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Week Ending FRIDAY January 21, 2011---------News Archive

Even Robots Must Be Babies First

Want to build a really tough robot? Forget about Terminator. Instead, imitate a tadpole turning into a frog.

University of Vermont robotics expert Josh Bongard built this simple robot from Legos to recreate the complex relationship between brain and body.

That’s what University of Vermont roboticist Josh Bongard has discovered, as he reports in the January 10 online edition of the Proceedings of the National Academy of Sciences.

In a first-of-its-kind experiment, Bongard both simulated and created actual robots that, just as tadpoles become frogs, change their body forms while learning how to walk. And, over generations, his simulated robots also evolved, spending less time in “infant” tadpole-like forms and more time in “adult” four-legged forms.

These evolving robots were able to learn to walk more rapidly than ones with fixed body forms. In their final form, the changing robots had developed a more robust gait and were better able to deal with being knocked with a stick than robots that had learned to walk using upright legs from the beginning.

“This paper shows that body change, morphological change, actually helps us design better robots,” Bongard says. “That’s never been attempted before.”

Bongard’s research, supported by the National Science Foundation, is part of a wider venture called evolutionary robotics. “We have an engineering goal,” he says “to produce robots as quickly and consistently as possible.” In this experimental case: upright four-legged robots that can move themselves to a light source without falling over.

So far, engineers have been largely unsuccessful at creating robots that can continually perform simple, yet adaptable, behaviors in unstructured or outdoor environments. Which is why Bongard, an assistant professor in UVM’s College of Engineering and Mathematical Sciences, and other robotics experts have turned to computer programs to design robots and develop their behaviors.

Using a sophisticated computer simulation, Bongard unleashed a series of synthetic beasts that move about in a 3-dimensional space. “Each creature - or, rather, generations of the creatures - run a software routine, called a genetic algorithm, that experiments with various motions until it develops a slither, shuffle, or walking gait - based on its body plan - that can get it to the light source without tipping over."

Some of the creatures begin flat to the ground, like tadpoles or, perhaps, snakes with legs; others have splayed legs, a bit like a lizard; and others ran the full set of simulations with upright legs, like mammals.

And why do the generations of robots that progress from slithering to wide legs and, finally, to upright legs, ultimately perform better, getting to the desired behavior faster?

“The snake and reptilian robots are, in essence, training wheels,” says Bongard, “they allow evolution to find motion patterns quicker, because those kinds of robots can’t fall over. So evolution only has to solve the movement problem, but not the balance problem, initially. Then gradually over time it’s able to tackle the balance problem after already solving the movement problem.”

Sound anything like how a human infant first learns to roll, then crawl, then cruise along the coffee table and, finally, walk?

“Yes,” says Bongard, “We’re copying nature, we’re copying evolution, we’re copying neural science when we’re building artificial brains into these robots.” But the key point is that his robots don’t only evolve their artificial brain - the neural network controller - but rather do so in continuous interaction with a changing body plan. A tadpole can’t kick its legs, because it doesn’t have any yet; it’s learning some things legless and others with legs.

And this may help to explain the most surprising - and useful - finding in Bongard’s study: the changing robots were not only faster in getting to the final goal, but afterward were more able to deal with new kinds of challenges that they hadn’t before faced, like efforts to tip them over.

Bongard thinks this is because controllers that evolved in the robots whose bodies changed over generations learned to maintain the desired behavior over a wider range of sensor-motor arrangements than controllers evolved in robots with fixed body plans. It seems that learning to walk first flat, then squat, and finally upright, gave the evolving robots resilience to stay upright when faced with new disruptions. Perhaps what a tadpole learns before it has legs makes it better able to use its legs once they grow.

Bongard writes in his PNAS paper “This is an inheritance from traditional artificial intelligence in which computer programs were developed that had no body with which to affect, and be affected by, the world. One thing that had been left out is the obvious fact that in nature it’s not that the animal’s body stays fixed and its brain gets better over time,” he says, “in natural evolution animals bodies and brains are evolving together all the time.”

A human infant, even if she knew how, couldn’t walk: her bones and joints aren’t up to the task until she starts to experience stress on the foot and ankle.

That hasn’t been done in robotics before because “it’s very hard to change a robot’s body,” Bongard says, “it’s much easier to change the programming inside its head.”

Still, Bongard gave it a try. After running 5000 simulations on the parallel processors in UVM’s Vermont Advanced Computing Center -- “it would have taken 50 or 100 years on a single machine,” Bongard says—he took the task into the real world.

“We built a relatively simple robot, out of a couple of Lego Mindstorm kits, to demonstrate that you actually could do it,” he says. This physical robot is four-legged, like in the simulation, but the Lego creature wears a brace on its front and back legs. “The brace gradually tilts the robot, so that the legs go from horizontal to vertical, from reptile to quadruped.

“While the brace is bending the legs, the controller is causing the robot to move around, so it’s able to move its legs, and bend its spine,” Bonard says, “it’s squirming around like a reptile flat on the ground and then it gradually stands up until, at the end of this movement pattern, it’s walking like a coyote.”

