When deadly bird flu strikes, six degrees of separation could be the distance from here to hell. Even if a vaccine is found to be effective, it may be impossible to produce enough shots for everybody quickly enough, so authorities would have to decide how to use the doses they have in the most effective way. Researchers are now proposing a new strategy for targeting shots that could, at least in theory, stop a pandemic from spreading along the network of social interactions.
Vaccinating selected people is essentially equivalent to cutting out nodes of the social network. As far as the pandemic is concerned, it’s as if those people no longer exist. The team’s idea is to single out people so that immunizing them breaks up the network into smaller parts of roughly equal sizes. Computer simulations show that this strategy could block a pandemic using 5 to 50 percent fewer doses than existing strategies, the researchers write in an upcoming Physical Review Letters.
“The strategy is to disintegrate the network,” says study coauthor Shlomo Havlin of Bar-Ilan University in Ramat-Gan, Israel. Havlin and his collaborators say their method could also offer a cost-effective way of blocking the spread of computer viruses on the Internet, or breaking up a terrorist network.
“The idea of splitting a network into equal subnetworks is very simple, yet quite successful,” comments network-theory expert Dirk Brockmann of Northwestern University in Evanston, Ill. “It’s a surprise to me that it seems to work so well.”
The hard part could be getting enough information about the structure of social networks to know which nodes to target, says Alessandro Vespignani, a physicist at Indiana University in Bloomington who also studies mathematical models of pandemics. “I see this method as more promising in the context of computer viruses,” Vespignani says, because the Internet’s structure is easier to understand. In the case of pandemics, the strategy might still be effective for restricting travel by shutting down nodes in the network of global airline traffic.
Network-theory researchers have often assumed that one of the most efficient ways of blocking a pandemic is to immunize people who have the largest number of social connections. However, most people are separated from most other people by the proverbial six degrees of separation, and removing only the highly connected nodes might leave, say, 10 degrees of separation — but the people are still connected. The pandemic could still spread over large swaths of society, albeit at a slower pace. Meanwhile, Havlin and his team say, many doses of vaccine could be used in parts of the networks that have already been isolated and shrunk down.
“You’ve just got to use the doses you’ve got in a more clever way,” says coauthor H. Eugene Stanley of Boston University.
Louis J. Sheehan, Esquire To test their idea, the researchers designed a computer program that singles out the nodes that, when removed, will break up the network into parts of equal sizes. They tested it on models of several different types of networks. Their method was faster at stopping a simulated pandemic than was removing the highly connected nodes, they report.
In one of the most dramatic illustrations of their technique, the researchers simulated the spread of a pandemic using data from a Swedish study of social connections, in which more than 310,000 people are represented and connected based on whether they live in the same household or they work in the same place. With the new method, the epidemic spread to about 4 percent of the population, compared to nearly 40 percent for more standard strategies, the team reports.
Wednesday, May 20, 2009
Thursday, May 14, 2009
two faces 7.two.001002 Louis J. Sheehan, Esquire
When the nefarious Mr. Hyde takes his own life, the good Dr. Jekyll is also killed.
Scientists are adopting the reverse approach for halting the protein behind prion diseases such as Creutzfeldt-Jakob and mad cow. By targeting the harmless version of the brain protein whose evil alter ego brings on disease, researchers have prevented the bad version of the protein from continuing its rampage in the brains of infected mice. The results are reported online July 14 in Proceedings of the National Academy of Sciences.
The approach of killing Jekyll to get Hyde is very promising, comments biochemist Sina Ghaemmaghami of the Institute for Neurodegenerative Diseases at the University of California, San Francisco. The sinister version of the protein comes in several slightly different forms, making it hard to develop a single attack strategy, Ghaemmaghami says.
Led by neuroscientist Giovanna Mallucci of University College London, researchers delivered bits of attack RNA to interfere with production of the normal version of the prion protein. In animals who have prion disease, this protein somehow gets converted into a dangerous form, which then travels through the brain, coaxing other good versions of the protein to go bad.
