University Times

Pollinator shortage could imperil some species

In biodiversity hot spots like tropical rainforests, a dearth of pollinators could be putting many species at risk of extinction, according to a new study that includes three Pitt researchers. The finding is raising concerns that more may need to be done to protect the Earth’s most biologically rich areas.

The study, “Pollination Decays in Biodiversity Hotspots,” appeared in the Jan. 16 issue of the journal Proceedings of the National Academy of Sciences.

As the number of birds, bees and other pollen transporters declines around the world, competition for their attention is becoming increasingly fierce for plants that need their services for reproduction — to the point where species in the most fertile areas of the world are struggling for survival.

“Pollinators are on the decline globally because of habitat loss and destruction, pesticide use, invasive species and extinction of vertebrates,” said Tia-Lynn Ashman, associate professor of biological sciences at Pitt, who was involved in the study along with former Pitt biology graduate students Janette A. Steets, now of the University of Alaska-Fairbanks, and Tiffany Knight, now of Washington University in St. Louis, and colleagues at other institutions.

The researchers reviewed more than 1,000 pollen limitation studies from around the world and found that, in areas where there is a great deal of plant diversity, including South American and Southeast Asian jungles and the rich shrubland of South Africa, plants suffer lower pollination and reproductive success. For some plant species, this reduction in fruit and seed production could push them toward extinction.

“Wild plant species in biodiversity hotspots are an important world resource for the ecosystem services they provide, including medicine, food, nutrient cycling and alternative resources for pollinators of domesticated crops,” Ashman said.

Further research will be done to determine what causes pollen limitation worldwide. When many species exist in the same place, plants become more separated from other individuals of the same species, causing pollinators to fly long distances to deliver pollen. When pollinators do arrive, they may deliver unusable pollen from other plant species.

This research was supported by the National Science Foundation’s National Center for Ecological Analysis and Synthesis.

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Dots pave way for quantum computer development

Pitt researchers have developed a way to create semiconductor islands smaller than 10 nanometers in scale, known as quantum dots. The islands, made from germanium and placed on the surface of silicon with two-nanometer precision, are capable of confining single electrons.

“We believe this development moves us closer to our goal of constructing a quantum computer,” said Jeremy Levy, professor of physics and astronomy and director of the Center for Oxide-Semiconductor Materials for Quantum Computation. Levy and colleagues reported on the work in the journal Applied Physics Letters.

The next step, said Levy, is to perform electronic and optical measurements to prove that there is indeed one electron on each quantum dot and to probe the coupling between the spins of neighbor electrons. “We can do that now because we have this control over the spacing and the size,” he said.

The results achieved by Levy and colleagues are an example of “essentially nano” research, which involves manipulating properties at the smallest scales — from one to 20 nanometers.

Quantum computers do not yet exist, but it is known that they would bypass all known encryption schemes used today on the Internet. Quantum computers also would be capable of efficiently solving the most important equation in quantum physics: the Schrödinger equation, which describes the time-dependence of quantum mechanical systems. Hence, if quantum computers can be built, they likely will have as large an impact on technology as the transistor.

Other Pitt researchers who worked on the study were John T. Yates Jr., R.K. Mellon Professor of Chemistry and Physics, and former chemistry graduate student Olivier Guise.

This research was supported by the Defense Advanced Research Projects Agency’s Quantum Information Science and Technology Program.

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Wireless VNS device may fight seizures depression

Pitt researchers, with the help of a team of Pittsburgh high school science teachers, have developed a wireless device that is implanted in the neck to fight depression and epileptic seizures. The U.S. Food and Drug Administration already has approved a wired version of the device, but that one carries risks and several undesirable side effects.

It has been known for several years that stimulating the vagus nerve, which connects the brain to several major organs, can offset drug-resistant epileptic seizures. Last summer, the FDA approved vagus nerve stimulation (VNS) to treat severe depression as well.