“It’s a very simple prototype,” he says, “but it works; it’s a proof of concept.”

The Shape of The Epigenome

The new science of epigenetics is a field investigating how genes are altered without changing the DNA structure itself. Epigenetic scientists decipher the many ways enzymes act on the proteins surrounding DNA.

One group of proteins known as HATs (short for histone acetyltransferases) affect DNA by circling DNA-bound proteins called histones. This act is called acetlyation, and can modify DNA replication, transcription (reading the gene), and repair.

In the February 9 issue of the journal Structure, researchers at The Wistar Institute describe the atomic structure formed by a yeast HAT (known as Rtt109) and demonstrate how histone acetylation works, a crucial step in understanding epigenetic processes that underlie health and disease.

An acetylation complex fits like a halo around a histone.

According to the study's senior author, Ronen Marmorstein, Ph.D., two copies of Rtt109 bind to two copies of a "chaperone" protein to form a ring.

"The ring fits atop a histone much like a halo, and we find that the type of chaperone [protein] dictates exactly how the enzyme affects the histone by determining the exact position of acetylation," said Marmorstein. "The structure represents a nice model system for the regulation of protein acetylation, and teaches us something new about the biology of this enzyme, Rtt109."

Two Rtt109 enzymes (Purple and Gold) join with two Vsp75 "chaperones" (Blue and Green) to form a ring that fits precisely atop its target.
Acetylation adds an "acetyl group," a small chemical structure, to a lysine - one of the amino acids making up a particular protein. Altering one lysine can change the shape of a protein in a subtle way, redirecting how it functions.

The study is the first to physically show that chaperones form a ring. The laboratory created crystals of a protein complex and with a technique called X-ray crystallography, "saw" the structure of the complex by analyzing the patterns formed when X-rays bounce off the crystals.

Using the powerful X-ray at the Argonne National Laboratory's Advanced Photon Source, X-ray crystallography enabled the team to determine the structure of the protein complex at the atomic scale - at a resolution of 2.8 angstroms (2.8 billionths of a meter), which is smaller than the distance between individual rungs on the DNA ladder.

Since the Marmorstein laboratory began its work on HATs over a decade ago, several large-scale studies have shown that acetylation occurs to over 2000 proteins, not just on histones. According to Marmorstein, it appears there is an entire web of communication going on within cells directly attributable to protein acetylation, another level of complexity in an already-complex field.

"We have seen many different proteins over several different pathways become affected by acetylation, which can alter the processes of RNA metabolism, cell cycle control, cancer, and a number of different aspects of life. It looks like protein acetylation has much broader biological implications than initially appreciated," said Marmorstein.

"In many ways, it seems a lot like what we have seen in recent years with protein kinases and cell signaling," said Marmorstein. "What we're learning is that these HATs, and possibly other protein acetyltransferases, are regulated in much the same way. They have these profound effects within cells, but it is still very new to science. How it works is a big black box that we intend to decipher."

This work from the Marmorstein laboratory was supported by a grant from the National Institute of General Medical Sciences. The study's senior author is Ronen Marmorstein, Ph.D., professor and program leader of Wistar's Gene Expression and Regulation Program

The lead author of the study is Yong Tang, Ph.D., a staff scientist in the Marmorstein laboratory. Wistar co-authors also include Katrina Meeth, a research associate and Hua Yuan, Ph.D., a postdoctoral fellow in the Marmorstein laboratory. Collaborators include Philip A. Cole, Ph.D., and his laboratory at the Johns Hopkins University School of Medicine, including Marc A. Holbert, Ph.D.; and the laboratories of Alain Verreault, Ph.D., and Pierre Thibault, Ph.D., at the Institute for Research in Immunology and Cancer at the Université de Montréal; and their colleagues, including research associates, Neda Delgoshaie, Paul Drogaris, Chantal Durette, and Eun-Hye Lee, and postdoctoral fellows Hugo Wurtele, Ph.D., and Benoit Guillemette, Ph.D.

THURSDAY January 20, 2011---------News Archive

Watching Genome Turn DNA Into RNA Inside Cell

By combining biochemical techniques with new, fast DNA-sequencing technology and advanced computer technology, a University of California San Francisco (UCSF) team was able to examine with unprecedented resolution how a cell converts DNA into RNA – a molecular cousin of DNA that is used in the process of creating proteins that govern most biological functions. And they did so within the cell itself, rather than in a test tube.

UCSF researchers have developed a new approach to decoding the vast information embedded in an organism’s genome, while shedding light on exactly how cells interpret their genetic material to create RNA messages and launch new processes in the cell.

As a result, they were able to bridge an important gap in the understanding of what causes genes to be turned on and off. Their findings will appear in the Jan. 20 issue of the journal Nature online.

The main way the genome is “read” in a cell is through its transcription into RNA, the researchers explained. Until now, scientists have been able to detect which RNAs were produced, but have had a limited view of how much of the genome was being decoded, or “transcribed,” or what controls how fast these RNAs are made. The new technique enables them to watch this process directly.

