As stem cells in the blood grow older, genetic mutations accumulate that could be at the root of blood diseases that strike people as they age, according to work done in mice by researchers at the Stanford University School of Medicine.
"This and our previous work points out why older people are more likely to get blood diseases, such as leukemia or anemia, and are less likely to make new antibodies that would protect against infections like the flu," said senior author Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and of the Stanford Comprehensive Cancer Center. The work will be published in Nature.
In past studies, this group of researchers had shown that blood-forming stem cells in the bone marrow of mice became less able to divide and replenish the supply of blood cells as they aged. The question was why.
Researchers have put forward many theories about how cells age, said Derrick Rossi, PhD, postdoctoral scholar and co-first author of the paper. One of those theories has to do with cells accumulating genetic mutations. "The idea is that, over time, accumulated DNA damage progressively diminishes the cell's ability to perform its normal function," he said.
However, researchers had thought that mutations were unlikely to underlie aging in blood-forming stem cells because they very rarely divide, and most mutations crop up during division. The infrequent divisions were believed to protect the cells from acquiring new mutations.
Rossi, Weissman and the other first author, postdoctoral scholar David Bryder, PhD, tested that idea in two different sets of experiments. In the first, they studied the blood-forming stem cells of mice engineered to have single mutations that make them especially prone to accumulating additional genetic errors. In each of the three different types of mutant mice they studied, the stem cells appeared to behave normally and to produce new blood cells.
However, the full truth came out when they took blood-forming stem cells from any of the three types of mice and used those cells to repopulate the bone marrow of irradiated mice. This type of experiment is much like using a bone marrow transplant to bring back the bone marrow in a person who has undergone extensive chemotherapy.
Normally, a few stem cells are enough to completely replenish the bone marrow of mice and produce normal amounts of blood and immune cells. However, error-filled blood-forming stem cells taken from the mutant mice were much less effective at colonizing the depleted bone marrow than normal stem cells, and became even less effective when taken from older mutant mice.
Rossi said these results suggest that mutations accumulating in stem cells as they age were preventing them from doing their normal job of producing new blood and immune system cells. However, these results were in mutant mice. Rossi wanted to know if the stem cells in normal, healthy mice also accumulate damage as they age.
To address this, in the second set of experiments, Rossi isolated stem cells from the bone marrow of normal young and old mice, then stained those cells with a chemical that clings to a protein that's associated with DNA damage. This protein can act as a flag to highlight nearby DNA damage.
What he found is that young stem cells from normal mice contained no stain and therefore little or no DNA damage. Older stem cells, on the other hand, showed extensive staining.
All of this adds up to one thing: blood-forming stem cells do accumulate DNA damage with age even though they rarely divide, and that damage is passed on to the blood and immune system cells they make. Weissman said these findings could explain the origin of blood cancer (leukemia) and immune dysfunctions that occur as people age.
The next step is to show whether these results from mice hold true for human blood-forming stem cells. "If this work does extrapolate to humans, then it is absolutely consistent with the idea that blood-forming stem cells are the breeding ground for pre-leukemic mutations," said Weissman, the Virginia and D.K. Ludwig Professor for Clinical Investigation in Cancer Research.
Additional Stanford researchers who contributed to this work include postdoctoral scholar Jun Seita, MD, PhD.
Funding for this study came from the National Cancer Institute's Center for Cancer Research, the Damon Runyon Cancer Foundation, the California Institute of Regenerative Medicine, a Swedish Medical Research Council scholarship (STINT) and a Cancerfonden grant.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.
Contact: Amy Adams
Stanford University Medical Center /a>
вторник, 31 мая 2011 г.
понедельник, 30 мая 2011 г.
Toxicology-on-a-chip Tool Readies For Market
University and biotech company collaboration prepares MetaChip for technology transfer.
Recalls of popular prescription drugs are raising public concern about the general safety of new pharmaceuticals. A collaborative group of researchers says that identifying which drug candidates are toxic early in the discovery process can help prevent harmful pharmaceuticals from being placed on the market in the first place, and they have developed a tool to do it.
Researchers at Rensselaer Polytechnic Institute, University of California-Berkeley, and Solidus Biosciences Inc. have developed a biochip, called the MetaChip, which can analyze drug candidates for toxicity and eliminate harmful ones before they advance to pre-clinical stages. Now beginning the second phase of funding for the National Institutes of Health (NIH)-supported project, researchers are working to optimize the technology for the end user: pharmaceutical and biotechnology companies. The researchers are working to bring the MetaChip to market within a year.
"Compounds can be screened early, quickly, and effectively by the MetaChip to prevent toxic drugs from getting through the discovery process, being put on the market, and then getting recalled, such as we've seen with several high-profile cases recently," says Jonathan Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer.
"Weeding out toxic compounds earlier would also allow pharmaceutical companies to evaluate more compounds and more efficiently identify those that are most likely to become successful drugs," adds Douglas Clark of the Chemical Engineering Department at the University of California-Berkeley.
Dordick and Clark are also the co-founders of Solidus Biosciences, a biotech company located at the Rensselaer Incubator for start-up businesses.
The MetaChip (metabolizing enzyme toxicology assay chip) mimics the effects of metabolism in the human liver where enzymes break down, neutralize, and excrete chemicals from food and pharmaceuticals. In many cases, the metabolized chemicals, called metabolites, are harmless or even beneficial. But some metabolites are toxic, and this toxicity can be difficult to predict or find at early stages of drug discovery with current testing methods.
"The relatively slow pace of technology development in toxicology and clinical safety evaluation that could be used in early phases of drug development continues to hinder the progression of lead compounds to pharmaceuticals," Dordick says. "In addition to safety concerns, drug discovery is an extremely costly process with more than $1 billion invested in each approved drug. For the first time, the MetaChip can enable the initial and high-throughput analysis of metabolism-induced toxicology to be performed before significant resources are invested in the drug's development."
Solidus Biosciences recently received a $1.7 million, three-year award from NIH through its Small Business Technology Transfer Program to optimize the MetaChip for market. Rensselaer will receive approximately $500,000 as a sub-contractor of the award. The technology has been patented by Rensselaer Polytechnic Institute and University of California-Berkeley and licensed exclusively to Solidus Biosciences.
The MetaChip uses a culturing method by combining enzyme catalysis with cell-based screening on a single microscale chip. The drug candidates are added to a chip containing approximately 2,000 combinations of the eight enzymes used in human liver metabolism and then sandwiched with a slide of human organ cells in order to detect toxic reactions to the compound. When toxic reactions are detected, the toxic drug compounds are eliminated as potential candidates for further development as new pharmaceuticals. The researchers are also working to develop an automated MetaReader device to quickly analyze the results.
Dordick, Clark, and collaborators published findings on the MetaChip in the Jan. 25, 2005 issue of Proceedings of the National Academy of Sciences in a paper titled "Metabolizing Enzyme Toxicology Assay Chip (MetaChip) for High-Throughput Microscale Toxicity Analyses." The peer-reviewed publication defines the technology and results of testing in more detail.
Development of the MetaChip technology is part of several NIH-funded research projects at Rensselaer seeking more efficient ways to synthesize and identify compounds that merit further development as possible new drugs.
Biotechnology and Interdisciplinary Studies at Rensselaer
At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences and engineering to encourage discovery and innovation. Rensselaer's four biotechnology research constellations - biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology - engage a multidisciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world's most advanced research facilities, the Rensselaer Center for Biotechnology and Interdisciplinary Studies provides a state-of-the-art platform for collaborative research and world-class programs and symposia.
About Rensselaer
Rensselaer Polytechnic Institute, founded in 1824, is the nation's oldest technological university. The university offers bachelor's, master's, and doctoral degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research conducted in a wide range of fields, with particular emphasis in biotechnology, nanotechnology, information technology, and the media arts and technology. The Institute is well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.
Tiffany Lohwater
lohwatrpi
Rensselaer Polytechnic Institute
rpi/dept/NewsComm
Recalls of popular prescription drugs are raising public concern about the general safety of new pharmaceuticals. A collaborative group of researchers says that identifying which drug candidates are toxic early in the discovery process can help prevent harmful pharmaceuticals from being placed on the market in the first place, and they have developed a tool to do it.
Researchers at Rensselaer Polytechnic Institute, University of California-Berkeley, and Solidus Biosciences Inc. have developed a biochip, called the MetaChip, which can analyze drug candidates for toxicity and eliminate harmful ones before they advance to pre-clinical stages. Now beginning the second phase of funding for the National Institutes of Health (NIH)-supported project, researchers are working to optimize the technology for the end user: pharmaceutical and biotechnology companies. The researchers are working to bring the MetaChip to market within a year.
"Compounds can be screened early, quickly, and effectively by the MetaChip to prevent toxic drugs from getting through the discovery process, being put on the market, and then getting recalled, such as we've seen with several high-profile cases recently," says Jonathan Dordick, the Howard P. Isermann '42 Professor of Chemical and Biological Engineering at Rensselaer.
"Weeding out toxic compounds earlier would also allow pharmaceutical companies to evaluate more compounds and more efficiently identify those that are most likely to become successful drugs," adds Douglas Clark of the Chemical Engineering Department at the University of California-Berkeley.
Dordick and Clark are also the co-founders of Solidus Biosciences, a biotech company located at the Rensselaer Incubator for start-up businesses.
The MetaChip (metabolizing enzyme toxicology assay chip) mimics the effects of metabolism in the human liver where enzymes break down, neutralize, and excrete chemicals from food and pharmaceuticals. In many cases, the metabolized chemicals, called metabolites, are harmless or even beneficial. But some metabolites are toxic, and this toxicity can be difficult to predict or find at early stages of drug discovery with current testing methods.
"The relatively slow pace of technology development in toxicology and clinical safety evaluation that could be used in early phases of drug development continues to hinder the progression of lead compounds to pharmaceuticals," Dordick says. "In addition to safety concerns, drug discovery is an extremely costly process with more than $1 billion invested in each approved drug. For the first time, the MetaChip can enable the initial and high-throughput analysis of metabolism-induced toxicology to be performed before significant resources are invested in the drug's development."
Solidus Biosciences recently received a $1.7 million, three-year award from NIH through its Small Business Technology Transfer Program to optimize the MetaChip for market. Rensselaer will receive approximately $500,000 as a sub-contractor of the award. The technology has been patented by Rensselaer Polytechnic Institute and University of California-Berkeley and licensed exclusively to Solidus Biosciences.
The MetaChip uses a culturing method by combining enzyme catalysis with cell-based screening on a single microscale chip. The drug candidates are added to a chip containing approximately 2,000 combinations of the eight enzymes used in human liver metabolism and then sandwiched with a slide of human organ cells in order to detect toxic reactions to the compound. When toxic reactions are detected, the toxic drug compounds are eliminated as potential candidates for further development as new pharmaceuticals. The researchers are also working to develop an automated MetaReader device to quickly analyze the results.
Dordick, Clark, and collaborators published findings on the MetaChip in the Jan. 25, 2005 issue of Proceedings of the National Academy of Sciences in a paper titled "Metabolizing Enzyme Toxicology Assay Chip (MetaChip) for High-Throughput Microscale Toxicity Analyses." The peer-reviewed publication defines the technology and results of testing in more detail.
Development of the MetaChip technology is part of several NIH-funded research projects at Rensselaer seeking more efficient ways to synthesize and identify compounds that merit further development as possible new drugs.
Biotechnology and Interdisciplinary Studies at Rensselaer
At Rensselaer, faculty and students in diverse academic and research disciplines are collaborating at the intersection of the life sciences and engineering to encourage discovery and innovation. Rensselaer's four biotechnology research constellations - biocatalysis and metabolic engineering, functional tissue engineering and regenerative medicine, biocomputation and bioinformatics, and integrative systems biology - engage a multidisciplinary mix of faculty and students focused on the application of engineering and physical and information sciences to the life sciences. Ranked among the world's most advanced research facilities, the Rensselaer Center for Biotechnology and Interdisciplinary Studies provides a state-of-the-art platform for collaborative research and world-class programs and symposia.
About Rensselaer
Rensselaer Polytechnic Institute, founded in 1824, is the nation's oldest technological university. The university offers bachelor's, master's, and doctoral degrees in engineering, the sciences, information technology, architecture, management, and the humanities and social sciences. Institute programs serve undergraduates, graduate students, and working professionals around the world. Rensselaer faculty are known for pre-eminence in research conducted in a wide range of fields, with particular emphasis in biotechnology, nanotechnology, information technology, and the media arts and technology. The Institute is well known for its success in the transfer of technology from the laboratory to the marketplace so that new discoveries and inventions benefit human life, protect the environment, and strengthen economic development.
Tiffany Lohwater
lohwatrpi
Rensselaer Polytechnic Institute
rpi/dept/NewsComm
воскресенье, 29 мая 2011 г.
NASA Summer School Helps Create Pipeline Of Space Scientists
Students and scientists from around the globe and from throughout the U.S. have come to New York this month to participate in the fourth annual NASA Space Radiation Summer School at the U.S. Department of Energy's Brookhaven National Laboratory. The group will work in Brookhaven Lab's Medical Department and NASA Space Radiation Laboratory (NSRL) -- a unique facility that simulates the harsh radiation environment of outer space -- to study the possible risks astronauts may face during future long-term space flights. Thirty-nine students have participated in the program to date.
As NASA plans a mission to Mars, an outpost on the Moon, and exploration of near-Earth asteroids, many potential health risks to astronauts remain unknown. It is vitally important to learn how human space travelers will be affected by deep-space radiation and how best to protect them from harm. Space radiobiology, a relatively new field that blends the disciplines of physics and biology, addresses these questions.
"While there is a wealth of data describing the effects of conventional radiation like x-rays, the same is not true for the types of radiation present in space. It is essential to define the potential risks of exposure to space radiation and, if necessary, develop effective countermeasures to permit safe missions of longer durations than in the past," explained Peter Guida, Medical Department Liaison Scientist for this program at Brookhaven Lab. Guida is working with Eleanor Blakely of Lawrence Berkeley National Laboratory, the 2007 NASA Summer School Director.
Said Blakely, "Our goal is to attract the highest quality students from diverse scientific backgrounds and help train them to be the next wave of space radiation researchers." The program has three scientific modules: physics (led by Cary Zeitlin of Lawrence Berkeley), biology (led by Gregory Nelson of Loma Linda University Medical Center), and experimental methods (led by Betsy Sutherland of Brookhaven Lab).
Fifteen graduate students, post-doctoral fellows and working scientists, and four auditing professionals are participating in this year's summer school. The program is sponsored by NASA and organized and managed by Brookhaven Lab, Loma Linda University Medical Center, and Universities Space Research Association (a consortium of universities, research organizations, and governmental groups involved in space research).
The intensive, three-week course offers a unique physical and intellectual environment not duplicated in the nation's universities, medical schools or research institutes. Students participate in both classroom activities and scientific experiments, working side-by-side with top space scientists from research organizations such as NASA, Brookhaven Lab, Lawrence Berkeley, Loma Linda University, Columbia University, University of Pennsylvania, California Institute of Technology, UT Southwestern Medical Center and University of Maryland, Baltimore County. Experimental creativity and interdisciplinary approaches are emphasized. "This year's crop of students is the most internationally diverse yet, with 11 different countries represented," said Guida. "Even though the program is only in its fourth year, many of our graduates are already making contributions to the field."
Studies at NSRL (bnl/medical/NASA/LTSF.asp) simulate space radiation to learn how the intense rays may promote the development of cancer, as well as how this radiation can affect the central nervous system and other organ systems of the body. NSRL researchers are also looking at ways to protect against these dangers through shielding and other strategies to minimize the risk to space travelers.
NSRL is a $34-million facility that was built by Brookhaven Lab with funding from NASA with the cooperation of the Office of Nuclear Physics within the U.S. Department of Energy's Office of Science. Operational since 2003, the facility is part of the Lab's collider-accelerator complex, which is maintained by the DOE Office of Science's nuclear physics program and receives incremental operations and maintenance funding from NASA. It employs beams of heavy ions extracted from Brookhaven's Booster accelerator that are the best in the U.S. for studying the effects of radiation on living organisms. Scientists from more than 20 research institutions from throughout the U.S. and abroad work year-round at NSRL, supported mainly by NASA funding, to learn about the possible risks to space explorers exposed to deep-space radiation.
One of ten national laboratories overseen and funded primarily by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
For information on NASA Summer Student Program sponsors, please visit nasa/ (NASA),
usra/ (Universities Space Research Association), and
llu/ (Loma Linda University Medical Center).
Contact: Kelly Peterson
M Booth & Associates
As NASA plans a mission to Mars, an outpost on the Moon, and exploration of near-Earth asteroids, many potential health risks to astronauts remain unknown. It is vitally important to learn how human space travelers will be affected by deep-space radiation and how best to protect them from harm. Space radiobiology, a relatively new field that blends the disciplines of physics and biology, addresses these questions.