VNS has few of the side effects of traditional treatments for depression: no sexual dysfunction or memory impairment and minimal sleep disturbance and weight gain, which are often associated with antidepressants or shock therapy. However, there is a risk of infection due to the surgical incisions, and the long wire lead may cause painful adhesions and restricted movement.

Additionally, side effects include hoarseness, shortness of breath and voice alteration, although these are alleviated when the device is turned off.

Patients who use the wired VNS device have a pulse generator surgically implanted into the left side of the chest with a wire extending from the device up through the left side of the neck to wrap around the nerve. Patients must undergo additional surgery to change the battery every three to eight years. The device can be turned off at any time with a magnetic wand.

Last summer, eight teachers from City of Pittsburgh high schools came to Pitt under a National Science Foundation-funded program in which they divided their time between Pitt’s Learning Research and Development Center and a research project of their choosing. Four of the teachers chose to work on a device to prevent seizures under the guidance of Marlin Mickle, Nickolas A. DeCecco Professor of Electrical and Computer Engineering, director of the University’s Radio Frequency Identification Center for Excellence and of the John A. Swanson Institute for Technical Excellence; Michael Lovell, associate professor of industrial and mechanical engineering and associate dean for research in the School of Engineering; Robert Sclabassi, professor of neurological surgery, neuroscience, psychiatry, electrical and mechanical engineering, and bioengineering and director of UPMC’s Center for Clinical Neurophysiology, and electrical engineering graduate student Steven Hackworth.

The group hoped to treat seizures by modifying a method for deep-brain stimulation (DBS), which Mickle, Lovell and Hackworth had developed, that uses radio frequency technology to help treat diseases such as Parkinson’s. The major technical challenge they had to overcome was to convert the voltage source required for DBS to the current source required for the seizure treatment.

The solution they developed is the Radio Frequency-powered Neural Stimulator (RFNS).

The RFNS is made up of a receiving device implanted under the skin of the neck and a powering device placed near the skin at the same site, under a collar. Because this requires only one surgical incision, rather than the two required by VNS, the risk of infection is reduced. Other advantages of RFNS over the existing VNS system include no invasive tunneling from the shoulder to the neck region and an external battery, which reduces the need for subsequent surgeries and further lowers the risk of infection.

The next step for the researchers is to license the technology to a company, which then would need FDA approval.

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Carbon monoxide protects transplanted kidneys in rats

Carbon monoxide (CO), a highly toxic gas often called the “silent killer,” may prove useful for extending the life of transplanted organs, suggests a Pitt study that found prolonged, low-dose exposure to be protective against chronic rejection in a rat kidney transplant model. Chronic rejection is the primary reason that patients require second or third transplant operations.

In the study, to be published in an upcoming issue of the American Journal of Physiology-Renal Physiology and now available on line, the researchers report minimal signs of inflammation and tissue damage indicative of chronic rejection following kidney transplantation in rats housed for 30 days in cages with air consisting of 20 parts per million of CO. In contrast, the kidneys transplanted into rats maintained in normal air conditions began to deteriorate almost immediately, and microscopic examination revealed progressive rejection. Both groups were given a six-day course of the anti-rejection drug tacrolimus.

Although CO is toxic at high concentrations, at low concentrations it appears to function as a signaling molecule that protects cells against bombardment by the inflammatory immune response, said senior author Noriko Murase, associate professor of surgery at the Thomas E. Starzl Transplantation Institute at the Pitt School of Medicine. The idea to study the effects of carbon monoxide in the transplant setting came from co-author Augustine Choi, professor of medicine and chief of the Division of Pulmonary, Allergy and Critical Care Medicine, an expert on the effects of carbon monoxide.

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Predicting heart disease risk improved by measuring more inflammatory markers

Measuring levels of several inflammatory markers rather than a single marker can improve assessment of cardiovascular disease (CVD) risk substantially, according to a study published in the American Heart Journal.

