Functional electrical stimulation cycling promotes recovery in chronic spinal cord injury

Public release date: 4-Mar-2013
[ | E-mail | Share ]

Contact: Cynthia Chen
cchen@spectrumscience.com
202-955-6222
Kennedy Krieger Institute

Study by Kennedy Krieger's International Center for Spinal Cord Injury suggests activity-based restorative therapy programs may provide substantial benefits for persons with chronic SCI

(Baltimore, MD) A new study by Kennedy Krieger Institute's International Center for Spinal Cord Injury (Epub ahead of print) finds that long-term lower extremity functional electrical stimulation (FES) cycling, as part of a rehabilitation regimen, is associated with substantial improvements in individuals with chronic spinal cord injury (SCI). Improvements include neurological and functional gains, as well as enhanced physical health demonstrated by decreased fat, increased muscle mass and improved lipid profile. Prior to this study's publication today in the Journal of Spinal Cord Medicine, the benefits of activity-based restorative therapy (ABRT) programs, such as FES cycling, were largely anecdotal despite publicity in conjunction with the recovery of actor and activist Christopher Reeve.

In FES, small electrical pulses are applied to paralyzed muscles to stimulate movement. In the case of FES cycling, FES pulses prompt the legs of an individual with SCI to "cycle" on an adapted stationary recumbent bicycle. The repetitive activity offers cardiovascular exercise similar to that which an able-bodied individual achieves through walking, but this new research shows that the results go far beyond basic health benefits.

"Exercise has not been commonly advocated for individuals with paralysis because of the assumption that it is of little benefit and it is challenging to exercise limbs that an individual cannot voluntarily move," said John W. McDonald, M.D., Ph.D., senior study author and director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute. "However, we found that FES cycling is a practical form of exercise that provides substantial benefits, including improved physical integrity, enhanced neurological and functional performance, increased muscle size and strength, reduced muscle spasticity and improved quality of life."

Participants in the study included 45 individuals diagnosed with chronic SCI, defined as paralysis continuing more than 16 months following injury. Twenty-five patients with chronic SCI were assigned to the FES cycling group at the Washington University Spinal Cord Injury Program, where Dr. McDonald was section head until 2004. These patients were matched by age, gender, injury level/severity and duration of injury to 20 control patients who received no active physical therapy.

On average, patients did FES cycling for 29.5 months, with an average distance of 10,466 complete cycles of the two pedals per week, the equivalent of taking 20,931 steps. In the retrospective analysis conducted by Kennedy Krieger researchers, improved motor function was observed in 80 percent of the FES group, compared to only 45 percent of control subjects. Clinically important gains in neurological function were also observed in the FES group; response in pinprick sensation was observed in 56 percent of the FES group compared with 25 percent of the control group, while 14 of the 25 FES subjects showed response in light touch scores compared to six of the 20 controls.

Results also showed that FES cycling enhanced muscle strength without increasing spasticity, a common side effect of paralysis that varies from mild muscle stiffness to severe, uncontrollable leg movements. The FES group was found to be on fewer anti-spasticity medications with lower doses than the control group, suggesting that the lower level of spasticity observed in the FES group was not due medication differences between the participants.

FES cycling was also associated with improvements in quality of life and correlated with overall improved health. FES and control groups showed no significant difference in total thigh volume; however, total thigh fat, measured by MRI, was 44.2 percent less in the FES group than in the controls.

According to Dr. McDonald, this is a key finding because intramuscular fat is associated with glucose intolerance, a complication affecting nearly two-thirds of individuals with chronic SCI.

The results of this study support the hypothesis that activity-based rehabilitative strategies can play an important role in promoting physical integrity and functional recovery, even when implemented years after an injury, and provide rationale for a large prospective randomized clinical trial to evaluate the efficacy of ABRT using FES in persons with chronic SCI.

