PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

Gene linked to severity of autism's social dysfunction

2011-04-07
(Press-News.org) With the help of two sets of brothers with autism, Johns Hopkins scientists have identified a gene associated with autism that appears to be linked very specifically to the severity of social interaction deficits.

The gene, GRIP1 (glutamate receptor interacting protein 1), is a blueprint for a traffic-directing protein at synapses — those specialized contact points between brain cells across which chemical signals flow.

Identified more than a decade ago by Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator, GRIP1 regulates how fast receptors travel to a cell's surface, where they are activated by a brain-signaling chemical called glutamate, allowing neurons to communicate with one another.

The new study, which tracked two versions of GRIP1 in the genomes of 480 people with autism, was published March 22 in the Proceedings of the National Academy of Sciences, and lends support to a prevailing theory that autism spectrum disorders (ASD), molecularly speaking, reflect an imbalance between inhibitory and excitatory signaling at synapses.

"The GRIP1 variants we studied are not sufficient to cause autism by themselves, but appear to be contributing factors that can modify the severity of the disease," says Tao Wang, M.D., Ph.D., assistant professor, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine. "GRIP1 mutations seem to contribute to social interaction deficits in the patients we studied."

The Johns Hopkins researchers examined a part of the genomes of 480 patients with autism and compared these with 480 people of similar ethnicity without the disorder. They analyzed about 50 genes known to make proteins involved in a brain-signaling pathway, ultimately focusing their investigation on GRIP1, a protein found at both inhibitory and excitatory synapses, according to Wang.

Initially, looking under a microscope at normal mouse neurons and neurons with a mutant version of GRIP1, the investigators marked the receptor proteins with green fluorescence, added a chemical that promotes their "disappearance" deep inside a cell and timed the rates at which they disappeared — leaving a cell unable to respond to signals from other cells. They also timed the reemergence of the protein back to the cell surface. With the GRIP1 mutant neurons, the receptors recycled to the surface twice as fast as in the normal neurons.

"If the receptors are recycling faster, the number of receptors on the surface is greater, so the cells are more sensitive to glutamate," Huganir explains. "The quicker the recycling, the more receptors on the surface and the stronger the excitatory transmission."

Even if just the excitatory synapses are affected, and the inhibitory ones don't change, that alone affects the relative balance of signaling, Huganir says.

Next, using 10 mice genetically engineered to lack both normal and mutant GRIP proteins, researchers watched what happened when each animal was put into a box where it could choose between spending time with a mouse it hadn't encountered before, or an inanimate object. They compared the behaviors of these mice with 10 normal mice put into the same social situation. Mice lacking both GRIP1 and GRIP2 spent twice as much time as wild-type (normal) mice interacting with other mice as they did with inanimate objects.

"These results support a role for GRIP1 in social behavior and implicate its variants in modulating autistic behavior," Wang says.

Finally, the team looked at the behavioral analyses of individuals in two families, each with two autistic brothers, and correlated their scores on standard diagnostic tests that assessed social interaction with their genotypes for GRIP1 variants.

In one family, the brother with two copies of the GRIP1 mutant variety scored lower on social interaction tests than his brother who had only one copy of the GRIP1 variant. The boys' mother, although not diagnosed as autistic, had a history of restricted interests, poor eye contact and repetitive behavior. Tests showed she also carried one copy of the variant.

In a second family, the autistic brother with one copy of the GRIP1 variant had lower social interaction scores than his autistic sibling without a GRIP1 variant.

Because the GRIP1 gene resides in synapses where other genes also implicated in autism have been found, this location is potentially important in terms of clinical relevance, says Huganir. The team plans to sequence hundreds more synaptic proteins in autistic patients to look for mutations and then follow up with functional analyses.

INFORMATION:

This study was supported in part by research grants from Autism Speaks Foundation and the National Institute of Child Health and Human Development. Authors on the paper from Johns Hopkins, in addition to Huganir and Wang, are Rebeca Mejias, Abby Adamczyk, Victor Anggono, Tejasvi Niranjan, Gareth M. Thomas, Kamal Sharma, M. Daniele Fallin, Walter E. Kaufmann, Mikhail Pletnikov and David Valle.

