The Visible Embryo News Archive

Mom’s Flu in Pregnancy May Increase Baby's Risk of Schizophrenia

The study is the first done with monkeys examining the effects of flu during pregnancy.

Rhesus monkey babies born to mothers who had the flu while pregnant had smaller brains and showed other brain changes similar to those observed in human patients with schizophrenia, a study at the University of Wisconsin-Madison in collaboration with the University of North Carolina at Chapel Hill has found.

The study is published online by the journal Biological Psychiatry. Results support findings from rodent research suggesting this type of infection may increase the risk of schizophrenia in their offspring, said lead author Sarah J. Short, Ph.D., a post-doctoral fellow at UNC working with John H. Gilmore, M.D., professor of psychiatry in the UNC School of Medicine.

“While these results aren’t directly applicable to humans, I do think they reinforce the idea, as recommended by the Centers for Disease Control and Prevention, that pregnant women should get flu shots, before they get sick” Short said.

In the study, 12 rhesus macaques were infected with a mild influenza A virus, 1 month before their baby’s due date, early in the third trimester of pregnancy. For comparison, the study also included 7 pregnant monkeys who did not have the flu.

When the babies were 1 year old, magnetic resonance imaging (MRI) scans were taken of their brains. Researchers also assessed the babies’ behavioral development at that time.

The babies born to flu-infected mothers showed no evidence of direct viral exposure. Their birth weight, gestation length and neuromotor, behavioral and endocrine responses were all normal.

However, the MRI scans revealed significant reductions in overall brain size in the flu-exposed babies. The scans also found significant reductions of “gray matter” (the portion of brain tissue that is dark in color) especially in areas of the brain called the cingulate and parietal lobe, and significant reductions of “white matter” (brain tissue that is lighter in color) in the parietal lobe.

The cingulate is located in the middle of the brain, but spans a broad distance from front to back and relays information from both halves of the brain.

This structure is important for numerous functions related to emotions, learning, memory, and executive control to aid in decision-making and anticipation of rewards.

The cingulate also plays a role in regulating autonomic processes, such as blood pressure and respiratory control. The parietal lobe makes up a large section on both sides of the brain between the frontal lobes and the occipital lobes, in the back of the brain where information from all the senses are integrated, and is especially important for combining visual and spatial information.

“The brain changes that we found in the monkey babies are similar to what we typically see in MRI scans of humans with schizophrenia,” said Gilmore. “This suggests that human babies whose mothers had the flu while pregnant may have a greater risk of developing schizophrenia later in life than babies whose mothers did not have the flu. Normally that risk affects about 1 of every 100 births. Studies in humans suggest that for flu-exposed babies, the risk is 2 or 3 per 100 births.”

Most of the work of the study was done at the Harlow Center for Biological Psychology, which is part of Wisconsin’s Department of Psychology. The center’s director, Christopher Coe, Ph.D., is senior author of the study. Gilmore, a schizophrenia researcher who has led several studies that used MRI scans of newborn human brains, led the analysis of MRI data in the pregnancy and influenza study.

Quantum Dots Show DNA-Repair Proteins in Motion

Repair proteins appear to efficiently scan the genome for errors by jumping like fleas between DNA molecules, sliding along the strands, and perhaps pausing at suspicious spots.

Researchers at the University of Pittsburgh, the University of Essex and the University of Vermont tagged the proteins with quantum dots to watch the action unfold. The findings are available today in Molecular Cell.

Everyone is constantly bombarded with environmental toxins that inflict small errors in the DNA code, so a rapid repair system is essential to maintain the integrity of the sequences for proper cell function, explained senior author Bennett Van Houten, Ph.D. and Richard M. Cyert Professor of Molecular Oncology and leader, University of Pittsburgh Cancer Institute (UPCI).

"How this system works is an important unanswered question in this field," he said. "It has to be able to identify very small mistakes in a 3-dimensional morass of gene strands. It's akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour."

The researchers sought to unravel the mystery by tagging two repair proteins, called UvrA and UvrB, with quantum dots - which are semi-conductor nanocrystals - that light up in different colors. They also stretched the usually clumped DNA into multiple "tightropes" to see the process more clearly.

They watched while UvrA proteins randomly jumped from one DNA molecule to the next, holding on to one spot for about seven seconds before hopping to another site. But when UvrA formed a complex with two UvrB molecules (UvrAB), a new and more efficient search technique emerged: the complex slid along the DNA tightrope for as long as 40 seconds before detaching itself and jumping to another molecule.

"If an E.coli bacterium had only one UvrAB complex, 13 hours would elapse before the entire genome was scanned for errors," said lead researcher Neil M. Kad, Ph.D., Department of Biological Sciences, University of Essex, United Kingdom. "About 40 complexes, comparable to the estimates of what occurs naturally, would be needed to scan it within the bacterium's 20-minute doubling time."