“This lets you capture the cell in the process of turning the DNA into RNA at unprecedented resolution,” said Jonathan S. Weissman, PhD, a professor in the UCSF Department of Cellular and Molecular Pharmacology and senior author on the paper. “Before, we were typically studying the end product. Now, we can directly watch how these RNA messages are produced in vivo.”

The advance enables researchers to make sense of the vast amounts of data generated by the Human Genome Project and the multiple genome sequencing efforts worldwide, while providing new tools for studying basic processes like the reprogramming of stem cells, Weissman said.

“The genome is the hard drive of the cell,” explained L. Stirling Churchman, PhD, who was the first author of the two-author paper and last year was honored for this work with the Dale F. Frey for Breakthrough Scientists award of the Damon Runyon Cancer Research Foundation. “Until now, we’ve been able to see the information that the hard drive contains as well as see the result after the cell has read that information, but we didn’t know which precise data it was accessing.

“Here, we’ve been able to see which data it is accessing, with a high enough resolution to also be able to see how it’s actually working,” she said.

Until quite recently, many scientists thought that less than 5 percent of the human genome was actually transcribed into RNA and therefore used in the cell’s function, Churchman said. Recent advances in the field have revealed a tremendous complexity in that process, with new understanding that the majority of DNA is transcribed. Much of the product is still considered “junk RNA” – simply a byproduct of the process.

“Now, the question is not, ‘Why is that DNA there?’ but, ‘Why is that RNA there?’” said Churchman, a physicist and post-doctoral scholar at UCSF. “It could be junk RNA, but we don’t know.”

The research focused on DNA transcription in baker’s yeast, largely because that organism’s genome has been extensively studied. As a result, previous scientists had already developed maps of the genome and identified the positions of nucleosomes along it. Nucleosomes are grape-like structures formed by strands of DNA wrapped like vines around histone proteins, and serve to organize enormously long DNA molecules.

Histone proteins are known to have many marks that dictate whether a gene should be turned on or off, among other functions, while retaining a history of what has happened recently in that part of the gene code and a “plan” for what should happen in the future.

By overlaying those maps with their own maps of RNA production, the scientists were able to observe for the first time that polymerase comes in direct contact with the histone proteins during the transcription process, while also seeing how the nucleosomes acted as a speed bump for the polymerase enzyme as it moved along the genome transcribing DNA into RNA. In addition, the research showed that the organization of histone marks controlled whether “junk RNA” was produced from a given region of DNA.

This new approach gives researchers a precise view of the process in action, as well as insights on general trends in how histone proteins and their marks affect transcription.

“There is a long history of trying to look at how genes are turned on,” Weissman said. “So far, nothing has been analogous at this resolution and depth.”

The research was supported by the Damon Runyon Cancer Research Foundation and by the Howard Hughes Medical Institute. The authors declare no conflicts of interest.

Churchman and Weissman were the sole co-authors on the paper. Both are affiliated with the UCSF Department of Cellular and Molecular Pharmacology and the California Institute for Quantitative Biosciences, at UCSF. Weissman is also an investigator with the Howard Hughes Medical Institute.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

The Secret(ase) for Building Neural Circuits

By isolating genes associated with Alzheimer's disease, researchers at Salk Institute have revealed an important link between the formation of normal neural circuits and neurodegenerative failure.

The mutant presenilin gene is infamous for its role in the most aggressive form of Alzheimer's disease - early onset familial Alzheimer's - which can strike people as early as their 30s. However, researchers at the Salk Institute have uncovered a productive side to presenilin: It helps embryonic motor neurons navigate through a maze of chemical cues that pull, push and control how they grow to specific targets. Without presenilin, budding motor neurons misread guiding chemical signals and get stuck in the spinal cord.

"It was a bit of a surprise since we always thought about presenilin in the context of severing neuronal connections rather than wiring the nervous system during embryonic development," says Howard Hughes Medical Institute investigator Samuel Pfaff, Ph.D., a professor in the Gene Expression Laboratory, who led the study.

Presenilin, better known for its role in Alzheimer's disease, aids with the correct wiring of the embryonic nervous system.
Image: Dr. Samuel Pfaff, Salk Institute for Biological Studies
Presenilin is also a component of the enzyme gamma secretase, which cuts up the amyloid precursor protein. It functionally creates beta amyloid fragments. In Alzheimer's, these fragments form hard, insoluble plaques, one of the hallmarks of the disease.

Even so, many embryonic guiding molecules persist in the adult central nervous system, where they help maintain, repair and keep plastic neural circuits.

"This could explain how a deregulation of guidance signaling by abnormal presenilin may play a role in the pathogenesis of Alzheimer's disease," proposes Pfaff.

The Salk study adds an important new piece to the mechanism that guides growing nerve cells through the embryo - a clockwork precise task that depends as much on timing as on spatial accuracy. Understanding and being able to control how axons find their destinations may eventually be helpful to restoring movement in people following spinal cord injury, or in those with motor neuron diseases such as Lou Gehrig's, spinal muscle atrophy and post-polio syndrome.

