Small Molecule Triggers Bacterial Community
While bacterial cells tend to be rather solitary individuals, they are also known to form intricately structured communities called biofilms. But until now, no one has known the mechanisms that cause isolated bacteria to suddenly aggregate into a social network. New insights from the lab of Harvard Medical School microbial geneticist Roberto Kolter reveal previously unknown communication pathways that cause such social phenomenon.
Using the non-pathogenic Bacillus subtilis as a model organism, Kolter and postdoctoral researcher Daniel Lopez discovered a group of natural, soil-based products that trigger communal behavior in bacteria. One molecule in particular, surfactin, is produced by B. subtilis. Biofilm formation begins when surfactin, and other similar molecules, cause bacteria to leak potassium. As potassium levels decline, a membrane protein on the bacterium stimulates a cascade of gene activity that signals neighboring cells to form a quorum. As a result, biofilms form.
The authors note that it’s still unclear how biofilm formation benefits the bacteria, and they hypothesize that it might be an antibacterial defense against competing species. Still, the notion that a single small molecule can induce multicellularity intrigues the researchers.
“Typically, scientists try to discover new antibiotics through some rather blunt means, like simply looking to see if one bacterium can kill another,” says Kolter. “This discovery of a single molecule causing such a dramatic response in bacteria hints at a new and potentially effective way to possibly discover antibiotics.”
These findings are published in the Proceedings of the National Academy of Sciences.
Saturday, December 27, 2008
Spinning Spigots: 'Missing Link' in Spider Evolution Discovered
New interpretations of fossils have revealed an ancient missing link between today’s spiders and their long-extinct ancestors. The research by scientists at the University of Kansas and at Virginia’s Hampden-Sydney College may help explain how spiders came to weave webs.
The research focuses on fossil animals called Attercopus fimbriunguis. While modern spiders make silk threads with modified appendages called spinnerets, the fossil animals wove broad sheets of silk from spigots on plates attached to the underside of their bodies. Unlike spiders, they had long tails.
The research findings by Paul Selden, Gulf-Hedberg Distinguished Professor of Invertebrate Paleontology at KU and William Shear, Trinkle Professor of Biology at Hampden-Sydney College, were published this week in the Proceedings of the National Academy of Sciences.
Selden and Shear first discovered the fossils almost 20 years ago. At that time the specimens were thought to be the oldest spider fossils known, dating back to the Devonian Period, about 380 million years ago. Unearthed in upstate New York, the fossils were among the first animals to live on land in North America.
New finds near the same location, in Gilboa, New York, caused the paleontologists to reinterpret their original findings. The new fossils included silk-spinning organs, called spigots, arranged on the edges of broad plates making up the undersides of the animals. The researchers identified parts of a long, jointed tail not found in any previously known spider, but common among some of the spiders’ more primitive relatives.
“We think these ‘tailed spiders’ represent an entirely new kind of animal, not known before from living or fossil examples.” Shear said. “They were more primitive than spiders in many ways, and may be spider ancestors.” Besides having tails and spinning silk from broad plates, the animals also seem to lack poison glands.
Selden added, “This new information also allows us to reinterpret other fossils once thought to be spiders, and this evidence suggests these Uraraneida, or pre-spiders, existed for more than 100 million years, living alongside real spiders, which evolved later.”
The paleontologists think that Attercopus developed silk-spinning spigots in order to line burrows, make homing trails, and possibly to subdue prey, but were not capable of making webs because of the limited mobility of the spigots. True spiders may have arisen when the genetic information for certain appendages was “turned back on” and the spigots moved onto them. The appendages became the modern spiders’ spinnerets, which can move freely and create patterned webs.
Selden is director of the KU Paleontological Institute at the Biodiversity Institute, one of eight designated research centers on campus that report to the KU Office of Research and Graduate Studies.
New interpretations of fossils have revealed an ancient missing link between today’s spiders and their long-extinct ancestors. The research by scientists at the University of Kansas and at Virginia’s Hampden-Sydney College may help explain how spiders came to weave webs.
The research focuses on fossil animals called Attercopus fimbriunguis. While modern spiders make silk threads with modified appendages called spinnerets, the fossil animals wove broad sheets of silk from spigots on plates attached to the underside of their bodies. Unlike spiders, they had long tails.
