A team of Michigan State University scientists - using a new cooling method they created - has uncovered the inner workings of a key iron-containing enzyme, a discovery that could help researchers develop new medicines or understand how enzymes repair DNA.
Taurine/alpha-ketoglutarate dioxygenase, known as TauD, is a bacterial enzyme that is important in metabolism. Enzymes in this family repair DNA, sense oxygen and help produce antibiotics.
Specifically, the MSU team was interested in how iron and oxygen atoms reacted together in the enzyme. Understanding how TauD works, which serves as a model for many other proteins, has implications in the scientific and medical fields, said Robert Hausinger, MSU professor of microbiology and molecular genetics.
"This is a broad enzyme family with similar mechanisms," he said. "Understanding how TauD works sheds light on how many other enzymes function from bacteria to humans. This can be applicable to a wide variety of essential enzymes of medical and agricultural interest."
For example, Hausinger said, understanding how the enzyme works can help scientists design inhibitors to prevent it from doing its job, which is a key step in preventing diseases. Also, understanding how the iron inserts oxygen atoms into other molecules provides insight into how enzymes metabolize the majority of medical drugs or environmental pollutants in the human body.
As understanding how enzymes work can be very complicated - such reactions often are complex, fast and require multiple steps - the MSU team developed a new method to follow the TauD reaction. The difficult part for researchers was to slow down the reaction enough that the individual steps can be observed; one way to slow down an enzymatic reaction is to cool it.
The team used a stream of cold nitrogen gas to slow down the reaction at -36 C (-33 F). To prevent freezing and to keep the reaction going, the scientists used ethylene glycol - the same antifreeze that goes in vehicles.
Once the reaction started, the team used lasers - in an advanced method called Raman spectroscopy - to follow the vibrations of iron and oxygen atoms in TauD to determine how the reaction progressed. They found never seen before steps in the TauD reaction, overturning conventional thought.
The project was a collaboration between the laboratories of Hausinger and Denis Proshlyakov of MSU's Department of Biochemistry and Molecular Biology, with support from MSU colleague Piotr Grzyska and Evan Appelman of the Argonne National Laboratory in Chicago.
The research, supported by the National Institutes of Health, was recently published in the Proceedings of National Academy of Science Early Edition.
Source:
Jason Cody
Michigan State University
понедельник, 20 июня 2011 г.
воскресенье, 19 июня 2011 г.
Light Shed On Modern Pandemic By Ancient Retrovirus
Human resistance to a retrovirus that infected chimpanzees and other nonhuman primates 4 million years ago ironically may be at least partially responsible for the susceptibility of humans to HIV infection today.
These findings, reported by a team of researchers at Fred Hutchinson Cancer Research Center in Science, provide a better understanding of this modern pandemic infection through the study of an ancient virus called Pan troglodytes endogenous retrovirus, or PtERV1.
"This ancient virus is a battle that humans have already won. Humans are not susceptible to it and have probably been resistant throughout millennia," said senior author Michael Emerman, Ph.D., a member of the Human Biology and Basic Sciences divisions at the Hutchinson Center. "However, we found that during primate evolution, this innate immunity to one virus may have made us more vulnerable to HIV."
Evidence of human immunity to this ancient retrovirus first emerged with the sequencing of the chimpanzee genome. "When the chimp genome was sequenced, a team of scientists at the University of Washington led by Evan Eichler found the largest difference overall between the chimp and human genomes was the presence or absence of PtERV1," Emerman said. "Chimps have 130 copies of PtERV1 and humans have none."
It is believed that retroviruses have been entering the genome for many millions of years, and so humans share many retroviral DNA fragments with their primate cousins. Such vestiges of primitive infection, rendered inactive by eons of genetic mutation, make up about 8 percent of the human genome.
Innate protection against PtERV1 in humans could be credited, the researchers believe, to the presence of an ancient, rapidly evolving antiviral defense gene called TRIM5a, which produces a protein that binds to and destroys the virus before it can replicate within the body.
"We know that PtERV1 infected chimps, gorillas and old-world monkeys 4 million years ago but left no traces of having infected humans. Our theory is that this is because humans had this innate viral defense system," Emerman said.
To test their hypothesis, Emerman and co-authors Harmit Singh Malik, Ph.D., an evolutionary biologist and an assistant member of the Center's Basic Sciences Division, and Shari Kaiser, a graduate student in Emerman's laboratory, used DNA sequences from the chimp genome to reconstruct a small part of the PtERV1 virus.
They reassembled about one-fifth of the virus by taking dozens of PtERV1 sequences and aligning them to create an "ancestral" sequence, teasing out areas of commonality between them. They then used this information to make a partial viral genome. During reconstruction the viral segment was debilitated, enabling only one round of infection in cells. Working with cells in the laboratory, the researchers found that the human antiviral protein TRIM5a effectively neutralizes this extinct retrovirus, which never successfully fixed into the human genome.
"However, while TRIM5a may have served humans well millions of years ago, the antiviral protein does not seem to be good at defending against any of the retroviruses that currently infect humans, such as HIV-1," Emerman said. "In the end, this drove human evolution to be more susceptible to HIV." For example, the researchers found that changes in TRIM5a that make it better at fighting HIV actually inhibit its ability to stop PtERV1 and vice versa, which indicates that this antiviral gene may only be good at fighting off one virus at a time.
Uncovering the story of TRIM5a's role in battling one ancient retrovirus while increasing human susceptibility to modern-day HIV "is a lot like doing archaeology -- figuring out how humans have become who we are today and why we are or are not susceptible to modern viruses that presently circulate," Emerman said.
In fact, this emerging area of research, which seeks to better understand modern infections by studying ancient viruses, is known as "paleovirology." "Ultimately," said co-author Malik, "if we want to understand why our defenses are the way they are, the answers inevitably lie in these ancient viruses more so than the ones that have affected us only recently, such as HIV."
This work was supported by National Institutes of Health grants to Emerman, a Searle Scholar Award to Malik and a National Science Foundation graduate fellowship to Kaiser.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit ffhcrc/.
Contact: Kristen Woodward
Fred Hutchinson Cancer Research Center
These findings, reported by a team of researchers at Fred Hutchinson Cancer Research Center in Science, provide a better understanding of this modern pandemic infection through the study of an ancient virus called Pan troglodytes endogenous retrovirus, or PtERV1.
"This ancient virus is a battle that humans have already won. Humans are not susceptible to it and have probably been resistant throughout millennia," said senior author Michael Emerman, Ph.D., a member of the Human Biology and Basic Sciences divisions at the Hutchinson Center. "However, we found that during primate evolution, this innate immunity to one virus may have made us more vulnerable to HIV."
Evidence of human immunity to this ancient retrovirus first emerged with the sequencing of the chimpanzee genome. "When the chimp genome was sequenced, a team of scientists at the University of Washington led by Evan Eichler found the largest difference overall between the chimp and human genomes was the presence or absence of PtERV1," Emerman said. "Chimps have 130 copies of PtERV1 and humans have none."
It is believed that retroviruses have been entering the genome for many millions of years, and so humans share many retroviral DNA fragments with their primate cousins. Such vestiges of primitive infection, rendered inactive by eons of genetic mutation, make up about 8 percent of the human genome.
Innate protection against PtERV1 in humans could be credited, the researchers believe, to the presence of an ancient, rapidly evolving antiviral defense gene called TRIM5a, which produces a protein that binds to and destroys the virus before it can replicate within the body.
"We know that PtERV1 infected chimps, gorillas and old-world monkeys 4 million years ago but left no traces of having infected humans. Our theory is that this is because humans had this innate viral defense system," Emerman said.
To test their hypothesis, Emerman and co-authors Harmit Singh Malik, Ph.D., an evolutionary biologist and an assistant member of the Center's Basic Sciences Division, and Shari Kaiser, a graduate student in Emerman's laboratory, used DNA sequences from the chimp genome to reconstruct a small part of the PtERV1 virus.
They reassembled about one-fifth of the virus by taking dozens of PtERV1 sequences and aligning them to create an "ancestral" sequence, teasing out areas of commonality between them. They then used this information to make a partial viral genome. During reconstruction the viral segment was debilitated, enabling only one round of infection in cells. Working with cells in the laboratory, the researchers found that the human antiviral protein TRIM5a effectively neutralizes this extinct retrovirus, which never successfully fixed into the human genome.
"However, while TRIM5a may have served humans well millions of years ago, the antiviral protein does not seem to be good at defending against any of the retroviruses that currently infect humans, such as HIV-1," Emerman said. "In the end, this drove human evolution to be more susceptible to HIV." For example, the researchers found that changes in TRIM5a that make it better at fighting HIV actually inhibit its ability to stop PtERV1 and vice versa, which indicates that this antiviral gene may only be good at fighting off one virus at a time.
Uncovering the story of TRIM5a's role in battling one ancient retrovirus while increasing human susceptibility to modern-day HIV "is a lot like doing archaeology -- figuring out how humans have become who we are today and why we are or are not susceptible to modern viruses that presently circulate," Emerman said.
In fact, this emerging area of research, which seeks to better understand modern infections by studying ancient viruses, is known as "paleovirology." "Ultimately," said co-author Malik, "if we want to understand why our defenses are the way they are, the answers inevitably lie in these ancient viruses more so than the ones that have affected us only recently, such as HIV."
This work was supported by National Institutes of Health grants to Emerman, a Searle Scholar Award to Malik and a National Science Foundation graduate fellowship to Kaiser.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams of world-renowned scientists and humanitarians work together to prevent, diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers, including three Nobel laureates, bring a relentless pursuit and passion for health, knowledge and hope to their work and to the world. For more information, please visit ffhcrc/.
Contact: Kristen Woodward
Fred Hutchinson Cancer Research Center
суббота, 18 июня 2011 г.
Moving Closer To Solving Lou Gehrig's Disease Mystery
Chemists from UCLA and the University of Florence in Italy may have solved an important mystery about a protein that plays a key role in a particular form of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, a progressive, fatal neurodegenerative disorder that strikes without warning.
Joan Selverstone Valentine, UCLA professor of chemistry and biochemistry, has studied the protein - copper-zinc superoxide dismutase - since the 1970s, long before it was implicated in ALS in 1993. Since the link was discovered, Valentine's laboratory has made more than two dozen mutant, ALS-causing enzymes, most of which have only one wrong amino acid out of 153, to try to understand their properties and learn what makes them toxic.
"Some of the mutant proteins are very different from the normal protein, but others are virtually identical to the normal protein - yet they all cause the disease," said Valentine, a member of UCLA's Molecular Biology Institute. "That was the real mystery. You wrack your brain: What is similar among all these proteins" They seem so different. How can they all cause the same disease""
Now Valentine and her colleagues, including Ivano Bertini, professor of chemistry at the University of Florence and director of the European Magnetic Resonance Center, think they know. In ALS patients, the protein's copper and zinc may not be there at all. They present evidence for this hypothesis in new research published in Proceedings of the National Academy of Sciences, online and available in the journal's July 3 print edition.
"If we keep the metals entirely out of the protein, we can explain the toxicity, since even the normal protein forms aggregate at physiological conditions when the metals are gone," Valentine said. "It was such a puzzle, but this hypothesis can solve it."
If scientists can figure out why ALS patients lack the copper and zinc, that would be a major advance that could lead to treatment, she said.
The research team is testing the hypothesis. Valentine, who was elected to the National Academy of Sciences in 2005 and to the American Academy of Arts and Sciences this year, praised her colleagues. "This research is the result of a long, successful international collaboration between UCLA and the University of Florence," she said. "Our colleagues in Italy are exceptional scientists."
Co-authors on the Proceedings of the National Academy of Sciences research are Lucia Banci, a professor of chemistry at the University of Florence who is affiliated with the FiorGen Foundation; Armando Durazo, a UCLA graduate student of chemistry and biochemistry; Stefania Girotto, a postdoctoral scholar at the University of Florence; Edith Butler Gralla, a senior research chemist at UCLA; Manuele Martinelli and Miguela Vieru, graduate students at the University of Florence; and Julian P. Whitelegge, an adjunct professor at the Semel Institute for Neuroscience and Human Behavior at UCLA and UCLA's Brain Research Institute.
Copper-zinc superoxide dismutase, which was discovered in the 1960s, is an antioxidant enzyme that protects cells from free radicals, unstable atoms or molecules that can cause cell damage. The link with ALS came when researchers sequenced the genes of people who have the inherited form of ALS and found that some of them have mutations in the gene that codes for this enzyme. While the inherited form represents only a fraction of all ALS cases, this marked the first time there was any indication of a cause for any form of ALS, Valentine said.
For many years, Valentine's laboratory has studied the normal version of the protein. While the normal protein has copper and zinc, scientists can make it with no metals. When it is first made inside the cell, it has no metals and only acquires them later, Valentine said.
"We studied what happens to the protein if you have the metals, if you have no metals and if you have part of the metals," she said.
