Ubiquitination is a key part of the process by which proteins are broken down and recycled within human cells. But understanding how ubiquitination works and its role in disease has eluded researchers for decades.
Now a key part in this puzzle has been solved by researchers at Weill Cornell Medical College who developed a method to clarify the role that ubiquitination plays in a variety of diseases, including breast cancer and Parkinson's disease. It is hoped that their discovery will lead both to better treatments as well as finding ways to delay and even prevent these illnesses.
The research team's breakthrough findings were published online in the July 18 issue of Nature Biotechnology. Since then, they have had inquiries from researchers around the world.
Cell division, DNA repair, and parts of the immune defense system are all governed by ubiquitin-mediated protein degradation. However, when this process does not work correctly, it causes illnesses, including cancers.
"We know that the cell functions as a highly efficient checking station where proteins are built up and broken down," says Dr. Samie R. Jaffrey, associate professor of pharmacology at Weill Cornell Medical College and the lead author of the paper. "During this process, broken proteins are given a molecular label and then fed into proteasomes where they are destroyed. The 'label' is the molecule ubiquitin, which fastens to the protein to be destroyed and accompanies it to the proteasome where it is 'recognized,' signaling that a protein is on the way for disassembly."
In his studies of brain development, Dr. Jaffrey had observed that proteins were being rapidly ubiquitinated, and that this ubiquitination was required to enable neurons to form proper connections in the brain. However, methods to identify the proteins that were being degraded during this dynamic process were not available. "We predicted that finding the proteins that were ubiquitinated would tell us how neurons form connections throughout the brain."
To test their hypothesis, the team developed a new strategy to profile ubiquitination across the proteome by utilizing a monoclonal antibody that allows ubiquitinated proteins to be recovered from tissue extracts and then quantified using high-throughput mass spectrometry. The ubiquitination targets included proteins that are involved in brain development, as well as disease-related proteins such as BRCA-1 (one of two breast cancer genes) and TNF receptor-associated proteins -- genes involved in cell growth, cell division, and repair of damage to DNA.
In addition to identifying several hundred proteins that were ubiquitinated, they were also able to identify the specific portion of the protein that was modified. Nearly three quarters of the proteins were not previously known to be ubiquitinated and 92 percent of these ubiquitination sites were not previously known. Strikingly, the ubiquitin tags were observed to rapidly increase following treatments that stimulated cell growth or death, suggesting that ubiquitination may regulate these cellular processes. "Ubiquitination has long been extremely difficult to study, but our method has opened the door to clarifying the role of ubiquitination in a variety of diseases," Dr. Jaffrey says. "A surprisingly number of diseases have been linked to defective ubiquitination, such as breast cancer, myeloma and Parkinson's disease. We hope our findings will also allow researchers to screen drugs for their ability to inhibit ubiquitination and ultimately come up with better treatments."
In 2009, Dr. Jaffrey was among a select group of researchers awarded a competitive grant from the National Institutes of Health (NIH) called the NIH Director's Transformative R01 (T-R01) Awards. According to the NIH, the grants were given to "encourage investigators to explore bold ideas that have the potential to catapult fields forward and speed the translation of research into improved health."
Besides Dr. Jaffrey, contributing authors to the study published in Nature Biotechnology included Weill Cornell's Dr. Guoqiang Xu, and Jeremy S. Paige, a graduate student of the Department of Pharmacology.
Dr. Jaffrey, is a co-founder and co-owner of Lucerna Technologies, and is a member of its advisory board. Lucerna Technologies is a biotechnology company focused on developing and commercializing nucleic acid-based florescent sensors for point-of-care therapeutic diagnostics. Additionally Lucerna offers antibodies for proteomic research.
Source:
Weill Cornell Medical College
вторник, 31 мая 2011 г.
понедельник, 30 мая 2011 г.
With Fruit Fly Sex, Researchers Find Mind-body Connection
Male fruit flies are smaller and darker than female flies. The hair-like bristles on their forelegs are shorter, thicker. Their sexual equipment, of course, is different, too.
"Doublesex" is the gene largely responsible for these body differences. Doublesex, new research shows, is responsible for behavior differences as well. The finding, made by Brown University biologists, debunks the notion that sexual mind and sexual body are built by separate sets of genes. Rather, researchers found, doublesex acts in concert with the gene "fruitless" to establish the wing-shaking come-ons and flirtatious flights that mark male and female fly courtship.
Results are published in Nature Genetics.
"What we found here, and what is becoming increasingly clear in the field, is that genetic interactions that influence behavior are more complex than we thought," said Michael McKeown, a Brown biologist who led the research. "In the case of sex-differences in flies, there isn't a simple two-track genetic system - one that shapes body and one that shapes behavior. Doublesex and fruitless act together to help regulate behavior in the context of other developmental genes."
How genes contribute to behavior, from aggression to alcoholism, is a growing and contentious area of biology. For more than a decade, McKeown has been steeped in the science, using the fruit fly as a model to understand how genes build a nervous system that, in turn, controls complex behaviors. Since humans and flies have thousands of genes in common, the work can shine a light on the biological roots of human behavior. For example, McKeown recently helped discover a genetic mutation that causes flies to develop symptoms similar to Alzheimer's disease - a gene very similar to one found in humans.
Some of McKeown's recent work focuses on understanding gene networks that control sexual behavior. Research on the topic is often contradictory. Some scientists suggest that the fruitless gene, active only in males, controls courtship and sexual receptivity by repressing female behavior and activating male behavior. Other scientists have found that a web of interacting genes control courtship and receptivity. McKeown wanted to settle the debate.
McKeown suspected that multiple genes shape behavior and that doublesex played a role. But experimenting with doublesex is difficult. When both copies of the gene are removed - a powerful way to test gene function - flies have the physical features of both sexes. As a result, these mutant females are not recognized by normal males and these mutant males are not recognized by normal females - and none of the mutants can mate. So this makes it difficult for scientists to categorize their behavior as gender appropriate.
So McKeown raised flies missing one of two copies of doublesex, a process that didn't completely remove the gene's influence but drastically reduced it. The result: Flies' sexual equipment was intact, but, theoretically, their sexual behavior might be different. McKeown and graduate student Troy Shirangi also reduced the activity of the fruitless gene as well as one called "retained."
Shirangi and McKeown did, indeed, see a doublesex influence. Doublesex helped the males act macho during courting - chasing females, shaking their wings to "sing" love songs, tapping or licking their intended mates. In females, doublesex worked together with the gene retained to make them more receptive to this wooing; Females with two good copies of the gene were more likely to listen to love songs and to copulate. Interestingly, reducing the activity of doublesex or retained also allowed females to court like males, even though they lack the male-behavior-inducing activity of fruitless.
By manipulating fruitless and retained in other experiments, McKeown and his team found critical interactions, or overlaps, in the "mind" and "body" pathways. Retained acts in both sexes, repressing male courting behavior and boosting female receptivity. Fruitless and doublesex act together, as a switch system, to affect this sexual behavior.
"The big story is the crossover between the 'mind' and 'body' pathways," McKeown said. "If sexual behaviors are genetically controlled in humans, I expect that this system would be just as much, if not more, complicated."
Shirangi, a graduate student in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown, was lead author of the Nature Genetics article. Barbara Taylor, an associate professor of zoology at Oregon State University, also took part in the fly research.
The National Science Foundation and the National Institutes of Health funded the work.
Contact: Wendy Lawton
Brown University
"Doublesex" is the gene largely responsible for these body differences. Doublesex, new research shows, is responsible for behavior differences as well. The finding, made by Brown University biologists, debunks the notion that sexual mind and sexual body are built by separate sets of genes. Rather, researchers found, doublesex acts in concert with the gene "fruitless" to establish the wing-shaking come-ons and flirtatious flights that mark male and female fly courtship.
Results are published in Nature Genetics.
"What we found here, and what is becoming increasingly clear in the field, is that genetic interactions that influence behavior are more complex than we thought," said Michael McKeown, a Brown biologist who led the research. "In the case of sex-differences in flies, there isn't a simple two-track genetic system - one that shapes body and one that shapes behavior. Doublesex and fruitless act together to help regulate behavior in the context of other developmental genes."
How genes contribute to behavior, from aggression to alcoholism, is a growing and contentious area of biology. For more than a decade, McKeown has been steeped in the science, using the fruit fly as a model to understand how genes build a nervous system that, in turn, controls complex behaviors. Since humans and flies have thousands of genes in common, the work can shine a light on the biological roots of human behavior. For example, McKeown recently helped discover a genetic mutation that causes flies to develop symptoms similar to Alzheimer's disease - a gene very similar to one found in humans.
Some of McKeown's recent work focuses on understanding gene networks that control sexual behavior. Research on the topic is often contradictory. Some scientists suggest that the fruitless gene, active only in males, controls courtship and sexual receptivity by repressing female behavior and activating male behavior. Other scientists have found that a web of interacting genes control courtship and receptivity. McKeown wanted to settle the debate.
McKeown suspected that multiple genes shape behavior and that doublesex played a role. But experimenting with doublesex is difficult. When both copies of the gene are removed - a powerful way to test gene function - flies have the physical features of both sexes. As a result, these mutant females are not recognized by normal males and these mutant males are not recognized by normal females - and none of the mutants can mate. So this makes it difficult for scientists to categorize their behavior as gender appropriate.
So McKeown raised flies missing one of two copies of doublesex, a process that didn't completely remove the gene's influence but drastically reduced it. The result: Flies' sexual equipment was intact, but, theoretically, their sexual behavior might be different. McKeown and graduate student Troy Shirangi also reduced the activity of the fruitless gene as well as one called "retained."
Shirangi and McKeown did, indeed, see a doublesex influence. Doublesex helped the males act macho during courting - chasing females, shaking their wings to "sing" love songs, tapping or licking their intended mates. In females, doublesex worked together with the gene retained to make them more receptive to this wooing; Females with two good copies of the gene were more likely to listen to love songs and to copulate. Interestingly, reducing the activity of doublesex or retained also allowed females to court like males, even though they lack the male-behavior-inducing activity of fruitless.
By manipulating fruitless and retained in other experiments, McKeown and his team found critical interactions, or overlaps, in the "mind" and "body" pathways. Retained acts in both sexes, repressing male courting behavior and boosting female receptivity. Fruitless and doublesex act together, as a switch system, to affect this sexual behavior.
"The big story is the crossover between the 'mind' and 'body' pathways," McKeown said. "If sexual behaviors are genetically controlled in humans, I expect that this system would be just as much, if not more, complicated."
Shirangi, a graduate student in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown, was lead author of the Nature Genetics article. Barbara Taylor, an associate professor of zoology at Oregon State University, also took part in the fly research.
The National Science Foundation and the National Institutes of Health funded the work.
Contact: Wendy Lawton
Brown University
воскресенье, 29 мая 2011 г.
Technique Monitors Thousands Of Molecules Simultaneously
It's electric
A chemist at Washington University in St. Louis is making molecules the new-fashioned way - selectively harnessing thousands of minuscule electrodes on a tiny computer chip that do chemical reactions and yield molecules that bind to receptor sites. Kevin Moeller, Ph.D., Washington University professor of chemistry in Arts & Sciences, is doing this so that the electrodes on the chip can be used to monitor the biological behavior of up to 12,000 molecules at the same time.
Lock and key
The work is motivated by a desire to map the three-dimensional requirements of biological receptors on cell surfaces. Typically, receptors bind small molecules through a lock and key mechanism where the molecule is the key and the receptor the lock. The nature and shape of molecules that serve as keys tells about the binding requirements of the receptor. Traditionally, probing a receptor this way has been done by making a library of molecules, treating it with the receptor, washing away any excess receptor that has not found a key, and then treating the bound receptors with an antibody that recognizes the receptor and is tagged to a fluorescent label. The washing step risks removing a bound receptor if it does not bind the molecular key strongly enough. But, with an electrochemically addressable computer chip, provided in great abundance by one of his sponsor's, CombiMatrix in Seattle, Moeller saw a way of probing the binding of a library with a receptor without the need for washing by putting each member of the molecular library by an electrode that can then be used to monitor its behavior.
The electrochemically addressable chips being used represent a new environment for synthetic organic chemistry, changing the way chemists and biomedical researchers make molecules, build molecular libraries and understand the mechanisms by which molecules bind to receptor sites.
"We believe we can move most of modern synthetic organic chemistry to this electrochemically addressable chip. In this way, a wide variety of molecules can be generated and then probed for their biological behavior in real-time," said Moeller. "It's a tool, still being developed, to map receptors. We're right at the cusp of things."
Moeller published on the technology in a recent article in the Journal of the American Chemical Society, Vol. 28 16020, 2006. He will discuss the work at the 211th National Meeting of the Electrochemistry Society in Chicago, May 7, 2007. The National Science Foundation and the CombiMatrix Corp. in Seattle fund the work.
The Great Wall of China syndrome
Moeller said that the standard problem for synthetic organic chemists has typically been a structural one - how do we build molecules having novel structures?
"We've worked very hard to develop new chemical reactions that allow us to make new structures that are either difficult or impossible to make with the synthetic tools available," he said. "But now for the first time it's not just a matter of structure, but rather a matter of location and scale - a logistical problem."
He offered the Great Wall of China as an example of a classic logistics problem - the structure itself was simple, but getting the tools and manpower necessary for the task to the remote regions it was built in on the scale necessary was "a logistical nightmare."
Getting 12,000 electrodes per square centimeter to selectively do your chemical bidding is Moeller's logistical nightmare. How do you get chemical reactions to happen at just one of the electrodes? Here's how he and his colleagues addressed it.
Scientists at CombiMatrix initially pioneered an approach for covering the chip with a polymer, attaching a substrate to the polymer right above the electrode, and then using the electrode to initiate a chemical reaction that modified the substrate and converted it into a product. Putting a confining agent into the solution destroys the reagent made, keeping it from going to another electrode. This was done for the generation of acids and bases and applied to the synthesis of DNA and peptide polymers. But could this approach be used to make the more difficult to synthesize shaped molecules needed for mapping a receptor? This would require a diverse array of reactions to be compatible with the chips, particularly reactions that capitalized on modern, state-of-the-art metal-based reagents.
Working with his students, Moeller started by running a well-known electrochemical Wacker oxidation reaction, which converts an olefin into a ketone using palladium(II) on selected electrodes on the chip. In order to do this, the palladium(II) reagent needed at a selected electrode was actually made at the desired site using the electrode. This allowed for the desired reaction at only electrodes that were turned on. To keep the palladium(II) from going to a neighboring electrode a second reagent was added to the solution above the chip that destroyed the palladium(II) reagent. In this way, nothing happened at electrodes that were not being used.
Reversing the polarity of things
"The chip is an ongoing battle between active reagent and inactive reagent," Moeller said. "The active reagent is fine - it does the chemistry I want it to do - but as soon as it gets away from the turned-on electrode the reaction that inactivates it needs to take over."
With an overall strategy in place, Moeller and his collaborators are working to expand the scope of reactions that can be done. For example, they have carried out the oxidation of an alcohol to form a carbonyl and then used the carbonyl to put a dye down. They placed a green dye at alternating electrodes in a checkerboard pattern, and then used the alternate set of electrodes to put down a red dye. The result was a red and green chip, Washington University's colors. This, Moeller said, is a striking image of the technique's ability to do chemistry at specific electrodes. "What electrochemistry does best is to reverse the polarity of things," Moeller said. "It takes things that are electron-poor and makes them electron-rich and vice versa; it can take an oxidant and turn it into a reductant; a reductant into an oxidant; a base into an acid and an acid into a base; and so on. In the end, almost any chemical reagent can be made at an electrode and used on the chips."
Moeller said that , along with emphasizing new reactions, he and his collaborators are working to better identify the molecules they make on the chips, and perfect the signaling techniques used to monitor molecules on the chips. He praised the time-of-flight secondary-ion-mass spectrometry work of his Washington University colleague Amy Walker, Ph.D., assistant professor of chemistry, in the monitoring of his system.
Contact: Kevin Moeller
Washington University in St. Louis
A chemist at Washington University in St. Louis is making molecules the new-fashioned way - selectively harnessing thousands of minuscule electrodes on a tiny computer chip that do chemical reactions and yield molecules that bind to receptor sites. Kevin Moeller, Ph.D., Washington University professor of chemistry in Arts & Sciences, is doing this so that the electrodes on the chip can be used to monitor the biological behavior of up to 12,000 molecules at the same time.
Lock and key
The work is motivated by a desire to map the three-dimensional requirements of biological receptors on cell surfaces. Typically, receptors bind small molecules through a lock and key mechanism where the molecule is the key and the receptor the lock. The nature and shape of molecules that serve as keys tells about the binding requirements of the receptor. Traditionally, probing a receptor this way has been done by making a library of molecules, treating it with the receptor, washing away any excess receptor that has not found a key, and then treating the bound receptors with an antibody that recognizes the receptor and is tagged to a fluorescent label. The washing step risks removing a bound receptor if it does not bind the molecular key strongly enough. But, with an electrochemically addressable computer chip, provided in great abundance by one of his sponsor's, CombiMatrix in Seattle, Moeller saw a way of probing the binding of a library with a receptor without the need for washing by putting each member of the molecular library by an electrode that can then be used to monitor its behavior.