"While there is a wealth of data describing the effects of conventional radiation like x-rays, the same is not true for the types of radiation present in space. It is essential to define the potential risks of exposure to space radiation and, if necessary, develop effective countermeasures to permit safe missions of longer durations than in the past," explained Peter Guida, Medical Department Liaison Scientist for this program at Brookhaven Lab. Guida is working with Eleanor Blakely of Lawrence Berkeley National Laboratory, the 2007 NASA Summer School Director.
Said Blakely, "Our goal is to attract the highest quality students from diverse scientific backgrounds and help train them to be the next wave of space radiation researchers." The program has three scientific modules: physics (led by Cary Zeitlin of Lawrence Berkeley), biology (led by Gregory Nelson of Loma Linda University Medical Center), and experimental methods (led by Betsy Sutherland of Brookhaven Lab).
Fifteen graduate students, post-doctoral fellows and working scientists, and four auditing professionals are participating in this year's summer school. The program is sponsored by NASA and organized and managed by Brookhaven Lab, Loma Linda University Medical Center, and Universities Space Research Association (a consortium of universities, research organizations, and governmental groups involved in space research).
The intensive, three-week course offers a unique physical and intellectual environment not duplicated in the nation's universities, medical schools or research institutes. Students participate in both classroom activities and scientific experiments, working side-by-side with top space scientists from research organizations such as NASA, Brookhaven Lab, Lawrence Berkeley, Loma Linda University, Columbia University, University of Pennsylvania, California Institute of Technology, UT Southwestern Medical Center and University of Maryland, Baltimore County. Experimental creativity and interdisciplinary approaches are emphasized. "This year's crop of students is the most internationally diverse yet, with 11 different countries represented," said Guida. "Even though the program is only in its fourth year, many of our graduates are already making contributions to the field."
Studies at NSRL (bnl/medical/NASA/LTSF.asp) simulate space radiation to learn how the intense rays may promote the development of cancer, as well as how this radiation can affect the central nervous system and other organ systems of the body. NSRL researchers are also looking at ways to protect against these dangers through shielding and other strategies to minimize the risk to space travelers.
NSRL is a $34-million facility that was built by Brookhaven Lab with funding from NASA with the cooperation of the Office of Nuclear Physics within the U.S. Department of Energy's Office of Science. Operational since 2003, the facility is part of the Lab's collider-accelerator complex, which is maintained by the DOE Office of Science's nuclear physics program and receives incremental operations and maintenance funding from NASA. It employs beams of heavy ions extracted from Brookhaven's Booster accelerator that are the best in the U.S. for studying the effects of radiation on living organisms. Scientists from more than 20 research institutions from throughout the U.S. and abroad work year-round at NSRL, supported mainly by NASA funding, to learn about the possible risks to space explorers exposed to deep-space radiation.
One of ten national laboratories overseen and funded primarily by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. Brookhaven is operated and managed for DOE's Office of Science by Brookhaven Science Associates, a limited-liability company founded by the Research Foundation of State University of New York on behalf of Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
For information on NASA Summer Student Program sponsors, please visit nasa/ (NASA),
usra/ (Universities Space Research Association), and
llu/ (Loma Linda University Medical Center).
Contact: Kelly Peterson
M Booth & Associates
Royal Society Invests In Innovation
The Royal Society has today announced that its Enterprise Fund is open for business with an initial ВЈ5 million raised through donations from several of the UK's most highly respected business leaders
The Royal Society Enterprise Fund will open its doors to scientific enterprises and innovators seeking early stage investment of between ВЈ250,000 and ВЈ2 million. The Fund's initial focus will be on backing commercially exciting opportunities based on advances in the physical sciences and engineering.
"There is a lot of talk in the UK at the moment about innovation but the Royal Society is taking action in the hope of stimulating a genuine cultural change. We have successful scientific entrepreneurs in the UK but we should have a lot more. Challenges such as climate change offer great opportunities for the UK to provide global economic leadership based on scientific endeavour." Said Sir Peter Williams, Vice-President of the Royal Society.
The Royal Society believes that innovation is essential in today's knowledge economy and to bring the maximum benefit of science to pressing human and environmental challenges. By leading this effort, the Society seeks to catalyse a fundamental culture change within the scientific community by encouraging scientists and engineers to seek entrepreneurial applications of their research.
Andrew Mackintosh, Chief Executive of the Royal Society Enterprise Fund, commented: "Our mission is to create a bridge between today's early scientific ideas and tomorrow's technological and commercial winners. Early stage ventures present the highest commercial and financial risk and are therefore starved of investment. Our philanthropic structure combined with our highly commercial approach and unrivalled access to the UK science base will unlock new technologies and ideas that will bring significant and lasting economic and societal benefits to the UK."
The Society has identified three key gaps within the UK innovation environment: a financing gap for early-stage, seed investments under ВЈ2 million; a preparedness gap with technology businesses going to the market for financing too early; and a research gap with comparatively poor funding of physical sciences and engineering ventures.
The Enterprise Fund will encourage this culture change and address these gaps by raising ВЈ20 million from donations using a model of venture philanthropy to support science. The philanthropic structure of the Enterprise Fund will enable all financial gains to be returned to the Fund for reinvestment in future scientific innovations, making it a sustainable living endowment. Within 7 months of its launch, The Royal Society is pleased to announce that it has secured donations amounting to over ВЈ5 million from a number of the UK's most highly regarded business leaders, entrepreneurs and philanthropists. Lead donors to the Enterprise Fund include:
- Lord Sainsbury of Turville, former Science Minister and Chair of the Royal Society 350th Anniversary Campaign
- Roger Brooke, Founder of Candover Investments and a founding director of IP Group
- Adrian Beecroft, Senior Managing Partner of Apax Partners, Member of the Royal Society 350th Anniversary Campaign Board
- Stelio Stefanou, Former Chairman of Accord Plc
The Fund will be run on a commercial basis and will leverage the unrivalled market and technical assessment capabilities of the Fellows of the Royal Society who represent all areas of science, engineering and medicine. The Fellows form a global scientific network of the highest calibre, which includes nearly 70 Nobel Laureates.
Donor and advisor to the Enterprise Fund, Roger Brooke said: "The Enterprise Fund is an exciting, measurable, sustainable and high impact model of philanthropy strengthening science and our future economic health. The Royal Society is uniquely placed to drive this forward. I have become involved to help ensure the UK has a strong future and the fruits of science are brought to society."
Over the coming months, the Enterprise Fund will seek to raise funds from additional donors towards its target fund size of ВЈ20 million. Lead gifts are sought from visionary leaders who wish to support scientific innovation in the UK and will become members of the prestigious Royal Society Presidents' Circle, joining like-minded leaders who have made major benefactions to the Royal Society's ВЈ100 million 350th Anniversary Campaign.
1. The Royal Society is an independent academy promoting the natural and applied sciences. Founded in 1660, the Society has three roles, as the UK academy of science, as a learned Society, and as a funding agency. It responds to individual demand with selection by merit, not by field. As we prepare for our 350th anniversary in 2010, we are working to achieve five strategic priorities to:
- Invest in future scientific leaders and in innovation
- Influence policymaking with the best scientific advice
- Invigorate science and mathematics education
- Increase access to the best science internationally
- Inspire an interest in the joy, wonder and excitement of scientific discovery
2. A panel of business experts provides strategic guidance to the Enterprise Fund. They include:
- Adrian Beecroft, FInstP, Senior Managing Partner, Apax Partners
- Roger Brooke, Founder of Candover Investments, and a founding director of IP Group
- Stephen Brooke, Founder and Managing Partner of Swarraton Partners
- Anne Glover, Founder and CEO of Amadeus Capital Partners
- Sir Peter Williams CBE FREng FRS, Treasurer of the Royal Society
3. Further information on the process for making philanthropic donations and the Royal Society's ВЈ100 million fundraising campaign for 2010 can be found at royalsociety/campaign
4. Further information on submitting investment proposals to the Royal Society Enterprise Fund can be found on the Royal Society's website at royalsociety/enterprisefund/
The Royal Society
The Royal Society Enterprise Fund will open its doors to scientific enterprises and innovators seeking early stage investment of between ВЈ250,000 and ВЈ2 million. The Fund's initial focus will be on backing commercially exciting opportunities based on advances in the physical sciences and engineering.
"There is a lot of talk in the UK at the moment about innovation but the Royal Society is taking action in the hope of stimulating a genuine cultural change. We have successful scientific entrepreneurs in the UK but we should have a lot more. Challenges such as climate change offer great opportunities for the UK to provide global economic leadership based on scientific endeavour." Said Sir Peter Williams, Vice-President of the Royal Society.
The Royal Society believes that innovation is essential in today's knowledge economy and to bring the maximum benefit of science to pressing human and environmental challenges. By leading this effort, the Society seeks to catalyse a fundamental culture change within the scientific community by encouraging scientists and engineers to seek entrepreneurial applications of their research.
Andrew Mackintosh, Chief Executive of the Royal Society Enterprise Fund, commented: "Our mission is to create a bridge between today's early scientific ideas and tomorrow's technological and commercial winners. Early stage ventures present the highest commercial and financial risk and are therefore starved of investment. Our philanthropic structure combined with our highly commercial approach and unrivalled access to the UK science base will unlock new technologies and ideas that will bring significant and lasting economic and societal benefits to the UK."
The Society has identified three key gaps within the UK innovation environment: a financing gap for early-stage, seed investments under ВЈ2 million; a preparedness gap with technology businesses going to the market for financing too early; and a research gap with comparatively poor funding of physical sciences and engineering ventures.
The Enterprise Fund will encourage this culture change and address these gaps by raising ВЈ20 million from donations using a model of venture philanthropy to support science. The philanthropic structure of the Enterprise Fund will enable all financial gains to be returned to the Fund for reinvestment in future scientific innovations, making it a sustainable living endowment. Within 7 months of its launch, The Royal Society is pleased to announce that it has secured donations amounting to over ВЈ5 million from a number of the UK's most highly regarded business leaders, entrepreneurs and philanthropists. Lead donors to the Enterprise Fund include:
- Lord Sainsbury of Turville, former Science Minister and Chair of the Royal Society 350th Anniversary Campaign
- Roger Brooke, Founder of Candover Investments and a founding director of IP Group
- Adrian Beecroft, Senior Managing Partner of Apax Partners, Member of the Royal Society 350th Anniversary Campaign Board
- Stelio Stefanou, Former Chairman of Accord Plc
The Fund will be run on a commercial basis and will leverage the unrivalled market and technical assessment capabilities of the Fellows of the Royal Society who represent all areas of science, engineering and medicine. The Fellows form a global scientific network of the highest calibre, which includes nearly 70 Nobel Laureates.
Donor and advisor to the Enterprise Fund, Roger Brooke said: "The Enterprise Fund is an exciting, measurable, sustainable and high impact model of philanthropy strengthening science and our future economic health. The Royal Society is uniquely placed to drive this forward. I have become involved to help ensure the UK has a strong future and the fruits of science are brought to society."
Over the coming months, the Enterprise Fund will seek to raise funds from additional donors towards its target fund size of ВЈ20 million. Lead gifts are sought from visionary leaders who wish to support scientific innovation in the UK and will become members of the prestigious Royal Society Presidents' Circle, joining like-minded leaders who have made major benefactions to the Royal Society's ВЈ100 million 350th Anniversary Campaign.
1. The Royal Society is an independent academy promoting the natural and applied sciences. Founded in 1660, the Society has three roles, as the UK academy of science, as a learned Society, and as a funding agency. It responds to individual demand with selection by merit, not by field. As we prepare for our 350th anniversary in 2010, we are working to achieve five strategic priorities to:
- Invest in future scientific leaders and in innovation
- Influence policymaking with the best scientific advice
- Invigorate science and mathematics education
- Increase access to the best science internationally
- Inspire an interest in the joy, wonder and excitement of scientific discovery
2. A panel of business experts provides strategic guidance to the Enterprise Fund. They include:
- Adrian Beecroft, FInstP, Senior Managing Partner, Apax Partners
- Roger Brooke, Founder of Candover Investments, and a founding director of IP Group
- Stephen Brooke, Founder and Managing Partner of Swarraton Partners
- Anne Glover, Founder and CEO of Amadeus Capital Partners
- Sir Peter Williams CBE FREng FRS, Treasurer of the Royal Society
3. Further information on the process for making philanthropic donations and the Royal Society's ВЈ100 million fundraising campaign for 2010 can be found at royalsociety/campaign
4. Further information on submitting investment proposals to the Royal Society Enterprise Fund can be found on the Royal Society's website at royalsociety/enterprisefund/
The Royal Society
суббота, 28 мая 2011 г.
2 UCSD Physician-Scientists Named To Association Of American Physicians
The Association of American Physicians (AAP) has elected two physician-scientists from the University of California, San Diego School of Medicine faculty as new members: Patricia Finn, M.D., Ph.D., Chief of Pulmonary and Critical Care Medicine and Anthony Wynshaw-Boris, M.D., Ph.D., Director, Center for Human Genetics and Genomics Chief, Division of Genetics, Department of Pediatrics.
The Association of American Physicians is a nonprofit, professional organization founded for "the advancement of scientific and practical medicine." Today, the Association is composed of about 1,000 active members and approximately 550 emeritus and honorary members from the United States, Canada and other countries.
Each year, the Council of the Association elects 60 new members. This year, 67 inductees were announced at the AAP national meeting.
Finn was recognized for her pioneering research regarding the mechanisms behind the development of asthma and other inflammatory lung diseases. Finn is especially interested in understanding how asthma develops early in life and discovering new ways to prevent and treat asthma and other related diseases.
Wynshaw-Boris' focus is on the genetic manipulation of mice to generate a number of mouse models which replicate human diseases. He has used the insights obtained from these animals to define novel pathways for disease pathogenesis and therapeutics.
Contact: Kimberly Edwards
University of California - San Diego
The Association of American Physicians is a nonprofit, professional organization founded for "the advancement of scientific and practical medicine." Today, the Association is composed of about 1,000 active members and approximately 550 emeritus and honorary members from the United States, Canada and other countries.
Each year, the Council of the Association elects 60 new members. This year, 67 inductees were announced at the AAP national meeting.
Finn was recognized for her pioneering research regarding the mechanisms behind the development of asthma and other inflammatory lung diseases. Finn is especially interested in understanding how asthma develops early in life and discovering new ways to prevent and treat asthma and other related diseases.
Wynshaw-Boris' focus is on the genetic manipulation of mice to generate a number of mouse models which replicate human diseases. He has used the insights obtained from these animals to define novel pathways for disease pathogenesis and therapeutics.
Contact: Kimberly Edwards
University of California - San Diego
пятница, 27 мая 2011 г.
Sex Differences In Responsiveness To Begging In A Cooperative Mammal
In many animals, parents feed hungry young in response to begging, with mothers often responding more than fathers.
In species living in cooperative groups, both parents and helpers feed young, but less is known about how they respond to begging.
We played low and high rate begging calls to meerkats and found that, while parents and helpers respond in the same way, females are better at feeding hungrier young than males.
This may be because female meerkats stay in the group and survival of the pups matters more to them.
Biology Letters publishes short, high-quality articles from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of cutting-edge research communications.
Biology Letters
In species living in cooperative groups, both parents and helpers feed young, but less is known about how they respond to begging.
We played low and high rate begging calls to meerkats and found that, while parents and helpers respond in the same way, females are better at feeding hungrier young than males.
This may be because female meerkats stay in the group and survival of the pups matters more to them.
Biology Letters publishes short, high-quality articles from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of cutting-edge research communications.
Biology Letters
четверг, 26 мая 2011 г.
Novel Mouse Model Of Demyelinating Disorder
In the February 1st issue of G&D, Dr. Brian Popko (The University of Chicago) and colleagues describe how mutation of a gene called ZFP191 leads to disordered CNS myelination in mice -- reminiscent of what is seen in human multiple sclerosis (MS) patients.
The paper will be released online ahead of print at genesdev.
MS is a chronic autoimmune disorder, in which the body attacks and destroys the myelin sheath that insulates and protects nerve fibers of the central nervous system (the brain, spinal cord and optic nerves). Demyelination disrupts the conduction of electrical impulses along nerve fibers, and results in regional neural deficits. MS symptoms range from tingling and numbness in limbs, to loss of vision and paralysis.
It is estimated that MS affects 400,000 people in the US and approximately 2.5 million worldwide.
Dr. Popko and colleagues identified a gene called ZFP191 as being necessary for the development of oligodendrocyte cells, which - in their fully mature form - produce myelin. The researchers found that mice harboring a single mutation in ZFP191 display tremors and seizures, caused by a severe deficiency in CNS myelination.
ZFP191 appears to be the first factor identified to be critical for the myelinating function of oligodendrocytes.
The failure of Zfp191-mutant mouse oligodendrocytes to successfully myelinate their targets is reminiscent of human MS lesions, where re-myelination of damaged tracts fails to occur efficiently even when apparently mature oligodendrocytes are present in the area.
While further research to delineate the precise targets of ZFP191 is needed, this work holds promising clinical value as a potential therapeutic pathway to promote re-myelination, reduce the accumulation of MS lesions and slow disease progression.
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
The paper will be released online ahead of print at genesdev.