The research findings by Paul Selden, Gulf-Hedberg Distinguished Professor of Invertebrate Paleontology at KU and William Shear, Trinkle Professor of Biology at Hampden-Sydney College, were published this week in the Proceedings of the National Academy of Sciences.
Selden and Shear first discovered the fossils almost 20 years ago. At that time the specimens were thought to be the oldest spider fossils known, dating back to the Devonian Period, about 380 million years ago. Unearthed in upstate New York, the fossils were among the first animals to live on land in North America.
New finds near the same location, in Gilboa, New York, caused the paleontologists to reinterpret their original findings. The new fossils included silk-spinning organs, called spigots, arranged on the edges of broad plates making up the undersides of the animals. The researchers identified parts of a long, jointed tail not found in any previously known spider, but common among some of the spiders’ more primitive relatives.
“We think these ‘tailed spiders’ represent an entirely new kind of animal, not known before from living or fossil examples.” Shear said. “They were more primitive than spiders in many ways, and may be spider ancestors.” Besides having tails and spinning silk from broad plates, the animals also seem to lack poison glands.
Selden added, “This new information also allows us to reinterpret other fossils once thought to be spiders, and this evidence suggests these Uraraneida, or pre-spiders, existed for more than 100 million years, living alongside real spiders, which evolved later.”
The paleontologists think that Attercopus developed silk-spinning spigots in order to line burrows, make homing trails, and possibly to subdue prey, but were not capable of making webs because of the limited mobility of the spigots. True spiders may have arisen when the genetic information for certain appendages was “turned back on” and the spigots moved onto them. The appendages became the modern spiders’ spinnerets, which can move freely and create patterned webs.
Selden is director of the KU Paleontological Institute at the Biodiversity Institute, one of eight designated research centers on campus that report to the KU Office of Research and Graduate Studies.
Saturday, December 20, 2008
Discovery: New Tooth Cavity Protection
Clarkson University Center for Advanced Materials Processing Professor Igor Sokolov and graduate student Ravi M. Gaikwad have discovered a new method of protecting teeth from cavities by ultrafine polishing with silica nanoparticles.
The researchers adopted polishing technology used in the semiconductor industry (chemical mechanical planarization) to polish the surface of human teeth down to nanoscale roughness. Roughness left on the tooth after the polishing is just a few nanometers, which is one-billionth of a meter or about 100,000 times smaller than a grain of sand.
Sokolov and Gaikwad showed that teeth polished in this way become too “slippery” for the "bad" bacteria that is responsible for the destruction of dental enamel. As a result the bacteria can be removed fairly easily before they cause damage to the enamel.
Although silica particles have been used before for tooth polishing, polishing with nanosized particles has not been reported. The researchers hypothesized that such polishing may protect tooth surfaces against the damage caused by cariogenic bacteria, because the bacteria can be removed easily from such polished surfaces.
The Clarkson researchers' findings were published in the October issue of the Journal of Dental Research, the dentistry journal with the top worldwide scientific impact index.
Sokolov is a professor of physics, professor of chemical and biomolecular science, and director of Clarkson's Nanoengineering and Biotechnology Laboratories Center (NABLAB). Gaikwad is a graduate student in physics.
Read more at http://jdr.iadrjournals.org/cgi/content/short/87/10/980.
Saturday, December 13, 2008
Selenium, Vitamin E Do Not Prevent Prostate Cancer
Findings from one of the largest cancer chemoprevention trials ever conducted have concluded that selenium and vitamin E taken alone or in combination for an average of five and a half years did not prevent prostate cancer, according to a team of researchers coordinated by the Southwest Oncology Group (SWOG) and led by scientists at The University of Texas M. D. Anderson Cancer Center and Cleveland Clinic.
Data and analysis gathered through Oct. 23, 2008, from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were published in the Dec. 9 issue of the Journal of the American Medical Association (JAMA) by Scott M. Lippman, M.D., professor and chair of Thoracic/Head and Neck Medical Oncology at M. D. Anderson, Eric A. Klein, M.D., of the Cleveland Clinic Lerner College of Medicine, and 30 coauthors from the United States, Puerto Rico and Canada.
