University Times

Mercury ID made easier

Pitt researchers have developed a simple and quick method for detecting mercury in fish and dental samples, two substances at the center of public concern about mercury contamination.

The technique involves a fluorescent substance that glows bright green when it comes into contact with oxidized mercury, the researchers report in the current online edition of the Journal of the American Chemical Society. The intensity of the glow indicates the amount of mercury present.

Developed in the laboratory of chemistry professor Kazunori Koide, the test can detect mercury in 30-60 minutes for dental fillings (amalgams) or 10-30 minutes for fish, Koide said. “Our method could be used in the fish market or the dentist office,” he said. “We have developed a reliable indicator for mercury that a person could easily and safely use at home.”

The fluorescence results from the reaction of mercury ions with hydrocarbons called alkynes; the alkyne is converted into a ketone and creates a fluorescent molecule. Koide’s method differs from similar mercury indicators in that it withstands the oxidation process mercury samples must undergo prior to testing, Koide said. The mercury variety found in most fish and dental amalgams — such as the toxic methyl mercury — must be converted into a safer variety of mercury with an oxidizing agent. Other fluorescent detectors often are not compatible with samples that have been oxidized.

In testing fish, Koide and his team oxidized a piece of salmon (about the size of a fingertip) in water mixed with a chlorine solution similar to household bleach. The conversion process is safe and relatively simple, Koide said. Afterward, the team added the alkyne solution and the mixture glowed bright green.

The Pitt researchers also tested for mercury leaching from dental amalgam, a common tooth filling composed primarily of mercury mixed with smaller amounts of other metals. Concern exists about the mercury seeping from a filling into a person’s body and about the disposal of unused amalgam by dentist offices (which is not federally regulated in the United States).

To test for leaching, the team pressed a cloth to a tooth with an amalgam filling for one minute; the sample glowed when exposed to the mercury-detecting agent. They also submerged two amalgam-filled teeth in the amino acid cysteine to mimic sulfur-rich foods, which are thought to increase mercury seepage from amalgam. Again, the cysteine solution turned bright green when the indicator was added, suggesting that Koide’s method also can be used to monitor mercury leaching caused by sulfur-rich food.

In terms of amalgam disposal, Koide suggested that his method could be used to test dentist office wastewater for mercury content on site without sending samples to analytical laboratories.

The paper can be found at pubs.acs.org/doi/abs/10.1021/ja805678r.

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Stem cells repair heart tissue

Researchers at Children’s Hospital have been able to repair damaged heart muscle using stem cells derived from human skeletal muscle tissue.

The research team was led by Johnny Huard, a professor in the departments of orthopaedic surgery, molecular genetics, biochemistry, bioengineering and pathology. The team transplanted stem cells purified from human muscle-derived blood vessels into the hearts of mice that had heart damage similar to damage that would occur in people who had suffered a heart attack.

These transplanted myoendothelial cells repaired the injured muscle, stimulated the growth of new blood vessels in the heart and reduced scar tissue from the injury, thereby dramatically improving the function of the injured left ventricle, said Huard, director of the Stem Cell Research Center at Children’s Hospital.

The myoendothelial cells used in this study were more effective at repairing the injured cardiac muscle and reducing scar tissue than previous approaches that have used muscle cells known as myoblasts, according to Huard.

“This study confirms our belief that this novel population of stem cells discovered in our laboratory holds tremendous promise for the future of regenerative medicine. Specifically, myoendothelial cells show potential as a therapy for people who have suffered a myocardial infarction,” said Huard, who also is the Henry J. Mankin Endowed Chair in Orthopaedic Surgery Research, deputy director for cellular therapy at the McGowan Institute for Regenerative Medicine and an associate director of the Pittsburgh Tissue Engineering Initiative.

“The important benefit of our approach is that as a therapy, it would be an autologous transplant. This means that for a patient who suffers a heart attack, we would take a muscle biopsy from his or her muscle, isolate and purify the myoendothelial cells and re-inject them into the injured heart muscle, thereby avoiding any risk of rejection by introducing foreign cells.”

Results of this study were published in the Dec. 2 issue of the Journal of the American College of Cardiology.

More information on Huard’s research is available at www.chp.edu by clicking on “Research.”

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More fund choices not always better

As the number of mutual funds offered by employers grows, less-knowledgeable investors are making increasingly riskier decisions in the allocations of their 401(k) retirement savings, according to “Saving for Retirement: The Effects of Fund Assortment Size and Investor Knowledge on Asset Allocation Strategies,” which recently appeared in the Journal of Consumer Affairs.