MS is a chronic autoimmune disorder, in which the body attacks and destroys the myelin sheath that insulates and protects nerve fibers of the central nervous system (the brain, spinal cord and optic nerves). Demyelination disrupts the conduction of electrical impulses along nerve fibers, and results in regional neural deficits. MS symptoms range from tingling and numbness in limbs, to loss of vision and paralysis.
It is estimated that MS affects 400,000 people in the US and approximately 2.5 million worldwide.
Dr. Popko and colleagues identified a gene called ZFP191 as being necessary for the development of oligodendrocyte cells, which - in their fully mature form - produce myelin. The researchers found that mice harboring a single mutation in ZFP191 display tremors and seizures, caused by a severe deficiency in CNS myelination.
ZFP191 appears to be the first factor identified to be critical for the myelinating function of oligodendrocytes.
The failure of Zfp191-mutant mouse oligodendrocytes to successfully myelinate their targets is reminiscent of human MS lesions, where re-myelination of damaged tracts fails to occur efficiently even when apparently mature oligodendrocytes are present in the area.
While further research to delineate the precise targets of ZFP191 is needed, this work holds promising clinical value as a potential therapeutic pathway to promote re-myelination, reduce the accumulation of MS lesions and slow disease progression.
Source: Heather Cosel-Pieper
Cold Spring Harbor Laboratory
Link Between Diabetes And Heart Disease Study Funded By NIH Award
A multidisciplinary team of researchers from Columbia University Medical Center has received a $10.8 million, five-year Program Project Grant (PPG) from the National Institutes of Health to investigate why people with type 2 diabetes are dangerously susceptible to heart disease, the leading cause of death for people suffering from diabetes.
In a 2006 Nature Medicine op-ed, Elizabeth (Betsy) G. Nabel, M.D., director of The National Heart Lung and Blood Institute (NHLBI) and Allen M. Spiegel, M.D., then director of The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), called for researchers from different disciplines to study the two top killers of Americans -- diabetes and heart disease -- in a more unified fashion and specifically to investigate the connection between insulin signaling and atherosclerosis.
Ira Tabas, M.D., Ph.D., professor and vice-chairman of research in the Department of Medicine at Columbia's College of Physicians & Surgeons, Alan Tall, M.D., a professor of medicine in the Division of Molecular Medicine, and Domenico Accili, M.D., a professor of medicine and the co-director of research at CUMC's Naomi Berrie Diabetes Center, answered that call. The three investigators bring distinctly unique expertise in their respective disciplines and years of experience to bear on the problem of atherosclerosis and its effects on diabetes.
"The worldwide epidemic of obesity has led to staggering rates of type 2 diabetes and, in turn, the deadly consequences of heart disease," said Dr. Tabas, the grant's principal investigator. "If we could better understand the role that insulin resistance plays in the progression of atherosclerosis, we may be able to develop therapies to prevent the serious consequences from both of these diseases."
Expansion of Earlier Work on Macrophage Death's Link to Atherosclerosis
The molecular and cellular mechanisms linking the insulin resistance found in diabetics to atherosclerosis are presently poorly understood. Columbia researchers will use this grant to identify pathways that contribute to accelerated atherosclerotic lesion progression in insulin-resistant states. They will focus on two cell types -- macrophages and hepatocytes.
Earlier research led by Dr. Tabas explained what causes the death of macrophages, the white blood cells that accumulate in the cholesterol-laden plaques in arteries of patients with atherosclerosis. Those dead macrophages pile up to form what Dr. Tabas calls a "macrophage graveyard" or necrotic core causing plaque rupture. The rupture can stimulate the formation of clots that can block blood flow and cause heart attacks and strokes. According to Dr. Tabas, the biggest danger in atherosclerosis comes not so much from the plaque growing to a point that it blocks the artery, as is often believed, but rather from smaller plaques becoming unstable and prone to rupture. According to Dr. Tabas, it turns out that plaques from subjects with diabetes have larger necrotic cores, raising the possibility that amplified plaque macrophage death is an important factor in the higher rate of heart disease in diabetics.
Dr. Tall, working with Drs. Tabas and Accili, focused on the fact that macrophages ordinarily contain insulin receptors, but patients with type 2 diabetes are insulin-resistant, meaning these receptors function poorly. The Columbia researchers found in earlier research, published in Cell Metabolism in 2006, that more macrophage death and plaque necrosis occurred in a mouse model of macrophage insulin resistance. This suggests that in patients with type 2 diabetes, insulin resistance promotes macrophage death, which can lead to atherosclerosis.
Exploring Role of Lipoproteins, Insulin Action on Artery Degeneration
Dr. Tall's laboratory uses molecular, genomic and cellular approaches to investigate basic aspects of the pathogenesis of atherosclerosis. In addition to working with Dr. Tabas on macrophage death pathways, Dr. Tall will work with Dr. Accili to investigate pathways involved in production of lipoproteins, such as very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL, often called bad cholesterol), in insulin-resistant states. This will offer clues as to how high atherogenic lipoprotein levels contribute to heart disease in people with diabetes.
Dr. Domenico Accili 's research is focused on the pathogenesis of insulin action and resistance and its role in type 2 diabetes. He plans to use new mouse models to investigate potentially pro-atherogenic or plaque-causing insulin actions in the liver and macrophages as part of this NIH grant. Dr. Accili's lab has recently shown that insulin action in liver, brain and beta cells is sufficient to confer insulin sensitivity onto the whole organism and protect against the development of diabetes in mice.
In addition, the lead investigators will call upon the biostatistical and mouse modeling expertise of Carrie L. Welch, Ph.D., associate research scientist, and Rajasekhar Ramakrishnan, Sc.D., research scientist and acting director of the division of biomathematics, to help with the design and analysis of mouse phenotype data and microarray experiments.
This program project grant is jointly funded by the NIDDK the NHLBI. The NIH program project grant mechanism is designed to support research in which the funding of several interdependent projects as a group offers significant scientific advantages over support of these same projects as individual regular research grants.
Heart Disease & Diabetes Stats
Chronic heart disease -- usually caused by atherosclerosis or fatty deposits in the inner walls of the arteries that carry blood throughout the body from the heart -- can lead to heart attacks, stroke and sudden death. Heart disease accounts for 65 percent of diabetic deaths each year, according to NIDDK. NIDDK estimates that adults with diabetes have heart disease death rates about two to four times higher than adults without diabetes. The risk for stroke is two to four times higher among people with diabetes.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions.
Source: Elizabeth Streich
Columbia University Medical Center
In a 2006 Nature Medicine op-ed, Elizabeth (Betsy) G. Nabel, M.D., director of The National Heart Lung and Blood Institute (NHLBI) and Allen M. Spiegel, M.D., then director of The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), called for researchers from different disciplines to study the two top killers of Americans -- diabetes and heart disease -- in a more unified fashion and specifically to investigate the connection between insulin signaling and atherosclerosis.
Ira Tabas, M.D., Ph.D., professor and vice-chairman of research in the Department of Medicine at Columbia's College of Physicians & Surgeons, Alan Tall, M.D., a professor of medicine in the Division of Molecular Medicine, and Domenico Accili, M.D., a professor of medicine and the co-director of research at CUMC's Naomi Berrie Diabetes Center, answered that call. The three investigators bring distinctly unique expertise in their respective disciplines and years of experience to bear on the problem of atherosclerosis and its effects on diabetes.
"The worldwide epidemic of obesity has led to staggering rates of type 2 diabetes and, in turn, the deadly consequences of heart disease," said Dr. Tabas, the grant's principal investigator. "If we could better understand the role that insulin resistance plays in the progression of atherosclerosis, we may be able to develop therapies to prevent the serious consequences from both of these diseases."
Expansion of Earlier Work on Macrophage Death's Link to Atherosclerosis
The molecular and cellular mechanisms linking the insulin resistance found in diabetics to atherosclerosis are presently poorly understood. Columbia researchers will use this grant to identify pathways that contribute to accelerated atherosclerotic lesion progression in insulin-resistant states. They will focus on two cell types -- macrophages and hepatocytes.
Earlier research led by Dr. Tabas explained what causes the death of macrophages, the white blood cells that accumulate in the cholesterol-laden plaques in arteries of patients with atherosclerosis. Those dead macrophages pile up to form what Dr. Tabas calls a "macrophage graveyard" or necrotic core causing plaque rupture. The rupture can stimulate the formation of clots that can block blood flow and cause heart attacks and strokes. According to Dr. Tabas, the biggest danger in atherosclerosis comes not so much from the plaque growing to a point that it blocks the artery, as is often believed, but rather from smaller plaques becoming unstable and prone to rupture. According to Dr. Tabas, it turns out that plaques from subjects with diabetes have larger necrotic cores, raising the possibility that amplified plaque macrophage death is an important factor in the higher rate of heart disease in diabetics.
Dr. Tall, working with Drs. Tabas and Accili, focused on the fact that macrophages ordinarily contain insulin receptors, but patients with type 2 diabetes are insulin-resistant, meaning these receptors function poorly. The Columbia researchers found in earlier research, published in Cell Metabolism in 2006, that more macrophage death and plaque necrosis occurred in a mouse model of macrophage insulin resistance. This suggests that in patients with type 2 diabetes, insulin resistance promotes macrophage death, which can lead to atherosclerosis.
Exploring Role of Lipoproteins, Insulin Action on Artery Degeneration
Dr. Tall's laboratory uses molecular, genomic and cellular approaches to investigate basic aspects of the pathogenesis of atherosclerosis. In addition to working with Dr. Tabas on macrophage death pathways, Dr. Tall will work with Dr. Accili to investigate pathways involved in production of lipoproteins, such as very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL, often called bad cholesterol), in insulin-resistant states. This will offer clues as to how high atherogenic lipoprotein levels contribute to heart disease in people with diabetes.
Dr. Domenico Accili 's research is focused on the pathogenesis of insulin action and resistance and its role in type 2 diabetes. He plans to use new mouse models to investigate potentially pro-atherogenic or plaque-causing insulin actions in the liver and macrophages as part of this NIH grant. Dr. Accili's lab has recently shown that insulin action in liver, brain and beta cells is sufficient to confer insulin sensitivity onto the whole organism and protect against the development of diabetes in mice.
In addition, the lead investigators will call upon the biostatistical and mouse modeling expertise of Carrie L. Welch, Ph.D., associate research scientist, and Rajasekhar Ramakrishnan, Sc.D., research scientist and acting director of the division of biomathematics, to help with the design and analysis of mouse phenotype data and microarray experiments.
This program project grant is jointly funded by the NIDDK the NHLBI. The NIH program project grant mechanism is designed to support research in which the funding of several interdependent projects as a group offers significant scientific advantages over support of these same projects as individual regular research grants.
Heart Disease & Diabetes Stats
Chronic heart disease -- usually caused by atherosclerosis or fatty deposits in the inner walls of the arteries that carry blood throughout the body from the heart -- can lead to heart attacks, stroke and sudden death. Heart disease accounts for 65 percent of diabetic deaths each year, according to NIDDK. NIDDK estimates that adults with diabetes have heart disease death rates about two to four times higher than adults without diabetes. The risk for stroke is two to four times higher among people with diabetes.
Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, nurses, dentists, and public health professionals at the College of Physicians & Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions.
Source: Elizabeth Streich
Columbia University Medical Center
среда, 25 мая 2011 г.
2.4 Million Euros Awarded For Promotion Of The Healing Process After A Heart Attack
Prof. Stefanie Dimmeler, a researcher and director of the Institute for Cardiovascular Regeneration at Frankfurt's University Hospital has been awarded an 'ERC Advanced Grant' from the European Research Council to support her research work over the next five years. She will be investigating how to improve the healing process following a heart attack by promoting cardiovascular regeneration and the repair of heart tissue. This research application is one of eleven - Life Science - projects in Germany to be selected for funding, chosen from approximately 800 competitive applications from all over Europe.
Heart attacks and circulatory disease are still the most common cause of death in Western industrialised nations. According to recent findings, small pieces of composed of ribonucleic acids (micro-RNAs) affect the synthesis of hundreds of proteins that play a role in these diseases. The aim is to discover new inhibitors for this regulatory system so that heart tissue can recover after it has been deprived of oxygen. These micro-RNAs and their inhibitors also appear to be suitable for the targeted activation of stem cells, which are already successfully being used at the Frankfurt University Hospital to treat patients who have had a heart attack or suffer from cardiac insufficiency. Since the risk of heart disease increases with age, the researchers will also be looking at how micro-RNAs affect cellular malfunction and degeneration during aging.
Stefanie Dimmeler is the fourth research scientist at Frankfurt's Goethe University to have been selected by the Scientific Council of the ERC. Prof. Roman Inderst, an economic scientist, has been awarded an ERC Advanced Grant for his work on 'Regulating Retail Finance' and an ERC Starting Grant was won by Kira Kosnick, a cultural anthropologist and Junior Professor at the university, who is investigating Вґ Ethnic Club Cultures in Urban Europe. Prof. Magnus Rueping, a chemist, is also among the successful candidates in the first round of the ERC Starting Grants.
ERC grants, initiated by the European Research Council in 2007, are intended to support high-risk and demanding projects at research institutions in EU Member States or associated countries, regardless of the nationality of the researcher. Through these grants, the ERC hopes to go some way towards mitigating the brain drain to the United States, and to make Europe an attractive option for top scientists in the face of worldwide competition.
Goethe - University Frankfurt will serve as applicant host institution for a young Russian physicist from a research institution in California in the current ERC Starting Grant Call 2008, an example of a promising attempt to reverse the brain drain in favour of Europe.
For further information please contact:
Prof. Dr. Stefanie Dimmeler, (Assistant: Larissa Hill), Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Campus Niederrad, Frankfurt am Main, Germany
Source: Larissa Hill
Goethe University Frankfurt
Heart attacks and circulatory disease are still the most common cause of death in Western industrialised nations. According to recent findings, small pieces of composed of ribonucleic acids (micro-RNAs) affect the synthesis of hundreds of proteins that play a role in these diseases. The aim is to discover new inhibitors for this regulatory system so that heart tissue can recover after it has been deprived of oxygen. These micro-RNAs and their inhibitors also appear to be suitable for the targeted activation of stem cells, which are already successfully being used at the Frankfurt University Hospital to treat patients who have had a heart attack or suffer from cardiac insufficiency. Since the risk of heart disease increases with age, the researchers will also be looking at how micro-RNAs affect cellular malfunction and degeneration during aging.
Stefanie Dimmeler is the fourth research scientist at Frankfurt's Goethe University to have been selected by the Scientific Council of the ERC. Prof. Roman Inderst, an economic scientist, has been awarded an ERC Advanced Grant for his work on 'Regulating Retail Finance' and an ERC Starting Grant was won by Kira Kosnick, a cultural anthropologist and Junior Professor at the university, who is investigating Вґ Ethnic Club Cultures in Urban Europe. Prof. Magnus Rueping, a chemist, is also among the successful candidates in the first round of the ERC Starting Grants.
ERC grants, initiated by the European Research Council in 2007, are intended to support high-risk and demanding projects at research institutions in EU Member States or associated countries, regardless of the nationality of the researcher. Through these grants, the ERC hopes to go some way towards mitigating the brain drain to the United States, and to make Europe an attractive option for top scientists in the face of worldwide competition.
Goethe - University Frankfurt will serve as applicant host institution for a young Russian physicist from a research institution in California in the current ERC Starting Grant Call 2008, an example of a promising attempt to reverse the brain drain in favour of Europe.
For further information please contact:
Prof. Dr. Stefanie Dimmeler, (Assistant: Larissa Hill), Institute of Cardiovascular Regeneration, Centre for Molecular Medicine, Campus Niederrad, Frankfurt am Main, Germany
Source: Larissa Hill
Goethe University Frankfurt
вторник, 24 мая 2011 г.
Link Between Key Protein Molecule And Diverse Human Chronic Inflammatory Diseases
Liwu Li, associate professor of biological sciences at Virginia Tech, has revealed a common connection between the cellular innate immunity network and human chronic inflammatory diseases, including atherosclerosis, Type 2 Diabetes, and neurodegenerative diseases. The finding presents a viable cellular and molecular target for the diagnosis and treatment of serious human inflammatory diseases, according to Li.
"Researchers and physicians have long recognized that there is an association between these conditions. For example, obesity increases the risk of heart attack or stroke, Type 2 Diabetes or insulin resistance, and Alzheimer's Disease," said Li, who is the founding director of the Inflammation Center at Virginia Tech.
"Inflammation is the common mechanism," he said. "Inflammation is a double-edged sword. Proper inflammation is necessary to fend off infection and abnormal cell growth. On the other hand, excessive inflammation contributes to diverse chronic diseases, including atherosclerosis, diabetes, and lupus." However, the complex cellular and molecular networks controlling inflammation are still poorly understood, he said. "The lack of understanding impedes our progress in treating serious chronic inflammatory diseases."