The electrochemically addressable chips being used represent a new environment for synthetic organic chemistry, changing the way chemists and biomedical researchers make molecules, build molecular libraries and understand the mechanisms by which molecules bind to receptor sites.
"We believe we can move most of modern synthetic organic chemistry to this electrochemically addressable chip. In this way, a wide variety of molecules can be generated and then probed for their biological behavior in real-time," said Moeller. "It's a tool, still being developed, to map receptors. We're right at the cusp of things."
Moeller published on the technology in a recent article in the Journal of the American Chemical Society, Vol. 28 16020, 2006. He will discuss the work at the 211th National Meeting of the Electrochemistry Society in Chicago, May 7, 2007. The National Science Foundation and the CombiMatrix Corp. in Seattle fund the work.
The Great Wall of China syndrome
Moeller said that the standard problem for synthetic organic chemists has typically been a structural one - how do we build molecules having novel structures?
"We've worked very hard to develop new chemical reactions that allow us to make new structures that are either difficult or impossible to make with the synthetic tools available," he said. "But now for the first time it's not just a matter of structure, but rather a matter of location and scale - a logistical problem."
He offered the Great Wall of China as an example of a classic logistics problem - the structure itself was simple, but getting the tools and manpower necessary for the task to the remote regions it was built in on the scale necessary was "a logistical nightmare."
Getting 12,000 electrodes per square centimeter to selectively do your chemical bidding is Moeller's logistical nightmare. How do you get chemical reactions to happen at just one of the electrodes? Here's how he and his colleagues addressed it.
Scientists at CombiMatrix initially pioneered an approach for covering the chip with a polymer, attaching a substrate to the polymer right above the electrode, and then using the electrode to initiate a chemical reaction that modified the substrate and converted it into a product. Putting a confining agent into the solution destroys the reagent made, keeping it from going to another electrode. This was done for the generation of acids and bases and applied to the synthesis of DNA and peptide polymers. But could this approach be used to make the more difficult to synthesize shaped molecules needed for mapping a receptor? This would require a diverse array of reactions to be compatible with the chips, particularly reactions that capitalized on modern, state-of-the-art metal-based reagents.
Working with his students, Moeller started by running a well-known electrochemical Wacker oxidation reaction, which converts an olefin into a ketone using palladium(II) on selected electrodes on the chip. In order to do this, the palladium(II) reagent needed at a selected electrode was actually made at the desired site using the electrode. This allowed for the desired reaction at only electrodes that were turned on. To keep the palladium(II) from going to a neighboring electrode a second reagent was added to the solution above the chip that destroyed the palladium(II) reagent. In this way, nothing happened at electrodes that were not being used.
Reversing the polarity of things
"The chip is an ongoing battle between active reagent and inactive reagent," Moeller said. "The active reagent is fine - it does the chemistry I want it to do - but as soon as it gets away from the turned-on electrode the reaction that inactivates it needs to take over."
With an overall strategy in place, Moeller and his collaborators are working to expand the scope of reactions that can be done. For example, they have carried out the oxidation of an alcohol to form a carbonyl and then used the carbonyl to put a dye down. They placed a green dye at alternating electrodes in a checkerboard pattern, and then used the alternate set of electrodes to put down a red dye. The result was a red and green chip, Washington University's colors. This, Moeller said, is a striking image of the technique's ability to do chemistry at specific electrodes. "What electrochemistry does best is to reverse the polarity of things," Moeller said. "It takes things that are electron-poor and makes them electron-rich and vice versa; it can take an oxidant and turn it into a reductant; a reductant into an oxidant; a base into an acid and an acid into a base; and so on. In the end, almost any chemical reagent can be made at an electrode and used on the chips."
Moeller said that , along with emphasizing new reactions, he and his collaborators are working to better identify the molecules they make on the chips, and perfect the signaling techniques used to monitor molecules on the chips. He praised the time-of-flight secondary-ion-mass spectrometry work of his Washington University colleague Amy Walker, Ph.D., assistant professor of chemistry, in the monitoring of his system.
Contact: Kevin Moeller
Washington University in St. Louis
Health Canada To Host 2010 World Health Organization Scientific Experts Meeting On Bisphenol A
The Honourable Leona Aglukkaq, Minister of Health, announced that Canada will be hosting a World Health Organization meeting of scientific experts to discuss Bisphenol A (BPA) in food packaging. The meeting will take place in October 2010 in Ottawa.
"The health and safety of Canadians, and particularly of our children, is a priority for our Government" said Minister Aglukkaq. "The Government of Canada has taken a leadership role on the issue of Bisphenol A in consumer products and food packaging, and we continue that leadership by hosting the World Health Organization for these important discussions."
The meeting, which is organized by the World Health Organization's Food Safety Program, will involve scientific experts from around the world. The goal is to develop guidance for food safety regulators internationally on the potential risks associated with the use of this chemical in food packaging materials, based on the latest scientific information, and to identify any additional knowledge gaps.
Data stemming from the Government of Canada's Research Program on BPA, announced in 2008, will be submitted to this experts meeting as part of the review.
In addition to this work, Health Canada is also committed to working to reduce exposure to BPA for infants and young children to levels as low as reasonably achievable. As part of this work, the department has asked for a progress report from the food packaging industry on the implementation of measures to reduce levels of BPA in infant formula products.
Bisphenol A (BPA) is an industrial chemical used to make a hard, clear plastic known as polycarbonate, which is used in many consumer products. Bisphenol A is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans.
More information on the Government of Canada's work on BPA in food is available on the Health Canada Web site.
Source
Health Canada
"The health and safety of Canadians, and particularly of our children, is a priority for our Government" said Minister Aglukkaq. "The Government of Canada has taken a leadership role on the issue of Bisphenol A in consumer products and food packaging, and we continue that leadership by hosting the World Health Organization for these important discussions."
The meeting, which is organized by the World Health Organization's Food Safety Program, will involve scientific experts from around the world. The goal is to develop guidance for food safety regulators internationally on the potential risks associated with the use of this chemical in food packaging materials, based on the latest scientific information, and to identify any additional knowledge gaps.
Data stemming from the Government of Canada's Research Program on BPA, announced in 2008, will be submitted to this experts meeting as part of the review.
In addition to this work, Health Canada is also committed to working to reduce exposure to BPA for infants and young children to levels as low as reasonably achievable. As part of this work, the department has asked for a progress report from the food packaging industry on the implementation of measures to reduce levels of BPA in infant formula products.
Bisphenol A (BPA) is an industrial chemical used to make a hard, clear plastic known as polycarbonate, which is used in many consumer products. Bisphenol A is also found in epoxy resins, which act as a protective lining on the inside of metal-based food and beverage cans.
More information on the Government of Canada's work on BPA in food is available on the Health Canada Web site.
Source
Health Canada
суббота, 28 мая 2011 г.
Aggressive Monopolisation Of Mobile Caregivers - Proceedings Of The Royal Society B: Biological Sciences
In groups of a social mammal, the banded mongoose, the majority of pups each form a stable exclusive association with an adult group member (its 'escort') that is its principal care provider.
In spite of pups within the communal litter being closely related, each pup aggressively defends access to its escort, preventing other pups approaching, and therefore monopolises the care provided by its escort.
The distribution of care from parents and helpers to young is therefore due to competitive actions of the young rather than preference of the adults. Conflict is as rife as cooperation in this social mammal.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
In spite of pups within the communal litter being closely related, each pup aggressively defends access to its escort, preventing other pups approaching, and therefore monopolises the care provided by its escort.
The distribution of care from parents and helpers to young is therefore due to competitive actions of the young rather than preference of the adults. Conflict is as rife as cooperation in this social mammal.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
пятница, 27 мая 2011 г.
Multidisciplinary Laboratory Columbus Safely Installed On International Space Station
NASA's space shuttle Atlantis, which successfully delivered ESA's Columbus laboratory to the International Space Station, has safely returned to Earth with its crew of seven. Landing was at 14:07 UTC (15:07 CET) on 20 February at Kennedy Space Center, Florida.
On this STS-122 mission, the shuttle spent nearly 13 days in space, including 9 days docked to the Station to conduct a major ISS assembly task: delivery of Europe's first permanent manned outpost in orbit. The 7-m long 12.8-tonne Columbus module, a state-of-the-art multidisciplinary laboratory, was attached to the Harmony (Node 2) module on 11 February.
Once leak checks and initial electrical, fluid and data connections were completed, the module's hatch was opened on 12 February, marking Europe's new status as a full partner and co-owner of the ISS. Outfitting work inside Columbus began only a few hours later, as the laboratory entered its commissioning phase, which was commanded and controlled by the Columbus Control Centre (Col-CC) located in Oberpfaffenhoffen near Munich, Germany.
Two ESA astronauts, Hans Schlegel of Germany and LГ©opold Eyharts of France, were ferried to the Station by Atlantis and both contributed directly to this success. As a member of the STS-122 crew, Hans Schlegel performed one of the three spacewalks during the mission with fellow astronaut Rex Walheim of NASA. He also coordinated the other two spacewalks, supporting the Columbus module's transfer from the shuttle payload bay to the ISS, plus the transfer of two payload suites, SOLAR and EuTEF, to external platforms on the Columbus module. Hans Schlegel returned to Earth with Atlantis.
After formal crew responsibility hand-over tasks following the docking of Atlantis with the Station, LГ©opold Eyharts became part of the resident ISS crew (Expedition 16), trading places with NASA astronaut Dan Tani. He provided support for Columbus docking from inside the Harmony module, activating the motorised bolts to secure the junction, and assisted the third spacewalk by operating the station's robotic arm.
Unlike Schlegel, Eyharts remained on the ISS when Atlantis undocked two days ago. He will spend the next month in space to complete the Columbus module's commissioning and to perform a series of experiments, both in the laboratory and in the other science facilities already operating in the Station. LГ©opold Eyharts is scheduled to return to earth with the next shuttle ISS mission (Endeavour/STS-123), at the end of March.
ESA builds up its contribution to the ISS
With the addition of Columbus, the pressurised volume of the Space Station was increased by a mere 15%, but its science capacity was nearly doubled. Two modules of the Japanese laboratory will be added in March and May, and a Russian Multi-Purpose Laboratory Module (MLM) will follow in 2011.
A new era is also beginning for ESA's activities onboard. As a fully-fledged partner of the ISS programme, ESA will now not only enjoy the benefits of Columbus but will also have to contribute to ISS operations. This will be achieved through the launch of unmanned servicing missions carried out by the Automated Transfer Vehicle, designed to deliver speares, scientific experiments, crew support equipment (food, clothing), fluids and propellant and to perform reboost to compensate for orbital decay of the ISS. The first ATV , Jules Verne, will be launched by an Ariane 5 on 8 March.
But ESA will also benefit from the Station by conducting experiments within its many science facilities, and by regularly sending European astronauts to perform long-duration stays onboard as members of the resident crew. Two ESA astronauts are already training for such missions: Frank de Winne of Belgium who will fly as a member of the ISS Expedition 19 crew in 2009; and AndrГ© Kuipers of the Netherlands who will be his backup. More will follow.
Further European-built ISS elements are still under preparation to be launched to the ISS within the decade, such as the Material Science Laboratory (MSL), the Muscle Atrophy Resistive Exercise System (MARES), the European Robotic Arm (ERA), the Node 3 module and the Cupola observation deck.
As Columbus is coming to life, so too is the network of nine User Support and Operations Centres (USOCs), which has been set up all over Europe to facilitate the interface between researchers and the science payloads onboard, and to allow investigators to control their experiments and receive real-time data on their results, through an interconnection provided via the Columbus Control Centre.
Commissioning of the European laboratory has proceeded well and faster than planned. The two external payloads SOLAR and EuTEF have been deployed outside Columbus and already provide data. WAICO, the first experiment to be conducted inside the lab, will start this week inside Biolab. The Geoflow experiment will start up in early March inside the Fluid Science Laboratory.
Over the coming weeks and months, the USOC network's activity will increase dramatically as the science equipment and experiments already onboard Columbus are commissioned and switched to operational status, and as more science payloads are delivered to the module by the upcoming logistics missions.
Columbus was designed to support some 500 experiments per year for ten years, in cell and plant biology, astrobiology, human physiology, fluid and material sciences, fundamental physics, astronomy, remote sensing and technology. For the European science community and industrial R&D, a new era of research has just begun.
Source: ESA Media Relations Office
European Space Agency
On this STS-122 mission, the shuttle spent nearly 13 days in space, including 9 days docked to the Station to conduct a major ISS assembly task: delivery of Europe's first permanent manned outpost in orbit. The 7-m long 12.8-tonne Columbus module, a state-of-the-art multidisciplinary laboratory, was attached to the Harmony (Node 2) module on 11 February.
Once leak checks and initial electrical, fluid and data connections were completed, the module's hatch was opened on 12 February, marking Europe's new status as a full partner and co-owner of the ISS. Outfitting work inside Columbus began only a few hours later, as the laboratory entered its commissioning phase, which was commanded and controlled by the Columbus Control Centre (Col-CC) located in Oberpfaffenhoffen near Munich, Germany.
Two ESA astronauts, Hans Schlegel of Germany and LГ©opold Eyharts of France, were ferried to the Station by Atlantis and both contributed directly to this success. As a member of the STS-122 crew, Hans Schlegel performed one of the three spacewalks during the mission with fellow astronaut Rex Walheim of NASA. He also coordinated the other two spacewalks, supporting the Columbus module's transfer from the shuttle payload bay to the ISS, plus the transfer of two payload suites, SOLAR and EuTEF, to external platforms on the Columbus module. Hans Schlegel returned to Earth with Atlantis.
After formal crew responsibility hand-over tasks following the docking of Atlantis with the Station, LГ©opold Eyharts became part of the resident ISS crew (Expedition 16), trading places with NASA astronaut Dan Tani. He provided support for Columbus docking from inside the Harmony module, activating the motorised bolts to secure the junction, and assisted the third spacewalk by operating the station's robotic arm.
Unlike Schlegel, Eyharts remained on the ISS when Atlantis undocked two days ago. He will spend the next month in space to complete the Columbus module's commissioning and to perform a series of experiments, both in the laboratory and in the other science facilities already operating in the Station. LГ©opold Eyharts is scheduled to return to earth with the next shuttle ISS mission (Endeavour/STS-123), at the end of March.
ESA builds up its contribution to the ISS
With the addition of Columbus, the pressurised volume of the Space Station was increased by a mere 15%, but its science capacity was nearly doubled. Two modules of the Japanese laboratory will be added in March and May, and a Russian Multi-Purpose Laboratory Module (MLM) will follow in 2011.
A new era is also beginning for ESA's activities onboard. As a fully-fledged partner of the ISS programme, ESA will now not only enjoy the benefits of Columbus but will also have to contribute to ISS operations. This will be achieved through the launch of unmanned servicing missions carried out by the Automated Transfer Vehicle, designed to deliver speares, scientific experiments, crew support equipment (food, clothing), fluids and propellant and to perform reboost to compensate for orbital decay of the ISS. The first ATV , Jules Verne, will be launched by an Ariane 5 on 8 March.
But ESA will also benefit from the Station by conducting experiments within its many science facilities, and by regularly sending European astronauts to perform long-duration stays onboard as members of the resident crew. Two ESA astronauts are already training for such missions: Frank de Winne of Belgium who will fly as a member of the ISS Expedition 19 crew in 2009; and AndrГ© Kuipers of the Netherlands who will be his backup. More will follow.
Further European-built ISS elements are still under preparation to be launched to the ISS within the decade, such as the Material Science Laboratory (MSL), the Muscle Atrophy Resistive Exercise System (MARES), the European Robotic Arm (ERA), the Node 3 module and the Cupola observation deck.
As Columbus is coming to life, so too is the network of nine User Support and Operations Centres (USOCs), which has been set up all over Europe to facilitate the interface between researchers and the science payloads onboard, and to allow investigators to control their experiments and receive real-time data on their results, through an interconnection provided via the Columbus Control Centre.
Commissioning of the European laboratory has proceeded well and faster than planned. The two external payloads SOLAR and EuTEF have been deployed outside Columbus and already provide data. WAICO, the first experiment to be conducted inside the lab, will start this week inside Biolab. The Geoflow experiment will start up in early March inside the Fluid Science Laboratory.
Over the coming weeks and months, the USOC network's activity will increase dramatically as the science equipment and experiments already onboard Columbus are commissioned and switched to operational status, and as more science payloads are delivered to the module by the upcoming logistics missions.
Columbus was designed to support some 500 experiments per year for ten years, in cell and plant biology, astrobiology, human physiology, fluid and material sciences, fundamental physics, astronomy, remote sensing and technology. For the European science community and industrial R&D, a new era of research has just begun.