Funded by the National Cancer Institute (NCI) with some additional contribution from the National Center for Complementary and Alternative Medicine, the Phase III trial began recruitment in August 2001 and aimed to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in relatively healthy men. The study followed 35,533 participants from 427 sites in the United States, Canada and Puerto Rico. The randomized, placebo-controlled and double-blind trial divided the participants into four intervention groups: selenium, vitamin E, both selenium and vitamin E, and placebos.
Supplement Cases 5-year prostate cancer diagnosis
Placebo 416 4.43 percent
Selenium 432 4.56 percent
Vitamin E 473 4.93 percent
Selenium + Vitamin E 437 4.56 percent
The study found no evidence of benefit from selenium, vitamin E, or both. Additionally, the data showed two statistically non-significant findings of concern: slightly increased risks of prostate cancer in the vitamin E group and type two diabetes mellitus in the selenium group. Both trends may be due to chance and were not observed in the group taking selenium and vitamin E together.
An independent data and safety monitoring committee reached the same conclusion and recommended supplementation be discontinued Oct. 23 for lack of evidence of benefit.
"SELECT presented a unique opportunity to improve the lives of men from every social and ethnic background through chemoprevention," said Lippman, who serves as a national study coordinator. "Although supplementation has been discontinued, we will continue to follow these men and monitor their health for approximately three more years, conducting regular prostate screening tests and questioning them about diabetes and other health issues. Doing so is critical not only to determine any possible long-term effects of the selenium and vitamin E, but also in order to gain a better understanding of prostate and other cancers and age-related disease."
Prostate cancer is the most common male cancer in the U.S. and the second leading cause of cancer deaths overall. The American Cancer Society estimates that more than 180,000 American men will be diagnosed with prostate cancer this year and nearly 29,000 will die from the disease. African-American men have a 60 percent higher incidence rate of prostate cancer and are two times more likely to die from the disease compared with Caucasian men.
Elise Cook, M.D., an associate professor in M. D. Anderson's Department of Clinical Cancer Prevention and the location's principal investigator, served as the chair of SELECT's Minority and Medically Underserved Subcommittee. "Our site has placed a strong emphasis on recruiting African-American men to participate. Of the 387 men we follow, 101 of those are African-American. It is important we continue to follow these men to determine long-term effects and complete the ancillary studies in which many participate," said Cook.
SELECT was based upon the secondary outcomes from two previous cancer prevention trials. The first, a 1996 study of selenium versus placebo to prevent non-melanoma skin cancer, showed that although the supplement did not reduce the risk of skin cancer, selenium did reduce prostate cancer by two-thirds; and in the second, a 1998 study conducted by Finnish researchers determined that although vitamin E did not prevent lung cancer in more than 29,000 male smokers, it did result in 32 percent fewer prostate cancers in men taking the supplement.
"Preliminary data suggesting benefits - no matter how promising - cannot reliably result in new clinical recommendations until they've been tested in definitive trials," said Ernest T. Hawk, M.D., vice president and division head of M. D. Anderson's Cancer Prevention and Population Sciences.
Although the SELECT trial did not turn out as we'd hoped - identifying a new way to reduce men's risk of prostate cancer - it was nevertheless extremely valuable by generating definitive evidence. Cancer prevention advances by rigorous science."
Identity of SELECT participants will remain blinded to prevent the introduction of any unintentional bias, however, they may be unblinded upon request. The sub-studies, funded and conducted by the National Institutes of Health's National Heart, Lung and Blood Institute, the National Institute of Aging, the National Eye Institute and the NCI, will continue without the participants taking any supplementation. These ancillary studies were evaluating the effects of selenium and vitamin E on chronic obstructive pulmonary disease, the development of Alzheimer's disease, the development of age-related macular degeneration and cataracts, and the development of colon polyps.
Lippman commented, "We are grateful to each of the 387 Houston-area men who committed to participating in this study through M. D. Anderson. Prevention trials are an important direction for the future of cancer research. SELECT played an important role in the study of the prevention of prostate cancer and we hope to learn more about why these supplements didn't do more to prevent prostate cancer as the study continues."
Co-authors with Lippman, Klein and Cook include 30 colleagues from the Southwest Oncology Group.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For four of the past six years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.