In a series of studies published throughout the last decade*, Li's group has defined several critical signaling networks essential for the modulation of inflammation. In particular, a key cellular protein kinase named interlukin-1 receptor associated kinase 1 (IRAK-1) was shown to be critical for processing diverse inflammatory signals, including microbial products, cytokines, and insulin. Li's group discovered that excessive IRAK-1 activation is linked with the risk of atherosclerosis and diabetes. Using transgenic mice without the IRAK-1 gene, Li's group demonstrated that IRAK-1 deficient mice are protected from developing atherosclerosis and insulin resistance.
At the molecular level, Li's laboratory discovered that IRAK-1 prefers to phosphorylate transcription factors harboring the Serine-Proline motif including STAT-3 and NFAT. Subsequently, STAT-3 and NFAT are involved in modulating the expression of distinct inflammatory mediators responsible for the excessive activation of specialized macrophages and T cells. These cells eventually contribute to diverse inflammatory symptoms including cardiovascular diseases, diabetes, Alzheimer's diseases, and lupus. "Chemical compounds targeting this molecule will have enormous therapeutic potential," Li said.
"There is still a long way to go for finding the actual cure for these diseases," he said. "That is why we are combining expertise from various disciplines, including experimental biology and computational simulation. The Inflammation Center integrates faculties with expertise in experimental molecular biology, cutting edge imaging of inflamed cells and tissues, computational simulation of cellular signaling networks, human and animal studies, and nano-technologies designing novel intervention."
Virginia Tech Intellectual Properties Inc. (VTIP) filed a patent application for Li's discovery and its use as a diagnostic tool and treatment strategy. "This technology will still take some time before there is a product," said Li.
Li's research is funded by the National Institutes of Health.
*The most recent publication from Li's group appeared in the September 2008 issue of Molecular Immunology, "The interleukin-1 receptor associated kinase 1 contributes to the regulation of NFAT," by Dongmei Wang, Stephan Fasciano, Liwu Li (available online Aug. 8, 2008.), pages 3902-3908.
Learn more about Li's research at: biology.vt/faculty/li
For more information about the patent, visit: vtip/availableTech/technology.php?id=185933li
Source: Susan Trulove
Virginia Tech
"Researchers and physicians have long recognized that there is an association between these conditions. For example, obesity increases the risk of heart attack or stroke, Type 2 Diabetes or insulin resistance, and Alzheimer's Disease," said Li, who is the founding director of the Inflammation Center at Virginia Tech.
"Inflammation is the common mechanism," he said. "Inflammation is a double-edged sword. Proper inflammation is necessary to fend off infection and abnormal cell growth. On the other hand, excessive inflammation contributes to diverse chronic diseases, including atherosclerosis, diabetes, and lupus." However, the complex cellular and molecular networks controlling inflammation are still poorly understood, he said. "The lack of understanding impedes our progress in treating serious chronic inflammatory diseases."
In a series of studies published throughout the last decade*, Li's group has defined several critical signaling networks essential for the modulation of inflammation. In particular, a key cellular protein kinase named interlukin-1 receptor associated kinase 1 (IRAK-1) was shown to be critical for processing diverse inflammatory signals, including microbial products, cytokines, and insulin. Li's group discovered that excessive IRAK-1 activation is linked with the risk of atherosclerosis and diabetes. Using transgenic mice without the IRAK-1 gene, Li's group demonstrated that IRAK-1 deficient mice are protected from developing atherosclerosis and insulin resistance.
At the molecular level, Li's laboratory discovered that IRAK-1 prefers to phosphorylate transcription factors harboring the Serine-Proline motif including STAT-3 and NFAT. Subsequently, STAT-3 and NFAT are involved in modulating the expression of distinct inflammatory mediators responsible for the excessive activation of specialized macrophages and T cells. These cells eventually contribute to diverse inflammatory symptoms including cardiovascular diseases, diabetes, Alzheimer's diseases, and lupus. "Chemical compounds targeting this molecule will have enormous therapeutic potential," Li said.
"There is still a long way to go for finding the actual cure for these diseases," he said. "That is why we are combining expertise from various disciplines, including experimental biology and computational simulation. The Inflammation Center integrates faculties with expertise in experimental molecular biology, cutting edge imaging of inflamed cells and tissues, computational simulation of cellular signaling networks, human and animal studies, and nano-technologies designing novel intervention."
Virginia Tech Intellectual Properties Inc. (VTIP) filed a patent application for Li's discovery and its use as a diagnostic tool and treatment strategy. "This technology will still take some time before there is a product," said Li.
Li's research is funded by the National Institutes of Health.
*The most recent publication from Li's group appeared in the September 2008 issue of Molecular Immunology, "The interleukin-1 receptor associated kinase 1 contributes to the regulation of NFAT," by Dongmei Wang, Stephan Fasciano, Liwu Li (available online Aug. 8, 2008.), pages 3902-3908.
Learn more about Li's research at: biology.vt/faculty/li
For more information about the patent, visit: vtip/availableTech/technology.php?id=185933li
Source: Susan Trulove
Virginia Tech
понедельник, 23 мая 2011 г.
New Reagent Delivers A Chemical Breakthrough At FSU
"Build a better mousetrap," the saying goes, "and the world will beat a path to your door." In the complex field of organic chemistry, that path leads to Florida State University, where a newly developed substance could make the jobs of scientists throughout the world a little easier as they work to develop new drugs and other chemicals that benefit humanity.
Researchers from the Dudley Laboratory at FSU have invented a reagent - a substance used in a chemical reaction to detect, measure, examine or produce other substances - that can trap specific regions of complex molecules in such a way that those molecules can be released at a later time. This will allow scientists to perform complex experiments involving chemical synthesis much more easily and precisely.
"It isn't every day that one can put a new product on the market," said Gregory B. Dudley, an assistant professor of chemistry and biochemistry at FSU whose research lab bears his name.
"Even more exciting for me is the knowledge that scientific breakthroughs in biomedical research and various other areas of organic chemistry might be made possible as a result of this reagent," Dudley said.
The Sigma-Aldrich Chemical Company has licensed Dudley's patent-pending reagent from FSU and recently began marketing it to chemical research labs worldwide under the name "Bn-OPT" - short for BeNzylOxyPyridinium Triflate. FSU will receive royalties from Sigma-Aldrich in the amount of 5 percent of net sales of the reagent.
Bn-OPT is designed to be employed as part of what Dudley refers to as "protecting group strategies" in organic synthesis. 2-Benzyloxy-1-methylpyridinium trifluoromethanesulfonate - the rather unwieldy chemical name for the new reagent - converts vulnerable hydroxy groups, also known as alcohols, into benzyl ethers upon warming. These less-reactive benzyl ethers provide "protection" for alcohols during chemical synthesis. Bn-OPT emerged from his lab's basic research in organic chemistry, and researchers now are studying the reagent in search of new applications.
"Benzyl ethers have always played an important role in organic chemistry, but their use has been limited by difficulties in preparing them," Dudley said. "This reagent solves some of the problems associated with making benzyl ethers."
Professor Joseph Schlenoff, the interim chairman of FSU's department of chemistry and biochemistry, hailed Dudley as a young educator whose work is helping others both in and out of the classroom.
"Greg is one of our rising stars, both in teaching and research in the area of synthetic organic chemistry," Schlenoff said. "His discovery of this important new chemical reagent will bring significant attention to our department and to the cutting-edge research that is being conducted here."
A scientific paper written by Dudley and an FSU postdoctoral associate, Wing C. "Kevin" Poon, was published last year in the prestigious Journal of Organic Chemistry. To view that paper, which describes the process for creating the reagent, click here
Dudley and his doctoral students last made headlines in 2005 with their research on roseophilin, a naturally occurring compound that has emerged as a promising new avenue for cancer research. Dudley's ongoing goal in that project is to find ways to produce synthetic versions of roseophilin (pronounced rose-ee-oh-FILL-in) both cheaply and efficiently so that it can be produced in quantities large enough to enable further cancer research. To read more click here.
Contact: Gregory B. Dudley
Florida State University
Researchers from the Dudley Laboratory at FSU have invented a reagent - a substance used in a chemical reaction to detect, measure, examine or produce other substances - that can trap specific regions of complex molecules in such a way that those molecules can be released at a later time. This will allow scientists to perform complex experiments involving chemical synthesis much more easily and precisely.
"It isn't every day that one can put a new product on the market," said Gregory B. Dudley, an assistant professor of chemistry and biochemistry at FSU whose research lab bears his name.
"Even more exciting for me is the knowledge that scientific breakthroughs in biomedical research and various other areas of organic chemistry might be made possible as a result of this reagent," Dudley said.
The Sigma-Aldrich Chemical Company has licensed Dudley's patent-pending reagent from FSU and recently began marketing it to chemical research labs worldwide under the name "Bn-OPT" - short for BeNzylOxyPyridinium Triflate. FSU will receive royalties from Sigma-Aldrich in the amount of 5 percent of net sales of the reagent.
Bn-OPT is designed to be employed as part of what Dudley refers to as "protecting group strategies" in organic synthesis. 2-Benzyloxy-1-methylpyridinium trifluoromethanesulfonate - the rather unwieldy chemical name for the new reagent - converts vulnerable hydroxy groups, also known as alcohols, into benzyl ethers upon warming. These less-reactive benzyl ethers provide "protection" for alcohols during chemical synthesis. Bn-OPT emerged from his lab's basic research in organic chemistry, and researchers now are studying the reagent in search of new applications.
"Benzyl ethers have always played an important role in organic chemistry, but their use has been limited by difficulties in preparing them," Dudley said. "This reagent solves some of the problems associated with making benzyl ethers."
Professor Joseph Schlenoff, the interim chairman of FSU's department of chemistry and biochemistry, hailed Dudley as a young educator whose work is helping others both in and out of the classroom.
"Greg is one of our rising stars, both in teaching and research in the area of synthetic organic chemistry," Schlenoff said. "His discovery of this important new chemical reagent will bring significant attention to our department and to the cutting-edge research that is being conducted here."
A scientific paper written by Dudley and an FSU postdoctoral associate, Wing C. "Kevin" Poon, was published last year in the prestigious Journal of Organic Chemistry. To view that paper, which describes the process for creating the reagent, click here
Dudley and his doctoral students last made headlines in 2005 with their research on roseophilin, a naturally occurring compound that has emerged as a promising new avenue for cancer research. Dudley's ongoing goal in that project is to find ways to produce synthetic versions of roseophilin (pronounced rose-ee-oh-FILL-in) both cheaply and efficiently so that it can be produced in quantities large enough to enable further cancer research. To read more click here.
Contact: Gregory B. Dudley
Florida State University
воскресенье, 22 мая 2011 г.
If Junk DNA Is Useful, Why Is It Not Shared Out More Equally?
DNA was originally thought to have a single function: to help cells make the proteins they need. Any DNA that is not immediately required to produce proteins was written off as "junk" and deemed unworthy of study. Recently, however, it has become clear that junk DNA performs a wide range of important tasks. As a result, attention is shifting to asking why some organisms have so much of it and other organisms so little. A particular puzzle is posed by so-called "introns", stretches of DNA that interrupt the sequence of genes. Ashley Farlow, Eshwar Meduri and Christian Schlötterer of the University of Veterinary Medicine, Vienna now propose a mechanism to account for the range of intron numbers observed between different species. Their theory is published in the current issue of the journal Trends in Genetics.
The presence of introns in genes requires cells to process "messenger RNA" molecules before synthesizing proteins, a process that is costly and often error-prone. It was long believed that this was simply part of the price organisms paid for the flexibility to create new types of protein but recent work has made it clear that introns themselves have a number of important functions. And so attention is gradually shifting to asking why some organisms have so few introns and others so many.
It seems likely that new introns are added to DNA when double-stranded DNA breaks which may arise from a variety of mechanisms are not repaired "correctly" but the newly created ends are instead joined to other fragments of DNA. Farlow and colleagues at the Institute of Population Genetics of the University of Veterinary Medicine, Vienna reasoned that introns may be lost by a similar mechanism. An examination of areas of DNA where introns are known to have been lost in organisms such as worms and flies provides support for their idea.
DNA breaks may be treated in one of two ways: correct repair (by a relatively time-consuming process known as "homologous recombination") or the rapid and error-prone joining of non-homologous ends. The two pathways are essentially separate and can compete with each other for DNA breaks to work with. The scientists at the University of Veterinary Medicine, Vienna now suggest that species-specific differences in the relative activity of these two pathways might underlie the observed variation in intron number.
The theory represents a fundamental change in the way we think about the evolution of DNA. Evolution has seen periods of large scale intron loss alternating with periods of intron gain and this has been interpreted as the result of changing selection pressure. However, the rates at which single species have gained and lost introns throughout evolution have been found to vary in parallel, consistent with Farlow's notion that the two processes are related. The new theory provides an alternative interpretation: changes in the activities of the "homologous" and "non-homologous" pathways for repairing DNA breaks could cause introns to be lost faster than they are gained, or vice versa.
The idea is consistent with what we currently know about intron numbers, which range from a handful in some simple eukaryotes to more than 180,000 in the human genome. And as Farlow says, "Linking intron gain and loss to the repair of DNA breaks offers a neat explanation for how intron number can change over time. This theory may account for the huge diversity we seen in intron number between different species."
Sources: Veterinärmedizinische Universität Wien, AlphaGalileo Foundation.
The presence of introns in genes requires cells to process "messenger RNA" molecules before synthesizing proteins, a process that is costly and often error-prone. It was long believed that this was simply part of the price organisms paid for the flexibility to create new types of protein but recent work has made it clear that introns themselves have a number of important functions. And so attention is gradually shifting to asking why some organisms have so few introns and others so many.
It seems likely that new introns are added to DNA when double-stranded DNA breaks which may arise from a variety of mechanisms are not repaired "correctly" but the newly created ends are instead joined to other fragments of DNA. Farlow and colleagues at the Institute of Population Genetics of the University of Veterinary Medicine, Vienna reasoned that introns may be lost by a similar mechanism. An examination of areas of DNA where introns are known to have been lost in organisms such as worms and flies provides support for their idea.
DNA breaks may be treated in one of two ways: correct repair (by a relatively time-consuming process known as "homologous recombination") or the rapid and error-prone joining of non-homologous ends. The two pathways are essentially separate and can compete with each other for DNA breaks to work with. The scientists at the University of Veterinary Medicine, Vienna now suggest that species-specific differences in the relative activity of these two pathways might underlie the observed variation in intron number.
The theory represents a fundamental change in the way we think about the evolution of DNA. Evolution has seen periods of large scale intron loss alternating with periods of intron gain and this has been interpreted as the result of changing selection pressure. However, the rates at which single species have gained and lost introns throughout evolution have been found to vary in parallel, consistent with Farlow's notion that the two processes are related. The new theory provides an alternative interpretation: changes in the activities of the "homologous" and "non-homologous" pathways for repairing DNA breaks could cause introns to be lost faster than they are gained, or vice versa.
The idea is consistent with what we currently know about intron numbers, which range from a handful in some simple eukaryotes to more than 180,000 in the human genome. And as Farlow says, "Linking intron gain and loss to the repair of DNA breaks offers a neat explanation for how intron number can change over time. This theory may account for the huge diversity we seen in intron number between different species."
Sources: Veterinärmedizinische Universität Wien, AlphaGalileo Foundation.
суббота, 21 мая 2011 г.
Seizure Drug That Reverses Cellular Effects Discovered By Scripps Research Scientists
In the new research, published in the May 28, 2008 edition of The Journal of Neuroscience, the scientists found that gabapentin normalizes the action of certain brain cells altered by chronic alcohol abuse in an area of the brain known as the central amygdala, which plays an important role in fear- and stress-related behaviors, as well as in regulating alcohol drinking. In the study, alcohol-dependent rodents receiving gabapentin drank less alcohol.
"The results are exciting," said Scripps Research Assistant Professor Marisa Roberto, Ph.D., who was first author of the study. "Our research shows that gabapentin not only changes the alcohol-consumption patterns of addicted rats (and not of the control group), but also may reverse some of the effects of addiction on a specific neurotransmitter in the brain."
"This is an example of the strength of the translational approach of the Pearson Center, where the clinical uses of gabapentin led us to hypothesize that gabapentin may act to restore homeostatic dysregulation of the GABAergic system," said George Koob, Ph.D., chair of the Scripps Research Committee on the Neurobiology of Addictive Disorders and co-director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research. "Cellular and behavioral studies converged to suggest that indeed gabapentin could normalize GABAergic tone in a specific brain region known to be dysregulated in dependent animals. Such results provide a strong rationale for translating these observations back to the clinical setting for the treatment of alcoholism."
In previous studies, gabapentin has been shown to effectively treat alcohol withdrawal and reduce alcohol consumption and cravings following detoxification in alcoholics. However, how gabapentin could act to combat alcohol dependence in the brain has been unclear. The new study sheds light on this question by detailing the action of gabapentin (known commercially as Neurontin) - a structural analogue of the inhibitory synaptic transmitter gamma aminobutyric acid (GABA) - on neural signaling in the brain.