Source: ESA Media Relations Office
European Space Agency
четверг, 26 мая 2011 г.
Nanomaterials Used By Scientists To Localize And Control Drug Delivery
Using nanotechnology, scientists from UCLA and Northwestern University have developed a localized and controlled drug delivery method that is invisible to the immune system, a discovery that could provide newer and more effective treatments for cancer and other diseases.
The study, published Jan. 22, 2008 in the journal ACS Nano, provides an example of the enormous potential and clinical significance that nanomaterials may represent in such fields as oncology, endocrinology and cardiology.
The researchers used nanoscale polymer films, about four nanometers per layer, to build a sort of matrix or platform to hold and slowly release an anti-inflammatory drug. The films are orders of magnitude thinner than conventional drug deliver coatings, said Genhong Cheng, a researcher at UCLA's Jonsson Comprehensive Cancer Center and one of the study's authors. A nanometer is one billionth of a meter.
"Using this system, drugs could be released slowly and under control for weeks or longer," said Cheng, a professor of microbiology, immunology and molecular genetics. "A drug that is given orally or through the bloodstream travels throughout the system and dissipates from the body much more quickly. Using a more localized and controlled approach could limit side effects, particularly with chemotherapy drugs."
Researchers coated tiny chips with layers of the nanoscale polymer films, which are inert and helped provide a Harry Potter-like invisibility cloak for the chips, hiding them from the body's natural defenses. They then added Dexamethasone, an anti-inflammatory drug, between the layers. The chips were implanted in mice, and researchers found that the Dexamethasone-coated films suppressed the expression of cytokines, proteins released by the cells of the immune system to initiate a response to a foreign invader. Mice without implants and those with uncoated implants were studied to compare immune response.
The uncoated implants generated an inflammatory response from the surrounding tissue, which ultimately would have led to the body's rejection of the implant and the breakdown of its functionality. However, tissue from the mice without implants and the mice with the nano-cloaked implants were virtually identical, proving that the film-coated implants were effectively shielded from the body's defense system, said Edward Chow, a former UCLA graduate student who participated in the study and is one of its authors.
"The polymer films provided a cloak of invisibility for the implants, keeping the immune system from attacking," Chow said.
The nanomaterial technology serves as a non-invasive and biocompatible platform for the delivery of a broad range of therapeutics, said Dean Ho, an assistant professor of biomedical and mechanical engineering with the McCormick School of Engineering and Applied Science, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the study's senior author.
The technology also may prove to be an effective approach for delivering multiple drugs, controlling the sequence of multi-drug delivery strategies and enhancing the life spans of commonly implanted devises such as cardiac stents, pacemakers and continuous glucose monitors.
"For chemotherapy, this system could enhance treatment efficacy while preventing uncontrolled delivery and the resultant patient side effects," Ho said. "Furthermore, as implantable devices continue to find widespread application in cardiovascular medicine, neural disorders and diabetes, the nano-cloaking capabilities can serve as a widely applicable approach to enhance the lifetime of these devices. This would eliminate unnecessary surgeries and enhance the efficiency of patient care."
Many cancer drugs, chemotherapies for example, are delivered systemically through the blood stream. The drugs attack cancer cells, but also other fast growing cells causing side effects such as anemia, nausea and hair loss. If the chemotherapy could be delivered by implant directly to the tumor site, such side effects would be limited, said Cheng, who also is a member of the Center for Cell Control at the UCLA Henry Samueli School of Engineering and Applied Sciences.
"Say you have a localized cancer such as breast cancer, the drugs we give are not directly targeted to the breast," Cheng said. "If we could apply the treatment locally and control the release of the drugs, the therapy might be more effective in treating the cancer."
Chemotherapy drugs could potentially be placed in high concentration between the polymer films and an implant placed at the tumor site. The drugs would be released slowly, over time, delivering more of the toxic chemicals directly to the cancer cells.
This study provided the proof of principle that implants in animal models could be coated with materials that made them invisible to the immune system. Cheng and Ho are now testing in animal models whether cancer therapies can be effectively and safely administered and locally delivered using the nanomaterials.
The study was funded by the Center for Cell Control and Northwestern University, with additional support from the Jonsson Cancer Center, National Institute of Allergy and Infectious Disease of the National Institutes of Health and the V Foundation for Cancer Research. The Center for Cell Control (centerforcellcontrol/) is one of the Nanomedicine Development Centers funded by the National Institutes of Health through the Roadmap for Medical Research.
UCLA's Jonsson Comprehensive Cancer Center comprises about 235 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2007, the Jonsson Cancer Center was named the best cancer center in California by U.S. News & World Report, a ranking it has held for eight consecutive years. For more information on the Jonsson Cancer Center, visit our Web site at cancer.mednet.ucla/.
Source: Kim Irwin
University of California - Los Angeles
The study, published Jan. 22, 2008 in the journal ACS Nano, provides an example of the enormous potential and clinical significance that nanomaterials may represent in such fields as oncology, endocrinology and cardiology.
The researchers used nanoscale polymer films, about four nanometers per layer, to build a sort of matrix or platform to hold and slowly release an anti-inflammatory drug. The films are orders of magnitude thinner than conventional drug deliver coatings, said Genhong Cheng, a researcher at UCLA's Jonsson Comprehensive Cancer Center and one of the study's authors. A nanometer is one billionth of a meter.
"Using this system, drugs could be released slowly and under control for weeks or longer," said Cheng, a professor of microbiology, immunology and molecular genetics. "A drug that is given orally or through the bloodstream travels throughout the system and dissipates from the body much more quickly. Using a more localized and controlled approach could limit side effects, particularly with chemotherapy drugs."
Researchers coated tiny chips with layers of the nanoscale polymer films, which are inert and helped provide a Harry Potter-like invisibility cloak for the chips, hiding them from the body's natural defenses. They then added Dexamethasone, an anti-inflammatory drug, between the layers. The chips were implanted in mice, and researchers found that the Dexamethasone-coated films suppressed the expression of cytokines, proteins released by the cells of the immune system to initiate a response to a foreign invader. Mice without implants and those with uncoated implants were studied to compare immune response.
The uncoated implants generated an inflammatory response from the surrounding tissue, which ultimately would have led to the body's rejection of the implant and the breakdown of its functionality. However, tissue from the mice without implants and the mice with the nano-cloaked implants were virtually identical, proving that the film-coated implants were effectively shielded from the body's defense system, said Edward Chow, a former UCLA graduate student who participated in the study and is one of its authors.
"The polymer films provided a cloak of invisibility for the implants, keeping the immune system from attacking," Chow said.
The nanomaterial technology serves as a non-invasive and biocompatible platform for the delivery of a broad range of therapeutics, said Dean Ho, an assistant professor of biomedical and mechanical engineering with the McCormick School of Engineering and Applied Science, a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University and the study's senior author.
The technology also may prove to be an effective approach for delivering multiple drugs, controlling the sequence of multi-drug delivery strategies and enhancing the life spans of commonly implanted devises such as cardiac stents, pacemakers and continuous glucose monitors.
"For chemotherapy, this system could enhance treatment efficacy while preventing uncontrolled delivery and the resultant patient side effects," Ho said. "Furthermore, as implantable devices continue to find widespread application in cardiovascular medicine, neural disorders and diabetes, the nano-cloaking capabilities can serve as a widely applicable approach to enhance the lifetime of these devices. This would eliminate unnecessary surgeries and enhance the efficiency of patient care."
Many cancer drugs, chemotherapies for example, are delivered systemically through the blood stream. The drugs attack cancer cells, but also other fast growing cells causing side effects such as anemia, nausea and hair loss. If the chemotherapy could be delivered by implant directly to the tumor site, such side effects would be limited, said Cheng, who also is a member of the Center for Cell Control at the UCLA Henry Samueli School of Engineering and Applied Sciences.
"Say you have a localized cancer such as breast cancer, the drugs we give are not directly targeted to the breast," Cheng said. "If we could apply the treatment locally and control the release of the drugs, the therapy might be more effective in treating the cancer."
Chemotherapy drugs could potentially be placed in high concentration between the polymer films and an implant placed at the tumor site. The drugs would be released slowly, over time, delivering more of the toxic chemicals directly to the cancer cells.
This study provided the proof of principle that implants in animal models could be coated with materials that made them invisible to the immune system. Cheng and Ho are now testing in animal models whether cancer therapies can be effectively and safely administered and locally delivered using the nanomaterials.
The study was funded by the Center for Cell Control and Northwestern University, with additional support from the Jonsson Cancer Center, National Institute of Allergy and Infectious Disease of the National Institutes of Health and the V Foundation for Cancer Research. The Center for Cell Control (centerforcellcontrol/) is one of the Nanomedicine Development Centers funded by the National Institutes of Health through the Roadmap for Medical Research.
UCLA's Jonsson Comprehensive Cancer Center comprises about 235 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2007, the Jonsson Cancer Center was named the best cancer center in California by U.S. News & World Report, a ranking it has held for eight consecutive years. For more information on the Jonsson Cancer Center, visit our Web site at cancer.mednet.ucla/.
Source: Kim Irwin
University of California - Los Angeles
The Introduction Of Overhead Funding Welcomed By DFG
The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) welcomes the introduction of 'overhead funding' for research. "This is a crucial step, which boosts research and rewards successful scientists and universities," explained DFG president Matthias Klein in Bonn, following the agreement of the leaders of the federal government and states to the financing of indirect overhead costs as part of the 'Higher Education Pact 2020'.
With this overhead cost funding, the research projects funded by the DFG will in future receive an additional 20% of their respective funding amounts. The funds should be used to cover maintenance costs for test facilities, the renting of laboratory space, software licenses, general administrative costs and other expenses that have an indirect relation to the research project. Until now, the costs have had to be paid by the universities or non-university institutions themselves, and were thus not available for the actual research work. "Essentially, this amounted to a penalty against strong research institutions," recalls Kleiner. "The more third-party funding a university received from the DFG, the more money they themselves had to add to the pot. This Pyrrhic victory had a high cost for the most successful of them." For this reason, the DFG has supported the idea of full cost funding for a long time.
According to Kleiner, the introduction of full cost funding, which has now been achieved, is a further incentive to universities and non-university institutions to intensify their research activities and to acquire greater national and international prominence. This applies equally to institutions that already have strong research reputations and to those which have not yet had great success in obtaining third-party funding from the DFG. "This will also encourage competition in research," underlined Kleiner.
Following the signing of the Higher Education Pact 2020, the Collaborative Research Centres, Research Centres and Research Training Groups funded by the DFG will receive their 20% overhead cost payments this year, and all newly approved funding projects will receive them from 2008 onwards.
After the agreement, the DFG President gave special thanks to the leaders of the federal government, which will be providing all of the overhead funding until 2010. Kleiner applauded the fact that this additional investment is not at the expense of previous funding. It is just as important that the universities and research institutions, or even the states, do not offset this bonus in other areas. The DFG considers it desirable in the long run that university management and participating scientists make a joint decision regarding the use of the overhead cost funding.
Finally, Kleiner pointed out that this step is only the beginning. "In many subjects and projects, the actual indirect programme costs are significantly higher than 20%." In many countries, substantially higher overhead cost funding has been granted. In the United Kingdom, for example, more than 50%, and in the USA, between 70% and 90%, of indirect research costs are already being allocated in addition to normal funding. "Therefore, we must strive for an increase to an average of 40% in Germany too, if only with a view to international competitiveness," said the DFG President.
Contact: Eva-Maria Streier
Deutsche Forschungsgemeinschaft
With this overhead cost funding, the research projects funded by the DFG will in future receive an additional 20% of their respective funding amounts. The funds should be used to cover maintenance costs for test facilities, the renting of laboratory space, software licenses, general administrative costs and other expenses that have an indirect relation to the research project. Until now, the costs have had to be paid by the universities or non-university institutions themselves, and were thus not available for the actual research work. "Essentially, this amounted to a penalty against strong research institutions," recalls Kleiner. "The more third-party funding a university received from the DFG, the more money they themselves had to add to the pot. This Pyrrhic victory had a high cost for the most successful of them." For this reason, the DFG has supported the idea of full cost funding for a long time.
According to Kleiner, the introduction of full cost funding, which has now been achieved, is a further incentive to universities and non-university institutions to intensify their research activities and to acquire greater national and international prominence. This applies equally to institutions that already have strong research reputations and to those which have not yet had great success in obtaining third-party funding from the DFG. "This will also encourage competition in research," underlined Kleiner.
Following the signing of the Higher Education Pact 2020, the Collaborative Research Centres, Research Centres and Research Training Groups funded by the DFG will receive their 20% overhead cost payments this year, and all newly approved funding projects will receive them from 2008 onwards.
After the agreement, the DFG President gave special thanks to the leaders of the federal government, which will be providing all of the overhead funding until 2010. Kleiner applauded the fact that this additional investment is not at the expense of previous funding. It is just as important that the universities and research institutions, or even the states, do not offset this bonus in other areas. The DFG considers it desirable in the long run that university management and participating scientists make a joint decision regarding the use of the overhead cost funding.
Finally, Kleiner pointed out that this step is only the beginning. "In many subjects and projects, the actual indirect programme costs are significantly higher than 20%." In many countries, substantially higher overhead cost funding has been granted. In the United Kingdom, for example, more than 50%, and in the USA, between 70% and 90%, of indirect research costs are already being allocated in addition to normal funding. "Therefore, we must strive for an increase to an average of 40% in Germany too, if only with a view to international competitiveness," said the DFG President.
Contact: Eva-Maria Streier
Deutsche Forschungsgemeinschaft
среда, 25 мая 2011 г.
News From The American Chemical Society, 3-Nov-2008
Tiny DNA tweezers can catch and release objects on-demand
Researchers in China are reporting development of a new DNA "tweezers" that are the first of their kind capable of grasping and releasing objects on-demand. The microscopic tweezers could have several potential uses, the researchers note. Those include microsurgery, drug and gene delivery for gene therapy, and in the manufacturing of nano-sized circuits for futuristic electronics. Their study is scheduled for the November 12 issue of the weekly Journal of the American Chemical Society.
Zhaoxiang Deng and colleagues note that other scientists have developed tweezers made of DNA, the double helix molecule and chemical blueprint of life. Those tweezers can open and close by responding to complementary chemical components found in DNA's backbone. However, getting the tweezers to grasp and release objects like real tweezers has remained a bioengineering challenge until now.
The scientists describe development of a pair of DNA tweezers composed of four DNA strands - three which act as the "arms." In laboratory studies, the scientists showed that they could grab a piece of target DNA in the arms of the tweezers and release it on-demand using a controlled series of hydrogen bonding and pH changes. The scientists used fluorescent gel imaging to confirm the effectiveness of the tweezers' operation. - MTS
ARTICLE: "Catch and Release: DNA Tweezers that Can Capture, Hold, and Release an Object under Control"
DOWNLOAD FULL TEXT ARTICLE: dx.doi/10.1021/ja805945r
CONTACT:
Zhaoxiang Deng, Ph.D.
University of Science and Technology of China
Anhui, China
DNA fingerprinting method may thwart false labeling of shark meat
Researchers in Spain are reporting that a new DNA identification method could thwart false labeling of shark species used in various seafood products, including the expensive Chinese delicacy known as shark fin soup. Their study is scheduled for the November 26 issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.
Maria Blanco, Ricardo Perez-Martin, and Carmen G. Sotelo note that consumption of shark meat appears to be on the rise worldwide, with some seafood companies reportedly having substituted cheaper shark species for more expensive species and incorrectly labeling their products. European Union regulations now require listing the species name on shark products to avoid fraud and to help conserve certain shark species. However, a fast, reliable method for distinguishing between different species of shark remains elusive.
The scientists describe the use of a relatively new technique called forensically informative nucleotide sequencing (FINS), in which DNA isolated from unknown biologic samples is compared to a database of DNA markers from known species. In the new study, the scientists collected DNA markers from nine different commercial seafood samples containing shark meat and compared them to known DNA markers from 23 different shark species. The scientists found that two of the nine shark products analyzed had been labeled with incorrect species names, demonstrating the effectiveness for the FINS method. - MTS
ARTICLE: "Identification of Shark Species in Seafood Products by Forensically Informative Nucleotide Sequencing"
DOWNLOAD FULL TEXT ARTICLE: dx.doi/10.1021/jf8015128
CONTACT:
Maria Blanco, Ph.D.
Consejo Superior de Investigaciones Cientificas (CSIC)
Vigo, Spain
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
Researchers in China are reporting development of a new DNA "tweezers" that are the first of their kind capable of grasping and releasing objects on-demand. The microscopic tweezers could have several potential uses, the researchers note. Those include microsurgery, drug and gene delivery for gene therapy, and in the manufacturing of nano-sized circuits for futuristic electronics. Their study is scheduled for the November 12 issue of the weekly Journal of the American Chemical Society.