###

This study was funded by the Deans Fund at Washington University School of Medicine, Barnes-Jewish Hospital Foundation, The Barnes-Jewish Hospital Auxiliary Foundation, Christopher Reeve Paralysis Foundation, the Nextsteps Foundation, the Sam Schmidt Foundation, Gateway to a Cure Foundation, the Eric Westacott Foundation and, in part, by the Intramural Research Program at the NIH Clinical Center.

About the International Center for Spinal Cord Injury

The International Center for Spinal Cord Injury (ICSCI) at Kennedy Krieger Institute was founded in 2005 on the philosophy that individuals with paralysis can always hope for recovery of sensation, function, mobility, and independence, months and even years after injury. ICSCI is one of the first facilities in the world to combine innovative research with a unique focus on restoration and rehabilitation for children and adults with chronic paralysis. More than 2,000 patients from the U.S. and around the world have received treatment at the Center.

About the Kennedy Krieger Institute

Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 19,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on the Kennedy Krieger Institute, visit www.kennedykrieger.org.

About the Journal of Spinal Cord Medicine (JSCM)

Serves the international community of professionals dedicated to improving the lives of people with injuries/disorders of the spinal cord. JSCM is the peer-reviewed official journal of the Academy of Spinal Cord Injury Professionals, a US-based multidisciplinary organization serving scientists, physicians, psychologists, nurses, therapists and social workers in the field of spinal cord injury care and research. The editor is Donald Bodner, MD, of the School of Medicine, Case Western University, Cleveland, Ohio. JSCM is published 6 times a year by Maney Publishing.

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Public release date: 4-Mar-2013
[ | E-mail | Share ]

Contact: Cynthia Chen
cchen@spectrumscience.com
202-955-6222
Kennedy Krieger Institute

Study by Kennedy Krieger's International Center for Spinal Cord Injury suggests activity-based restorative therapy programs may provide substantial benefits for persons with chronic SCI

(Baltimore, MD) A new study by Kennedy Krieger Institute's International Center for Spinal Cord Injury (Epub ahead of print) finds that long-term lower extremity functional electrical stimulation (FES) cycling, as part of a rehabilitation regimen, is associated with substantial improvements in individuals with chronic spinal cord injury (SCI). Improvements include neurological and functional gains, as well as enhanced physical health demonstrated by decreased fat, increased muscle mass and improved lipid profile. Prior to this study's publication today in the Journal of Spinal Cord Medicine, the benefits of activity-based restorative therapy (ABRT) programs, such as FES cycling, were largely anecdotal despite publicity in conjunction with the recovery of actor and activist Christopher Reeve.

In FES, small electrical pulses are applied to paralyzed muscles to stimulate movement. In the case of FES cycling, FES pulses prompt the legs of an individual with SCI to "cycle" on an adapted stationary recumbent bicycle. The repetitive activity offers cardiovascular exercise similar to that which an able-bodied individual achieves through walking, but this new research shows that the results go far beyond basic health benefits.

"Exercise has not been commonly advocated for individuals with paralysis because of the assumption that it is of little benefit and it is challenging to exercise limbs that an individual cannot voluntarily move," said John W. McDonald, M.D., Ph.D., senior study author and director of the International Center for Spinal Cord Injury at the Kennedy Krieger Institute. "However, we found that FES cycling is a practical form of exercise that provides substantial benefits, including improved physical integrity, enhanced neurological and functional performance, increased muscle size and strength, reduced muscle spasticity and improved quality of life."

Participants in the study included 45 individuals diagnosed with chronic SCI, defined as paralysis continuing more than 16 months following injury. Twenty-five patients with chronic SCI were assigned to the FES cycling group at the Washington University Spinal Cord Injury Program, where Dr. McDonald was section head until 2004. These patients were matched by age, gender, injury level/severity and duration of injury to 20 control patients who received no active physical therapy.

