World News

Small Changes in Protein Chemistry Play Large Role in Huntington's Disease

In Huntington's disease, a mutated protein in the body becomes toxic to brain cells. Recent studies have demonstrated that a small region adjacent to the mutated segment plays a major role in the toxicity. Two new studies supported by the National Institutes of Health show that very slight changes to this region can eliminate signs of Huntington's disease in mice.

Researchers do not fully understand why the protein (called mutant huntingtin) is toxic, but one clue is that it accumulates in ordered clumps of fibrils, perhaps clogging up the cells' internal machinery.

"These studies shed light on the structure and biochemistry of the mutant huntingtin protein and on potentially modifiable factors that affect its toxicity," said Margaret Sutherland, Ph.D., a program director at NIH's National Institute of Neurological Disorders and Stroke (NINDS). "They reveal sites within the huntingtin protein and within broader disease pathways that could serve as targets for drug therapy."

Both studies were published online this week. One study, published in the Journal of Cell Biology, was led by Leslie Thompson, Ph.D., and Joan Steffan, Ph.D., of the University of California, Irvine. The other study, in Neuron, was led by X. William Yang, M.D., Ph.D., of the University of California, Los Angeles in collaboration with Ron Wetzel, Ph.D., of the University of Pittsburgh School of Medicine.

Huntington's disease is inherited, and usually strikes in middle age, producing uncontrollable movements of the legs and arms, a loss of muscle coordination, and changes in personality and intellect. It is inexorably progressive and leads to death of affected persons usually within 20 years after symptoms first appear. Individuals with the disease carry mutations that affect the huntingtin protein. The mutations involve a triple repeat DNA sequence, a type of genetic miscue similarly found in Friedreich's ataxia, Kennedy's disease, fragile X syndrome, and other neurodegenerative disorders.

The normal huntingtin protein consists of about 3,150 amino acids (which are the building blocks for all proteins). In individuals with Huntington’s disease, the mutated protein contains an abnormally long string of a single amino acid repeat; lengthier chains are associated with worse symptoms and earlier onset of the disease. In recent years, however, researchers have begun looking at the effects of other, nearby amino acids in this large protein — and in particular, biochemical changes to those amino acids.

In their study, Drs. Steffan and Thompson investigated how a process called phosphorylation affects huntingtin. Phosphorylation is the attachment of chemical tags, known as phosphates, onto the amino acids in a protein. The process occurs naturally and is a way of marking proteins for destruction by cellular waste handling systems. The researchers liken it to putting a sign on a pile of junk that tells the garbage collectors to take it away. Their study shows that phosphorylation of just two amino acids, located at one end of huntingtin, targets the protein for destruction and protects against the toxic effects of the mutant protein.

"Clearance of mutant huntingtin is likely regulated at many levels, but our data establish that these two amino acids are critical," Dr. Steffan said.

Could boosting phosphorylation of those two amino acids reduce the buildup of huntingtin and improve symptoms of the disease? In parallel with the UC Irvine research, Dr. Yang and his team at UCLA were asking that question using an animal model of Huntington’s disease. Previously, Dr. Yang had created mice that carry the mutant huntingtin gene. These mice develop symptoms reminiscent of Huntington’s disease in humans, including poor coordination, mental changes such as increased anxiety, loss of brain tissue, and accumulation of clumps of huntingtin in brain cells.

Through further genetic engineering, Dr. Yang altered the same two critical amino acids at the end of the mutant huntingtin protein to either mimic phosphorylation (phosphomimetic) or resist it (phosphoresistant). Mice with the phosphoresistant version of the protein developed symptoms of Huntington's, but mice with the phosphomimetic version remained free of symptoms and huntingtin clumps up to one year.

Meanwhile, test tube experiments by Dr. Wetzel's group in Pittsburgh showed that phosphomimetic modification of a huntingtin fragment reduced its tendency to form clumps. Together, data from the mouse and test tube experiments provide strong support for the idea that phosphorylation acts as a molecular switch to alter clumping of the mutant protein, the researchers said.

