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University of Pittsburgh

January 22, 2009

RESEARCH NOTES

Evolution of motor cortex area shown

An area of the cerebral cortex has evolved to enable humans and higher primates to pick up small objects and deftly use tools, according to neuroscientists at the School of Medicine and Pittsburgh’s Veterans Affairs Medical Center. The findings have been published in the early online edition of the Proceedings of the National Academy of Sciences.

The brain’s primary motor cortex turns out to have neighboring “old” and “new” parts. In most animals, including cats, rats and some monkeys, the old primary motor cortex controls movement indirectly through the circuitry of the spinal cord, explained senior author Peter Strick, professor in the Department of Neurobiology at the School of Medicine and senior career scientist at the VA Medical Center.

But in humans, the great apes and some monkeys, another area of the motor cortex developed and is now home to a special set of cortico-motoneuronal (CM) cells, he said. These cells directly control spinal cord motor neurons, which are the nerve cells responsible for causing contraction of shoulder, elbow and finger muscles. The direct control exerted by CM cells bypasses the limitations imposed by spinal cord circuitry and permits the development of highly complex patterns of movement, such as the independent finger action needed for playing an instrument or typing.

“What we’ve shown is that along with evolution of direct control over motor neurons, a new cortical area has evolved that’s right next to the old one,” Strick said. “We still have much the same spinal machinery the frog has, but the new cortical area with CM cells endows humans with the superior hand skills to manufacture and use tools — an especially human trait.”

Strick noted that the direct connection from the cortex to motor neurons is not present at birth, but develops during the first few months of life and becomes fully mature around two years of age. Thus, the progress of an infant’s motor skills is a display of the establishment of these connections.

Strick and co-author Jean-Alban Rathelot, a research associate in his lab, based their conclusions on a series of experiments in which rabies virus was injected into single muscles in the shoulders, elbows or fingers of monkeys. The virus, chosen because of its unique ability to travel between networked nerve cells, was tracked to locate CM cells in the primary motor cortex.

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Swahili book project funded

Pitt-Titusville faculty member Linda Winkler has been awarded a Hewlett International Grant for her project, “Developing a Children’s Book on Rumanika, Last Chief of Karagwe Chiefdom in Tanzania.”

This book is part of an ongoing project that has resulted in several children’s books in Swahili.

The books are used in Tanzanian schools in the area where Winkler has led the Pitt in Tanzania study-abroad program.

Winkler has collaborated with New York City-based artist Katie Moran on the last three books.

The new book on Rumanika will tell the story of the last in a long line of powerful chiefs. Rumanika is said to have had supernatural powers, including the ability to produce rain.

As with the previous books, this book will be published in Swahili and provided free of charge to schools in Tanzania.

Winkler is professor of anthropology and biology and vice president for academic affairs at UPT.

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ULS partners to preserve mining maps

The University Library System (ULS) has received a public/private pledge of $200,000 to catalogue and preserve a collection of local, historical coal maps for widespread public use. The project brings together professionals from academic, state and federal arenas specializing in conservation, preservation, environmental protection, mining, digitization and geographic information systems.

The commitment represents a joint partnership in not only funding, but in work efforts between CONSOL Energy, the Pennsylvania Department of Environmental Protection (DEP) and the U.S. Department of the Interior Office of Surface Mining (OSM).

CONSOL Energy has pledged a total of $100,000 to be paid over five years, while DEP contributed $25,000 and OSM contributed $75,000. This collaboration endeavors to assemble information about the maps of underground coal mines in the state, build on the web-based database for maps and map location information, digitize vital maps and preserve the original work. The project has implications for mine safety, mining operations, land reclamation, new development and research.

Rush Miller, Hillman University Librarian and director of ULS, stated, “That the Department of Environmental Protection, the Office of Surface Mining and CONSOL Energy have joined forces to support this project is clear recognition of just how important this project is. Our mining maps cover an enormous region in southwestern Pennsylvania, including the heavily urban areas as well as rural communities. Together, we will work in collaborative ways to ensure that our collection is accessible to all.”

In 2000, CONSOL Energy provided ULS with its substantial holdings of mine maps dating to as early as the 1850s as well as coal mine artifacts and other historical items.

Many of the hardback maps are in need of conservation repair in order to facilitate the evaluation and cataloguing process as well as the work of the state DEP in scanning the hardback maps that are part of this collection.

Enhancing access is among the primary goals of the project, which involves processing and generating an inventory of the collection to create an encoded archival description finding aid.

In addition, the University, DEP, OSM and CONSOL Energy are collaborating to catalogue and accurately describe this collection and input the inventory into the DEP’s Pennsylvania Historical Underground Mine Maps Inventory System (PHUMMIS), which eventually will provide the enhanced public access through both PHUMMIS and the Pennsylvania Spatial Data Access system.