Zhaoxiang Deng and colleagues note that other scientists have developed tweezers made of DNA, the double helix molecule and chemical blueprint of life. Those tweezers can open and close by responding to complementary chemical components found in DNA's backbone. However, getting the tweezers to grasp and release objects like real tweezers has remained a bioengineering challenge until now.
The scientists describe development of a pair of DNA tweezers composed of four DNA strands - three which act as the "arms." In laboratory studies, the scientists showed that they could grab a piece of target DNA in the arms of the tweezers and release it on-demand using a controlled series of hydrogen bonding and pH changes. The scientists used fluorescent gel imaging to confirm the effectiveness of the tweezers' operation. - MTS
ARTICLE: "Catch and Release: DNA Tweezers that Can Capture, Hold, and Release an Object under Control"
DOWNLOAD FULL TEXT ARTICLE: dx.doi/10.1021/ja805945r
CONTACT:
Zhaoxiang Deng, Ph.D.
University of Science and Technology of China
Anhui, China
DNA fingerprinting method may thwart false labeling of shark meat
Researchers in Spain are reporting that a new DNA identification method could thwart false labeling of shark species used in various seafood products, including the expensive Chinese delicacy known as shark fin soup. Their study is scheduled for the November 26 issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.
Maria Blanco, Ricardo Perez-Martin, and Carmen G. Sotelo note that consumption of shark meat appears to be on the rise worldwide, with some seafood companies reportedly having substituted cheaper shark species for more expensive species and incorrectly labeling their products. European Union regulations now require listing the species name on shark products to avoid fraud and to help conserve certain shark species. However, a fast, reliable method for distinguishing between different species of shark remains elusive.
The scientists describe the use of a relatively new technique called forensically informative nucleotide sequencing (FINS), in which DNA isolated from unknown biologic samples is compared to a database of DNA markers from known species. In the new study, the scientists collected DNA markers from nine different commercial seafood samples containing shark meat and compared them to known DNA markers from 23 different shark species. The scientists found that two of the nine shark products analyzed had been labeled with incorrect species names, demonstrating the effectiveness for the FINS method. - MTS
ARTICLE: "Identification of Shark Species in Seafood Products by Forensically Informative Nucleotide Sequencing"
DOWNLOAD FULL TEXT ARTICLE: dx.doi/10.1021/jf8015128
CONTACT:
Maria Blanco, Ph.D.
Consejo Superior de Investigaciones Cientificas (CSIC)
Vigo, Spain
The American Chemical Society - the world's largest scientific society - is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
вторник, 24 мая 2011 г.
Key Stress Protein Linked To Toxicities Responsible For Parkinson's, Alzheimer's
Researchers at the Burnham Institute for Medical Research have discovered a mechanistic link between cellular stress caused by free radicals and accumulation of misfolded proteins that lead to nerve cell injury and death in neurodegenerative disorders such as Alzheimer's and Parkinson's Disease. That link is Protein Disulphide Isomerase (PDI), a chaperone protein that is necessary for proper protein folding in times of cellular stress. Published in today's issue of Nature, these findings revealed that in patients with Alzheimer's and Parkinson's Disease, overproduction of free radicals, specifically nitric oxide (NO), causes inhibition of PDI by a reaction called S-nitrosylation, thereby reducing PDI's neuroprotective benefits. This data provides the first molecular link between NO free radicals and protein misfolding, which is currently thought to be a common pathway in the pathogenesis of virtually all neurodegenerative conditions. Such conditions also include ALS (or Lou Gehrig's disease), Huntington's disease, and many others. Understanding the PDI pathway may lead to the development of new therapeutic approaches for these neurodegenerative diseases and other disorders associated with abnormal protein accumulations due to cellular stress.
"To our knowledge, this is the first published evidence of a link between protein misfolding due to enzymatic machinery malfunction found in a number of degenerative diseases and free radical stress in nerve cells," said Stuart A. Lipton, M.D., Ph.D., Professor and Director of the Del E. Webb Center for Neurosciences and Aging at the Burnham Institute and senior author of the study. Dr. Lipton is also a clinical neurologist in La Jolla. "Our data demonstrate a previously unrecognized relationship between NO and protein misfolding in degenerative disorders, showing that PDI can be a target of NO in cellular models of Parkinson's disease and human neurodegenerative disease."
A protein's structure determines its function. Genetic defects as well as exposure to free radicals or possibly other types of cellular stress can cause small structural defects that lead to protein misfolding. If the misfolded proteins cannot be refolded properly or degraded, they may build up in the cell to cause dysfunction. Defects in either the protein folding or degradation pathways can lead to accumulation of misfolded proteins. The accumulation of misfolded proteins is a common pathogenic mechanism in many diseases, including neurodegenerative disorders.
In normal circumstances, PDI levels increase in response to accumulation of misfolded proteins due to cellular stress. PDI acts as a chaperone for aggregated proteins, rearranging their chemical bonds and thus refolding the proteins to function normally. The new research by Dr. Lipton and his colleagues shows that molecules related to the free radical NO, which is present in elevated levels in neurodegenerative diseases, attacks PDI via a chemical S-nitroyslation reaction, altering PDI's structure and blocking its normal neuroprotective function, which ultimately leads to nerve cell injury and even death. These new results also show that this altered form of PDI is present in elevated amounts in patients with Alzheimer's and Parkinson's Disease, indicating that it is a potential marker for the disease as well as a potential therapeutic target.
This article titled "S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration," is authored by Drs. Takashi Uehara, Tomohiro Nakamura, Dongdong Yao, Zhong-Qing Shi, and Zezong Gu (all in Dr. Lipton's laboratory), Yuliang Ma (in the Protein Analysis Facility at the Burnham), Eliezer Masliah (at UCSD), Yasuyuki Nomura (at Hokkaido University in Sapporo, Japan), and Dr. Lipton, the senior author. (Dr. Uehara recently joined the faculty of Hokkaido University.)
This research was supported by grants from the National Institutes of Health, the American Parkinson's Disease Association, San Diego Chapter, an Ellison Senior Scholars Award in Aging, the Mitsubishi Pharma Research Foundation, and a grant-in-aid from the Ministry of Education, Culture, Sports and Technology of Japan.
About the Burnham Institute for Medical Research
The Burnham Institute for Medical Research, founded in 1976, is an independent not-for-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge and providing the foundation for tomorrow's medical therapies. The Institute is home to three major centers: the Cancer Center, the Del E. Webb Neuroscience and Aging Center, and the Infectious and Inflammatory Disease Center. Since 1981, the Institute's Cancer Center has been a member of the National Cancer Institute's prestigious Cancer Centers program. Discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disease, heart disease and several forms of cancer. Today the Institute employs over 725, including more than 550 scientists. The majority of the Institute's funding derives from federal sources, but private philanthropic support is essential to continuing bold and innovative research. For additional information about the Institute and ways to support the research efforts of the Institute, visit burnham
Nancy Beddingfield
nbeddingfieldburnham
Burnham Institute
burnham-inst/
"To our knowledge, this is the first published evidence of a link between protein misfolding due to enzymatic machinery malfunction found in a number of degenerative diseases and free radical stress in nerve cells," said Stuart A. Lipton, M.D., Ph.D., Professor and Director of the Del E. Webb Center for Neurosciences and Aging at the Burnham Institute and senior author of the study. Dr. Lipton is also a clinical neurologist in La Jolla. "Our data demonstrate a previously unrecognized relationship between NO and protein misfolding in degenerative disorders, showing that PDI can be a target of NO in cellular models of Parkinson's disease and human neurodegenerative disease."
A protein's structure determines its function. Genetic defects as well as exposure to free radicals or possibly other types of cellular stress can cause small structural defects that lead to protein misfolding. If the misfolded proteins cannot be refolded properly or degraded, they may build up in the cell to cause dysfunction. Defects in either the protein folding or degradation pathways can lead to accumulation of misfolded proteins. The accumulation of misfolded proteins is a common pathogenic mechanism in many diseases, including neurodegenerative disorders.
In normal circumstances, PDI levels increase in response to accumulation of misfolded proteins due to cellular stress. PDI acts as a chaperone for aggregated proteins, rearranging their chemical bonds and thus refolding the proteins to function normally. The new research by Dr. Lipton and his colleagues shows that molecules related to the free radical NO, which is present in elevated levels in neurodegenerative diseases, attacks PDI via a chemical S-nitroyslation reaction, altering PDI's structure and blocking its normal neuroprotective function, which ultimately leads to nerve cell injury and even death. These new results also show that this altered form of PDI is present in elevated amounts in patients with Alzheimer's and Parkinson's Disease, indicating that it is a potential marker for the disease as well as a potential therapeutic target.
This article titled "S-Nitrosylated protein-disulphide isomerase links protein misfolding to neurodegeneration," is authored by Drs. Takashi Uehara, Tomohiro Nakamura, Dongdong Yao, Zhong-Qing Shi, and Zezong Gu (all in Dr. Lipton's laboratory), Yuliang Ma (in the Protein Analysis Facility at the Burnham), Eliezer Masliah (at UCSD), Yasuyuki Nomura (at Hokkaido University in Sapporo, Japan), and Dr. Lipton, the senior author. (Dr. Uehara recently joined the faculty of Hokkaido University.)
This research was supported by grants from the National Institutes of Health, the American Parkinson's Disease Association, San Diego Chapter, an Ellison Senior Scholars Award in Aging, the Mitsubishi Pharma Research Foundation, and a grant-in-aid from the Ministry of Education, Culture, Sports and Technology of Japan.
About the Burnham Institute for Medical Research
The Burnham Institute for Medical Research, founded in 1976, is an independent not-for-profit biomedical research institution dedicated to advancing the frontiers of scientific knowledge and providing the foundation for tomorrow's medical therapies. The Institute is home to three major centers: the Cancer Center, the Del E. Webb Neuroscience and Aging Center, and the Infectious and Inflammatory Disease Center. Since 1981, the Institute's Cancer Center has been a member of the National Cancer Institute's prestigious Cancer Centers program. Discoveries by Burnham scientists have contributed to the development of new drugs for Alzheimer's disease, heart disease and several forms of cancer. Today the Institute employs over 725, including more than 550 scientists. The majority of the Institute's funding derives from federal sources, but private philanthropic support is essential to continuing bold and innovative research. For additional information about the Institute and ways to support the research efforts of the Institute, visit burnham
Nancy Beddingfield
nbeddingfieldburnham
Burnham Institute
burnham-inst/
понедельник, 23 мая 2011 г.
Science Review On Cancer Metabolism
Agios Pharmaceuticals, the first biopharmaceutical company focused on discovering and developing novel cancer metabolism drugs, announced that the leading scientific journal Science has published a review article, "Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation," authored by two of its founders, Lewis C. Cantley, Ph.D., Director of the Cancer Center at Beth Israel Deaconess Medical Center and Professor of Systems Biology and Craig B. Thompson, M.D., Director, Abramson Cancer Center, University of Pennsylvania, and one of its scientific advisors, Matthew Vander Heiden, M.D., Ph.D., Instructor of Medicine, Dana Farber Cancer Institute and Harvard Medical School.
"As this review highlights, there is an incredible opportunity in front of us to bring together decades of independent cancer and metabolic scientific research into an integrated approach to novel cancer therapies," said Dr. Vander Heiden, Agios scientific advisor. "It is exciting to see the broad scientific engagement that is driving this field rapidly forward to ultimately provide new options for physician and their patients."
Cancer metabolism is a new and exciting field of biology that represents a breakthrough understanding of how cancer cells become addicted to using more nutrients than normal cells to ensure their survival and growth. The new understanding of a fundamental mechanism of cancer growth and survival represents a powerful Achilles' heel to target this deadly disease.
The Science review article summarizes the current state of the emerging biological field of cancer metabolism and suggests that "a better understanding of anabolic cellular metabolism and how growth control impacts its regulation may lead to new targets and improved therapy for human cancer." The review, which provides a meta-analysis of the field, highlights key advancements ranging from Otto Warburg's discovery in 1929, that cancer cells utilize sugar differently than normal cells, to a 2008 study published in the journal Nature showing that cancer cells 'switch on' the same highly active metabolizing enzymes as those found in fetal cells to promote rapid growth. This latter finding explains why cancer cells are able to divide and grow better than normal cells.
The vision of Agios is to lead the development and translation of cancer metabolism biology and decades of metabolic biochemistry into novel cancer therapeutics that will make a difference for patients. To date, Agios has put in place a world-class scientific team of more than 40 people, built a fully integrated cell metabolism platform within the largest research laboratory dedicated to cancer metabolism and created an emerging product development pipeline of novel Cancer Metabolism drugs.
"The Agios team, pipeline, platform and business strategy that we have built in a short time is exclusively focused on developing a deep biological understanding of the nexus of cancer and metabolism as the key driver behind where, when and how to cripple and kill a cancer cell," said Michael Su, Ph.D., Agios co-founder and Vice President, Drug Discovery. "This Science review, along with many other recent scientific advancements, continues to highlight the significance of the field and Agios' unique ability and position to lead the therapeutic exploration of cancer metabolism."
Source:
Kathryn Morris
Yates Public Relations
"As this review highlights, there is an incredible opportunity in front of us to bring together decades of independent cancer and metabolic scientific research into an integrated approach to novel cancer therapies," said Dr. Vander Heiden, Agios scientific advisor. "It is exciting to see the broad scientific engagement that is driving this field rapidly forward to ultimately provide new options for physician and their patients."
Cancer metabolism is a new and exciting field of biology that represents a breakthrough understanding of how cancer cells become addicted to using more nutrients than normal cells to ensure their survival and growth. The new understanding of a fundamental mechanism of cancer growth and survival represents a powerful Achilles' heel to target this deadly disease.
The Science review article summarizes the current state of the emerging biological field of cancer metabolism and suggests that "a better understanding of anabolic cellular metabolism and how growth control impacts its regulation may lead to new targets and improved therapy for human cancer." The review, which provides a meta-analysis of the field, highlights key advancements ranging from Otto Warburg's discovery in 1929, that cancer cells utilize sugar differently than normal cells, to a 2008 study published in the journal Nature showing that cancer cells 'switch on' the same highly active metabolizing enzymes as those found in fetal cells to promote rapid growth. This latter finding explains why cancer cells are able to divide and grow better than normal cells.
The vision of Agios is to lead the development and translation of cancer metabolism biology and decades of metabolic biochemistry into novel cancer therapeutics that will make a difference for patients. To date, Agios has put in place a world-class scientific team of more than 40 people, built a fully integrated cell metabolism platform within the largest research laboratory dedicated to cancer metabolism and created an emerging product development pipeline of novel Cancer Metabolism drugs.
"The Agios team, pipeline, platform and business strategy that we have built in a short time is exclusively focused on developing a deep biological understanding of the nexus of cancer and metabolism as the key driver behind where, when and how to cripple and kill a cancer cell," said Michael Su, Ph.D., Agios co-founder and Vice President, Drug Discovery. "This Science review, along with many other recent scientific advancements, continues to highlight the significance of the field and Agios' unique ability and position to lead the therapeutic exploration of cancer metabolism."
Source:
Kathryn Morris
Yates Public Relations
воскресенье, 22 мая 2011 г.
Critical Function Of Proteins In The Gut
Researchers from the European Molecular Biology Laboratory (EMBL) have discovered that proteins that regulate the body's iron household play a vital role in making sure enough nutrients and water are absorbed in the intestine. Mice lacking these proteins suffer from weight loss and dehydration, the scientists report in the current issue of Cell Metabolism.
Iron is a central component of red blood cells and has many other important functions throughout the body. Since too little or too much iron is dangerous for our health a range of regulatory proteins tightly controls iron metabolism. EMBL scientists now assessed the role of two of these proteins, iron regulatory proteins 1 and 2 (IRPs), for the first time in living mice and found that their effects are much broader than previously assumed.
"We generated the first living organism lacking both IRPs in one of its organs," says Bruno Galy, who carried out the research in the lab of Matthias Hentze at EMBL. "This was extremely challenging, because if both proteins are switched off throughout the whole body, the mouse dies before birth. But if you switch off only one IRP, the one that is still intact substitutes and you can hardly see any effects."
Surprisingly, the lack of IRPs in the intestine did not upset the mice's iron household in blood and tissues. Instead the mice suffered from other, unexpected problems: they weighed only half of their normal littermates, suffered from severe dehydration and died only 4 weeks after birth. The general nutrient and water absorption in the gut was impaired. A closer look at the intestinal tissues revealed that their structure and organisation were completely disturbed, which likely affects all absorption processes that happen in intestinal cells. The findings show that IRPs are essential for intestinal function and the survival of an organism, but the details of how they accomplish their effects is unclear.
Although the global iron household was unaffected by the lack of intestinal IRPs, the scientists observed changes in the local handling of iron in the gut. IRPs control the abundance of iron transporters in the membrane of intestinal cells. Without the IRPs less iron importers are found in the membrane facing the gut, but iron exporters on the interface with the blood stream are increased. The results are less iron absorption, but more export of the metal into the bloodstream. In the short term this will keep the global iron content stable while depleting the iron stores of intestinal cells, which could be the reason for their disturbed structure and tissue organisation.