The research of the UCLA-University of Florence team has indicated it is the metal-free protein that is likely to be toxic. The protein misfolds when the copper and zinc are not present, but folds properly when they are there.
"Before copper and zinc are inserted, the protein can misfold under physiological conditions," Valentine said.
There is evidence that ALS is associated with this misfolding of the protein, which becomes toxic in some way that is not known and has properties similar to misfolded proteins associated with other neurodegenerative disorders like Alzheimer's and Parkinson's diseases, Valentine said.
Is there a way to slow down this process to give the cell more time to eliminate the misfolded proteins in all of these diseases" Would a strategy to reduce or prevent protein misfolding work against these and other diseases" These are avenues for further investigation by researchers.
When Valentine first began working on copper-zinc superoxide dismutase, she was not a biochemist but a biological inorganic chemist and hardly knew what ALS was. She was interested in the enzyme, which is unique in that it has copper and zinc so close together.
Her laboratory isolated and characterized the enzyme, but Valentine was less interested in its biological properties than in the inorganic chemistry. She was more interested, for example, in how the protein influenced the reactivity of the copper or zinc, or how the copper and zinc influenced the structure of the enzyme. She and her colleagues were among the pioneers in taking the copper and zinc out and putting other metals in to see what would happen. Her laboratory put more emphasis on biological factors over time.
"When I moved to UCLA in 1980, we started working on copper-zinc superoxide dismutase in yeast, a model organism, using the then new tools of molecular biology to redesign the protein and make new mutant forms of the protein that would have different inorganic properties," she said. "We were making mutant forms of this enzyme to study, but with no connection to disease."
"I remember the day in March 1993 that the announcement came - it was on the front page of The New York Times - that ALS has been linked to superoxide dismutase (SOD), but the article didn't say which superoxide dismutase; I was hoping it was our enzyme. It took me all day to track down the scientists to find out which SOD it actually was. It was our SOD. It was a very exciting day."
"When we made the mutant proteins, each one seemed to be totally different," she said. "Some of the mutant proteins that cause the disease are identical to the normal protein in every property we measure."
Valentine and Bertini have known each other since she was a graduate student and he was a research associate at Princeton University. Initially, they were both inorganic chemists who did not intend to do biological research. They have just published an authoritative new textbook called "Biological Inorganic Chemistry: Structure and Reactivity," with co-authors Harry Gray at the California Institute of Technology and the late Edward Stiefel from Princeton University. The textbook is designed for both undergraduate and graduate students.
"All of us who work in the field hope our research will lead to a treatment of ALS," Valentine said. "What we really want is to diagnose and prevent ALS before its onset. We're still a long way from that, but we're making progress."
Valentine's research was federally funded by the National Institutes of Health.
UCLA is California's largest university, with an enrollment of nearly 37,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university's 11 professional schools feature renowned faculty and offer more than 300 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Four alumni and five faculty have been awarded the Nobel Prize.
Contact: Stuart Wolpert
University of California - Los Angeles
Joan Selverstone Valentine, UCLA professor of chemistry and biochemistry, has studied the protein - copper-zinc superoxide dismutase - since the 1970s, long before it was implicated in ALS in 1993. Since the link was discovered, Valentine's laboratory has made more than two dozen mutant, ALS-causing enzymes, most of which have only one wrong amino acid out of 153, to try to understand their properties and learn what makes them toxic.
"Some of the mutant proteins are very different from the normal protein, but others are virtually identical to the normal protein - yet they all cause the disease," said Valentine, a member of UCLA's Molecular Biology Institute. "That was the real mystery. You wrack your brain: What is similar among all these proteins" They seem so different. How can they all cause the same disease""
Now Valentine and her colleagues, including Ivano Bertini, professor of chemistry at the University of Florence and director of the European Magnetic Resonance Center, think they know. In ALS patients, the protein's copper and zinc may not be there at all. They present evidence for this hypothesis in new research published in Proceedings of the National Academy of Sciences, online and available in the journal's July 3 print edition.
"If we keep the metals entirely out of the protein, we can explain the toxicity, since even the normal protein forms aggregate at physiological conditions when the metals are gone," Valentine said. "It was such a puzzle, but this hypothesis can solve it."
If scientists can figure out why ALS patients lack the copper and zinc, that would be a major advance that could lead to treatment, she said.
The research team is testing the hypothesis. Valentine, who was elected to the National Academy of Sciences in 2005 and to the American Academy of Arts and Sciences this year, praised her colleagues. "This research is the result of a long, successful international collaboration between UCLA and the University of Florence," she said. "Our colleagues in Italy are exceptional scientists."
Co-authors on the Proceedings of the National Academy of Sciences research are Lucia Banci, a professor of chemistry at the University of Florence who is affiliated with the FiorGen Foundation; Armando Durazo, a UCLA graduate student of chemistry and biochemistry; Stefania Girotto, a postdoctoral scholar at the University of Florence; Edith Butler Gralla, a senior research chemist at UCLA; Manuele Martinelli and Miguela Vieru, graduate students at the University of Florence; and Julian P. Whitelegge, an adjunct professor at the Semel Institute for Neuroscience and Human Behavior at UCLA and UCLA's Brain Research Institute.
Copper-zinc superoxide dismutase, which was discovered in the 1960s, is an antioxidant enzyme that protects cells from free radicals, unstable atoms or molecules that can cause cell damage. The link with ALS came when researchers sequenced the genes of people who have the inherited form of ALS and found that some of them have mutations in the gene that codes for this enzyme. While the inherited form represents only a fraction of all ALS cases, this marked the first time there was any indication of a cause for any form of ALS, Valentine said.
For many years, Valentine's laboratory has studied the normal version of the protein. While the normal protein has copper and zinc, scientists can make it with no metals. When it is first made inside the cell, it has no metals and only acquires them later, Valentine said.
"We studied what happens to the protein if you have the metals, if you have no metals and if you have part of the metals," she said.
The research of the UCLA-University of Florence team has indicated it is the metal-free protein that is likely to be toxic. The protein misfolds when the copper and zinc are not present, but folds properly when they are there.
"Before copper and zinc are inserted, the protein can misfold under physiological conditions," Valentine said.
There is evidence that ALS is associated with this misfolding of the protein, which becomes toxic in some way that is not known and has properties similar to misfolded proteins associated with other neurodegenerative disorders like Alzheimer's and Parkinson's diseases, Valentine said.
Is there a way to slow down this process to give the cell more time to eliminate the misfolded proteins in all of these diseases" Would a strategy to reduce or prevent protein misfolding work against these and other diseases" These are avenues for further investigation by researchers.
When Valentine first began working on copper-zinc superoxide dismutase, she was not a biochemist but a biological inorganic chemist and hardly knew what ALS was. She was interested in the enzyme, which is unique in that it has copper and zinc so close together.
Her laboratory isolated and characterized the enzyme, but Valentine was less interested in its biological properties than in the inorganic chemistry. She was more interested, for example, in how the protein influenced the reactivity of the copper or zinc, or how the copper and zinc influenced the structure of the enzyme. She and her colleagues were among the pioneers in taking the copper and zinc out and putting other metals in to see what would happen. Her laboratory put more emphasis on biological factors over time.
"When I moved to UCLA in 1980, we started working on copper-zinc superoxide dismutase in yeast, a model organism, using the then new tools of molecular biology to redesign the protein and make new mutant forms of the protein that would have different inorganic properties," she said. "We were making mutant forms of this enzyme to study, but with no connection to disease."
"I remember the day in March 1993 that the announcement came - it was on the front page of The New York Times - that ALS has been linked to superoxide dismutase (SOD), but the article didn't say which superoxide dismutase; I was hoping it was our enzyme. It took me all day to track down the scientists to find out which SOD it actually was. It was our SOD. It was a very exciting day."
"When we made the mutant proteins, each one seemed to be totally different," she said. "Some of the mutant proteins that cause the disease are identical to the normal protein in every property we measure."
Valentine and Bertini have known each other since she was a graduate student and he was a research associate at Princeton University. Initially, they were both inorganic chemists who did not intend to do biological research. They have just published an authoritative new textbook called "Biological Inorganic Chemistry: Structure and Reactivity," with co-authors Harry Gray at the California Institute of Technology and the late Edward Stiefel from Princeton University. The textbook is designed for both undergraduate and graduate students.
"All of us who work in the field hope our research will lead to a treatment of ALS," Valentine said. "What we really want is to diagnose and prevent ALS before its onset. We're still a long way from that, but we're making progress."
Valentine's research was federally funded by the National Institutes of Health.
UCLA is California's largest university, with an enrollment of nearly 37,000 undergraduate and graduate students. The UCLA College of Letters and Science and the university's 11 professional schools feature renowned faculty and offer more than 300 degree programs and majors. UCLA is a national and international leader in the breadth and quality of its academic, research, health care, cultural, continuing education and athletic programs. Four alumni and five faculty have been awarded the Nobel Prize.
Contact: Stuart Wolpert
University of California - Los Angeles
пятница, 17 июня 2011 г.
Exercise To Avoid Gallstones!
A new University of Illinois study shows that exercise-trained mice get far fewer gallstones than sedentary mice and identifies potential mechanisms to explain why this occurs.
The study, recently published in the Journal of Applied Physiology, can be viewed online at: jap.physiology/cgi/reprint/01292.2007v1.
"For the first time, we have direct evidence that physical activity reduces gallstone formation, adding to the ever-increasing number of reasons that people should get more exercise," said Kenneth Wilund, a faculty member in the U of I Division of Nutritional Sciences and an Assistant Professor in Kinesiology and Community Health.
Gallbladder disease affects 10 to 25 percent of adults in the United States, although some persons who are affected may not have symptoms. It has the second highest cost of any digestive disease at $5.8 billion annually and results in over 800,000 hospitalizations each year.
Gallstones form when bile cholesterol levels become high enough to precipitate, fall out of solution, and solidify, Wilund said.
In the study, 50 mice from a gallstone-susceptible strain were fed a high-fat diet containing cholic acid, which helps increase cholesterol absorption. They were then divided into two groups. One group of mice ran on treadmills 45 minutes per day five days a week; the other group did not exercise.
After 12 weeks, the scientists removed the animals' gallbladders, pooling the stones from each group and weighing them. The gallstones in the sedentary group weighed two and a half times more than the stones in the exercised group.
"You could see through the gallbladders in the exercise-trained group, whereas the gallbladders in the sedentary group were full of stones," Wilund said.
To understand more about why this happened, the scientists then measured the expression of selected genes in the liver and intestine that are involved in cholesterol absorption and may affect gallstone development.
"In the exercised mice, we saw an increase in the expression of two genes (LDLr and SRB1) that help bring cholesterol into the liver to 'clear' it from the circulation. But we also found that a protein called Cyp27 was upregulated about two a half times; this resulted in there being more bile acids to solubilize the increased cholesterol so it didn't turn into gallstones.
"Taken together, the differences in gene expression between the exercised and sedentary mice in this study show how exercise training could simultaneously improve cholesterol levels while also inhibiting gallstone formation," he said.
Previous observational studies have suggested that people who are physically fit have fewer gallstones and lower cholesterol, but laboratory studies had not confirmed the link.
Wilund said these mice are a useful model because humans have a similar set of genes that regulate liver and bile cholesterol metabolism. He also said that human studies would be difficult to perform because of the number of years it takes for people to develop gallstones.
"We certainly found the changes in gene expression in the exercised animals very intriguing," he said. "The results add to a body of evidence that supports the importance of physical activity for good health."
Co-authors of the study are Laura A. Feeney, Emily J. Tomayko, and Hae R. Chung of the University of Illinois and Kijin Kim of Keimyung University in Daegu, Korea. Funding was provided by the University of Illinois Research Board.
Source: Phyllis Picklesimer
University of Illinois at Urbana-Champaign
The study, recently published in the Journal of Applied Physiology, can be viewed online at: jap.physiology/cgi/reprint/01292.2007v1.
"For the first time, we have direct evidence that physical activity reduces gallstone formation, adding to the ever-increasing number of reasons that people should get more exercise," said Kenneth Wilund, a faculty member in the U of I Division of Nutritional Sciences and an Assistant Professor in Kinesiology and Community Health.
Gallbladder disease affects 10 to 25 percent of adults in the United States, although some persons who are affected may not have symptoms. It has the second highest cost of any digestive disease at $5.8 billion annually and results in over 800,000 hospitalizations each year.
Gallstones form when bile cholesterol levels become high enough to precipitate, fall out of solution, and solidify, Wilund said.
In the study, 50 mice from a gallstone-susceptible strain were fed a high-fat diet containing cholic acid, which helps increase cholesterol absorption. They were then divided into two groups. One group of mice ran on treadmills 45 minutes per day five days a week; the other group did not exercise.
After 12 weeks, the scientists removed the animals' gallbladders, pooling the stones from each group and weighing them. The gallstones in the sedentary group weighed two and a half times more than the stones in the exercised group.
"You could see through the gallbladders in the exercise-trained group, whereas the gallbladders in the sedentary group were full of stones," Wilund said.
