BIOCHEMICAL PATHWAY DETOXIFIES HEAVY METALS | FUEL CELL USING LIQUID DIESEL | GENE CARRIES MESSAGES FROM CIRCADIAN CLOCK | 'HEART SENSE' GAME PASSES EARLY TEST

Biochemical Pathway Detoxifies Heavy Metals

Biologists at Penn have discovered the first biochemical pathway in animals responsible for the detoxification of heavy metals such as arsenic, mercury and cadmium. They have established that the enzyme phytochelatin synthase, which had previously been found only in plants and some fungi, is also present in some animals.

The team led by Dr. Philip A. Rea, professor of biology, and including plant scientist Dr. Olena K. Vatamaniuk and animal cell and developmental biologists Dr. Elizabeth A. Bucher and Dr. James T. Ward made the discovery in work with the nematode worm Caenorhabditis elegans. They reported their results in the Journal of Biological Chemistry.

"Despite two decades of research into the biochemical basis of heavy metal detoxification in animals, never before had the involvement of phytochelatins been even cursorily mentioned or speculated," said Dr. Rea, a member of Penn's Plant Science Institute. "Discovery of this pathway in C. elegans establishes a firm basis for determining its ubiquity in other animals and for clarifying how animals eliminate, sequester and metabolize heavy metals."

Because preliminary work suggests that genes encoding PC synthase may also be found in parasitic invertebrates, the findings of Dr. Rea's group could help guard against growing resistance to certain heavy metal-based drugs. Diseases caused by these parasites, which include elephantitis and lymphatic filariasis, kill millions of people worldwide each year, but physicians have noted with some alarm that traditional treatments are waning in effectiveness.

C. elegans is the third organism in which a gene for PC synthase has been found, following the plant Arabidopsis thaliana and the yeast Schizosaccharomyces pombe. The three metals processed by PC synthase-arsenic, mercury and cadmium -all rank among the 10 most common contaminants at EPA Superfund sites, and increasing emissions pose an acute problem for all organisms. These metals harm organisms, including humans, by displacing essential heavy metals such as copper and zinc from their cellular binding sites, by undergoing aberrant reactions with proteins and enzymes, and by promoting the formation of destructive active oxygen species.

This work was funded by the National Science Foundation.

BIOCHEMICAL PATHWAY DETOXIFIES HEAVY METALS | FUEL CELL USING LIQUID DIESEL | GENE CARRIES MESSAGES FROM CIRCADIAN CLOCK | 'HEART SENSE' GAME PASSES EARLY TEST

Engineers Develop Fuel Cell Using Liquid Diesel

Chemical engineers at Penn have developed a prototype fuel cell that's the first to run on a readily available liquid fuel source, in this case ordinary diesel fuel. The work nudges fuel cells closer to viability, offering the promise of compact, portable power sources that offer much more bang for the buck than combustion engines or existing batteries.

Dr. Raymond J. Gorte, professor of chemical engineering, and colleague Dr. John M. Vohs, professor and chair of chemical engineering, shook the fuel cell world in March 2000 with the publication of a Nature paper in which they reported developing a fuel cell that could run on butane, the first fuel cell to operate on a fuel other than hydrogen. With the development of a fuel cell that runs directly on liquid diesel of the type sold at gas stations, the team has sidestepped the thorny problem of "reforming" fuels to hydrogen to run fuel cells.

"In our earlier work, we were unable to feed liquid diesel to the fuel cell because we did not have a means for vaporizing fuels that have a low vapor pressure at room temperature," Dr. Gorte said. "This paper demonstrated that we could feed these liquids to a fuel cell using a method analogous to a fuel injector in an internal combustion engine and still get stable operation of the fuel cell."

Smaller than a penny, the prototype fuel cell developed by Dr. Gorte, Dr. Vohs, graduate student Hyuk Kim and postdoctoral researcher Seungdoo Park, operates in a furnace set at 700 degrees Celsius. A commercial, self-contained fuel cell would ideally generate that heat itself using the fuel placed in it.

Although unlikely to replace household batteries for small appliances and portable electronics, researchers have suggested that fuel cells might be appropriate for powering cars and laptop computers. Fuel cells could also make possible electric generators that operate on propane or butane.

Dr. Gorte, Dr. Vohs, Mr. Kim and Dr. Park's work with solid oxide fuel cells was funded by the Office of Naval Research and published in the July issue of Journal of the Electrochemical Society.