On average, patients did FES cycling for 29.5 months, with an average distance of 10,466 complete cycles of the two pedals per week, the equivalent of taking 20,931 steps. In the retrospective analysis conducted by Kennedy Krieger researchers, improved motor function was observed in 80 percent of the FES group, compared to only 45 percent of control subjects. Clinically important gains in neurological function were also observed in the FES group; response in pinprick sensation was observed in 56 percent of the FES group compared with 25 percent of the control group, while 14 of the 25 FES subjects showed response in light touch scores compared to six of the 20 controls.

Results also showed that FES cycling enhanced muscle strength without increasing spasticity, a common side effect of paralysis that varies from mild muscle stiffness to severe, uncontrollable leg movements. The FES group was found to be on fewer anti-spasticity medications with lower doses than the control group, suggesting that the lower level of spasticity observed in the FES group was not due medication differences between the participants.

FES cycling was also associated with improvements in quality of life and correlated with overall improved health. FES and control groups showed no significant difference in total thigh volume; however, total thigh fat, measured by MRI, was 44.2 percent less in the FES group than in the controls.

According to Dr. McDonald, this is a key finding because intramuscular fat is associated with glucose intolerance, a complication affecting nearly two-thirds of individuals with chronic SCI.

The results of this study support the hypothesis that activity-based rehabilitative strategies can play an important role in promoting physical integrity and functional recovery, even when implemented years after an injury, and provide rationale for a large prospective randomized clinical trial to evaluate the efficacy of ABRT using FES in persons with chronic SCI.

###

This study was funded by the Deans Fund at Washington University School of Medicine, Barnes-Jewish Hospital Foundation, The Barnes-Jewish Hospital Auxiliary Foundation, Christopher Reeve Paralysis Foundation, the Nextsteps Foundation, the Sam Schmidt Foundation, Gateway to a Cure Foundation, the Eric Westacott Foundation and, in part, by the Intramural Research Program at the NIH Clinical Center.

About the International Center for Spinal Cord Injury

The International Center for Spinal Cord Injury (ICSCI) at Kennedy Krieger Institute was founded in 2005 on the philosophy that individuals with paralysis can always hope for recovery of sensation, function, mobility, and independence, months and even years after injury. ICSCI is one of the first facilities in the world to combine innovative research with a unique focus on restoration and rehabilitation for children and adults with chronic paralysis. More than 2,000 patients from the U.S. and around the world have received treatment at the Center.

About the Kennedy Krieger Institute

Internationally recognized for improving the lives of children and adolescents with disorders and injuries of the brain and spinal cord, the Kennedy Krieger Institute in Baltimore, MD serves more than 19,000 individuals each year through inpatient and outpatient clinics, home and community services and school-based programs. Kennedy Krieger provides a wide range of services for children with developmental concerns mild to severe, and is home to a team of investigators who are contributing to the understanding of how disorders develop while pioneering new interventions and earlier diagnosis. For more information on the Kennedy Krieger Institute, visit www.kennedykrieger.org.

About the Journal of Spinal Cord Medicine (JSCM)

Serves the international community of professionals dedicated to improving the lives of people with injuries/disorders of the spinal cord. JSCM is the peer-reviewed official journal of the Academy of Spinal Cord Injury Professionals, a US-based multidisciplinary organization serving scientists, physicians, psychologists, nurses, therapists and social workers in the field of spinal cord injury care and research. The editor is Donald Bodner, MD, of the School of Medicine, Case Western University, Cleveland, Ohio. JSCM is published 6 times a year by Maney Publishing.

---

[ | E-mail | Share ]

?

AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert! system.

Source: http://www.eurekalert.org/pub_releases/2013-03/kki-fes030413.php

creighton new smyrna beach st. joseph puerto rico primary manning peyton florida state

GM to Boost Electric Vehicle Production 20 Percent | The Energy ...

After a difficult first year in 2011, during which Chevrolet sold a mere 7,671 Volts, sales of the vehicle shot up to a respectable 23,461 car sales for 2012 ? driven largely by consumer demand reacting to high gas prices. According to the Washington Post (hat tip to Treehugger) that surge looks likely to continue: General Motors will be upping 2013?s production to 36,000 units.