The study was conducted by researchers at the Joseph M. Katz Graduate School of Business, Rutgers School of Business-Camden and the McCombs School of Business, University of Texas-Austin.

The results indicate that less-knowledgeable investors change their asset allocation strategies when more investment options are offered, allocating a significantly higher proportion of dollars to stocks when choosing from the larger assortment.

The results are based upon a decision simulation conducted among 211 adults whose task was to invest in a 401(k) retirement plan.

“We would suggest that more options are better, because more-knowledgeable investors are able to handle larger assortments and prefer them,” says Pitt researcher J. Jeffrey Inman, Albert Wesley Frey Professor of Marketing and professor of business administration. “On the other hand, our results suggest that investment counseling is key for employees who are less knowledgeable about investing.”

In the study, the proportion of dollars allocated to stocks (vs. bonds or cash) more than doubled for less-knowledgeable investors when the number of options increased, whereas the number of options had no significant impact on the allocation strategies for more-knowledgeable investors.

Inman notes that while it is not necessarily undesirable for less-knowledgeable investors to allocate more of their dollars to stocks, it is disconcerting that merely changing the total number of funds offered in the plan has such a large impact on the risk profile for their investment portfolios.

Inman suggests that employers offer a “Test Your Investing IQ” quiz for their employees to assess which are at the greatest risk.

“Another course of action is for employers to advise all employees to set target allocations for the three asset classes (stocks, bonds, and money market funds) before they begin to consider the specific investment alternatives.”

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New target for schizophrenia found

New research could expand the options for controlling schizophrenia by identifying a brain region that responds to more than one type of antipsychotic drug. The findings illustrate for the first time that the orbitofrontal cortex could be a promising target for developing future antipsychotic drugs — even those that have very different mechanisms of action.

The study appears in the online edition of the journal Proceedings of National Academy of Sciences.

Bita Moghaddam, professor in the Department of Neuroscience and the paper’s lead author, working with UPMC neurology resident Houman Homayoun, found that schizophrenia-like activity in the orbitofrontal cortex — a brain region responsible for cognitive activity such as decision-making — could be triggered by the two different neurotransmitters linked to schizophrenia: dopamine and glutamate. Brain activity then was normalized both by established antipsychotic medications that regulate only dopamine and by experimental treatments that specifically target glutamate.

“The orbitofrontal cortex is an area that’s been somewhat neglected in schizophrenia research. This study should encourage researchers to focus on this brain region in imaging and other human studies, and also to use as a model for developing antipsychotic drugs,” Moghaddam said. “Schizophrenia appears to be caused by very diverse and sometimes rare genetic mutations. Diverse mutations can end up causing the same disease if they disrupt the function of a common group of neurons or networks of neurons. We think that the key to understanding the pathophysiology of schizophrenia and finding better treatments is to identify these networks. [These data suggest] that the orbitofrontal cortex may be a critical component in networks affected by schizophrenia.”

The paper can be found at www.pnas.org.

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Evolution of genders studied

Pitt research published in the Nov. 20 edition of Heredity finally could provide evidence of the first stages of the evolution of separate sexes, a theory that holds that males and females developed from hermaphroditic ancestors. These early stages are not understood completely because the majority of animal species developed into separate sexes too long ago for scientists to observe the transition.

However, Tia-Lynn Ashman, a plant evolutionary ecologist in the Department of Biological Sciences, documented early separate-sex evolution in a wild strawberry species still transitioning from hermaphroditism.

These findings also apply to animals (via the unified theory) and provide the first evidence in support of the theory that the establishment of separate sexes stemmed from a genetic mutation in hermaphroditic genes that led to male and female sex chromosomes. With the ability to breed but spared the inbred defects of hermaphrodites, the separate sexes flourished.

“This is an important test of the theory of the early stages of sex chromosome evolution and part of the process of understanding the way we are today,” Ashman said. She added that the study also shows that plants can lend insight into animal and human evolution. “We have the opportunity to observe the evolution of sex chromosomes in plants because that development is more recent. We wouldn’t see this in animals because the sex chromosomes developed so long ago. Instead, we can study a species that is in that early stage now and apply it to animals based on the unified theory that animal and plant biology often overlaps.”

Ashman and postdoctoral research associate Rachel Spigler worked with a wild strawberry species in which the evolution of separate sexes is not complete, so hermaphrodites exist among male and female plants. Sex chromosomes in these plants have two loci — or positions of genes on a chromosome — one that controls sterility and fertility in males and the other in females. Offspring that inherit both fertility versions are hermaphrodites capable of self-breeding. Plants that possess one fertility and one sterility version become either male or female. Those with both sterility versions cannot reproduce.

