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RESEARCH BRIEFS
Study Links p73 to Hippocampal Growth, Pheromone ResponsesDeleting the p73 gene in mice impairs pheromone sensing ability and the development of the hippocampus, according to a study in the March 2 Nature. The new findings provide a more definitive glimpse into the gene's function. When p73 was first reported in 1997 by Frank McKeon, HMS professor of cell biology, and Daniel Caput of Sanofi Recherche in France, it seemed that the gene was another tumor suppressor. It was highly homologous to p53, which is mutated in a majority of human cancers. However, many of its properties differed from those of p53. Determined to find its true function, researchers from several HMS-affiliated laboratories collaborated with Caput's group. The team included lead author Annie Yang, a research associate in McKeon's group, and Arlene Sharpe, HMS associate professor of pathology at Brigham and Women's Hospital.
The hippocampus developed abnormally in mice missing the p73 gene. There was an unusual arrangement of the pyramidal layer (arrow) and the dentate gyrus (circle). The researchers deleted p73 in mice and, surprisingly, they did not develop tumors as do p53 null mice. Instead they developed a wide range of unexpected abnormalities. Structural defects were observed in the hippocampus (see figure). The researchers discovered that at the root of the problem was p73's role in the survival of a certain subpopulation of neurons. McKeon says this finding is especially significant because it was thought that these "pioneer," or Cajal-Retzius, neurons control the development of another region of the brain, the cerebral cortex. Male mice showed little interest in mating and were less aggressive with other males. Suspecting a defect in pheromone sensing ability, the researchers examined the vomeronasal organ, which detects these substances. Indeed, pheromone receptors were missing. The researchers also observed that female mice were unable to conceive after mating with wild-type males. McKeon concludes that "p73 plays a major role in sexual, social, and reproductive functions." —Lorene Leiter
Young Med School Faculty Most Likely to Be Denied Access to DataAlthough timely disclosure and free and open sharing of data and materials is the ideal for nurturing progress in science, 12.5 percent of 2,366 medical school faculty recently polled reported that they have been refused access to their colleagues' research results within the last three years. This study, conducted by Eric Campbell, HMS instructor in medicine, and his colleagues at Massachusetts General Hospital and HMS, examined the characteristics of scientists most likely to run into data withholding. The authors say that young, highly productive university scientists who hold academic positions and may be engaged in commercial research are the most likely to report being denied access to requested data and materials. Published in the February 2000 issue of Research Policy, this study builds upon earlier research conducted by co-author David Blumenthal, HMS professor of medicine and director of the MGH Institute for Health Policy. Faculty from at least two clinical and two nonclinical departments at each of the 117 traditional medical schools in the U.S. were randomly selected for the study. Authors report that the most senior faculty and faculty with medical degrees were the least likely to be denied access to data compared to younger faculty members and those without medical degrees. Faculty who had published more than 21 articles in the last three years were more likely to have been denied access to requested data, compared to scientists who were less productive. No significant differences were found across gender or academic rank. The authors speculate that an "underground economy" of exchange networks informally regulates data access in the scientific community. Established scientists may have extensive exchange networks that young investigators have not had the time to develop. Denial of information to the most productive young scientists could pose a serious impediment to the progress of science and the cure and prevention of human disease. To minimize the likelihood of these consequences, the authors suggest that senior scientists devote particular attention to helping younger researchers gain access to data and encourage policymakers to consider passing resolutions that support datasharing. Study Finds Gene Involved in Transporting Iron to the BloodIn a significant development in the field of iron metabolism, HMS researchers report in the Feb. 17 Nature the discovery of a gene responsible for transporting iron from the intestine to the blood. The gene DMT1 brings iron into the intestine, but the gene responsible for delivering iron from the intestine into the circulation has eluded investigators. Ferroportin1, the newly identified gene, also appears to be required for transferring iron from maternal circulation across the placenta and into the embryo. Iron export from Kupffer cells, a population of macrophages residing in the liver, may also be regulated by ferroportin1. These cells are involved in recycling iron from senescent red blood cells. The study's leader, Leonard Zon, Howard Hughes Medical Institute associate investigator and HMS associate professor of pediatrics at Children's Hospital, believes the discovery of ferroportin1 will lead to a better understanding of diseases of iron metabolism. For example, in hemochromatosis, one of the most common, patients absorb excessive amounts of iron, damaging the liver, heart, and other organs. Zon says that "inhibiting ferroportin1 might help prevent organ damage in these patients." The researchers, including lead author Adriana Donovan, a Harvard graduate student, found the gene in zebrafish. Aiding in their search was the availability of a certain severely anemic mutant fish, weissherbst. Once they implicated ferroportin1 in the weissherbst phenotype, the researchers proved its role by injecting a wild-type version of the gene into weissherbst embryos. Indeed, the mutants began making hemoglobin, whose synthesis depends on iron. As further evidence of its function, ferroportin1 appeared in prominent sites of iron transport in both zebrafish and mice. Study Finds Vigorous Exercise May Be BestThough everyone knows that exercise is good for your health, many people may be confused about what kind of exercise—moderate or vigorous—is best. Now HSPH researchers report evidence to support the latter. In a study of 13,485 men appearing in the Feb. 1 American Journal of Epidemiology, they found that vigorous exercise was more clearly associated with longer life than moderate exercise. The study's lead author, I-Min Lee, HSPH assistant professor of epidemiology, believes it is important that people get the message about the advantages of vigorous over moderate exercise. Otherwise, she says, "We may be misleading the public into complacency, thinking that moderate exercise will do it all." Yet she also emphasizes that moderate exercise is better than no exercise. Indeed, in the study, although vigorous exercise was most beneficial, people who engaged in moderate activities lived longer than those who were less active. The research subjects were participants in the Harvard Alumni Health Study. Men who attended Harvard between 1916 and 1950 responded to questionnaires in 1977, reporting on their physical activity during the previous year. The researchers classified as "vigorous" such activities as jogging, swimming laps, and shoveling snow. Activities such as golfing, dancing, or gardening were termed "moderate." "Light" activities included bowling, boating, and housekeeping. After examining the death records of men who had died between 1977 and 1992, the researchers discovered that those who had participated in vigorous activities lived, on average, a year and a half longer than those who engaged in light activities. They found a trend toward somewhat longer life associated with moderate activity. In their paper, Lee and co-author Ralph Paffenbarger, an adjunct professor at HSPH and emeritus professor at Stanford, say that while observational studies such as theirs do not directly prove cause and effect, it makes sense that physical activity helps postpone mortality. Exercise improves cardiac function, blood pressure, glucose tolerance, and many other biological responses. —This and brief above by Lorene Leiter |