To understand more about why this happened, the scientists then measured the expression of selected genes in the liver and intestine that are involved in cholesterol absorption and may affect gallstone development.
"In the exercised mice, we saw an increase in the expression of two genes (LDLr and SRB1) that help bring cholesterol into the liver to 'clear' it from the circulation. But we also found that a protein called Cyp27 was upregulated about two a half times; this resulted in there being more bile acids to solubilize the increased cholesterol so it didn't turn into gallstones.
"Taken together, the differences in gene expression between the exercised and sedentary mice in this study show how exercise training could simultaneously improve cholesterol levels while also inhibiting gallstone formation," he said.
Previous observational studies have suggested that people who are physically fit have fewer gallstones and lower cholesterol, but laboratory studies had not confirmed the link.
Wilund said these mice are a useful model because humans have a similar set of genes that regulate liver and bile cholesterol metabolism. He also said that human studies would be difficult to perform because of the number of years it takes for people to develop gallstones.
"We certainly found the changes in gene expression in the exercised animals very intriguing," he said. "The results add to a body of evidence that supports the importance of physical activity for good health."
Co-authors of the study are Laura A. Feeney, Emily J. Tomayko, and Hae R. Chung of the University of Illinois and Kijin Kim of Keimyung University in Daegu, Korea. Funding was provided by the University of Illinois Research Board.
Source: Phyllis Picklesimer
University of Illinois at Urbana-Champaign
четверг, 16 июня 2011 г.
Shared Facilities, Resources And Programs To Further Stem Cell Research
Research institutions across Southern California have joined forces to advance stem cell research by establishing the Southern California Stem Cell Scientific Collaboration (SC3). Members of the collaboration include the University of Southern California, Childrens Hospital Los Angeles, City of Hope, University of California, Santa Barbara, California Institute of Technology and the House Ear Institute.
"The potential applications for stem cell research in medicine are enormous," says Martin Pera, Ph.D., director of USC's Center for Stem Cell and Regenerative Medicine. "Tackling these complex problems requires scientists with diverse expertise. We are delighted to have an opportunity to work with such an outstanding collection of scientists to really accelerate the pace of discovery and translational research in regenerative medicine."
Through grants from organizations such as the California Institute for Regenerative Medicine (CIRM) and the National Institutes of Health, SC3 members have a long history of partnering on various research projects. The new agreement is a major step forward in supporting potential significant stem cell findings by allowing members to share training programs, scientific core facilities and expertise, and to team up on a wide range of research programs.
"For patients and their families, cures for cancer, HIV/AIDS and other diseases cannot come soon enough," says Michael A. Friedman, M.D., president and chief executive officer, City of Hope. "As an institution, City of Hope is working to speed advances in medical science to improve and save lives. We believe the SC3 collaboration provides a critical mass of expertise that will create new knowledge and significantly accelerate treatments for diseases that impact so many."
"Stem cell research is vibrant at Childrens Hospital Los Angeles because of the long-term, commitment of our hospital to support high quality research in general, and stem cell research in particular," says Gay M. Crooks, M.D., director of the Stem Cell Program at Childrens Hospital Los Angeles, and professor of pediatrics at the Keck School of Medicine of the University of Southern California. "We believe that such innovative research should be available to the children of California."
Each institution will appoint a faculty member to serve on a joint scientific advisory committee, which will serve as a forum to develop collaborative research ventures, facilitate access to scientific resources and provide expertise across the collaboration. Regional seminar programs and courses, such as the ongoing CIRM funded stem cell biology course between USC, Caltech and Childrens Hospital Los Angeles, will be expanded to allow additional participation. The agreement also ensures each member provides access to resources to investigators for training or to conduct short-term research projects.
"The SC3 collaboration is already engendering new ideas for collaborative projects between scientists at the participating institutions. UC Santa Barbara will benefit from shared resources and synergistic collaborations in stem cell research as part of a new proposed Center for Stem Cell Biology and Engineering," says Dennis Clegg, Chair of Molecular Biology and Director of the Stem Cell Program at UC Santa Barbara.
UC Santa Barbara has a CIRM-funded stem cell training program and a shared lab facility. Research in the proposed Center will focus on two areas of basic and discovery stem cell research: Molecular Mechanisms and Bioengineering. The long-term goal will be the application of results to the development of stem cell-based therapeutics for human disease, particularly macular degeneration.
"The ultimate goal of the collaborative stem cell research at the House Ear Institute is the regeneration or transplantation and successful functioning of sensory cells and other cell types in the inner ear to restore hearing," says David Lim, M.D., Executive Vice President of Research, House Ear Institute (HEI).
Scientists at HEI have discovered that sensory cell progenitors (stem cells) in the inner ear (cochlea) are supporting cells that may help manipulate hair cell regeneration to restore hearing. Future work seeks to more fully understand the biology of these two pathways, whilst at the same time examining their potential in therapeutic approaches to hair cell regeneration.
"We look forward to the establishment of this new stem cell collaboration. The shared facilities should move this important science along considerably faster," says Paul H. Patterson, professor of biological sciences and director of the stem cell training program at Caltech.
Contacts:
USC
Jon Weiner
House Ear Institute
Christa Spieth Nuber
City of Hope
Roya Alt
Childrens Hospital LA
Steve Rutledge
UC Santa Barbara
Paul Desruisseaux
Caltech
Kathy Svitil
Source: Jon Weiner
University of Southern California
"The potential applications for stem cell research in medicine are enormous," says Martin Pera, Ph.D., director of USC's Center for Stem Cell and Regenerative Medicine. "Tackling these complex problems requires scientists with diverse expertise. We are delighted to have an opportunity to work with such an outstanding collection of scientists to really accelerate the pace of discovery and translational research in regenerative medicine."
Through grants from organizations such as the California Institute for Regenerative Medicine (CIRM) and the National Institutes of Health, SC3 members have a long history of partnering on various research projects. The new agreement is a major step forward in supporting potential significant stem cell findings by allowing members to share training programs, scientific core facilities and expertise, and to team up on a wide range of research programs.
"For patients and their families, cures for cancer, HIV/AIDS and other diseases cannot come soon enough," says Michael A. Friedman, M.D., president and chief executive officer, City of Hope. "As an institution, City of Hope is working to speed advances in medical science to improve and save lives. We believe the SC3 collaboration provides a critical mass of expertise that will create new knowledge and significantly accelerate treatments for diseases that impact so many."
"Stem cell research is vibrant at Childrens Hospital Los Angeles because of the long-term, commitment of our hospital to support high quality research in general, and stem cell research in particular," says Gay M. Crooks, M.D., director of the Stem Cell Program at Childrens Hospital Los Angeles, and professor of pediatrics at the Keck School of Medicine of the University of Southern California. "We believe that such innovative research should be available to the children of California."
Each institution will appoint a faculty member to serve on a joint scientific advisory committee, which will serve as a forum to develop collaborative research ventures, facilitate access to scientific resources and provide expertise across the collaboration. Regional seminar programs and courses, such as the ongoing CIRM funded stem cell biology course between USC, Caltech and Childrens Hospital Los Angeles, will be expanded to allow additional participation. The agreement also ensures each member provides access to resources to investigators for training or to conduct short-term research projects.
"The SC3 collaboration is already engendering new ideas for collaborative projects between scientists at the participating institutions. UC Santa Barbara will benefit from shared resources and synergistic collaborations in stem cell research as part of a new proposed Center for Stem Cell Biology and Engineering," says Dennis Clegg, Chair of Molecular Biology and Director of the Stem Cell Program at UC Santa Barbara.
UC Santa Barbara has a CIRM-funded stem cell training program and a shared lab facility. Research in the proposed Center will focus on two areas of basic and discovery stem cell research: Molecular Mechanisms and Bioengineering. The long-term goal will be the application of results to the development of stem cell-based therapeutics for human disease, particularly macular degeneration.
"The ultimate goal of the collaborative stem cell research at the House Ear Institute is the regeneration or transplantation and successful functioning of sensory cells and other cell types in the inner ear to restore hearing," says David Lim, M.D., Executive Vice President of Research, House Ear Institute (HEI).
Scientists at HEI have discovered that sensory cell progenitors (stem cells) in the inner ear (cochlea) are supporting cells that may help manipulate hair cell regeneration to restore hearing. Future work seeks to more fully understand the biology of these two pathways, whilst at the same time examining their potential in therapeutic approaches to hair cell regeneration.
"We look forward to the establishment of this new stem cell collaboration. The shared facilities should move this important science along considerably faster," says Paul H. Patterson, professor of biological sciences and director of the stem cell training program at Caltech.
Contacts:
USC
Jon Weiner
House Ear Institute
Christa Spieth Nuber
City of Hope
Roya Alt
Childrens Hospital LA
Steve Rutledge
UC Santa Barbara
Paul Desruisseaux
Caltech
Kathy Svitil
Source: Jon Weiner
University of Southern California
среда, 15 июня 2011 г.
News From The American Chemical Society
Excess female to male births in Canada linked to chronic dioxin exposure
Almost 90 Canadian communities have experienced a shift in the normal 51:49 ratio of male to female births, so that more girls than boys are being born, according to two studies in ACS' Environmental Science & Technology, a semi-monthly journal. James Argo, who headed the research, attributes this so-called "inverted sex ratio" of the residents in those communities to dioxin air pollutants from oil refineries, paper mills, metal smelters and other sources.
The studies analyzed information in the Environmental Quality Database (EQDB), an inventory of pollution sources, cancer data, and other factors developed for Canadian government research on how early exposure to environmental contaminants affects the health of Canadians. Argo points out that the EQDB enables researchers to pinpoint the location of 126,000 homes relative to any of about 65 air pollution sources-types and the occurrence of cancer among residents of those homes.
Argo focused on air pollutants from those sources and the corresponding incidence of cancer among more than 20,000 residents and 5,000 controls. He identified inverted male sex ratios, sometimes as profound as 46:54 in almost all of the communities. The ratio indicated that more females than males were born, a situation that Argo attributed to chronic exposure of parents to dioxin, based on previous studies. The study "may represent one of only a few studies explicitly designed to identify the impact of carcinogens from industrial sources on residents at home," Agro stated.
"Chronic Disease and Early Exposure to Air-Borne Mixtures: 1. The Environmental Quality Database" and "Chronic Disease and Early Exposure to Air-Borne Mixtures: 2. Exposure Assessment"
CONTACT:
James Argo, Ph.D.
IntrAmericas Centre for Environment and Health
Ontario, Canada
Tiny capers pack big disease-fighting punch
Capers, used in such culinary delights as chicken piccata and smoked salmon, may be small. But they are an unexpectedly big source of natural antioxidants that show promise for fighting cancer and heart disease when added to meals, particularly meats, researchers in Italy are reporting in the current issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.
The flower buds of a small bush, capers have been used for centuries in Mediterranean cuisine, where they provide a salty tang and decorative flair to a variety of meats, salads, pastas and other foods. In the new study, Maria A. Livrea and colleagues note that other foods in the so-called Mediterranean diet have gotten plenty of attention for their health benefits. Capers, however, have been largely overlooked.
Their laboratory study involved adding caper extracts to grilled ground-turkey, and analyzing byproducts formed during simulated digestion. The scientists found that caper-extract helped prevent the formation of certain byproducts of digested meat that have been linked by others to an increased risk of cancer and heart disease. That beneficial effect occurred even with the small amounts of caper typically used to flavor food. "Caper may have beneficial health effects, especially for people whose meals are rich in fats and red meats," the study concluded.
"Bioactive Components of Caper (Capparis spinosa L.) from Sicily and Antioxidant Effects in a Red Meat Simulated Gastric Digestion"
CONTACT:
Maria A. Livrea, Ph.D.
Universita di Palermo
Palermo, Italy
Bacteria in the intestines can influence results of drug tests
Bacteria living in the intestines of laboratory rats -- those test tubes on four feet that stand in for humans in a wide range of research -- may influence the results of drug safety and other tests, scientists in Michigan are reporting. The findings are scheduled for the Dec. 7 issue of ACS' Chemical Research in Toxicology, a monthly journal.
Cynthia M. Rohde and colleagues note growing recognition of the hidden role of the approximately 100 trillion bacteria that thrive in the intestines of humans. Studies have shown that this so-called "gut microflora" can influence the immune system, how the body responds to foods, the action of drugs, and other functions. Researchers started the new study after noting that a genetically identical population of rats widely used in laboratory tests had developed two distinctively different metabolic types. The types involve differences in the way those animals metabolize, or breakdown, drugs and nutrients.
After detailed studies of substances in the urine of the rats, researchers concluded that the differences result from differences in the gut microbial populations between the two types. The report recommends that scientists in the future check lab rat populations for such metabolic differences due to gut microflora in order to assure accurate results, especially in experiments to evaluate the safety of new drugs.
"Metabonomic Evaluation of Schaedler Altered Microflora Rats"
CONTACT:
Cynthia M. Rohde, Ph.D.
