Neurobiology:
Ion Channel Protein in Inner Ear Is Likely Long-sought Key to Hearing
Anesthesia:
Study Finds How Aspirin Dampens Inflammation
Genetics:
Broken Calcium Gate Leads to Heart Syndrome with Related Autism
State of the School
Martin Draws Picture of Tangible Progress at HMS
Biomedical Computing:
Faculty Receive Funding for Two National Biomedical Computing Centers
Calcium Supplements During Pregnancy Linked to Healthy Blood Pressure in Children
Newly Found Cancer Gene Offers Model for Breast Tumor Development
Cell-Cell Interaction Not Needed for Normal Neuron Size in Retina
Scholars Program Maintains Growth in Junior Faculty Awards
Former HMS Professor Wins 2004 Nobel Prize
HMS Revamps Program in Medical Education
NIH Pioneer Award Funds Developmental Biology Research
Modeling Disease: New Windows on a Hidden World
Grant Promotes Clinician-scientists in Eye Research
NIH Roadmap Supports Pilot for Vision Research Center
HMS Unveils New Web Pages
Escape from the Stereotype Trap
Calcium Supplements During Pregnancy Linked to Healthy Blood Pressure in Children
Mothers who take calcium supplements midway through pregnancy may set up their children for a lifetime of healthier, lower blood pressure, HMS researchers report in the Oct. 5 Circulation.At six months of age, infants whose mothers had consumed the most calcium in supplements during the second trimester had the lowest blood pressure, said first author Matthew Gillman, HMS associate professor of ambulatory care and prevention at Harvard Pilgrim Health Care.
| The second trimester may be a critical period of development during which extra calcium can influence offspring's blood pressure. |
Almost all of the 936 women took multivitamins containing modest amounts of calcium. About one third of them more than doubled their doses in the form of calcium-rich antacids. Infants of mothers who took both multivitamins and additional calcium supplements had lower blood pressure than those whose mothers took multivitamins alone.
The second trimester may be a critical period of development during which extra calcium can influence offspring's blood pressure. The researchers found no effect from calcium supplements during the first trimester and no boost from the higher calcium in food at any time.
"No one study is proof," cautioned Gillman, who will be following the children's blood pressure as they grow older. This study confirms evidence from an animal model and human trial and extends the data by pinpointing the second trimester and calcium supplements. The mechanism remains a mystery.
The analysis comes from a prospective cohort study called Project Viva, which has been following more than 2,000 pregnant women and now their children since 1999 to assess fetal origins of adult disease. The researchers are particularly interested in maternal diet.
--Carol Cruzan Morton
Newly Found Cancer Gene Offers Model for Breast Tumor Development
Researchers at the Dana-Farber Cancer Institute have identified the protein AIB1 as a potent oncogene whose overexpression in mammary tissue leads to hyperplasia and malignant tumor formation, according to a paper in the Sept. 6 Cancer Cell. The study, led by HMS research fellow in medicine Maria Torres-Arzayus and HMS associate professor of medicine Myles Brown, was conducted in collaboration with Roderick Bronson, a lecturer in pathology at HMS, and William Sellers, an HMS associate professor of medicine at DFCI.
AIB1, short for amplified in breast cancer-1, is an estrogen receptor co-activator that is, as its name suggests, overexpressed in many breast cancers. When the receptor is bound to estradiol, it enters the nucleus and functions as a transcription factor. AIB1 modulates this activity, but its role in tumor formation had not previously been explored.
"Our studies were aimed at testing the idea that AIB1 is an oncogene," said Brown. The researchers made transgenic mice that overexpressed AIB1 in the mammary glands. They found that the mice had 30 to 40 percent larger mammary glands than their wild-type counterparts due to increased cell size and number and because of reduced apoptosis. After the weaning stage, the mammary glands from the transgenic mice did not involute properly and remained in a lactating state. As the transgenic mice aged, 76 percent of them developed one or more tumors in the mammary gland, pituitary gland, uterus, or lungs.
To look at the mechanism of AIB1 action, the authors created cell lines that overexpressed AIB1. They found that the oncogenic activity was due to an upregulation of the IGF-1 receptor/PI3 kinase/AKT/mTOR pathway, which is known to regulate protein synthesis and cell size. "It's a feed-forward loop," explained Brown, "because this pathway actually turns up AIB1 activity, which then further activates the pathway."
The AIB1-overexpressing mouse model may prove useful for studies of all stages of breast cancer development. "We now have a model for studying pre-malignancy, which is significant because our aim is to treat patients before tumor formation. We may even be able to use this model to study prevention," said Torres-Arzayus.
--Jillian Lokere
Cell-Cell Interaction Not Needed for Normal Neuron Size in Retina
Bigger tiles or more grout? Two Massachusetts General Hospital researchers have shown that retinal ganglion cells, which normally organize themselves in tightly packed tiling patterns, do not grow larger to compensate for a reduction in cell number. Instead, they maintain a low-density tiling pattern with large spaces between cells. The study, led by Bin Lin, an HMS research fellow in surgery, along with senior author Richard Masland, the Charles Anthony Pappas professor of neuroscience in the Department of Surgery, appears in the Aug. 19 Neuron.Tiling is a common way for neurons to cover sensory surfaces. In the retina, more than a dozen ganglion cell types each organize themselves into a particular mosaic pattern that maintains consistent cell-to-cell distance, cell size, and non-overlapping dendrite placement. The prevailing hypothesis has been that ganglion cells of the same type repulse each other, creating the tiled pattern.
Lin and Masland decided to test this hypothesis in mice carrying a genetic mutation that reduces the total number of ganglion cells in the retina. Lin examined the mutant retinas and found that each ganglion cell type was present at 5 to 20 percent of the normal number. He looked to see if the remaining cells became larger or expanded their dendrites. "We thought we'd see bigger tiles," said Masland.
Instead what they found was more grout: the cells maintained their normal size and dendritic field, but left large spaces between neighbors. "In some cases, there were millimeters between cells--that's like miles," Masland said.
This result changes the way neurobiologists think about tiling. Instead of cell-cell repulsion, it appears that cell size is limited by other signals. Repulsion may simply fine-tune the tiling pattern. "It is possible," Masland said, "that each cell contains more information about its own size and shape than we thought."
--Jillian Lokere