Inside this issueCover storiesAn indelible smile, and a caring heartLeading scientist is appointed new chair of Cell BiologyNew aid policy lowers debt, widens career choicesPartnershipsOpening up the lines of communicationGrants & contractsPeopleLifelines: Linda Mayes
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Advances
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Estradiol, a naturally occurring female sex hormone, supports skeletal health by balancing the ongoing processes of bone resorption and bone formation. When used as a component in estrogen replacement therapy for post-menopausal women, however, estradiol has been linked to increased risk of some kinds of cancers.
Working with rat-derived osteoblasts, cells that can build bone, School of Medicine scientists have isolated a substance that mimics estradiol but is functionally and chemically different, making it a possible new candidate for hormone replacement.
Studies in the laboratories of Thomas L. McCarthy, Ph.D., and Michael Centrella, Ph.D., of the Department of Surgery, identified the estrogen-like substance, which triggered several of the biochemical responses induced by estrogen receptor activation. They published their findings in the May 13 edition of the Proceedings of the National Academy of Sciences USA.
The scientists hope the osteoblast-derived molecule, which they labeled Ob-SERM, may be developed into a safer alternative to traditional estrogen replacement.
Clearing out Alzheimer’s plaques
Alzheimer’s disease (AD) patients tend to have elevated levels of TGF-ß, or transforming growth factor beta, an immune system molecule that plays a key role in activating immune response to injury.
A multi-center group of researchers has found that blocking TGF-ß pathways in mice genetically engineered to display symptoms of AD clears the amyloid plaques in the brain that are a hallmark of the disease. Mice with tamped-down TGF-ß also show minor improvements navigating certain mazes.
In the June issue of Nature Medicine, a team led by Terrence C. Town, Ph.D., of Cedars-Sinai Medical Center in Los Angeles, and Richard A. Flavell, Ph.D., chair and Sterling Professor of Immunobiology and Howard Hughes Medical Institute investigator, reports that interrupting TGF-ß pathways in the mice allowed immune cells to engulf and digest about 90 percent of the plaques in their brains. “It was like a vacuum cleaner had removed the plaques,” says Flavell.
Town, the study’s lead author, says that if these results are supported by studies in humans, “we may be able to develop a drug that could be introduced into the bloodstream to cause peripheral immune cells to target the amyloid plaques.”
Feminine pharaoh: a genetic anomaly?
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Akhenaten, a pharaoh of Egypt’s 18th dynasty, is portrayed (see photo) with a thin neck, elongated head, large buttocks, breasts and a prominent belly. These depictions have long intrigued Egyptologists, who have suggested that he was portrayed in this way for religious reasons, or that artists exaggerated his physical characteristics.
But Irwin M. Braverman, M.D., professor of dermatology, believes that ancient artists accurately captured the signs of two genetic conditions: aromatase excess syndrome, in which excess estrogen production can lead to feminization of the male body and early puberty in females, and craniosynostosis, a developmental defect that alters normal skull growth.
The pharaoh’s daughters are depicted with breasts, large hips and buttocks at age three and seven in some carvings, and a number of his relatives are shown with identical abnormalities, suggesting genetic causes, says Braverman, who presented his findings at the 14th annual Historical Clinicopathological Conference in May.
No mummy of Akhenaten exists, but Braverman says it may be possible to confirm his retrospective diagnosis with genetic tests on the mummies of Akhenaten’s kin.
Natural selection tames alcohol use
It is well known that some East Asians have a low tolerance for alcoholic drinks because they carry variants of genes that help regulate alcohol metabolism.
New research by Kenneth K. Kidd, Ph.D., professor of genetics, and first author and postdoctoral associate Hui Li, Ph.D., suggests that some environmental change in East Asia during the past few thousand years promoted the spread of one such variant protecting certain ethnic groups from vulnerability to alcoholism.
The new study, published in April in the online journal PLoS ONE, reports that a variant of a gene known as ADH1B became widespread specifically among the speakers of the Hmong and Altaic language families because of some relatively recent difference in these groups’ environments. Any number of factors—the variant may have conferred resistance to a novel parasite or toxin, for example—could have triggered the genetic change, the researchers say.
That these populations are less prone to alcoholism as a result is happenstance, Kidd says, but “something important in recent human history has affected the genetic composition of many East Asian populations.”