In addition to random jumping and sliding, the researchers also observed what they called "paused motion," in which UvrAB's motion seemed slower and purposeful.

"About one-third of the motile (moving) molecules in our study behaved this way," said co-author David M. Warshaw, Ph.D., professor and chair, Department of Molecular Physiology and Biophysics, University of Vermont. "Paused motion could represent UvrAB complexes checking for structural abnormalities associated with DNA damage."

The researchers are now exploring the possibility that the complexes are interacting with the DNA when sampling the shape/chemical configuration. An error could be altering the DNA structure, changing its handshake with the repair proteins and perhaps triggering a corrective response.

Human Cells Forage Like Amoebae and Bacteria

When cells move around in the body, they follow a pattern similar to one amoebae and bacteria use when searching for food, a team of Vanderbilt researchers have found.

"As far as we can tell, this is the first time this type of behavior has been reported in cells that are part of a larger organism," says Peter T. Cummings, John R. Hall Professor of Chemical Engineering, who directed the study published March 10 in the Public Library of Science journal PLoS ONE.

Prior to this study, the idea existed that the faster a given type of cancer cell moves through the body the more aggressive it is. "In the process, however, we began noticing that the cell movements were unexpectedly complicated." Cummings says.

The researchers' interest was piqued when reading about the movements of a variety of radio-tagged marine predators: sharks, sea turtles and penguins. The authors of a paper on these predators found that they use a foraging strategy very much like a walking pattern, called a Lévy walk. The "Lévy walk" is an optimal method for searching complex landscapes. The authors' noted that, "…Lévy-like behaviour seems to be widespread among diverse organisms, from microbes to humans, as a 'rule' that evolved in response to patchy resource distributions."

Cummings and his colleagues made the connection that mammalian cells also face problems - such as finding nutrients and growth factors - and therefore might move in patterns similar to single-celled organisms foraging for food.

With this perspective, Alka Potdar, now at Case Western Reserve University, followed and tracked the motion of cultured cells from three human mammary epithelial cell lines. Epithelial cells are found throughout the body lining organs and covering organ surfaces. Analyzing the epithelial cell movements, she found they followed the same pattern. Not the "Lévy walk" anticipated, but a closely related, two-phase movement called a bimodal correlated random walk (BCRW). In the first phase the cell travels primarily in one direction; in the second, it re-orients itself internally to move in a new direction.

In subsequent studies, the researchers found several other cell types (social amoeba, neutrophils, fibrosarcoma) also follow the same BCRW pattern. "For the first time, this gives us a general framework for analyzing the way cells move," says Potdar.

The discovery has a practical value for drug development. Using the BCRW movement in computer simulations of cell migration, such as in embryo development, bone remodeling, wound healing, infection and tumor growth, might improve the accuracy for predicting the effectiveness of potential therapies.

Behavior Problems in Childhood Doubles Risk of Chronic Pain in Adulthood

Bad behaviour in childhood is associated with long-term, chronic widespread pain in adult life, according to the findings of a study following nearly 20,000 people from birth in 1958 to the present day.

Chronic widespread pain is a common complaint that can have a major adverse effect on quality of life, often requiring referral to a hospital specialist for investigation and treatment. The research, published online in the journal Rheumatology (March 10, 2010), found that children with severe behaviour disturbances had approximately double the risk of chronic widespread pain by the time they reached the age of 45 than children who did not.

The association was not explained by social class, early reporting of symptoms or an already-known link between adult psychological distress and chronic widespread pain (CWP). Instead, scientists believe that a dysfunction in the interaction between the nervous system and hormones, occurring in early life, may have long-term consequences for adult health.

"We know already that severe adverse events in childhood such as hospitalization after a road traffic accident and separation from mothers are linked to CWP in adulthood. In addition, aspects of childhood behaviour are strongly related to children reporting CWP. However, until now, it was unknown whether maladjusted behaviour in children was a long-term marker for CWP in adulthood. Our study shows that it is." said Dr Dong Pang, an epidemiologist at the University of Aberdeen (UK).

"We are not sure what underlying biological mechanism underpins this relationship, but one possible explanation might be that both the childhood behaviour and the adult CWP are due to a long-term neuroendocrine dysfunction beginning in early life."

"The hypothalamic-pituitary-adrenal (HPA) axis, the primary neuroendocrine stress response system, has been shown to be associated with childhood behaviour. Similarly, altered HPA axis function has been reported to be associated with CWP. Early life experience, such as emotional stress due to past trauma, may have a lifelong impact on the neuroendocrine system (HPA axis), which in turn leads to behavioural problems in childhood and CWP in adulthood as well as other mental problems. Further research at molecular and genetic level are needed to clarify this." continued Dr. Pang.

A group of 18,558 children who were born in one week in 1958 in England, Scotland and Wales, and an additional 920 children who were born in the same week overseas and who came to the UK before the age of 16 were followed for the research.