Metabonomics Evaluation Group
Pfizer Global Research and Development
2800 Plymouth Road
Ann Arbor, Michigan 48105
Recycling of e-waste in China may expose mothers, infants to high dioxin levels
With China now the destination for 70 percent of the computers, TVs, cell phones, and other electronic waste (e-waste) recycled worldwide each year, a new study has concluded that Chinese recycling methods significantly increase dioxin levels in women and their breast-fed infants. The study is scheduled for the Nov. 15 issue of ACS' Environmental Science & Technology, a semi-monthly publication.
Ming H. Wong and colleagues did one of what they describe as "very few" studies of dioxin levels among women of child bearing age at an e-waste recycling site, and compared those levels to women in an area without e-waste recycling. They analyzed levels of dioxins -- compounds linked to cancer, developmental defects, and other health problems -- in samples of breast milk, placenta, and hair.
Samples from the e-waste site showed significantly higher levels of dioxins than those taken at the reference site. Researchers estimated that the daily intake of infants from 6 months of breast feeding at the recycling site was more than double that of the reference site. Therefore, this implies that these levels at the recycling site and the reference site were at least 25 times and 11 times higher, respectively, than the World Health Organization tolerable daily limit for adults regarding dioxins and dioxin-like PCBs. The study includes descriptions of recycling methods, which include heating scrap electronic components over coal fires in the open air.
"Body Loadings and Health Risk Assessment of Polychlorinated Dibenzo-p-dioxins and Dibenzofurans at an Intensive Electronic Waste Recycling Site in China"
CONTACT:
Ming H. Wong, Ph.D.
Hong Kong Baptist University
Kowloon Tong
Hong Kong
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
Almost 90 Canadian communities have experienced a shift in the normal 51:49 ratio of male to female births, so that more girls than boys are being born, according to two studies in ACS' Environmental Science & Technology, a semi-monthly journal. James Argo, who headed the research, attributes this so-called "inverted sex ratio" of the residents in those communities to dioxin air pollutants from oil refineries, paper mills, metal smelters and other sources.
The studies analyzed information in the Environmental Quality Database (EQDB), an inventory of pollution sources, cancer data, and other factors developed for Canadian government research on how early exposure to environmental contaminants affects the health of Canadians. Argo points out that the EQDB enables researchers to pinpoint the location of 126,000 homes relative to any of about 65 air pollution sources-types and the occurrence of cancer among residents of those homes.
Argo focused on air pollutants from those sources and the corresponding incidence of cancer among more than 20,000 residents and 5,000 controls. He identified inverted male sex ratios, sometimes as profound as 46:54 in almost all of the communities. The ratio indicated that more females than males were born, a situation that Argo attributed to chronic exposure of parents to dioxin, based on previous studies. The study "may represent one of only a few studies explicitly designed to identify the impact of carcinogens from industrial sources on residents at home," Agro stated.
"Chronic Disease and Early Exposure to Air-Borne Mixtures: 1. The Environmental Quality Database" and "Chronic Disease and Early Exposure to Air-Borne Mixtures: 2. Exposure Assessment"
CONTACT:
James Argo, Ph.D.
IntrAmericas Centre for Environment and Health
Ontario, Canada
Tiny capers pack big disease-fighting punch
Capers, used in such culinary delights as chicken piccata and smoked salmon, may be small. But they are an unexpectedly big source of natural antioxidants that show promise for fighting cancer and heart disease when added to meals, particularly meats, researchers in Italy are reporting in the current issue of ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.
The flower buds of a small bush, capers have been used for centuries in Mediterranean cuisine, where they provide a salty tang and decorative flair to a variety of meats, salads, pastas and other foods. In the new study, Maria A. Livrea and colleagues note that other foods in the so-called Mediterranean diet have gotten plenty of attention for their health benefits. Capers, however, have been largely overlooked.
Their laboratory study involved adding caper extracts to grilled ground-turkey, and analyzing byproducts formed during simulated digestion. The scientists found that caper-extract helped prevent the formation of certain byproducts of digested meat that have been linked by others to an increased risk of cancer and heart disease. That beneficial effect occurred even with the small amounts of caper typically used to flavor food. "Caper may have beneficial health effects, especially for people whose meals are rich in fats and red meats," the study concluded.
"Bioactive Components of Caper (Capparis spinosa L.) from Sicily and Antioxidant Effects in a Red Meat Simulated Gastric Digestion"
CONTACT:
Maria A. Livrea, Ph.D.
Universita di Palermo
Palermo, Italy
Bacteria in the intestines can influence results of drug tests
Bacteria living in the intestines of laboratory rats -- those test tubes on four feet that stand in for humans in a wide range of research -- may influence the results of drug safety and other tests, scientists in Michigan are reporting. The findings are scheduled for the Dec. 7 issue of ACS' Chemical Research in Toxicology, a monthly journal.
Cynthia M. Rohde and colleagues note growing recognition of the hidden role of the approximately 100 trillion bacteria that thrive in the intestines of humans. Studies have shown that this so-called "gut microflora" can influence the immune system, how the body responds to foods, the action of drugs, and other functions. Researchers started the new study after noting that a genetically identical population of rats widely used in laboratory tests had developed two distinctively different metabolic types. The types involve differences in the way those animals metabolize, or breakdown, drugs and nutrients.
After detailed studies of substances in the urine of the rats, researchers concluded that the differences result from differences in the gut microbial populations between the two types. The report recommends that scientists in the future check lab rat populations for such metabolic differences due to gut microflora in order to assure accurate results, especially in experiments to evaluate the safety of new drugs.
"Metabonomic Evaluation of Schaedler Altered Microflora Rats"
CONTACT:
Cynthia M. Rohde, Ph.D.
Metabonomics Evaluation Group
Pfizer Global Research and Development
2800 Plymouth Road
Ann Arbor, Michigan 48105
Recycling of e-waste in China may expose mothers, infants to high dioxin levels
With China now the destination for 70 percent of the computers, TVs, cell phones, and other electronic waste (e-waste) recycled worldwide each year, a new study has concluded that Chinese recycling methods significantly increase dioxin levels in women and their breast-fed infants. The study is scheduled for the Nov. 15 issue of ACS' Environmental Science & Technology, a semi-monthly publication.
Ming H. Wong and colleagues did one of what they describe as "very few" studies of dioxin levels among women of child bearing age at an e-waste recycling site, and compared those levels to women in an area without e-waste recycling. They analyzed levels of dioxins -- compounds linked to cancer, developmental defects, and other health problems -- in samples of breast milk, placenta, and hair.
Samples from the e-waste site showed significantly higher levels of dioxins than those taken at the reference site. Researchers estimated that the daily intake of infants from 6 months of breast feeding at the recycling site was more than double that of the reference site. Therefore, this implies that these levels at the recycling site and the reference site were at least 25 times and 11 times higher, respectively, than the World Health Organization tolerable daily limit for adults regarding dioxins and dioxin-like PCBs. The study includes descriptions of recycling methods, which include heating scrap electronic components over coal fires in the open air.
"Body Loadings and Health Risk Assessment of Polychlorinated Dibenzo-p-dioxins and Dibenzofurans at an Intensive Electronic Waste Recycling Site in China"
CONTACT:
Ming H. Wong, Ph.D.
Hong Kong Baptist University
Kowloon Tong
Hong Kong
The American Chemical Society -- the world's largest scientific society -- is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.
Source: Michael Woods
American Chemical Society
вторник, 14 июня 2011 г.
Research In The Bolivian Rainforest Suggests Ancient, Shared Roots Of Feeding Behaviours In Monkeys And Humans
Behavioural ecologists working in Bolivia have found that wild spider monkeys control their diets in a similar way to humans, contrary to what has been thought up to now. Rather than trying to maximize their daily energy intake, the monkeys tightly regulate their daily protein intake, so that it stays at the same level regardless of seasonal variation in the availability of different foods.
Tight regulation of daily protein intake is known to play a role in the development of obesity in humans, and the findings from this research suggest that the evolutionary origins of these eating patterns in humans may be far older than suspected. Until now it was thought humans' eating patterns originated in the Palaeolithic era (between 2.4 million and 10,000 years ago).
The research, published online yesterday in the journal Behavioral Ecology [1], also provides valuable information about which trees are important for the monkeys' diet, which is relevant to conservation; in addition, it may help to improve the care of captive primates, which can be prone to obesity and related health problems due to their diet.
Dr Annika Felton, a Departmental Visitor at the Fenner School of Environment and Society, The Australian National University, Canberra, Australia, spent a year in the Bolivian rainforest (in Departmento Santa Cruz) familiarising the Peruvian spider monkeys (Ateles chamek) to her presence and then observing their feeding habits.
She followed 15 individual monkeys (7 adult males, 8 adult females), conducting continuous observations of the same animal from dawn to dusk, and following each of the monkeys for at least one whole day a month. During observations she recorded everything they did and ate and for how long. Where possible, she counted every fruit and leaf they ate, and collected samples of what they had eaten from the actual trees the monkeys had chosen. The samples were then dried and sent to the laboratory in Australia where they were analysed for their nutritional content. It is unusual for a study of feeding habits in wild primates to be conducted in this detailed way. It enabled Dr Felton and her colleagues to calculate how much an individual monkey had consumed and the nutrients involved; usually, other field studies are only able to calculate averages for a group of animals.
Dr Felton said: "We found that the pattern of nutrient intake by wild spider monkeys, which are primarily fruit eaters, was almost identical to humans, which are omnivores. What spider monkeys and humans have in common is that they tightly regulate their daily protein intake, i.e. they appear to aim for a target amount of protein each day, regardless of whether they only ate ripe fruit or mixed in other vegetable matter as well. Finding this result in spider monkeys was unexpected because, previously, ripe fruit specialists were thought to be 'energy maximisers'. In other words, they would aim to maximise their daily energy intake. Our findings show this is not the case.
"The consequence of tight protein regulation is the same for monkeys and humans: if the diet is poor in protein but rich in carbohydrates and fats (energy dense food) individuals will end up ingesting a great deal of energy in order to obtain their protein target, which can lead to weight gain. This 'protein leverage effect' is thought to play a significant role in the human obesity problem found in modern western societies. Our results suggest that an adjustment of the nutritional balance of diets as a means to manage human obesity might similarly be an option for mitigating obesity in captive primates.
"Our findings are also interesting from an evolutionary point of view. Similarity in the regulatory pattern of protein intake between distantly related species, such as humans and spider monkeys, possessing very different dietary habits, may indicate that the evolutionary origins of such regulatory patterns are quite old, potentially far older than the Palaeolithic era. If we are not dealing with convergent evolution here - in other words that spider monkeys and humans have evolved this trait independently - then this trait may have been shared by our common ancestor. Spider monkeys are New World primates that split from the Old World primates about 40 million years ago.
"Finally, our research shows that nutritionally-balanced food sources that are used extensively by a wild population may need special attention in terms of conservation planning, perhaps by regulating logging and selecting certain tree species for re-planting. The majority of the monkeys' nourishment was sourced from a species of fig tree, Ficus boliviana, that is currently being harvested for timber in Bolivia."
Dr Felton and her colleagues found that the monkeys ate a wide variety of fruit and vegetables - 105 different plants belonging to 63 species during the 12 months of observation. Figs were particularly popular. The monkeys rarely ate insects, which are rich in protein.
The spider monkeys did not specifically select either the most energy-rich or the most protein-rich foods that were available, and the daily amount of food they ate varied quite widely, averaging about 1 kg a day, but sometimes as much as 2.4 kg a day. However, they maintained their daily protein intake around 0.2 MJ (11 grams), whereas their intake of carbohydrates and fats varied between 0.7-6.2 MJ. The availability of sweet, ripe fruit was significantly related to the variation in their daily energy intake - the more there was, the more they ate.
"To maintain a stable intake of protein, spider monkeys consumed large amounts of carbohydrates and fats when protein content in the food was low, for instance when their diet consisted entirely of ripe fruit, and consumed far fewer carbohydrates and fats when feeding on items rich in protein," said Dr Felton.
She concluded: "What is perhaps most fascinating about our paper is not the answers we provide, but the questions that our findings raise. For example, why do these frugivores have the same pattern of nutritional intake as human omnivores? Is this due to convergent evolution or is it a remaining trait from a common ancestor?
"I am also pleased that our findings can be applied to the management of captive primates (where obesity is a problem), and possibly the management of spider monkey forest habitat.
"Also, importantly, we have shown that the combination of intensive data collection and the application of an innovative analytical framework can dramatically change our perceptions of the nutritional ecology of a species."
[1] Protein content of diets dictates the daily energy intake of a free-ranging primate.
Behavioural Ecology.
doi:10.1093/beheco/arp021
Source
Behavioural Ecology
Tight regulation of daily protein intake is known to play a role in the development of obesity in humans, and the findings from this research suggest that the evolutionary origins of these eating patterns in humans may be far older than suspected. Until now it was thought humans' eating patterns originated in the Palaeolithic era (between 2.4 million and 10,000 years ago).