Current medical guidelines recommend measuring a particular inflammatory marker, called C-reactive protein, along with cholesterol levels, for assessing CVD risk. In this study, researchers from the UPMC Cardiovascular Institute and the Graduate School of Public Health (GSPH) analyzed blood samples taken from 580 women ages 31 to 85 looking for multiple inflammatory markers.

The investigators also performed coronary angiographies to detect any blockage of blood vessels in the heart and then followed the women for an average of almost five years. Of interest to the researchers was whether the women experienced any heart attacks (both nonfatal and fatal), strokes, or episodes of congestive heart failure.

Women with significantly elevated levels of at least two of three markers (interleukin-6, serum amyloid A, and C-reactive protein) had a risk of dying that was more than four times greater than women who had no elevated markers. Kevin E. Kip, GSPH assistant professor of epidemiology, said this was a higher risk indicator than any single marker alone, all of which were roughly equally predictive.

The authors, which also included researchers from the American Cardiovascular Research Institute, the University of Florida College of Medicine and Cedars-Sinai Medical Center, suggest the negative effects of inflammation on CVD may be due largely to other mechanisms than the most widely accepted theory of the effects of inflammation on CVD — promoting the buildup of plaques in the inner linings of arteries. Rather, they said inflammation might lead to the destabilization of vulnerable plaques.

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Many diabetics, African Americans, not using aspirin to avoid heart disease

In recent years, regular aspirin use by older adults to prevent heart disease has increased, particularly among those at high risk, according to a recent study conducted by researchers at the Graduate School of Public Health (GSPH) and others. However, the study, published in the November issue of the American Journal of Medicine, found that African Americans and diabetics — two groups that could benefit most from preventive aspirin therapy — are under-represented in this trend.

The Pitt investigators, along with collaborators from medical centers around the U.S. and in Europe, measured regular aspirin use among 2,163 African-American and Caucasian older adults without cardiovascular disease in the late 1990s and again between 2002 and 2003. They also determined 10-year heart disease risk scores for all participants.

During 1997 and 1998, 17 percent of the participants were regular aspirin users. Aspirin use increased with their risk of heart disease, from 13 percent in those with a 10-year low-risk profile to 23 percent in those with a 10-year high-risk profile. However, blacks were less likely to use aspirin (13 percent) than whites (20 percent). Between 1997-1998 and 2002-2003, aspirin use almost doubled (from 17 percent to 32 percent) among those still free of coronary heart disease. However, despite their particularly high heart disease risk, diabetics were not more likely to use aspirin than non-diabetic individuals, even in 2002-2003.

According to lead author Anne B. Newman, professor of epidemiology and medicine, aspirin therapy should be better targeted to high-risk individuals. This would decrease the incidence of side effects of aspirin therapy such as gastrointestinal bleeding and hemorrhagic stroke among those who are at low risk for heart disease.

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Mind over bladder

Millions of people have the sudden urge to urinate, often at the most inconvenient times — a condition called overactive bladder. Although little is known about the causes of overactive bladder in otherwise healthy people, new research reported in a recent issue of the Journal of Urology and at a recent meeting of the International Continence Society suggests part of the answer can be found in a certain area of the brain.

Using functional magnetic resonance imaging, or fMRI technology, Pitt researchers scanned the brains of six people with good bladder control and six people with poor bladder control while filling and withdrawing liquid from their bladders.

Those with good bladder control had increased activity in the orbitofrontal cortex, a region of the brain associated with deciding between alternative courses of action. In contrast, fMRI showed that those with poor bladder control had little activity in this part of the brain, even when their bladders were full. Instead, other parts of their brains were activated.

Lead author Derek Griffiths, professor of geriatric medicine in the School of Medicine, said the finding is consistent with clinical observations that stroke and other types of injury to the orbitofrontal cortex can cause bladder problems.

This study suggests that treatment strategies for overactive bladder should target the brain rather than the bladder, Griffiths said.

