinician intentionally advised weight gain above the guidelines to avoid causing the patient anxiety and another thought the IOM weight gain guidelines are too high.

Of more than four million births annually in the United States, nearly 60 percent of mothers begin pregnancy either overweight or obese, so prenatal care can be an opportune time for healthcare providers to help women make positive lifestyle changes in nutrition and physical activity that affect weight, Stotland said.

During pregnancy, perhaps unlike any other time in a woman’s life, most women see a healthcare provider frequently to receive prenatal care. Pregnant women may be especially motivated to make lifestyle changes out of concern for the health of their offspring.

“It is important to identify new tools that will enable clinicians to more easily and effectively counsel pregnant woman so that together they can determine strategies to achieve the healthiest weight for that individual,” Stotland said. “I also would encourage women to initiate the conversation if their doctors are not raising the topic of weight gain.”

“Simple messages from clinicians to patients about nutrition and physical activity during pregnancy have been shown to have an important positive impact on patient behaviors. We encourage clinicians to take this opportunity to improve the health of their patients. Every pregnant woman has the potential to leave pregnancy in better health than when she began pregnancy,” according to Barbara Gerbert, PhD, senior author of the study and professor in the Division of Behavioral Sciences, Professionalism, and Ethics, UCSF School of Dentistry.

The researchers conducted seven focus groups with a total of 52 participants from the San Francisco Bay Area. Obstetrician/gynecologists made up three groups, with two groups each of certified nurse midwives and nurse practitioners.

Infant Brain "Tunes" Into Emotional Tone of Voices

New research finds that the brains of infants as young as 7 months old demonstrate a sensitivity to the human voice and to emotions communicated through the voice that is remarkably similar to what is observed in the brains of adults.

The study, published by Cell Press in the March 25 issue of the journal Neuron, probes the origins of voice processing in the human brain and may provide important insight into neurodevelopmental disorders such as autism.

Dr. Tobias Grossmann from the Centre for Brain and Cognitive Development at the University of London led the study which was performed in Dr. Angela D. Friederici's laboratory at the Max Planck Institute for Human Cognitive and Brain Sciences in Germany.

The researchers used near-infrared spectroscopy to investigate when during development regions in temporal cortex become specifically sensitive to the human voice. These specific cortical regions have been shown to play a key role in processing spoken language in adults.

Grossmann and colleagues observed that 7-month-olds but not 4-month-olds showed adult-like increased responses in the temporal cortex in response to the human voice when compared to nonvocal sounds, suggesting that voice sensitivity emerges between 4 and 7 months of age.

Another important question addressed in this study was whether activity in infants' voice-sensitive brain regions is modulated by emotional prosody. Prosody, essentially the "music" of speech, can reflect the feelings of the speaker, thereby helping to convey the context of language. In humans, sensitivity to emotional prosody is crucial for social communication.

The researchers observed that a voice-sensitive region in the right temporal cortex showed increased activity when 7-month-old infants listened to words spoken with emotional (angry or happy) prosody. Such a modulation of brain activity by emotional signals is thought to be a fundamental brain mechanism to prioritize the processing of significant stimuli in the environment.

"Our findings demonstrate that voice-sensitive brain regions are already specialized and modulated by emotional information by the age of 7 months and raise the possibility that the critical neurodevelopmental processes underlying impaired voice-processing reported in disorders like autism might occur before 7 months," explains Dr. Grossmann.

"Therefore, in future work the current approach could be used to assess individual differences in infants' responses to voices and emotional prosody and might thus serve as one of potentially multiple markers that can help with an early identification of infants at risk for a neurodevelopmental disorder."

Mouse Gene Explains Embryonic Stem Cell Immortality

This breakthrough finding could have major implications for aging research, stem cell biology, regenerative medicine and cancer biology.

Researchers at the National Institute on Aging (NIA), part of the National Institutes of Health, have discovered a key to embryonic stem (ES) cell rejuvenation in a gene - Zscan4 - as reported in the March 24, 2010, online issue of Nature.