Cindy Skinner, Charles E. Schwartz and Roger Stevenson, all of the Greenwood Genetic Center, are also authors on the paper.

On the Web:

Tao Wang: http://www.hopkinsmedicine.org/geneticmedicine/People/Faculty/wang.html
Richard L. Huganir: http://neuroscience.jhu.edu/RichardHuganir.php
PNAS: http://www.pnas.org/

END



ELSE PRESS RELEASES FROM THIS DATE:

Treating newborn horses: A unique form of pediatrics

Treating newborn horses: A unique form of pediatrics
2011-04-07
CHAMPAIGN, Ill. — Like any other newborn, the neonatal horse can be a challenging patient. Its immune system is still under construction, its blood chemistry can vary wildly, and – like most infants – it wants to stay close to mom. These factors are magnified in the critically ill foal, said Pamela Wilkins, a professor of equine internal medicine and emergency/critical care at the University of Illinois and the author of a new paper on equine neonatal intensive care. The paper, in Clinical Laboratory Medicine, offers guidance to the large-animal veterinarian and demonstrates ...

Recovery Slow for Arizona's Stressed Economy

2011-04-07
In spite of the fact that the number of new bankruptcy filings actually fell for several straight months in 2010, the year still resulted in a record number of filings -- nearly 30,000 in all -- in the Phoenix metro area. That is higher than financial industry experts initially forecast and shows that much of Arizona's economy is still in recession mode. The new record is nearly 5,000 filings more than the previous one set back in 2005 (as thousands tried to take advantage of lax bankruptcy rules before sweeping changes took effect in October of that year). The high ...

Replacing batteries may become a thing of the past, thanks to 'soft generators'

Replacing batteries may become a thing of the past, thanks to soft generators
2011-04-07
Battery technology hasn't kept pace with advancements in portable electronics, but the race is on to fix this. One revolutionary concept being pursued by a team of researchers in New Zealand involves creating "wearable energy harvesters" capable of converting movement from humans or found in nature into battery power. A class of variable capacitor generators known as "dielectric elastomer generators" (DEGs) shows great potential for wearable energy harvesting. In fact, researchers at the Auckland Bioengineering Institute's Biomimetics Lab believe DEGs may enable light, ...

Common nanoparticles found to be highly toxic to Arctic ecosystem

Common nanoparticles found to be highly toxic to Arctic ecosystem
2011-04-07
Queen's researchers have discovered that nanoparticles, which are now present in everything from socks to salad dressing and suntan lotion, may have irreparably damaging effects on soil systems and the environment. "Millions of tonnes of nanoparticles are now manufactured every year, including silver nanoparticles which are popular as antibacterial agents," says Virginia Walker, a professor in the Department of Biology. "We started to wonder what the impact of all these nanoparticles might be on the environment, particularly on soil." The team acquired a sample of soil ...

Common Safety Myths Can Cause More Harm than Good to Motorcyclists

2011-04-07
There are many misunderstandings circulating about the best ways for motorcycle riders to avoid being involved in accidents with other cars. In some cases, these myths about motorcycle accidents can do more harm than good -- and put motorcyclists' lives at risk. Motorcycle riders are eight times more likely than those in passenger vehicles to be seriously injured in an accident and 35 times more likely to die in an accident. With these statistics in mind, it is important for motorcyclists to know the best ways to protect their safety - and what legal options they have ...

Micro aircraft IMPULLS improves avionic systems and sensors

Micro aircraft IMPULLS improves avionic systems and sensors
2011-04-07
A novel test aircraft of the TU Muenchen successfully completed its maiden flight yesterday at the airfield of the MFC Red Baron near Heimstetten. The micro aircraft christened "IMPULLS" (Innovative Modular Payload UAV – TUM LLS) will facilitate testing aviation sensors and systems. It was jointly developed by postgraduate students at the Institute of Aircraft Design and the Institute of Flight System Dynamics in Garching. Propelled by a compact electric motor, the aircraft flies quietly and free of emissions. A particularly important feature of the novel design is its ...