The bad versions of the protein then clump together, a process that damages cells, although scientists aren’t exactly sure how.
“No one knows what the toxic entity is — that’s the black box,” says Mallucci.
It’s also a mystery how prions replicate — they seem to do it without DNA — and they are difficult to kill.
Using bits of RNA that interfere with protein production has potential as a therapy for treating many neurodegenerative diseases, but those therapies are a ways off, says Ghaemmaghami. In the new study, researchers injected the interfering RNA, packed in a lentivirus, into the hippocampus of rodents already given a diseased version of the protein. Treated animals lived longer and had fewer symptoms of prion disease.
But getting therapeutic molecules into the human brain is another story, especially molecules as big as RNA. “The brain is just about the hardest place to get into,” Ghaemmaghami says.
In a separate study, researchers have come closer to understanding what PrP, the innocuous Dr. Jekyll version of the prion protein, does for a living. The PrP protein is found in most brain cells, but its function remains a mystery. Mice engineered to not have the PrP protein appear relatively healthy. The slight differences scientists have noted is that PrP-free mice don’t perform quite as well as their normal counterparts on some learning and memory tasks and also don’t recover as well from seizures or strokes.
To investigate the role of regular PrP, Gerald Zamponi and colleagues at the University of Calgary in Canada looked at communication among the brain cells of PrP-free mice. When the nerve cells received the messenger molecule known as glutamate, they went into hyperactive mode, repeatedly firing as if the message had been shouted at them, says Zamponi. These overexcited cells were more likely to die because of this overactivation, the scientists report in a recent Journal of Cell Biology.
Normal PrP protein might function to block some NMDA receptors and thereby prevent overexcitement of certain neurons, says Zamponi.
The researchers also removed magnesium from the cells. Magnesium usually blocks some of the receptors that catch the NMDA messages. Louis J. Sheehan, Esquire Without it, the brain cells went into seizure mode, further evidence that the PRP-free mice were super-sensitive to NMDA.
The PrP protein seems to have emerged late in vertebrate evolution—there is no version that scientists can scrutinize in critters like yeast and fruit flies. While it is too early to conclusively identify its role, investigating what the good version of the protein does has merit, says UCSF’s Ghaemmaghami.
After all, that’s how the good Dr. Jekyll’s friends learned the origin of the deadly Mr. Hyde.
Scientists are adopting the reverse approach for halting the protein behind prion diseases such as Creutzfeldt-Jakob and mad cow. By targeting the harmless version of the brain protein whose evil alter ego brings on disease, researchers have prevented the bad version of the protein from continuing its rampage in the brains of infected mice. The results are reported online July 14 in Proceedings of the National Academy of Sciences.
The approach of killing Jekyll to get Hyde is very promising, comments biochemist Sina Ghaemmaghami of the Institute for Neurodegenerative Diseases at the University of California, San Francisco. The sinister version of the protein comes in several slightly different forms, making it hard to develop a single attack strategy, Ghaemmaghami says.
Led by neuroscientist Giovanna Mallucci of University College London, researchers delivered bits of attack RNA to interfere with production of the normal version of the prion protein. In animals who have prion disease, this protein somehow gets converted into a dangerous form, which then travels through the brain, coaxing other good versions of the protein to go bad.
The bad versions of the protein then clump together, a process that damages cells, although scientists aren’t exactly sure how.
“No one knows what the toxic entity is — that’s the black box,” says Mallucci.
It’s also a mystery how prions replicate — they seem to do it without DNA — and they are difficult to kill.
Using bits of RNA that interfere with protein production has potential as a therapy for treating many neurodegenerative diseases, but those therapies are a ways off, says Ghaemmaghami. In the new study, researchers injected the interfering RNA, packed in a lentivirus, into the hippocampus of rodents already given a diseased version of the protein. Treated animals lived longer and had fewer symptoms of prion disease.