Findings from one of the largest cancer chemoprevention trials ever conducted have concluded that selenium and vitamin E taken alone or in combination for an average of five and a half years did not prevent prostate cancer, according to a team of researchers coordinated by the Southwest Oncology Group (SWOG) and led by scientists at The University of Texas M. D. Anderson Cancer Center and Cleveland Clinic.
Data and analysis gathered through Oct. 23, 2008, from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were published in the Dec. 9 issue of the Journal of the American Medical Association (JAMA) by Scott M. Lippman, M.D., professor and chair of Thoracic/Head and Neck Medical Oncology at M. D. Anderson, Eric A. Klein, M.D., of the Cleveland Clinic Lerner College of Medicine, and 30 coauthors from the United States, Puerto Rico and Canada.
Funded by the National Cancer Institute (NCI) with some additional contribution from the National Center for Complementary and Alternative Medicine, the Phase III trial began recruitment in August 2001 and aimed to determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases in relatively healthy men. The study followed 35,533 participants from 427 sites in the United States, Canada and Puerto Rico. The randomized, placebo-controlled and double-blind trial divided the participants into four intervention groups: selenium, vitamin E, both selenium and vitamin E, and placebos.
Supplement Cases 5-year prostate cancer diagnosis
Placebo 416 4.43 percent
Selenium 432 4.56 percent
Vitamin E 473 4.93 percent
Selenium + Vitamin E 437 4.56 percent
The study found no evidence of benefit from selenium, vitamin E, or both. Additionally, the data showed two statistically non-significant findings of concern: slightly increased risks of prostate cancer in the vitamin E group and type two diabetes mellitus in the selenium group. Both trends may be due to chance and were not observed in the group taking selenium and vitamin E together.
An independent data and safety monitoring committee reached the same conclusion and recommended supplementation be discontinued Oct. 23 for lack of evidence of benefit.
"SELECT presented a unique opportunity to improve the lives of men from every social and ethnic background through chemoprevention," said Lippman, who serves as a national study coordinator. "Although supplementation has been discontinued, we will continue to follow these men and monitor their health for approximately three more years, conducting regular prostate screening tests and questioning them about diabetes and other health issues. Doing so is critical not only to determine any possible long-term effects of the selenium and vitamin E, but also in order to gain a better understanding of prostate and other cancers and age-related disease."
Prostate cancer is the most common male cancer in the U.S. and the second leading cause of cancer deaths overall. The American Cancer Society estimates that more than 180,000 American men will be diagnosed with prostate cancer this year and nearly 29,000 will die from the disease. African-American men have a 60 percent higher incidence rate of prostate cancer and are two times more likely to die from the disease compared with Caucasian men.
Elise Cook, M.D., an associate professor in M. D. Anderson's Department of Clinical Cancer Prevention and the location's principal investigator, served as the chair of SELECT's Minority and Medically Underserved Subcommittee. "Our site has placed a strong emphasis on recruiting African-American men to participate. Of the 387 men we follow, 101 of those are African-American. It is important we continue to follow these men to determine long-term effects and complete the ancillary studies in which many participate," said Cook.
SELECT was based upon the secondary outcomes from two previous cancer prevention trials. The first, a 1996 study of selenium versus placebo to prevent non-melanoma skin cancer, showed that although the supplement did not reduce the risk of skin cancer, selenium did reduce prostate cancer by two-thirds; and in the second, a 1998 study conducted by Finnish researchers determined that although vitamin E did not prevent lung cancer in more than 29,000 male smokers, it did result in 32 percent fewer prostate cancers in men taking the supplement.
"Preliminary data suggesting benefits - no matter how promising - cannot reliably result in new clinical recommendations until they've been tested in definitive trials," said Ernest T. Hawk, M.D., vice president and division head of M. D. Anderson's Cancer Prevention and Population Sciences.
Although the SELECT trial did not turn out as we'd hoped - identifying a new way to reduce men's risk of prostate cancer - it was nevertheless extremely valuable by generating definitive evidence. Cancer prevention advances by rigorous science."
Identity of SELECT participants will remain blinded to prevent the introduction of any unintentional bias, however, they may be unblinded upon request. The sub-studies, funded and conducted by the National Institutes of Health's National Heart, Lung and Blood Institute, the National Institute of Aging, the National Eye Institute and the NCI, will continue without the participants taking any supplementation. These ancillary studies were evaluating the effects of selenium and vitamin E on chronic obstructive pulmonary disease, the development of Alzheimer's disease, the development of age-related macular degeneration and cataracts, and the development of colon polyps.