ES cells are unique because, along with the ability to develop into nearly any type of cell in the body, they can produce infinite generations of new, fully operational ES cells (daughter cells). ES cells are essentially immortal, meaning that they can divide indefinitely to produce additional generations of functional ES daughter cells.

Other cells can only produce a certain number of generations of daughter cells before they no longer function properly. This is partially because the telomere, the protective end of the chromosome which carries the cell's genetic information, shortens each time a cell divides. When a telomere becomes too short, it can no longer protect the cell. At that time, the cell dies, turns itself off, known as cell senescence, or produces abnormal and possibly dysfunctional cells.

Until now, the mechanism for the ES cell's immortality had been a mystery. The prevailing theory was that ES cells practiced "self-renewal," meaning that when they divided, they produced daughter cells that were completely unaltered (including telomere length) from the parent.

NIA researchers discovered that the process occurring in ES cells can be more appropriately described as "rejuvenation" than the "self-renewal."

As in other cells, when ES cells replicate, the daughter cells are not identical to the parent and the telomeres are shorter. However, ES cells express a unique Zscan4 gene that, when activated (or turned on), rejuvenates the ES cell, restoring it to its original vigor.

This rejuvenation includes telomere lengthening through recombination, when a shorter telomere combines with a longer telomere to elongate itself. Zscan4 then turns off.

The gene is not turned on every time that the cell replicates - approximately 5 percent of the cells will have an activated gene at any one point. The process is a cycle of cell replication (with telomere shortening) and intermittent activation of Zscan4 (cell rejuvenation).

Researchers are currently investigating whether a similar mechanism also operates in human cells.

New Theory of Down Syndrome Cause

Scientists have shown in a series of experiments that there are lower levels of a specific protein in the brains of humans and mice with Down syndrome than are present in humans and mice without the disorder.

Conventional wisdom among scientists for years has suggested that because individuals with Down syndrome have an extra chromosome, the disorder most likely results from the presence of too many genes or proteins contained in that additional structure.

But a recent study reveals that just the opposite could be true – that a deficiency of a protein in the brain of Down syndrome patients could contribute to the cognitive impairment and congenital heart defects that characterize the syndrome.

Scientists have shown in a series of experiments that there are lower levels of this protein in the brains of humans and mice with Down syndrome than are present in humans and mice without the disorder.

The researchers also showed that manually manipulating pieces of RNA that regulate the protein could increase protein levels in both human cell lines and mouse brains. In fact, an experimental drug that acts on those RNA segments returned this protein to normal levels in mice that model the syndrome.

When this RNA segment is overexpressed – meaning that more of it is present than needed in a cell – the protein level goes down, or is underexpressed. A total of at least five of these RNA segments are naturally overexpressed in persons with Down syndrome because the segments are housed on chromosome 21 – the chromosome that causes the disorder.

“We’re talking about a paradigm-shifting idea that maybe we should look for underexpressed proteins and not overexpressed proteins in Down syndrome,” said Terry Elton, senior author of the study and a professor of pharmacology at Ohio State University. “What this offers to the Down syndrome community is the potential for at least five new therapeutic targets to pursue.”

The Centers for Disease Control and Prevention estimates that about 13 of every 10,000 babies born in the United States each year have Down syndrome, characterized primarily by a mild-to-moderate range of intellectual disabilities, possible delayed language development and difficulties with physical coordination.

The study is published in a recent issue of the Journal of Biological Chemistry.

Elton, also interim director of Ohio State’s Davis Heart and Lung Research Institute, stumbled upon this theory about Down syndrome while working on a different protein associated with cardiovascular disease. It turns out the protein he has studied for 25 years was regulated by one of these microRNAs that is known to be housed on chromosome 21.

A key role of RNA in a cell is to make protein, and proteins are the building blocks of all life. But the process has many steps. MicroRNAs are small pieces of RNA that bind to messenger RNA, which contains the actual set of instructions for building proteins. When that connection is made, however, the microRNA inhibits the building of the protein. Why that occurs is not completely understood, but increasingly microRNAs are considered tiny molecules that have a big impact in a number of physiological processes.