The research, published online yesterday in the journal Behavioral Ecology [1], also provides valuable information about which trees are important for the monkeys' diet, which is relevant to conservation; in addition, it may help to improve the care of captive primates, which can be prone to obesity and related health problems due to their diet.
Dr Annika Felton, a Departmental Visitor at the Fenner School of Environment and Society, The Australian National University, Canberra, Australia, spent a year in the Bolivian rainforest (in Departmento Santa Cruz) familiarising the Peruvian spider monkeys (Ateles chamek) to her presence and then observing their feeding habits.
She followed 15 individual monkeys (7 adult males, 8 adult females), conducting continuous observations of the same animal from dawn to dusk, and following each of the monkeys for at least one whole day a month. During observations she recorded everything they did and ate and for how long. Where possible, she counted every fruit and leaf they ate, and collected samples of what they had eaten from the actual trees the monkeys had chosen. The samples were then dried and sent to the laboratory in Australia where they were analysed for their nutritional content. It is unusual for a study of feeding habits in wild primates to be conducted in this detailed way. It enabled Dr Felton and her colleagues to calculate how much an individual monkey had consumed and the nutrients involved; usually, other field studies are only able to calculate averages for a group of animals.
Dr Felton said: "We found that the pattern of nutrient intake by wild spider monkeys, which are primarily fruit eaters, was almost identical to humans, which are omnivores. What spider monkeys and humans have in common is that they tightly regulate their daily protein intake, i.e. they appear to aim for a target amount of protein each day, regardless of whether they only ate ripe fruit or mixed in other vegetable matter as well. Finding this result in spider monkeys was unexpected because, previously, ripe fruit specialists were thought to be 'energy maximisers'. In other words, they would aim to maximise their daily energy intake. Our findings show this is not the case.
"The consequence of tight protein regulation is the same for monkeys and humans: if the diet is poor in protein but rich in carbohydrates and fats (energy dense food) individuals will end up ingesting a great deal of energy in order to obtain their protein target, which can lead to weight gain. This 'protein leverage effect' is thought to play a significant role in the human obesity problem found in modern western societies. Our results suggest that an adjustment of the nutritional balance of diets as a means to manage human obesity might similarly be an option for mitigating obesity in captive primates.
"Our findings are also interesting from an evolutionary point of view. Similarity in the regulatory pattern of protein intake between distantly related species, such as humans and spider monkeys, possessing very different dietary habits, may indicate that the evolutionary origins of such regulatory patterns are quite old, potentially far older than the Palaeolithic era. If we are not dealing with convergent evolution here - in other words that spider monkeys and humans have evolved this trait independently - then this trait may have been shared by our common ancestor. Spider monkeys are New World primates that split from the Old World primates about 40 million years ago.
"Finally, our research shows that nutritionally-balanced food sources that are used extensively by a wild population may need special attention in terms of conservation planning, perhaps by regulating logging and selecting certain tree species for re-planting. The majority of the monkeys' nourishment was sourced from a species of fig tree, Ficus boliviana, that is currently being harvested for timber in Bolivia."
Dr Felton and her colleagues found that the monkeys ate a wide variety of fruit and vegetables - 105 different plants belonging to 63 species during the 12 months of observation. Figs were particularly popular. The monkeys rarely ate insects, which are rich in protein.
The spider monkeys did not specifically select either the most energy-rich or the most protein-rich foods that were available, and the daily amount of food they ate varied quite widely, averaging about 1 kg a day, but sometimes as much as 2.4 kg a day. However, they maintained their daily protein intake around 0.2 MJ (11 grams), whereas their intake of carbohydrates and fats varied between 0.7-6.2 MJ. The availability of sweet, ripe fruit was significantly related to the variation in their daily energy intake - the more there was, the more they ate.
"To maintain a stable intake of protein, spider monkeys consumed large amounts of carbohydrates and fats when protein content in the food was low, for instance when their diet consisted entirely of ripe fruit, and consumed far fewer carbohydrates and fats when feeding on items rich in protein," said Dr Felton.
She concluded: "What is perhaps most fascinating about our paper is not the answers we provide, but the questions that our findings raise. For example, why do these frugivores have the same pattern of nutritional intake as human omnivores? Is this due to convergent evolution or is it a remaining trait from a common ancestor?
"I am also pleased that our findings can be applied to the management of captive primates (where obesity is a problem), and possibly the management of spider monkey forest habitat.
"Also, importantly, we have shown that the combination of intensive data collection and the application of an innovative analytical framework can dramatically change our perceptions of the nutritional ecology of a species."
[1] Protein content of diets dictates the daily energy intake of a free-ranging primate.
Behavioural Ecology.
doi:10.1093/beheco/arp021
Source
Behavioural Ecology
понедельник, 13 июня 2011 г.
Basic Science And Medical Practic - Bridging The Gap
The UC Davis School of Medicine is among 13 innovative graduate programs in the nation to receive funds from the Howard Hughes Medical Institute to foster the translation of basic science discoveries into new medical treatments. The goal of the $10 million national initiative is to train scientists with a better understanding of medicine so they are better equipped to conduct research that benefits the diagnosis and treatment of human disease.
"The gap between basic biology and medical practice is growing," said Ann Bonham, executive associate dean for research and education at the School of Medicine and principal investigator of the grant. "As knowledge in molecular genetics and cell biology accelerates, the biomedical community is finding it increasingly hard to harness the explosion of new information and translate it into medical practice. Grants that support the training of scientists who know the process and language of medicine are crucial to bridging the information gap and finding innovative solutions to human health problems."
The $700,000 grant complements a strong translational research focus already under way at UC Davis School of Medicine and specifically supports expanded training for eight postdoctoral students who will enroll in a new, one-year curriculum beginning in the summer of 2006. Known as the Integrating Medicine into Basic Science scholars program, the new training builds on basic Ph.D. training through an array of clinical experiences and rotations, new courses, and a variety of small-group, interdisciplinary, active learning experiences with medical students, basic scientists and physician-educators.
"We've organized our postdoctoral and faculty scholars into Clinical Medicine-Basic Science Learning Groups to offer a comprehensive, hands on training experience in the area of vascular disease," said Bonham. "We've also established a dynamic, new summer institute that enables postdoctoral students to learn the fundamentals of clinical medicine using some of the most engaging components of our medical school curriculum."
Through the school's innovative Doctoring Course, for example, postdoctoral students work side-by-side with medical students, assessing realistic patient cases and actively exploring the dynamics of patient communication, clinical problem solving, and the application of psychosocial, cultural, bioethical and basic science concepts. Similarly, a new course on Medical Anatomy, Physiology and Pathophysiology enhances the study of the human body and its disease states with hands-on training with patient simulators at the UC Davis Center for Virtual Care.
Other program components include: rotations in clinical settings to expose scholars to the medical challenges; participation in clinical trial studies at the General Clinical Research Center and the Clinical/Translational Research Investigator Services Program; and new seminars and workshops that emphasize interactions with legislators, state officials, community advocates, medically underserved groups and other stakeholders.
The first class of postdoctoral students will focus on cutting-edge research in vascular biology, a key area of excellence at UC Davis that encompasses heart and vascular diseases, stroke and related areas of metabolic syndrome, nutrition and obesity. There are plans to later increase enrollment to 10 students per year and expand the areas of study to include cancer, neurological disease, infectious disease and other primary areas of research.
"Our goal is to create a ground-breaking translational research program that embraces cross-disciplinary teamwork to make bold new changes in how we train our basic scientist students so they can discover answers to medical challenges," said Bonham. "We are training the next generation of scientist scholars who will become the leaders of tomorrow. We want to prepare them to collaborate with their clinical colleagues and work as a team to transform basic research discoveries into high-impact clinical applications."
Media Contact:
Carole Gan, UC Davis Health System
E-mail: carole.ganucdmc.ucdavis
UC Davis Health System is an integrated, academic health system encompassing UC Davis School of Medicine, the 577-bed acute-care hospital and clinical services of UC Davis Medical Center, and the 800-member physician group known as UC Davis Medical Group.
Public Affairs
UC Davis Health System
4900 Broadway, Suite 1200
Sacramento, CA 95820
E-mail: publicaffairsucdmc.ucdavis
Web address:ucdmc.ucdavis/newsroom/
Contact: Carole Gan
carole.ganucdmc.ucdavis
University of California, Davis - Health System
"The gap between basic biology and medical practice is growing," said Ann Bonham, executive associate dean for research and education at the School of Medicine and principal investigator of the grant. "As knowledge in molecular genetics and cell biology accelerates, the biomedical community is finding it increasingly hard to harness the explosion of new information and translate it into medical practice. Grants that support the training of scientists who know the process and language of medicine are crucial to bridging the information gap and finding innovative solutions to human health problems."
The $700,000 grant complements a strong translational research focus already under way at UC Davis School of Medicine and specifically supports expanded training for eight postdoctoral students who will enroll in a new, one-year curriculum beginning in the summer of 2006. Known as the Integrating Medicine into Basic Science scholars program, the new training builds on basic Ph.D. training through an array of clinical experiences and rotations, new courses, and a variety of small-group, interdisciplinary, active learning experiences with medical students, basic scientists and physician-educators.
"We've organized our postdoctoral and faculty scholars into Clinical Medicine-Basic Science Learning Groups to offer a comprehensive, hands on training experience in the area of vascular disease," said Bonham. "We've also established a dynamic, new summer institute that enables postdoctoral students to learn the fundamentals of clinical medicine using some of the most engaging components of our medical school curriculum."
Through the school's innovative Doctoring Course, for example, postdoctoral students work side-by-side with medical students, assessing realistic patient cases and actively exploring the dynamics of patient communication, clinical problem solving, and the application of psychosocial, cultural, bioethical and basic science concepts. Similarly, a new course on Medical Anatomy, Physiology and Pathophysiology enhances the study of the human body and its disease states with hands-on training with patient simulators at the UC Davis Center for Virtual Care.
Other program components include: rotations in clinical settings to expose scholars to the medical challenges; participation in clinical trial studies at the General Clinical Research Center and the Clinical/Translational Research Investigator Services Program; and new seminars and workshops that emphasize interactions with legislators, state officials, community advocates, medically underserved groups and other stakeholders.
The first class of postdoctoral students will focus on cutting-edge research in vascular biology, a key area of excellence at UC Davis that encompasses heart and vascular diseases, stroke and related areas of metabolic syndrome, nutrition and obesity. There are plans to later increase enrollment to 10 students per year and expand the areas of study to include cancer, neurological disease, infectious disease and other primary areas of research.
"Our goal is to create a ground-breaking translational research program that embraces cross-disciplinary teamwork to make bold new changes in how we train our basic scientist students so they can discover answers to medical challenges," said Bonham. "We are training the next generation of scientist scholars who will become the leaders of tomorrow. We want to prepare them to collaborate with their clinical colleagues and work as a team to transform basic research discoveries into high-impact clinical applications."
Media Contact:
Carole Gan, UC Davis Health System
E-mail: carole.ganucdmc.ucdavis
UC Davis Health System is an integrated, academic health system encompassing UC Davis School of Medicine, the 577-bed acute-care hospital and clinical services of UC Davis Medical Center, and the 800-member physician group known as UC Davis Medical Group.
Public Affairs
UC Davis Health System
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E-mail: publicaffairsucdmc.ucdavis
Web address:ucdmc.ucdavis/newsroom/
Contact: Carole Gan
carole.ganucdmc.ucdavis
University of California, Davis - Health System
воскресенье, 12 июня 2011 г.
How Neuronal Activity Is Timed In The Brain's Memory-Making Circuits
Theta oscillations are a type of prominent brain rhythm that orchestrates neuronal activity in the hippocampus, a brain area critical for the formation of new memories. For several decades these oscillations were believed to be "in sync" across the hippocampus, timing the firing of neurons like a sort of central pacemaker. A new study conducted by researchers at the California Institute of Technology (Caltech) argues that this long-held assumption needs to be revised. In a paper published in this week's issue of the journal Nature, the researchers showed that instead of being in sync, theta oscillations actually sweep along the length of the hippocampus as traveling waves.
"It was assumed that activity in the hippocampus is synchronized throughout," says Evgueniy Lubenov, a postdoctoral scholar at the Center for Biological Circuit Design at Caltech. "But when we looked simultaneously at many different anatomical locations across the hippocampus, we found instead a systematic delay in neuronal activity from site to site. Instead of the whole structure oscillating at once, we see traveling waves that propagate across the hippocampus in a consistent direction, along its long axis."
"In other words, the hippocampus has a series of local time zones, just like we have on Earth," adds Athanassios Siapas, associate professor of computation and neural systems and Bren Scholar at Caltech.
The hippocampus has long been known to be critical for the formation and maintenance of episodic memories - i.e., memories of experiences. In the rat, hippocampal neurons also function as "place cells," only firing when the animal is in a particular spot in its environment. Lubenov and Siapas began to analyze the theta oscillations generated when rats move around and explore their environment. They watched how - and when - the rat's neurons fired relative to the rat's position and to the phase of the theta oscillations. They did these studies using multiple tetrodes - electrodes with four recording sites - that allowed them to simultaneously isolate the spiking of many individual neurons.
