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January 20, 2005

Research Notes

Digital sky survey confirms gravity’s role in formation of stars, galaxies

University researchers and other institutions participating in the Sloan Digital Sky Survey (SDSS) have found evidence confirming the role of gravity in the formation of stars and galaxies, which was presented at the Jan. 11 meeting of the American Astronomical Society in San Diego.

Their paper, titled “Detection of the Baryon Acoustic Peak in the Large-Scale Correlation Function of SDSS Luminous Red Galaxies,” submitted to the Astrophysical Journal, provides confirmation for the cosmological theory of structure formation: Small irregularities in how matter is distributed throughout the universe gravitationally attract and accumulate nearby matter, eventually forming stars, galaxies, and clusters of galaxies.

“It’s a confirmation of the basic picture that we have of how the universe went from its early stages, where the distribution of matter and energy was very uniform, to the universe we see today, where there are lots of clusters of galaxies spread across the sky,” said Ryan Scranton, a postdoctoral fellow in the University’s Department of Physics and Astronomy and one of the paper’s coauthors, along with Andrew Connolly, an associate professor in the University’s Department of Physics and Astronomy.

The researchers, led by Daniel Eisenstein of the University of Arizona, studied ripples in the distribution of matter throughout the universe that are caused by the disparity between normal matter and “dark matter”: The first interacts with light, while the second does not. Last year, a survey of cosmic microwave background (CMB) showed such ripples. But in order to confirm that the same effect was taking place with galaxies, researchers needed to observe a larger volume of the universe than previous galaxy surveys contained. The SDSS was able to solve this problem with its unique combination of multicolor imaging and spectroscopy, which targeted a population of distant, luminous galaxies over a wide area of the sky.

“The CMB told us that the light, the energy in the early universe that was bound up in photons and radiation, was displaying this rippling behavior,” said Scranton. “With this galaxy survey, we have confirmation that the regular matter was doing the same thing.”

He added, “It happened exactly where we expected to see it, and the signal looked like what we expected to see, so it gives every indication that our theories for how matter and energy have organized themselves via gravity throughout the history of the universe are in the right ballpark.”

The paper is available online at

The SDSS is managed by the Astrophysical Research Consortium for the participating institutions, including the University of Pittsburgh. A complete list of institutions and authors may be found at

DOD funds research for breast cancer tumor growth

Vera S. Donnenberg, a Pitt School of Medicine researcher, has been awarded $3.6 million by the U.S. Department of Defense Breast Cancer Research Program (BCRP) for a project on a new and potentially important target for successful breast cancer therapy – the tumor stem cell.

Scientists know that normal stem cells have two critical features, the ability to self-renew and the ability to resist toxins through transporters that pump away foreign substances. According to Donnenberg, this very knowledge may provide a promising new paradigm to understanding the growth and spread of cancer.

The project will examine a subset of highly malignant cells in breast cancer tumors, which resemble adult stem cells, and may be responsible for the development of breast cancer. Referred to as tumor stem cells, these cells are hypothesized to give rise to rapidly growing cells that form the bulk of a cancerous tumor.

“Much like a seed is necessary for the growth of a plant, we believe that tumor stem cells exist at the heart of a tumor and perpetuate the growth of cancer,” explained Donnenberg, who is an assistant professor of surgery. “These cells appear able to induce the growth of cancer through characteristics similar to those of stem cells in that they are slow-growing, self-renewing and contain powerful drug-resistant pumps that withstand toxic substances such as those administered during chemotherapy.”

Donnenberg and colleagues will examine breast cancer tumors and surrounding tissue for cells expressing both markers associated with normal stem cells and breast cancer cells. They expect to find that early tumor stem cells will express drug-resistant pumps that can survive treatment while the majority of cancer cells, forming the mass of a tumor, will be destroyed by conventional chemotherapy. Follow-up studies on breast cancer patients who have undergone chemotherapy will help determine whether these tumor stem cell-like cells are still present following treatment.

“We believe that current breast cancer therapies, while effective against the bulk of a tumor, may be focused on targeting the wrong cells and, as a result, are unable to effectively protect against cancer spread and recurrence,” Donnenberg said. “Findings resulting from this project may indicate the need for a critical adjunct to conventional therapy – one that directly targets tumor stem cells and the activity of their drug-resistant pumps.”

The project is supported by the BCRP’s Era of Hope Scholar Award and is one of five in the country awarded in fiscal year 2004. The award was established by the BCRP in 1992 to promote innovative research directed toward eradicating breast cancer.

Co-polymer acts like super sunscreen for antioxidants

University researchers have developed a way that could prolong the effectiveness of antioxidants that are commonly used in products to protect against the harmful effects caused by sun and air exposure. According to the Jan. 10 print edition of Biomacromolecules, a journal of the American Chemical Society, Pitt researchers described a chemically formulated co-polymer that in laboratory studies was able to withstand significantly longer periods of intense ultraviolet light than other formulations.

Antioxidants are added to many types of products, from sunscreens and cosmetics to exterior paints and industrial and consumer plastics, in order to stave off oxidation – a process whereby UV radiation or oxygen in air or water produces a chemical reaction to the surface of an object. Oxidation causes skin to burn or wrinkle, iron to rust and plastics to turn yellow or crack. Yet even the addition of antioxidants cannot provide complete protection. Eventually, the antioxidants themselves become vulnerable to oxidation caused by UV light, hence the need to reapply sunscreen, repaint homes and replace sun-damaged materials.