Bronx Bus Accident Claims 15 NYC Lives, Negligent Hiring Suspected

2011-04-07
Witnesses to a recent fatal bus crash in the Bronx told law enforcement that the bus was veering erratically before flipping onto one side and striking a sign post. The post sliced through the passenger compartment almost to the rear of the vehicle, creating horrific carnage in the passenger area and nearly removing the roof. The bus was returning from a Connecticut casino to Chinatown in Manhattan when the accident occurred early on a Saturday morning, just after the bus entered the Bronx from Westchester County. A host of reports soon after indicated that the driver, ...

Seeing rice with X-rays may improve crop yields

2011-04-07
College Park, Md. (April 6, 2011) -- Most people experience X-ray computed tomography (CT) scanners when they are evaluated for a suspected tumor or blood clot. But in the lab of Dr. Quin Liu, PhD., in Wuhan China, rice plants were the patients in a novel use of CT scanners as part of an agriculture study to increase rice yield. Into the CT scanner on a conveyor belt went little potted rice plants in an automated facility that could process 4,320 rice plants a day. The non-invasive CT energy analyzed tissues and matched their traits against a computer program to aid ...

Malpractice Case Highlights Expert Testimony Disclosure in Connecticut

2011-04-07
When it comes to arguing and proving medical malpractice claims at trial, providing strong expert testimony to support these cases is crucial. The Supreme Court of Connecticut recently decided a case, Klein v. Norwalk, which highlights this important tactic, as well as the standard for disclosing what points an expert will make during testimony. Although this case had a long and difficult journey through multiple Connecticut courts, and continues to make waves, the Connecticut Supreme Court made Klein v. Norwalk a noteworthy opinion. Klein's Claim According to the ...

Here's looking at you!

2011-04-07
CORAL GABLES, FL (April 6, 2011)—Learning how babies communicate can teach us a lot about the development of human social interactions. Psychologist Daniel Messinger, from the University of Miami (UM), studies infants' interactions and has found that babies are not simply living in the moment. Instead, infants seem to have particular interests that create historical footprints reflected in the infants' visual engagement over time. The findings were published today, in a study titled, 'Are You Interested, Baby?' Young Infants Exhibit Stable Patterns of Attention during Interaction." ...

LAST 30 PRESS RELEASES:

Development of a global innovative drug in eye drop form for treating dry age-related macular degeneration

Scientists unlock secrets behind flowering of the king of fruits

Texas A&M researchers illuminate the mysteries of icy ocean worlds

Prosthetic material could help reduce infections from intravenous catheters

Can the heart heal itself? New study says it can

Microscopic discovery in cancer cells could have a big impact

Rice researchers take ‘significant leap forward’ with quantum simulation of molecular electron transfer

Breakthrough new material brings affordable, sustainable future within grasp

How everyday activities inside your home can generate energy

Inequality weakens local governance and public satisfaction, study finds

Uncovering key molecular factors behind malaria’s deadliest strain

UC Davis researchers help decode the cause of aggressive breast cancer in women of color

Researchers discovered replication hubs for human norovirus

SNU researchers develop the world’s most sensitive flexible strain sensor

Tiny, wireless antennas use light to monitor cellular communication

Neutrality has played a pivotal, but under-examined, role in international relations, new research shows

Study reveals right whales live 130 years — or more

Researchers reveal how human eyelashes promote water drainage

Pollinators most vulnerable to rising global temperatures are flies, study shows

DFG to fund eight new research units

Modern AI systems have achieved Turing's vision, but not exactly how he hoped

Quantum walk computing unlocks new potential in quantum science and technology

Construction materials and household items are a part of a long-term carbon sink called the “technosphere”

First demonstration of quantum teleportation over busy Internet cables

Disparities and gaps in breast cancer screening for women ages 40 to 49

US tobacco 21 policies and potential mortality reductions by state

AI-driven approach reveals hidden hazards of chemical mixtures in rivers

Older age linked to increased complications after breast reconstruction

ESA and NASA satellites deliver first joint picture of Greenland Ice Sheet melting

Early detection model for pancreatic necrosis improves patient outcomes

[Press-News.org] Gene linked to severity of autism's social dysfunction