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Vaccine cuts spread of meningitis

A standard pediatric vaccine used to prevent several common types of life-threatening infections also effectively reduced the rates of another disease, pneumococcal meningitis, in children and adults, according to a multi-center study led by Pitt’s School of Medicine. The study, published in the Jan. 15 issue of the New England Journal of Medicine and based on a detailed review of pneumococcal meningitis cases, also noted an increase in strains of pneumococcal meningitis not covered by the vaccine and those resistant to antibiotics.

After reviewing 1,379 cases of pneumococcal meningitis from 1998 through 2005, study authors found rates of the disease decreased in children and adults after the introduction of pediatric pneumococcal conjugate vaccine (PCV7) in 2000. PCV7 protects against seven of the most common pneumococcal types, which account for more than 80 percent of pneumococcal disease in young children. PCV7 is not administered to adults. 

According to the study, incidence rates for pneumococcal meningitis in all age groups declined 30.1 percent from 1998-1999 to 2004-2005. After PCV7 was made available, the incidence of meningitis decreased by 64 percent in children and by 54 percent in older adults.

Lee Harrison, professor of medicine and senior author of the study, explained: “When you immunize children, they are much less likely to carry pneumococcal strains covered by the vaccine in the back of the throat. When vaccinated children don’t carry these virulent strains, they don’t end up transmitting them to other children, their parents and grandparents.”

Prior to the study, conflicting data existed on the vaccine’s effect on the incidence of meningitis in adults, he said.

The authors also observed that non-PCV7 strains increased by 60.5 percent from 1998-99 to 2004-05, and the percentage of strains that were not sensitive to penicillin, which initially declined, increased from 19.4 percent in 2003 to 30.1 percent in 2005.   

“PCV7 has been highly successful in preventing pneumococcal meningitis, but it remains a very serious and deadly disease,” said Harrison. “Of the patients in our study, 8 percent of children and 22 percent of adults died. These findings indicate the need to continue to explore new methods of prevention with a special emphasis on strains that are not covered by PCV7 and strains that are drug resistant. Next-generation vaccines are in development and patients and physicians need to avoid unnecessary use of antibiotics.”

Other Pitt co-authors were graduate epidemiology student Heather Hsu and Kathleen Shutt, a research associate in the Department of Medicine.

The study was funded by the Centers for Disease Control and Prevention (CDC) and the National Institute of Allergy and Infectious Diseases and conducted at eight active bacterial core surveillance sites throughout the United States. ABCs are a component of the CDC-funded emerging infections program network.

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Pancreatic beta cells replicated

School of Medicine researchers have induced human insulin-producing cells, known as beta cells, to replicate robustly in a living animal as well as in the lab. The discovery not only could improve models and methods for studying diabetes, but also opens up new possibilities for treating the condition.

“Most scientists thought that these important pancreatic cells could not be induced to regenerate, or could only replicate very slowly,” said senior author Andrew F. Stewart, professor of medicine and chief of the medical school’s Division of Endocrinology and Metabolism. “This work provides proof-of-principle that the production of human beta cells can be stimulated, and that the newly generated cells function effectively both in the lab and in a living animal.”

The findings are in the early online version of Diabetes, one of the journals of the American Diabetes Association.

Lead authors Nathalie Fiaschi-Taesch, of the endocrinology division, and Todd A. Bigatel, a graduate of the postdoctoral fellowship program, identified molecules that play key roles in human beta, or islet, cell replication, building on previous work conducted by co-author Irene Cozar-Castellano, also an instructor of endocrinology, who performed similar studies using mouse cells.

They found that, unlike rodents, human beta cells contain a significant amount of a protein called cdk-6. When cdk-6 production was increased using a viral vector carrying the cdk-6 gene, the cells replicated. Stimulation was enhanced further by increasing production of another cell cycle molecule called cyclin D1. Untreated human islets did not replicate.

“After we transplanted some of these engineered human beta cells under the outer layer of a kidney in a diabetic mouse, we saw that replication continued and blood sugar levels normalized,” explained Fiaschi-Taesch. “When we took out the kidney that contained the insulin-producing cells, the mouse immediately developed diabetes again.”

The team’s work was funded by grants from the National Institutes of Health, the American Diabetes Association and the Juvenile Diabetes Research Foundation.

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Mindset impacts senior mileage

A study on the impact of psychological and physiological factors (such as gait speed, fall history and balance performance) on walking activity in older adults has found that senior citizens who perceive their overall health and balance to be good walk farther than those with negative perceptions of those factors.

The research by faculty members Jaime B. Talkowski and Jennifer S. Brach of the Department of Physical Therapy; Stephanie Studenski, professor in the Department of Medicine’s Division of Geriatric Medicine, and Anne B. Newman, professor in the Department of Epidemiology, appeared in the December issue of the journal Physical Therapy, available at www.ptjournal.org.

The study evaluated 2,269 older adults. After controlling for demographics, cognition and health status, the researchers found that health and balance perception and gait speed were associated with more walking, whereas fall history and balance performance were not.

“Specifically, a good perception for health and balance and walking at a near-normal gait speed were associated with more walking activity,” the researchers reported.

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