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NFL players recover faster than high schoolers from concussions

National Football League (NFL) players showed more rapid recovery from concussions than high school football players in a research study undertaken by the NFL’s Committee on Mild Traumatic Brain Injury (MTBI), the results of which appear in the February issue of the scientific journal Neurosurgery.

The study is the first to provide a direct comparison of neurocognitive recovery in professional and younger athletes, within days of concussion occurrence, by using a computerized neurocognitive testing tool, ImPACT (Immediate Post-Concussion Assessment and Cognitive Testing).

As a group, NFL players returned to pre-injury baseline neurocognitive performance in one week, with the majority of athletes having normal performance two days after injury. By comparison, the high school athletes demonstrated a slower injury recovery and longer lasting neuropsychological effects from concussions than the NFL athletes, according to study principal investigator Elliott Pellman, chairman of the NFL MTBI committee. “The most dramatic difference was evident on tests measuring reaction time and speed: NFL athletes demonstrated rapid return to expected normal levels of functioning while the high school group lagged behind,” said Pellman.

“This project is an example of how research at the NFL level is providing valuable information to help improve injury management at all levels of competition as well as directly contributing to the care of the NFL athlete,” he said.

“Results of this study support previously published findings that indicate that NFL athletes recover quickly. We evaluated the athletes by using formal tests of reaction time, concentration and memory,” said Mark Lovell, director of neuropsychological testing for the NFL and director of the UPMC Sports Medicine concussion program.

“These current findings also underscore the critical need for careful evaluation and management of concussions in younger athletes and caution in not allowing a concussed young athlete to return to play until they have recovered,” Lovell said.

The potential reasons for the difference between professional and high school athletes, the authors suggest, include neuro-developmental factors that may put children at greater risk and different tolerance levels between the two groups. Also, NFL players are a highly select population of elite, conditioned and skilled athletes who may be less prone to injury than less athletically conditioned and skilled amateur athletes.

The study was funded by NFL Charities.

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Nanotube channels can detect DNA mutations

Pitt assistant professor of chemistry Alexander Star and colleagues at a California-based company, Nanomix, Inc., have developed devices made of carbon nanotubes that can find mutations in genes causing hereditary diseases, they report in the Jan. 16 issue of the journal Proceedings of the National Academy of Science. This method is less expensive and takes less time than conventional techniques.

Carbon nanotubes are rolled-up sheets of graphite only a few nanometers wide — about the width of a molecule of DNA. The researchers used these nanotubes’ electrical properties to find a particular mutation in the gene that causes hereditary hemochromatosis, a disease in which too much iron accumulates in body tissues.

“The size compatibility between the detector and the detected species — DNA molecules in this case — makes this approach very attractive for further development of label-free electronic methods,” said Star.

Star and his colleagues at Nanomix also tested fluorescently labeled DNA molecules in order to confirm that DNA had attached to the nanotube surfaces and subsequently was hybridized, or matched to its complementary DNA.

“We have found that electrical measurement of carbon nanotube devices produces sensor results that are comparable to state-of-the-art optical techniques,” Star said. “The applications of our method for detection of other, more serious genetic diseases can be seen.”

Label-free electronic detection of DNA has several advantages over state-of-the-art optical techniques, including cost, time and simplicity. “Our technology can bring to market hand-held, field-ready devices for genetic screening, as opposed to laboratory methods using labor-intense labeling and sophisticated optical equipment,” Star said.

This research was supported in part by the National Science Foundation’s small business innovation research program.

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Cell research boosts Schwartz’s theory of evolution

An article by Pitt professor of anthropology Jeffrey H. Schwartz and University of Salerno professor of biochemistry Bruno Maresca, published Jan. 30 in the New Anatomist journal, shows that the emerging understanding of cell structure lends strong support to Schwartz’s theory of evolution, originally explained in his 2000 work, “Sudden Origins: Fossils, Genes, and the Emergence of Species.”

