A team of researchers at the University of Alberta has discovered a gene that is able to block HIV, and in turn prevent the onset of AIDS.
Stephen Barr, a molecular virologist in the Department of Medical Microbiology and Immunology, says his team has identified a gene called TRIM22 that can block HIV infection in a cell culture by preventing the assembly of the virus.
"When we put this gene in cells, it prevents the assembly of the HIV virus," said Barr, a postdoctoral fellow. "This means the virus cannot get out of the cells to infect other cells, thereby blocking the spread of the virus."
Barr and his team also prevented cells from turning on TRIM22 - provoking an interesting phenomenon: the normal response of interferon, a protein that co-ordinates attacks against viral infections, became useless at blocking HIV infection.
"This means that TRIM22 is an essential part of our body's ability to fight off HIV. The results are very exciting because they show that our bodies have a gene that is capable of stopping the spread of HIV."
One of the greatest challenges in battling HIV is the virus' ability to mutate and evade medications. Antiretroviral drugs introduced during the late 1990s interfere with HIV's ability to produce new copies of itself - and even they are beneficial, the drugs are unable to eradicate the virus. Barr and his team have discovered a gene that could potentially do the job naturally.
"There are always newly emerging drug-resistant strains of HIV so the push has been to develop more natural means of blocking the virus. The discovery of this gene, which is natural in our cells, might provide a different avenue," said Barr. "The gene prevents the assembly of the virus so in the future the idea would be to develop drugs or vaccines that can mimic the effects of this gene."
"We are currently trying to figure out why this gene does not work in people infected with HIV and if there is a way to turn this gene on in those individuals," he added. "We hope that our research will lead to the design of new drugs, or vaccines that can halt the person-to-person transmission of HIV and the spread of the virus in the body, thereby blocking the onset of AIDS."
The researchers are now investigating the gene's ability to battle other viruses.
Barr's research is funded by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council and the Alberta Heritage Foundation for Medical Research. The findings are published in the Public Library of Science Pathogens.
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Saturday, March 1, 2008
First Peek Into Deepest Recesses Of Human Brain
The scientists believe they may be opening the door to inquiries into a region that acts as the staging area for the brain chemicals whose overabundance or absence in other parts of the brain are at the root of many neuropsychiatric disorders, like addiction, schizophrenia and Parkinson's disease.
Reporting in the Feb. 28 edition of Science, the scientists describe using functional magnetic resonance imaging to study brainstem activity in dehydrated humans. The scanning technique allows researchers to watch the brain in action.
The subjects were participating in classical conditioning experiments in which they were presented with a visual clue, then, at varying intervals, given a drink. The researchers were able to track changes in blood flow in areas of the brainstem associated with enhanced activity of the brain chemical dopamine -- as the person experienced either pleasure or disappointment at receiving or not receiving the reward.
"For a long time, scientists have tried looking at this area of the brain and have been unsuccessful -- it's just too small," said Kimberlee D'Ardenne, the lead author on the paper. Until now, scientists wanting to use brain scans to study brain chemicals like dopamine were relegated to watching its effects in other more accessible parts of the brain, like the prefrontal cortex and ventral striatum. However, this was downstream of its source, and therefore possibly much less accurate, D'Ardenne said.
"We wanted to try because the brainstem is so important to activities in the rest of the brain," said D'Ardenne, a postdoctoral student in the Department of Chemistry. "We believe it could be a key to understanding all kinds of important behavior."
For the research, D'Ardenne collaborated with Jonathan Cohen, co-director of the Princeton Neuroscience Institute, and Samuel McClure and Leigh Nystrom, other institute scientists. They conducted the studies on the University's own brain scanner located on campus in Green Hall.
Cohen noted that these findings provide a critical link between studies in non-human animals that have looked directly at the activity of dopamine cells in the brainstem and studies in humans of behaviors thought to be related to dopamine. "It could also open up entirely new avenues of study," he said.
The team was able to develop high-resolution images that tracked the activity of tiny clusters of dopamine neurons. They weeded out distortions caused by many pulsing blood vessels in the brainstem. They also employed computerized rules of thumb known as algorithms and imaging techniques to reduce the effects of head movement and combine images from different subjects.
The MRI device produces three-dimensional images that show what portions of the brain engage during actions and thought processes. This allows the investigators to correlate physical processes with mental activities with unprecedented precision.
The brain stem, a tiny, root-shaped structure, is the lower part of the brain and sits atop the spinal cord. The area controls brain functions necessary for survival, such as breathing, digestion, heart rate, blood pressure and arousal. The brain structure also serves as the home base for the brain chemicals, also known as neuromodulators, such as dopamine, serotonin and norepinephrine. The chemicals spring forth into other brain regions from there, zipping along routes called axons.
The team's experiments confirmed results already seen in animal studies. Blood flow increased in dopamine centers of the brainstem when test subjects were happily surprised with a reward. However, there was no activity when participants received less than what they expected, a finding that is different from the results of previous studies looking farther downstream.
"We are just at the beginning of understanding these crucial pathways," D'Ardenne said. "But it gives us a hint about what is possible to know."
The tiny clumps of cells containing neuromodulator chemicals in the brainstem, called nuclei, have long been known to play a critical role in the regulation of brain function, and disturbances of these systems have been implicated in most psychiatric disorders, from addiction to schizophrenia, D'Ardenne said.
The Princeton group wants to understand how the brain's physical structures give rise to the functions of the mind, a field known as cognitive neuroscience.
