Intramural Research Briefs
COMPILED BY TANIA LOMBO, EDITORIAL INTERN
ROCKY MOUNTAIN LABORATORIES, NIAID
Scanning electron micrograph of house dust, which can contain allergens such as hair, pollen, insect fecal matter, and animal dander. NIEHS scientists documented a protein in dust that can worsen allergic responses to indoor allergens.
NIEHS: BACTERIAL PROTEIN IN HOUSE DUST TRIGGERS ASTHMA
Household dust typically contains many allergens including those derived from dust mites, cockroaches, and animal dander. A bacterial protein called flagellin in the dust may worsen allergic responses to indoor allergens, according to research conducted by NIEHS and Duke University (Durham, N.C.) scientists. The finding is the first to document the presence of flagellin in house dust, bolstering the link between allergic asthma and the environment. After inhaling house dust, mice that were able to respond to flagellin displayed all of the common symptoms of allergic asthma, including more mucus production, airway obstruction, and airway inflammation. However, mice lacking a gene that detects the presence of flagellin had weaker symptoms. In addition to the mouse study, the research team also determined that people with asthma have higher concentrations of antibodies against flagellin in their blood than do non-asthmatic people. Reducing the amount of flagellated bacteria by cleaning might help to reduce the incidence of allergic asthma, but more studies are necessary to confirm the observations. (NIEHS authors: R.H. Wilson, S. Maruoka, G.S. Whitehead, J.F. Foley, G.P. Flake, M.L. Sever, D.C. Zeldin, S. Garantziotis, H. Nakano, and D.N Cook; Nature Med 18:1705—1711, 2012)
NIDCD: LET YOUR BRAIN BE FREE TO FOLLOW THE BEAT
NIDCD researchers are gaining insights into the creative process by using functional magnetic resonance imaging to study the brain activity of rappers when they are “freestyling”—spontaneously improvising lyrics in real time. The findings reveal that this form of vocal improvisation is associated with a unique functional reallocation of brain activity in the prefrontal cortex. The researchers propose a novel neural network that appears to be intimately involved in improvisatory and creative endeavors. The scientists scanned the brains of 12 freestyle rappers while they performed two tasks using an identical eight-bar music track. In the first task, they improvised rhyming lyrics and rhythmic patterns guided only by the beat; in the second task, they performed a well-rehearsed set of lyrics. During freestyle rapping, there was increased brain activity in the medial prefrontal cortex, a brain region responsible for motivation of thought and action, but decreased activity in dorsolateral prefrontal regions that normally play a supervisory or monitoring role. The findings also suggest that that improvisation engages a brain network that links motivation, language, mood, and action. Further studies could offer more insights into the creative process. (NIH authors: S. Liu, H.M. Chow, Y. Xu, M.G. Erkkinen, K.E. Swett, M.W. Eagle, D.A. Rizik-Baer, and A.R. Braun; Scientific Reports 2:834, 2012)
NIDDK: MODEST DIET AND EXERCISE CAN SUSTAIN WEIGHT LOSS
Exercise and healthy eating reduce body fat and preserve muscle in adults better than diet alone, according to an NIDDK study that analyzed data from 11 participants in the reality television program “The Biggest Loser.” The program shows obese adults losing large amounts of weight over several months. The researchers measured body fat, total energy expenditure, and resting metabolic rate three times: at the start of the program, at week 6, and at week 30, which was at least 17 weeks after participants returned home. Participation in the program led to an average weight loss of 128 pounds, with about 82 percent of that coming from body fat and the rest from lean tissue such as muscle. Using a mathematical computer model of human metabolism, the researchers calculated the diet and exercise changes underlying the observed body weight loss. Diet alone was calculated to be responsible for more weight loss than exercise, with 65 percent of the weight loss consisting of body fat and 35 percent consisting of lean mass like muscle. In contrast, the model calculated that exercise alone resulted in participants losing only fat and no muscle. The findings also suggest that the participants could sustain their weight loss and avoid weight regain by adopting more moderate lifestyle changes—like 20 minutes of daily vigorous exercise and a 20 percent calorie restriction—than those demonstrated on the television program. (NIDDK author: K.D. Hall; Obesity DOI:10.1002/oby.20065)
NCI: LEISURE-TIME PHYSICAL ACTIVITY EXTENDS LIFE EXPECTANCY
The U.S. Department of Health and Human Services recommends that adults ages 18 to 64 engage in regular, weekly aerobic physical activity for 2.5 hours at moderate intensity or 1.25 hours at vigorous intensity. Recent scientific findings suggest that such leisure-time physical activity is associated with longer life expectancy. Recently, NCI researchers led a study that examined data from 650,000 adults, mostly age 40 and older, who took part in one of six population-based studies that were designed to evaluate various aspects of cancer risk. After accounting for other factors that could affect life expectancy, the researchers found that life expectancy was 3.4 years longer for people who reported they got the recommended level of physical activity. People who reported leisure-time physical activity at twice the recommended level gained 4.2 years of life. The researchers even saw a benefit at low levels of activity in people who got half the recommended amount of physical activity—they added 1.8 years to their life. (NCI authors: S.C. Moore, A.V. Patel, C.E. Matthews, A.B. de Gonzalez, Y. Park, H.A. Katki, M.S. Linet, and P. Hartge; PLoS Med 9:1–14, 2012).
