A maternal link to prostate cancer? Retinal chips Addressing disparities in cardiovascular health Safer teens behind the wheel In search of a better transplant drug Aging with less grace, spatially speaking Junk DNA and social behavior	Finding missing cases of HIV Female sex hormone reduces stress response Treating depression, deep within the brain Easy on the heart and wallet Applying nanotechnology to cardiovascular disease Eat mor veggees
	A maternal link to prostate cancer? More than 20 million men in the united states with a particular set of inherited characteristics and mutations in mitochondrial DNA (mtDNA) are at significantly increased risk for developing renal and prostate cancers, according to research at Emory. Mitochondrial DNA, which contains a small number of genes inherited mainly from the mother, is found in the hundreds of mitochondria located in the cytoplasm outside of each cell’s nucleus.      Emory urologist John Petros has found variations in the mtDNA of men from the general population compared with men with renal and prostate cancer. His study showed that only 9.6% of the general population of Caucasian American participants had mtDNA in haplogroup U. By contrast, 16.7% of prostate cancer patients and 20.7% of renal cancer patients exhibited the haplogroup U signature. A haplotype is a combination of variations in a gene. In addition to variations in haplogroup, Petros also found that 12% of prostate cancer patients had mutations in the COI gene, an mtDNA cytochrome oxidase subunit, compared with less than 2% of patients who were cancer-free.      In a second Emory study on prostate cancer, led by Winship Cancer Institute’s Jin-Tang Dong, researchers found that a gene named ATBF1 may contribute to the development of prostate cancer through acquired mutations and/or loss of expression. Although previous research has suggested that a section of chromosome 16 harbors a tumor-suppressor gene in several types of human cancers, the particular gene responsible has not been identified previously.      By studying the genes within the section of chromosome 16, the Emory team found that ATBF1 was a strong candidate for an important tumor-suppressor gene because its function is frequently lost in prostate cancer through gene mutations and/or loss of expression. In addition, ATBF1 was found to inhibit cell growth in culture dishes. A tumor-suppressor gene is a gene whose loss of function contributes to the development of cancer.      ATBF1 helps regulate the expression of other genes. If its function is impaired by mutations or loss of expression, a cell could lose the control of cancer genes. The Myb oncogene, for example, is normally inhibited by ATBF1, but it can be activated if ATBF1 is lost.      “Sporadic cancers often are the result of multiple genetic alterations that accumulate over time,” says Dong, “but only a small number of genes have been shown to undergo these frequent mutations. Because ATBF1 inhibits cell proliferation, frequent acquired mutations that inhibit the gene, such as the ones we found, could lead to a lack of growth control in prostate cancer. Because gene deletion in chromosome 16 is common in many types of cancer, including lung, head and neck, nasopharynx, stomach, breast, and ovary, ATBF1 could be involved in the development of these cancers as well.”
	TOP
	Retinal chips     In an expanded clinical trial, Emory surgeons have implanted a tiny retina microchip, much smaller than a penny, in several patients with retinitis pigmentosa to determine if it will improve functional or slow progression of vision loss. Five patients with moderate-to-severe vision loss participated in the experimental treatment, developed by Optobionics Corp. Researchers hope the retinal chips will improve the quality of life for patients with this debilitating disease.
	TOP
	Addressing disparities in cardiovascular health     The NIH has awarded Emory and Morehouse School of Medicine $6 million for a five-year partnership to address health disparities between African Americans and Caucasians at high risk for cardiovascular disease. The program is one of six nationwide funded by the National Heart, Lung and Blood Institute.      Known as META-Health (Morehouse and Emory are Teaming up to eliminAte Health Disparities), the Atlanta program will focus on metabolic syndrome, a cluster of health risk factors that includes hypertension, abnormal cholesterol, high triglycerides, abdominal obesity, and elevated blood glucose. People with three of these factors are identified as having metabolic syndrome, indicating a high risk for diabetes and cardiovascular disease.      The first goal of the study is to identify differences in risk factors in African Americans and Caucasians. The research team then will develop and test targeted interventions aimed at improving overall cardiovascular health.      Earlier studies indicate that African Americans and Caucasians experience metabolic syndrome differently, according to cardiologist Arshed Quyyumi, who is leading Emory’s team. African Americans appear to have lower incidence of cholesterol and triglyceride abnormalities with a similar frequency of insulin resistance, factors that contribute to underdiagnosis of the condition.      In addition, evidence suggests that children of patients with the syndrome are at increased risk of developing obesity and insulin resistance. META-Health researchers hope to establish a genomic database to identify genetic differences that would account for some of these complications and disparities.
	TOP
	Safer teens behind the wheel Georgia’s strong teen driving laws are working. In 1997, the Teenage and Adult Driver Responsibility Act went into effect, ushering in incentives to deter excessive speeding, consumption of alcohol while driving, and other dangerous driving behaviors. It also introduced graduated licensing, with provisions to restrict late-night driving and the number of passengers in a teen’s vehicle. Emory researchers—led by Emergency Medicine Chair Arthur Kellermann—recently completed a study to evaluate the law’s long-term impact. They found that the rate of fatal crashes among 16-year-olds was 36.8% less than in the previous 5-1/2 years for the same age group. Fatal crashes involving 17-year-olds also were reduced. In comparing the driving results of 21-year-olds in 1997 with those who turned 21 after the law’s enactment, researchers found a 38% lower fatal crash rate for the group who learned to drive under the new rules.