For his cardiovascular disease research, Elton found that a genetic trait in some people caused one specific microRNA to be bad at its job, leading to high protein levels that contribute to cardiovascular disease. This malfunctioning molecule is called microRNA-155, or miR-155.

“So we became interested in miR-155, and it is on chromosome 21. That’s how we jumped to Down syndrome,” Elton said.

There is also a strong link between the heart and Down syndrome. About half of those with the syndrome are born with congenital heart defects – problems with the heart’s anatomy, not coronary arteries. But they do not experience cardiovascular disease or high blood pressure.

The advent of biomedical informatics has allowed scientists to use supercomputers to explore the human genome in a search for genes and their various relationships in the context of human disease. Elton consulted a bioinformatic database and found that five microRNAs sit on chromosome 21, and he and colleagues demonstrated in previous research that all five of them are overexpressed in the tissues, brains and hearts of Down syndrome patients.

“That means that whatever proteins these microRNAs work with are underexpressed,” Elton said.

Further database exploration suggested that these five microRNAs target 1,695 proteins, all of which could cause problems in Down syndrome because they are underexpressed. To narrow that to a more manageable number, Elton’s group had to make an educated guess based on a variety of data, including which proteins that are connected to these microRNAs are made by cells in the brain and heart – two areas most commonly affected by Down syndrome.

A protein surfaced as an attractive target to study: methyl-CpG-binding protein 2, known as MeCP2. Among the reasons it seemed important: A mutation in this protein is already known to lead to Rett syndrome, a cognitive disorder.

“So we thought that it was more than a coincidence that this protein plays a role in normal brain development, and if the protein doesn’t function right, you’re going to have cognitive impairment. Maybe this is the connection,” Elton said. “We still don’t know if this is the most important protein related to Down syndrome. But we were able to go on and prove scientifically that MeCP2 is a target of these microRNAs on chromosome 21.”

The researchers used just two of the five microRNAs on chromosome 21 for the experiments in this study, miR-155 and miR-802, to match the only microRNAs available in the genetically engineered mouse model of Down syndrome.

First, the researchers made copies of the relevant microRNAs. In human brain cell lines, they manipulated levels of those two molecules to show the inverse relationship with the protein. If the microRNAs were more active, the level of the MeCP2 protein went down. When the microRNAs were underexpressed, the protein levels went up.

Next, the researchers examined adult and fetal human brain tissue from healthy and Down syndrome samples obtained from a national tissue bank.

“In both adult and fetal Down syndrome brain samples, it didn’t matter which area of the brain we were looking at, the MeCP2 proteins were down. These are just observations with no manipulation on our part, and the MeCP2 is almost non-existent in the Down syndrome brain,” Elton said. “We marked the protein with a fluorescent molecule, and by comparison, we could visualize and appreciate how much MeCP2 was being made by neurons in the control samples.”

MeCP2 is a transcription factor, meaning it turns genes on and off. If its levels are too low in the brain, this suggests that genes influenced by its presence should be malfunctioning, too. Based on previous research by another group, Elton and colleagues focused on two genes affected by the MeCP2 protein for their next set of experiments.

Looking again at the human brain tissue samples, they found that the genes were indeed affected by the lowered protein level in Down syndrome brains – one gene that MeCP2 normally silences was in abundance, and the gene that should have been activated was underexpressed. Because the two genes examined have known roles in neural development, Elton said the results suggested even more strongly that the lowered protein’s effects on the genes likely contribute to cognitive problems associated with Down syndrome.

Finally, the researchers tested an experimental drug called an antagomir on mice that serve as models for Down syndrome research. Antagomirs are relatively new agents that render microRNAs inactive. The scientists injected an antagomir into the brains of these mice to silence the miR-155 with the intent to increase levels of the MeCP2 protein. Seven days after the injection, the level of the protein in the treated mouse brains resembled levels in normal mouse brains.

“We showed that we can fix the protein abnormality in mice that model Down syndrome. But we can’t undo the pathology that has already occurred,” Elton said. “It’s a starting point, but it appears that we have new therapeutic targets to consider.”