"Since IRPs were discovered 20 years ago we have not been able to pin down what exactly they are doing," says Matthias Hentze, Associate Director and group leader at EMBL. "The new insights provided by our mouse model greatly advance our understanding of their function in iron metabolism and reveal that IRPs play a vital role for the survival of an organism." The findings might help inform the development of strategies to control iron absorption in the intestine, which might pave the way for alternative therapeutic approaches to treat iron overload disorders such as hemochromatosis.
Source: Anna-Lynn Wegener
European Molecular Biology Laboratory
Iron is a central component of red blood cells and has many other important functions throughout the body. Since too little or too much iron is dangerous for our health a range of regulatory proteins tightly controls iron metabolism. EMBL scientists now assessed the role of two of these proteins, iron regulatory proteins 1 and 2 (IRPs), for the first time in living mice and found that their effects are much broader than previously assumed.
"We generated the first living organism lacking both IRPs in one of its organs," says Bruno Galy, who carried out the research in the lab of Matthias Hentze at EMBL. "This was extremely challenging, because if both proteins are switched off throughout the whole body, the mouse dies before birth. But if you switch off only one IRP, the one that is still intact substitutes and you can hardly see any effects."
Surprisingly, the lack of IRPs in the intestine did not upset the mice's iron household in blood and tissues. Instead the mice suffered from other, unexpected problems: they weighed only half of their normal littermates, suffered from severe dehydration and died only 4 weeks after birth. The general nutrient and water absorption in the gut was impaired. A closer look at the intestinal tissues revealed that their structure and organisation were completely disturbed, which likely affects all absorption processes that happen in intestinal cells. The findings show that IRPs are essential for intestinal function and the survival of an organism, but the details of how they accomplish their effects is unclear.
Although the global iron household was unaffected by the lack of intestinal IRPs, the scientists observed changes in the local handling of iron in the gut. IRPs control the abundance of iron transporters in the membrane of intestinal cells. Without the IRPs less iron importers are found in the membrane facing the gut, but iron exporters on the interface with the blood stream are increased. The results are less iron absorption, but more export of the metal into the bloodstream. In the short term this will keep the global iron content stable while depleting the iron stores of intestinal cells, which could be the reason for their disturbed structure and tissue organisation.
"Since IRPs were discovered 20 years ago we have not been able to pin down what exactly they are doing," says Matthias Hentze, Associate Director and group leader at EMBL. "The new insights provided by our mouse model greatly advance our understanding of their function in iron metabolism and reveal that IRPs play a vital role for the survival of an organism." The findings might help inform the development of strategies to control iron absorption in the intestine, which might pave the way for alternative therapeutic approaches to treat iron overload disorders such as hemochromatosis.
Source: Anna-Lynn Wegener
European Molecular Biology Laboratory
суббота, 21 мая 2011 г.
Researchers Crack 'Splicing Code,' Solve A Mystery Underlying Biological Complexity
Researchers at the University of Toronto have discovered a fundamentally new view of how living cells use a limited number of genes to generate enormously complex organs such as the brain.
In a paper published on May 6 in the journal Nature entitled "Deciphering the Splicing Code," a research team led by Professors Brendan Frey and Benjamin Blencowe of the University of Toronto describes how a hidden code within DNA explains one of the central mysteries of genetic research - namely how a limited number of human genes can produce a vastly greater number of genetic messages. The discovery bridges a decade-old gap between our understanding of the genome and the activity of complex processes within cells, and could one day help predict or prevent diseases such as cancers and neurodegenerative disorders.
When the human genome was fully sequenced in 2004, approximately 20,000 genes were found. However, it was discovered that living cells use those genes to generate a much richer and more dynamic source of instructions, consisting of hundreds of thousands of genetic messages that direct most cellular activities. Frey, who has appointments in Engineering and Medicine, likens this discovery to "hearing a full orchestra playing behind a locked door, and then when you pry the door open, you discover only three or four musicians generating all that music."
To figure out how living cells generate vast diversity in their genetic information, Frey and postdoctoral fellow Yoseph Barash developed a new computer-assisted biological analysis method that finds 'codewords' hidden within the genome that constitute what is referred to as a 'splicing code'. This code contains the biological rules that are used to govern how separate parts of a genetic message copied from a gene can be spliced together in different ways to produce different genetic messages (messenger RNAs). "For example, three neurexin genes can generate over 3,000 genetic messages that help control the wiring of the brain," says Frey.
"Previously, researchers couldn't predict how the genetic messages would be rearranged, or spliced, within a living cell," Frey said. "The splicing code that we discovered has been successfully used to predict how thousands of genetic messages are rearranged differently in many different tissues." Blencowe's group, including graduate student John Calarco, generated experimental data used to derive and test predictions from the code. "That the splicing code can make accurate predictions on such a large scale is a major step forward for the field," says Blencowe.
Frey and Blencowe attribute the success of their project to the close collaboration between their team of talented computational and experimental biologists. "Understanding a complex biological system is like understanding a complex electronic circuit. Our team 'reverse-engineered' the splicing code using large-scale experimental data generated by the group," Frey said.
Prof. Frey has appointments to the Canadian Institute for Advanced Research and the U of T's Department of Electrical and Computer Engineering, the Banting & Best Department of Medical Research (BBDMR) and the Department of Computer Science. Prof. Blencowe works in the University's Donnelly Centre for Cellular & Biomolecular Research and has appointments in the BBDMR and Department of Molecular Genetics
The research was supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute, the Canadian Institutes of Health Research, National Cancer Institute of Canada, and Microsoft Research. Frey is an NSERC EWR Steacie Fellow and said that the fellowship was critical in freeing up resources so he could complete the project. The authors of the study are: Yoseph Barash, John A. Calarco, Weijun Gao, Qun Pan, Xinchen Wang Ofer Shai, Benjamin J. Blencowe & Brendan J. Frey.
Source:
Mario Pidutti
University of Toronto
In a paper published on May 6 in the journal Nature entitled "Deciphering the Splicing Code," a research team led by Professors Brendan Frey and Benjamin Blencowe of the University of Toronto describes how a hidden code within DNA explains one of the central mysteries of genetic research - namely how a limited number of human genes can produce a vastly greater number of genetic messages. The discovery bridges a decade-old gap between our understanding of the genome and the activity of complex processes within cells, and could one day help predict or prevent diseases such as cancers and neurodegenerative disorders.
When the human genome was fully sequenced in 2004, approximately 20,000 genes were found. However, it was discovered that living cells use those genes to generate a much richer and more dynamic source of instructions, consisting of hundreds of thousands of genetic messages that direct most cellular activities. Frey, who has appointments in Engineering and Medicine, likens this discovery to "hearing a full orchestra playing behind a locked door, and then when you pry the door open, you discover only three or four musicians generating all that music."
To figure out how living cells generate vast diversity in their genetic information, Frey and postdoctoral fellow Yoseph Barash developed a new computer-assisted biological analysis method that finds 'codewords' hidden within the genome that constitute what is referred to as a 'splicing code'. This code contains the biological rules that are used to govern how separate parts of a genetic message copied from a gene can be spliced together in different ways to produce different genetic messages (messenger RNAs). "For example, three neurexin genes can generate over 3,000 genetic messages that help control the wiring of the brain," says Frey.
"Previously, researchers couldn't predict how the genetic messages would be rearranged, or spliced, within a living cell," Frey said. "The splicing code that we discovered has been successfully used to predict how thousands of genetic messages are rearranged differently in many different tissues." Blencowe's group, including graduate student John Calarco, generated experimental data used to derive and test predictions from the code. "That the splicing code can make accurate predictions on such a large scale is a major step forward for the field," says Blencowe.
Frey and Blencowe attribute the success of their project to the close collaboration between their team of talented computational and experimental biologists. "Understanding a complex biological system is like understanding a complex electronic circuit. Our team 'reverse-engineered' the splicing code using large-scale experimental data generated by the group," Frey said.
Prof. Frey has appointments to the Canadian Institute for Advanced Research and the U of T's Department of Electrical and Computer Engineering, the Banting & Best Department of Medical Research (BBDMR) and the Department of Computer Science. Prof. Blencowe works in the University's Donnelly Centre for Cellular & Biomolecular Research and has appointments in the BBDMR and Department of Molecular Genetics
The research was supported by the Government of Canada through Genome Canada and the Ontario Genomics Institute, the Canadian Institutes of Health Research, National Cancer Institute of Canada, and Microsoft Research. Frey is an NSERC EWR Steacie Fellow and said that the fellowship was critical in freeing up resources so he could complete the project. The authors of the study are: Yoseph Barash, John A. Calarco, Weijun Gao, Qun Pan, Xinchen Wang Ofer Shai, Benjamin J. Blencowe & Brendan J. Frey.
Source:
Mario Pidutti
University of Toronto
пятница, 20 мая 2011 г.
Study Uncovers Genetic Hierarchy In Plant Sperm Formation, May Meet The Demands Of Food Shortage And Food Price Inflation
Biologists at the University of Leicester have published results of a new study into the intricacies of sex in flowering plants.
They have found that a gene in plants, called DUO1, acts as a master switch to ensure twin fertile sperm cells are made in each pollen grain.
The research identifies for the first time that DUO1 switches on a battery of genes that together govern sperm cell production and their ability to produce seeds..
The findings have implications for plant fertility, seed production - and could be used to help produce improved crops to help meet food shortages. This work also formed part of one of the author's PhD thesis (Dr Michael Borg, University of Leicester).
The new study is reported in the journal The Plant Cell and was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Professor David Twell and colleagues in the Department of Biology at the University of Leicester previously reported the discovery of a master regulator protein called DUO1 that has a critical role in allowing precursor reproductive cells to divide once to form twin sperm cells. The discovery of a battery of genes governed by DUO1 has shed light on the mechanisms by which plants control sperm cell formation and fertility.
Professor Twell said: "Unlike animals, flowering plants require not one, but two sperm cells for successful reproduction. These two sperm cells are housed within pollen grains, which act as a vehicle to deliver the sperm cells to the female sex cells within a flower.
"One sperm cell will join with the egg cell to produce the future plant or embryo, whilst the other will join with a second cell deep within the flower (the central cell) to produce a nutrient-rich tissue called the endosperm. Together these two structures make up the seeds and grains that form the staple food of humans and livestock across the globe.
"A mystery in this 'double fertilisation' event was how each pollen grain could produce the pair of sperm cells needed to make seeds. We now report that the regulatory gene DUO1 switches on a battery of genes that together govern sperm cell production and their ability to fuse with the egg and central cells. So in effect DUO1 acts as a master switch to ensure twin fertile sperm cells are made. "
Their new study expands on their previous work on pollen development and has identified a battery of new genes that collectively ensure male fertility in flowering plants.
The study of genes active within plant sperm is technically challenging because their sperm cells are not only tiny, but they are encased within tough pollen grains and as such are difficult to isolate. "We overcame this problem by genetically forcing plants to make DUO1 in plant roots, a place it is not normally found because DUO1 is normally restricted to sperm cells. By studying these genetically modified plants, we were able to survey the target genes switched on by DUO1."
The researchers also report on the mechanism by which DUO1 switches on its target genes. Being a regulatory protein, DUO1 was shown to bind to short DNA sequences near the genes that it targets, which in turn allows DUO1 to control a wide variety of processes needed for sperm cell production.
"This work provides insight into the genetic mechanisms by which fertile gamete production is achieved in flowering plants. Such knowledge will also be helpful in devising strategies for the targeted manipulation of sperm cells, enabling plant breeders to control crossing behaviour in crop plants." This work also provides new molecular tools for the manipulation of plant fertility and hybrid seed production as well the means to control gene flow in transgenic crops where the male contribution may need to be eliminated.
Professor Twell added that the study is timely given the challenges of breeding improved crops to meet the demands of food shortage and food price inflation the world is currently facing.
Source:
David Twell
University of Leicester
They have found that a gene in plants, called DUO1, acts as a master switch to ensure twin fertile sperm cells are made in each pollen grain.
The research identifies for the first time that DUO1 switches on a battery of genes that together govern sperm cell production and their ability to produce seeds..
The findings have implications for plant fertility, seed production - and could be used to help produce improved crops to help meet food shortages. This work also formed part of one of the author's PhD thesis (Dr Michael Borg, University of Leicester).
The new study is reported in the journal The Plant Cell and was funded by the Biotechnology and Biological Sciences Research Council (BBSRC).
Professor David Twell and colleagues in the Department of Biology at the University of Leicester previously reported the discovery of a master regulator protein called DUO1 that has a critical role in allowing precursor reproductive cells to divide once to form twin sperm cells. The discovery of a battery of genes governed by DUO1 has shed light on the mechanisms by which plants control sperm cell formation and fertility.
Professor Twell said: "Unlike animals, flowering plants require not one, but two sperm cells for successful reproduction. These two sperm cells are housed within pollen grains, which act as a vehicle to deliver the sperm cells to the female sex cells within a flower.
"One sperm cell will join with the egg cell to produce the future plant or embryo, whilst the other will join with a second cell deep within the flower (the central cell) to produce a nutrient-rich tissue called the endosperm. Together these two structures make up the seeds and grains that form the staple food of humans and livestock across the globe.
"A mystery in this 'double fertilisation' event was how each pollen grain could produce the pair of sperm cells needed to make seeds. We now report that the regulatory gene DUO1 switches on a battery of genes that together govern sperm cell production and their ability to fuse with the egg and central cells. So in effect DUO1 acts as a master switch to ensure twin fertile sperm cells are made. "
Their new study expands on their previous work on pollen development and has identified a battery of new genes that collectively ensure male fertility in flowering plants.
The study of genes active within plant sperm is technically challenging because their sperm cells are not only tiny, but they are encased within tough pollen grains and as such are difficult to isolate. "We overcame this problem by genetically forcing plants to make DUO1 in plant roots, a place it is not normally found because DUO1 is normally restricted to sperm cells. By studying these genetically modified plants, we were able to survey the target genes switched on by DUO1."
The researchers also report on the mechanism by which DUO1 switches on its target genes. Being a regulatory protein, DUO1 was shown to bind to short DNA sequences near the genes that it targets, which in turn allows DUO1 to control a wide variety of processes needed for sperm cell production.
"This work provides insight into the genetic mechanisms by which fertile gamete production is achieved in flowering plants. Such knowledge will also be helpful in devising strategies for the targeted manipulation of sperm cells, enabling plant breeders to control crossing behaviour in crop plants." This work also provides new molecular tools for the manipulation of plant fertility and hybrid seed production as well the means to control gene flow in transgenic crops where the male contribution may need to be eliminated.
Professor Twell added that the study is timely given the challenges of breeding improved crops to meet the demands of food shortage and food price inflation the world is currently facing.
Source:
David Twell
University of Leicester
четверг, 19 мая 2011 г.
Double Binding Sites On Tumor Target May Provide Future Combination Therapy
Researchers from the University of Pennsylvania School of Medicine and colleagues at Merck Serono Research in Germany have found that two drugs bind to receptor sites on some tumors in different places at the same time, suggesting the possibility of a new combination therapy for certain types of cancer.
An increasing number of therapies targeting tumors that have proteins called epidermal growth factor receptors (EGFR) sitting on their surface are already being used in the clinic or are in late stages of development. For example, Herceptin is an established treatment for certain types of breast cancer and Erbitux and Vectibix are in use for other types of cancer. An additional drug called matuzumab is in phase II clinical trials.
Three years ago, Kate Ferguson, PhD, Assistant Professor of Physiology, and colleagues determined the precise molecular details of how Erbitux, a colorectal and head and neck cancer drug, binds to its target on cancer cells. EGFR drugs halt cell proliferation by blocking EGFR's molecular doorway, keeping hormones from binding and signaling tumor growth. X-ray crystallography provided a snapshot of the interaction between Erbitux and the extracellular component of the cancer cell's receptors.
As is characteristic of many epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to kick off a series of reactions that signal the cancerous cell to replicate and divide.
In the present study, published in Cancer Cell, Ferguson and Merck colleagues found again using X-ray crystallography -- that matuzumab binds in a different place from Erbitux. Their binding does not overlap, and they can bind to EGFR at the same time.
"These findings imply that a combination therapy using both types of EGFR drugs could be developed and tested," says Ferguson. "This has important implications for the clinical use of matuzumab and for developing new therapies that target EGFR."
The research was governed by a Supported Research Agreement between Merck KGaA and the Trustees of the University of Pennsylvania and is financially supported in part by Merck KGaA, and the National Cancer Institute. Kate Ferguson is the Dennis and Marsha Dammerman Scholar of the Damon Runyon Cancer Research Foundation.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
View drug information on Erbitux; Herceptin; Vectibix.