During normal development, trillions of neurons reach to other neurons with long, slender extensions to connect and wire the budding nervous system. As the hair-like protrusions, called axons, grope around in the developing embryo trying to find their proper targets, molecular "ushers" stationed along their path steer them in the right direction.

"Because of the vast number of neurons in the nervous system, ensuring that every single cell is on target creates more biological complexity than we can account for with the genetic information encoded in our genome," says Pfaff. "There are an estimated 100 trillion connections in our brain and only about 20,000 genes."

To find their course, growing neurons navigate their path one small segment at a time - especially motor neurons which need to travel very long distances to reach their targets. They are guided at each intersection by chemical cues that attract or repel approaching axons. It is a tightly regulated choreography where axons often switch allegiances at critical junctions.

"It [presenilin] provides a way of creating some of these intermediate temporal steps," explains postdoctoral researcher and first author Ge Bai. "It allows the use of a small number of genes to regulate axonal growth by regulating the signals' effects in a very precise temporal and spatial ways."

He and his team found presenilin's unexpected role in guiding axon signals while searching for genes involved in the development of the fetal nervous system. The team had engineered mice so that all of their motor neurons glow green. This fluorescence allowed the researchers to visually identify mutant mice with errors in motor neuron development.

One mouse with a specific defect mapped to the gene coding for presenilin, stood out. The motor neurons of this mouse failed to exit the spinal cord, getting stuck in a row of cells lying in the middle of the developing embryo. Bai discovered that in the presenilin mutant mice, motor neurons were irresistibly attracted to the protein Netrin, also found in the midline of the embryonic mouse.

In normal mice, motor neurons are able to ignore Netrin as they are blocked by Slit - which is a midline repellant molecule - and the Roundabout (Robo) receptor that avoids the midline of the embryo. Together, they prevent longitudinal axons from crossing the midline of the brain and spinal cord. In presenilin mutant mice, Netrin receptor fragments are resistant to Slit/Robo silencing and accumulate in the midline, failing to reach normal targets.

"The most satisfying thing we have learned about presenilin is that this is a component that is not directly involved in the detection of signals either as a ligand or a receptor but functions as a very important regulator of their spatiotemporal activity," says Bai.

Results are published in the Jan. 7, 2011, issue of the journal Cell.

Researchers who also contributed to the work include Onanong Chivatakarn, Dario Bonanomi, Karen Lettieri, and Laura Franco at the Salk Institute; Caihong Xia and Le Ma at the Zilkha Neurogenetic Institute at the University of of Southern California in Los Angeles; Elke Stein in the Department of Molecular, Cellular and Developmental Biology at Yale University, New Haven, CT; and Joseph W. Lewcock, formerly a postdoc in the Pfaff lab and now in the Department of Neurobiology at Genentech, San Francisco.

The work was funded in part by the Howard Hughes Medical Institute and the National Institutes of Health.

WEDNESDAY January 19, 2011---------News Archive

Mom's Stem Cells Help Treat Fetal Genetic Disease

Through a series of mouse model experiments, a University of California (UCSF) research team determined that a mother's immune response prevents a fetus from accepting transplanted blood stem cells, and yet this response can be overcome simply by transplanting cells harvested from the mother herself.

UCSF researchers have tackled a decade-long scientific conundrum, and their discovery is expected to lead to significant advances in using stem cells to treat genetic diseases before birth.

"This research is really exciting because it offers us a straightforward, elegant solution that makes fetal stem cell transplantation a reachable goal," said senior author Tippi MacKenzie, MD, an assistant professor of pediatric surgery at UCSF and fetal surgeon at UCSF Benioff Children's Hospital. "We now, for the first time, have a viable strategy for treating congenital stem cell disorders before birth."

Scientists have long viewed in-utero blood stem cell transplantation as a promising treatment strategy for many genetic diseases diagnosed as early as the first trimester of pregnancy, including sickle cell disease and certain immune disorders.

Fetal stem cell transplantation involves taking healthy cells from the bone marrow of a donor and transplanting them into the fetus through ultrasound-guided injections. When successful, the implanted cells, or graft, replenish the patient's supply of healthy blood-forming cells.

In theory, the developing fetus with an immature immune system should be a prime target for successful transplantation, since the risk of graft rejection is low and the need for long-term immunosuppressive therapy may be avoided. However, most previous attempts to transplant blood stem cells into a human fetus have been unsuccessful, prompting some researchers to lose interest in this promising field, according to MacKenzie, who also is an investigator with the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research.

Findings from the study will appear online January 18, 2011, in the Journal of Clinical Investigation, available at www.jci.org. They also will be published in the journal's February 2011 issue.

"The fact that fetal stem cell transplantation has not been very successful has been puzzling, especially given the widely accepted dogma that the immature fetal immune system can adapt to tolerate foreign substances," said co-senior author Qizhi Tang, PhD, an assistant professor of transplant surgery and director of the UCSF Transplantation Research Lab. "The surprising finding in our study is that the mother's immune system is to blame."