This work was supported by grants from the National Institutes of Health and the Foundation Jerome Lejeune.

Film from June 24, 2008, depicting how science investigates Down Syndrome, the most common chromosomal abnormality. Fetal stem cell research demonstrates that it is not only the presence of the additional chromosome 21, but also what the genes are missing, that impedes the development of a Down Syndrome brain.

High-fructose Corn Syrup Prompts Obesity

A Princeton University research team has demonstrated that all sweeteners are not equal when it comes to weight gain: Rats with access to high-fructose corn syrup gained significantly more weight than those with access to table sugar, even when their overall caloric intake was the same.

In addition to causing significant weight gain in lab animals, long-term consumption of high-fructose corn syrup also led to abnormal increases in body fat, especially in the abdomen, and a rise in circulating blood fats called triglycerides. The researchers say the work sheds light on the factors contributing to obesity trends in the United States.

"Some people have claimed that high-fructose corn syrup is no different than other sweeteners when it comes to weight gain and obesity, but our results make it clear that this just isn't true, at least under the conditions of our tests," said psychology professor Bart Hoebel, who specializes in the neuroscience of appetite, weight and sugar addiction. "When rats are drinking high-fructose corn syrup at levels well below those in soda pop, they're becoming obese - every single one, across the board. Even when rats are fed a high-fat diet, you don't see this; they don't all gain extra weight."

A Princeton University research team has demonstrated that rats with access to high-fructose corn syrup - a sweetener found in many popular sodas - gain significantly more weight than those with access to water sweetened with table sugar, even when they consume the same number of calories. The work may have important implications for understanding obesity trends in the United States.

In results published online March 18 by the journal Pharmacology, Biochemistry and Behavior, the researchers from the Department of Psychology and the Princeton Neuroscience Institute reported on two experiments investigating the link between the consumption of high-fructose corn syrup and obesity.

The first study showed that male rats given water sweetened with high-fructose corn syrup in addition to a standard diet of rat chow gained much more weight than male rats that received water sweetened with table sugar, or sucrose, in conjunction with the standard diet. The concentration of sugar in the sucrose solution was the same as is found in some commercial soft drinks, while the high-fructose corn syrup solution was half as concentrated as most sodas.

The second experiment - the first long-term study of the effects of high-fructose corn syrup consumption on obesity in lab animals - monitored weight gain, body fat and triglyceride levels in rats with access to high-fructose corn syrup over a period of six months. Compared to animals eating only rat chow, rats on a diet rich in high-fructose corn syrup showed characteristic signs of a dangerous condition known in humans as the metabolic syndrome, including abnormal weight gain, significant increases in circulating triglycerides and augmented fat deposition, especially visceral fat around the belly. Male rats in particular ballooned in size: Animals with access to high-fructose corn syrup gained 48 percent more weight than those eating a normal diet. In humans, this would be equivalent to a 200-pound man gaining 96 pounds.

"These rats aren't just getting fat; they're demonstrating characteristics of obesity, including substantial increases in abdominal fat and circulating triglycerides," said Princeton graduate student Miriam Bocarsly. "In humans, these same characteristics are known risk factors for high blood pressure, coronary artery disease, cancer and diabetes." In addition to Hoebel and Bocarsly, the research team included Princeton undergraduate Elyse Powell and visiting research associate Nicole Avena, who was affiliated with Rockefeller University during the study and is now on the faculty at the University of Florida. The Princeton researchers note that they do not know yet why high-fructose corn syrup fed to rats in their study generated more triglycerides, and more body fat that resulted in obesity.