Information was collected at the ages of 7, 11 and 16, and at 42 and 45 in adulthood. Parents and teachers independently assessed the children's behaviour on aspects of restlessness, worrying, solitariness, ability to make friends, obedience, stealing, sucking thumbs and biting nails, lying, bullying, truanting etc. At the age of 42 the participants completed a questionnaire asking about psychological distress in adult life, and at the age 45 they completed another questionnaire about pain.

The study found that CWP was slightly more common in women than in men (12.9% versus 11.7%).

Children whose teachers had reported severe persistent behaviour problems at all ages (7, 11 and 16) had more than double the risk of CWP in adulthood compared with children without behaviour problems at all ages. If the children had severe behaviour problems at 11 and 16, then they had nearly double the risk of CWP in later life.

Similar, but weaker associations were shown for parent-reported behaviour, which the researchers believe is because teachers tend to be better at providing objective assessments of behaviour as they have more children to compare.

The researchers saw not just CWP associated with bad behaviour in childhood. Other adult problems include long-term depression and anxiety, suicidal behaviour, substance abuse and treatment for psychiatric illness. The researchers suggest that all these problems may be outcomes of the chain of events set in motion by the dysfunctioning neuroendocrine system.

If further research proves this correct, then it might be possible to intervene in early life to prevent these problems occurring later in adulthood.

Professor Gary Macfarlane, the leader of the research group, said: "This study helps us to understand the factors in childhood that can lead someone to get on a trajectory of ill-health, including chronic pain. The disruption to the hypothalamic-pituitary-adrenal (stress-response) axis is one biological marker of the effect of such experiences and this could help to identify persons at higher risk of chronic pain. Interventions would be lifestyle focussed and would include identification and treatment of behavioural and emotional factors, but would also address lifestyle factors such as increased physical activity.

"We plan to undertake some studies in children to understand what range of factors cause a disturbance to the stress-response axis; such work can then inform what intervention studies may be appropriate."

Kids' Temporary Hearing Loss Can Lead to 'Lazy Ear'

Scientists have gained new insight into why a relatively short-term hearing deprivation during childhood may lead to persistent hearing deficits, long after hearing is restored to normal.

Research published in the March 11 issue of the journal Neuron, reveals that development of the auditory cortex is quite vulnerable if it does not receive the correct stimulation at just the right time.

It is well established that poor sensory intake during critical periods of childhood development can have detrimental effects on the brain and behavior. A classic example, amblyopia - or lazy eye - can arise when balanced visual signals are not transmitted from each eye to the brain during a critical period in the development of the visual cortex.

"An analogous problem may exist in the realm of hearing, in that children commonly experience a buildup of viscous fluid in the middle ear cavity, called otitis media with effusion, which can degrade the quality of acoustic signals reaching the brain and has been associated with long-lasting loss of auditory perceptual acuity," explains senior study author, Dr. Daniel Polley from the Massachusetts Eye and Ear Infirmary.

Dr. Polley and his colleague Dr. Maria Popescu from Vanderbilt University implemented a method to block hearing in one ear in infant, juvenile, and adult rats, then they looked at how auditory brain areas were impacted by this temporary hearing loss.

They observed that the temporary hearing loss in one ear distorted auditory patterning in the brain, weakening the deprived ear's representation and strengthening the open ear's representation.

The scope of reorganization was most striking in the cortex and was more pronounced when hearing deprivation began in infancy. It appears that the lack of plasticity in the developing auditory cortex might underlie "amblyaudio," in a similar way to the visual cortex plasticity in amblyopia.

"The good news about amblyaudio is that it is unlikely to be a permanent problem for most people", concludes Dr. Polley. "Even if the acoustic signal isn't improved within the critical period, the mature auditory cortex still expresses a remarkable degree of plasticity. We know that properly designed visual training can improve visual acuity in adult amblyopia patients. We are gearing up now to study whether auditory perceptual training may also be a promising approach to accelerate recovery in individuals with unresolved auditory processing deficits stemming from childhood hearing loss."

Pregnant Moms with Metal-on-Metal Hip Implants Pass Metal Ions to Offspring

Women with metal-on-metal hip implants, where both the ball of the joint and the surface of the socket are made of metal, pass metal ions to their offspring during pregnancy, according to a study by researchers at Rush University Medical Center. The ions are the result of wear and corrosion as the metal parts rub against one another.

The data showed a correlation between levels of cobalt and chromium – components of metal implants – in mothers and their babies at the time of delivery.

The study will be presented March 9 at the 2010 Annual Meeting of the American Academy of Orthopaedic Surgeons in New Orleans.

"We don't know whether metal ions pose any health risks for pregnant women and their babies," said Dr. Joshua Jacobs, professor and chairman of orthopedic surgery at Rush, "but as metal-on-metal implants increase in popularity and use, especially among young, active patients, women of child-bearing age and their doctors need to be aware of these findings when considering options for hip replacements."

