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Deadly duo. What do aging and cancer prevention have in common? According to a new study by Barbara Gilchrest, a BUSM professor and chair of the department of dermatology, and a team of researchers at the school, both result from a mechanism that swings into action when a specific repeated sequence of DNA bases is detected in a cell. Furthermore, Gilchrest says, researchers may be able to harness this mechanism to create new cancer prevention strategies.

It is widely known that human cells senesce -- they can divide only a limited number of times, about 20 in a healthy adult. This limit is associated with shortening of telomeres, the loop-like structures at each end of the central, gene-containing portion of the chromosome. Telomeres, like all DNA, are double stranded, but one strand ends in an overhang composed of the six-base sequence TTAGGG, which repeats for a length of approximately 150 to 200 bases. T, A, and G (thymidine, adenine, and guanine) are three of the four building blocks, or bases, that make up DNA (the fourth is C, or cytosine). The overhang is normally concealed inside a loop structure at the chromosome end.

The researchers hypothesized that as telomeres shorten in normal aging or are damaged by other factors, such as stress, ultraviolet light, or carcinogens, the overhang sequences are exposed, setting in motion a series of reactions causing the cells to stop replicating, or even to commit suicide (apoptosis). To test this the researchers introduced small DNA fragments with the same TTAGGG sequence into cells in culture. They observed that the fragments were rapidly taken into the cell nucleus (where the chromosomes are located), and senescence or apoptosis resulted.

“The cell responses were identical to those activated after acute DNA damage or experimental disruption of the telomere loop,” says Guang-Zhi Li, a postdoctoral fellow in dermatology and the study’s first author.

“If a cell is at high risk for becoming cancerous because of acute DNA damage or simply aging, which exposes cells to environmental carcinogens over many years, nature wants to protect the tissue,” says Gilchrest. She and her colleagues propose that by triggering DNA damage responses without actually damaging DNA -- by providing telomere-mimicking DNA fragments -- they may be able to develop new treatments for cancer, a condition in which cells seem to have lost their ability to senesce or otherwise recognize and respond to abnormal DNA. In a series of earlier publications, MED Research Associate Professor Mark Eller, a coauthor of the present study, showed that the DNA fragments can stimulate tanning and enhance DNA repair capacity, widely acknowledged cancer prevention strategies.

This research was reported in the January 7 Proceedings of the National Academy of Science.


Buying, selling, or sitting tight. Using the powerful analytical tools of statistical mechanics to examine the complex fluctuations of the financial marketplace, CAS Physics Professor H. Eugene Stanley and research associates Vasiliki Plerou (GRS’96) and Parameswaran Gopikrishnan (GRS’01) at the Center for Polymer Studies (CPS) have discovered and described a new phenomenon -- a critical threshold separating two distinct behavioral phases of financial markets. The operating principles, according to Stanley, CPS director, are virtually identical to those of phase transitions in physical systems in which individual atoms behave in a collective way at a critical threshold, such as in the transition from water to ice.

Plerou and her collaborators analyzed every transaction of the 116 most actively traded stocks over a two-year period (1994 and 1995) -- more than 100,000,000 transactions. They calculated the difference between the number of shares sold and the number of shares bought for each 15-minute interval during active market trading.

Their analysis revealed the existence of two distinct phases. The first, described by the researchers as the equilibrium phase, is characterized by balance -- neither buying nor selling predominates. During the price equilibrium phase the probability of a transaction being buyer-initiated is equal to the probability of a transaction being seller-initiated; there is statistically no net demand. The study’s authors suggest that during this period those who trade either misperceive the information or act for idiosyncratic reasons.

The second, or out-of-equilibrium phase, is bimodal, characterized by an excess of either buyers (demand) or sellers (supply). During this phase the stock price is moving to a new fair value according to the market’s evaluation. In this scenario, the researchers contend, the trading arises from informed traders who possess superior information about the stock.

The mechanisms at work in this context, according to the authors, are identical to those of all phase-transition phenomena where a qualitative change in a system occurs at a critical threshold.

This approach to empirical analysis of market phenomena is known as econophysics -- a term coined by Stanley and others who view financial markets as complex, evolving systems driven by the collective behavior of thousands of investors, traders, and speculators, in much the same way that natural systems result from the collective behavior of electrons or molecules.

The research by the BU scientists was reported in the January 9 issue of the journal Nature.

"Research Briefs" is written by Joan Schwartz in the Office of the Provost. To read more about BU research, visit http://www.bu.edu/research.

       

15 May 2003
Boston University
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