In the new study, the scientists first tested the effects of gabapentin on the behavior of alcohol-dependent and non-dependent rats. The researchers found that alcohol-dependent rats that received gabapentin drank significantly less alcohol and demonstrated fewer anxiety-like behaviors in the face of alcohol abstinence than those who did not receive the drug. The behavior of non-dependent rats receiving gabapentin remained unaffected. These results were observed both when the rats received gabapentin systemically and when the medication was infused directly into the central amygdala region of the brain.
At the cellular level, dependence on alcohol has been associated with increased strength of inhibitory synapses (junctions between two nerve cells) in the central amygdala. In the new study, the scientists found gabapentin, like alcohol, increased the strength of these central amygdala inhibitory synapse cells from non-dependent rats, but decreased their strength in cells from alcohol-dependent rats.
Interestingly, these effects of gabapentin disappeared in the presence of a specific inhibitor of so-called GABAB receptors, indicating that gabapentin's cellular mechanisms likely involve changes in release of the transmitter GABA at the inhibitory synapses. The scientists also found that the sensitivity of GABAB receptors decreased with alcohol dependence, suggesting a biological mechanism for the development of alcohol dependence in general and for gabapentin's contrasting effects before and after long-term alcohol exposure in particular.
The scientists plan to further explore the mechanism of action of gabapentin in the brain. In addition, clinical trials on the effectiveness of gabapentin as a treatment for alcohol dependence are currently under way at The Scripps Research Institute.
In addition to Roberto and Koob, the study "Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence" was authored by Nicholas W. Gilpin, Maureen T. Cruz, and George R. Siggins of Scripps Research; Laura E. O'Dell of the University of Texas at El Paso; and Andrew C. Morse of Brain Cells.
The work was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, the Harold L. Dorris Neurological Research Institute at Scripps Research, and The Scripps Research Institute.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus by 2009.
Source: Keith McKeown
Scripps Research Institute
View drug information on Neurontin.
"The results are exciting," said Scripps Research Assistant Professor Marisa Roberto, Ph.D., who was first author of the study. "Our research shows that gabapentin not only changes the alcohol-consumption patterns of addicted rats (and not of the control group), but also may reverse some of the effects of addiction on a specific neurotransmitter in the brain."
"This is an example of the strength of the translational approach of the Pearson Center, where the clinical uses of gabapentin led us to hypothesize that gabapentin may act to restore homeostatic dysregulation of the GABAergic system," said George Koob, Ph.D., chair of the Scripps Research Committee on the Neurobiology of Addictive Disorders and co-director of the Pearson Center for Alcoholism and Addiction Research at Scripps Research. "Cellular and behavioral studies converged to suggest that indeed gabapentin could normalize GABAergic tone in a specific brain region known to be dysregulated in dependent animals. Such results provide a strong rationale for translating these observations back to the clinical setting for the treatment of alcoholism."
In previous studies, gabapentin has been shown to effectively treat alcohol withdrawal and reduce alcohol consumption and cravings following detoxification in alcoholics. However, how gabapentin could act to combat alcohol dependence in the brain has been unclear. The new study sheds light on this question by detailing the action of gabapentin (known commercially as Neurontin) - a structural analogue of the inhibitory synaptic transmitter gamma aminobutyric acid (GABA) - on neural signaling in the brain.
In the new study, the scientists first tested the effects of gabapentin on the behavior of alcohol-dependent and non-dependent rats. The researchers found that alcohol-dependent rats that received gabapentin drank significantly less alcohol and demonstrated fewer anxiety-like behaviors in the face of alcohol abstinence than those who did not receive the drug. The behavior of non-dependent rats receiving gabapentin remained unaffected. These results were observed both when the rats received gabapentin systemically and when the medication was infused directly into the central amygdala region of the brain.
At the cellular level, dependence on alcohol has been associated with increased strength of inhibitory synapses (junctions between two nerve cells) in the central amygdala. In the new study, the scientists found gabapentin, like alcohol, increased the strength of these central amygdala inhibitory synapse cells from non-dependent rats, but decreased their strength in cells from alcohol-dependent rats.
Interestingly, these effects of gabapentin disappeared in the presence of a specific inhibitor of so-called GABAB receptors, indicating that gabapentin's cellular mechanisms likely involve changes in release of the transmitter GABA at the inhibitory synapses. The scientists also found that the sensitivity of GABAB receptors decreased with alcohol dependence, suggesting a biological mechanism for the development of alcohol dependence in general and for gabapentin's contrasting effects before and after long-term alcohol exposure in particular.
The scientists plan to further explore the mechanism of action of gabapentin in the brain. In addition, clinical trials on the effectiveness of gabapentin as a treatment for alcohol dependence are currently under way at The Scripps Research Institute.
In addition to Roberto and Koob, the study "Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence" was authored by Nicholas W. Gilpin, Maureen T. Cruz, and George R. Siggins of Scripps Research; Laura E. O'Dell of the University of Texas at El Paso; and Andrew C. Morse of Brain Cells.
The work was supported by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health, the Harold L. Dorris Neurological Research Institute at Scripps Research, and The Scripps Research Institute.
About The Scripps Research Institute
The Scripps Research Institute is one of the world's largest independent, non-profit biomedical research organizations, at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its discoveries in immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune, cardiovascular, and infectious diseases, and synthetic vaccine development. Established in its current configuration in 1961, it employs approximately 3,000 scientists, postdoctoral fellows, scientific and other technicians, doctoral degree graduate students, and administrative and technical support personnel. Scripps Research is headquartered in La Jolla, California. It also includes Scripps Florida, whose researchers focus on basic biomedical science, drug discovery, and technology development. Currently operating from temporary facilities in Jupiter, Scripps Florida will move to its permanent campus by 2009.
Source: Keith McKeown
Scripps Research Institute
View drug information on Neurontin.
пятница, 20 мая 2011 г.
As The World Drowns In Data, Researchers Are Embracing Automation And Raising Questions About Its Impact On Science
As science fiction plot lines go, the unintended consequences of yielding tasks too complicated or dangerous for human hands to computers and robots is a popular one. Yet real life scientists are increasingly doing just that, creating automated systems and devices that can not only help collect, organize and analyze scientific data, but that are also able to intelligently and independently draw up new hypotheses and approaches to research based on the data they receive.
In a perspectives piece in the journal Science, David Waltz of the Center for Computational Learning Systems at Columbia University and Bruce G. Buchanan of the computer science department at the University of Pittsburgh discuss this brave new world of scientific research and its implications for the way science is conducted. They see this all as a promising trend, but caution that researchers need to consider what tasks are best suited for automation and which should be left to the human mind.
Waltz and Buchanan point out that computer-aided automation has been a part of scientific research for decades, from simple programs that plotted ballistic arcs to databases that held and organized scientific data. All of these systems, however, required a "human in the loop" to shape the research, examine the results and determine how to apply the outcome to future endeavors.
Now the frontiers of automation can now make the human scientist seem obsolete. Waltz and Buchanan write that, "it is possible for one computer program ... to conduct a continuously looping procedure that starts with a question, carries out experiments to answer the question, evaluates the results, and reformulates new questions."
The authors argue that these new systems are arriving just when they are needed the most. As sensors and other instruments get more capable and complex, the scientific world is drowning in data, and having computer-based assistants who can actively sift through the data may be the only way to make sense of it all.
According to Waltz and Buchanan, the prospect of automating science also brings up a number of questions that need to be considered as these new technologies become widely adopted and deployed, e.g., how we determine what to automate, what should be left to human intervention, and how this newly automated research will affect the results and the scientific process. It is also possible, Waltz and Buchanan suggest, that these new tools will generate even more data to be considered, and will therefore contribute to one of the problems they are meant to solve.
Moving forward, the authors suggest that the best approach is to think of these tools as intelligent assistants that can do different types of tasks associated with scientific research. Scientists can then determine which assistants are the best choice for different aspects of their research.
So, does employing these automated assistants mean that students studying science should consider another major? The authors say no, indicating that for all of their capabilities, automated science systems will not do to researchers what robots have done to autoworkers--but they will change how scientists do their jobs.
Said Walter, "Regardless of specialty--biology, physics, chemistry, etc.--scientists may need to add knowledge and skills in artificial intelligence, machine learning, and knowledge representation."
Source:
Dana W. Cruikshank
National Science Foundation
In a perspectives piece in the journal Science, David Waltz of the Center for Computational Learning Systems at Columbia University and Bruce G. Buchanan of the computer science department at the University of Pittsburgh discuss this brave new world of scientific research and its implications for the way science is conducted. They see this all as a promising trend, but caution that researchers need to consider what tasks are best suited for automation and which should be left to the human mind.
Waltz and Buchanan point out that computer-aided automation has been a part of scientific research for decades, from simple programs that plotted ballistic arcs to databases that held and organized scientific data. All of these systems, however, required a "human in the loop" to shape the research, examine the results and determine how to apply the outcome to future endeavors.
Now the frontiers of automation can now make the human scientist seem obsolete. Waltz and Buchanan write that, "it is possible for one computer program ... to conduct a continuously looping procedure that starts with a question, carries out experiments to answer the question, evaluates the results, and reformulates new questions."
The authors argue that these new systems are arriving just when they are needed the most. As sensors and other instruments get more capable and complex, the scientific world is drowning in data, and having computer-based assistants who can actively sift through the data may be the only way to make sense of it all.
According to Waltz and Buchanan, the prospect of automating science also brings up a number of questions that need to be considered as these new technologies become widely adopted and deployed, e.g., how we determine what to automate, what should be left to human intervention, and how this newly automated research will affect the results and the scientific process. It is also possible, Waltz and Buchanan suggest, that these new tools will generate even more data to be considered, and will therefore contribute to one of the problems they are meant to solve.
Moving forward, the authors suggest that the best approach is to think of these tools as intelligent assistants that can do different types of tasks associated with scientific research. Scientists can then determine which assistants are the best choice for different aspects of their research.
So, does employing these automated assistants mean that students studying science should consider another major? The authors say no, indicating that for all of their capabilities, automated science systems will not do to researchers what robots have done to autoworkers--but they will change how scientists do their jobs.
Said Walter, "Regardless of specialty--biology, physics, chemistry, etc.--scientists may need to add knowledge and skills in artificial intelligence, machine learning, and knowledge representation."
Source:
Dana W. Cruikshank
National Science Foundation
четверг, 19 мая 2011 г.
How World's Smallest 'Coffee Ring' May Help Biosensors Detect Disease
The field of biosensing has recently found an unlikely partner in the quest for increased sensitivity: coffee rings. The next time you spill your coffee on a table, look at the spot left after the liquid has evaporated, and you'll notice it has a darker ring around its perimeter that contains a much higher concentration of particles than the center.
Because this "coffee ring" phenomenon occurs with many liquids after they have evaporated, scientists have suggested that such rings can be used for examining blood or other fluids for disease markers by using biosensing devices. But a better understanding of how these rings behave at the micro- and nano-scale would probably be needed for practical bionsensors.
"Understanding micro- and nano-particle transportation within evaporating liquid droplets has great potential for several technological applications, including nanostructure self-assembly, lithography patterning, particle coating, and biomolecule concentration and separation," said Chih-Ming Ho, the Ben Rich-Lockheed Martin Professor at the UCLA Henry Samueli School of Engineering and Applied Science and director of the UCLA Center for Cell Control. "However, before we can engineer biosensing devices to do these applications, we need to know the definitive limits of this phenomenon. So our research turned to physical chemistry to find the lowest limits of coffee-ring formation."
A research group led by Ho, a member of the National Academy of Engineering, has now found the definitive microscopic minimal threshold of coffee-ring formation, which can be used to set standards for biosensor devices for multiple disease detection, as well as other uses. The research appears in the current issue of the Journal of Physical Chemistry B and is available online.
"If we consider human blood, or saliva, it has a lot of micro- and nano-scale molecules or particles that carry important health information," said Tak-Sing Wong, one of the researchers and a postdoctoral scholar in UCLA Engineering's department of mechanical and aerospace engineering. "If you put this blood or saliva on a surface, and then it dries, these particles will be collected in a very small region in the ring. By doing so, we can quantify these biomarkers by various sensing techniques, even if they are very small and in a small amount in the droplets."
As water evaporates from a droplet, particles that are suspended inside the liquid move to the droplet's edges. Once all the water has evaporated, the particles are concentrated in a ring around the stain that is left behind. However, if a droplet is small enough, the water will evaporate faster than the particles move. Rather than a ring, there will be a relatively uniform concentration in the stain, as the particles have not had enough time to move to the edges while still in the liquid.
"It is the competition between the timescale of the evaporation of the droplet and the timescale of the movement of the particles that dictates coffee-ring formation," said Xiaoying Shen, the paper's lead author and a senior microelectronics major at Peking University in China, who worked on these experiments while at the UCLA Cross Disciplinary Scholars in Science and Technology (CSST) program last summer.
To determine the smallest droplet size that would still show a coffee ring after evaporation, the research team manufactured a special surface coated in a checkerboard pattern that featured alternating hydrophilic, or water-loving, material and hydrophobic, or water-repelling, material.
The group then placed latex particles, ranging in size from 100 nanometers to 20 nanometers, in water. The particles were similar in size to disease-marker proteins that biosensors would look for.
The group washed the new surface with the particle-infused water. The remaining water lined up as droplets on the hydrophilic spots, much like checkers on a checkerboard. The group repeated the experiments with smaller grid patterns until the coffee-ring phenomenon was no longer evident. For the 100-nanometer sized particles, this occurred at a droplet diameter of approximately 10 micrometers, or about 10 times smaller than the width of a human hair. At this point, the water evaporated before the particles had enough time to move to the perimeter.
"Knowing the minimum size of this so-called coffee ring will guide us in making the smallest biosensors possible," Wong said. "This means that we can pack thousands, even millions, of small micro-biosensors onto a lab-on-a-chip, allowing one to perform a large number of medical diagnostics on a single chip. This may also open the doors to potentially detecting multiple diseases in one sitting."
"There's another important advantage - this whole process is very natural, it's just evaporation," Wong added. "We don't need to use additional devices, such as an electrical power source or other sophisticated instruments to move the particles. Evaporation provides a very simple way of concentrating particles and has potential in medical diagnosis. For example, researchers at Vanderbilt University were recently awarded a Gates Foundation Research Fund for proposing the use of the coffee-ring phenomenon for malaria detection in developing countries."
The researchers are currently optimizing the ring formation parameters and will then explore the application of this approach toward biosensing technologies that are being developed in Ho's laboratory.
The research was supported by the Center for Cell Control through the National Institutes of Health's Roadmap for Nanomedicine and by the Center for Scalable and Integrated Nanomanufacturing through the National Science Foundation. Shen received financial support from UCLA's Cross Disciplinary Scholars in Science and Technology (CSST) program.
Source:
Matthew Chin
University of California - Los Angeles
Because this "coffee ring" phenomenon occurs with many liquids after they have evaporated, scientists have suggested that such rings can be used for examining blood or other fluids for disease markers by using biosensing devices. But a better understanding of how these rings behave at the micro- and nano-scale would probably be needed for practical bionsensors.
"Understanding micro- and nano-particle transportation within evaporating liquid droplets has great potential for several technological applications, including nanostructure self-assembly, lithography patterning, particle coating, and biomolecule concentration and separation," said Chih-Ming Ho, the Ben Rich-Lockheed Martin Professor at the UCLA Henry Samueli School of Engineering and Applied Science and director of the UCLA Center for Cell Control. "However, before we can engineer biosensing devices to do these applications, we need to know the definitive limits of this phenomenon. So our research turned to physical chemistry to find the lowest limits of coffee-ring formation."
A research group led by Ho, a member of the National Academy of Engineering, has now found the definitive microscopic minimal threshold of coffee-ring formation, which can be used to set standards for biosensor devices for multiple disease detection, as well as other uses. The research appears in the current issue of the Journal of Physical Chemistry B and is available online.
"If we consider human blood, or saliva, it has a lot of micro- and nano-scale molecules or particles that carry important health information," said Tak-Sing Wong, one of the researchers and a postdoctoral scholar in UCLA Engineering's department of mechanical and aerospace engineering. "If you put this blood or saliva on a surface, and then it dries, these particles will be collected in a very small region in the ring. By doing so, we can quantify these biomarkers by various sensing techniques, even if they are very small and in a small amount in the droplets."
As water evaporates from a droplet, particles that are suspended inside the liquid move to the droplet's edges. Once all the water has evaporated, the particles are concentrated in a ring around the stain that is left behind. However, if a droplet is small enough, the water will evaporate faster than the particles move. Rather than a ring, there will be a relatively uniform concentration in the stain, as the particles have not had enough time to move to the edges while still in the liquid.
"It is the competition between the timescale of the evaporation of the droplet and the timescale of the movement of the particles that dictates coffee-ring formation," said Xiaoying Shen, the paper's lead author and a senior microelectronics major at Peking University in China, who worked on these experiments while at the UCLA Cross Disciplinary Scholars in Science and Technology (CSST) program last summer.
To determine the smallest droplet size that would still show a coffee ring after evaporation, the research team manufactured a special surface coated in a checkerboard pattern that featured alternating hydrophilic, or water-loving, material and hydrophobic, or water-repelling, material.