"Each of these neurons fires only in a restricted region of space," Lubenov says. "Furthermore, the spikes don't just happen any time - they pay attention to the phase of the ongoing theta oscillation. If you have access to the phase at which the neuron fired, you have additional information about where the rat was in space."
When the data about neuronal firing, oscillation phase, and rat location were combined, the researchers were able to show that neuronal activity indeed sweeps across the hippocampus in a wave, with its peak appearing in one region, then another, then another, rather than hitting the entire hippocampus in one synchronized pulse.
"This changes our notion of how spatial information is represented in the rat brain," notes Lubenov. "It was believed that the firing of hippocampal neurons encodes the physical location of the rat in its environment - in other words, a point of physical space. Our findings suggest that what is encoded is actually a portion of the rat's trajectory - that is, a segment of physical space."
"Such segments may be the elementary unit of hippocampal computation," adds Siapas. "Assume the path a rat takes in an environment is represented and stored as a sequence of point locations. If the rat visits the same location more than once, the representation becomes ambiguous. Representing the rat trajectory as a sequence of segments oriented in space resolves such ambiguities."
This finding may also have significant implications for understanding how information is transmitted from the hippocampus to other areas of the brain. "Different portions of the hippocampus are connected to different areas in other parts of the brain. The fact that hippocampal activity forms a traveling wave means that these target areas receive inputs from the hippocampus in a specific sequence rather than all at once," explains Siapas.
In addition, Siapas notes, it's unlikely that this behavior is found only in rat brains; after all, theta oscillations are ubiquitous in mammalian brains. "I would expect the traveling-wave nature of theta oscillations to be a general finding, applicable to humans as well," he says.
And while it is not known whether human hippocampal cells function as place cells, as they do in rats, "it may turn out to be the case that the human hippocampus plays a role in providing spatial cues that are important to episodic memory," Lubenov speculates. "We don't know yet."
What we do know is that, by showing that theta oscillations travel across the hippocampus, the Caltech team will likely change the way neuroscientists think about how the hippocampus works.
The work described in the Nature paper, "Hippocampal theta oscillations are travelling waves," was supported by the Caltech Information Science and Technology Center for Biological Circuit Design, a 21st Century McDonnell Foundation Award, the Bren Foundation, and the McKnight Foundation.
The paper's abstract can be accessed at dx.doi/10.1038/nature08010.
Source:
Lori Oliwenstein
California Institute of Technology
"It was assumed that activity in the hippocampus is synchronized throughout," says Evgueniy Lubenov, a postdoctoral scholar at the Center for Biological Circuit Design at Caltech. "But when we looked simultaneously at many different anatomical locations across the hippocampus, we found instead a systematic delay in neuronal activity from site to site. Instead of the whole structure oscillating at once, we see traveling waves that propagate across the hippocampus in a consistent direction, along its long axis."
"In other words, the hippocampus has a series of local time zones, just like we have on Earth," adds Athanassios Siapas, associate professor of computation and neural systems and Bren Scholar at Caltech.
The hippocampus has long been known to be critical for the formation and maintenance of episodic memories - i.e., memories of experiences. In the rat, hippocampal neurons also function as "place cells," only firing when the animal is in a particular spot in its environment. Lubenov and Siapas began to analyze the theta oscillations generated when rats move around and explore their environment. They watched how - and when - the rat's neurons fired relative to the rat's position and to the phase of the theta oscillations. They did these studies using multiple tetrodes - electrodes with four recording sites - that allowed them to simultaneously isolate the spiking of many individual neurons.
"Each of these neurons fires only in a restricted region of space," Lubenov says. "Furthermore, the spikes don't just happen any time - they pay attention to the phase of the ongoing theta oscillation. If you have access to the phase at which the neuron fired, you have additional information about where the rat was in space."
When the data about neuronal firing, oscillation phase, and rat location were combined, the researchers were able to show that neuronal activity indeed sweeps across the hippocampus in a wave, with its peak appearing in one region, then another, then another, rather than hitting the entire hippocampus in one synchronized pulse.
"This changes our notion of how spatial information is represented in the rat brain," notes Lubenov. "It was believed that the firing of hippocampal neurons encodes the physical location of the rat in its environment - in other words, a point of physical space. Our findings suggest that what is encoded is actually a portion of the rat's trajectory - that is, a segment of physical space."
"Such segments may be the elementary unit of hippocampal computation," adds Siapas. "Assume the path a rat takes in an environment is represented and stored as a sequence of point locations. If the rat visits the same location more than once, the representation becomes ambiguous. Representing the rat trajectory as a sequence of segments oriented in space resolves such ambiguities."
This finding may also have significant implications for understanding how information is transmitted from the hippocampus to other areas of the brain. "Different portions of the hippocampus are connected to different areas in other parts of the brain. The fact that hippocampal activity forms a traveling wave means that these target areas receive inputs from the hippocampus in a specific sequence rather than all at once," explains Siapas.
In addition, Siapas notes, it's unlikely that this behavior is found only in rat brains; after all, theta oscillations are ubiquitous in mammalian brains. "I would expect the traveling-wave nature of theta oscillations to be a general finding, applicable to humans as well," he says.
And while it is not known whether human hippocampal cells function as place cells, as they do in rats, "it may turn out to be the case that the human hippocampus plays a role in providing spatial cues that are important to episodic memory," Lubenov speculates. "We don't know yet."
What we do know is that, by showing that theta oscillations travel across the hippocampus, the Caltech team will likely change the way neuroscientists think about how the hippocampus works.
The work described in the Nature paper, "Hippocampal theta oscillations are travelling waves," was supported by the Caltech Information Science and Technology Center for Biological Circuit Design, a 21st Century McDonnell Foundation Award, the Bren Foundation, and the McKnight Foundation.
The paper's abstract can be accessed at dx.doi/10.1038/nature08010.
Source:
Lori Oliwenstein
California Institute of Technology
суббота, 11 июня 2011 г.
Duckweed Can Undo Pollution, Fight Global Warming And Alleviate World Hunger
Three plant biologists at Rutgers' Waksman Institute of Microbiology are obsessed with duckweed, a tiny aquatic plant with an unassuming name. Now they have convinced the federal government to focus its attention on duckweed's tremendous potential for cleaning up pollution, combating global warming and feeding the world.
This enterprise builds upon Rutgers' burgeoning energy and environmental research and the important contributions Waksman Institute scientists have already made to plant genomics, including the sequencing of rice, sorghum and corn.
At the behest of the Rutgers scientists and their colleagues from five other institutions, the U.S. Department of Energy (DOE) will channel resources at its national laboratories into sequencing the genome of the lowly duckweed. The DOE's Joint Genome Institute announced on July 2 that its Community Sequencing Program will support the genomic sequencing of duckweed (Spirodela polyrhiza) as one of its priority projects for 2009 directed toward new biomass and bioenergy programs.
According to the researchers, duckweed plants can extract nitrogen and phosphate pollutants from agricultural and municipal wastewater. They can reduce algae growth, coliform bacterial counts and mosquito larvae on ponds, while concentrating heavy metals, capturing or degrading toxic chemicals, and encourage the growth of other aquatic animals such as frogs and fowl. These plants produce biomass faster than any other flowering plant, serve as high-protein feed for domestic animals and show clear potential as an alternative for biofuel production.
Todd Michael, a member of the Waksman Institute and an assistant professor of plant biology and pathology at Rutgers, The State University of New Jersey, led the multi-institutional initiative to have the DOE's Joint Genome Institute perform high-throughput sequencing of this smallest, fastest growing and simplest of flowering plants.
"The Spirodela genome sequence could unlock the remarkable potential of a rapidly growing aquatic plant for absorbing atmospheric carbon dioxide, ecosystem carbon cycling and biofuel production," said Michael, who is also a member of the faculty of the School of Environmental and Biological Sciences.
His collaborators in this undertaking include professors Randall Kerstetter and Joachim Messing of the Waksman Institute, and scientists at Brookhaven National Laboratory, the Institut fГјr Integrative Biologie (Switzerland), the University of Jena (Germany), Kyoto University (Japan) and Oregon State University.
The DOE's Joint Genome Institute is operated by the University of California and includes five national laboratories - Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge and Pacific Northwest - and the Stanford Human Genome Center.
With the passage of the Energy Policy Act of 2005 and recent increases in food prices worldwide, the drive to develop sustainable feedstocks and processing protocols for biofuel production has intensified. The search for new biomass species has revealed the potential of duckweed species in this regard as well as for bioremediation and environmental carbon capture.
Source: Joseph Blumberg
Rutgers University
This enterprise builds upon Rutgers' burgeoning energy and environmental research and the important contributions Waksman Institute scientists have already made to plant genomics, including the sequencing of rice, sorghum and corn.
At the behest of the Rutgers scientists and their colleagues from five other institutions, the U.S. Department of Energy (DOE) will channel resources at its national laboratories into sequencing the genome of the lowly duckweed. The DOE's Joint Genome Institute announced on July 2 that its Community Sequencing Program will support the genomic sequencing of duckweed (Spirodela polyrhiza) as one of its priority projects for 2009 directed toward new biomass and bioenergy programs.
According to the researchers, duckweed plants can extract nitrogen and phosphate pollutants from agricultural and municipal wastewater. They can reduce algae growth, coliform bacterial counts and mosquito larvae on ponds, while concentrating heavy metals, capturing or degrading toxic chemicals, and encourage the growth of other aquatic animals such as frogs and fowl. These plants produce biomass faster than any other flowering plant, serve as high-protein feed for domestic animals and show clear potential as an alternative for biofuel production.
Todd Michael, a member of the Waksman Institute and an assistant professor of plant biology and pathology at Rutgers, The State University of New Jersey, led the multi-institutional initiative to have the DOE's Joint Genome Institute perform high-throughput sequencing of this smallest, fastest growing and simplest of flowering plants.
"The Spirodela genome sequence could unlock the remarkable potential of a rapidly growing aquatic plant for absorbing atmospheric carbon dioxide, ecosystem carbon cycling and biofuel production," said Michael, who is also a member of the faculty of the School of Environmental and Biological Sciences.
His collaborators in this undertaking include professors Randall Kerstetter and Joachim Messing of the Waksman Institute, and scientists at Brookhaven National Laboratory, the Institut fГјr Integrative Biologie (Switzerland), the University of Jena (Germany), Kyoto University (Japan) and Oregon State University.
The DOE's Joint Genome Institute is operated by the University of California and includes five national laboratories - Lawrence Berkeley, Lawrence Livermore, Los Alamos, Oak Ridge and Pacific Northwest - and the Stanford Human Genome Center.
With the passage of the Energy Policy Act of 2005 and recent increases in food prices worldwide, the drive to develop sustainable feedstocks and processing protocols for biofuel production has intensified. The search for new biomass species has revealed the potential of duckweed species in this regard as well as for bioremediation and environmental carbon capture.
Source: Joseph Blumberg
Rutgers University
пятница, 10 июня 2011 г.
Mood Dysfunction Improved In Gene Knockout Mice
Removing the PKCI/HINT1 gene from mice has an anti-depressant-like and anxiolytic-like effect. Researchers writing in the open access journal BMC Neuroscience applied a battery of behavioral tests to the PKCI/HINT1 knockout animals, concluding that the deleted gene may have an important role in mood regulation.
Elisabeth Barbier and Jia Bei Wang, from the School of Pharmacy at the University of Maryland, USA, carried out the experiments to investigate the role of the gene in regulating mood function. Wang, the corresponding author of the paper, said, "The knockout mice displayed behaviors indicative of changes in mood function, such as increased perseverance and reduced anxiety in open spaces".
The causes of mood dysfunction, as seen in depressive and bipolar disorders, are still not fully understood. They are believed to be multifactorial, involving heredity, changes in neurotransmitter levels, altered neuro-endocrine function, and psychosocial factors. Speaking about these results, Wang said, "Although we don't yet know why the deletion of the gene altered the mood status of the mice, what we have learned about the importance of this gene in mood function and its involvement in human mental disorders is interesting. The protein encoded by this gene could be a potential drug target for development of diagnostic or therapeutic agents that one day might be used for depression, bipolar or schizophrenia disorders. In addition, the knockout mice might be useful as a model to study mania, as there is no other animal model available yet.
Notes:
Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level
Elisabeth Barbier and Jia Bei Wang
BMC Neuroscience (in press)
biomedcentral/bmcneurosci/
Source: Graeme Baldwin
BioMed Central
Elisabeth Barbier and Jia Bei Wang, from the School of Pharmacy at the University of Maryland, USA, carried out the experiments to investigate the role of the gene in regulating mood function. Wang, the corresponding author of the paper, said, "The knockout mice displayed behaviors indicative of changes in mood function, such as increased perseverance and reduced anxiety in open spaces".