	TOP
	In search of a better transplant drug         For the past 20 years, doctors have treated transplant patients with cyclosporine to suppress the immune system and prevent organ rejection. However, the medication shuts down the immune system, increases the risk of heart attacks, and can damage the kidneys.      An investigational medication, known as LEA29Y (belatacept), is proving effective in preserving transplanted kidney function while avoiding those toxic side effects. The preclinical research conducted with nonhuman primates at the Yerkes National Primate Research Center has led to human clinical trials to develop an effective alternative to current therapies.      Chris Larsen (above) and Thomas Pearson of the Emory Transplant Center with colleagues at Bristol-Myers Squibb developed LEA29Y to selectively block the second of two cellular signals—the co-stimulatory signal—that the body needs to trigger an immune response. Blocking this signal prevents organ rejection while allowing the body to continue fighting other infections. Cyclosporine, by contrast, indiscriminately targets and blocks other cellular signal pathways.      Following in vitro studies, during which the researchers observed LEA29Y was 10 times more effective than cyclosporine in blocking the co-stimulatory immune signal, Larsen and Pearson tested the drug in nonhuman primates and found it significantly prolonged survival of transplanted kidneys.      The research team recently completed a phase 2 clinical study comparing LEA29Y with cyclosporine in human kidney transplant patients.
	TOP
	Aging with less grace, spatially speaking When it comes to aging, women may have another advantage over men. Research conducted at Yerkes National Primate Research Center shows that male nonhuman primates are more susceptible to age-related cognitive decline than females.      In the study, neuroscientists Agnes Lacreuse and James Herndon observed young and elderly nonhuman primates performing tasks that measured spatial memory, which records environmental and spatial-orientation information. The researchers presented each animal with an increasing number of identical disks, and the animals had to identify each disk as it appeared in a new location.      The young adult males outperformed the females, a finding consistent with human data that shows men have a higher capacity than women for maintaining or updating spatial information. Among older nonhuman primates, the researchers found cognitive decline in both sexes. However, sex differences in the spatial memory performance tasks had disappeared. The finding suggests that spatial abilities declined at a greater rate in males than in females as they got older.      On the human front, an NIH clinical trial that included Emory researchers examined the ability of drugs to prevent or delay the onset of Alzheimer’s disease. Patients with mild cognitive impairment who were treated with Aricept had a lower rate of progression to symptoms of Alzheimer’s during the early part of treatment. Vitamin E, however, was found to have no benefit in delaying the disease.
	TOP
	Junk DNA and social behavior     Why are some people shy while others are outgoing? A recent study in Science demonstrates for the first time that social behavior may be shaped by differences in the length of seemingly nonfunctional DNA, sometimes referred to as junk DNA. The finding by researchers at Yerkes National Primate Research Center and the Center for Behavioral Neuroscience has implications for understanding human social behavior and disorders, such as autism.      The study examined whether the junk DNA, formally known as microsatellite DNA, associated with the vasopressin receptor gene affects social behavior in male prairie voles, a rodent species. Researchers bred two groups of prairie voles with short and long versions of the junk DNA. By comparing the behavior of male offspring after they matured, they discovered microsatellite length affects gene expression patterns in the brain.      In the prairie voles, males with long microsatellites had higher levels of vasopressin receptors in brain areas involved in social behavior and parental care, particularly the olfactory bulb and lateral septum. These males spent more time investigating social odors and approached strangers more quickly. They also were more likely to form bonds with mates, and they spent more time nurturing their offspring.
	TOP
	Finding missed cases of HIV Although standard tests that measure antibody response to HIV have become increasingly sensitive, cases are still missed. In a recent study, researchers at Emory, the University of North Carolina at Chapel Hill, and the Georgia Department of Human Resources used nucleic acid amplification testing (NAAT) in addition to standard tests to screen clients at urban clinics and HIV testing sites in Atlanta. The combined approach, they found, uncovered 6% more cases of HIV infection than current standard practice.      NAAT-based screening can identify people with acute HIV infection earlier when they may be most infectious and at risk for spreading the virus, according to Emory infectious disease specialist Frances Priddy (above), who recently presented the findings at the 12th Conference on Retroviruses and Opportunistic Infections.
	TOP
	Female sex hormone reduces stress response     A steroid hormone released during the metabolism of progesterone reduces the brain’s response to stress in rats, according to research by scientists at Emory School of Medicine, Yerkes National Primate Research Center, and the Center for Behavioral Neuroscience. The researchers found that allopregnanolone, a progesterone metabolite, reduces the brain’s response to corticotropin-releasing factor (CRF), a hormone that plays an important role in the stress response.      In a test to gauge stress and anxiety, the researchers compared how female rats with different levels of estrogen and progesterone reacted to loud noises after injections of CRF. These injections usually increase the acoustic startle response. In comparing the acoustic startle responses after CRF injection in three groups—estrogen-only, estrogen-plus-progesterone, and a control group—the researchers found that the startle response was unaffected in both the estrogen-only and control groups. However, in the estrogen-plus-progesterone group, CRF-enhanced startle was significantly lower.      The experiment and others led the scientists to conclude that progesterone inhibits the effect of CRF on the acoustic startle response. This finding correlates with clinical evidence that some people suffering from depression and anxiety have low allopregnanolone levels that normalize after treatment with anti-depressant medications. The research, published in the Journal of Neuroscience, could lead to drug development and new approaches for controlling mood disorders in women.