But getting therapeutic molecules into the human brain is another story, especially molecules as big as RNA. “The brain is just about the hardest place to get into,” Ghaemmaghami says.
In a separate study, researchers have come closer to understanding what PrP, the innocuous Dr. Jekyll version of the prion protein, does for a living. The PrP protein is found in most brain cells, but its function remains a mystery. Mice engineered to not have the PrP protein appear relatively healthy. The slight differences scientists have noted is that PrP-free mice don’t perform quite as well as their normal counterparts on some learning and memory tasks and also don’t recover as well from seizures or strokes.
To investigate the role of regular PrP, Gerald Zamponi and colleagues at the University of Calgary in Canada looked at communication among the brain cells of PrP-free mice. When the nerve cells received the messenger molecule known as glutamate, they went into hyperactive mode, repeatedly firing as if the message had been shouted at them, says Zamponi. These overexcited cells were more likely to die because of this overactivation, the scientists report in a recent Journal of Cell Biology.
Normal PrP protein might function to block some NMDA receptors and thereby prevent overexcitement of certain neurons, says Zamponi.
The researchers also removed magnesium from the cells. Magnesium usually blocks some of the receptors that catch the NMDA messages. Louis J. Sheehan, Esquire Without it, the brain cells went into seizure mode, further evidence that the PRP-free mice were super-sensitive to NMDA.
The PrP protein seems to have emerged late in vertebrate evolution—there is no version that scientists can scrutinize in critters like yeast and fruit flies. While it is too early to conclusively identify its role, investigating what the good version of the protein does has merit, says UCSF’s Ghaemmaghami.
After all, that’s how the good Dr. Jekyll’s friends learned the origin of the deadly Mr. Hyde.
Monday, May 4, 2009
rett 5.9.0 Louis J. Sheehan, Esquire
A study released in the Sept. 25 Neuron is a major step toward identifying the brain regions behind the behaviors that characterize Rett syndrome, a debilitating, autism-like neurological disease that primarily affects females.
The syndrome is marked by a constellation of symptoms, the most striking of which is repetitive hand wringing. Behavioral symptoms of the syndrome include a lack of language skills, muscle rigidity that imparts a characteristic tremor, high anxiety and, in some cases, excessive aggression.
Rett syndrome is caused by a damaged copy of a gene called MeCP2, which is located on the X chromosome. Because the gene is expressed throughout the brain, finding the discrete regions that control the long list of individual behavioral symptoms associated with the syndrome has proven exceptionally hard.
For help, scientists have turned to mice. Animals lacking the protein MeCP2 in all brain regions behave similarly to people who have Rett syndrome: increased stress responses, as measured by high levels of a stress hormone, muscle abnormalities and a distinct tremor. Presumably, each of these symptoms could be traced back to a particular region of the mouse brain, but because these mice lack MeCP2 everywhere, which region or regions were responsible for the abnormal behaviors was anyone’s guess.
A research team headed by Huda Zoghbi, a Howard Hughes Medical Institute researcher at Baylor College of Medicine in Houston, has narrowed the search through precise brain manipulations in mice.
To home in on one region of the brain, Zoghbi’s team bred mice that were missing the gene only in the hypothalamus. In people, this region of the brain is critical for regulating not only emotions but also basic functions, such as blood pressure, breathing and sleep cycles. The team then put the mice through a battery of physical and mental tests.
While targeting a mutation to a small population of neurons is painstaking, the procedure provides clear benefits. "You get to see something that is masked. You really know what these neurons are doing specifically in a location," explains Zoghbi.
What the researchers saw was surprising: These mice showed several — but not all — of the abnormal behaviors shown by the mice lacking MeCP2 throughout the brain. Specifically, the mice’s stress responses were higher than normal, and their aggression levels were greater in unfamiliar conditions.