An increasing number of therapies targeting tumors that have proteins called epidermal growth factor receptors (EGFR) sitting on their surface are already being used in the clinic or are in late stages of development. For example, Herceptin is an established treatment for certain types of breast cancer and Erbitux and Vectibix are in use for other types of cancer. An additional drug called matuzumab is in phase II clinical trials.
Three years ago, Kate Ferguson, PhD, Assistant Professor of Physiology, and colleagues determined the precise molecular details of how Erbitux, a colorectal and head and neck cancer drug, binds to its target on cancer cells. EGFR drugs halt cell proliferation by blocking EGFR's molecular doorway, keeping hormones from binding and signaling tumor growth. X-ray crystallography provided a snapshot of the interaction between Erbitux and the extracellular component of the cancer cell's receptors.
As is characteristic of many epithelial cancers - such as cancers of the colon, head and neck, breast, ovary, lung, and pancreas - the surface of cancer cells possess abnormally high levels of EGFR. In a cancer cell, an extracellular hormone binds to the outer piece of EGFR, and causes the inside part to kick off a series of reactions that signal the cancerous cell to replicate and divide.
In the present study, published in Cancer Cell, Ferguson and Merck colleagues found again using X-ray crystallography -- that matuzumab binds in a different place from Erbitux. Their binding does not overlap, and they can bind to EGFR at the same time.
"These findings imply that a combination therapy using both types of EGFR drugs could be developed and tested," says Ferguson. "This has important implications for the clinical use of matuzumab and for developing new therapies that target EGFR."
The research was governed by a Supported Research Agreement between Merck KGaA and the Trustees of the University of Pennsylvania and is financially supported in part by Merck KGaA, and the National Cancer Institute. Kate Ferguson is the Dennis and Marsha Dammerman Scholar of the Damon Runyon Cancer Research Foundation.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System.
Penn's School of Medicine is currently ranked #3 in the nation in U.S.News & World Report's survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation's "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation's first hospital; and Penn Presbyterian Medical Center a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
University of Pennsylvania School of Medicine
3600 Market St., Ste 240
Philadelphia, PA 19104
United States
med.upenn
View drug information on Erbitux; Herceptin; Vectibix.
среда, 18 мая 2011 г.
Cell Phone Exposure May Protect Against And Reverse Alzheimer's Disease
The millions of people who spend hours every day on a cell phone may have a new excuse for yakking. A surprising new study in mice provides the first evidence that long-term exposure to electromagnetic waves associated with cell phone use may actually protect against, and even reverse, Alzheimer's disease. The study, led by University of South Florida researchers at the Florida Alzheimer's Disease Research Center (ADRC), was published today in the Journal of Alzheimer's Disease.
"It surprised us to find that cell phone exposure, begun in early adulthood, protects the memory of mice otherwise destined to develop Alzheimer's symptoms," said lead author Gary Arendash, PhD, USF Research Professor at the Florida ADRC. "It was even more astonishing that the electromagnetic waves generated by cell phones actually reversed memory impairment in old Alzheimer's mice."
The researchers showed that exposing old Alzheimer's mice to electromagnetic waves generated by cell phones erased brain deposits of the harmful protein beta-amyloid, in addition to preventing the protein's build-up in younger Alzheimer's mice. The sticky brain plaques formed by the abnormal accumulation of beta amyloid are a hallmark of Alzheimer's disease. Most treatments against Alzheimer's try to target beta-amyloid.
The highly-controlled study allowed researchers to isolate the effects of cell phone exposure on memory from other lifestyle factors such as diet and exercise. It involved 96 mice, most of which were genetically altered to develop beta-amyloid plaques and memory problems mimicking Alzheimer's disease as they aged. Some mice were non-demented, without any genetic predisposition for Alzheimer's, so researchers could test the effects of electromagnetic waves on normal memory as well.
Both the Alzheimer's and normal mice were exposed to the electromagnetic field generated by standard cell phone use for two 1-hour periods each day for seven to nine months. The mice didn't wear tiny headsets or have scientists holding cell phones up to their ears; instead, their cages were arranged around a centrally-located antenna generating the cell phone signal. Each animal was housed the same distance from the antenna and exposed to electromagnetic waves typically emitted by a cell phone pressed up against a human head.
If cell phone exposure was started when the genetically-programmed mice were young adults -- before signs of memory impairment were apparent -- their cognitive ability was protected. In fact, the Alzheimer's mice performed as well on tests measuring memory and thinking skills as aged mice without dementia. If older Alzheimer's mice already exhibiting memory problems were exposed to the electromagnetic waves, their memory impairment disappeared. Months of cell phone exposure even boosted the memories of normal mice to above-normal levels. The memory benefits of cell phone exposure took months to show up, suggesting that a similar effect in humans would take years if cell phone-level electromagnetic exposure was provided.
Based on their promising and unexpected findings in mice, the researchers concluded that electromagnetic field exposure could be an effective, non-invasive and drug-free way to prevent and treat Alzheimer's disease in humans. They are currently evaluating whether different sets of electromagnetic frequencies and strengths will produce more rapid and even greater cognitive benefits than those found in their current study.
"If we can determine the best set of electromagnetic parameters to effectively prevent beta-amyloid aggregation and remove pre-existing beta amyloid deposits from the brain, this technology could be quickly translated to human benefit against AD" said USF's Chuanhai Cao, PhD, the other major study author. "Since production and aggregation of ОІ-amyloid occurs in traumatic brain injury, particularly in soldiers during war, the therapeutic impact of our findings may extend beyond Alzheimer's disease."
The memory test used to evaluate the effects of cell phone exposure in mice was closely designed from a sensitive test used to determine if Alzheimer's disease, or its very early signs (mild cognitive impairment), are present in humans. "Since we selected electromagnetic parameters that were identical to human cell phone use and tested mice in a task closely analogous to a human memory test, we believe our findings could have considerable relevance to humans," Arendash said.
The researchers found a slight increase in brain temperature during the two one-hour periods when mice were exposed to electromagnetic waves each day. This increase in brain temperature was seen only in the Alzheimer's mice, and only after months of exposure. The researchers suggest the increase in brain temperature helped the Alzheimer's brain to remove newly-formed beta-amyloid by causing brain cells to release it.
The researchers were particularly surprised to discover that months of cell phone exposure actually boosted the memory of non-demented (normal mice) to above-normal levels. They suspect that the main reason for this improvement involves the ability of electromagnetic exposure to increase brain activity, promoting greater blood flow and increased energy metabolism in the brain. "Our study provides evidence that long-term cell phone use is not harmful to brain," Dr. Cao said. "To the contrary, the electromagnetic waves emitted by cell phones could actually improve normal memory and be an effective therapy against memory impairment"
"It will take some time to determine the exact mechanisms involved in these beneficial memory effects," Arendash said. "One thing is clear, however - the cognitive benefits of long-term electromagnetic exposure are real, because we saw them in both protection- and treatment-based experiments involving Alzheimer's mice, as well as in normal mice."
Previous human studies of electromagnetic waves from cell phones involved only brief exposures given to normal humans. While some studies reported small improvements in attention or memory (not enough to impact daily life), others reported no memory effects from short-term exposure. The new study by Arendash, Cao, and their colleagues is the first to investigate the effects of long-term electromagnetic exposure over many months on memory function in either humans or animals. The findings indicate that "long-term" exposure to cell phone level electromagnetic waves is needed to observe enhanced memory in normal or memory-impaired mice.
The USF researchers began investigating the effects of cell phone use on Alzheimer's disease several years ago, after several observational studies in humans linked a possible increased risk of Alzheimer's with "low-frequency" electromagnetic exposure -- like the energy waves generated by power and telephone lines. However, cell phones emit "high-frequency" electromagnetic waves, which are very different because they can have beneficial effects on brain cell function, such as increasing brain cell activity, Arendash said.
There has been recent controversy about whether electromagnetic waves from cell phones cause brain cancer. Some researchers argue that the risk of glioma (40 percent of all brain tumors) doubles after 10 or more years of cell phone use. However, others argue that since the overall lifetime risk of developing a brain tumor of any type is less than 1 percent, any doubling of this risk would still be very low. Groups such as the World Health Organization, the American Cancer Society, and the National Institutes of Health, have all concluded that scientific evidence to date does not support any adverse health effects associated with the use of cell phones. Consistent with the view of these organizations, the researchers found no autopsy evidence of abnormal growth in brains of the Alzheimer's mice following many months of exposure to cell phone-level electromagnetic waves. They also found all major peripheral organs, such as the liver and lungs, to be normal.
The research was conducted by an interdisciplinary group of neuroscientists, electrical engineers, and neurologists from universities in Japan and China as well as from the Florida ADRC at the University of South Florida. The study was supported by funds from the Florida ADRC, a statewide project sponsored by the National Institute on Aging, and the USF Health Byrd Alzheimer's Institute.
Journal citation:
Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer's Disease Mice. Gary W. Arendash, Juan Sanchez-Ramos, Takashi Mori, Malgorzata Mamcarz, Xiaoyang Lin, Melissa Runfeldt, Li Want, Guixin Zhang, Vasyl Sava, Juan Tan and Chuanhai Cao. Journal of Alzheimer's Disease, Volume 19:1 (January 2010).
Source:
Gary Arendash
University of South Florida Health
"It surprised us to find that cell phone exposure, begun in early adulthood, protects the memory of mice otherwise destined to develop Alzheimer's symptoms," said lead author Gary Arendash, PhD, USF Research Professor at the Florida ADRC. "It was even more astonishing that the electromagnetic waves generated by cell phones actually reversed memory impairment in old Alzheimer's mice."
The researchers showed that exposing old Alzheimer's mice to electromagnetic waves generated by cell phones erased brain deposits of the harmful protein beta-amyloid, in addition to preventing the protein's build-up in younger Alzheimer's mice. The sticky brain plaques formed by the abnormal accumulation of beta amyloid are a hallmark of Alzheimer's disease. Most treatments against Alzheimer's try to target beta-amyloid.
The highly-controlled study allowed researchers to isolate the effects of cell phone exposure on memory from other lifestyle factors such as diet and exercise. It involved 96 mice, most of which were genetically altered to develop beta-amyloid plaques and memory problems mimicking Alzheimer's disease as they aged. Some mice were non-demented, without any genetic predisposition for Alzheimer's, so researchers could test the effects of electromagnetic waves on normal memory as well.
Both the Alzheimer's and normal mice were exposed to the electromagnetic field generated by standard cell phone use for two 1-hour periods each day for seven to nine months. The mice didn't wear tiny headsets or have scientists holding cell phones up to their ears; instead, their cages were arranged around a centrally-located antenna generating the cell phone signal. Each animal was housed the same distance from the antenna and exposed to electromagnetic waves typically emitted by a cell phone pressed up against a human head.
If cell phone exposure was started when the genetically-programmed mice were young adults -- before signs of memory impairment were apparent -- their cognitive ability was protected. In fact, the Alzheimer's mice performed as well on tests measuring memory and thinking skills as aged mice without dementia. If older Alzheimer's mice already exhibiting memory problems were exposed to the electromagnetic waves, their memory impairment disappeared. Months of cell phone exposure even boosted the memories of normal mice to above-normal levels. The memory benefits of cell phone exposure took months to show up, suggesting that a similar effect in humans would take years if cell phone-level electromagnetic exposure was provided.
Based on their promising and unexpected findings in mice, the researchers concluded that electromagnetic field exposure could be an effective, non-invasive and drug-free way to prevent and treat Alzheimer's disease in humans. They are currently evaluating whether different sets of electromagnetic frequencies and strengths will produce more rapid and even greater cognitive benefits than those found in their current study.
"If we can determine the best set of electromagnetic parameters to effectively prevent beta-amyloid aggregation and remove pre-existing beta amyloid deposits from the brain, this technology could be quickly translated to human benefit against AD" said USF's Chuanhai Cao, PhD, the other major study author. "Since production and aggregation of ОІ-amyloid occurs in traumatic brain injury, particularly in soldiers during war, the therapeutic impact of our findings may extend beyond Alzheimer's disease."
The memory test used to evaluate the effects of cell phone exposure in mice was closely designed from a sensitive test used to determine if Alzheimer's disease, or its very early signs (mild cognitive impairment), are present in humans. "Since we selected electromagnetic parameters that were identical to human cell phone use and tested mice in a task closely analogous to a human memory test, we believe our findings could have considerable relevance to humans," Arendash said.
The researchers found a slight increase in brain temperature during the two one-hour periods when mice were exposed to electromagnetic waves each day. This increase in brain temperature was seen only in the Alzheimer's mice, and only after months of exposure. The researchers suggest the increase in brain temperature helped the Alzheimer's brain to remove newly-formed beta-amyloid by causing brain cells to release it.
The researchers were particularly surprised to discover that months of cell phone exposure actually boosted the memory of non-demented (normal mice) to above-normal levels. They suspect that the main reason for this improvement involves the ability of electromagnetic exposure to increase brain activity, promoting greater blood flow and increased energy metabolism in the brain. "Our study provides evidence that long-term cell phone use is not harmful to brain," Dr. Cao said. "To the contrary, the electromagnetic waves emitted by cell phones could actually improve normal memory and be an effective therapy against memory impairment"
"It will take some time to determine the exact mechanisms involved in these beneficial memory effects," Arendash said. "One thing is clear, however - the cognitive benefits of long-term electromagnetic exposure are real, because we saw them in both protection- and treatment-based experiments involving Alzheimer's mice, as well as in normal mice."
Previous human studies of electromagnetic waves from cell phones involved only brief exposures given to normal humans. While some studies reported small improvements in attention or memory (not enough to impact daily life), others reported no memory effects from short-term exposure. The new study by Arendash, Cao, and their colleagues is the first to investigate the effects of long-term electromagnetic exposure over many months on memory function in either humans or animals. The findings indicate that "long-term" exposure to cell phone level electromagnetic waves is needed to observe enhanced memory in normal or memory-impaired mice.
The USF researchers began investigating the effects of cell phone use on Alzheimer's disease several years ago, after several observational studies in humans linked a possible increased risk of Alzheimer's with "low-frequency" electromagnetic exposure -- like the energy waves generated by power and telephone lines. However, cell phones emit "high-frequency" electromagnetic waves, which are very different because they can have beneficial effects on brain cell function, such as increasing brain cell activity, Arendash said.
There has been recent controversy about whether electromagnetic waves from cell phones cause brain cancer. Some researchers argue that the risk of glioma (40 percent of all brain tumors) doubles after 10 or more years of cell phone use. However, others argue that since the overall lifetime risk of developing a brain tumor of any type is less than 1 percent, any doubling of this risk would still be very low. Groups such as the World Health Organization, the American Cancer Society, and the National Institutes of Health, have all concluded that scientific evidence to date does not support any adverse health effects associated with the use of cell phones. Consistent with the view of these organizations, the researchers found no autopsy evidence of abnormal growth in brains of the Alzheimer's mice following many months of exposure to cell phone-level electromagnetic waves. They also found all major peripheral organs, such as the liver and lungs, to be normal.
The research was conducted by an interdisciplinary group of neuroscientists, electrical engineers, and neurologists from universities in Japan and China as well as from the Florida ADRC at the University of South Florida. The study was supported by funds from the Florida ADRC, a statewide project sponsored by the National Institute on Aging, and the USF Health Byrd Alzheimer's Institute.
Journal citation:
Electromagnetic Field Treatment Protects Against and Reverses Cognitive Impairment in Alzheimer's Disease Mice. Gary W. Arendash, Juan Sanchez-Ramos, Takashi Mori, Malgorzata Mamcarz, Xiaoyang Lin, Melissa Runfeldt, Li Want, Guixin Zhang, Vasyl Sava, Juan Tan and Chuanhai Cao. Journal of Alzheimer's Disease, Volume 19:1 (January 2010).
Source:
Gary Arendash
University of South Florida Health
вторник, 17 мая 2011 г.
Public Information Affects Breeding Dispersal In A Colonial Bird: Kittiwakes Cue On Neighbours
Recent studies suggested that individuals may use the reproductive performance of conspecifics as a source of public information on breeding patch quality, but experimental evidence is still limited for species breeding in colonies, such as seabirds.
Using an experimental approach in a natural population of Black-legged kittiwakes, we found that the behaviour of individuals was strongly affected by the performance of their neighbours: individuals used information conveyed by conspecifics to make decisions relative to breeding site selection.
This process can amplify the response of populations to environmental change and may have contributed to the evolution of colonial breeding.
Royal Society journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
publishing.royalsociety/biologyletters
Using an experimental approach in a natural population of Black-legged kittiwakes, we found that the behaviour of individuals was strongly affected by the performance of their neighbours: individuals used information conveyed by conspecifics to make decisions relative to breeding site selection.
This process can amplify the response of populations to environmental change and may have contributed to the evolution of colonial breeding.
Royal Society journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
publishing.royalsociety/biologyletters
понедельник, 16 мая 2011 г.
Cell Signaling Discovery Yields Heart Disease Clues
A pulsing heart cell is giving Oregon Health & Science University researchers insight into how it sends and receives signals, and that's providing clues into how heart disease and other disorders develop.