The group then placed latex particles, ranging in size from 100 nanometers to 20 nanometers, in water. The particles were similar in size to disease-marker proteins that biosensors would look for.
The group washed the new surface with the particle-infused water. The remaining water lined up as droplets on the hydrophilic spots, much like checkers on a checkerboard. The group repeated the experiments with smaller grid patterns until the coffee-ring phenomenon was no longer evident. For the 100-nanometer sized particles, this occurred at a droplet diameter of approximately 10 micrometers, or about 10 times smaller than the width of a human hair. At this point, the water evaporated before the particles had enough time to move to the perimeter.
"Knowing the minimum size of this so-called coffee ring will guide us in making the smallest biosensors possible," Wong said. "This means that we can pack thousands, even millions, of small micro-biosensors onto a lab-on-a-chip, allowing one to perform a large number of medical diagnostics on a single chip. This may also open the doors to potentially detecting multiple diseases in one sitting."
"There's another important advantage - this whole process is very natural, it's just evaporation," Wong added. "We don't need to use additional devices, such as an electrical power source or other sophisticated instruments to move the particles. Evaporation provides a very simple way of concentrating particles and has potential in medical diagnosis. For example, researchers at Vanderbilt University were recently awarded a Gates Foundation Research Fund for proposing the use of the coffee-ring phenomenon for malaria detection in developing countries."
The researchers are currently optimizing the ring formation parameters and will then explore the application of this approach toward biosensing technologies that are being developed in Ho's laboratory.
The research was supported by the Center for Cell Control through the National Institutes of Health's Roadmap for Nanomedicine and by the Center for Scalable and Integrated Nanomanufacturing through the National Science Foundation. Shen received financial support from UCLA's Cross Disciplinary Scholars in Science and Technology (CSST) program.
Source:
Matthew Chin
University of California - Los Angeles
среда, 18 мая 2011 г.
News From The Journal Of Clinical Investigation, June 12, 2008
New target to enhance anticancer drug sensitivity found in translation
The development of resistance to anticancer chemotherapeutic agents remains a large problem. In some cases, such resistance is associated with altered control of a cellular process known as translation, which is central to the generation of proteins. New data, generated by Jerry Pelletier and colleagues, at McGill University, Montreal, have identified a drug that can enhance the sensitivity of mouse cancer cells to standard anticancer chemotherapeutic agents.
In the study, small molecules were screened for their ability to inhibit the initiation of translation by modifying the function of a protein known as eIF4A, which has a central role in translation initiation. A class of natural drugs known as cyclopenta[b]benzofuran flavaglines were found to have the desired effects and one member of this class of compounds was shown to reverse the resistance of cancer cells to anticancer chemotherapeutic agents in a mouse model of lymphoma. The authors therefore suggest that developing approaches to inhibit translation initiation by targeting eIF4A might provide a way to altering drug resistance in cancers exhibiting altered control of translation initiation.
TITLE: Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model
AUTHOR CONTACT:
Jerry Pelletier
McGill University, Montreal, Quebec, Canada.
View the PDF of this article at: https://the-jci/article.php?id=34753
Tumor cells want no contact with immune cells
As tumors progress they develop ways to escape recognition and attack by cells of the immune system. However, the mechanisms by which tumors modify the immune system have not been clearly determined. New insight into the way in which chronic lymphocytic leukemia (CLL) cells limit immune cell attack has now been provided by John Gribben and colleagues, at Barts and The London School of Medicine, United Kingdom.
For immune cells known as CD4+ and CD8+ T cells to become activated they must contact other cells known as APCs. The area of contact is known as the immunological synapse and it is highly organized. In the study, CD4+ and CD8+ T cells from patients with CLL were found to exhibit defective immunological synapse formation with APCs. Further, if CD4+ and CD8+ T cells from healthy individuals were cultured with CLL APCs, they also showed defective immunological synapse formation. As treatment with an immune system-modifying drug improved immunological synapse formation, the authors suggest that approaches to overcoming immunological synapse defects might improve the efficacy of new ways to treat cancer that are currently being developed and that are based on enhancing the antitumor activity of CD4+ and CD8+ T cells.
TITLE: Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug
AUTHOR CONTACT:
John G. Gribben
Barts and The London School of Medicine, London, United Kingdom.
View the PDF of this article at: https://the-jci/article.php?id=35017
How bone growth can be stunted in mice
Hiroshi Kawaguchi and colleagues, at the University of Tokyo, Japan, have provided new insight into the molecules that control the growth of the mouse skeleton.
Mice lacking a protein known as cGKII are dramatically smaller than mice expressing normal levels of this protein, because the bones of their legs and body are much shorter. In the study, it was found that the shorter bones were a result of a defect in bone growth, specifically in a process known as chondrocyte hypertrophy. Further analysis showed that in normal mouse chondrocytes, cGKII inhibited the function of a protein known as GSK-3-beta and that this was important for enhancing chondrocyte hypertrophy. In addition, the bone defects in mice lacking cGKII were partially rescued if the mice were engineered to express reduced levels of GSK-3-beta. These data indicate an important role for cGKII inhibition of GSK-3-beta function in skeletal growth and the authors are now investigating ways in which this information can be used to develop new therapeutics for skeletal disorders that result in dwarfism.
TITLE: Phosphorylation of GSK-3-beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes
AUTHOR CONTACT:
Hiroshi Kawaguchi
University of Tokyo, Tokyo, Japan.
View the PDF of this article at: https://the-jci/article.php?id=35243
FABP molecules help link inflammation to obesity-related metabolic diseases
Individuals who are obese are predisposed to a variety of metabolic conditions, including type 2 diabetes. A characteristic of the fat tissue (adipose tissue) of individuals who are obese is that it is inflammed, and understanding the relationship between such inflammation and the onset of the metabolic conditions is of importance in combating what has become a large public health problem. In a new mouse study, Gökhan Hotamisligil and colleagues, at the Harvard School of Public Health, Boston, found that interactions between adipocytes (fat cells) and inflammatory cells called macrophages seem to underlie the inflammation-related metabolic deterioration associated with obesity.
In the study, when adipocytes isolated from mice lacking proteins known as FABPs, which are molecules that govern metabolic and inflammatory responses, were cultured with normal macrophages, the macrophages expressed reduced levels of inflammatory molecules. Likewise, when macrophages isolated from mice lacking FABPs were cultured with normal adipocyes, the adipocytes responded more to insulin and took up more glucose. Similar results, indicating that FABPs from both adipocytes and macrophages contribute to the inflammatory basis for metabolic deterioration, were obtained in vivo. The authors therefore suggest that this FABP-related pathway may be a novel target for metabolism-related disorders.
TITLE: Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
AUTHOR CONTACT:
Gökhan S. Hotamisligil
Harvard School of Public Health, Boston, Massachusetts, USA.
View the PDF of this article at: https://the-jci/article.php?id=34750
Source: Karen Honey
Journal of Clinical Investigation
The development of resistance to anticancer chemotherapeutic agents remains a large problem. In some cases, such resistance is associated with altered control of a cellular process known as translation, which is central to the generation of proteins. New data, generated by Jerry Pelletier and colleagues, at McGill University, Montreal, have identified a drug that can enhance the sensitivity of mouse cancer cells to standard anticancer chemotherapeutic agents.
In the study, small molecules were screened for their ability to inhibit the initiation of translation by modifying the function of a protein known as eIF4A, which has a central role in translation initiation. A class of natural drugs known as cyclopenta[b]benzofuran flavaglines were found to have the desired effects and one member of this class of compounds was shown to reverse the resistance of cancer cells to anticancer chemotherapeutic agents in a mouse model of lymphoma. The authors therefore suggest that developing approaches to inhibit translation initiation by targeting eIF4A might provide a way to altering drug resistance in cancers exhibiting altered control of translation initiation.
TITLE: Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model
AUTHOR CONTACT:
Jerry Pelletier
McGill University, Montreal, Quebec, Canada.
View the PDF of this article at: https://the-jci/article.php?id=34753
Tumor cells want no contact with immune cells
As tumors progress they develop ways to escape recognition and attack by cells of the immune system. However, the mechanisms by which tumors modify the immune system have not been clearly determined. New insight into the way in which chronic lymphocytic leukemia (CLL) cells limit immune cell attack has now been provided by John Gribben and colleagues, at Barts and The London School of Medicine, United Kingdom.
For immune cells known as CD4+ and CD8+ T cells to become activated they must contact other cells known as APCs. The area of contact is known as the immunological synapse and it is highly organized. In the study, CD4+ and CD8+ T cells from patients with CLL were found to exhibit defective immunological synapse formation with APCs. Further, if CD4+ and CD8+ T cells from healthy individuals were cultured with CLL APCs, they also showed defective immunological synapse formation. As treatment with an immune system-modifying drug improved immunological synapse formation, the authors suggest that approaches to overcoming immunological synapse defects might improve the efficacy of new ways to treat cancer that are currently being developed and that are based on enhancing the antitumor activity of CD4+ and CD8+ T cells.
TITLE: Chronic lymphocytic leukemia T cells show impaired immunological synapse formation that can be reversed with an immunomodulating drug
AUTHOR CONTACT:
John G. Gribben
Barts and The London School of Medicine, London, United Kingdom.
View the PDF of this article at: https://the-jci/article.php?id=35017
How bone growth can be stunted in mice
Hiroshi Kawaguchi and colleagues, at the University of Tokyo, Japan, have provided new insight into the molecules that control the growth of the mouse skeleton.
Mice lacking a protein known as cGKII are dramatically smaller than mice expressing normal levels of this protein, because the bones of their legs and body are much shorter. In the study, it was found that the shorter bones were a result of a defect in bone growth, specifically in a process known as chondrocyte hypertrophy. Further analysis showed that in normal mouse chondrocytes, cGKII inhibited the function of a protein known as GSK-3-beta and that this was important for enhancing chondrocyte hypertrophy. In addition, the bone defects in mice lacking cGKII were partially rescued if the mice were engineered to express reduced levels of GSK-3-beta. These data indicate an important role for cGKII inhibition of GSK-3-beta function in skeletal growth and the authors are now investigating ways in which this information can be used to develop new therapeutics for skeletal disorders that result in dwarfism.
TITLE: Phosphorylation of GSK-3-beta by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes
AUTHOR CONTACT:
Hiroshi Kawaguchi
University of Tokyo, Tokyo, Japan.
View the PDF of this article at: https://the-jci/article.php?id=35243
FABP molecules help link inflammation to obesity-related metabolic diseases
Individuals who are obese are predisposed to a variety of metabolic conditions, including type 2 diabetes. A characteristic of the fat tissue (adipose tissue) of individuals who are obese is that it is inflammed, and understanding the relationship between such inflammation and the onset of the metabolic conditions is of importance in combating what has become a large public health problem. In a new mouse study, Gökhan Hotamisligil and colleagues, at the Harvard School of Public Health, Boston, found that interactions between adipocytes (fat cells) and inflammatory cells called macrophages seem to underlie the inflammation-related metabolic deterioration associated with obesity.
In the study, when adipocytes isolated from mice lacking proteins known as FABPs, which are molecules that govern metabolic and inflammatory responses, were cultured with normal macrophages, the macrophages expressed reduced levels of inflammatory molecules. Likewise, when macrophages isolated from mice lacking FABPs were cultured with normal adipocyes, the adipocytes responded more to insulin and took up more glucose. Similar results, indicating that FABPs from both adipocytes and macrophages contribute to the inflammatory basis for metabolic deterioration, were obtained in vivo. The authors therefore suggest that this FABP-related pathway may be a novel target for metabolism-related disorders.
TITLE: Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice
AUTHOR CONTACT:
Gökhan S. Hotamisligil
Harvard School of Public Health, Boston, Massachusetts, USA.
View the PDF of this article at: https://the-jci/article.php?id=34750
Source: Karen Honey
Journal of Clinical Investigation
вторник, 17 мая 2011 г.
NSF, NIH Award Ecology Of Infectious Disease Grants
Unprecedented changes in biodiversity have coincided with the emergence and re-emergence of infectious diseases around the world.
To address this problem, the National Science Foundation (NSF) and the National Institutes of Health (NIH) have announced $16 million in funding for eight projects under the Ecology of Infectious Diseases (EID) program, a multi-year, joint-agency effort now in its ninth year of funding.
"In a time of rapid global change, the one certainty is that emerging infectious diseases will be more common," said James Collins, NSF assistant director for biological sciences. "These new EID research awards will support the basic studies needed to predict the timing and severity of the emergence and spread of these diseases."
NSF's contribution to the EID program is from its Directorates for Biological Sciences; Geosciences; and Social, Behavioral & Economic Sciences.
Interdisciplinary projects funded through the EID program will study how large-scale environmental events -- such as climate change, habitat destruction, biological invasions, pollution and a variety of interventions -- alter the risks of viral, parasitic and bacterial diseases in humans and animals.
"Ecological studies of infectious diseases are beginning to move from basic science to translational research," said Joshua Rosenthal, EID program director at NIH's Fogarty International Center. "The results will help us to better manage these diseases."
The studies will contribute knowledge and analytical tools that will help public-health officials, wildlife managers, farmers and others to control the spread of diseases among humans, domestic and wild animals, and crops, say EID scientists.
This year's awards support research on:
Bacterial pathogens and human infectious diseases in an estuary subjected to extreme climatic events (Rachel Noble, University of North Carolina at Chapel Hill);
Virulence trade-offs in a vertebrate virus--infectious haematopoietic necrosis (IHN)--a disease of salmon and trout (Benjamin Kerr, University of Washington);
Agricultural antibiotics and human health, using a multi-scale ecological approach to the development and spread of antibiotic resistance (Joseph Eisenberg, University of Michigan);
Environmental determinants favorable for the presence and transmission of vibrios, bacteria typically found in saltwater and important human pathogens (Crystal Johnson, University of Southern Mississippi);
Eco-epidemiology of West Nile virus emergence in urban areas (Tony Goldberg, University of Wisconsin at Madison);
"Immune landscapes" of human influenza in households, towns and cities of southern China (Derek Cummings, Johns Hopkins University);
Ecology, emergence and pandemic potential of Nipah virus, a virus harbored in fruit bats, in Bangladesh (Peter Daszak, Center for Conservation Medicine);
Ecology of anaplasmosis, a tick-borne disease in cattle, and the relationship of disease reservoirs, risk and incidence (Felicia Keesing, Bard College).
The coincidence of broad-scale environmental changes and the emergence of infectious diseases points to underlying and predictable ecological relationships, said Rosenthal.
"The EID program links these components to produce a comprehensive understanding of disease transmission," he said.
Potential benefits of the EID program include development of more advanced disease transmission theory; improved understanding of unintended health effects of development projects; increased capacity to forecast outbreaks; and better comprehension of how diseases emerge and re-emerge.
nsf/news/news_summ.jsp?cntn_id=112249&org=NSF
Source: Cheryl Dybas
National Science Foundation
To address this problem, the National Science Foundation (NSF) and the National Institutes of Health (NIH) have announced $16 million in funding for eight projects under the Ecology of Infectious Diseases (EID) program, a multi-year, joint-agency effort now in its ninth year of funding.
"In a time of rapid global change, the one certainty is that emerging infectious diseases will be more common," said James Collins, NSF assistant director for biological sciences. "These new EID research awards will support the basic studies needed to predict the timing and severity of the emergence and spread of these diseases."
NSF's contribution to the EID program is from its Directorates for Biological Sciences; Geosciences; and Social, Behavioral & Economic Sciences.
Interdisciplinary projects funded through the EID program will study how large-scale environmental events -- such as climate change, habitat destruction, biological invasions, pollution and a variety of interventions -- alter the risks of viral, parasitic and bacterial diseases in humans and animals.
"Ecological studies of infectious diseases are beginning to move from basic science to translational research," said Joshua Rosenthal, EID program director at NIH's Fogarty International Center. "The results will help us to better manage these diseases."
The studies will contribute knowledge and analytical tools that will help public-health officials, wildlife managers, farmers and others to control the spread of diseases among humans, domestic and wild animals, and crops, say EID scientists.
This year's awards support research on:
Bacterial pathogens and human infectious diseases in an estuary subjected to extreme climatic events (Rachel Noble, University of North Carolina at Chapel Hill);
Virulence trade-offs in a vertebrate virus--infectious haematopoietic necrosis (IHN)--a disease of salmon and trout (Benjamin Kerr, University of Washington);
Agricultural antibiotics and human health, using a multi-scale ecological approach to the development and spread of antibiotic resistance (Joseph Eisenberg, University of Michigan);
Environmental determinants favorable for the presence and transmission of vibrios, bacteria typically found in saltwater and important human pathogens (Crystal Johnson, University of Southern Mississippi);
Eco-epidemiology of West Nile virus emergence in urban areas (Tony Goldberg, University of Wisconsin at Madison);
"Immune landscapes" of human influenza in households, towns and cities of southern China (Derek Cummings, Johns Hopkins University);
Ecology, emergence and pandemic potential of Nipah virus, a virus harbored in fruit bats, in Bangladesh (Peter Daszak, Center for Conservation Medicine);
Ecology of anaplasmosis, a tick-borne disease in cattle, and the relationship of disease reservoirs, risk and incidence (Felicia Keesing, Bard College).