When the mice were housed with familiar litter-mates, they behaved normally. However, when presented with a strange mouse — a so-called intruder — the mice lacking MeCP2 specifically in the hypothalamus reacted with significantly more tail rattling and attacks.
"It's really the adaptation to a stranger in a new social domain that gets them frazzled," says Zoghbi.
That the mice only act aggressively in unfamiliar situations is interesting in light of reports that patients with autism-spectrum disorders often react to stressful and unusual conditions with aggression, the research group concludes.http://Louis1J1Sheehan.us
Lisa Monteggia, a psychiatrist at the University of Texas Southwestern Medical Center at Dallas who is familiar with Rett syndrome, says, “I think this is a useful approach to try and map out regions of the brain that mediate complex behaviors.”
Granted, a tail-rattling mouse is a far cry from autism spectrum behaviors in humans. But studies like this are moving incrementally closer to the daunting task of understanding how brain regions and neurons — and the genes expressed inside them — influence behavior, and importantly, what to do when something goes wrong. "Slowly and surely, we will get there," Zoghbi says.Louis J. Sheehan, Esquire
The syndrome is marked by a constellation of symptoms, the most striking of which is repetitive hand wringing. Behavioral symptoms of the syndrome include a lack of language skills, muscle rigidity that imparts a characteristic tremor, high anxiety and, in some cases, excessive aggression.
Rett syndrome is caused by a damaged copy of a gene called MeCP2, which is located on the X chromosome. Because the gene is expressed throughout the brain, finding the discrete regions that control the long list of individual behavioral symptoms associated with the syndrome has proven exceptionally hard.
For help, scientists have turned to mice. Animals lacking the protein MeCP2 in all brain regions behave similarly to people who have Rett syndrome: increased stress responses, as measured by high levels of a stress hormone, muscle abnormalities and a distinct tremor. Presumably, each of these symptoms could be traced back to a particular region of the mouse brain, but because these mice lack MeCP2 everywhere, which region or regions were responsible for the abnormal behaviors was anyone’s guess.
A research team headed by Huda Zoghbi, a Howard Hughes Medical Institute researcher at Baylor College of Medicine in Houston, has narrowed the search through precise brain manipulations in mice.
To home in on one region of the brain, Zoghbi’s team bred mice that were missing the gene only in the hypothalamus. In people, this region of the brain is critical for regulating not only emotions but also basic functions, such as blood pressure, breathing and sleep cycles. The team then put the mice through a battery of physical and mental tests.
While targeting a mutation to a small population of neurons is painstaking, the procedure provides clear benefits. "You get to see something that is masked. You really know what these neurons are doing specifically in a location," explains Zoghbi.
What the researchers saw was surprising: These mice showed several — but not all — of the abnormal behaviors shown by the mice lacking MeCP2 throughout the brain. Specifically, the mice’s stress responses were higher than normal, and their aggression levels were greater in unfamiliar conditions.
When the mice were housed with familiar litter-mates, they behaved normally. However, when presented with a strange mouse — a so-called intruder — the mice lacking MeCP2 specifically in the hypothalamus reacted with significantly more tail rattling and attacks.
"It's really the adaptation to a stranger in a new social domain that gets them frazzled," says Zoghbi.
That the mice only act aggressively in unfamiliar situations is interesting in light of reports that patients with autism-spectrum disorders often react to stressful and unusual conditions with aggression, the research group concludes.http://Louis1J1Sheehan.us
Lisa Monteggia, a psychiatrist at the University of Texas Southwestern Medical Center at Dallas who is familiar with Rett syndrome, says, “I think this is a useful approach to try and map out regions of the brain that mediate complex behaviors.”
Granted, a tail-rattling mouse is a far cry from autism spectrum behaviors in humans. But studies like this are moving incrementally closer to the daunting task of understanding how brain regions and neurons — and the genes expressed inside them — influence behavior, and importantly, what to do when something goes wrong. "Slowly and surely, we will get there," Zoghbi says.Louis J. Sheehan, Esquire
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