Lippman commented, "We are grateful to each of the 387 Houston-area men who committed to participating in this study through M. D. Anderson. Prevention trials are an important direction for the future of cancer research. SELECT played an important role in the study of the prevention of prostate cancer and we hope to learn more about why these supplements didn't do more to prevent prostate cancer as the study continues."
Co-authors with Lippman, Klein and Cook include 30 colleagues from the Southwest Oncology Group.
About M. D. Anderson
The University of Texas M. D. Anderson Cancer Center in Houston ranks as one of the world's most respected centers focused on cancer patient care, research, education and prevention. M. D. Anderson is one of only 41 Comprehensive Cancer Centers designated by the National Cancer Institute. For four of the past six years, M. D. Anderson has ranked No. 1 in cancer care in "America's Best Hospitals," a survey published annually in U.S. News and World Report.
Friday, December 05, 2008
Researchers Test Mobile Alert System for Cell Phones
In the first field trial of its kind, Georgia Tech’s Wireless Emergency Communications project tested the Federal Communications Commission’s (FCC) Commercial Mobil Alert System to see how well it met the needs of people with vision and hearing impairments. They found three areas where they will recommend changes to the FCC.
• Although 90 percent of participants who are blind or have low vision found the alert attention signal to be loud enough and long enough to get their attention, only 70 percent of deaf and hard of hearing participants indicated the same regarding the vibrating cadence. Comments regarding the vibrating cadence suggested that it would only be effective if the individual were holding the phone in their hand, but easily missed if in a purse or even in one’s pocket.
• All hearing participants expressed concern that the early part of the message was missed because the tone went too quickly into the 90-character spoken alert, causing the first few words of the message to be missed. The required Commercial Mobile Alert System message format places the event type first (i.e., tornado, flood, etc.) so crucial information may not be heard by blind consumers using text-to-speech software on their mobile phones to access the alerts. Many suggested the need for a header such as “This is a…” to allow for more clarity. Such a header is currently employed by the Emergency Alert System (EAS) messages broadcast on television, radio and cable systems.
• Deaf and hard of hearing participants commented that they would like to see enhancements such as strobe lights, screen flashes and stronger vibrating cadences. While these enhancements can be addressed by cell phone manufacturers, they aren’t required to do so by the FCC.
The tests were conducted on November 12, 2008, with 30 subjects. The results will be presented to the FCC and others during the State of Technology conference in September.
The FCC established the Commercial Mobile Alert System in 2008 to provide a framework for commercial mobile service providers to voluntarily transmit emergency alerts to their subscribers. The Rehabilitation Engineering Research Center for Wireless Technologies’ Wireless Emergency Communications project has been developing software and conducting field tests on how to make the emergency alert system accessible for people with sensory disabilities who use mobile devices.
Tech’s Wireless Emergency Communications project received additional federal funding to field test the provisions of Commercial Mobile Alert System that affect accessibility, such as the limitation of 90 characters, not permitting URLs, and volume limits including specific vibrating cadences and alert tones. By conducting this field test, they will provide the FCC and the wireless industry with concrete evidence from the perspective of end-users on how the Commercial Mobile Alert System would be better able to serve the specific needs of people with sensory disabilities. Most recommendations, however, would render the system more effective for all consumers. For example, participants suggested repeating the attention signal and vibrating cadences in intervals until they are shut off by the user to ensure the receipt of the alert by an individual who is away from their phone, asleep, driving or unable to hear or see.
The field test recruited participants from the Atlanta Area School for the Deaf, Atlanta Public School System, the Wireless Rehabilitation Engineering Research Center Consumer Advisory Network and the Georgia Radio Reading Service (GaRRS). Subjects were as diverse in their sensory limitations as they were in their technical skill level, ranging from those who were fully deaf or fully blind to those with enhanced hearing (hearing aid/cochlear implants) or enhanced vision (glasses/contacts).
Though field test participant’s names are usually held in the strictest confidence, one participant agreed to go on the record.