The nearly complete lack of any signs of disease in the phosphomimetic Huntington mice may point toward new strategies to treat the disorder someday. Dr. Yang said, "Drugs that enhance or mimic the effects of phosphorylation may help to detoxify the mutant huntingtin protein."

If such drugs could be developed, Drs. Steffan and Thompson theorize, they would likely be most effective at early stages of the disease, but less so at later stages, when the clearance machinery appears to run down. Dr. Yang said he plans to examine older mice carrying the phosphomimetic version of mutant huntingtin to determine how long they are protected from the disease.

The researchers received major funding from NINDS, with additional support from the National Institute on Aging, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of General Medical Sciences. Several nonprofit foundations also contributed to the research, including the Hereditary Disease Foundation, the Fox Family Foundation and CHDI Inc.

Co-authors of the Journal of Cell Biology study included J. Lawrence Marsh, Ph.D. and Lan Huang, Ph.D., at UC Irvine; Ana Maria Cuervo, M.D., Ph.D., at Albert Einstein College of Medicine, New York City; Donald C. Lo, Ph.D. at Duke University, Durham, N.C.; Paul H. Patterson, Ph.D., at California Institute of Technology, Pasadena; and Steven Finkbeiner, M.D., Ph.D., at the University of California, San Francisco.

Co-authors of the Neuron study included Xiaofeng Gu, M.D., Ph.D., and Erin Greiner at UCLA; Rakesh Mishra and Ravindra Kodali, Ph.D., at the University of Pittsburgh; Alex Osmand, Ph.D., at the University of Tennessee, Knoxville; and Dr. Finkbeiner at UCSF.

NINDS (www.ninds.nih.gov) is the nation’s primary supporter of biomedical research on the brain and nervous system. NIA (www.nia.nih.gov) leads the federal effort supporting and conducting research on aging and the medical, social and behavioral issues of older people. NICHD (www.nichd.nih.gov) sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NIGMS (www.nigms.nih.gov) supports basic biomedical research that is the foundation for advances in disease diagnosis, treatment and prevention.

For more information about Huntington's disease, visit http://www.ninds.nih.gov/disorders/huntington/huntington.htm.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

HHS Announces New Health IT Workforce Grants

Source: HHS

The Office of the National Coordinator for Health Information Technology (ONC) in the Department of Health and Human Services (HHS) announced today the availability of two additional grant programs to support the training and development of the skilled workforce required to support broad adoption and use of health information technology (health IT). These programs are titled Information Technology Professionals in Health Care: Program of Assistance for University-Based Training Programs (University-Based Training Program) and Information Technology Professionals in Health Care: Competency Examination for Individuals (Competency Examination Program).

Authorized by the American Recovery and Reinvestment Act (ARRA), the grants will work to help strengthen and support the health IT workforce. The new grant programs will award $32 million to establish university-based certificate and advanced degree health IT training programs and $6 million dollars to develop a health IT competency examination program. These awards, together with the previous announced $80 million in workforce program grants (Community College Consortia on Nov. 24, 2009, and Curriculum Development Centers on Dec. 15, 2009), recognize the critical importance of developing a well-trained health IT workforce to support the adoption and meaningful use of health IT.

For the University-Based Training Program, ONC anticipates issuing approximately eight to twelve one-time funding awards to support academic programs that rapidly increase the availability of individuals qualified to serve in specific health IT professional roles requiring university-level training. The training supported by this program will emphasize programs that can be completed by the trainee in one year or less. Awards are for a 39-month project period. Four-year colleges and universities are eligible to apply. Applications are due by Jan. 25, 2010, with final awards expected in March 2010.

For the Competency Examination Program, ONC anticipates issuing a single one-time funding award to support the development and initial administration of a set of health IT competency examinations. The examinations will assess basic competency for individuals trained through short-duration, non-degree health IT programs, and for members of the workforce with relevant experience or other types of training who are seeking to demonstrate their competency in certain health IT workforce roles integral to achieving meaningful use of electronic health information. The award is for a two-year project period. Applications are due by Jan. 25, 2010, and the final award is expected in March 2010.