The causes of mood dysfunction, as seen in depressive and bipolar disorders, are still not fully understood. They are believed to be multifactorial, involving heredity, changes in neurotransmitter levels, altered neuro-endocrine function, and psychosocial factors. Speaking about these results, Wang said, "Although we don't yet know why the deletion of the gene altered the mood status of the mice, what we have learned about the importance of this gene in mood function and its involvement in human mental disorders is interesting. The protein encoded by this gene could be a potential drug target for development of diagnostic or therapeutic agents that one day might be used for depression, bipolar or schizophrenia disorders. In addition, the knockout mice might be useful as a model to study mania, as there is no other animal model available yet.
Notes:
Anti-depressant and anxiolytic like behaviors in PKCI/HINT1 knockout mice associated with elevated plasma corticosterone level
Elisabeth Barbier and Jia Bei Wang
BMC Neuroscience (in press)
biomedcentral/bmcneurosci/
Source: Graeme Baldwin
BioMed Central
четверг, 9 июня 2011 г.
Studying Vioxx Side Effects
Vioxx and related pain medications were taken off the market in 2004 because they caused dangerous heart problems in some people. A group of scientists, led by Timothy Hla at the University of Connecticut, may now have figured out how these drugs trigger these life-threatening side-effects. The new study is published online in the The Journal of Experimental Medicine.
The target of these drugs is an enzyme called COX-2, which is produced in response to infection or injury and releases pain- and fever-inducing byproducts. Thus blocking COX-2 reduces pain. But blocking Cox-2 in mice, according to the new study, also stimulated the production of a protein called tissue factor, or TF, which initiates blood clotting. As heart attacks and strokes are often triggered by blood clots, it is possible that the production of TF is in part responsible for the drug's adverse side-effects in humans.
In the drug-treated mice, the high levels of TF in the blood were countered by administering TF-reducing drugs. Thus it is theoretically possible to treat people safely with Vioxx and other Cox-2 inhibitors if existing TF-blocking drugs are given simultaneously.
Source: Hema Bashyam
Journal of Experimental Medicine
View drug information on Vioxx.
The target of these drugs is an enzyme called COX-2, which is produced in response to infection or injury and releases pain- and fever-inducing byproducts. Thus blocking COX-2 reduces pain. But blocking Cox-2 in mice, according to the new study, also stimulated the production of a protein called tissue factor, or TF, which initiates blood clotting. As heart attacks and strokes are often triggered by blood clots, it is possible that the production of TF is in part responsible for the drug's adverse side-effects in humans.
In the drug-treated mice, the high levels of TF in the blood were countered by administering TF-reducing drugs. Thus it is theoretically possible to treat people safely with Vioxx and other Cox-2 inhibitors if existing TF-blocking drugs are given simultaneously.
Source: Hema Bashyam
Journal of Experimental Medicine
View drug information on Vioxx.
среда, 8 июня 2011 г.
Nanotech Medicine
To rebuild damaged parts of a human body from scratch is a dream that has long fired human imagination, from Mary Shelley's Doctor Frankenstein to modern day surgeons. Now, a team of European scientists has made a promising contribution to reconstructive surgery thanks to an original multidisciplinary approach matching cutting-edge medicine to the latest developments in nanotechnology.
According to the World Health Organisation (WHO), an estimated 322,000 deaths globally per year are linked to severe injuries from fire and in many of these cases death could have been avoided with surgical intervention.
In this type of intervention, when major burns patients have insufficient skin left to graft on the most damaged part of their body, new skin has literally to be grown from the patient's own skin cells. However, the long delay in growing the skin can expose the burns patient to increased risk of infection and dehydration; so to help those cells to multiply, specialists use a particular kind of component called polymeric material. Because of their extraordinary range of properties, polymeric materials play a ubiquitous role in our daily life. This role ranges from familiar synthetic plastics: plastic bags or yoghurt cups, to natural biopolymers such as wood or proteins that are present in the human body.
New nano-structured materials
It has been known for the last few years that man made synthetic polymeric materials have the potential to grow and multiply human cells. 'About 10 years ago, scientists discovered the important influence that nano-structures had on the way a line of cells would develop. It was the beginning of an entire new scientific field, somewhere between medicine and nanotechnology,' says Professor Johannes Heitz, Senior Research Associate at the University of Linz, Austria and main coordinator of the ModPolEUV project.
In the case of human skin cells, re-implantation of the tissue can be performed once a sufficient amount of skin is obtained, by growing it on a polymeric material surface. However, in many cases, imperfections in the material structure can make the process relatively long and sometimes inefficient, with cells developing erratically. The team of Austrian, Czech and Polish scientists involved in the research project managed to develop a new and simple way to create nano-structured materials that would allow a better development of human cells.
The Polish partner in the team, the Military University of Technology of Warsaw, has been in charge of the development of the new laser-based technology called EUV (Extreme Ultra-Violet) that was used for the creation of the nano-structured polymer surfaces. A beam of EUV light formed with a unique mirror developed by the Czech partner REFLEX S.R.O is directed on the surface allowing the creation of new kinds of polymeric materials. This innovative technique allows for a very high degree of precision, from 10 to 20 nanometres, whereas conventional techniques allowed only for a maximal precision level of 100 nanometres. 'One of the newest theories in the field of cell growing is that the smaller the structure, the wider the possibilities to manipulate cells,' says Professor Heitz.
A wide range of human cells
The EUV technique, thanks to its particular level of precision, also allows for the conservation of the material's structure, which was not the case with other methods used to modify the polymer. 'A regular structure is essential if the material is to be used for the purpose of growing human cells,' says Dr Henryk Fiederowicz, Professor at the Military University of Technology.
The story does not end there. Nano-structures built through the EUV technique have the ability to influence the behaviour of organic cells and different kind of cells can be grown better and faster depending on the type of polymer surface used.
The variety of material used to grow human stem cells will determinate the way cells will differentiate, meaning that they will transform into another human cell type. In other words: 'Using one type of polymer material or another will help you grow different types of muscle, nerves, cells adapted to a human heart, bone or any other part of the human body,' says Professor Heitz.
Thanks to their affinity to human tissue and cells, polymeric materials could also be used for designing entire artificial implants. Indeed, many types of implants are already being made out of polymer materials, such as heart valves and bloods vessels. Using the EUV technique would reduce the odds of implant rejection, as the range of new materials created could be adapted to interact perfectly with specific parts of a patient's body.
Broad applications
All partners agree on the fact that EUREKA has helped them to find elsewhere in Europe the expertise and skills unavailable in their own countries. The next step is to bring their innovation to the market.
The Military Institute of Technology has already handled several EUV installations to laboratories in the USA, Germany, the Czech Republic, France, Japan, China and South Korea. It is now preparing for a full commercial phase, in partnership with the Polish company PREVAC, a leader in the market of high-precision instruments.
Applications of this novel technique could go far beyond nano-medicine and bio-technologies. An important potential market could be the one of micro-electronics, with its ever-expanding need for high-precision lithography; applications could be proposed to every type of industry where nano-structures are used. For instance, in micro-mechanics, integrated optics, wear reduction or the production of nano-composite materials.
For researchers at Linz University, the cell-growing technology is still in a testing phase and Professor Heitz prefers not to be overwhelmed by enthusiasm, even though he concedes that results have been 'very encouraging so far'. 'The interaction of cells with which structure dimensions are below 100 nanometres is currently the topic of a huge international effort,' he says. Despite the importance of the innovation 'our contribution is very small when compared to the many other laboratories working in this field at the moment'.
According to Professor Heitz, 'recreating whole organs is still a scientist's dream'. Yet the outcome of the E! 3892 ModPolEUV project might just have brought the dream a little closer to reality.
Source:
Piotr Pogorzelski
EUREKA
According to the World Health Organisation (WHO), an estimated 322,000 deaths globally per year are linked to severe injuries from fire and in many of these cases death could have been avoided with surgical intervention.
In this type of intervention, when major burns patients have insufficient skin left to graft on the most damaged part of their body, new skin has literally to be grown from the patient's own skin cells. However, the long delay in growing the skin can expose the burns patient to increased risk of infection and dehydration; so to help those cells to multiply, specialists use a particular kind of component called polymeric material. Because of their extraordinary range of properties, polymeric materials play a ubiquitous role in our daily life. This role ranges from familiar synthetic plastics: plastic bags or yoghurt cups, to natural biopolymers such as wood or proteins that are present in the human body.
New nano-structured materials
It has been known for the last few years that man made synthetic polymeric materials have the potential to grow and multiply human cells. 'About 10 years ago, scientists discovered the important influence that nano-structures had on the way a line of cells would develop. It was the beginning of an entire new scientific field, somewhere between medicine and nanotechnology,' says Professor Johannes Heitz, Senior Research Associate at the University of Linz, Austria and main coordinator of the ModPolEUV project.
In the case of human skin cells, re-implantation of the tissue can be performed once a sufficient amount of skin is obtained, by growing it on a polymeric material surface. However, in many cases, imperfections in the material structure can make the process relatively long and sometimes inefficient, with cells developing erratically. The team of Austrian, Czech and Polish scientists involved in the research project managed to develop a new and simple way to create nano-structured materials that would allow a better development of human cells.
The Polish partner in the team, the Military University of Technology of Warsaw, has been in charge of the development of the new laser-based technology called EUV (Extreme Ultra-Violet) that was used for the creation of the nano-structured polymer surfaces. A beam of EUV light formed with a unique mirror developed by the Czech partner REFLEX S.R.O is directed on the surface allowing the creation of new kinds of polymeric materials. This innovative technique allows for a very high degree of precision, from 10 to 20 nanometres, whereas conventional techniques allowed only for a maximal precision level of 100 nanometres. 'One of the newest theories in the field of cell growing is that the smaller the structure, the wider the possibilities to manipulate cells,' says Professor Heitz.
A wide range of human cells
The EUV technique, thanks to its particular level of precision, also allows for the conservation of the material's structure, which was not the case with other methods used to modify the polymer. 'A regular structure is essential if the material is to be used for the purpose of growing human cells,' says Dr Henryk Fiederowicz, Professor at the Military University of Technology.
The story does not end there. Nano-structures built through the EUV technique have the ability to influence the behaviour of organic cells and different kind of cells can be grown better and faster depending on the type of polymer surface used.
The variety of material used to grow human stem cells will determinate the way cells will differentiate, meaning that they will transform into another human cell type. In other words: 'Using one type of polymer material or another will help you grow different types of muscle, nerves, cells adapted to a human heart, bone or any other part of the human body,' says Professor Heitz.
Thanks to their affinity to human tissue and cells, polymeric materials could also be used for designing entire artificial implants. Indeed, many types of implants are already being made out of polymer materials, such as heart valves and bloods vessels. Using the EUV technique would reduce the odds of implant rejection, as the range of new materials created could be adapted to interact perfectly with specific parts of a patient's body.
Broad applications
All partners agree on the fact that EUREKA has helped them to find elsewhere in Europe the expertise and skills unavailable in their own countries. The next step is to bring their innovation to the market.
The Military Institute of Technology has already handled several EUV installations to laboratories in the USA, Germany, the Czech Republic, France, Japan, China and South Korea. It is now preparing for a full commercial phase, in partnership with the Polish company PREVAC, a leader in the market of high-precision instruments.
Applications of this novel technique could go far beyond nano-medicine and bio-technologies. An important potential market could be the one of micro-electronics, with its ever-expanding need for high-precision lithography; applications could be proposed to every type of industry where nano-structures are used. For instance, in micro-mechanics, integrated optics, wear reduction or the production of nano-composite materials.
For researchers at Linz University, the cell-growing technology is still in a testing phase and Professor Heitz prefers not to be overwhelmed by enthusiasm, even though he concedes that results have been 'very encouraging so far'. 'The interaction of cells with which structure dimensions are below 100 nanometres is currently the topic of a huge international effort,' he says. Despite the importance of the innovation 'our contribution is very small when compared to the many other laboratories working in this field at the moment'.
According to Professor Heitz, 'recreating whole organs is still a scientist's dream'. Yet the outcome of the E! 3892 ModPolEUV project might just have brought the dream a little closer to reality.
Source:
Piotr Pogorzelski
EUREKA
вторник, 7 июня 2011 г.
Tails Now Being Designed For Robots, But Could Also Aid Astronauts
How useful is an animal's tail? For the gecko, unlike most animals, it could be a matter of life or death, according to new research from the University of California, Berkeley.
In a paper appearing this week in the online early edition of the journal Proceedings of the National Academy of Sciences, UC Berkeley biologists report that geckos rely on their tails to keep from falling off vertical surfaces and, if they do fall, to right themselves in midair and maneuver like a skydiver gliding to a safe landing.
The discovery is already helping engineers design better climbing robots and may aid in the design of unmanned gliding vehicles or spacecraft. Perhaps, the researchers say, an "active" tail could help astronauts maneuver in space.