Able to run on electrical or gasoline power, the Volt ? along with other hybrids, electric vehicles, and fuel-efficient cars ? has helped boost job growth in the automotive sector in the face of a sluggish economy. This happened despite a storm of right-wing contempt for fuel-efficient automobile technology over the last few years, which focused largely on the Volt as a symbol of President Obama?s (largely successful) attempts to give the American automotive industry a chance to retool itself and get back on its feet.

Since then, overall hybrid sales increased 50 percent in 2012 from the previous model year, sales of plug-in electric vehicles tripled, and GM itself captured 7 percent of the hybrid market ? up 2 percent from the year before. And now the company is looking to bulk up its Volt production by 20 percent:

General Motors Co. is planning to build as many as 36,000 Chevrolet Volts and other plug-in hybrids for worldwide delivery this year, 20 percent more than in 2012, two people familiar with the effort said.

GM is planning to build 1,500 to 3,000 of the fuel- efficient vehicles a month, said the people, who didn?t want to be identified because the target isn?t public. GM sold about 30,000 Volt and similar Opel Ampera cars globally in 2012, said Jim Cain, a company spokesman, who declined to give a target for this year.

Chief Executive Officer Dan Akerson has struggled to compete against more successful alternative-power vehicles such as Toyota Motor Corp.?s Prius. The CEO originally touted the Volt?s gasoline-and-electric system as the technology of the future and forecast global Volt sales of 60,000 in 2012, before settling for half that amount.

The 36,000 target is ?probably a doable number,? Jim Hall, principal of consultancy 2953 Analytics, said. ?It will have a full calendar year in Europe? and GM will probably sell more this year now that the Volt is eligible for the car-pool lane in California, he said.

Admittedly, these numbers remain behind GM?s previous hoped-for targets. It still lags Toyota, which boosted its hybrid sales 70 percent in 2012 over the previous model year, dominating the market with 892,519 sales of its various Prius hybrid models worldwide. The Prius starts at $24,200 ? and a subcompact Prius model sells for $19,080 ? which undercuts GM?s $39,145 four-seat Volt.

So good news for electric and hybrid cars as a whole, and thus for fuel efficiency and the environment. But less so for the Volt itself.

Still, the Chevy Volt has several factors going in its favor. It was selected as 2011?s North American Car of the Year ? with 92 percent of those surveyed telling Consumer Reports they would buy open again. Meanwhile, fuel standards are set to require 54.5 miles per gallon by 2025, technological moves on the horizon promise to make the car?s lithium ion battery technology lighter and more efficient, and there?s every reason to think high gas prices are here to stay.

Connect:

Authored by:

Joseph Romm

Joe Romm is a Fellow at American Progress and is the editor of Climate Progress, which New York Times columnist Tom Friedman called "the indispensable blog" and Time magazine named one of the 25 "Best Blogs of 2010." In 2009, Rolling Stone put Romm #88 on its list of 100 "people who are reinventing America." Time named him a "Hero of the Environment? and ?The Web?s most influential ...

See complete profile

Source: http://theenergycollective.com/josephromm/193551/gm-electric-vehicle-production-2013

derek fisher lyrid meteor shower hippocrates andrew breitbart red wings penguins the band

Scientists say baby born with HIV apparently cured

WASHINGTON (AP) ? A baby born with the AIDS virus appears to have been cured, scientists announced Sunday, describing the case of a child from Mississippi who's now 2? and has been off medication for about a year with no signs of infection.

There's no guarantee the child will remain healthy, although sophisticated testing uncovered just traces of the virus' genetic material still lingering. If so, it would mark only the world's second reported cure.

Specialists say Sunday's announcement, at a major AIDS meeting in Atlanta, offers promising clues for efforts to eliminate HIV infection in children, especially in AIDS-plagued African countries where too many babies are born with the virus.