Jacobs and his colleagues evaluated three women who had metal-on-metal hip implants and gave birth two to six years after their surgeries.

Maternal and umbilical cord blood was gathered at the time of delivery and tested for blood serum concentrations of titanium, nickel, cobalt and chromium using inductively coupled plasma mass spectrometry, a highly sensitive technique that can detect trace amounts of metals in biological samples.

Researchers found that mothers with metal-on-metal implants and their offspring had significantly higher levels of chromium and cobalt compared with a control group of seven women and their offspring who were also tested at the time of delivery. The levels of these metals in the blood of mothers with implants correlated with the levels found in the umbilical cords. Cobalt levels in newborns were about half that in the mothers' blood, while chromium levels were about 15 percent of the mothers' chromium levels. In the control group, no correlation existed.

The lower levels in the umbilical cords indicated that the placenta provided at least some barrier to the transfer of metal ions from mother to fetus, but not a complete barrier, Jacobs said.

Levels of titanium or nickel showed no significant difference between the two groups.

It is unknown whether metal ions in the bloodstream – for pregnant mothers, developing fetuses or newborns – pose any significant health risk. According to Jacobs, medical device companies are working to improve the wear and corrosion properties of metal implants to reduce the release of metal ions.

Model To Help Us Understand Embryo Stem Cells

A mathematical model developed at Purdue University can predict complex signal patterns that determine how stem cells in an embryo become specific tissues.

During embryo development, proteins attach to cell receptors starting a cascade of reactions.

Understanding those reactions is difficult because feedback signals going out to the proteins and other molecules along the cascade, constantly change reaction patterns. The outcomes of those reactions and the feedback mechanisms - or inputs - are known because they can be observed, but how the inputs lead to the outputs isn't understood.

"We want to understand how stem cells become tissue-specific so that we can manipulate that process to create cells that could be used to treat injuries and diseases," said David Umulis, a Purdue assistant professor of agricultural and biological engineering. "Using a model approach, we can simulate these complex signaling patterns to get a better handle on the process."

Umulis created a model that predicts accurate outcomes when different feedback mechanisms are inserted. His results are published in the current issue of the journal Developmental Cell.

"Fruit fly embryos are a fantastic system to peer into early development since input/output relationships are easy to observe. You have a mutation and an output, but we don't typically know what happens in the middle," he said. "Realistic model embryos proved an additional tool that can be used to aid in that understanding. Models can link that cause and effect."

The study looked at fruit flies, or drosophila, embryos during very early development to figure out what controls the differentiation of their stem cells at specific locations.

During early development, cells take on identities that define specific tissue types in the adult organism. Before these cues dictate specific tissues, stem cells are capable of becoming any tissue.

Using a mathematical model to analyze the signals cells are receiving may help to understand how to control similar cells in a laboratory setting.

Umulis said his model is a sort of template to allow researchers to test a number of ideas before conducting actual experiments. The information gotten from realistic 3-D models can guide the process and facilitate rapid discoveries.

Umulis' next step is to count the number of molecules needed to initiate specific cell types during embryo development.

The National Institutes of Health and Purdue University funded his work.

‘Sonic hedgehog’ Gene Challenges Scientists’ Understanding of Limb Growth

Sonic hedgehog, a gene that plays a crucial rule in the position and growth of limbs, fingers and toes, has been found in an unexpected place in developing mice embryos - the layer of cells that creates skin.

Named for the video game character, Sonic hedgehog describes both a gene and the protein produced in the body.

It was thought to be exclusively present in the mesoderm cell layer that builds bone and muscle. But University of Florida Genetics Institute researchers have discovered it is also in mice limb buds in what is known as the ectoderm, the cell layer that gives rise to the skin in vertebrates.

Finding Sonic hedgehog in this layer of cells is something like discovering that yeast has crept out of the batter and into the frosting of the cake, where it limits how much the cake will rise. Sonic hedgehog seems to act as a failsafe mechanism to keep additional digits from developing.

“Sonic hedgehog protein determines how your limbs form, and why your pinky is at the bottom of your hand and your thumb is at the top,” said Brian D. Harfe, an associate professor of molecular genetics and microbiology at the UF College of Medicine. “But what’s been previously published is only part of the picture. We determined that Sonic hedgehog signaling is required in the ectoderm to have normal digit formation. Get rid of it, and an extra digit forms.”

When scientists disrupted Sonic hedgehog signaling in a small region of the limb buds of embryonic mice, an additional digit began to grow in what would be the mouse paw.

The discovery, appearing online in this week’s Proceedings of the National Academy of Sciences, suggests that Sonic hedgehog’s role in the growth of appendages is far more complex. Biologists may have to rethink established theories about how limbs are patterned in vertebrates - to provide new insight into human birth defects.