In the study's first phase, researchers examined the cellular content of fetal mouse blood and found a large proportion of maternal blood cells in the fetus. Their analyses indicated that up to 10 percent of the fetus' blood cells came from the mother – a significantly larger percentage of maternal cells than what is found anywhere else in the fetus.

"We had previously known that a minute amount of cells travel from the mother into a developing fetus and that this is an important tolerance mechanism in all healthy pregnancies," MacKenzie said. "However, the unexpectedly large proportion of maternal blood cells in the fetus made us think that perhaps it was the maternal, rather than the fetal, immune response that poses the real barrier to effective stem cell transplantation."

To further investigate this theory, the team transplanted fetal mice with blood stem cells from a second strain of mice that were not matched to the fetus or the mother. Following transplantation, the researchers observed an influx of T cells – the major driving force behind an immune response – from the mother into the fetus, which subsequently led to rejection of the transplanted graft.

However, if the researchers removed T cells only from the mother before carrying out the transplant, nearly 100 percent of the injected fetuses engrafted, or accepted the transplanted cells, indicating that maternal T cells play the critical role in triggering transplant rejection.

Finally, the researchers transplanted fetal mice with blood stem cells matched to the mother, which, as expected, resulted in a very high success rate.

"As long as the transplanted stem cells are matched to the mother, it does not seem to matter if they are matched to the fetus," said first author Amar Nijagal, MD, a postdoctoral research fellow and surgery resident at UCSF. "Transplanting stem cells harvested from the mother makes sense because the mother and her developing fetus are prewired to tolerate each other."

In the next phase of study, researchers will need to confirm that the findings are consistent in humans and also will investigate how exactly maternal T cells cause a graft rejection.

"Now that we know a fetus can become tolerant to a foreign stem cell source, we can really think big and consider looking at how other types of stem cells might be used to treat everything from neurological disorders to muscular disorders before birth," MacKenzie added.

Additional authors include Marta Wegorzewska, Erin Jarvis, and Tom Le, all with the Eli and Edythe Broad Center of Regeneration Medicine and the UCSF Department of Surgery.

The study was funded through support from the Irene Perstein Award, UCSF Sandler Funds, the American Pediatric Surgical Association, the National Institutes of Health, the California Institute for Regenerative Medicine, the National Science Foundation, and the Joslin Diabetes and Endocrinology Research Center.

Taking Right Food Supplements While Pregnant?

Study shows risky knowledge gaps exist for pregnant women about when and how many supplements to take.

Nutrients, vitamins, minerals – during pregnancy a woman's body needs more of all of them.

For most nutrients this increase in demand can be covered with a balanced diet. However, mothers-to-be should take some nutrients in the form of pills or tablets. And research conducted by Nutritional Medicine at the Technische Universitaet Muenchen (TUM) indicates there are knowledge gaps about what needs to be done. According to this study, pregnant women often start taking sensible dietary supplements too late or not at all. Also, some micronutrients are unwittingly overdosed when their effects during pregnancy have not yet been studied.

Current research indicates that a balanced diet is generally sufficient to ensure the healthy development of an unborn child. However, folic acid, iodine and iron, are in deficit during pregnancy under current nutritional conditions in Germany. For this reason various professional associations recommend iodine and folic acid food supplements, and the additional intake of low-dose, iron-based supplements. But do women looking to have children and those who are already pregnant really follow these recommendations?

"In spite of existing recommendations, many pregnant women and their doctors are not well-informed about the sensible use of supplements," explains Professor Hans Hauner, an expert on nutritional medicine at TUM.

In a survey conducted at three clinics in and around Munich, his team interviewed 522 women who had just given birth three days prior. The women included Germans and foreigners with different levels of education, both first-time mothers and women who had been pregnant before.

The largest proportion of the women polled, 97 percent, had taken at least one supplement during their pregnancy, and almost two thirds had started before getting pregnant. The doses, though, varied enormously. The intake of folic acid ranged between 0.2 and 5 mg per day, and for iron-based products the range was even greater, between 4 and 600 mg per day.

Age, ethnic origin, level of education and the number of pregnancies had a negligible influence on the general supplement taking behavior of the women. However, good medical consultation did make a difference. Over 40 percent of the women polled named their gynecologist as the most important source of information when it comes to dietary supplements.

"The details are important – for example, regarding the intake of folic acid, which can prevent neural tube defects in newborns," says professor Hans Hauner - over 85 percent of the women polled had taken folic acid during the first trimester of their pregnancy. But only about a third had followed the recommendation to begin taking at least 0.4 mg per day of folic acid at least four weeks before becoming pregnant. This means in many cases the folic acid intake was started too late for early brain development; and, those taking pre-pregnancy folic acid frequently took too much. Around 8 percent of the women took more than 1 mg per day – significantly more than recommended. Professor Hauner: "[Too much folic acid] can conceal a vitamin B-12 deficiency and should thus be avoided."