“To realize the widespread adoption of EHRs and achieve the vision of a transformed health system that health IT can facilitate, the workforce needs to be expanded and properly trained to facilitate rapid uptake of health IT by health care providers,” said the National Coordinator for Health Information Technology, Dr. David Blumenthal. “The workforce development program is expected to generate highly skilled professionals in key roles to meet 85 percent of the estimated need for expansion of the health IT workforce, who will in turn support health care providers and hospitals implement and maintain electronic health records and use them to strengthen the delivery of care.”

Information about the HITECH grants available through the workforce development program is available at http://HealthIT.HHS.gov/ and www.grants.gov.

For information about other HHS Recovery Act programs, see http://www.hhs.gov/recovery.

NASA Flight Tests Unique Jumbo Jet; Plane's Airborne Telescope Will Be Used to Unlock Secrets of the Cosmos

Source: NASA

EDWARDS, Calif. -- A NASA jumbo jet that will help scientists unlock the origins of the universe with infrared observations reached a milestone Friday when doors covering the plane's telescope were fully opened in flight.

The Stratospheric Observatory for Infrared Astronomy, a modified 747 jet known as SOFIA, flew for one hour and 19 minutes, which included two minutes with the telescope's doors fully opened. The goal was to allow engineers to understand how air flows in and around the telescope. It was the first time outside air has interacted with the part of the plane that carries the 98-inch infrared telescope.

"Today we opened the telescope cavity door, the first time we have fully exposed the telescope and the largest cavity ever flown while in flight," said Bob Meyer, SOFIA program manager at NASA's Dryden Flight Research Center in Edwards, Calif. "This is a significant step toward certifying NASA's next great observatory for future study of the universe."

Besides these test flights of the airplane, two flights to operate and verify the scientific capabilities of the telescope assembly are planned for spring 2010. Telescope systems such as the vibration isolation system, the inertial stabilization system and the pointing control system will be tested during daytime flights.

These flights will prepare the telescope assembly for the first flight with the telescope operating. That first flight will be the initial opportunity scientists have to use the telescope and begin the process of quantifying its performance to prepare for SOFIA's planned 20-year science program.

SOFIA is a joint venture of NASA and the German Aerospace Center. NASA supplied the aircraft. The telescope was built in Germany.

Dryden manages the SOFIA program. The aircraft is based at NASA's Dryden Aircraft Operations Facility in Palmdale, Calif. NASA's Ames Research Center at Moffett Field, Calif., manages SOFIA's scientific program. The Universities Space Research Association, in Columbia, Md., and the German SOFIA Institute in Stuttgart, Germany, operate SOFIA's scientific program.

To see a picture of SOFIA with the doors to the telescope cavity open, visit:

http://www.nasa.gov/centers/dryden/multimedia/imagegallery/SOFIA/ED09-0279-07.html

Video from SOFIA's flight will air on NASA Television. For NASA TV streaming video, schedules, and downlink information, visit:

http://www.nasa.gov/ntv

For more details about SOFIA and its mission, visit:

http://www.nasa.gov/sofia

Crew Lifts Off From Kazakhstan to Begin Science and Construction Work Aboard the International Space Station

Source: NASA

HOUSTON -- NASA astronaut T.J. Creamer, Russian cosmonaut Oleg Kotov and Japan Aerospace Exploration Agency astronaut Soichi Noguchi safely launched aboard a Soyuz spacecraft to the International Space Station on Sunday. Liftoff occurred at 3:52 p.m. CST from the Baikonur Cosmodrome in Kazakhstan.

The three Soyuz crew members are scheduled to dock with their new home at 4:58 p.m., Tuesday. They will join Expedition 22 crew members Jeff Williams, a NASA astronaut and the station commander, and Max Suraev, a Russian cosmonaut and station flight engineer, aboard the orbiting laboratory.