“I applaud PBA and Georgia Tech for their effort in bringing this very important issue to the public,” said Georgia State Representative Bob Smith. “We must continue to make this a priority, to seek innovative and creative ways to notify people with disabilities and tirelessly work to improve and perfect the notification system. It is paramount that Georgians are aware that people with various disabilities, more than any time in our history, need to be informed of catastrophic events.”
This is the second field test hosted by project partner Public Broadcasting Atlanta. PBA recognized the importance of this community project and how it aligned with its vision of implementing a Local Education Network System (LENS) capable of convening individuals, organizations and communities. MetroCast Atlanta, a component of LENS, would serve as an emergency information network for schools, city officials and citizens in the event of natural or terrorist disaster.
The mobile devices and cellular service used in this field test were the result of a generous donation from WEC industry partner AT&T. For more information on WEC, go to www.wirelessrerc.org. Funding for the CMAS parameter field test was made possible by the U.S. Department of Education’s National Institute on Disability and Rehabilitation Research, grant # H133E060061.
In the first field trial of its kind, Georgia Tech’s Wireless Emergency Communications project tested the Federal Communications Commission’s (FCC) Commercial Mobil Alert System to see how well it met the needs of people with vision and hearing impairments. They found three areas where they will recommend changes to the FCC.
• Although 90 percent of participants who are blind or have low vision found the alert attention signal to be loud enough and long enough to get their attention, only 70 percent of deaf and hard of hearing participants indicated the same regarding the vibrating cadence. Comments regarding the vibrating cadence suggested that it would only be effective if the individual were holding the phone in their hand, but easily missed if in a purse or even in one’s pocket.
• All hearing participants expressed concern that the early part of the message was missed because the tone went too quickly into the 90-character spoken alert, causing the first few words of the message to be missed. The required Commercial Mobile Alert System message format places the event type first (i.e., tornado, flood, etc.) so crucial information may not be heard by blind consumers using text-to-speech software on their mobile phones to access the alerts. Many suggested the need for a header such as “This is a…” to allow for more clarity. Such a header is currently employed by the Emergency Alert System (EAS) messages broadcast on television, radio and cable systems.
• Deaf and hard of hearing participants commented that they would like to see enhancements such as strobe lights, screen flashes and stronger vibrating cadences. While these enhancements can be addressed by cell phone manufacturers, they aren’t required to do so by the FCC.
The tests were conducted on November 12, 2008, with 30 subjects. The results will be presented to the FCC and others during the State of Technology conference in September.
The FCC established the Commercial Mobile Alert System in 2008 to provide a framework for commercial mobile service providers to voluntarily transmit emergency alerts to their subscribers. The Rehabilitation Engineering Research Center for Wireless Technologies’ Wireless Emergency Communications project has been developing software and conducting field tests on how to make the emergency alert system accessible for people with sensory disabilities who use mobile devices.
Tech’s Wireless Emergency Communications project received additional federal funding to field test the provisions of Commercial Mobile Alert System that affect accessibility, such as the limitation of 90 characters, not permitting URLs, and volume limits including specific vibrating cadences and alert tones. By conducting this field test, they will provide the FCC and the wireless industry with concrete evidence from the perspective of end-users on how the Commercial Mobile Alert System would be better able to serve the specific needs of people with sensory disabilities. Most recommendations, however, would render the system more effective for all consumers. For example, participants suggested repeating the attention signal and vibrating cadences in intervals until they are shut off by the user to ensure the receipt of the alert by an individual who is away from their phone, asleep, driving or unable to hear or see.
The field test recruited participants from the Atlanta Area School for the Deaf, Atlanta Public School System, the Wireless Rehabilitation Engineering Research Center Consumer Advisory Network and the Georgia Radio Reading Service (GaRRS). Subjects were as diverse in their sensory limitations as they were in their technical skill level, ranging from those who were fully deaf or fully blind to those with enhanced hearing (hearing aid/cochlear implants) or enhanced vision (glasses/contacts).
Though field test participant’s names are usually held in the strictest confidence, one participant agreed to go on the record.
“I applaud PBA and Georgia Tech for their effort in bringing this very important issue to the public,” said Georgia State Representative Bob Smith. “We must continue to make this a priority, to seek innovative and creative ways to notify people with disabilities and tirelessly work to improve and perfect the notification system. It is paramount that Georgians are aware that people with various disabilities, more than any time in our history, need to be informed of catastrophic events.”