"You could call this about as close to a cure, if not a cure, that we've seen," Dr. Anthony Fauci of the National Institutes of Health, who is familiar with the findings, told The Associated Press.

A doctor gave this baby faster and stronger treatment than is usual, starting a three-drug infusion within 30 hours of birth. That was before tests confirmed the infant was infected and not just at risk from a mother whose HIV wasn't diagnosed until she was in labor.

"I just felt like this baby was at higher-than-normal risk, and deserved our best shot," Dr. Hannah Gay, a pediatric HIV specialist at the University of Mississippi, said in an interview.

That fast action apparently knocked out HIV in the baby's blood before it could form hideouts in the body. Those so-called reservoirs of dormant cells usually rapidly reinfect anyone who stops medication, said Dr. Deborah Persaud of Johns Hopkins Children's Center. She led the investigation that deemed the child "functionally cured," meaning in long-term remission even if all traces of the virus haven't been completely eradicated.

Next, Persaud's team is planning a study to try to prove that, with more aggressive treatment of other high-risk babies. "Maybe we'll be able to block this reservoir seeding," Persaud said.

No one should stop anti-AIDS drugs as a result of this case, Fauci cautioned.

But "it opens up a lot of doors" to research if other children can be helped, he said. "It makes perfect sense what happened."

Better than treatment is to prevent babies from being born with HIV in the first place.

About 300,000 children were born with HIV in 2011, mostly in poor countries where only about 60 percent of infected pregnant women get treatment that can keep them from passing the virus to their babies. In the U.S., such births are very rare because HIV testing and treatment long have been part of prenatal care.

"We can't promise to cure babies who are infected. We can promise to prevent the vast majority of transmissions if the moms are tested during every pregnancy," Gay stressed.

The only other person considered cured of the AIDS virus underwent a very different and risky kind of treatment ? a bone marrow transplant from a special donor, one of the rare people who is naturally resistant to HIV. Timothy Ray Brown of San Francisco has not needed HIV medications in the five years since that transplant.

The Mississippi case shows "there may be different cures for different populations of HIV-infected people," said Dr. Rowena Johnston of amFAR, the Foundation for AIDS Research. That group funded Persaud's team to explore possible cases of pediatric cures.

It also suggests that scientists should look back at other children who've been treated since shortly after birth, including some reports of possible cures in the late 1990s that were dismissed at the time, said Dr. Steven Deeks of the University of California, San Francisco, who also has seen the findings.

"This will likely inspire the field, make people more optimistic that this is possible," he said.

In the Mississippi case, the mother had had no prenatal care when she came to a rural emergency room in advanced labor. A rapid test detected HIV. In such cases, doctors typically give the newborn low-dose medication in hopes of preventing HIV from taking root. But the small hospital didn't have the proper liquid kind, and sent the infant to Gay's medical center. She gave the baby higher treatment-level doses.

The child responded well through age 18 months, when the family temporarily quit returning and stopped treatment, researchers said. When they returned several months later, remarkably, Gay's standard tests detected no virus in the child's blood.

Ten months after treatment stopped, a battery of super-sensitive tests at half a dozen laboratories found no sign of the virus' return. There were only some remnants of genetic material that don't appear able to replicate, Persaud said.

In Mississippi, Gay gives the child a check-up every few months: "I just check for the virus and keep praying that it stays gone."

The mother's HIV is being controlled with medication and she is "quite excited for her child," Gay added.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/bbd825583c8542898e6fa7d440b9febc/Article_2013-03-03-HIV-Baby%20Cure?/id-e98195c27d894a2ba1a526343cdecaba

patricia heaton arsenic and old lace leslie varez ward solar storms uganda the parent trap

Gridlock: No budging at the budget-cuts deadline (tbo)

Share With Friends: | | Politics - Top Stories Stories, News Feeds and News via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/288473841?client_source=feed&format=rss

ground hog groundhog day 2012 serrano staten island chuck dr jekyll and mr hyde edwin jackson punksatony phil

Namibia to cut corporate tax to encourage investment

WINDHOEK (Reuters) - Namibia, one of the world's largest diamond producers, announced plans to cut its corporate tax rate to 32 percent over the next two years in its 2013/14 budget on Tuesday to encourage investment.