The UF research was sparked by studies of gene activity in the limb buds of mice by William J. Scott, a professor of pediatrics at the University of Cincinnati. Scott examined gene expression in the ectoderm of mice limb buds, finding activity that could not be possible without the presence of Sonic hedgehog.

“The view had been if you reduce signaling, if anything you would get fewer fingers,” said Scott, who did not participate in the UF research. “We now know we can’t disregard Sonic hedgehog signaling in the ectoderm. It still has its predominant effect in the tissue where it is made, but it does something more than we thought it did previously.”

Harfe said the next phase of the work will be to observe what happens when Sonic hedgehog signaling is disrupted through larger segments of the ectodermal layer. “We would like to repair limb defects in humans and enhance regeneration of limbs, helping people who might cut off fingers in an accident, for example,” Harfe said.

The work was funded by the UF College of Medicine.

In Mice, Mom's Diet Affects Boys More Than Girls

Eating for two. The placentas of pregnant mice fed a high-fat diet seem to do better if they're nourishing a female versus a male fetus.

Moms-to-be think a lot about what they eat and how it might affect their growing baby. Now, new research suggests that boys are more sensitive than girls to the diet their mother ingests while they are in utero.

Previous studies hinted that maternal diet affects the health of male and female fetuses differently.

For example, Cheryl Rosenfeld, a reproductive biologist at the University of Missouri, Columbia, conducted a study in 2003 showing that expectant mouse moms who consume low-calorie diets tend to carry more females to term than males - indicating that male fetuses are the more sensitive sex in utero and miscarry at higher rates.

That made Rosenfeld wonder if diet causes genes to behave differently in wombs with male or female fetuses.

To find out, Rosenfeld and her team studied pregnant mice that were divvied up into three dietary groups: very high fat, high carbohydrate/low fat, and moderate fat. About 12.5 days after conception - or about halfway through the gestational period and before the fetus starts to produce sex hormones that, like diet, can also alter gene expression, the scientists terminated the pregnancies and removed the animals' placentas.

The researchers scanned 40,000 genes in the placentas to determine whether their activity varied depending on a mom's diet.

They found that 211 genes differed significantly between the low-fat and high-fat groups. The genes changed expression most often from the low-fat to the high-fat female placentas, suggesting that placentas nourishing females do a better job of responding to diet - and potentially protecting the fetus from harmful ingredients - than do those connected to males.

So, in a classic double-edged sword, high-fat maternal diets appear to help male fetuses survive to term, but that same diet may expose male fetuses to harmful compounds.

As for the genes that seemed to be key: Rosenfeld's group was surprised to find genes that regulate smell and nutrient filtering (as in the kidney) are in the placenta.

"We thought we'd see genes related to metabolism, and we saw some of that, but what really came up were these genes that related to the ability of the placenta to smell or sense nutrient compounds," Rosenfeld says. "That's a very novel idea." Those genes were also expressed more strongly in female placentas than in male placentas. "There is clearly dialogue that's occurring between the mom and the fetus, and each sex responds differently to ... maternal diet," Rosenfeld says.

The idea that the placenta has more functions than previously thought doesn't surprise Jared Friedman, a reproductive biologist at the University of Colorado, Boulder.

For the fetus, "it's your lung, it's your kidney, it's your gut. I guess if it expresses these olfactory genes, it's now your nose," he says.

But Friedman, who also studies how obese mice affect their offspring's health, isn't ready to call the placenta sexist just yet. Males, he says, seem to lag behind females in all stages of development.

Maybe those olfactory genes become more active in the male placenta as the pregnancy continues, he says. "Instead of 12.5 days, go to 19.5 and see if the differences are magnified or if the males catch up." Or, he says, maybe male fetuses' early exposure to harmful nutrients helps them adapt to a high-fat diet later in life.

Staci Bilbo, a developmental neuroscientist at Duke University in Durham, North Carolina, agrees that researchers don't know how these differences play out later in life or whether they apply to people.

But what Bilbo finds so striking is that the placenta behaves differently with male and female fetuses right from the get-go, "at the moment of conception," she says.

The findings appear online today in the Proceedings of the National Academy of Sciences.

Infectious Herpesvirus Hides in Chromosomes and Can be Passed from Parent to Child

Virologists surprised to discover that a common herpesvirus hidden in chromosomes of some people can be reactivated to become infectious.

Human herpesvirus 6 (HHV-6) infects nearly 100 percent of humans in early childhood, and the infection then lasts for the rest of a person's life.

Now, a team led by Peter Medveczky, MD, a professor in the Department of Molecular Medicine at the University of South Florida (USF), has discovered that in some individuals, HHV-6 causes such a permanent infection by inserting or "integrating" its DNA into human chromosomes. From this harbor, the viral DNA cannot be eliminated by the immune system.

The USF team also confirmed preliminary results by other investigators that, a long time ago, the virus inserted its DNA into the DNA of human sperm and egg cells. As a result, some people (about 1 percent of people in the U.S.) are born with the virus's DNA in every cell in their body.