The coincidence of broad-scale environmental changes and the emergence of infectious diseases points to underlying and predictable ecological relationships, said Rosenthal.
"The EID program links these components to produce a comprehensive understanding of disease transmission," he said.
Potential benefits of the EID program include development of more advanced disease transmission theory; improved understanding of unintended health effects of development projects; increased capacity to forecast outbreaks; and better comprehension of how diseases emerge and re-emerge.
nsf/news/news_summ.jsp?cntn_id=112249&org=NSF
Source: Cheryl Dybas
National Science Foundation
понедельник, 16 мая 2011 г.
Hopkins Researchers Put Proteins Right Where They Want Them
Using a method they developed to watch moment to moment as they move a molecule to precise sites inside live human cells, Johns Hopkins scientists are closer to understanding why and how a protein at one location may signal division and growth, and the same protein at another location, death.
Their research, published Feb. 14 in Nature Methods, expands on a more limited method using a chemical tool to move proteins inside of cells to the periphery, a locale known as the plasma membrane.
"Where a particular protein is activated and the timing of that activation influence how a cell responds to outside stimulus," says Takanari Inoue, Ph.D., an assistant professor of cell biology at Johns Hopkins University School of Medicine. "Our goal with this newly expanded tool is to manipulate protein activities in many places in cells on a rapid timescale."
Cells cleverly have resolved the predicament of needing to respond to a near infinite array of external stimuli - temperature, for instance - even though they employ only a limited number of molecular players. The notion is that a single protein assumes multiple roles by changing its location or altering the speed and duration of activation.
Chemical signaling inside cells connects protein molecules through complex feedback loops and crosstalk, Inoue says, so knowing exactly how each protein contributes to which signals at what locations requires the ability to rapidly move proteins of interest to specific organelles found in cells. These include mitochondria (the power generators of cells) and Golgi bodies (the delivery systems of cells).
The Hopkins team chose the signaling protein Ras as the molecule it would attempt to send packing throughout a cell's interior. A regulator of cell growth that's often implicated in cancer, Ras has been long studied and it's known to be a molecular switch. However, no one has had the ability to discern what Ras does at different locations such as Golgi bodies and mitrochondria, much less what happens when Ras is activated simultaneously at any combination of these and other organelles.
Working with live human HeLa cells and Ras under a microscope, the team used a dimerization probe consisting of a special small molecule that simultaneously attracts two proteins that wouldn't normally have an affinity for each other and binds them together. In this system, one of the partner proteins is anchored to an organelle and the other is free floating inside the cell. Adding a chemical dimerizer induces the free protein to join the tethered one.
Using scissor-like enzymes, the team sliced and diced the DNA of the paired proteins to change the molecular address of its destination. They cut out the "mailing address" - known as a targeting sequence - that formerly delivered the protein unit to the plasma membrane and replaced it with new addresses (targeting sequences) that shipped it instead to specific organelles.
"We were able to manipulate protein activities in situ and very rapidly on each individual organelle," Inoue said. "Ultimately, this will help us to better understand protein function at these critical cellular components."
This study was funded by the National Institutes of Health.
In addition to Inoue, authors of this paper are Toru Komatsu, Igor Kukelyansky, J. Michael McCaffery, Tasuku Ueno and Lidenys C. Varela, all of Johns Hopkins.
Source
Johns Hopkins Medicine
Their research, published Feb. 14 in Nature Methods, expands on a more limited method using a chemical tool to move proteins inside of cells to the periphery, a locale known as the plasma membrane.
"Where a particular protein is activated and the timing of that activation influence how a cell responds to outside stimulus," says Takanari Inoue, Ph.D., an assistant professor of cell biology at Johns Hopkins University School of Medicine. "Our goal with this newly expanded tool is to manipulate protein activities in many places in cells on a rapid timescale."
Cells cleverly have resolved the predicament of needing to respond to a near infinite array of external stimuli - temperature, for instance - even though they employ only a limited number of molecular players. The notion is that a single protein assumes multiple roles by changing its location or altering the speed and duration of activation.
Chemical signaling inside cells connects protein molecules through complex feedback loops and crosstalk, Inoue says, so knowing exactly how each protein contributes to which signals at what locations requires the ability to rapidly move proteins of interest to specific organelles found in cells. These include mitochondria (the power generators of cells) and Golgi bodies (the delivery systems of cells).
The Hopkins team chose the signaling protein Ras as the molecule it would attempt to send packing throughout a cell's interior. A regulator of cell growth that's often implicated in cancer, Ras has been long studied and it's known to be a molecular switch. However, no one has had the ability to discern what Ras does at different locations such as Golgi bodies and mitrochondria, much less what happens when Ras is activated simultaneously at any combination of these and other organelles.
Working with live human HeLa cells and Ras under a microscope, the team used a dimerization probe consisting of a special small molecule that simultaneously attracts two proteins that wouldn't normally have an affinity for each other and binds them together. In this system, one of the partner proteins is anchored to an organelle and the other is free floating inside the cell. Adding a chemical dimerizer induces the free protein to join the tethered one.
Using scissor-like enzymes, the team sliced and diced the DNA of the paired proteins to change the molecular address of its destination. They cut out the "mailing address" - known as a targeting sequence - that formerly delivered the protein unit to the plasma membrane and replaced it with new addresses (targeting sequences) that shipped it instead to specific organelles.
"We were able to manipulate protein activities in situ and very rapidly on each individual organelle," Inoue said. "Ultimately, this will help us to better understand protein function at these critical cellular components."
This study was funded by the National Institutes of Health.
In addition to Inoue, authors of this paper are Toru Komatsu, Igor Kukelyansky, J. Michael McCaffery, Tasuku Ueno and Lidenys C. Varela, all of Johns Hopkins.
Source
Johns Hopkins Medicine
воскресенье, 15 мая 2011 г.
'Fasting Switch' Disabled By Chronically Elevated Blood Sugar Levels
Continually revved up insulin production, the kind that results from overeating and obesity, slowly dulls the body's response to insulin. As a result, blood sugar levels start to creep up, setting the stage for diabetes-associated complications such as blindness, stroke and renal failure. To make matters even worse, chronically elevated blood sugar concentrations exacerbate insulin resistance.
The vicious circle gets rolling, researchers at the Salk Institute for Biological Studies discovered, when out-of-control blood sugar levels disable the molecular switch that normally shuts off sugar production in the liver in response to rising levels of insulin.
Their findings, published in the March 7 issue of Science suggest that appropriate inhibitors of the enzymatic pathway that blocks the "sugar-off"-switch might be useful in lowering glucose levels in diabetic individuals and reducing long-term complications associated with the disease.
"The islet cells in the pancreas can compensate with increased insulin production only for so long when confronted with chronic obesity and inactivity," says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. "As a result glucose levels start to rise causing a host of problems."
Just like a flex-fuel vehicle that can run on either gasoline or ethanol, the human body can switch between different types of fuel: During the day the body mostly burns glucose, and during the night or prolonged fasting, it burns primarily fat. But neither flex-fuel engines nor human brains can run on ethanol or fat alone - a little bit of gasoline or glucose needs to be thrown into the mix to keep either one of them humming.
Three years ago, Montminy discovered a "fasting switch" called CRTC2 (formerly known as TORC2) that flips on glucose production in the liver when blood glucose levels run low during the night. After a meal, the hormone insulin normally shuts down CRTC2 ensuring that blood sugar levels don't rise too high.
In many patients with type II diabetes, however, CRTC2 no longer responds to rising insulin levels and as a result the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. The Salk researchers were interested in the molecular mechanism that leads to the breakdown of the normally tightly regulated feedback loop.
Mice whose livers light up - courtesy of the luciferase gene, which produces the glow in fireflies - as soon as CRTC2 is turned on, led post-doctoral fellow and first author Renaud Dentin, Ph.D., onto the trail of the hexosamine biosynthetic pathway. Activation of the pathway promotes the addition of sugar molecules to proteins, a process also known as O-glycosylation. "It had been known that increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway," says Dentin. "But we had no idea that the resulting O-glycosylation would lock CRTC2 in the 'on'-position."
Normally, the rise in insulin after a meal activates a liver enzyme called SIK2. The enzyme chemically tags CRTC2 with a phosphate group, marooning the protein outside the cell's nucleus. Unable to reach the genes involved in gluconeogenesis, CRTC2 is powerless to turn them on and glucose production in the liver ceases.
In the presence of excessive glucose levels, however, the hexosamine biosynthetic pathway is activated and blocks crucial phosporylation sites on CRTC2 by adding sugar molecules instead. CRTC2 can no longer be phosphorylated in response to rising insulin levels and is now free to slip into the nucleus and keep the gluconeogenic program going.
Shutting down the O-glycosylation pathway should then get the body's own glucose production under control, the researchers reasoned. Just as predicted, glucose tolerance and insulin sensitivity markedly improved in insulin resistant diabetic mice and mice fed a high fat diet - who both suffered from hyperglycemia - when Dentin and his colleagues decreased the activity of the hexosamine biosynthetic pathway in the liver of these animals.
"What I really would like to do is to use the glowing mice to screen for drugs that decrease gluconeogenesis," says Montminy. "Imagine hyperglycemic mice whose livers light up because CRTC2 is on all the time. When you feed them a drug that inhibits O-glycosylation the light dims and you know you have compound that's effective in living animals and you know how it works."
Researchers who also contributed to the study include research assistant Susan Hedrick, in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute, Jianxin Xie, Ph.D., at Cell Signaling Technology in Danvers, Massachusetts, and professor John Yates III, Ph.D., at the Scripps Research Institute in La Jolla, California.
This work was supported by NIH grant RO1 GM037828, by the Clayton Medical Research Foundation, Inc., and by the Kiekhefer Foundation.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Source: Gina Kirchweger
Salk Institute
The vicious circle gets rolling, researchers at the Salk Institute for Biological Studies discovered, when out-of-control blood sugar levels disable the molecular switch that normally shuts off sugar production in the liver in response to rising levels of insulin.
Their findings, published in the March 7 issue of Science suggest that appropriate inhibitors of the enzymatic pathway that blocks the "sugar-off"-switch might be useful in lowering glucose levels in diabetic individuals and reducing long-term complications associated with the disease.
"The islet cells in the pancreas can compensate with increased insulin production only for so long when confronted with chronic obesity and inactivity," says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. "As a result glucose levels start to rise causing a host of problems."
Just like a flex-fuel vehicle that can run on either gasoline or ethanol, the human body can switch between different types of fuel: During the day the body mostly burns glucose, and during the night or prolonged fasting, it burns primarily fat. But neither flex-fuel engines nor human brains can run on ethanol or fat alone - a little bit of gasoline or glucose needs to be thrown into the mix to keep either one of them humming.
Three years ago, Montminy discovered a "fasting switch" called CRTC2 (formerly known as TORC2) that flips on glucose production in the liver when blood glucose levels run low during the night. After a meal, the hormone insulin normally shuts down CRTC2 ensuring that blood sugar levels don't rise too high.
In many patients with type II diabetes, however, CRTC2 no longer responds to rising insulin levels and as a result the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. The Salk researchers were interested in the molecular mechanism that leads to the breakdown of the normally tightly regulated feedback loop.
Mice whose livers light up - courtesy of the luciferase gene, which produces the glow in fireflies - as soon as CRTC2 is turned on, led post-doctoral fellow and first author Renaud Dentin, Ph.D., onto the trail of the hexosamine biosynthetic pathway. Activation of the pathway promotes the addition of sugar molecules to proteins, a process also known as O-glycosylation. "It had been known that increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway," says Dentin. "But we had no idea that the resulting O-glycosylation would lock CRTC2 in the 'on'-position."
Normally, the rise in insulin after a meal activates a liver enzyme called SIK2. The enzyme chemically tags CRTC2 with a phosphate group, marooning the protein outside the cell's nucleus. Unable to reach the genes involved in gluconeogenesis, CRTC2 is powerless to turn them on and glucose production in the liver ceases.
In the presence of excessive glucose levels, however, the hexosamine biosynthetic pathway is activated and blocks crucial phosporylation sites on CRTC2 by adding sugar molecules instead. CRTC2 can no longer be phosphorylated in response to rising insulin levels and is now free to slip into the nucleus and keep the gluconeogenic program going.
Shutting down the O-glycosylation pathway should then get the body's own glucose production under control, the researchers reasoned. Just as predicted, glucose tolerance and insulin sensitivity markedly improved in insulin resistant diabetic mice and mice fed a high fat diet - who both suffered from hyperglycemia - when Dentin and his colleagues decreased the activity of the hexosamine biosynthetic pathway in the liver of these animals.
"What I really would like to do is to use the glowing mice to screen for drugs that decrease gluconeogenesis," says Montminy. "Imagine hyperglycemic mice whose livers light up because CRTC2 is on all the time. When you feed them a drug that inhibits O-glycosylation the light dims and you know you have compound that's effective in living animals and you know how it works."
Researchers who also contributed to the study include research assistant Susan Hedrick, in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute, Jianxin Xie, Ph.D., at Cell Signaling Technology in Danvers, Massachusetts, and professor John Yates III, Ph.D., at the Scripps Research Institute in La Jolla, California.
This work was supported by NIH grant RO1 GM037828, by the Clayton Medical Research Foundation, Inc., and by the Kiekhefer Foundation.
The Salk Institute for Biological Studies in La Jolla, California, is an independent nonprofit organization dedicated to fundamental discoveries in the life sciences, the improvement of human health and the training of future generations of researchers. Jonas Salk, M.D., whose polio vaccine all but eradicated the crippling disease poliomyelitis in 1955, opened the Institute in 1965 with a gift of land from the City of San Diego and the financial support of the March of Dimes.
Source: Gina Kirchweger
Salk Institute
суббота, 14 мая 2011 г.
Free IPhone App For Molecule Of The Week Unveiled By American Chemical Society
The American Chemical Society's (ACS) Molecule of the Week (MOTW) is one of the most popular destinations on the ACS Web site, and it may be getting more popular. The reason: ACS has unveiled a MOTW mobile application for iTunes.
Current MOTW enthusiasts - and everyone else interested in science - also can download the new app from acs/motwapp.
Each week, the MOTW presents a different molecule, with a description, image of the molecular structure, links to records from the Chemical Abstracts (CAS) RegistrySM, and other information. From allicin (the molecule responsible for the odor of crushed garlic) and ascorbic acid (vitamin C) to xylitol (the sugar substitute) and zingerone (which gives ginger a hot taste), there are always fascinating molecules that relate chemistry to everyday life.
The new app automatically delivers these features (plus a game quiz) to the convenience of an iPhone, iPod Touch and the just-released iPad. There are other cool features as well - such as a clue that appears with a shake of an iPhone or iPod - all designed to make the MOTW iPhone app not only informative but fun, too.
Source:
Michael Bernstein
American Chemical Society
Current MOTW enthusiasts - and everyone else interested in science - also can download the new app from acs/motwapp.
Each week, the MOTW presents a different molecule, with a description, image of the molecular structure, links to records from the Chemical Abstracts (CAS) RegistrySM, and other information. From allicin (the molecule responsible for the odor of crushed garlic) and ascorbic acid (vitamin C) to xylitol (the sugar substitute) and zingerone (which gives ginger a hot taste), there are always fascinating molecules that relate chemistry to everyday life.
The new app automatically delivers these features (plus a game quiz) to the convenience of an iPhone, iPod Touch and the just-released iPad. There are other cool features as well - such as a clue that appears with a shake of an iPhone or iPod - all designed to make the MOTW iPhone app not only informative but fun, too.
Source:
Michael Bernstein
American Chemical Society
пятница, 13 мая 2011 г.
Gene Mutation Uncovered That Cuts Colon Polyps And May Suppress Cancer
Cancer biologists at the Kimmel Cancer Center at Jefferson have found a gene mutation that can dramatically reduce the number of colon polyps that develop, and in turn, potentially cut the risk of cancer.
In experiments with mice genetically prone to develop polyps, researchers discovered that animals carrying one copy of the damaged gene, Atp5a1, had about 90 percent fewer polyps in the small intestine and colon. Because people with large numbers of such polyps are at significantly higher risk to develop colon cancer, the finding may provide new ways to diagnose, prevent and treat colon cancer, the scientists say. They report their findings online in the journal Genome Research.
The researchers, led by Arthur Buchberg, Ph.D., and Linda Siracusa, Ph.D., both associate professors of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, studied a type of mice called Min (multiple intestinal neoplasia). Such mice carry mutations in the Apc gene, which causes the development of intestinal tumors in mice. An alteration in the corresponding human gene, APC, is the first step in most cases of the development of colon polyps and the majority of colorectal cancers.
It turns out that Atp5a1, which is crucial for the cell's energy production, is also a 'modifier' gene. Modifier genes play roles in individual susceptibility to cancers. "Modifier genes alter a phenotype dictated by other genes," explains Dr. Siracusa. "If a person inherits a mutation in the APC gene, a modifier gene can make that number of polyps - and tumors - either higher or lower, and can mean a person is more prone or resistant to developing polyps and tumors."