It also said it would cut income tax by adjusting tax bands and expects economic growth to accelerate slightly this year to 4.3 percent.

Corporation tax in Namibia, which is also a major producer of uranium, is now 34 percent, one of the highest in southern Africa and compares with 28 percent in South Africa.

The tax rate does not apply to mining companies, including Anglo American and Rio Tinto, which pay higher tax rates averaging 37.5 percent and as high as 55 percent for diamond miners, plus other levies on top.

Finance Minister Saara Kuugongelwa-Amadhila, presenting the budget to parliament, said corporate tax would be lowered to 33 percent in the financial year ending in March 2014, and to 32 percent in 2014/15.

Kuugongelwa-Amadhila also announced higher spending, mostly on health and education, for 2013/14. That will help push the budget deficit up to 6.4 percent of gross domestic product, from an estimated 2.8 percent in 2012/13, she said.

The minister said slowing economic growth and chronic income inequality had put pressure on public finances.

"Although our fiscal position is not as robust as it was four years ago, it nonetheless remains relatively strong," she said. "We, therefore, have limited room to pursue moderate fiscal expansion in a targeted matter."

She said a major financial markets reform bill was under consultation, while regulations to tighten capital outflows and increase domestic investment were about to be finalised.

A new Banking Institutions Bill that will limit foreign shareholding in Namibia's South African-owned banks, will be implemented this year.

Namibia's economy grew by an estimated 4 percent last year, slowing after a 4.8 percent expansion in 2011.

Foreign firms are also exploring the southern Africa country for gold, lead, zinc and iron ore.

Namibia expects government debt to grow to 27.8 percent of GDP next year, from 26.3 percent last year, the finance minister said.

Source: http://news.yahoo.com/namibia-cut-corporate-tax-encourage-investment-051026962--business.html

daylight savings time 2012 Where To Vote james harden breeders cup Mitch Lucker Red Cross CMA Awards 2012

AP source: LSU in talks to bring in Cameron as OC

Former Baltimore Ravens offensive coordinator Cam Cameron is in talks with LSU coach Les Miles to run the Tigers' offense, said a person familiar with the situation.

The person spoke to The Associated Press on condition of anonymity Friday because the deal was not yet complete. The person says LSU hopes to have an official announcement next week.

The 52-year-old Cameron was fired by Ravens coach John Harbaugh after a Week 14 loss to the Washington Redskins. Following some late-season struggles, Baltimore went on to win the Super Bowl with former Colts coach Jim Caldwell as offensive coordinator.

Greg Studrawa has been LSU's offensive coordinator the past two seasons. He is expected to be retained as offensive line coach.

LSU went 10-3 last season and finished No. 14 in the nation, but the offense struggled with a new quarterback and an offensive line that was beset with injuries. The Tigers ranked 10th out of 14 teams in the Southeastern Conference in total offense, and first-year starting quarterback Zach Mettenberger finished near the bottom of the conference in efficiency rating. LSU was 92nd in the nation in passing.

Studrawa became offensive coordinator shortly before the 2011 season began when Steve Kragthorpe, who had been hired a few months earlier to run the offense, was diagnosed with Parkinson's disease. Miles shuffled his staff and Kragthorpe, the former Louisville and Tulsa coach, remained on as the quarterbacks coach.

Miles and Cameron go way back. The two worked together from 1987-93 as assistants under Bo Schembechler at Michigan.

Cameron was head coach at Indiana from 1997-2001. He never had a winning record with the Hoosiers, but his offenses with Antwaan Randle-El at quarterback were productive. After that he spent five seasons as offensive coordinator with the San Diego Chargers, developing a prolific offense with Phillips Rivers and LaDainian Tomlinson.