The situation is much better with regard to iodine. A quarter of the women polled took the trace element - which is so important for the development of an unborn child's brain - prior to becoming pregnant, and almost four fifths took it during pregnancy.

On the other hand, iron supplements – important for the oxygen supply to the fetus – seemed to be far too high. "Of the women polled, around two thirds took iron-based supplements even though only about a third had displayed an iron deficit," explains Hauner. "This careless use of iron-based supplements is not only pointless, it can even harm the unborn child given the very high doses often taken. Unfortunately, there are no conclusive studies on the subject, yet."

Furthermore, it was established that three quarters of the pregnant women in the study supplemented magnesium , while over 40 percent took Omega-3 fatty acids. According to current research, both are either superfluous or have little evidence of benefit – magnesium is recommended by doctors only in very specific cases, though Omega-3 fatty acids might contribute to the development of cognitive abilities.

"In light of the lack of research on the side effects of overdosed supplements, the motto for certain dietary supplements during pregnancy should be: less is more," says Hauner in summing up the results. "However, folic acid and iodine should definitely be supplemented with the recommended dose by women who want to become pregnant."

Based on the results of the survey, the TUM nutritional expert is calling for in-depth studies to be conducted in the future, not only on the benefits but also on the risks of supplements during pregnancy.

Technische Universitaet Muenchen (TUM) is one of Europe's leading universities. It has roughly 460 professors, 7,500 academic and non-academic staff (including those at the university hospital "Rechts der Isar"), and 26,000 students. It focuses on the engineering sciences, natural sciences, life sciences, medicine, and economic sciences. After winning numerous awards, it was selected as an "Elite University" in 2006 by the Science Council (Wissenschaftsrat) and the German Research Foundation (DFG). The university's global network includes an outpost in Singapore. TUM is dedicated to the ideal of a top-level research based entrepreneurial university. http://www.tum.de

TUESDAY January 18, 2011---------News Archive

Organic Milk Better - Whatever the Weather

Wetter, cooler summers can have a detrimental effect on the milk we drink, according to new research published by Newcastle University.

Researchers found milk collected during a particularly poor UK summer and the following winter had significantly higher saturated fat content and far less beneficial fatty acids than in a more ‘normal’ year.

But they also discovered that switching to organic milk could help overcome these problems. Organic supermarket milk showed higher levels of nutritionally beneficial fatty acids compared with ‘ordinary’ milk regardless of the time of year or weather conditions.

The study, which is published in this month’s Journal of Dairy Science (January 2011), leads on from previous research undertaken nearly three years ago which looked at the difference between organic and conventional milk at its source – on the farms.

“We wanted to check if what we found on farms also applies to milk available in the shops,” said Gillian Butler, who led the study. “Surprisingly, the differences between organic and conventional milk were even more marked. Whereas on the farms the benefits of organic milk were proven in the summer but not the winter, in the supermarkets it is significantly better quality year round.”

There was also greater consistency between organic suppliers, where the conventional milk brands were of variable quality.

“We were surprised to see obvious differences between the conventional brands, with the more expensive ones not necessarily better,” said Mrs Butler. “Some brands - which promote their suppliers as wholesome and grazing on fresh pastures - actually sold milk that appeared to be from very intensive farms.”

Low levels of omega-3 and polyunsaturated fatty acids were discovered in some of these brands, which are indicative of a diet low in fresh grass. These samples also showed evidence of the cows being supplemented with a saturated fat product derived from palm oil.

Mrs Butler puts the differences down to a lower reliance on grazing and fertiliser suppressing clover on conventional farms. “The results suggest greater uniformity of feeding practice on farms supplying organic milk since there were no brands which differed consistently in fat composition,” she said. “This implies a fairly uniform approach to feeding practised across these suppliers.”

Organic dairying standards prescribe a reliance on forage, especially grazing, and, in the absence of nitrogen fertiliser, tend to encourage swards of red and white clover, which have been shown to alter the fatty acid intake and composition of milk.

While protein, antioxidants, vitamins, minerals and some mono and polyunsaturated fatty acids in milk are considered beneficial, saturated fatty acids are believed to have a negative effect on human health.

“We’re always being told to cut down on the saturated fat we consume and switching to organic milk and dairy products provides a natural way to increase our intake of nutritionally desirable fatty acids, vitamins and antioxidants without increasing our intake of less desirable fatty acids,” said Mrs Butler.

“By choosing organic milk you can cut saturated fats by 30-50 percent and still get the same intake of beneficial fatty acids, as the omega-3 levels are higher but omega-6 is not, which helps to improve the crucial ratio between the two.”

While undertaking their research into the differences between organic and conventional milk, the researchers discovered the surprising link between milk quality and our changing climate. Their results suggest that if we continue to have wetter, cooler summers then farmers may have to rethink their current dairy practices.

There was a considerable difference between the milk bought in the first sampling period (July 2006 and January 2007) and corresponding times a year later. The second set of samples, following a particularly wet summer in 2007, was higher in saturated fat and lower in beneficial fatty acids.