When male rats were given water sweetened with high-fructose corn syrup in addition to a standard diet of rat chow, the animals gained much more weight than male rats that received water sweetened with table sugar, or sucrose, along with the standard diet. The concentration of sugar in the sucrose solution was the same as is found in some commercial soft drinks, while the high-fructose corn syrup solution was half as concentrated as most sodas, including the orange soft drink shown here. (Photo: Denise Applewhite)

High-fructose corn syrup and sucrose are both compounds that contain the simple sugars fructose and glucose, but there at least two clear differences between them. First, sucrose is composed of equal amounts of the two simple sugars - it is 50 percent fructose and 50 percent glucose - but the typical high-fructose corn syrup used in this study features a slightly imbalanced ratio, containing 55 percent fructose and 42 percent glucose. Larger sugar molecules called higher saccharides make up the remaining 3 percent of the sweetener. Second, as a result of the manufacturing process for high-fructose corn syrup, the fructose molecules in the sweetener are free and unbound, ready for absorption and utilization. In contrast, every fructose molecule in sucrose that comes from cane sugar or beet sugar is bound to a corresponding glucose molecule and must go through an extra metabolic step before it can be utilized.

This creates a fascinating puzzle. The rats in the Princeton study became obese by drinking high-fructose corn syrup, but not by drinking sucrose. The critical differences in appetite, metabolism and gene expression that underlie this phenomenon are yet to be discovered, but may relate to the fact that excess fructose is being metabolized to produce fat, while glucose is largely being processed for energy or stored as a carbohydrate, called glycogen, in the liver and muscles.

In the 40 years since the introduction of high-fructose corn syrup as a cost-effective sweetener in the American diet, rates of obesity in the U.S. have skyrocketed, according to the Centers for Disease Control and Prevention. In 1970, around 15 percent of the U.S. population met the definition for obesity; today, roughly one-third of the American adults are considered obese, the CDC reported. High-fructose corn syrup is found in a wide range of foods and beverages, including fruit juice, soda, cereal, bread, yogurt, ketchup and mayonnaise. On average, Americans consume 60 pounds of the sweetener per person every year.

"Our findings lend support to the theory that the excessive consumption of high-fructose corn syrup found in many beverages may be an important factor in the obesity epidemic," Avena said.

The new research complements previous work led by Hoebel and Avena demonstrating that sucrose can be addictive, having effects on the brain similar to some drugs of abuse.

In the future, the team intends to explore how the animals respond to the consumption of high-fructose corn syrup in conjunction with a high-fat diet - the equivalent of a typical fast-food meal containing a hamburger, fries and soda - and whether excessive high-fructose corn syrup consumption contributes to the diseases associated with obesity. Another step will be to study how fructose affects brain function in the control of appetite.

The research was supported by the U.S. Public Health Service.

Link Between Sunlight and Multiple Sclerosis Explored

For more than 30 years, scientists have known that multiple sclerosis (MS) is much more common in higher latitudes than in the tropics. Because sunlight is more abundant near the equator, many researchers have wondered if the high levels of vitamin D engendered by sunlight could explain this unusual pattern of prevalence.

Vitamin D may reduce the symptoms of MS, says Hector DeLuca, Steenbock Research Professor of Biochemistry at University of Wisconsin-Madison, but in a study published in PNAS this week, he and first author Bryan Becklund suggest that the ultraviolet portion of sunlight may play a bigger role than vitamin D in controlling MS.

Multiple sclerosis is a painful neurological disease caused by a deterioration in the nerve's electrical conduction; an estimated 400,000 people have the disabling condition in the United States. In recent years, it's become clear the patients' immune systems are destroying the electrical insulation on the nerve fibers.

The ultraviolet (UV) portion of sunlight stimulates the body to produce vitamin D, and both vitamin D and UV can regulate the immune system and perhaps slow MS. But does the immune regulation result directly from the UV, indirectly from the creation of vitamin D, or both?

The study was designed to distinguish the role of vitamin D and UV light in explaining the high rate of MS away from the equator, says DeLuca, a world authority on vitamin D.

"Since the 1970s, a lot of people have believed that sunlight worked through vitamin D to reduce MS," says DeLuca. "It's true that large doses of the active form of vitamin D can block the disease in the animal model. That causes an unacceptably high level of calcium in the blood, but we know that people at the equator don't have this high blood calcium, even though they have a low incidence of MS. So it seems that something other than vitamin D could explain this geographic relationship."

