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Archive - Mar 28, 2011

Scientists ID Gene Region Associated with Attempted Suicide

A genome-wide association study of thousands of people with bipolar disorder suggests that genetic risk factors may influence the decision to attempt suicide. Johns Hopkins scientists and an international team of collaborators, reporting online on March 22, 2011, in the journal Molecular Psychiatry, have identified a small region on chromosome 2 that is associated with increased risk for attempted suicide. This small region contains four genes, including the ACP1 gene, and the researchers found above normal levels of the ACP1 protein in the brains of people who had committed suicide. This protein is thought to influence the same biological pathway as lithium, a medication known to reduce the rate of suicidal behavior. The researchers said the findings could lead to better suicide prevention efforts by providing new directions for research and drug development. "We have long believed that genes play a role in what makes the difference between thinking about suicide and actually doing it," said study leader Dr. Virginia L. Willour, Ph.D., an assistant professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine. Dr. Willour and her colleagues studied DNA samples from nearly 2,700 adults with bipolar disorder, 1,201 of them with a history of suicide attempts and 1,497 without. They found that those with one copy of a genetic variant in the region of chromosome 2 where ACP1 is located were 1.4 times more likely to have attempted suicide, and those with two copies were almost 3 times as likely. Dr. Willour and her colleagues were able to replicate their findings in another group of samples: This one comprised DNA from more than 3,000 people with bipolar disorder.

New Nano-Based Device Can Detect Single Cancer Cells

A Harvard bioengineer and an MIT aeronautical engineer have created a new device that can detect single cancer cells in a blood sample, potentially allowing doctors to quickly determine whether cancer has spread from its original site. The microfluidic device, described in the March 17, 2011 online edition of the journal Small, is about the size of a dime, and might also detect viruses such as HIV. It could eventually be developed into low-cost tests for doctors to use in developing countries where expensive diagnostic equipment is hard to come by, said Dr. Mehmet Toner, professor of biomedical engineering at Harvard Medical School and a member of the Harvard-MIT Division of Health Sciences and Technology. Dr. Toner built an earlier version of the device four years ago. In that original version, blood taken from a patient flows past tens of thousands of tiny silicon posts coated with antibodies that stick to tumor cells. Any cancer cells that touch the posts become trapped. However, some cells might never encounter the posts at all. Dr. Toner thought if the posts were porous instead of solid, cells could flow right through them, making it more likely they would stick. To achieve that, he enlisted the help of Dr. Brian Wardle, an MIT associate professor of aeronautics and astronautics, and an expert in designing nano-engineered advanced composite materials to make stronger aircraft parts. Out of that collaboration came the new microfluidic device, studded with carbon nanotubes, that collects cancer cells eight times better than the original version. Circulating tumor cells (cancer cells that have broken free from the original tumor) are normally very hard to detect, because there are so few of them — usually only several cells per 1-milliliter sample of blood, which can contain tens of billions of normal blood cells.

Plant Pathologists ID Key Metabolite in Systemic Immunity

University of Kentucky plant pathologists recently discovered a metabolite that plays a critical role early on in the ability of plants, animals, humans and one-celled microorganisms to fend off a wide range of pathogens at the cellular level, which is known as systemic immunity. This mode of resistance has been known for more than 100 years, but the key events that stimulate that resistance have remained a mystery. The findings of the UK College of Agriculture researchers, led by Dr. Pradeep Kachroo and Dr. Aardra Kachroo, were published online in Nature Genetics on March 27, 2011. Researchers from the UK Department of Statistics and Washington State University also contributed to the article. "If you can generate systemic immunity, you can have great benefits in disease resistance," Dr. Kachroo said. "It is particularly gratifying to be able to describe a mechanism for a type of immunity; pioneering studies were incidentally carried out by our own emeritus faculty, Joe Kuc." Using soybeans and Arabidopsis, a model laboratory plant, the scientists were able to identify the metabolite glycerol-3-phosphate as a key mobile regulator of systemic immunity. A metabolite is a substance produced in the body through normal metabolic processes. The glycerol-3-phosphate is transformed into an unknown compound and uses a protein, called DIR1 to signal systemic immunity. Scientists already identified the protein as a necessary component to trigger systemic immunity. "The metabolite and protein are dependent on each other to transport immunity from one location in the plant tissue to the other," Dr. Kachroo said. "Metabolite levels increase in plant tissues after the plant has been inoculated by a pathogen." While the research was conducted on plants, Dr.

Infrared Light Activates Heart and Ear Cells; Great Clinical Potential

University of Utah scientists and colleagues have used invisible infrared light to make rat heart cells contract and toadfish inner-ear cells send signals to the brain. The discovery someday might improve cochlear implants for deafness and lead to devices to restore vision, maintain balance and treat movement disorders like Parkinson's. "We're going to talk to the brain with optical infrared pulses instead of electrical pulses," which now are used in cochlear implants to provide deaf people with limited hearing, said Dr. Richard Rabbitt, a professor of bioengineering and senior author of the heart-cell and inner-ear-cell studies published in the March 15, 2011 issue of The Journal of Physiology. The studies also raise the possibility of developing cardiac pacemakers that use optical signals rather than electrical signals to stimulate heart cells. But Rabbitt says that because electronic pacemakers work well, "I don't see a market for an optical pacemaker at the present time." The scientific significance of the studies is the discovery that optical signals – short pulses of an invisible wavelength of infrared laser light delivered via a thin, glass optical fiber – can activate heart cells and inner-ear cells related to balance and hearing. In addition, the research showed infrared activates the heart cells, called cardiomyocytes, by triggering the movement of calcium ions in and out of mitochondria, the organelles or components within cells that convert sugar into usable energy. The same process appears to occur when infrared light stimulates inner-ear cells. Infrared light can be felt as heat, raising the possibility the heart and ear cells were activated by heat rather than the infrared radiation itself.

Sindbis Virus Replicase May Be Potential Cancer Therapy

Alpha viruses, such as Sindbis virus, carry their genetic information on a single strand of RNA. On infection they use a protein, replicase, to produce double-stranded RNA (dsRNA) which is used as genetic material to make more viruses. However, the body recognizes dsRNA as foreign, and infected cells initiate an immune response. New research published on March 28, 2011, in BioMed Central's open-access journal BMC Cancer demonstrates that an artificial plasmid coding for the replicase genes of Sindbis virus causes regression and destruction of lung cancer and melanoma cells in mice. Previous attempts to use synthetic dsRNA to destroy tumor cells have met with problems, including side effects at an effective dose, but there are also concerns about using attenuated viruses, to deliver dsRNA inside cells. Researchers from the University of Texas at Austin and collaborating institutions have instead used a plasmid containing Sindbis replicase genes (nsp1-4) to force cells to produce dsRNA themselves. For ten days, mice were given daily injections of plasmid into the site of a tumor. After another 15 days most of the tumors had begun to regress, and by day 37 all of the tumors had either regressed or been destroyed. Professor Zhengrong Cui, senior author of the study, said, "The anti-cancer action of the plasmid seemed to be two-fold. Firstly, accumulation of dsRNA resulted in cell death and secondly the presence of dsRNA, and the foreign, unmethylated, plasmid DNA, inside a cell activated both innate and adaptive immune responses." Professor Cui continued, "In our study both highly immunogenic and poorly immunogenic tumors were receptive to treatment with an RNA replicase-based plasmid.