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RESEARCH BRIEFS
Gene Found Essential for Cell Polarity, OrganizationHMS researchers have discovered a gene that is required for maintaining the architecture of epithelial cells. Lining the surface of the gut, skin, and many other organs, epithelial cells line up side by side to form sheets with distinctive top and bottom, or apical and basolateral, surfaces facing, respectively, the "outside" (e.g., the cavity of the gut) or "inside" (the body or organ). David Bilder, HMS research fellow in genetics, and Norbert Perrimon, Howard Hughes investigator and HMS professor of genetics, noticed irregularities in the fruit fly Drosophila's hard outer layer, the cuticle, after mutating a certain gene. Secreted by underlying epithelial cells, the cuticle, instead of being a smooth sheet, was wrinkled and filled with holes. The researchers reasoned that disorganization of the epithelial cell layer underneath the cuticle was the likely culprit and examined these cells during embryonic development. Indeed, rather than forming a neat columnar monolayer, the cells were rounded, irregularly shaped, and piled up on each other (see figure). The researchers learned that the new gene, which they named scribble, or scrib for short, affects epithelial organization by disrupting cellular polarity. Polarity, achieved by the segregation of specific proteins into apical and basolateral compartments, is critical for epithelial cell shape and function. Mutations in scrib specifically affected the apical region. Certain proteins, such as Crumbs, normally restricted to the apical membrane, were distributed elsewhere in the cell. The researchers propose two theories of how scrib might work. It may act as a fence within epithelial cells, preventing apical proteins from entering the basolateral region. Or it may help to direct apical and basolateral proteins to their proper locations. The study appears in the Feb. 10 Nature.
In wild-type Drosophila embryos, epithelial cells form regular columnar monolayers (top); but in scrib mutants, the cells are rounded, irregularly shaped, and piled up on each other (bottom). Steroid Abuse, Eating Disorders Common in Women BodybuildersAccording to a study in the current (January/February) Psychotherapy and Psychosomatics, many women bodybuilders abuse anabolic–androgenic steroids (AAS). Researchers Amanda Gruber, HMS instructor in psychiatry, and Harrison Pope, HMS professor of psychiatry, both at McLean Hospital, believe their study is the first to examine AAS abuse in these women. They say their findings "imply that AAS use among women, once restricted only to a small number of elite athletes, may now be evolving into a commoner public health problem in the U.S." The study may also be the first to describe distinctive psychiatric syndromes in women bodybuilders. For example, many were found to have eating disorders and an excessive preoccupation with their bodies. Stereotypically masculine gender roles were also common. The data were collected from 75 women who had competed at least once in a bodybuilding or fitness contest, or who had lifted weights at least five days per week for a minimum of two years. Thirty-three percent of the women reported current or past AAS use. Users were also more likely to have taken other performance-enhancing drugs, such as amphetamines or thyroid hormones, compared to nonusers. Many of the women reported similar rigid dietary practices, a condition the researchers call "eating disorder, bodybuilder type." Present in 84 percent of AAS users and 68 percent of nonusers, the condition is characterized by a strict adherence to a high-protein, high-calorie, low-fat diet eaten at regularly scheduled intervals in precisely measured quantities. Any disruption in this daily routine typically produces extreme anxiety. Nontraditional gender roles were found in 88 percent of users and 66 percent of nonusers. Although these women did not express a desire to be men, they described a preference for stereotypically masculine clothing, occupations, games, or pastimes. The majority of women in the study (100 percent of AAS users and 80 percent of nonusers) were excessively preoccupied with the unrealistic belief that their bodies were not sufficiently lean or muscular. In many, the obsession to pursue their all-consuming lifestyle caused them to give up important social and occupational opportunities. —Briefs above by Lorene Leiter Dose of Antibodies May Prevent HIV Transmission From Mother to ChildPreventing transmission of HIV from mothers to infants has long been a major goal of AIDS research, and is critically important in Africa, where tens of thousands of infected children are born each year. A study led by Dana–Farber Cancer Institute researchers raises hope that newborns could be protected from HIV by giving both mother and baby a combination of potent antibodies shortly before and after birth. Although the virus can pass from mother to infant either during pregnancy, at birth, or through breast feeding, the most common time is shortly before or during delivery. An obstacle in earlier studies has been the coat protein of HIV, which is covered with so many sugar molecules that antibodies have a hard time finding the viral epitopes they need to bind and block entry into the cell. In the new study, monkeys were passively immunized using three antibodies from people who had been infected with HIV, but whose antibodies were unusually effective in blocking replication. The antibodies had proved synergistic in vitro, enhancing one another's neutralizing ability. After exposure to a virus called SHIV-vpu+, which contains parts of HIV and its simian counterpart, SIV, none of the immunized monkeys had detectable blood levels of virus, while non-immunized monkeys were infected. "This demonstrates that passive immunization with these antibodies can protect against HIV transmission during delivery and birth," says senior author Ruth Ruprecht, HMS professor of medicine at DFCI. "If this approach works as successfully in humans, and if the antibodies can be produced inexpensively, it may offer a practical way of preventing mother-to-infant transmission of the AIDS virus even in the developing world." Insights gained from the research may someday prove useful in developing an AIDS vaccine, she added. An article describing the study was published in the February Nature Medicine by researchers from DFCI, the University of Texas M.D. Anderson Cancer Center, the Institute of Applied Microbiology in Vienna, and Memorial Sloan-Kettering Cancer Center in New York. Bird Brain Yields Bright Idea on Brain RepairA little bird told Jeff Macklis that it might be possible, one day, to awaken the birth of new neurons inside a person's brain without transplantation of stem cells from other sources. In the February Neuron, the HMS associate professor of neurology at Children's Hospital reports with his collaborators Constance Scharff and Fernando Nottebohm of Rockefeller University and others that they have coaxed high-level neurons in adult zebra finches to be replaced by the bird's endogenous precursor cells. "This is, we believe, the first example demonstrating that one can induce the birth of new neurons and that they actually contribute to a complex behavior," Macklis says. The study plays on one of the brain's more amazing feats: every fall, a population of song-generating neurons in the so-called high vocal center of canaries dies off and the birds fall quiet. Winter sees a wave of rebirth of the same kind—and same number—of neurons, and in the spring, the canaries learn their songs anew. Zebra finches lack this seasonal cycle; their brains generate a constant yet tiny trickle of new neurons. This more limited ability resembles that of mammals. Scientists now agree that multipotent precursors line the inner ventricles of mammal brains, but only two specific types of neuron are known to regrow at low levels. When the researchers selectively killed one kind of song-related neuron in zebra finches, they found that these birds, too, partially lost their song. Within three months, however, the finches had more or less restored it, and the neurons had reappeared in numbers similar to the annual rebirth in canary brains. The finches' re-emerging songs make them suitable for studying a big question of research aimed at future repair of brain function, namely whether newly incorporated neurons can function in an existing complex circuitry and contribute to behavior. |