In a study appearing in today's edition of Nature, John Scott, Ph.D., a Howard Hughes Medical Institute investigator and senior scientist at OHSU's Vollum Institute, found that heart muscle cells become enlarged when an intricate intracellular signaling pathway regulated by a messenger molecule called muscle-specific A-kinase anchoring proteins, or mAKAPs, is perturbed.
The cells' growth, known as cardiomyocyte hypertrophy, can lead to congestive heart failure and other forms of cardiovascular disease, which affect more than 70 million Americans and cause about 1.4 million deaths each year.
A cell communicates with another cell by sending over a messenger molecule, typically a hormone, which activates a secondary regulatory messenger molecule - cyclic AMP (cAMP) - within a particular compartment in the recipient cell. This causes cAMP to stimulate an enzyme that triggers the activity of proteins involved in altering a cell's physiology and governing other biochemical events.
According to Scott, mAKAPs tether the enzyme, called protein kinase A (PKA), to particular locations in the cell.
"Hypertrophy is a fairly good laboratory model for certain forms of heart failure, and the PKA signaling pathway is perturbed in certain cases of heart disease," said Scott, whose laboratory was the among the first in the world to track AKAP interaction. "That's why this study may have a high translational and clinical impact."
According to the study, the mAKAP signaling system has been linked to excessive heart cell enlargement, which increases the potential for heart disease. One technique involves using drugs, such as a growth hormone, to activate a molecule known as ERK5, which suppresses the enzyme phosphodiesterase. This causes cAMP, which is normally metabolized by phosphodiesterase, to accumulate in certain parts of the cell.
"Many, many phosphodiesterases are drug targets," Scott noted. "So potentially, drugs that could target this particular phosphodiesterase, particularly, could be very useful. That's still a long way away, but that's where the work will go. Plus, it fits into a large body of work implicating these molecules as markers for certain forms of heart disease. Heart rate, for example, is controlled by calcium, and there's some level of regulation by cyclic AMP as well."
To show the signal transduction process in a heart muscle cell, Scott and his colleagues used a fluorescent microscope that captures protein molecules stained with various colored dyes to show PKA activity in a cell. In one set of images, captured over six minutes, a greenish-yellow ring appears to expand around the cell's nucleus before quickly shrinking.
"That's showing the rise in PKA activity, and the drop," Scott said.
Scott compares a cell to a highly organized city containing a variety of organizations serving particular functions, such as fire and police departments, an airport, a city hall and other entities. They all use one communication system, but information is delivered to, and interpreted by, each entity differently.
"The idea is that the cell is like this three-dimensional city, and at different times of the day, different things happen in the city," he explained. "This family of molecules we work on serves to pinpoint enzymes within three dimensions of the cell, and that's very important because it means that these enzymes act very locally. What the imaging data in this paper shows is that not only do they work in three dimensions, but there's this fourth dimension - time."
In addition, he said, "phosphodiesterase is a great drug target that could be something of importance in terms of pharmaceutical intervention at a later date."
The study was funded by the National Institutes of Health and the American Heart Association.
To access all OHSU news releases, visit ohsu/news
Jonathan Modie
modiejohsu
503-494-8231
Oregon Health & Science University
ohsu
In a study appearing in today's edition of Nature, John Scott, Ph.D., a Howard Hughes Medical Institute investigator and senior scientist at OHSU's Vollum Institute, found that heart muscle cells become enlarged when an intricate intracellular signaling pathway regulated by a messenger molecule called muscle-specific A-kinase anchoring proteins, or mAKAPs, is perturbed.
The cells' growth, known as cardiomyocyte hypertrophy, can lead to congestive heart failure and other forms of cardiovascular disease, which affect more than 70 million Americans and cause about 1.4 million deaths each year.
A cell communicates with another cell by sending over a messenger molecule, typically a hormone, which activates a secondary regulatory messenger molecule - cyclic AMP (cAMP) - within a particular compartment in the recipient cell. This causes cAMP to stimulate an enzyme that triggers the activity of proteins involved in altering a cell's physiology and governing other biochemical events.
According to Scott, mAKAPs tether the enzyme, called protein kinase A (PKA), to particular locations in the cell.
"Hypertrophy is a fairly good laboratory model for certain forms of heart failure, and the PKA signaling pathway is perturbed in certain cases of heart disease," said Scott, whose laboratory was the among the first in the world to track AKAP interaction. "That's why this study may have a high translational and clinical impact."
According to the study, the mAKAP signaling system has been linked to excessive heart cell enlargement, which increases the potential for heart disease. One technique involves using drugs, such as a growth hormone, to activate a molecule known as ERK5, which suppresses the enzyme phosphodiesterase. This causes cAMP, which is normally metabolized by phosphodiesterase, to accumulate in certain parts of the cell.
"Many, many phosphodiesterases are drug targets," Scott noted. "So potentially, drugs that could target this particular phosphodiesterase, particularly, could be very useful. That's still a long way away, but that's where the work will go. Plus, it fits into a large body of work implicating these molecules as markers for certain forms of heart disease. Heart rate, for example, is controlled by calcium, and there's some level of regulation by cyclic AMP as well."
To show the signal transduction process in a heart muscle cell, Scott and his colleagues used a fluorescent microscope that captures protein molecules stained with various colored dyes to show PKA activity in a cell. In one set of images, captured over six minutes, a greenish-yellow ring appears to expand around the cell's nucleus before quickly shrinking.
"That's showing the rise in PKA activity, and the drop," Scott said.
Scott compares a cell to a highly organized city containing a variety of organizations serving particular functions, such as fire and police departments, an airport, a city hall and other entities. They all use one communication system, but information is delivered to, and interpreted by, each entity differently.
"The idea is that the cell is like this three-dimensional city, and at different times of the day, different things happen in the city," he explained. "This family of molecules we work on serves to pinpoint enzymes within three dimensions of the cell, and that's very important because it means that these enzymes act very locally. What the imaging data in this paper shows is that not only do they work in three dimensions, but there's this fourth dimension - time."
In addition, he said, "phosphodiesterase is a great drug target that could be something of importance in terms of pharmaceutical intervention at a later date."
The study was funded by the National Institutes of Health and the American Heart Association.
To access all OHSU news releases, visit ohsu/news
Jonathan Modie
modiejohsu
503-494-8231
Oregon Health & Science University
ohsu
воскресенье, 15 мая 2011 г.
FDA Identifies First Steps In Requirements For Safety Plans For Certain Drugs And Biologics
The U.S. Food and Drug Administration has identified 25 drugs and biologic products that will be required to submit safety plans called Risk Evaluation and Mitigation Strategy (REMS), the FDA said in a Federal Register notice published recently.
Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), FDA can require manufacturers to submit a REMS when a drug first comes on the market, or later if FDA becomes aware of new safety data about the drug. The manufacturers of the 25 drugs and biologic products identified in today's notice must submit to the agency a proposed REMS by Sept. 21, 2008.
Certain drugs present a dilemma: They can provide an important benefit to patients, but they can be especially dangerous if not used properly. For example, certain drugs may be safe and effective for patients, but if taken while pregnant can harm the fetus or cause miscarriage. Rather than deny FDA approval of such drugs, the agency has granted approval and required that the manufacturer develop a safety plan, or REMS, to help ensure that health care professionals prescribe the drug correctly and that patients use it safely. While FDA has previously approved some drugs and biologics with these safety plans, the new law makes explicit FDA's authority to require them and contains specific enforcement authority when violations or noncompliance with the plan's requirements occur.
"These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use," said Jane Axelrad, associate director for policy, Center for Drug Evaluation and Research, FDA. "The FDA approved the drugs identified today before the new law was passed, and they will now be brought under the new statutory authority to require and enforce REMS."
In addition to issuing this Federal Register notice about drugs approved before March 25, 2008, the FDA also is implementing the new authority for drugs that will be approved after March 25, 2008, as well as for already marketed drugs for which new risks are identified after March 25.
The FDA also advised the public to notify the agency if they believe other drugs should be considered to have REMS under the new statutory provisions.
The Federal Register notice, which includes a list of the 25 drugs and biologic products that will be required to submit REMS, is available here.
fda
Under the Food and Drug Administration Amendments Act of 2007 (FDAAA), FDA can require manufacturers to submit a REMS when a drug first comes on the market, or later if FDA becomes aware of new safety data about the drug. The manufacturers of the 25 drugs and biologic products identified in today's notice must submit to the agency a proposed REMS by Sept. 21, 2008.
Certain drugs present a dilemma: They can provide an important benefit to patients, but they can be especially dangerous if not used properly. For example, certain drugs may be safe and effective for patients, but if taken while pregnant can harm the fetus or cause miscarriage. Rather than deny FDA approval of such drugs, the agency has granted approval and required that the manufacturer develop a safety plan, or REMS, to help ensure that health care professionals prescribe the drug correctly and that patients use it safely. While FDA has previously approved some drugs and biologics with these safety plans, the new law makes explicit FDA's authority to require them and contains specific enforcement authority when violations or noncompliance with the plan's requirements occur.
"These safety plans allow patients to have continued access to certain medicines for which there are safety concerns that can be managed through appropriate use," said Jane Axelrad, associate director for policy, Center for Drug Evaluation and Research, FDA. "The FDA approved the drugs identified today before the new law was passed, and they will now be brought under the new statutory authority to require and enforce REMS."
In addition to issuing this Federal Register notice about drugs approved before March 25, 2008, the FDA also is implementing the new authority for drugs that will be approved after March 25, 2008, as well as for already marketed drugs for which new risks are identified after March 25.
The FDA also advised the public to notify the agency if they believe other drugs should be considered to have REMS under the new statutory provisions.
The Federal Register notice, which includes a list of the 25 drugs and biologic products that will be required to submit REMS, is available here.
fda
суббота, 14 мая 2011 г.
News From The Journals Of The American Society For Microbiology
Protozoa May Enable Food-Borne Pathogens on Leafy Vegetables
Protozoa found on lettuce and spinach may sequester harmful food-borne pathogens ultimately contributing to their survival on produce surfaces say researchers from Tennessee Technological University, Cookeville and the Produce Safety and Microbiology Research Unit, Albany, California. They report their findings in the April 2008 issue of the journal Applied and Environmental Microbiology.
Several outbreaks of food-borne illnesses attributed to Escherichia coli O157:H7 and Salmonella enterica have received national attention in recent years. The Centers for Disease Control and Prevention reported that fresh produce was the most significant source of food-borne illness in 2005. Protozoa are single-celled organisms whose main function is bacterial consumption. They are commonly found in the natural microflora of plants and several species of amoebae have been associated with fresh salad vegetables. The recent occurrence of multiple outbreaks has encouraged researchers to further examine the interaction between food-borne pathogens and protozoa.
In the study protozoa (Glaucoma sp., Colpoda steinii, and Acanthamoeba palestinensis) as well as the soil-borne strain, Tetrahymena pyriformis, were cultured from store-bought spinach and lettuce and washed and allowed to graze on green fluorescent protein- or red fluorescent protein-labeled enteric pathogens including E. coli O157:H7, S. enterica, and Listeria monocytogenes. They were then monitored for their ability to sequester the bacteria and for vesicle production (food vacuoles released by protozoa offering a means of protection to some bacteria). Results showed Glaucoma produced vesicles with all bacterial strains and Tetrahymena also displayed vesicle production, but only of E. coli O157:H7 and S. enterica, not L. monocytogenes. Further studies of E. coli O157:H7 following vesicle production revealed that 4 hours after the addition of spinach extract, the bacteria had multiplied and escaped the vesicles. C. steinii did not produce any vesicles from any of the pathogens.
"The presence of protozoa on leafy vegetables and their sequestration of enteric bacteria in vesicles indicate that they may play an important role in the ecology of human pathogens on produce," say the researchers.
(P. Gourabathini, M.T. Brandl, K.S. Redding, J.H. Gunderson, S.G. Berk. 2008. Interactions between food-borne pathogens and protozoa isolated from lettuce and spinach. Applied and Environmental Microbiology, 74. 8: 2518-2525.)
Leaf Age May Contribute to Contamination of Lettuce with E. coli and Salmonella
A new study presents the first evidence that harmful pathogens frequently linked with food-borne illnesses are more commonly found on younger inner leaves than on older outer leaves of romaine lettuce. The researchers from the Produce Safety and Microbiology Research Unity, Albany, California and the University of California, Berkley report their findings in the April 2008 issue of the journal Applied and Environmental Microbiology.
Lettuce (Lactuca sativa) is the fresh produce item most commonly implicated in epidemics of food-borne illness, while Escherichia coli O157:H7 and Salmonella enterica are the most frequently attributed bacterial agents. Although previous studies have focused on E. coli O157:H7 colonization on cut or shredded lettuce leaves, little is known of its ability to colonize whole lettuce leaves in both pre- and post-harvest environments.
In the study researchers investigated the growth of E. coli O157:H7 and S. enterica on romaine lettuce leaves both pre- and post-harvest. The increased population size of E. coli O157:H7 on young lettuce plants ranged from 16- to 100-fold in the presence of warm temperatures and free water on the leaves. The increase in population size also varied significantly with leaf age, however the colonization was consistently 10-fold higher on the young (inner) leaves than on the middle leaves. Growth rates of S. enterica were found to be similarly leaf age dependent. Both bacterial pathogens also displayed higher population rates on younger leaves than on middle leaves harvested from mature lettuce heads.
"Our results indicate that leaf age and nitrogen content contribute to shaping the bacterial communities of preharvest and postharvest lettuce and that young lettuce leaves may be associated with a greater risk of contamination with E. coli O157:H7.
(M.T. Brandl, R. Amundson. 2008. Leaf age as a risk factor in contamination of lettuce with Escherichia coli O157:H7 and Salmonella enterica. Applied and Environmental Microbiology, 74. 8: 2298-2306.)
New Method Simultaneously Tests for Fifteen Respiratory Viruses
A new test capable of simultaneously detecting 15 respiratory viruses may allow for quicker diagnosis and treatment of potentially deadly respiratory infections in children and adults worldwide. The researchers from The Netherlands report their findings in the April 2008 issue of the Journal of Clinical Microbiology.
Acute respiratory infections (RTIs) are responsible for high rates of morbidity and mortality throughout the world, however the cause remains inconclusive in over half of all reported cases. Respiratory viruses are believed to be among the pathogens contributing to a significant number of undiagnosed infections, but clinical presentation of patients with RTIs are generally not pathogen specific. While cell culture is still considered the "gold standard" for laboratory detection of respiratory viruses, slow response time and low sensitivity are suboptimal for routine detection practices.
In the study a new multiparameter test called RespiFinder was developed to detect 15 respiratory viruses in one reaction. Researchers then used the RespiFinder, as well as the cell culture method and a respiratory syncytial virus (RSV)-specific immunochromatography assay (ICA) to examine 144 clinical samples and compared the results. In most cases the RespiFinder was as effective or nearly as effective (more than 95%) as the cell culture, or "gold standard", in both sensitivity and specificity. Only test results for rhinovirus and RSV came in under 95%. In addition, compared to the RSV-specific ICA, the RespiFinder showed a specificity and sensitivity of approximately 80%.
"The RespiFinder assay provides a user-friendly and high-throughput tool for the simultaneous detection of 15 respiratory viruses with excellent overall performance statistics," say the researchers.
(M. Reijans, G. Dingemans, C.H. Klaassen, J.F. Meis, J. Keijdener, B. Mulders, K. Eadie, W. van Leeuwen, A. van Belkum, A.M. Horrevorts, G. Simons. 2008. RespiFinder: a new multiparameter test to differentially identify fifteen respiratory viruses. Journal of Clinical Microbiology, 46. 4: 1232-1240.)
Source: Carrie Slijepcevic
American Society for Microbiology
Protozoa found on lettuce and spinach may sequester harmful food-borne pathogens ultimately contributing to their survival on produce surfaces say researchers from Tennessee Technological University, Cookeville and the Produce Safety and Microbiology Research Unit, Albany, California. They report their findings in the April 2008 issue of the journal Applied and Environmental Microbiology.
Several outbreaks of food-borne illnesses attributed to Escherichia coli O157:H7 and Salmonella enterica have received national attention in recent years. The Centers for Disease Control and Prevention reported that fresh produce was the most significant source of food-borne illness in 2005. Protozoa are single-celled organisms whose main function is bacterial consumption. They are commonly found in the natural microflora of plants and several species of amoebae have been associated with fresh salad vegetables. The recent occurrence of multiple outbreaks has encouraged researchers to further examine the interaction between food-borne pathogens and protozoa.