NICHD: BENEFITS OF HPV VACCINATION IN HIV-INFECTED WOMEN
NICHD researchers and colleagues found that women infected with the human immunodeficiency virus (HIV) may benefit from the human papilloma virus (HPV) vaccine even if they’ve already been exposed to HPV. HPV is the most common sexually transmitted infection worldwide, and high-risk forms can cause cancer, including cancer of the cervix. The Centers for Disease Control and Prevention recommend vaccination against HPV for girls ages 11 to 26. For those who haven’t been exposed to HPV, the vaccine can protect against four types of the virus: HPV-16 and HPV-18, which cause 70 percent of cervical cancers; HPV-6 and HPV-11, which cause 90 percent of genital warts. But the researchers found that even for HIV-positive women who test positive for one type of HPV, the vaccine may effectively prevent infection with other, especially high-risk, variants that can cause cancer. (NICHD authors: B.G. Kapogiannis and C. Worrell; J Acquir Immune Defic Syndr 61:390–399, 2012)
NIAID: WHITE-NOSE SYNDROME IN BATS MAY PROVIDE CLUES TO HUMAN HEALTH
Studies on lab animals result in gains in human health. But here’s a case in which insight into a human disease might help animals . . . and humans. The mysterious white-nose syndrome (WNS) has decimated eastern North American bat populations. The condition, named for a distinctive fungal growth around the muzzles and on the wings of hibernating bats, has killed at least five million bats since it was first discovered in a cave in central New York in 2006. According to a hypothesis proposed by NIAID and U.S. Geological Survey scientists, these bats might have immune reconstitution inflammatory syndrome (IRIS). IRIS was first described in HIV-AIDS patients about 20 years ago (http://www.ncbi.nlm.nih.gov/pubmed/1472334). As the immune system begins to recover as a result of antiretroviral drug therapy, it might react to a previously acquired infection with an overwhelming inflammatory response resulting in severe and potentially fatal inflammation and tissue damage in the infected areas. Whereas HIV-AIDS suppresses the immune system in humans, hibernation has the same effect on bats, allowing the fungal infection to spread. If the bats survive the infection through winter, they often face intense inflammation at the sites of infection when they awake and their immune system kicks in. The inflammation can be fatal. The scientists say there is evidence that the reaction seen in bats is IRIS. If so, this would be the first time the syndrome has been seen beyond humans. This new insight into the immune response, if verified, could ultimately help both humans and bats. (NIAID authors: D. Barber and J.N. Mandl; Virulence 3:583–588, 2012)
NIEHS: IMPROVING THE DELIVERY OF THERAPEUTIC MEDICINES TO THE BRAIN
P-glycoprotein is one of the major obstacles that prevent medicinal drugs from crossing the blood-brain barrier and reaching their intended targets in the brain. But NIEHS scientists may have found a way to treat brain and spinal cord injuries, brain cancer, epilepsy, neurological complications of the human immunodeficiency virus, and other neurological disorders by turning off P-glycoprotein. In a two-pronged approach, the research team first determined that treating rat brain capillaries with the multiple sclerosis drug marketed as Gilenya (fingolimod) stimulated a specific biochemical signaling pathway in the blood-brain barrier that rapidly and reversibly turned off P-glycoprotein. Team members then pretreated rats with fingolimod and administered three other drugs that P-glycoprotein usually transports away from the brain. They observed a dramatic decline in P-glycoprotein transport activity, which led to a threefold to fivefold increase in brain uptake of each of the three drugs. The findings open a new way of thinking about targets for drug design. (NIH authors: R.E. Cannon, J.C. Peart, C.R. Campos, and D.S. Miller; Proc Natl Acad Sci U S A 109:15930–15935, 2012)
OFFICE OF TECHNOLOGY TRANSFER (OTT)
TREATMENT FOR RARE MUSCLE DISEASE
Investigators from NHGRI and the National Center for Advancing Translational Sciences’ (NCATS) Therapeutics for Rare and Neglected Diseases (TRND) program have launched a clinical trial at the NIH Clinical Center to evaluate the drug candidate DEX-M74 (an amino sugar) as a treatment for a rare degenerative muscle disease, hereditary inclusion body myopathy (HIBM). HIBM, which is caused by mutations in an enzyme that catalyzes the first two steps of sialic acid synthesis, has no approved therapy. The clinical study is being conducted as part of a collaboration of the laboratories of Marjan Huizing (NHGRI) and William Gahl (NHGRI), the NCATS TRND program, and New Zealand Pharmaceuticals Limited, which received an exclusive license from the NIH Office of Technology Transfer for the development of DEX-M74. The underlying technology, which is a new use for a previously known compound, was discovered by Huizing, Gahl, Eirini Manoli, and Riki Klootwijk.
MUTING WORKPLACE NOISE
A team at the NIAID Office of Research Operations (ORO), led by Judit Quasney, invented the sound-attenuation canopy (SAC) to address the workplace problem of ambient noise. The SAC traps and mutes noise transmitted through the open space of a common suspended ceiling system. The Office of Technology Transfer and the NIAID Office of Technology Development collaborated with ORO to transfer this technology to a well-established manufacturer of architectural systems. The SAC improves working conditions and productivity, acts as a fire retardant and debris barrier, and increases energy efficiency. The SAC has been installed in one NIAID building, and plans are in the works to fabricate and install it in NIAID’s new office building on Fishers Lane (Rockville, Md.).