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April 16, 2009


Shell patterns model neural function

Computer models that retrace how mollusks build dazzling shells illustrate how memory and sensory input influence action, researchers report in Proceedings of the National Academy of Sciences.

G. Bard Ermentrout, a University Professor of Mathematics, worked with the paper’s lead authors, Alistair Boettiger and George Oster of Berkeley, to model the neural network of mollusks and design a computer program that can generate the complex patterns and shapes of most mollusk shells.

The researchers traced the trail of brain activity that begins with a mollusk’s tongue-like organ called a mantle and leads to the cells that produce the shell and pigmentation.

The team supposed that as mollusks build their shells, they retrace their previous work with the mantle and use those “memories” to continue the pattern. At the same time, the new pigment and shell growth are influenced by external factors that result in the varied patterns and shell structures.

Boettiger, Ermentrout and Oster simulated the neural network with integral equations that retrace the previous pattern but can be manipulated to accurately predict how a shell will form under specific conditions. The resulting models help illustrate how neural networks — including mammalian cortices — function in response to a combination of sensory information and experience, the team reported in PNAS. The project was supported by the National Science Foundation.

“These models demonstrate the combined influence of sensory input and memories on brain activity,” Ermentrout said. “Brains convert sensory information into action. If a ball is thrown at you, you duck or catch it because you know that the ball could hit you. That knowledge and the sight of the ball coming at you dictate your action. A mollusk collects sensory information from its previous pigmentation and converts it into motor action by producing more pigmentation and continuing the pattern.”

To construct their model, the team studied electron microscope images of mollusk mantles to understand the neurons that connect the mantle’s sensing cells with the cells that secrete calcium carbonate and pigmented proteins. The team found that the excitatory and inhibitory synapses, which promote or diminish cell activity, surrounding the secretory cells and the cells’ firing thresholds act as a neural network that determines how much calcium and pigment the mollusk secretes. Different rates of calcium carbonate secretion determine the shape of the shell, while different amounts of pigment result in a pattern unique to each species.

For instance, shell ridges result from one cell increasing calcium carbonate secretion while depressing secretion from surrounding cells. With striped shells, a pigment-secreting cell inhibits secretion of pigment by neighboring cells but not itself, so that the same pattern is repeated day after day, yielding a stripe. Bands parallel to the growing edge form when pigment secreted one day inhibits secreting cells for a few days, resulting in an on/off pattern.

“Traveling wave” patterns of diamonds, zigzags, arrowheads and other shapes come about when a pigment inhibits future secretion at that site but excites secretion in surrounding cells, so that pigment moves laterally on successive days like a wave.

The paper can be found at

Video and photos of the shell simulations are available at


Corneas cleared by stem cell therapy 

Stem cells collected from human corneas restore transparency and don’t trigger a rejection response when injected into eyes that are scarred and hazy, School of Medicine researchers report in the journal Stem Cells. The findings, based on experiments conducted in mice, suggest that cell-based therapies might be an effective way to treat human corneal blindness and vision impairment due to the scarring that occurs after infection, trauma and other eye problems, said ophthalmology professor James L. Funderburgh, senior investigator of the study.

“Our experiments indicate that after stem cell treatment, mouse eyes that initially had corneal defects looked no different than mouse eyes that had never been damaged,” Funderburgh said.

The ability to grow millions of the cells in the lab could make it possible to create an off-the-shelf product.

“Corneal scars are permanent, so the best available solution is corneal transplant,” Funderburgh said. However, the popularity of LASIK eye surgery is expected to reduce the availability of donor tissue because the procedure makes it unsuitable for transplantation.

Funderburgh and other Pitt researchers previously identified stem cells in a layer of the cornea called the stroma, and recently showed that even after many rounds of expansion in the lab, these cells continued to produce the biochemical components, or matrix, of the cornea. One such protein is called lumican, which plays a critical role in giving the cornea the correct structure to make it transparent.

Mice that lack the ability to produce lumican develop opaque areas of their corneas comparable to the scar tissue that human eyes form in response to trauma and inflammation, Funderburgh said. But three months after the lumican-deficient mouse eyes were injected with human adult corneal stem cells, transparency was restored. 

The cornea and its stromal stem cells themselves appear to be “immune privileged,” meaning they don’t trigger a significant immune response even when transplanted across species.

The researchers intend to use the stem cells to treat lab animals that have corneal scars to see if they, too, can be repaired with stem cells. Under the auspices of UPMC Eye Center’s recently established Center for Vision Restoration, researchers also plan to develop the necessary protocols to enable clinical testing of the cells.

Other Pitt authors were Yiqin Du and Martha L. Funderburgh of ophthalmology.  

The research was supported by the National Institutes of Health, the Eye and Ear Foundation and Research to Prevent Blindness.


Gotta dance? UPB research examines why

Why do people dance? Pitt-Bradford sociology professor Helene Lawson, who took up tap dancing five years ago, interviewed 75 adult dance students to discover their motivations. The results are published in the winter 2008/2009 edition of Music and Arts in Action, published by the University of Exeter.

She discovered that the reasons could be grouped into six categories: keeping fit; seeking stability; seeking a sense of community; seeking to capture life; seeking to free one’s spirit, or seeking a new identity.   

