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Research Briefs

	Clues to neurodegenerative disease found in image of live cell
	Hormones modify protein production
	Molecule mediates DNA repair
	Cardiovascular benefits of aspirin outweigh gastrointestinal risks

Clues to neurodegenerative disease found in image of live cell

The differing abilities of cellular machinery to clear a mutated protein from the cell nucleus could provide researchers with clues about treating diseases such as spinal cerebellar ataxia type 1 (SCA-1) and other neurodegenerative diseases, said a scientist at Baylor College of Medicine.

In a report appearing in Nature Cell Biology, David Stenoien, PhD, Marilyn Mielke, PhD, and Michael Mancini, PhD, describe how they monitored nuclear inclusions made of mutant ataxin 1 (which causes SCA-1) in living cells. Using laser-based digital microscopy and fluorescently engineered proteins, the group reports that the inclusions are metabolized at different speeds, and can appear completely fluid. These new observations give scientists clues how to attack the fatal neurodegenerative disease that usually occurs in adulthood, as well as other neurodegenerations associated with misfolded proteins.

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Hormones modify protein production

Naturally occurring hormones such as estrogen, progesterone and cortisol play an important role in determining what kind of protein the cell makes in response to a genetic message, said researchers at Baylor College of Medicine in a report in the Oct. 11 issue of the journal Science.

"These steroid hormones are some of the things that change the protein that comes from a gene," said Bert O'Malley, chairman of the molecular and cellular biology department at Baylor and senior author of the paper. When a gene is activated, its DNA is transcribed or translated into messenger RNA, which carries the message about which protein is to be made to the assembly apparatus of the cell. However, one gene can produce different kinds of messenger RNAs, resulting in different proteins. The process is called "alternative splicing." "This explains how 30,000 human genes can result in more than 100,000 proteins," said O'Malley.

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Molecule mediates DNA repair

A molecule called 53BP1 binds to a major tumor suppressor gene called p53 and acts as a mediator of the damage response in which p53, as guardian of the genome, plays a key role, said scientists at Baylor College of Medicine in a report in a recent issue of the journal Science.

Using a new technique called small interfering RNAs, Stephen Elledge, PhD, a professor in the department of biochemistry and molecular biology at Baylor, and colleagues destroyed the message that tells the cell to make 53BP1. By testing the cells that lacked 53BP1, they found that necessary repair proteins can't get to the site of DNA damage," said Elledge. The molecule appears crucial to the assembly of these proteins into foci that are repair complexes for the cell's DNA, he said.

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Cardiovascular benefits of aspirin outweigh gastrointestinal risks

The benefits of aspirin in reducing the risk of a second heart attack or stroke outweigh the risks of bleeding in the gastrointestinal tract, said researchers in a report in the current issue of the Archives of Internal Medicine.

The authors, David Y. Graham, MD, chief of gastroenterology at the Veterans Affairs Medical Center and the section of gastroenterology at Baylor College of Medicine in Houston and Steve Weisman, PhD, of Innovative Science Solutions LLC in Morristown New Jersey, said that concern over the risks of aspirin may have persuaded many patients not to take aspirin or make their physicians leery of prescribing it.

In a meta-analysis of six different studies involving more than 6,000 patients and designed to test aspirin's effectiveness in reducing the risk of second heart attack and stroke, the scientists found that "there were approximately 18 percent fewer deaths, 20 percent fewer strokes and 30 percent fewer myocardial infarctions (heart attacks) in the people who took aspirin," said Graham. The doses ranged from 50 milligrams to 325 mg. per day and were given to the patients who had already had a heart attack or stroke.

This study was funded by Bayer Corporation, Consumer Care Division in Morristown, N.J.

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