Using mice that are genetically susceptible to MS-like disease, the researchers triggered the disease by injecting a protein from nerve fibers. The researchers then exposed the mice to moderate levels of UV radiation for a week. After they initiated disease by injecting the protein, they irradiated the mice every second or third day.

The UV exposure (equivalent to two hours of direct summer sun) did not change how many mice got the MS-like disease, but it did reduce the symptoms of MS, especially in the animals that were treated with UV every other day, DeLuca says.

The research group also found that although the UV exposure did increase the level of vitamin D, that effect, by itself, could not explain the reduced MS symptoms.

In some situations, radiation does reduce immune reactions, but it's not clear what role that might play in the current study. "We are looking to identify what compounds are produced in the skin that might play a role, but we honestly don't know what is going on," DeLuca says. "Somehow it makes the animal either tolerate what's going on, or have some reactive mechanism that blocks the autoimmune damage."

MS is a progressive neurological disease with few effective treatments, but DeLuca stresses that the study, however hopeful, may or may not lead to a new mode of treatment. "There are several ways this could go. If we can find out what the UV is producing, maybe we could give that as a medicine. In the short term, if we can define a specific wavelength of light that is active, and it does not overlap with the wavelengths that cause cancer, we could expose patients who have been diagnosed with MS to that wavelength."

Does this information change the common prescription to avoid excessive sun exposure? "If you have an early bout with MS, then you have to think about your options," says DeLuca. "Remember, this is just experimental work at this stage. Whether it can be translated into practical applications on MS remains to be seen."

Perils of Plastics: Risks to Health and Environment

Although modern life would be hard to imagine without this versatile chemistry, products composed of plastics also have a dark side, due in part to the very characteristics that make them so desirable - their durability and longevity.

Plastics surround us. A vital manufacturing ingredient for nearly every existing industry, these materials appear in a high percentage of the products we use every day.

Now Rolf Halden, associate professor in the School of Sustainable Engineering at Arizona State University and assistant director of Environmental Biotechnology at the Biodesign Institute has undertaken a survey of existing scientific literature concerning the hazards of plastics to human health and to the ecosystems we depend on. His findings, which appear in the latest issue of the Annual Review of Public Health, are sobering.

Today, plastics accumulate in garbage dumps and landfills and are sullying the world's oceans in ever-greater quantity. And plastics and their additives aren't just around us, they are inside virtually every one of us - present in our blood and urine in measureable amounts, ingested with the food we eat, the water we drink and from other sources.

Halden's study reiterates the fact that the effects to the environment from plastic waste are acute. Measurements from the most contaminated regions of the world's oceans show that the mass of plastics exceeds that of plankton sixfold. Patches of oceanic garbage - some as large as the state of Texas - hold a high volume of non-biodegradable plastics. Aquatic birds and fish are increasingly victims because biodegradation processes are inadequate to eliminate this durable refuse.

The magnitude of society's burden of plastic waste is only beginning to be fully appreciated. In the U.S., the average person produces a half-pound of plastic waste every day. Around the world, some 300 million tons of the material are produced each year - a figure poised to expand, as new forms of plastics are devised to serve a voracious global appetite. As Halden points out, this annual production alone would fill a series of train cars encircling the globe. "We're doomed to live with yesterday's plastic pollution and we are exacerbating the situation with each day of unchanged behavior," he said.

Adverse effects to human health remain a topic of fierce controversy, though a growing consensus is emerging that plastics and their additives are not always the benign companions we once assumed them to be. Halden says he accepted the invitation to write about plastics and human health "because the topic showcases the bigger problem of how to create a sustainable future for modern civilization."

Two broad classes of plastic-related chemicals are of critical concern for human health - bisphenol-A or BPA, and additives used in the synthesis of plastics, which are known as phthalates. Halden explains that plastics are polymers - long chains of molecules usually made of carbon, hydrogen, oxygen and/or silicon, which are chemically linked together or polymerized. Different polymer chains can be used to create forms of plastics with unique and useful properties.