In that book, Schwartz refers to earlier theories that suggest that the Darwinian model of evolution as a continual and gradual adaptation to the environment glosses over gaps in the fossil record by assuming the intervening fossils simply have not been found yet. Schwartz argues the fossils don’t exist, since evolution is not necessarily gradual, but often sudden, dramatic expressions of change on the cellular level caused by radical environmental stressors such as extreme heat, cold or crowding years earlier.

Schwartz and Maresca say the mechanism for change operates when environmental upheaval causes genes to mutate. Those altered genes remain in a recessive state, spreading silently through the population until offspring appear with two copies of the new mutation and change suddenly. Those changes may be significant and beneficial (like teeth or limbs) or, more likely, deadly to the organism.

Why does it take an environmental drama to cause mutations? Why don’t cells subtly and constantly change in small ways over time, as Darwin suggests?

Schwartz and Maresca explain that cells in their ordinary states have suites of molecules — various kinds of proteins — whose jobs are to eliminate errors that could derail the functioning of their cell. For instance, some proteins work to keep the cell membrane intact. Other proteins bring molecules to their proper locations in the cell, and so on. With that kind of protection from change, it is very difficult for mutations to gain a foothold. But extreme stress pushes cells beyond their capacity to produce protective proteins, and then mutation can occur.

This idea has enormous implications for the notion that organisms routinely change to adapt to the environment. Schwartz argues that it is the environment that knocks them off their equilibrium and as likely ultimately kills them as changes them. And so, they are not adapting to the environment; they are being rocked by it.

The article’s conclusions also have important implications for the notion of “fixing” the environment to protect endangered species. While it is indeed the environment causing the mutation, the resulting organism is in an altogether different environment by the time the novelty finally escapes its recessive state and expresses itself.

“You just can’t do a quick fix on the environment to prevent extinction because the cause of the mutation occurred some time in the past, and you don’t know what the cause of the stress was at that time,” Schwartz said.

“This new understanding of how organisms change provides us with an opportunity to forestall the damage we might cause by unthinking disruption of the environment,” said Schwartz. “The Sudden Origins theory, buttressed by modern cell biology, underscores the need to preserve the environment — not only to enhance life today, but to protect life generations from now.”

Schwartz, who also is a professor of the history and philosophy of science, has been named a fellow in both Pitt’s Center for the Philosophy of Science and the World Academy of Arts and Science.

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Research will help improve mobility in older adults

The inability to get around as well as they once did is a serious problem for many older adults. It can inhibit daily activities, contribute to injuries and ultimately result in the loss of their independence. Jennifer Brach, assistant professor of physical therapy in the School of Health and Rehabilitation Sciences, is hoping to prevent these outcomes by finding ways to test and rehabilitate elderly patients who show the earliest signs of mobility impairment.

Brach has been given a Paul Beeson Career Development Award by the National Institute on Aging and the American Federation for Aging Research to study variations in stride, pace and other mechanisms of walking in older adults.

Minor changes in gait can foretell a bigger problem, such as an increased risk of falling, so Brach will work to identify methods for detecting such changes as well as interventions that may prevent further deterioration or even reverse existing mobility problems.

Brach is one of only 11 researchers nationwide awarded Beeson funding and is the first person without a medical degree to receive the prestigious award, which totals $700,000 over five years.

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Future speech pathologists will plug in to computerized diagnostic tools

Patients who have had a stroke or other brain damage often will work with speech-language pathologists who address language disorders so that patients may recover their ability to understand and respond to written and verbal communications.

Early in the course of treatment, many practitioners rely on the Revised Token Test — an instrument that measures a person’s ability to comprehend and follow simple instructions — in order to diagnose and identify an appropriate course of treatment for conditions like aphasia, in which focal brain damage causes the inability to use or understand language.

Malcolm McNeil, professor and chair of communication sciences and disorders in the School of Health and Rehabilitation Sciences, along with colleagues at the University of Florida, received a two-year, $250,000 grant from the U.S. Veterans Administration Rehabilitation Research and Development Service to develop a computerized reading adaptation of the Revised Token Test. A computerized version may allow practitioners to make diagnoses more efficiently and to diagnose patients in remote areas, making it accessible to a broad range of populations. The study will assess reading as well as auditory comprehension using the computerized Revised Token Test.