According to Lawson, “Re-examining the dancers’ motivations, I see that they experience a documented exhilaration from dancing together and especially from public performance as a troupe.”

In addition to addressing why people dance in her paper, “Why Dance? The Motivations of an Unlikely Group of Dancers,” Lawson also writes about how dancers are affected by recitals, which she said are emotional roller coasters, and why some of them eventually dropped out of class despite the benefits they originally claimed to receive from dancing.


Angiography aids cardiac patient survival 

People who suffer cardiac arrests and then receive coronary angiography are twice as likely to survive without significant brain damage than those who don’t have the procedure, according to a study by School of Medicine researchers.

The study, published in the May/June issue of the Journal of Intensive Care Medicine, showed that patient outcomes improved with coronary angiography, regardless of certain clinical and demographic factors that influenced who received the procedure.  

Jon C. Rittenberger, corresponding author of the study and professor of emergency medicine, said, “Given the low odds of survival — about 6 percent — for patients who suffer out-of-hospital cardiac arrests, it’s important to understand which treatments might make a difference in these dismal outcomes.” The importance of prompt coronary angiography is well established for cardiac arrest patients with certain types of heart problems. “But our study, which shows that angiography is independently associated with good neurologic outcomes, suggests that clinicians should consider the procedure for all post-cardiac arrest patients.”  

Coronary angiography uses a contrast dye and X-rays to see the blood vessels and chambers of the heart. The procedure is usually done in conjunction with catheterization. Dye is injected into the catheter to highlight any blockages in blood flow, which are visible by X-ray.

The researchers analyzed the charts of 241 adult cardiac arrest patients. Just over half of patients who received coronary angiography had a good clinical outcome — defined as being discharged to home or to an acute rehabilitation facility — compared to 24.8 percent of patients who did not have the procedure.

Early angiography, performed within 24 hours of a patient’s arrival, was not associated with improved survival when compared to having the procedure done later, but researchers noted that the small number of patients might have made it impossible to prove a difference.

“Coronary angiography appears to put patients on a more proactive path of care, which may lead to a better outcome,” said Rittenberger.

Researchers found no significant differences between those who received angiography and those who did not with respect to age, history of cardiac disease and use of therapeutic hypothermia, a procedure used to prevent brain damage in patients who remain comatose after resuscitation following cardiac arrest. However, patient sex, location of the arrest, the initial heart rhythm disturbance and certain coronary and neurologic abnormalities were among the predictors of who would receive angiography.

Men who suffered cardiac arrests outside of the hospital were more likely to have the procedure. The researchers also found that coronary angiography was more likely to be performed on patients with better neurological status. However, with the use of therapeutic hypothermia, patients may not reveal their true neurological state for several days after the return of spontaneous blood circulation, they noted.

Other Pitt authors were Clifton W. Callaway, emergency medicine; Samar R. El Khoudary, epidemiology; Charity G. Moore and Rene J. Alvarez, medicine, and Joshua C. Reynolds, now at the University of Maryland.

Rittenberger is supported by the National Center for Research Resources and the National Association of EMS Physicians/Zoll EMS Resuscitation Research Fellowship.


Genetic variation linked to lung development

Mutations in a gene may cause poor lung development in children, making them more vulnerable to diseases such as chronic obstructive pulmonary disease (COPD) later in life, say researchers at the Graduate School of Public Health and the German Research Center for Environmental Health. Their study, published online in Physiological Genomics, measured expression levels of the superoxide dismutase 3 (SOD3) gene and its variants in both mouse lungs and children ages 9-11. 

SOD3 has been shown to protect lungs from the effects of asbestos and oxidative stress. 

Study author George Leikauf, professor of occupational and environmental health at GSPH, said, “People lose lung function as they age, so it’s important to identify possible genetic targets that control healthy development of the lungs during childhood.” 

The researchers compared SOD3 expression levels in strains of mice with poor lung function to a strain of mice with more efficient airways and lungs two times the size. As with people, the lungs of mice fully form as they mature to adulthood.

The better-functioning mice maintained levels of SOD3 four times higher at the final stage of lung development. The presence of single nucleotide polymorphisms (variations in DNA sequences) in SOD3 was linked to lung function in mice. 

After analyzing DNA from 1,555 German children who were part of the International Study of Asthma and Allergy in Children, researchers discovered two common single nucleotide polymorphisms associated with poorer lung function. One of these likely alters the expression levels of SOD3.  

Previously, genetic variants in SOD3 have been associated with loss of lung function in COPD, which is mainly caused by cigarette smoking. “We know SOD3 protects the lung against injury caused by chemicals in cigarette smoke, and it could be a link between childhood exposure to environmental tobacco smoke and poor lung development,” said Leikauf. In the future it might be possible to identify at-risk children and to develop a medication that would foster optimal lung development, he added.

The researchers also are exploring sex differences in SOD3 gene expression and lung development; girls appear to be at greater risk than boys.

The study was funded by NIH and the German Research Center for Environmental Health.

Other Pitt authors were Kifai Bein, Cheryl Fattman and Fei Gao of environmental and occupational health and Tim D. Oury of pathology. The study can be viewed at


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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