BPA is a basic building block of polycarbonate plastics, such as those used for bottled water, food packaging and other items. While it has been considered benign in the form of a heavily cross-linked polymer, its bonds can break down over time, when plastics are repeatedly washed, exposed to heat or other stresses, liberating the building blocks of the chemical, which are toxic. BPA has been recognized since the 1940s as an endocrine disrupting chemical that interferes with normal hormonal function.

Adding to the health risks associated with BPA is the fact that other ingredients - such as plasticizers - are commonly added to plastics. Many of these potentially toxic components also can leach out over time. Among the most common is a chemical known as di-ethylhexyl phthalate or DEHP. In some products, notably medical devices including IV bags or tubing, additives like DEHP can make up 40 or 50 percent of the product. "If you're in a hospital, hooked up to an IV drip," Halden explains, "the chemical that oozes out goes directly into your bloodstream, with no opportunity for detoxification in the gut. This can lead to unhealthy exposure levels, particularly in susceptible populations such as newborns."

What are the overall effects of the plastics we unwittingly ingest? The literature Halden surveyed is ambiguous on this point, despite more than half a century of study. Part of the difficulty lies in the absence of good controls for studying health outcomes, as plastic exposure is a global phenomenon, and finding unexposed subjects for comparison is nearly impossible. It is known however that health effects vary depending on who is exposed - and when. Infants and pregnant or nursing mothers are at heightened risk for toxic exposure or passage of BPA and additives like DEHP.

This January, the FDA announced an important reversal of its 2008 claims regarding the safety of bisphenol-A, expressing new concern about "potential effects of BPA on the brain, behavior and prostate gland of fetuses, infants and children," and pledging to collaborate with other federal health agencies to reevaluate the chemical's safety.

Studying the effects of low-dose exposure is tricky, usually requiring a very large number of study subjects. Instead, epidemiologists tracking the problem frequently base their conclusions on data gathered from individuals known to have unusually high levels of a chemical—often the result of high-level occupational exposure. Halden insists that further study on low-dose exposure is essential to settle the matter of health risks, noting some evidence in the literature suggests that high-dose studies may be inadequate to properly understand toxic effects from continuous low-level exposures.

Halden explains that while plastics have legitimate uses of benefit to society, their brazen misuse has led to a radically unsustainable condition. "Today, there's a complete mismatch between the useful lifespan of the products we consume and their persistence in the environment." Prominent examples of offending products are the ubiquitous throwaway water bottles, Teflon-coated dental floss and cotton swabs made with plastic PVC sticks. All are typically used for a matter of seconds or minutes, yet are essentially non-biodegradable and will persist in the environment, sometimes for millennia.

Despite the scourge of discarded plastics and the health risks these substances pose, Halden is optimistic that society can begin to make wiser choices and develop more sustainable products, formed from biodegradable, non-toxic chemical building blocks.

New forms of polymer, some made from renewable materials that are digestible by microorganisms, are being explored.

Ultimately, converting to petroleum-free construction materials for use in smart and sustainable plastics will become a necessity, driven not only by health and environmental concerns but by the world's steadily declining oil supply. As Halden emphasizes, the manufacture of plastics currently accounts for about 8 percent of the world's petroleum use, a sizeable chunk, which ultimately contributes to another global concern - the accumulation of carbon dioxide in the atmosphere.

"We are at a critical juncture," Halden warns, "and cannot continue under the modus that has been established. If we're smart, we'll look for replacement materials, so that we don't have this mismatch—good for a minute and contaminating for 10,000 years."

Women Do Make Men Throw Caution To The Wind

Testosterone levels and risk-taking rise in young men performing for girls.

The presence of an attractive woman elevates testosterone levels and physical risk taking in young men, according to a recent study in the inaugural issue of Social Psychological and Personality Science (published by SAGE).

Researchers asked young adult men to perform both easy and difficult tricks on skateboards, first in front of another male and then in front of a young, attractive female. The skateboarder's testosterone levels were measured after each trick.