In earlier work, the husband and wife team had identified the general region on the chromosome for the mutation. "Now, we've identified the gene and it's very important - it encodes a subunit of the ATP synthase protein, which is known as the molecular motor in the mitochondria, and responsible for the production of ATP and energy in cells," says Dr. Buchberg. They have dubbed Atp5a1 'Mom2,' for Modifier of Min 2 gene, having previously identified the first modifier of Min mice, Mom1.
"No one as far as we know has ever found a mutation in this gene," says Dr. Siracusa, noting that both gene mutations - Apc and Atp5a1 - are on mouse chromosome 18. "If the other normal chromosome is lost for some reason, or mice have two copies of the mutant Atp5a1, they die in embryonic development, presumably because the cells lack an energy source."
The corresponding human gene, ATP5A1, is also located on chromosome 18, in a region that sometimes shows genetic mutations in colon tumors.
Colorectal cancer is currently the second leading cause of cancer death in the United States. The work was supported by grants from the National Institutes of Health (NIH) and the National Cancer Institute (NCI).
Contact:
Steve Benowitz or Jackie Kozloski
Thomas Jefferson University
In experiments with mice genetically prone to develop polyps, researchers discovered that animals carrying one copy of the damaged gene, Atp5a1, had about 90 percent fewer polyps in the small intestine and colon. Because people with large numbers of such polyps are at significantly higher risk to develop colon cancer, the finding may provide new ways to diagnose, prevent and treat colon cancer, the scientists say. They report their findings online in the journal Genome Research.
The researchers, led by Arthur Buchberg, Ph.D., and Linda Siracusa, Ph.D., both associate professors of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, studied a type of mice called Min (multiple intestinal neoplasia). Such mice carry mutations in the Apc gene, which causes the development of intestinal tumors in mice. An alteration in the corresponding human gene, APC, is the first step in most cases of the development of colon polyps and the majority of colorectal cancers.
It turns out that Atp5a1, which is crucial for the cell's energy production, is also a 'modifier' gene. Modifier genes play roles in individual susceptibility to cancers. "Modifier genes alter a phenotype dictated by other genes," explains Dr. Siracusa. "If a person inherits a mutation in the APC gene, a modifier gene can make that number of polyps - and tumors - either higher or lower, and can mean a person is more prone or resistant to developing polyps and tumors."
In earlier work, the husband and wife team had identified the general region on the chromosome for the mutation. "Now, we've identified the gene and it's very important - it encodes a subunit of the ATP synthase protein, which is known as the molecular motor in the mitochondria, and responsible for the production of ATP and energy in cells," says Dr. Buchberg. They have dubbed Atp5a1 'Mom2,' for Modifier of Min 2 gene, having previously identified the first modifier of Min mice, Mom1.
"No one as far as we know has ever found a mutation in this gene," says Dr. Siracusa, noting that both gene mutations - Apc and Atp5a1 - are on mouse chromosome 18. "If the other normal chromosome is lost for some reason, or mice have two copies of the mutant Atp5a1, they die in embryonic development, presumably because the cells lack an energy source."
The corresponding human gene, ATP5A1, is also located on chromosome 18, in a region that sometimes shows genetic mutations in colon tumors.
Colorectal cancer is currently the second leading cause of cancer death in the United States. The work was supported by grants from the National Institutes of Health (NIH) and the National Cancer Institute (NCI).
Contact:
Steve Benowitz or Jackie Kozloski
Thomas Jefferson University
среда, 11 мая 2011 г.
Fingerprints Provide Clues To More Than Just Identity
Fingerprints can reveal critical evidence, as well as an identity, with the use of a new technology developed at Purdue University that detects trace amounts of explosives, drugs or other materials left behind in the prints.
The new technology also can distinguish between overlapping fingerprints left by different individuals - a difficult task for current optical forensic methods.
A team led by R. Graham Cooks, Purdue's Henry Bohn Hass Distinguished Professor of Analytical Chemistry, has created a tool that reads and provides an image of a fingerprint's chemical signature. The technology can be used to determine what a person recently handled.
"The classic example of a fingerprint is an ink imprint showing the unique swirls and loops used for identification, but fingerprints also leave behind a unique distribution of molecular compounds," Cooks said. "Some of the residues left behind are from naturally occurring compounds in the skin and some are from other surfaces or materials a person has touched."
The team's research will be detailed in a paper published in Friday's (Aug. 8) issue of Science.
Demian R. Ifa, a Purdue postdoctoral researcher and the paper's lead author, said the technology also can easily uncover fingerprints buried beneath others.
"Because the distribution of compounds found in each fingerprint can be unique, we also can use this technology to pull one fingerprint out from beneath layers of other fingerprints," Ifa said. "By looking for compounds we know to be present in a certain fingerprint, we can separate it from the others and obtain a crystal clear image of that fingerprint. The image could then be used with fingerprint recognition software to identify an individual."
Researchers examined fingerprints in situ or lifted them from different surfaces such as glass, metal and plastic using common clear plastic tape. They then analyzed them with a mass spectrometry technique developed in Cooks' lab.
Mass spectrometry works by first turning molecules into ions, or electrically charged versions of themselves, so their masses can be analyzed. Conventional mass spectrometry requires chemical separations, manipulations of samples and containment in a vacuum chamber for ionization and analysis. Cooks' technology performs the ionization step in the air or directly on surfaces outside of the mass spectrometer's vacuum chamber, making the process much faster and more portable, Ifa said.
The Purdue procedure performs the ionization step by spraying a stream of water in the presence of an electric field to create positively charged water droplets. Water molecules in the droplets contain an extra proton and are called ions. When the charged water droplets hit the surface of the sample being tested, they transfer their extra proton to molecules in the sample, turning them into ions. The ionized molecules are then vacuumed into the mass spectrometer to be measured and analyzed.
Researchers placed a section of tape containing a lifted fingerprint on a moving stage in front of the spectrometer. The spectrometer then sprayed small sections of the sample with the charged water droplets, obtaining data for each section and combining the data sets to create an analysis of the sample as a whole, Ifa said. Software was used to map the information and create an image of the fingerprint from the distribution and intensity of selected ions.
Additional co-authors of the paper are Nicholas E. Manicke and Allison L. Dill, graduate students in Purdue's chemistry department.
The research was performed within Purdue's Center for Analytical Instrumentation Development located at the Bindley Biosciences Center in Purdue's Discovery Park.
Cooks' device, called desorption electrospray ionization or DESI, has been commercialized by Indianapolis-based Prosolia Inc., and the research was funded by Office of Naval Research and Prosolia Inc.
Writer: Elizabeth K. Gardner
Photo
purdue
The new technology also can distinguish between overlapping fingerprints left by different individuals - a difficult task for current optical forensic methods.
A team led by R. Graham Cooks, Purdue's Henry Bohn Hass Distinguished Professor of Analytical Chemistry, has created a tool that reads and provides an image of a fingerprint's chemical signature. The technology can be used to determine what a person recently handled.
"The classic example of a fingerprint is an ink imprint showing the unique swirls and loops used for identification, but fingerprints also leave behind a unique distribution of molecular compounds," Cooks said. "Some of the residues left behind are from naturally occurring compounds in the skin and some are from other surfaces or materials a person has touched."
The team's research will be detailed in a paper published in Friday's (Aug. 8) issue of Science.
Demian R. Ifa, a Purdue postdoctoral researcher and the paper's lead author, said the technology also can easily uncover fingerprints buried beneath others.
"Because the distribution of compounds found in each fingerprint can be unique, we also can use this technology to pull one fingerprint out from beneath layers of other fingerprints," Ifa said. "By looking for compounds we know to be present in a certain fingerprint, we can separate it from the others and obtain a crystal clear image of that fingerprint. The image could then be used with fingerprint recognition software to identify an individual."
Researchers examined fingerprints in situ or lifted them from different surfaces such as glass, metal and plastic using common clear plastic tape. They then analyzed them with a mass spectrometry technique developed in Cooks' lab.
Mass spectrometry works by first turning molecules into ions, or electrically charged versions of themselves, so their masses can be analyzed. Conventional mass spectrometry requires chemical separations, manipulations of samples and containment in a vacuum chamber for ionization and analysis. Cooks' technology performs the ionization step in the air or directly on surfaces outside of the mass spectrometer's vacuum chamber, making the process much faster and more portable, Ifa said.
The Purdue procedure performs the ionization step by spraying a stream of water in the presence of an electric field to create positively charged water droplets. Water molecules in the droplets contain an extra proton and are called ions. When the charged water droplets hit the surface of the sample being tested, they transfer their extra proton to molecules in the sample, turning them into ions. The ionized molecules are then vacuumed into the mass spectrometer to be measured and analyzed.
Researchers placed a section of tape containing a lifted fingerprint on a moving stage in front of the spectrometer. The spectrometer then sprayed small sections of the sample with the charged water droplets, obtaining data for each section and combining the data sets to create an analysis of the sample as a whole, Ifa said. Software was used to map the information and create an image of the fingerprint from the distribution and intensity of selected ions.
Additional co-authors of the paper are Nicholas E. Manicke and Allison L. Dill, graduate students in Purdue's chemistry department.
The research was performed within Purdue's Center for Analytical Instrumentation Development located at the Bindley Biosciences Center in Purdue's Discovery Park.
Cooks' device, called desorption electrospray ionization or DESI, has been commercialized by Indianapolis-based Prosolia Inc., and the research was funded by Office of Naval Research and Prosolia Inc.
Writer: Elizabeth K. Gardner
Photo
purdue
вторник, 10 мая 2011 г.
Potential Targeted Treatment For Rare Form Of Anemia
University of Cincinnati (UC) researchers have identified the specific biological mechanisms believed to lead to a rare and incurable blood disease known as Diamond Blackfan anemia (DBA). Scientists say with further investigation, their discoveries could result in drastic changes to current thinking about treatment for this disease and may lead to promising new drug therapies.
George Thomas, PhD, Stefano Fumagalli, PhD, and collaborators reported their findings online ahead of print in the journal Nature Cell Biology on Sunday, March 15, 2009. The research will also appear in the April print issue of the journal and was presented at the 10th annual International Diamond Blackfan Anemia Consensus Conference in New York.
DBA is a rare blood disorder characterized by the bone marrow's failure to produce red blood cells. This failure is due to an intrinsic defect that makes the red blood cells prone to cell death before they mature. Red blood cells travel through the bloodstream to deliver oxygen to the body's tissues, which is critical to the health and proper function of all tissues.
According to the Centers for Disease Control and Prevention, approximately 25-35 new cases of DBA are diagnosed each year, with the majority of patients being identified before age 1. The most common treatments include blood transfusions and corticosteroids. The disease is characterized by extreme anemia - with a propensity to develop into leukemia - and often has no cure.
Using a preclinical laboratory model, Thomas' team was able to explain how cell death occurs in DBA and identified a specific step in the biological chain of events leading to disease onset where targeted medical intervention may effectively slow - or even stop - red blood cell death.
DBA has recently been attributed to a ribosomal protein defect that the UC team hypothesizes leads to abnormal activation of p53, causing premature death of red blood cells. P53 is a protein that normally functions to trigger "cell suicide" in response to severe cellular damage, therefore protecting the body from overgrowth of defective cells.
Previous research has attributed p53 activation to the passive diffusion of ribosomal protein L11 from the nucleolus, the part of the nucleus where ribosomes are produced to the nucleoplasm.
The UC research, however, suggests that p53 activation is not due to nucleolar breakdown, but is actually the result of an active increase in the production of L11. They suggest that in DBA, a series of L11 interactions results in cell cycle arrest and ultimately leads to cell death and anemia.
"Previous studies suggested L11 was passively coming out of the nucleolus when ribosome production was disrupted. Our study actually showed that the nucleolus stayed intact as ribosomes were still being produced, suggesting selective upregulation of L11," explains Thomas, the John and Gladys Strauss endowed professor of cancer biology at UC and scientific director at UC's Genome Research Institute. "If we can target the L11 interaction, we might be able to spare other stress pathways that mediate potential benefits of p53 induction."
Thomas believes DBA slowly evolves into cancer when this specific molecular checkpoint is lost. This results in the body being genetically reprogrammed over time, leading to the onset of additional medical problems, particularly leukemia, in DBA patients later in life.
"By understanding the chain of biological events leading to this abnormal cell death and targeting the specific molecular checkpoint that controls cell death, we may be able to develop new drugs that would interrupt or stop the process and allow the body to recover, rebuilding healthy bone marrow," adds Thomas.
Notes:
This research was funded in part by the National Cancer Institute's Mouse Models in Human Cancer Consortium. In addition to Thomas and Funagalli, manuscript co-authors include Sandy Schwemberger, PhD, and George Babcock, MD, and Arti Neb-Gulati of UC; Alessandro Di Cara, PhD of Friedrich Miescher Institute for Biomedical Research in Switzerland; Francois Natt and Jonathan Hall of Novartis Institutes for Biomedical Research in Switzerland; Rosa Bernardi MD, PhD, of San Raffaele, Institute Via Olgettina in Italy; and Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston.
"It is our hope that these discoveries will lead to new treatments for the disease. As anyone can imagine, in any disease where more than 90 percent of patients present before 1 year of age the families clamor for additional breakthroughs," adds Marie Arturi, executive director of the Daniella Maria Arturi Foundation. "We are deeply indebted to all who help in this effort."
Source: Amanda J. Harper
University of Cincinnati
George Thomas, PhD, Stefano Fumagalli, PhD, and collaborators reported their findings online ahead of print in the journal Nature Cell Biology on Sunday, March 15, 2009. The research will also appear in the April print issue of the journal and was presented at the 10th annual International Diamond Blackfan Anemia Consensus Conference in New York.
DBA is a rare blood disorder characterized by the bone marrow's failure to produce red blood cells. This failure is due to an intrinsic defect that makes the red blood cells prone to cell death before they mature. Red blood cells travel through the bloodstream to deliver oxygen to the body's tissues, which is critical to the health and proper function of all tissues.
According to the Centers for Disease Control and Prevention, approximately 25-35 new cases of DBA are diagnosed each year, with the majority of patients being identified before age 1. The most common treatments include blood transfusions and corticosteroids. The disease is characterized by extreme anemia - with a propensity to develop into leukemia - and often has no cure.
Using a preclinical laboratory model, Thomas' team was able to explain how cell death occurs in DBA and identified a specific step in the biological chain of events leading to disease onset where targeted medical intervention may effectively slow - or even stop - red blood cell death.
DBA has recently been attributed to a ribosomal protein defect that the UC team hypothesizes leads to abnormal activation of p53, causing premature death of red blood cells. P53 is a protein that normally functions to trigger "cell suicide" in response to severe cellular damage, therefore protecting the body from overgrowth of defective cells.
Previous research has attributed p53 activation to the passive diffusion of ribosomal protein L11 from the nucleolus, the part of the nucleus where ribosomes are produced to the nucleoplasm.
The UC research, however, suggests that p53 activation is not due to nucleolar breakdown, but is actually the result of an active increase in the production of L11. They suggest that in DBA, a series of L11 interactions results in cell cycle arrest and ultimately leads to cell death and anemia.
"Previous studies suggested L11 was passively coming out of the nucleolus when ribosome production was disrupted. Our study actually showed that the nucleolus stayed intact as ribosomes were still being produced, suggesting selective upregulation of L11," explains Thomas, the John and Gladys Strauss endowed professor of cancer biology at UC and scientific director at UC's Genome Research Institute. "If we can target the L11 interaction, we might be able to spare other stress pathways that mediate potential benefits of p53 induction."
Thomas believes DBA slowly evolves into cancer when this specific molecular checkpoint is lost. This results in the body being genetically reprogrammed over time, leading to the onset of additional medical problems, particularly leukemia, in DBA patients later in life.
"By understanding the chain of biological events leading to this abnormal cell death and targeting the specific molecular checkpoint that controls cell death, we may be able to develop new drugs that would interrupt or stop the process and allow the body to recover, rebuilding healthy bone marrow," adds Thomas.
Notes:
This research was funded in part by the National Cancer Institute's Mouse Models in Human Cancer Consortium. In addition to Thomas and Funagalli, manuscript co-authors include Sandy Schwemberger, PhD, and George Babcock, MD, and Arti Neb-Gulati of UC; Alessandro Di Cara, PhD of Friedrich Miescher Institute for Biomedical Research in Switzerland; Francois Natt and Jonathan Hall of Novartis Institutes for Biomedical Research in Switzerland; Rosa Bernardi MD, PhD, of San Raffaele, Institute Via Olgettina in Italy; and Pier Paolo Pandolfi, MD, PhD, of Beth Israel Deaconess Medical Center in Boston.
"It is our hope that these discoveries will lead to new treatments for the disease. As anyone can imagine, in any disease where more than 90 percent of patients present before 1 year of age the families clamor for additional breakthroughs," adds Marie Arturi, executive director of the Daniella Maria Arturi Foundation. "We are deeply indebted to all who help in this effort."
Source: Amanda J. Harper
University of Cincinnati
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