“We wanted to identify a way to stabilize antioxidants against the deleterious effects of photo-oxidation caused by the sun. This has been a major obstacle that has limited the effectiveness of antioxidants to protect materials against oxidation,” said Bhalchandra S. Lele, research associate at the University’s McGowan Institute for Regenerative Medicine and the department of bioengineering in Pitt’s School of Engineering.

Lele and principal author Alan J. Russell, professor of surgery at the University’s School of Medicine and director of the McGowan Institute, developed a co-polymer that acts as a super sunscreen of sorts, whereby one chemical sacrificially takes the hit of UV rays to allow its partner, the antioxidant, to work longer. Specifically, the co-polymer consists of benzotriazole, a chemical that absorbs UV light, and an antioxidant called Trolox, a water-soluble derivative of vitamin E that has been shown to protect against the harmful effects of UV radiation.

“We have not simply combined these two compounds to create this unique co-polymer. In fact, when mixed, the end product is no more effective than each of the individual compounds. Rather, for these two chemical structures to be synergistically effective we found that the key components must reside in the same molecule,” Russell explained.

As a single chain molecule – with the two components side by side – benzotriazole preferentially receives the UV, thereby protecting the Trolox from exposure, in much the same way that a tall building takes the bright sun while casting a cool shadow on a house next door.

Russell began working on the creation of a co-polymer that was both protective of and protected against photo-oxidation as part of his lab’s primary focus to develop materials that can be used as coatings on buildings or vehicles that simultaneously detect and decontaminate chemical and biological agents. With funding from the U.S. Department of Defense Multidisciplinary University Research Initiative program administered by the Army Research Office, Russell has been seeking ways to couple the power of biological detection with light-activated decontamination. The only way to use both simultaneously was to invent a way to protect the biological component that is capable of detection and decontamination (nature’s catalyst) from the sun and other oxidants.

In their current study, the researchers created the laboratory equivalent of an extreme outside environment, subjecting an enzyme to eight hours of UV light roughly seven times the intensity of a blazing summer sun. Under these harsh conditions, an enzyme called chymotrypsin quickly lost its ability to function. The researchers then coated the enzyme with mixtures of UV-absorbing molecules and antioxidants. Only when the UV-absorbing and antioxidant molecules were placed in the same polymer chain could the enzyme survive for long periods.

“This surprising result implied that the UV-absorber could protect the antioxidant in the co-polymer. More detailed studies showed this to be true even without the enzyme, and as such, we found a unique way to stabilize antioxidants from their own oxidation. Now we can modify our decontaminating coatings so that they are less vulnerable to oxidative reactions from sun, and there very well could be additional applications in which protection of antioxidants is important,” Russell said.

The University has applied for a U.S. patent for the process involved in using a UV-absorber to stabilize an antioxidant.

How cancer cells get out of control

Pitt researchers have identified how a single aberrant cell can duplicate to form cancerous tumors, suggesting a specific protein mechanism as a target for the treatment of cancer, according to “Spindle Multipolarity Is Prevented by Centrosomal Clustering,” published in the Jan. 7 issue of Science.

The team, led by William S. Saunders, associate professor of biological sciences in Pitt’s School of Arts and Sciences, found that overexpression of a single protein can cause changes in a cell associated with the formation of tumors.

“Virtually all cancer cells acquire the ability to change their genomic structure,” said Saunders. “Researchers in the field are looking for single events that can cause multiple mutational changes to the genome, and this research is an example of that.”

Before a normal cell divides, its chromosomes are duplicated and then pulled apart by a structure called a spindle, so that the two daughter cells each will have the same number of chromosomes.

At the end of a normal spindle is the spindle pole, also called the centrosome, which pulls the chromosomes outward. Cancer cells often have extra centrosomes. When a cell has more than two centrosomes, sometimes-but not always-the spindles will have more than one pole and cell division won’t work correctly, leading to the swapping of genetic material, uncontrolled cell division and the formation of tumors.

Why this doesn’t always happen when there are too many centrosomes was the focus of the Pitt researchers’ investigation. They found that as long as the extra centrosomes “cluster” together, the spindles will form normally, with two ends, and the cells would divide normally. “No one else appreciated that that was required, or what the mechanism was that separated them,” said Saunders.

But when the extra centrosomes don’t cluster together, the spindles don’t form normally, and cell division can become unstable, reported Nicholas J. Quintyne, a postdoctoral fellow working with Saunders and first author of the paper.

Investigating the mechanism by which this occurs, the researchers found that in cultured oral cancer cells a protein called dynein is missing from the spindle, and the centrosomes no longer cluster together.

Furthermore, the researchers discovered that in some types of tumors, dynein is inhibited by the overexpression of another protein called NuMA. Excess NuMA seems to prevent dynein from binding to the spindle. When they reduced the level of NuMA in cultured cancer cells, the dynein returned to the spindles, and the spindles were no longer multipolar.

“This finding suggests that a possible treatment for some types of cancer could be a drug that inhibits NuMA,” noted coauthor Susanne M. Gollin, professor of human genetics in Pitt’s Graduate School of Public Health and coinvestigator at the Oral Cancer Center of Discovery at the University of Pittsburgh Cancer Institute.

In the future, the researchers plan to look at other proteins that bind to NuMA and how these proteins interact in the process.

The research was supported by the National Institute of Dental and Craniofacial Research of the National Institutes of Health and by the American Cancer Society.

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