This is the second field test hosted by project partner Public Broadcasting Atlanta. PBA recognized the importance of this community project and how it aligned with its vision of implementing a Local Education Network System (LENS) capable of convening individuals, organizations and communities. MetroCast Atlanta, a component of LENS, would serve as an emergency information network for schools, city officials and citizens in the event of natural or terrorist disaster.
The mobile devices and cellular service used in this field test were the result of a generous donation from WEC industry partner AT&T. For more information on WEC, go to www.wirelessrerc.org. Funding for the CMAS parameter field test was made possible by the U.S. Department of Education’s National Institute on Disability and Rehabilitation Research, grant # H133E060061.
Monday, December 01, 2008
A balancing act : Aging and Alzheimer’s disease
Cognitive decline may occur during aging, or due to genetic mutations that predispose individuals to develop Alzheimer’s disease. Now, a team of scientists, led by Akihiko Takashima at the RIKEN Brain Science Institute in Wako, has found support for their hypothesis that a similar molecular abnormality could account for cognitive dysfunction during both Alzheimer’s disease and aging. They report their findings in a recent issue of PLoS ONE (1).
The researchers subjected aged mice (19–25 months) and adult mice (9–15 months) harboring genetic mutations associated with Alzheimer’s disease to a test of spatial memory—the Morris water maze. Both groups of mice were trained to find a platform submerged in a pool of water based on visual cues around the pool (Fig. 1). When this training period was complete, the researchers could assess how well the mice remembered the platform location by determining how much time the mouse spends near the platform during a ‘probe trial’. They found that both the aged mice and the mice with the Alzheimer’s disease mutations had spatial memory deficits.
The neurotransmitter GABA (γ-aminobutyric acid) controls inhibitory signaling in the brain, and GABA receptor blockers have previously been shown to improve cognition in aging rats. To see if this was also true in Alzheimer mutant mice, the researchers administered a GABA receptor blocker, and saw restoration of normal spatial memory in the Morris water maze. The treated mice were also better at recognizing a new object placed into their cage, which is a measure of ‘declarative memory’.
The researchers then examined synaptic plasticity in a part of the brain that plays a role in spatial memory—the hippocampus. They found deficits in synaptic plasticity in hippocampal slices from both aging and Alzheimer mutant mice. However, normal synaptic plasticity could be restored by adding a GABA receptor blocker. This suggests that both aging and Alzheimer’s disease mutations may affect memory by increasing GABA-mediated inhibitory signaling in the hippocampus.
These findings show that GABA receptor blockers may be an effective therapeutic strategy to enhance cognitive function during both aging and Alzheimer’s disease. This work also indicates that an imbalance between excitatory and inhibitory signaling in the brain may result in memory dysfunction. Yuji Yoshiike, the study’s first author, says the findings suggest that “even when memory declines because of the accumulation of neurotoxic molecules during aging, memory may be improved by restoring the balance between synaptic excitation and inhibition.”
Reference
1. Yoshiike, Y., Kimura, T., Yamashita, S., Furudate, H., Mizoroki, T., Murayama, M. & Takashima, A. GABAA receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS ONE 3, e3029 (2008).
Cognitive decline may occur during aging, or due to genetic mutations that predispose individuals to develop Alzheimer’s disease. Now, a team of scientists, led by Akihiko Takashima at the RIKEN Brain Science Institute in Wako, has found support for their hypothesis that a similar molecular abnormality could account for cognitive dysfunction during both Alzheimer’s disease and aging. They report their findings in a recent issue of PLoS ONE (1).
The researchers subjected aged mice (19–25 months) and adult mice (9–15 months) harboring genetic mutations associated with Alzheimer’s disease to a test of spatial memory—the Morris water maze. Both groups of mice were trained to find a platform submerged in a pool of water based on visual cues around the pool (Fig. 1). When this training period was complete, the researchers could assess how well the mice remembered the platform location by determining how much time the mouse spends near the platform during a ‘probe trial’. They found that both the aged mice and the mice with the Alzheimer’s disease mutations had spatial memory deficits.