“We didn’t expect to find differences between the sampling periods,” said Mrs Butler. “But this is likely to be down to the impact of the weather on availability and quality of forage.”

In North East England, for example, the summer of 2007 was particularly wet, with approximately 30 per cent higher recorded rainfall and 12 per cent lower temperatures compared with 2006.

“These conditions may affect the cows’ behaviour, reducing grazing intake and milk output,” said Mrs Butler. “Farmers also often increase supplementation with concentrated feeds or conserved forage to maintain milk yields in these conditions.”

During the region’s main silage making period (late May until the end of July) rainfall in 2007 was three times higher than the previous year, which also made for poorer quality silage and therefore the need for greater supplementation to compensate in winter diets.

“If these weather patterns continue, both forage and dairy management will have to adapt to maintain current milk quality,” said Mrs Butler. “The higher levels of beneficial fats in organic milk would more than compensate for the depression brought about by relatively poor weather conditions in the wet year.”

The researchers, who are part of the University’s Nafferton Ecological Farming Group and its Human Nutrition Centre, looked at the quality of milk in supermarkets across North East England at varying times of year over a two-year period.

They concluded that organic brands of milk available in supermarkets are higher in beneficial fatty acids such as CLA and omega-3 fatty acids in summer (as in their previous research) and winter (where previous research showed that the difference in the winter was not as noticeable).

Emma Hockridge, head of policy at the Soil Association, said: "This groundbreaking research proves for the first time that people buying organic milk will be benefitting from the higher levels of beneficial fatty acids in organic milk through the whole year.”

Dieting In Early Pregnancy Stunts Fetal Brain

Study shows that the fetal brain is vulnerable to moderate decreases in maternal nutrition

Eating less during early pregnancy impaired fetal brain development in a nonhuman primate model, researchers from The University of Texas Health Science Center San Antonio reported today.

The researchers found decreased formation of cell-to-cell connections, cell division and amounts of growth factors in the fetuses of mothers fed a reduced diet during the first half of pregnancy. "This is a critical time window when many of the neurons as well as the supporting cells in the brain are born," said Peter Nathanielsz, M.D., Ph.D., director of the Center for Pregnancy and Newborn Research in the Health Science Center School of Medicine.

The study included collaborators at the Southwest Foundation for Biomedical Research (SFBR) in San Antonio and Friedrich Schiller University in Jena, Germany. The team compared two groups of baboon mothers located at SFBR's Southwest National Primate Research Center. One group ate as much as they wanted during the first half of pregnancy while the other group was fed 30 percent less, a level of nutrition similar to what many prospective mothers in the U.S. experience.

"Our collaboration allowed us to determine that the nutritional environment impacts the fetal brain at both the cellular and molecular levels," said SFBR's Laura Cox, Ph.D. "That is, we found dysregulation of hundreds of genes, many of which are known to be key regulators in cell growth and development, indicating that nutrition plays a major role during fetal development by regulating the basic cellular machinery."

It is known that marked nutrient restriction, such as in famine conditions, adversely affects development of the fetal brain. Senior author Thomas McDonald, Ph.D., also of the Health Science Center, said the study "is the first demonstration of major effects caused by the levels of food insecurity that occur in sections of U.S. society and demonstrates the vulnerability of the fetus to moderate reduction in nutrients."

Dr. Nathanielsz noted other instances affecting maternal diet change:

  • In teenage pregnancy, the developing fetus is deprived of nutrients by the needs of the growing mother;
  • In pregnancies late in reproductive life, a woman's arteries are stiffer and the blood supply to the uterus decreases, inevitably affecting nutrient delivery to the fetus;
  • Diseases such as preeclampsia or high blood pressure in pregnancy can lead to decreased function of the placenta with decreased delivery of nutrients to the fetus.

"This study is a further demonstration of the importance of good maternal health and diet," Dr. McDonald said. "It supports the view that poor diets in pregnancy can alter development of fetal organs, in this case the brain, in ways that will have lifetime effects on offspring, potentially lowering IQ and predisposing to behavioral problems."

Developmental programming of lifetime health has been shown to play a role in later development of obesity, diabetes and heart disease. In light of this new finding, research should focus on effects of developmental programming in the context of autism, depression, schizophrenia and other brain disorders.

The study, published this week in Proceedings of the National Academy of Sciences, also forces researchers to review the commonly held notion that during pregnancy the mother is able to protect the fetus from dietary challenges such as poor nutrition, Dr. McDonald said.

The nonhuman primate model's brain developmental stages are very close to those of human fetuses, the researchers noted. Most previous research in this area was conducted in rats.

The University of Texas Health Science Center at San Antonio, one of the country's leading health sciences universities, ranks in the top 3 percent of all institutions worldwide receiving National Institutes of Health (NIH) funding.

MONDAY January 17, 2011---------News Archive

42 Toxic Chemicals Found in Pregnant Women

The bodies of virtually all U.S. pregnant women carry multiple chemicals, including some banned since the 1970s and others used in common products such as non-stick cookware, processed foods and personal care products, according to a new study from UCSF.