In the study protozoa (Glaucoma sp., Colpoda steinii, and Acanthamoeba palestinensis) as well as the soil-borne strain, Tetrahymena pyriformis, were cultured from store-bought spinach and lettuce and washed and allowed to graze on green fluorescent protein- or red fluorescent protein-labeled enteric pathogens including E. coli O157:H7, S. enterica, and Listeria monocytogenes. They were then monitored for their ability to sequester the bacteria and for vesicle production (food vacuoles released by protozoa offering a means of protection to some bacteria). Results showed Glaucoma produced vesicles with all bacterial strains and Tetrahymena also displayed vesicle production, but only of E. coli O157:H7 and S. enterica, not L. monocytogenes. Further studies of E. coli O157:H7 following vesicle production revealed that 4 hours after the addition of spinach extract, the bacteria had multiplied and escaped the vesicles. C. steinii did not produce any vesicles from any of the pathogens.
"The presence of protozoa on leafy vegetables and their sequestration of enteric bacteria in vesicles indicate that they may play an important role in the ecology of human pathogens on produce," say the researchers.
(P. Gourabathini, M.T. Brandl, K.S. Redding, J.H. Gunderson, S.G. Berk. 2008. Interactions between food-borne pathogens and protozoa isolated from lettuce and spinach. Applied and Environmental Microbiology, 74. 8: 2518-2525.)
Leaf Age May Contribute to Contamination of Lettuce with E. coli and Salmonella
A new study presents the first evidence that harmful pathogens frequently linked with food-borne illnesses are more commonly found on younger inner leaves than on older outer leaves of romaine lettuce. The researchers from the Produce Safety and Microbiology Research Unity, Albany, California and the University of California, Berkley report their findings in the April 2008 issue of the journal Applied and Environmental Microbiology.
Lettuce (Lactuca sativa) is the fresh produce item most commonly implicated in epidemics of food-borne illness, while Escherichia coli O157:H7 and Salmonella enterica are the most frequently attributed bacterial agents. Although previous studies have focused on E. coli O157:H7 colonization on cut or shredded lettuce leaves, little is known of its ability to colonize whole lettuce leaves in both pre- and post-harvest environments.
In the study researchers investigated the growth of E. coli O157:H7 and S. enterica on romaine lettuce leaves both pre- and post-harvest. The increased population size of E. coli O157:H7 on young lettuce plants ranged from 16- to 100-fold in the presence of warm temperatures and free water on the leaves. The increase in population size also varied significantly with leaf age, however the colonization was consistently 10-fold higher on the young (inner) leaves than on the middle leaves. Growth rates of S. enterica were found to be similarly leaf age dependent. Both bacterial pathogens also displayed higher population rates on younger leaves than on middle leaves harvested from mature lettuce heads.
"Our results indicate that leaf age and nitrogen content contribute to shaping the bacterial communities of preharvest and postharvest lettuce and that young lettuce leaves may be associated with a greater risk of contamination with E. coli O157:H7.
(M.T. Brandl, R. Amundson. 2008. Leaf age as a risk factor in contamination of lettuce with Escherichia coli O157:H7 and Salmonella enterica. Applied and Environmental Microbiology, 74. 8: 2298-2306.)
New Method Simultaneously Tests for Fifteen Respiratory Viruses
A new test capable of simultaneously detecting 15 respiratory viruses may allow for quicker diagnosis and treatment of potentially deadly respiratory infections in children and adults worldwide. The researchers from The Netherlands report their findings in the April 2008 issue of the Journal of Clinical Microbiology.
Acute respiratory infections (RTIs) are responsible for high rates of morbidity and mortality throughout the world, however the cause remains inconclusive in over half of all reported cases. Respiratory viruses are believed to be among the pathogens contributing to a significant number of undiagnosed infections, but clinical presentation of patients with RTIs are generally not pathogen specific. While cell culture is still considered the "gold standard" for laboratory detection of respiratory viruses, slow response time and low sensitivity are suboptimal for routine detection practices.
In the study a new multiparameter test called RespiFinder was developed to detect 15 respiratory viruses in one reaction. Researchers then used the RespiFinder, as well as the cell culture method and a respiratory syncytial virus (RSV)-specific immunochromatography assay (ICA) to examine 144 clinical samples and compared the results. In most cases the RespiFinder was as effective or nearly as effective (more than 95%) as the cell culture, or "gold standard", in both sensitivity and specificity. Only test results for rhinovirus and RSV came in under 95%. In addition, compared to the RSV-specific ICA, the RespiFinder showed a specificity and sensitivity of approximately 80%.
"The RespiFinder assay provides a user-friendly and high-throughput tool for the simultaneous detection of 15 respiratory viruses with excellent overall performance statistics," say the researchers.
(M. Reijans, G. Dingemans, C.H. Klaassen, J.F. Meis, J. Keijdener, B. Mulders, K. Eadie, W. van Leeuwen, A. van Belkum, A.M. Horrevorts, G. Simons. 2008. RespiFinder: a new multiparameter test to differentially identify fifteen respiratory viruses. Journal of Clinical Microbiology, 46. 4: 1232-1240.)
Source: Carrie Slijepcevic
American Society for Microbiology
пятница, 13 мая 2011 г.
Challenges In The Computational Design Of Proteins
Computational protein design aims at the engineering of proteins with targeted functions by using modelling and high-throughput computing.
We will discuss the main challenges faced by this approach before it will become a standardised technique in synthetic biology.
We also describe its integration with experimental techniques such as directed evolution. We finalise by presenting future perspectives in the field
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus, a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
Journal of the Royal Society Interface
We will discuss the main challenges faced by this approach before it will become a standardised technique in synthetic biology.
We also describe its integration with experimental techniques such as directed evolution. We finalise by presenting future perspectives in the field
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fifth in JCR's multidisciplinary category. The journal also incorporates Interface Focus, a peer-reviewed, themed supplement, each issue of which concentrates on a specific cross-disciplinary subject.
Journal of the Royal Society Interface
среда, 11 мая 2011 г.
Variable Light Illuminates The Distribution Of Picophytoplankton
Tiny photosynthetic plankton less than a millionth of a millimeter in
diameter numerically dominate marine phytoplankton. Their photosynthesis
uses
light to drive carbon dioxide uptake, fueling the marine food web over
vast areas of the oceans. A new study published in this week's PLoS ONE by
post-doctoral researcher Dr Christophe Six and a team of scientists from
Mount Allison University, Sackville, New Brunswick, Canada, illuminates
how
the environment regulates the distributions of these ecologically
important species.
Dr Doug Campbell, Canadian Research Chair in Environmental Processes and
co-author explains, "Phytoplankton are entrained in the water column and
are
thus subject to rapid changes in light as they mix through the upper layer
of the ocean."
Dr Christophe Six adds, "Phytoplankton need light for photosynthesis and
survival, but surprisingly this light also inactivates a key component of
the photosynthetic apparatus, photosystem II. This Photoinactivation of
photosystem II decreases photosynthesis and can even kill cells, unless
they
can counteract the damage through repair, which requires nutrients."
"We found the picophytoplankton species isolated from different regions of
the ocean have different abilities for this repair, and therefore have
different abilities to tolerate increases in light. Their repair
capacities are consistent with the different light and nutrient regimes in
their
local environments; species from deep ocean regions with stable light and
low nutrients have very limited repair capacity, but species from coastal
regions with more variable light and higher nutrients are more able to
cope with variable light through rapid repair."
This result indicates that picophytoplankton species' tolerance of
exposures to high light can help to explain how these organisms are
distributed
throughout the ocean. The group measures the rates of photoinactivation
and the rates of the counteracting repair in a wide variety of
phytoplankton
species, and next plans to contribute to ocean models to predict
phytoplankton carbon cycling in response to future climate change.
Citation: Six C, Finkel ZV, Irwin AJ, Campbell DA (2007) Light Variability
Illuminates Niche-Partitioning among Marine Picocyanobacteria. PLoS ONE
2(12): e1341. doi:10.1371/journal.pone.0001341
Please click here
Disclaimer
The following press releases refer to a selection of the upcoming articles
in PLoS ONE. The releases are provided by the article authors and/or their
institutions. Any opinions expressed in these releases or articles are the
personal views of the contributors, and do not necessarily represent the
views or policies of PLoS. PLoS expressly disclaims any and all warranties
and liability in connection with the information found in the releases and
articles and your use of such information.
PLoS ONE is the first journal of primary research from all areas of
science to employ both pre- and post-publication peer review to maximize
the
impact of every report it publishes. PLoS ONE is published by the Public
Library of Science (PLoS), the open access publisher whose goal is to make
the world's scientific and medical literature a public resource.
plosone
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific and
medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
diameter numerically dominate marine phytoplankton. Their photosynthesis
uses
light to drive carbon dioxide uptake, fueling the marine food web over
vast areas of the oceans. A new study published in this week's PLoS ONE by
post-doctoral researcher Dr Christophe Six and a team of scientists from
Mount Allison University, Sackville, New Brunswick, Canada, illuminates
how
the environment regulates the distributions of these ecologically
important species.
Dr Doug Campbell, Canadian Research Chair in Environmental Processes and
co-author explains, "Phytoplankton are entrained in the water column and
are
thus subject to rapid changes in light as they mix through the upper layer
of the ocean."
Dr Christophe Six adds, "Phytoplankton need light for photosynthesis and
survival, but surprisingly this light also inactivates a key component of
the photosynthetic apparatus, photosystem II. This Photoinactivation of
photosystem II decreases photosynthesis and can even kill cells, unless
they
can counteract the damage through repair, which requires nutrients."
"We found the picophytoplankton species isolated from different regions of
the ocean have different abilities for this repair, and therefore have
different abilities to tolerate increases in light. Their repair
capacities are consistent with the different light and nutrient regimes in
their
local environments; species from deep ocean regions with stable light and
low nutrients have very limited repair capacity, but species from coastal
regions with more variable light and higher nutrients are more able to
cope with variable light through rapid repair."
This result indicates that picophytoplankton species' tolerance of
exposures to high light can help to explain how these organisms are
distributed
throughout the ocean. The group measures the rates of photoinactivation
and the rates of the counteracting repair in a wide variety of
phytoplankton
species, and next plans to contribute to ocean models to predict
phytoplankton carbon cycling in response to future climate change.
Citation: Six C, Finkel ZV, Irwin AJ, Campbell DA (2007) Light Variability
Illuminates Niche-Partitioning among Marine Picocyanobacteria. PLoS ONE
2(12): e1341. doi:10.1371/journal.pone.0001341
Please click here
Disclaimer
The following press releases refer to a selection of the upcoming articles
in PLoS ONE. The releases are provided by the article authors and/or their
institutions. Any opinions expressed in these releases or articles are the
personal views of the contributors, and do not necessarily represent the
views or policies of PLoS. PLoS expressly disclaims any and all warranties
and liability in connection with the information found in the releases and
articles and your use of such information.
PLoS ONE is the first journal of primary research from all areas of
science to employ both pre- and post-publication peer review to maximize
the
impact of every report it publishes. PLoS ONE is published by the Public
Library of Science (PLoS), the open access publisher whose goal is to make
the world's scientific and medical literature a public resource.
plosone
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization of
scientists and physicians committed to making the world's scientific and
medical
literature a freely available public resource.
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
вторник, 10 мая 2011 г.
New Method Enables Gene Disruption In Destructive Fungal Pathogen
Blacksburg, Va. - Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech, Colorado State University, and Duke University Medical Center have developed a new method to determine gene function on a genome-wide scale in the fungal pathogen Alternaria brassicicola. This destructive fungus causes black spot disease, leading to considerable leaf loss in such economically important crops as canola, cabbage, and broccoli.
Genomic methods that allow the disruption of several thousand genes are needed because they allow high-throughput identification of genes and gene function. Such procedures are widely applicable and would be extremely useful in allowing scientists to investigate the key events that occur when a host interacts with a pathogen.
"The development of this protocol is timely as the genome sequence of A. brassicicola is scheduled for completion in 2006. We now have in our hands a versatile method that will allow us to dissect the pathogen's nucleotide sequence information and establish the function of many of the individual genes in this filamentous fungus," said Christopher Lawrence, associate professor at VBI, director of the project, and one of the authors of the study.
"A. brassicicola has consistently been used in studies with the weedy mustard plant Arabidopsis. The genome sequence of Arabidopsis was determined in 2001 and many methods are available to ascertain gene function in this plant," Lawrence said. "We now have a means to identify key fungal and plant genes that interact and ultimately lead to disease development or resistance. This is an extremely powerful research tool."
The generation of gene disruption mutants has been a limiting step for the analysis of gene function in most filamentous fungi. The new method takes advantage of a novel linear DNA construct that greatly improves the efficiency of targeted gene disruption. The DNA construct includes an antibiotic-resistance marker gene, which allows for easy selection of the new mutants, as well as a short partial target gene that integrates and disrupts genes in the pathogen's genome.
Richard Oliver, director of the Australian Centre for Necrotrophic Fungal Pathogens and professor of Molecular Plant Pathology at Murdoch University, Perth, commented: "The new disruption method looks highly promising as a tool for functional genomic studies. The authors looked at over 20 genes and were able to produce transformants and inactivated genes or knock-outs in each experiment. In most cases, the efficiency of gene disruption was 100 percent, which represents a considerable improvement over previously reported methods and makes large-scale functional analysis of individual genes feasible."
Yangrae Cho of VBI, lead scientist and author of the paper, said, "The high throughput system described in this study should allow for the systematic analysis of large sets of candidate genes in A. brassicicola, such as those encoding cell-wall-degrading enzymes and other genes of interest in pathogen-plant interactions."
The new gene disruption method may also find applications in the study of fungal pathogens that directly impact humans and human health. In addition to causing numerous plant diseases, Alternaria are involved in the development of such chronic airway diseases as asthma, allergy and chronic rhinosinusitis. Gene disruption methods could help in identifying molecules from the fungus that trigger inflammatory and other types of immune responses in humans. By understanding how fungi modulate immune responses in humans, new ways of developing therapeutics for these conditions could be identified.
The work was funded by the National Science Foundation under grant number 0443991.
The research appears in vol.19, no.1, 2006, of the journal Molecular Plant-Microbe Interactions, in the article "A high throughput targeted gene disruption method for Alternaria brassicicola functional genomics using linear minimal element (LME) constructs."
Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and plant sciences.
Contact: Barry Whyte
whytevbi.vt
Virginia Tech
Genomic methods that allow the disruption of several thousand genes are needed because they allow high-throughput identification of genes and gene function. Such procedures are widely applicable and would be extremely useful in allowing scientists to investigate the key events that occur when a host interacts with a pathogen.
"The development of this protocol is timely as the genome sequence of A. brassicicola is scheduled for completion in 2006. We now have in our hands a versatile method that will allow us to dissect the pathogen's nucleotide sequence information and establish the function of many of the individual genes in this filamentous fungus," said Christopher Lawrence, associate professor at VBI, director of the project, and one of the authors of the study.
"A. brassicicola has consistently been used in studies with the weedy mustard plant Arabidopsis. The genome sequence of Arabidopsis was determined in 2001 and many methods are available to ascertain gene function in this plant," Lawrence said. "We now have a means to identify key fungal and plant genes that interact and ultimately lead to disease development or resistance. This is an extremely powerful research tool."
The generation of gene disruption mutants has been a limiting step for the analysis of gene function in most filamentous fungi. The new method takes advantage of a novel linear DNA construct that greatly improves the efficiency of targeted gene disruption. The DNA construct includes an antibiotic-resistance marker gene, which allows for easy selection of the new mutants, as well as a short partial target gene that integrates and disrupts genes in the pathogen's genome.
Richard Oliver, director of the Australian Centre for Necrotrophic Fungal Pathogens and professor of Molecular Plant Pathology at Murdoch University, Perth, commented: "The new disruption method looks highly promising as a tool for functional genomic studies. The authors looked at over 20 genes and were able to produce transformants and inactivated genes or knock-outs in each experiment. In most cases, the efficiency of gene disruption was 100 percent, which represents a considerable improvement over previously reported methods and makes large-scale functional analysis of individual genes feasible."
Yangrae Cho of VBI, lead scientist and author of the paper, said, "The high throughput system described in this study should allow for the systematic analysis of large sets of candidate genes in A. brassicicola, such as those encoding cell-wall-degrading enzymes and other genes of interest in pathogen-plant interactions."
The new gene disruption method may also find applications in the study of fungal pathogens that directly impact humans and human health. In addition to causing numerous plant diseases, Alternaria are involved in the development of such chronic airway diseases as asthma, allergy and chronic rhinosinusitis. Gene disruption methods could help in identifying molecules from the fungus that trigger inflammatory and other types of immune responses in humans. By understanding how fungi modulate immune responses in humans, new ways of developing therapeutics for these conditions could be identified.
The work was funded by the National Science Foundation under grant number 0443991.
The research appears in vol.19, no.1, 2006, of the journal Molecular Plant-Microbe Interactions, in the article "A high throughput targeted gene disruption method for Alternaria brassicicola functional genomics using linear minimal element (LME) constructs."
Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the "disease triangle" of host-pathogen-environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today's key challenges in the biomedical, environmental and plant sciences.
Contact: Barry Whyte
whytevbi.vt
Virginia Tech
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