The station's five residents have some busy months ahead. Kotov and Suraev will conduct a planned spacewalk in January from the Pirs airlock, part of the station's Russian segment. Less than a week later, Williams and Suraev will fly the Soyuz spacecraft that brought them to the station from its current location on the end of the outpost's Zvezda service module to the new Poisk module. In February, the crew will welcome a Progress unmanned resupply ship and space shuttle Endeavour's STS-130 mission. Endeavour and its crew will deliver the new Tranquility node and its cupola, one of the last major portions of the station to be installed.

Coverage of the docking of Creamer, Kotov and Noguchi will begin on NASA Television at 4:30 p.m. NASA TV will return at 6 p.m. for coverage of the hatches opening and the welcoming ceremony between the two crews, which will take place at about 6:29 p.m. For NASA TV streaming video, schedule and downlink information, visit:

http://www.nasa.gov/ntv

For more information about the space station, visit:

http://www.nasa.gov/station

Undergraduate Students Fly High for Weightless Science

Source: NASA

HOUSTON -- NASA has selected 28 undergraduate student teams to test their science experiments in simulated weightlessness. The teams were selected to fly in the summer of 2010 with NASA's Reduced Gravity Student Flight Opportunities and Systems Engineering Educational Discovery (SEED) programs.

Selected teams will test and evaluate their experiments aboard an aircraft modified to simulate a reduced-gravity environment. The aircraft will fly approximately 30 roller-coaster-like climbs and dips during experiment flights to produce periods of weightlessness and hyper-gravity ranging from 0 g to 2 g.

"Today's students will be the ones going to the moon and beyond to live, explore and work," said Douglas Goforth, the Reduced Gravity Education Flight Program manager at NASA's Johnson Space Center in Houston."This project gives them a head start in preparing for those future ventures by allowing them to conduct hands-on research and engineering today in a unique reduced-gravity laboratory."

The Reduced Gravity Student Flight Opportunities Program provides a rare academic experience for undergraduate students to propose, design, fabricate, fly and evaluate a reduced-gravity experiment. The overall experience includes scientific research, hands-on experimental design, test operations and outreach activities.

Teams selected to participate in the Reduced Gravity Student Flight Opportunities Program are from Utah State University, San Jacinto College North, the College of New Jersey, State University of New York at Buffalo, West Virginia University, Purdue University, Yale University, Austin Community College, the University of Washington, the University of Wisconsin at Madison, two teams from Embry-Riddle Aeronautical University, and two teams from the University of Michigan. Teams also may invite a full-time, accredited journalist to fly with them and document the team's experiment and experiences.

Teams selected to participate in the SEED program will work with NASA scientists, engineers and researchers on systems engineering projects that use a reduced gravity environment to test spaceflight hardware, spacecraft components and spaceflight procedures. Each team is assigned a NASA principal investigator to help prepare their experiment for flight. The SEED teams also will participate in at least two videoconferences through NASA's Digital Learning Network to work with other engineering and agency organizations.

The SEED teams for 2010 are from Washington University, Massachusetts Institute of Technology, the University of Wisconsin, Auburn University, the Ohio State University, the University of Nebraska, the University of Toledo, Carthage College, Yale University, the University of Kentucky, the University of Colorado, and Boise State University, from which two teams were selected.

Under these programs, NASA continues its investment in the nation's education programs. It is directly tied the agency's education goal of strengthening NASA and the nation's future workforce. Through this and other college and university programs, NASA will identify and develop the critical skills and capabilities needed to carry out its space exploration mission.

The flights are provided in cooperation with the Reduced Gravity Office at NASA's Johnson Space Center. For more information about the Reduced Gravity Education Flight Program or to view abstracts of the selected team's experiments visit:

http://microgravityuniversity.jsc.nasa.gov

For more information about SEED, visit:

http://microgravityuniversity.jsc.nasa.gov/se

For more information about NASA's education programs, visit:

http://www.nasa.gov/education