	TOP
	Treating depression, deep within the brain Deep brain stimulation may have clinical benefits for people with severe depression who have failed other treatments, according to a study published in the March issue of Neuron. In previous studies at the University of Toronto, where she began the research, Helen Mayberg, now a professor in the Departments of Psychiatry and Behavioral Sciences and Neurology at Emory, found that the subgenual cingulate region of the brain (Cg25) plays a critical role in modulating sadness and negative mood states in both healthy and depressed people. She wondered if stimulation of this region could improve the treatment of depression, as with other neurologic disorders such as Parkinson’s disease, epilepsy, and dystonia.      Guided by MRI, Mayberg’s team implanted thin wire electrodes in the brain region of Cg25 in six patients. The wires were connected under the skin of the neck to a pacemaker-like device that directed the electric current.      During the six-month study, four of the six patients showed a significant response with sustained improvement. PET scans also showed a significant response in the frontal cortex, hypothalamus, and brainstem, consistent with findings seen with successful response to medication or psychotherapy in less severely ill patients. This study was the culmination of 15 years of research using brain imaging technology, says Helen Mayberg (shown above).
	TOP
	Easy on the heart and the wallet     The drug eplerenone, which blocks aldosterone—a hormone involved in regulating blood levels of sodium and potassium as well as the constriction of blood vessels—not only helps people with heart disease live longer, it also is cost-effective, according to an international study, led by the Emory Heart Center’s William Weintraub. Researchers found a significant decrease in mortality in patients with left ventricular systolic dysfunction and congestive heart failure following heart attack. Also, the drug added only about $3.60 (wholesale), on average, to treatment costs. In further analysis, researchers calculated the cost for each quality-life-year gained by patients treated with eplerenone at $13,178. “Health economists generally regard any price below $50,000 a year as cost-effective,” Weintraub says.
	TOP
	Applying nanotechnology to cardiovascular disease The National Heart, Lung and Blood Institute (NHLBI) of the NIH has awarded researchers from Georgia Institute of Technology and Emory $11.5 million to establish a new research program focused on creating advanced nanotechnologies to analyze plaque formation on the molecular level and detect plaque at its early stages.      The multidisciplinary program, part of NHLBI’s Program of Excellence in Nanotechnology (PEN), is headed by Gang Bao, a professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory. The program, one of four national PEN awards, includes 12 faculty from both institutions and is based at Emory. It will focus primarily on detecting plaque and pinpointing its genetic causes with three types of nanostructured probes—molecular beacons, semiconductor quantum dots, and magnetic nanoparticles.      A molecular beacon is a biosensor about 4 to 5 nanometers in size that can seek out and detect specific target genes. It is a short piece of single-stranded DNA (ssDNA) in the shape of a hairpin loop with a fluorescent dye molecule at one end and a “quencher” molecule at the other end. The ssDNA is synthesized to match a region on a specific messenger RNA (mRNA) that is unique to the gene. The fluorescence of the beacon is quenched, or suppressed, until it seeks out and binds to a complementary target mRNA, which causes the hairpin to open up and the beacon to emit light.      The level of gene expression within a cell can reflect susceptibility to disease. The fluorescence from the beacons will vary with the level of the target genes’ expression in each cell, creating a glowing marker if the cell has a detectable level of gene expression that is known to contribute to cardiovascular disease.      To complement these studies, the team will develop quantum dot nanocrystal probes and use them to study protein molecular signatures of cardiovascular disease. Quantum dots are nanometer-sized semiconductor particles that have unique electronic and optical properties due to their size and highly compact structure. Quantum dot-based probes can act as markers for specific proteins and cells and can be used to study protein-protein interactions in live cells or to detect diseased cells.      Other research will use magnetic nanoparticles to detect early-stage plaques. These particles will target specific proteins on the surface of cells in a plaque and serve as a contrast agent in MRI, providing an image of plaque formation.
	TOP
	Eat mor veggees     If the next 100 billion burgers sold under the Golden Arches were veggie-based rather than beef, Americans’ cholesterol levels, fiber intake, and overall health would improve, according to an article in the May issue of the American Journal of Preventive Medicine. Lead author Erica Frank of Emory’s Department of Family and Preventive Medicine compared the McVeggie burger (sold in Canada and some major cities across the United States) to the beef burger, finding that the switch to the plant-based choice would result in 1 billion more pounds of fiber, 550 million fewer pounds of saturated fat, 1.2 billion fewer total pounds of fat, and 660 million more pounds of protein. Supersize that, and you’ve got a healthier country.