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Improving immunity to Q-fever

Coxiella burnetii is a livestock bacterium that causes Q-fever, an often-fatal disease in farmers and slaughterhouse workers. Because it is highly pathogenic, can survive in the environment and is easily spread by aerosols, Coxiella burnetii potentially could be used as a bioterrorism agent.

Charles R. Rinaldo Jr., chairman of the Department of Infectious Diseases and Microbiology in the Graduate School of Public Health (GSPH), and professor of pathology in the School of Medicine, has been awarded a $3.3 million, four-year subcontract from the National Institute of Allergies and Infectious Diseases to aid University of Oklahoma researchers in defining the critical immune-stimulating proteins of Coxiella burnetii and two other highly contagious human pathogens: influenza A virus and West Nile virus. The project aims to isolate protein fragments from infected cells and use these in tests of disease-resistant individuals to identify the microbial proteins that are most critical for mounting an effective immune response. The ultimate objective of the project, to be led by Paolo Piazza, a research associate in the Department of Infectious Diseases and Microbiology, GSPH, and Robert Cook, a professor in the School of Medicine’s Department of Medicine, is to develop rapid-turnaround tests for immunity to vaccines for these and other highly pathogenic organisms.

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STAT1 protein may prevent head, neck tumor growth

A protein associated with the growth of head and neck tumors may be a tumor suppressor that could prevent the spread of cancer when it is expressed above normal levels, according to a study published in the Feb. 1 issue of the Journal of the National Cancer Institute (JNCI).

The study, led by Pitt School of Medicine professor of otolaryngology and pharmacology Jennifer Grandis, is the first to show that the expression of a protein called STAT1 may play a vital role in preventing head and neck tumor growth. STAT1 belongs to a family of proteins called signal transducers and activators of transcription that have been linked to tumor progression in many cancers.

“While the activation of STAT1 has been associated with increased survival in breast cancer patients, its role in head and neck cancer has not been clearly understood,” said Grandis. “Our study reveals that it is a critical survival pathway in head and neck cancer and that therapeutic strategies to restore its functioning may be of benefit to patients.”

Grandis, who also is director of the head and neck cancer pro-gram at the University of Pittsburgh Cancer Institute (UPCI), and colleagues compared the expression of STAT1 in squamous cell carcinoma of the head and neck tumors to its expression in normal tissue samples. They found that STAT1 was expressed in lower levels in the tumor cells than in the normal cells. And, when they chemically altered the expression of STAT1 to increase its levels, the cancer cells diminished and died.

To alter the expression of STAT1, the researchers treated cells with an agent that removes methyl groups and modifies gene expression. Some of the cancer cells then were treated with chemotherapy alone and others in combination with azacytidine, an agent that reversed the process and increased STAT1 production. Those cells treated with chemotherapy and azacytidine were more responsive to the treatment and more likely to stop growing and eventually die.

“When STAT1 signaling was silenced, the tumor cells grew, indicating to us that its loss promotes cancer growth,” said Grandis. “On the other hand, when the signaling was increased and combined with chemotherapy, cancer cells were more likely to die.”

More than two-thirds of head and neck cancer patients have a locally advanced stage when diagnosed. The disease has a poor five-year survival rate even after treatment. Current treatment options are limited and often cause disabling side effects.

The study was funded in part by a specialized program of research excellence grant in head and neck cancer awarded to UPCI by the National Cancer Institute in 2004. Co-authors on the study include Pitt researchers Sichuan Xi, Kevin F. Dyer, Mark Kimak, Qing Zhang, William E. Gooding, J. Richard Chaillet, Raymond Liu Chai, Robert E. Ferrell, Beth Zamboni and Jennifer Hunt.