The neurotransmitter GABA (γ-aminobutyric acid) controls inhibitory signaling in the brain, and GABA receptor blockers have previously been shown to improve cognition in aging rats. To see if this was also true in Alzheimer mutant mice, the researchers administered a GABA receptor blocker, and saw restoration of normal spatial memory in the Morris water maze. The treated mice were also better at recognizing a new object placed into their cage, which is a measure of ‘declarative memory’.
The researchers then examined synaptic plasticity in a part of the brain that plays a role in spatial memory—the hippocampus. They found deficits in synaptic plasticity in hippocampal slices from both aging and Alzheimer mutant mice. However, normal synaptic plasticity could be restored by adding a GABA receptor blocker. This suggests that both aging and Alzheimer’s disease mutations may affect memory by increasing GABA-mediated inhibitory signaling in the hippocampus.
These findings show that GABA receptor blockers may be an effective therapeutic strategy to enhance cognitive function during both aging and Alzheimer’s disease. This work also indicates that an imbalance between excitatory and inhibitory signaling in the brain may result in memory dysfunction. Yuji Yoshiike, the study’s first author, says the findings suggest that “even when memory declines because of the accumulation of neurotoxic molecules during aging, memory may be improved by restoring the balance between synaptic excitation and inhibition.”
Reference
1. Yoshiike, Y., Kimura, T., Yamashita, S., Furudate, H., Mizoroki, T., Murayama, M. & Takashima, A. GABAA receptor-mediated acceleration of aging-associated memory decline in APP/PS1 mice and its pharmacological treatment by picrotoxin. PLoS ONE 3, e3029 (2008).
Bringing Galatea to life
Inflammation is a key step in the progression of heterotopic ossification – where soft tissue turns into bone – according to research. The study shows that an inhibitor of the disease gene’s protein product is partially therapeutic, and therefore offers hope for this devastating condition.
In a reverse of the ancient myth of Pygmalion, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue ‘ossified’ — in effect, turning the patients into statues. A major form of heterotopic ossification is fibrodysplasia ossificans progressiva (FOP), which in about 98% of cases results from a mutation in a specific bone morphogenetic protein receptor.
A mouse model of FOP involving the same mutation found in people has yet to be made, but Paul Yu and colleagues have now developed a mouse model of the general phenomenon by expressing a related version of the mutated receptor. They found that just expressing the mutant version of the protein receptor was not sufficient to cause the disease – an inflammatory stimulus was also needed. Yu’s team also show that inhibiting inflammation with glucocorticoids—a treatment commonly used in the clinic—helps reduce the incidence of heterotopic ossification in their model.
Importantly, the authors also show that a small molecule inhibitor of the protein receptor likewise reduced the incidence of disease progression. This form of treatment represents a potential breakthrough, as long-term use of glucocorticoids causes severe side-effects. The authors caution, however, that much more research is needed before the drug could be considered for human trials.
Author contact:
Paul Yu (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
Tel: +1 617 643 3493; E-mail: pbyu@partners.org
Inflammation is a key step in the progression of heterotopic ossification – where soft tissue turns into bone – according to research. The study shows that an inhibitor of the disease gene’s protein product is partially therapeutic, and therefore offers hope for this devastating condition.
In a reverse of the ancient myth of Pygmalion, where a statue comes to life, sufferers of heterotopic ossification have their fibrous tissue ‘ossified’ — in effect, turning the patients into statues. A major form of heterotopic ossification is fibrodysplasia ossificans progressiva (FOP), which in about 98% of cases results from a mutation in a specific bone morphogenetic protein receptor.
A mouse model of FOP involving the same mutation found in people has yet to be made, but Paul Yu and colleagues have now developed a mouse model of the general phenomenon by expressing a related version of the mutated receptor. They found that just expressing the mutant version of the protein receptor was not sufficient to cause the disease – an inflammatory stimulus was also needed. Yu’s team also show that inhibiting inflammation with glucocorticoids—a treatment commonly used in the clinic—helps reduce the incidence of heterotopic ossification in their model.
Importantly, the authors also show that a small molecule inhibitor of the protein receptor likewise reduced the incidence of disease progression. This form of treatment represents a potential breakthrough, as long-term use of glucocorticoids causes severe side-effects. The authors caution, however, that much more research is needed before the drug could be considered for human trials.
Author contact:
Paul Yu (Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA)
Tel: +1 617 643 3493; E-mail: pbyu@partners.org
Subscribe to:
Posts (Atom)