The study marks the first time that the number of chemicals to which pregnant women are exposed has been counted.

You can also watch the following video on YouTube.

Analyzing data for 163 chemicals, researchers detected polychlorinated biphenyls (PCBs), organochlorine pesticides, perfluorinated compounds (PFCs), phenols, polybrominated diphenyl ethers (PBDEs), phthalates, polycyclic aromatic hydrocarbons (PAHs) and perchlorate in 99 to 100 percent of pregnant women.

Among the chemicals found in the study group were PBDEs, compounds used as flame retardants now banned in many states including California, and dichlorodiphenyltrichloroethane ( DDT), an organochlorine pesticide banned in the United States in 1972.

Bisphenol A (BPA), which makes plastic hard and clear, and is found in epoxy resins that are used to line the inside of metal food and beverage cans, was identified in 96 percent of the women surveyed. Prenatal exposure to BPA has been linked to adverse health outcomes, affecting brain development and increasing susceptibility to cancer later in life, according to the researchers.

Findings will be published in Environmental Health Perspectives on Jan. 14, and now are available on an embargoed basis.

The study was not designed to identify direct connections to adverse health outcomes.

"It was surprising and concerning to find so many chemicals in pregnant women without fully knowing the implications for pregnancy," said lead author Tracey Woodruff, PhD, MPH, director of the UCSF Program on Reproductive Health and the Environment.

"Several of these chemicals in pregnant women were at the same concentrations that have been associated with negative effects in children from other studies. In addition, exposure to multiple chemicals that can increase the risk of the same adverse health outcome can have a greater impact than exposure to just one chemical," said Woodruff, an associate professor in the UCSF Department of Obstetrics and Gynecology and Reproductive Sciences.

Exposure to chemicals during fetal development has been shown to increase the risk of adverse health consequences, including preterm birth and birth defects, childhood morbidity, and adult disease and mortality according to the research team. In addition, chemicals can cross the placenta and enter the fetus, and in other studies, a number of chemicals measured in maternal urine and serum have been found in amniotic fluid, cord blood and meconium, they state.

The researchers analyzed data for 268 pregnant women from the National Health and Nutritional Examination Survey (NHANES) 2003-2004, a nationally representative sample of the U.S. population.

"Our findings indicate several courses of action. First, additional research is needed to identify dominant sources of exposure to chemicals and how they influence our health, especially in reproduction," said Woodruff. "Second, while individuals can take actions in their everyday lives to protect themselves from toxins, significant, long-lasting change only will result from a systemic approach that includes proactive government policies."

Co-authors of the study are Ami R. Zota and Jackie M. Schwartz of the Program on Reproductive Health and the Environment, UCSF Department of Obstetrics and Gynecology and Reproductive Sciences.

Funding for the study was provided by the Pew Charitable Trusts and a grant from the Passport Science Innovation Fund.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. For more information, visit http://www.ucsf.edu.

Smoke Causes Immediate Damage On Inhaling

In research described as "a stark warning" to those tempted to start smoking, scientists are reporting that cigarette smoke begins to cause genetic damage within minutes - not years - after inhalation into the lungs.

Cigarette smoke damages DNA within minutes
of inhaling.
Their report, the first human study to detail the way certain substances in tobacco cause DNA damage linked to cancer, appears in Chemical Research in Toxicology, one of 38 peer-reviewed scientific journals published by the American Chemical Society.

Stephen S. Hecht, Ph.D., and colleagues point out in the report that lung cancer claims a global toll of 3,000 lives each day, largely as a result of cigarette smoking.

Smoking also is linked to at least 18 other types of cancer.

Evidence indicates that harmful substances in tobacco smoke termed polycyclic aromatic hydrocarbons, or PAHs, are one of the culprits in causing lung cancer. Until now, however, scientists had not detailed the specific way in which the PAHs in cigarette smoke cause DNA damage in humans.

The scientists added a labeled PAH, phenanthrene, to cigarettes and tracked its fate in 12 volunteers who smoked the cigarettes.

They found that phenanthrene quickly forms a toxic substance in the blood known to trash DNA, causing mutations that can cause cancer. The smokers developed maximum levels of the substance in a time frame that surprised even the researchers: Just 15-30 minutes after the volunteers finished smoking. Researchers said the effect is so fast that it's equivalent to injecting the substance directly into the bloodstream.

"This study is unique," writes Hecht, an internationally recognized expert on cancer-causing substances found in cigarette smoke and smokeless tobacco. "It is the first to investigate human metabolism of a PAH specifically delivered by inhalation in cigarette smoke, without interference by other sources of exposure such as air pollution or the diet. The results reported here should serve as a stark warning to those who are considering starting to smoke cigarettes," the article notes.

The authors were funded through the National Cancer Institute.

The American Chemical Society is a non-profit organization chartered by the U.S. Congress. With more than 161,000 members, ACS is the world's largest scientific society and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.


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