Indeed, HHV-6 is the first functional virus of any type reported to be passed through the human germ line.

The team presented clear evidence that the virus can insert its DNA specifically into telomeres – structures at the ends of each chromosome that play key roles in both aging and cancer.

Finally, the team showed that the chromosomally integrated HHV-6 (CIHHV-6) genomes can be reactivated to an infectious form.

The findings are a surprise, since other human herpesviruses cause permanent infection by a different mechanism. The round up their DNA into a little circle that resides inside the nucleus of the cell: they do not insert their DNA into the chromosomes.

There are many unanswered questions that the USF team hopes to sort out. "We would like to know whether the location of the integration has an impact on pathology," Dr. Medveczky said. "We'd also like to know more about which drugs can provoke reactivation in patients that carry this virus in every cell... It would be important for these patients to avoid drugs that may reactivate the virus."

HHV-6 was discovered in 1986 in the laboratory of Dr. Robert C. Gallo at the National Cancer Institute after Gallo asked his co-workers to look for a herpesvirus in AIDS lymphoma cases that might be triggering cancer. "In my mind these findings also should stimulate further studies on a possible role of HHV-6 in some cancers as suggested by others who have found a possible link to some lymphomas," Dr. Gallo commented.

HHV-6 causes roseola, a generally benign rash and fever in infants. The virus can reactivate in individuals with suppressed immune systems, sometimes causing serious consequences such as encephalitis, hepatitis, myocarditis, and pneumonia.

Recent research has suggested that HHV-6 may also be associated with diseases in people with apparently healthy immune systems: encephalitis, mesial temporal lobe epilepsy, multiple sclerosis, myocarditis, and idiopathic cardiomyopathy.

Previous studies had used a visual technique called fluorescence in situ hybridization (FISH), which showed that the viral DNA was present at the same location (near the telomeres) of the same chromosome in both parent and child. This strongly suggested - but did not prove - that the virus was inherited through the germ line in these children.

By determining the DNA sequence of the ends of the chromosome, the Medveczky team clearly demonstrated that the HHV-6 genome was integrated into telomere DNA. The team also showed that HHV-6 DNA, unlike other human herpesviruses, does not curl into a circle inside the nucleus.

The great majority of people, however, do not inherit HHV-6 DNA from their parents and do not have it in every cell of their body.

Yet nearly everyone becomes permanently infected with the virus. So Medveczky and colleagues wondered if the virus might take up permanent residence in the body by integrating its DNA into the chromosomes of just some cells.

To examine this possibility, the investigators took cells that had never been exposed to HHV-6 and infected them with HHV-6 that had been engineered to make infected cells glow bright green. Sure enough, once the infection died down, the green cells contained HHV-6 DNA integrated into the ends of the chromosomes. When the investigators stimulated the cells with chemicals known to activate other herpesviruses, cells with integrated viral DNA began producing infectious virus.

For the approximately 1 percent of the population born with viral DNA in every cell in their body, several questions arise. Are such people more prone to diseases because they have a greater risk of viral reactivation? If so, which diseases? If a person is born with viral proteins present from birth, would that person's immune system be "fooled" into thinking that the virus was not foreign and need not be attacked? If so, is that a bad thing or a good thing for a person's health?

Finally, the virus inserts itself into the telomeres and could theoretically disrupt the function of the telomeres. Since the telomeres are important in cellular aging and in cancer, could the insertion of viral DNA in the telomeres have any effect on a cell's tendency to age or to turn cancerous?

While unique among known human herpesviruses, the capacity of HHV-6 to integrate into human chromosomes is not unique in nature. A herpesvirus that infects chickens, called Marek's disease virus, appears to behave the same way. Interestingly, although the viruses are not otherwise closely related, the DNA sequence used by Marek's disease virus to integrate into chicken chromosomes is remarkably similar to the DNA sequence used for chromosomal integration by HHV-6.

The paper describing this research was published online March 8 in Proceedings of the National Academy of Sciences.

Testosterone, Can It Make You Nasty Or Nice?

Is aggression always the best response to a challenge? Testosterone may not necessarily cause aggression but behavior can drive testosterone secretion.

In an evaluation for Faculty of 1000, Robert Sapolsky highlights a study published in Nature which assessed how testosterone affects human behavior in a 'pro-social' situation – an environment where it is beneficial for a person to help someone else.

In an 'Ultimatum Game', a 'proposer' is given power to decide how a sum of money is divided between her and another player, 'the decider'. The decider can either accept the offer, and possibly receive less than a fair share, or reject it, in which case both players get nothing. The participants in the game were all women.

Women who were given testosterone unknowingly made fairer offers (a pro-social decision) than women who received a placebo. Interestingly, women who believed that testosterone has anti-social, aggression-causing effects and who thought they'd received testosterone made offers that were less fair, even when they had received a placebo.