That helped him land the job as Miami Dolphins head coach in 2007, but he was fired after one season. He went 1-15 as Nick Saban's replacement in Miami.

He joined the Ravens in 2008 and helped develop quarterback Joe Flacco.

Associated Press

Source: http://hosted2.ap.org/APDEFAULT/347875155d53465d95cec892aeb06419/Article_2013-02-08-FBC-LSU-Cameron/id-22192c1881fa4572832c61e7c5d7fd3a

san antonio weather mike daisey nicollette sheridan apple dividend snow white and the huntsman snow white and the huntsman rupaul drag race

Protein paves the way for correct stem cell differentiation

Feb. 7, 2013 ? A single embryonic stem cell can develop into more than 200 specialized cell types that make up our body. This maturation process is called differentiation and is tightly regulated through strict control of gene activity. If the regulation is lost, specialized cells cannot develop correctly during development. In adulthood, the specialized cells may forget their identity and develop into cancer cells. Research from BRIC, University of Copenhagen, has identified a crucial role of the molecule Fbxl10 in differentiation of embryonic stem cells and suggests the molecule as a new potential target for cancer therapy.

"Our new results show that this molecule is required for the function of one of the most important molecular switches that constantly regulates the activity of our genes. If Fbxl10 is not present in embryonic stem cells, the cells cannot differentiate properly and this can lead to developmental defects," says Professor Kristian Helin, who heads the research group behind the new findings.

Fbxl10 recruits and activates genetic switches

The Polycomb protein complexes PRC1 and PRC2 are some of the most important genetics switches, which control the fate of individual cells through negative regulation of gene activity. The mechanism by which PRCs are recruited to DNA has been elusive as they are not capable of binding DNA directly. The new results from the Helin research group provide a mechanism for how the PRCs are recruited to the genes that are to be silent.

"Our results show that Fbxl10 is essential for recruiting PRC1 to genes that are to be silenced in embryonic stem cells. Fbxl10 binds directly to DNA and to PRC1, and this way it serves to bring PRC1 to specific genes. When PRC1 is bound to DNA it can modify the DNA associated proteins, which lead to silencing of the gene to which it binds," says postdoc Xudong Wu, who has led the experimental part of the investigation.

Fbxl10 is a potential target for cancer therapy

Timing of gene activity is not only crucial during development, but has to be maintained throughout the lifespan of any cell. Some genes are active at a certain times, but inactive at other times.. Here PRC1 comes into play. PRC1 is dynamically recruited to and dissociated from genes according to the needs of our organism. When cancer strikes, this tight regulation of gene activity is often lost and the cells are locked in a less differentiated stage. This loss of differentiation and the accumulation of other mutations allow the cancer cells to undergo indefinite self-renewal through endless cell divisions, an ability that normal differentiated cells are prohibited from through tight gene regulation.

"Given the emerging relationship between cancer and stem cells, our findings may implicate that an aberrant activity of Fbxl10 can disturb PRC function and promote a lack of differentiation in our cells. This makes it worth studying whether blocking the function of Fbxl10 could be a strategy for tumour therapy," says Xudong Wu.

And that is exactly what the researchers want to try. In collaboration with the biotech company EpiTherapeutics, the researchers want to develop inhibitors to Fbxl10 as a potential novel therapy for cancer.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by University of Copenhagen.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Xudong Wu, Jens?Vilstrup Johansen, Kristian Helin. Fbxl10/Kdm2b Recruits Polycomb Repressive Complex 1 to CpG Islands and Regulates H2A Ubiquitylation. Molecular Cell, 2013; DOI: 10.1016/j.molcel.2013.01.016

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/Yy0b8Y4fWlo/130207172113.htm

Talk Like a Pirate Day raiders Demi Lovato iOS 6 Features big brother Shakira iOS 6