The single-sex plants breed not only with one another but also with hermaphroditic plants and pass on the mutation, which can result in single-sex offspring.

When inbreeding depression in hermaphrodites also is considered, Ashman said, a gradual decline in the number of hermaphroditic plants is to be expected. Consequently, fewer chromosomes with both fertility versions of the loci will be passed on and the frequency of single-sex individuals will increase.

The paper is available online at www.nature.com/hdy/journal/vaop/ncurrent/full/hdy2008100a.html.

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Research sheds light on galaxy’s shape

The bright pinwheels and broad star sweeps iconic of disk galaxies such as the Milky Way might all be the shrapnel from massive, violent collisions with other galaxies and galaxy-size chunks of dark matter, according to a multi-institutional project that includes a Pitt researcher.

Published in the Nov. 20 edition of The Astrophysical Journal, the findings challenge the longstanding theory that the bright extensions and rings surrounding galaxies are the remnants of smaller star clusters that struck a larger, primary galaxy then fragmented.

A team that included Andrew Zentner, Pitt professor of physics and astronomy, and researchers at the University of California-Irvine, Ohio State University, the University of Chicago and the NASA Jet Propulsion Laboratory at the California Institute of Technology, found that their computer simulations of galaxy formation suggest that disk galaxies most likely began as flat, centralized star clusters.

Smaller galaxies collided with and tore through these disks billions of years ago, casting disk stars outward into the wild extensions present now; the bright center is the original formation. In addition, vast bodies of dark matter — a low-density, high-gravity invisible mass thought to occupy nearly one-quarter of the universe — swept through these disks and further pulled stars from the main disk.

The researchers’ scenario largely applies to the formation of the rings and long flares of stars that surround such galaxies as the Milky Way, Zentner said. But the model also presents a possible solution to how star spirals — the arcs of stars that radiate from the center of some disk galaxies — maintain their shape. Spirals form as a result of any disturbance to the star disk, Zentner said. However, the prolonged disturbance of a galaxy and dark matter expanse passing through a disk explains why the spirals never seem to recede.

“Our model suggests that a violent collision throws stars everywhere and continues moving through the disk, disturbing its structure,” Zentner said. “It also has been known for some time that for star spirals to develop and maintain their well-known form, there must be a prolonged disturbance. We show that large masses moving through a galaxy could provide that disturbance.”

The team’s findings were serendipitous, Zentner explained. They were modeling disk galaxies for an unrelated astrological survey when they inadvertently discovered that stars in the main disk scattered when smaller galaxies passed through.

They shared their results with colleagues a year ago, and the results have since been replicated, Zentner said.

The paper is available on Pitt’s web site at www.pitt.edu/news2008/zentner_paper.pdf

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Test drug aids memory in schizophrenic patients

Pitt researchers have found an experimental agent that shows promise in addressing working memory impairments that occur in schizophrenia.

The results published in this month’s American Journal of Psychiatry break new ground in the strategy used to develop new drug treatments for schizophrenia, said lead author David Lewis, UPMC Endowed Chair in Translational Neuroscience in the departments of psychiatry and neuroscience at the School of Medicine.

“The drugs we use now to treat psychiatric disorders are based on serendipitous discoveries made several decades ago,” he said. “In contrast, in this study we have identified a faulty brain circuit in schizophrenia, found an agent with characteristics that affect a specific molecular target in that circuit and then tested it to see what happened.”

Earlier research indicated that a reduction of signaling by the neurotransmitter GABA in circuits in an area of the brain called the dorsolateral prefrontal cortex might be to blame for some of the cognitive problems in schizophrenia, Lewis said. To compensate for the lower levels of GABA, it appears that a biochemical feedback loop increases the number of a specific type of GABA receptor on neurons to capture more neurotransmitter. The study drug, MK-0777, binds to the alpha-2 subunit of the GABAA receptor and, when GABA is present, increases the flow of ions through the receptor, in essence turning up the volume on GABA signaling.

For the study, 15 men with schizophrenia were randomly assigned to take either MK-0777 or a placebo for four weeks. They underwent neuropsychological tests at baseline, two weeks and four weeks after starting the drug, as well as an electroencephalogram (EEG) assessment while doing a cognitive task.

The researchers found that the drug was well tolerated and that participants who took MK-0777 had improvements in both working memory (the ability to keep information in mind to guide behavior) and the EEG signal that accompanies working memory.

Still, because the study is small, more trials will have to be done to verify the value of the experimental compound, Lewis noted.

The study was funded by grants from Merck, the National Institute of Mental Health and the National Institutes of Health.

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