BIOCHEMICAL PATHWAY DETOXIFIES HEAVY METALS | FUEL CELL USING LIQUID DIESEL | GENE CARRIES MESSAGES FROM CIRCADIAN CLOCK | 'HEART SENSE' GAME PASSES EARLY TEST

Gene Carries Messages From Circadian Clock

Scientists have long known that the gene Nf1 is so important to development that when it is missing the condition known as Neurofibromatosis results, causing tumors and sometimes leading to cancer before the patient reaches adulthood.

Now researchers have discovered that the Nf1 gene serves a second major purpose: It is also necessary for circadian rhythm. The body can't maintain its rest-activity cycle without it. "There have been a lot of anecdotal reports by physicians that many patients suffering from neurofibromatosis also suffer from sleep disturbances. But this is the first time someone has definitively linked Nf1 to the circadian system," said Dr. Julie Williams, first author of the study by scientists at Penn's School of Medicine. Their finding, was published September 21, in the journal Science, represents a major advance in understanding the body's complex circadian mechanism. It moves the research beyond the question of what constitutes our biological clock, and how it responds to light, to the more specific question: How does it actually regulate changes within the body? Dr. Williams and her colleagues found that in the absence of the Nf1 protein, the body is unable to keep time. Although their research relied on the Drosophila fly model, the Penn scientists were also able to establish that the signaling pathway triggered by Nf1 in the fly is directly analogous to the Nf1 pathway in mammals.

"Our work shows that when Nf1 affects circadian rhythm in flies, it uses the same mechanism that is present in humans, which is the Ras/Mapk pathway. This validates the fly as the model to study this illness," said Dr. Amita Sehgal, who directed the study.

"We've found that Nf1 affects the circadian rhythm of the ‘rest' phase in the cycle, but it doesn't affect the clock itself," said Dr. Sehgal. "The clock is keeping time-but it can't send the message affecting ‘rest' without NF1," Dr. Sehgal said.

The research was funded by the Howard Hughes Medical Institute, NIH, Neurofibromatosis Foundation, American Cancer Society, and U.S. Army Medical Research command.

Others who participated in this study are: Dr. Henry S. Su; Dr. Jeffrey Michael Field, both Penn scientists, and Dr. Andre Bernards, of Massachusetts General Hospital Cancer Center in Boston.

BIOCHEMICAL PATHWAY DETOXIFIES HEAVY METALS | FUEL CELL USING LIQUID DIESEL | GENE CARRIES MESSAGES FROM CIRCADIAN CLOCK | 'HEART SENSE' GAME PASSES EARLY TEST

'Heart-Sense' Game Passes Early Test

A computer game developed at Penn to encourage prompt medical attention in the wake of a heart attack appears to have passed its first test: a preliminary study has shown that the game rendered its players more likely to respond to symptoms by calling 911 or reporting to the emergency room in a timely manner.

Dr. Barry G. Silverman, the creator of the Heart-Sense game, reported the finding in the September issue of the INFORMS Journal of Health Care Management Science.

Players of the game, which can be used on most personal computers equipped with CD-ROMs, find themselves encouraging citizens of an imaginary village to seek medical treatment for their heart attack symptoms.

"It's believed that people learn best by teaching others," said Dr. Silverman, a professor of systems engineering in the schools of SEAS and Medicine and the Wharton School. "This study indicates that even the most rudimentary version of the Heart-Sense game improves the likelihood that patients will seek medical attention for symptoms of a haeat attack."

"Initial results show that users of the game exhibit a significant shift in intention to call 911 and avoid delay ... as well as a better understanding of both symptoms and of the need to manage time during a heart attack," wrote Dr. Silverman and co-authors Dr. Ransom Weaver of SEAS and Dr. John Holmes, Dr. Stephen Kimmel, Dr. Charles Branas and Dr. Doug Ivins of the Center for Clinical Epidemiology and Biostatistics at the School of Medicine.

Cardiology researchers have documented that inaction in the face of heart attacks is a serious problem, with different studies placing the average delay at anywhere from two to 12 hours. It has been estimated that 26 to 44 percent of the 1.25 million Americans who suffer heart attacks annually delay more than four hours in seeking care.

Dr. Silverman's team has been developing the game for roughly two years, funded by the National Heart Attack Alert Program of the National Institutes of Health and the National Library of Medicine.