When skateboarders attempt tricks, they make a split-second decision about whether to abort the trick or try to land it, based on a mid-air evaluation of the likelihood of success and on the physical costs that failure might bring. It was that moment the researchers sought to examine because it resembles the type of risky decisions that young men make when behind the steering wheel of a car or when in physical confrontations with each other.

Consistent with predictions, the young men took greater risks in the presence of the attractive female even when they knew there was a greater chance that they would crash. Testosterone levels were significantly higher in these men than in the men who were in the presence of another male.

"This experiment provides evidence for an effect that has existed in art, mythology, and literature for thousands of years: Beautiful women lead men to throw caution to the wind," write authors Richard Ronay and William von Hippel. "These findings suggest that, for men, the adaptive benefits gained by enticing mates and intimidating rivals may have resulted in evolved hormonal and neurological mechanisms that facilitated greater risk taking in the presence of attractive women."

Pesticide Linked to Childhood Developmental Delays

Exposure to the pesticide chlorpyrifos - which is banned for use in U.S. households but is still widely used throughout the agricultural industry - is associated with early childhood developmental delays, according to a study by researchers at Columbia University's Mailman School of Public Health.

The study examined the association between exposure to the pesticide and mental and physical impairments in children in low-income areas of New York City neighborhoods in the South Bronx and Northern Manhattan. Chlorpyrifos was commonly used in these neighborhoods until it was banned for household use by the U.S. Environmental Protection Agency (EPA) in 2001. It is still used as an agricultural pesticide on fruits and vegetables. The EPA registration of chlorpyrifos for agricultural use is currently under review, with a public comment period scheduled for the coming months.

"This study helps to fill in the gaps about what is known about the effect of the pesticide chlorpyrifos on the development of young children by showing that there is a clear-cut association between this chemical and delayed mental and motor skill development in children even when there are other potentially harmful environmental factors present," said Gina Lovasi, PhD, lead author and Mailman School of Public Health assistant professor of epidemiology. Dr. Lovasi conducted the research as a Robert Wood Johnson Foundation Health & Society Scholar at the Mailman School.

As in previous research in the same study population, published in Pediatrics in 2006, this study controlled for gender, gestational age at birth, ethnicity, maternal education, maternal intelligence quotient, and exposure to secondhand smoke during pregnancy. What this study adds is that building dilapidation and community-level factors such as percentage of residents living in poverty do not explain the association. After controlling for these factors, the research indicates that high chlorpyrifos exposure (greater than 6.17 pg/g in umbilical cord blood at the time of birth) was associated with a 6.5-point decrease in the Psychomotor Development Index score and a 3.3-point decrease in the Mental Development Index score in 3-year-olds. "These associations remained statistically significant and similar in magnitude after accounting for dilapidated housing and neighborhood characteristics," noted Dr. Lovasi.

Of the 266 children included as study participants, 47 percent were male, 59 percent were Hispanic of Dominican descent and 41 percent were Black. In addition, children living in neighborhoods with the highest levels of poverty also had lower test scores—a finding that was not affected by pesticide exposure.

Young children have greater exposure to pesticides than adults, since they tend to play on the floor or in the grass—areas where pesticides are commonly applied—and to place their hands and objects in their mouths. Pregnant women exposed to pesticides can also expose their unborn children to the chemicals.

Those who advocate for further restrictions on the use of pesticides, including chlorpyrifos, contend that such chemicals drift from treated agricultural fields to nearby yards, homes and schools, placing pregnant women and children at risk.

"Although this pesticide has been banned for residential use in the United States, chlorpyrifos and other organophosphorus insecticides are still commonly used for a variety of agricultural purposes," said study co-author Virginia Rauh, ScD, professor of clinical population and family health, and co-deputy director for the Columbia Center for Children's Environmental Health at the Mailman School of Public Health. "We hope that the results of this study, further demonstrating the neurotoxicity of chlorpyrifos under a range of community conditions, may inform public health professionals and policy-makers about the potential hazards of exposure to this chemical for pregnant women and young children."

Findings of the study, "Chlorpyrifos Exposure and Urban Residential Environment Characteristics as Determinants of Early Childhood Neurodevelopment," are online in the American Journal of Public Health.