When given to the subject in a blind trial, testosterone can encourage pro-social as well as anti-social behaviour. However, as the authors note, "biology seems to exert less control over human behavior [than in other animals]," since awareness of having received testosterone drastically altered behavior.

So, not only can our own behavior be confounded by our prejudices but the effects of testosterone may be far more complex than previously thought. As Sapolsky says, "Despite the seeming power of the proposer, the decider ultimately has the most power, and the proposer seriously loses status if the decider rejects their offer."

Stem Cells from Adult Tissue, Are They Real?

Turning adult cells into potent stem cells capable of morphing into many different tissues — nerves, heart or liver — has been viewed by some as a way to circumvent the need for embryonic stem cells. But there are some problems.

In 2006, Shinya Yamanaka, MD, found a way to coax mature skin cells from mice into becoming potent stem cells. A year later he accomplished the same with human cells. The technique is viewed as a unique way to study the behavior of cells in inborn and chronic diseases. It is also key to personalizing cell therapy based on cells from patients.

Although the initial cells derived from Yamanaka's induced pluripotent stem (iPS) adult cells - now a UCSF faculty member and recipient of the 2009 Lasker Award for stem cell research - were created just a few years ago, hundreds of labs are now creating iPS cells in a burgeoning new field.

To generate an iPS cell, researchers manipulate a specialized adult cell, transforming it back to an unspecialized state. The ideal stem cell is a "blank slate", capable of becoming any other tissue as well as being immortal.

But in the past few weeks, the potential of iPS cells has been questioned in light of research showing that iPS cells differ from embryonic stem cells and suffer from the comparison.

According to stem cell scientist Robert Lanza, MD, nerve cells and blood cells grown from iPS cells grow and survive poorly - and age quickly - in comparison to embryonic stem cells. Lanza says iPS cells cannot be considered a practical choice for stem cell therapy. Lanza and colleagues published their findings in February in the journal Stem Cells. In February 16, 2010 of the Proceedings of the National Academy of Sciences, a team led by University of Wisconsin researcher Su-Chun Zhang, MD, PhD, also found that a variety of iPS cell lines were less efficient and reliable in generating nerve cells.

Differences Among Stem Cells

George Daley, MD, PhD, a leading stem cell researcher from Harvard Medical School believes that iPS cells and embryonic stem cells appear to be “functionally the same in a generic way.” But his own lab’s experiments show that there actually are significant differences. Many iPS cell lines are not really the blank slates that embryonic stem cells are.

Daley found that stem cells from iPS cell lines are better able to generate specialized cells similar to the cells from which they are derived. Stem cells made by reprogramming blood cells are better at forming types of blood cells than types of nerve cells, and iPS cells made by reprogramming nerve cells are better at regenerating nerve tissue.

In Search of Consistency

“We need to come up with strategies to attempt to get iPS cells back to a more uniform, embryonic-stem-cell-like state" says Daley.“As the field is emerging and lots of laboratories are jumping in to work on iPS cells, we have to adhere to strict criteria for documentation, so we know we are working with faithfully reprogrammed cells.”

Despite the variability in iPS cell lines, they still hold great promise, said UCSF stem cell researcher Robert Blelloch, MD, PhD, who attended Daley’s talk. He noted that researchers already have succeeded in growing mice from iPS cells. “I still believe in them,” Blelloch said. “There are going to be setbacks here and there, but overall the field is advancing at a remarkable pace.”

Vitamin D Crucial to Activating Immune Defenses

Scientists at the University of Copenhagen have discovered that Vitamin D is crucial to activating our immune defenses and that without sufficient intake of the vitamin, the killer cells of the immune system – T cells - will not be able to react to and fight off serious infections in the body.

For T cells to detect and kill foreign pathogens such as clumps of bacteria or viruses, the cells must first be 'triggered' into action and 'transform' from inactive and harmless immune cells into killer cells that are primed to seek out and destroy all traces of a foreign pathogen.

What researchers have found is that T cells rely on vitamin D in order to activate. Without vitamin D, T cells remain dormant, or 'naïve', to the possibility of threats to the immune system.

What is a T Cell?

In order for the specialized immune cells (T cells) to protect the body from dangerous viruses or bacteria, they must first be exposed to traces of a foreign pathogen - or toxin. This occurs when immune cells known as macrophages identify suspicious cell fragments. T cells then bind to that fragment, dividing and multiply it into hundreds of identical cells focused on this pathogen.

Professor Carsten Geisler from the Department of International Health, Immunology and Microbiology explains that "when a T cell is exposed to a foreign pathogen, it extends a signaling device or 'antenna' known as a vitamin D receptor, with which it searches for vitamin D. This means that the T cell must have vitamin D or activation of the cell will cease. If the T cells cannot find enough vitamin D in the blood, they won't even begin to mobilize. "

T cells that are successfully "turned on", or activated, transform into one of two types. They either become killer cells that attack and destroy all cells carrying traces of the foreign pathogen or they become helper cells. Helper cells send messages to the immune system, so that the immune system will recognize and remember a pathogen. T cells are part of the adaptive immune system, functioning by teaching the immune system to recognize and adapt to constantly changing threats.