For years, neuroscientists focused on the brain while psychologists dealt with the mind. The new field combines both and is being powered by scientific advances in brain imaging and gene manipulation that allows researchers to record and measure the activity of brain cells as humans or animals perform mental tasks.
Friday, February 29, 2008
Five myths about the satellite smash-up
Last week's Pentagon operation to bring down a falling spy satellite may have been widely termed a "shootdown" of precision accuracy — but the reality is more complex, and much messier.
As military officials take stock of the event's physical and political fallout, it's worth dispelling some of the misconceptions and myths that could otherwise cloud the thinking of policymakers and the public during the debate over past and future "shootdowns."
Reality: Hitting a satellite with a missile is not at all like hitting a bird with a bullet and watching it plummet to the ground. An orbiting satellite stays in orbit not because of its power or guidance, but merely because of its forward speed. An attack that does not substantially change that orbital velocity cannot drive the satellite out of orbit, no matter how much physical damage it does.
The only practical way to remove such targets from orbit is by slowing them down. In practice, that occurs as a result of air drag, an effect that can take hours, weeks, or centuries depending on the thickness of the air at the satellite’s altitude. Breaking a big spacecraft into smaller pieces does increase the effects of air drag — as demonstrated dramatically last week — but it is the key role of air drag that makes the critical causal link between "shooting" and "downing" the target.
Myth No. 2: Falling satellites aren’t really hazardous, and since they’ve never hurt anybody before, they were unlikely to hurt anybody this time. Hence, there must have been a secret "real reason" for the missile mission.
Reality: First, counting on a string of successfully dodging bullets is no open-ended guarantee of being bullet-proof forever. The odds have a way of catching up with you, and defying them is an all-too-common fallacy called “normalization of deviance.” At NASA, this attitude laid the foundation for the Challenger and Columbia shuttle disasters.
Second, it’s not true that past safe outcomes always occurred even when countries let their big satellites randomly fall to Earth. Just the opposite is true — for decades, major spacefaring powers have taken deliberate and expensive steps to mitigate the ground-impact hazards of satellites.
All Russian spacecraft and U.S. military satellites heavier than 15,000 pounds are deliberately steered into untraveled expanses of the far southern Pacific Ocean. NASA steered its Compton Gamma Ray Observatory into a precisely planned atmospheric re-entry in 2000, and tried (but failed) to do the same with the Skylab space station in 1978.
In last week's case, the Pentagon said it resorted to the missile-intercept option because the spy satellite's guidance system was inoperable. Now, the mix of motivations for making the missile attack can be debated — but the up-front official claim about mitigating hazard cannot be glibly dismissed.
Myth No. 3: The hydrazine on the spy satellite was unlikely to reach the ground in any concentration worth worrying about.
Reality: Space officials were so concerned about the satellite's full tank of hydrazine fuel because they believed it had frozen solid, due to the low temperatures aboard the spacecraft. They feared that the titanium-shielded "toxic iceberg" would survive intact all the way to the ground and disperse around the crash site, not in the upper atmosphere. Safety officials had never been faced with this type of falling material before.
How dangerous is hydrazine? The chemical is considered toxic as well as flammable. U.S. space workers have indeed survived massive short-term dosing by the chemical during fueling accidents, but they did so due to the immediate application of pre-deployed safety measures.
The U.S. might have been held legally responsible for damage following the impact of such a hazardous cargo in a region with active agricultural exports or tourism.
As with the Palomares incident 42 years ago, in which two U.S. nuclear weapons fell to earth in Spain after an aircraft accident, people outside the region might be so spooked that they stop buying the regional exports and stop visiting its recreational facilities. The lost business alone could have cost hundreds of millions of dollars — compared with the estimated $60 million cost of the missile intercept.
Myth No. 4: The missile was aimed directly at the fuel tank, in order to pierce it and let the hazardous contents leak out.
Reality: Sure, the fuel tank was the missile's main target — but the missile didn’t have to hit the tank to crack it open. It’s hard to imagine how the warhead’s guidance system could have spotted the tank anyhow, inside the blob that was the image of the entire satellite. Hitting the target dead center and thus smashing the entire satellite to smithereens was the easiest way to ensure maximum damage to the tank.
Myth No. 5: The satellite disintegrated into more than 3,000 pieces because the fuel exploded.
Reality: Some Pentagon officials seemed to imply this, as evidence that they had achieved the goal of destroying the tank. But the kinetic energy involved in the ultra-high-speed collision was more than enough to impart enough force to cause the violent shattering — it certainly was orders of magnitude greater than the chemical energy that would have been liberated from the ignition of the entire fuel supply, even assuming it wasn’t frozen. That collisional energy was also the reason that some pieces of the target satellite got thrown forward so energetically, even though the missile hit the satellite from the front.
Most of the pieces fell through the atmosphere and burned up within a couple of days of the intercept. As of Tuesday, the Air Force Space Command was reportedly tracking 17 fragments that were still in orbit.
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What's the harm in just letting all these myths lie? The danger is that the topic of weapons in space is a serious one requiring serious debate, especially in this election year. Hanging onto the technical myths could lead to misconceptions on one side of the debate ("our missiles were so accurate they could make a precision strike on the fuel tank") or the other ("the shootdown created a cloud of toxic debris that's still in orbit").
If we can "shoot down" the fuzzy thinking that has frustrated a serious exchange of views on this important national security issue, that would represent a much more enduring contribution to the safety of this planet than just protecting one random spot from half a ton of plummeting poison.
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