Turning the Immune System On and Off

For the research team, identifying the role of vitamin D in the activation of T cells has been a major breakthrough. "Scientists have known for a long time that vitamin D is important for calcium absorption and the vitamin has also been implicated in diseases such as cancer and multiple sclerosis, but what we didn't realize is how crucial vitamin D is for actually activating the immune system. "

The discovery provides much needed information about the immune system and possibly how to regulate an immune response. This is important after organ transplants, when T cells can attack the donor organ as a "foreign invader". Or in autoimmune disease, when hypersensitive T cells mistake fragments of the body's own cells for foreign pathogens, leading the body to attack itself.

The research team was also able to track the biochemical sequence of T cell transformation from inactive to active, and hope in the future to be able to intervene and modify immune response. Now knowing that inactive, or 'naïve', T cells crucially contain neither the vitamin D receptor nor a specific molecule called PLC-gamma1, that enables the cell to deliver an antigen specific response, gives scientific research immune system targets for reconstruction.

The findings, continues Professor Geisler "could help us to combat infectious diseases and global epidemics. They will be of particular use when developing new vaccines, which work precisely on the basis of both training our immune systems to react and suppressing the body's natural defenses in situations where this is important – as is the case with organ transplants and autoimmune disease."

Most Vitamin D is produced as a natural byproduct of the skin's exposure to sunlight. It can also be found in fish liver oil, eggs and fatty fish such as salmon, herring and mackerel or taken as a dietary supplement.

No definitive studies have been carried out for the optimal daily dosage of vitamin D but as a large proportion of the population have very low concentrations of vitamin D in the blood, a number of experts recommend between 25-50mg micrograms a day.

Low Levels Vitamin D Linked to Increased Muscle Fat, Decreased Strength in Young Women

First-of-a-kind study by investigator at The Research Institute of the MUHC finds “epidemic” of Vitamin D insufficiency.

Lack of vitamin D causes weight gain and stunts growth in girls, while Vitamin D supplements could fight Crohn's disease. However, there’s an epidemic in progress, and it has nothing to do with the flu.

A ground-breaking study published in the March 2010 Journal of Clinical Endocrinology and Metabolism found an astonishing 59 per cent of study subjects had too little Vitamin D in their blood. Nearly a quarter of the group had serious deficiencies (less than 20 ng/ml) of this important vitamin. Since Vitamin D insufficiency is linked to increased body fat, decreased muscle strength and a range of disorders, this is a serious health issue.

“Vitamin D insufficiency is a risk factor for other diseases,” explains principal investigator, Dr. Richard Kremer, co-director of the Musculoskeletal Axis of the Research Institute of the MUHC. “Because it is linked to increased body fat, it may affect many different parts of the body. Abnormal levels of Vitamin D are associated with a whole spectrum of diseases, including cancer, osteoporosis and diabetes, as well as cardiovascular and autoimmune disorders.”

The study is the first to show a clear link between Vitamin D levels and the accumulation of fat in muscle tissue – a factor in muscle strength and overall health. Scientists have known for years that Vitamin D is essential for muscle strength. Studies in the elderly have showed bedridden patients quickly gain strength when given Vitamin D.

The study results are especially surprising, because study subjects – all healthy young women living in California – could logically be expected to benefit from good diet, outdoor activities and ample exposure to sunshine – the trigger that causes the body to produce Vitamin D.

“We are not yet sure what is causing Vitamin D insufficiency in this group,” says Dr. Kremer who is also Professor of Medicine at McGill University. High levels of Vitamin D could help reduce body fat. Or, fat tissues might absorb or retain Vitamin D, so that people with more fat are likely to also be Vitamin D deficient.”

The results extend those of an earlier study by Dr. Kremer and Dr. Gilsanz, which linked low levels of Vitamin D to increased visceral fat in a young population.

“In the present study, we found an inverse relationship between Vitamin D and muscle fat,” Dr. Kremer says. “The lower the levels of Vitamin D the more fat in subjects’ muscles.”

While study results may inspire some people to start taking Vitamin D supplements, Dr. Kremer recommends caution. “Obviously this subject requires more study,” he says. “We don’t yet know whether Vitamin D supplementation would actually result in less accumulation of fat in the muscles or increase muscle strength. We need more research before we can recommend interventions. We need to take things one step at a time.”

This study was funded by a grant from the National Institutes of Health, the U.S, Department of the Army, the Canadian Institutes of Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Dimensional Fund Advisors Canada Inc (a subsidiary of U.S.-based Dimensional Fund Advisors).