According to senior author Robert J. Full, professor of integrative biology at UC Berkeley, previous experiments on geckos have focused on their unique toes as the key to running up a wall and hanging onto ceilings. Full discovered six years ago that, while claws help geckos climb rough surfaces, millions of microscopic toe hairs make it possible for them to climb smooth ones.
Only when engineers began building gecko-like robots, such as Boston Dynamics Inc.'s RiSE (Robot in Scansorial Environment), the University of Pennsylvania's DynaClimber and Stanford University robots Spinybot and Stickybot - all inspired by Full's findings - did they discover that a tail might be necessary to prevent the robot from pitching backward and falling when it slips on a vertical surface.
When Full and UC Berkeley graduate student Ardian Jusufi went back to the lab to look at how geckos, specifically the flat-tailed house gecko, Cosymbotus platyurus, of Southeast Asia, use their tails, they discovered that the tail is critical for dealing with slippery surfaces.
"When we ran all of our geckos on perfect surfaces, they never slipped, and they didn't use their tails," Full said. "But when we put in a slippery patch, we found that they have an active tail that functions like a fifth leg to keep them from tipping backward. This is an undiscovered function for tails that tells us a lot about how active tails could affect the performance of vertebrates."
With the help of high-speed video, the researchers discovered that when a gecko loses traction with one leg, it taps its tail on the surface to prevent pitch-back until the toes can grab hold again. This all happens in milliseconds, since geckos can run up a wall at speeds of 3 feet per second, stepping and peeling off their toes 30 times per second.
If a gecko loses traction with more than one foot, the researchers found, it will often flatten its tail to the surface to prevent a fall in a move that has the effect, says Full, of a bicycle kickstand. Using either the tail-tapping or tail-flattening technique, nearly all geckos were able to navigate across slippery patches on a vertical wall.
"We were really surprised to see that they could pitch back up to 60 degrees, return to the vertical surface and still traverse the slippery patches," Jusufi said.
The engineers with whom Full collaborates are now devising active tails for their robots to replicate these moves, which in a gecko are probably reflexive, Full said.
The researchers acknowledged the usefulness of tails in other animals: kangaroos lean on theirs; chameleons, lemurs and New World monkeys grasp with theirs; and dinosaurs may have used theirs for balance while running and walking. Unlike these more static uses, however, the gecko's tail actively helps in high-speed vertical climbing and gliding.
During the slippery wall experiments, Jusufi and Full noticed something else about the geckos when they fell. They nearly always made a four-point landing after using their tails to reorient themselves in mid-air. Using high-speed video to record geckos falling upside down from a fake leaf, they found that the geckos rotated their tails so that their bodies counter-rotated to face downward, then spread their legs and toes to parachute. This mid-air maneuver was possible because of the gecko's typically large tail, which can be filled with fat.
While this parachuting had been noticed before by other researchers, the role of the tail was first recognized by Full and Jusufi.
"Air righting in mammals is characterized by a bending and twisting of the spine," Jusufi said. Cats, whose mid-air twists have been particularly well studied since 1894, are able to land on four paws with or without a tail. In contrast, he said, "the gecko is keeping its limbs and spine absolutely immobile in nearly 70 percent of all trials, and only rotates its tail until it turns around."
Moreover, after turning face down, the geckos in the study often used their tails to maneuver in mid-air like a skydiver steering toward a targeted drop zone. In wind tunnel tests, geckos could actually hover in the air stream and, using their tails, steer toward a solid perch.
"Why go into this Superman posture?" Full asked. "We found that it allowed them to use their tails to turn or control yaw and pitch. In the wild, this might allow a gecko escaping a predator to just go off the end of a branch and maneuver to another place."
Pitch refers to a head-down versus tail-down position, while yaw is a rotation to the left or right around a vertical axis.
Jusufi is now observing geckos in the wild to determine how these aerobatic skills serve them in the forest.
"We believe these animals are using their tails instead of their bodies to simplify control," he said. "Geckos reorient mainly around one axis, whereas air-righting maneuvers in mammals involve several axes and appear to require far more coordination."
"This discovery is another example of how basic research leads to unexpected applications - new climbing and gliding robots, highly maneuverable unmanned aerial vehicles and even energy-efficient control in space vehicles," said Full, who directs UC Berkeley's new Center for Interdisciplinary Bio-inspiration in Education and Research (CiBER). CiBER's goal is to discover principles that will inspire engineers from academia and industry to develop new materials and design novel robots, but also to seek feedback from engineering successes and failures to suggest new biological hypotheses.
Jusufi and Full are continuing their study of how the gecko uses its tail, and they plan to look at other lizards to determine how widespread this behavior is.
Coauthors with Jusufi and Full are former UC Berkeley postdoctoral fellow Daniel Goldman, now a professor at the Georgia Institute of Technology, and UC Berkeley graduate student Shai Revzen.
The research was supported by grants from the Defense Advanced Research Projects Agency, the National Science Foundation, the Kurt and Barbara Gilgen Fund and The Burroughs Wellcome Fund.
Source: Robert Sanders
University of California - Berkeley
In a paper appearing this week in the online early edition of the journal Proceedings of the National Academy of Sciences, UC Berkeley biologists report that geckos rely on their tails to keep from falling off vertical surfaces and, if they do fall, to right themselves in midair and maneuver like a skydiver gliding to a safe landing.
The discovery is already helping engineers design better climbing robots and may aid in the design of unmanned gliding vehicles or spacecraft. Perhaps, the researchers say, an "active" tail could help astronauts maneuver in space.
According to senior author Robert J. Full, professor of integrative biology at UC Berkeley, previous experiments on geckos have focused on their unique toes as the key to running up a wall and hanging onto ceilings. Full discovered six years ago that, while claws help geckos climb rough surfaces, millions of microscopic toe hairs make it possible for them to climb smooth ones.
Only when engineers began building gecko-like robots, such as Boston Dynamics Inc.'s RiSE (Robot in Scansorial Environment), the University of Pennsylvania's DynaClimber and Stanford University robots Spinybot and Stickybot - all inspired by Full's findings - did they discover that a tail might be necessary to prevent the robot from pitching backward and falling when it slips on a vertical surface.
When Full and UC Berkeley graduate student Ardian Jusufi went back to the lab to look at how geckos, specifically the flat-tailed house gecko, Cosymbotus platyurus, of Southeast Asia, use their tails, they discovered that the tail is critical for dealing with slippery surfaces.
"When we ran all of our geckos on perfect surfaces, they never slipped, and they didn't use their tails," Full said. "But when we put in a slippery patch, we found that they have an active tail that functions like a fifth leg to keep them from tipping backward. This is an undiscovered function for tails that tells us a lot about how active tails could affect the performance of vertebrates."
With the help of high-speed video, the researchers discovered that when a gecko loses traction with one leg, it taps its tail on the surface to prevent pitch-back until the toes can grab hold again. This all happens in milliseconds, since geckos can run up a wall at speeds of 3 feet per second, stepping and peeling off their toes 30 times per second.
If a gecko loses traction with more than one foot, the researchers found, it will often flatten its tail to the surface to prevent a fall in a move that has the effect, says Full, of a bicycle kickstand. Using either the tail-tapping or tail-flattening technique, nearly all geckos were able to navigate across slippery patches on a vertical wall.
"We were really surprised to see that they could pitch back up to 60 degrees, return to the vertical surface and still traverse the slippery patches," Jusufi said.
The engineers with whom Full collaborates are now devising active tails for their robots to replicate these moves, which in a gecko are probably reflexive, Full said.
The researchers acknowledged the usefulness of tails in other animals: kangaroos lean on theirs; chameleons, lemurs and New World monkeys grasp with theirs; and dinosaurs may have used theirs for balance while running and walking. Unlike these more static uses, however, the gecko's tail actively helps in high-speed vertical climbing and gliding.
During the slippery wall experiments, Jusufi and Full noticed something else about the geckos when they fell. They nearly always made a four-point landing after using their tails to reorient themselves in mid-air. Using high-speed video to record geckos falling upside down from a fake leaf, they found that the geckos rotated their tails so that their bodies counter-rotated to face downward, then spread their legs and toes to parachute. This mid-air maneuver was possible because of the gecko's typically large tail, which can be filled with fat.
While this parachuting had been noticed before by other researchers, the role of the tail was first recognized by Full and Jusufi.
"Air righting in mammals is characterized by a bending and twisting of the spine," Jusufi said. Cats, whose mid-air twists have been particularly well studied since 1894, are able to land on four paws with or without a tail. In contrast, he said, "the gecko is keeping its limbs and spine absolutely immobile in nearly 70 percent of all trials, and only rotates its tail until it turns around."
Moreover, after turning face down, the geckos in the study often used their tails to maneuver in mid-air like a skydiver steering toward a targeted drop zone. In wind tunnel tests, geckos could actually hover in the air stream and, using their tails, steer toward a solid perch.
"Why go into this Superman posture?" Full asked. "We found that it allowed them to use their tails to turn or control yaw and pitch. In the wild, this might allow a gecko escaping a predator to just go off the end of a branch and maneuver to another place."
Pitch refers to a head-down versus tail-down position, while yaw is a rotation to the left or right around a vertical axis.
Jusufi is now observing geckos in the wild to determine how these aerobatic skills serve them in the forest.
"We believe these animals are using their tails instead of their bodies to simplify control," he said. "Geckos reorient mainly around one axis, whereas air-righting maneuvers in mammals involve several axes and appear to require far more coordination."
"This discovery is another example of how basic research leads to unexpected applications - new climbing and gliding robots, highly maneuverable unmanned aerial vehicles and even energy-efficient control in space vehicles," said Full, who directs UC Berkeley's new Center for Interdisciplinary Bio-inspiration in Education and Research (CiBER). CiBER's goal is to discover principles that will inspire engineers from academia and industry to develop new materials and design novel robots, but also to seek feedback from engineering successes and failures to suggest new biological hypotheses.
Jusufi and Full are continuing their study of how the gecko uses its tail, and they plan to look at other lizards to determine how widespread this behavior is.
Coauthors with Jusufi and Full are former UC Berkeley postdoctoral fellow Daniel Goldman, now a professor at the Georgia Institute of Technology, and UC Berkeley graduate student Shai Revzen.
The research was supported by grants from the Defense Advanced Research Projects Agency, the National Science Foundation, the Kurt and Barbara Gilgen Fund and The Burroughs Wellcome Fund.
Source: Robert Sanders
University of California - Berkeley
понедельник, 6 июня 2011 г.
Preventing Metastasis To 'Stop Cancer From Killing People'
Metastasis is the ability of cancer cells to spread from a primary site, to form tumours at distant sites. It is a complex process in which cell motility and invasion play a fundamental role. Essential to our understanding of how metastasis develops is identification of the molecules, and characterisation of the mechanisms that regulate cell motility. Hitherto, these mechanisms have been poorly understood. Now, a team of researchers lead by Professor Marco Falasca at Barts and The London School of Medicine and Dentistry has shown not only that the enzyme phospholipase CОі1 (PLCОі1) plays a crucial role in metastasis formation, but that down regulation of PLCОі1 expression is able to revert metastasis progression.
The team investigated the role of PLCОі1 in cell invasion and metastasis using different approaches to modulate its expression in highly invasive cancer cell lines. Their results showed that PLCОі1 is required for breast cancer cell invasion and activation of the protein Rac1. They revealed a functional link between PLCОі1 and Rac1 that provides insight into processes regulating cell invasion.
Professor Falasca explained: "Consistent with these data we detected an increase in PLC1 expression in metastases compared to primary tumours in breast cancer patients. Therefore PLCОі1 is critical for metastasis formation, and development and inhibition of this enzyme has a therapeutic potential in the treatment of metastasis dissemination."
"This is an exciting discovery. He has shown that turning off this molecule prevents metastasis. The simple fact is that if you stop metastasis, you stop cancer from killing people. We now need to focus on developing drugs that can block PLCОі1."
'Phospholipase CОі1 is Required for Metastasis Development and Progression' is published in Cancer Research.
The research was supported by The Association for International Cancer Research and by the European Commission FP6 program Apotherapy.
Notes:
Barts and The London School of Medicine and Dentistry
Barts and The London School of Medicine and Dentistry - at Queen Mary, University of London - offers international levels of excellence in research and teaching while serving a population of unrivalled diversity amongst which cases of diabetes, hypertension, heart disease, TB, oral disease and cancers are prevalent, within east London and the wider Thames Gateway. Through partnership with our linked trusts, notably Barts and The London NHS Trust, and our associated University Hospital trusts - Homerton, Newham, Whipps Cross and Queen's - the School's research and teaching is informed by an exceptionally wide ranging and stimulating clinical environment.
At the heart of the School's mission lies world class research, the result of a focused programme of recruitment of leading research groups from the UK and abroad and a ВЈ100 million investment in state-of-the-art facilities. Research is focused on translational research, cancer, cardiology, clinical pharmacology, inflammation, infectious diseases, stem cells, dermatology, gastroenterology, haematology, diabetes, neuroscience, surgery and dentistry.
The School is nationally and internationally recognised for research in these areas, reflected in the ВЈ40 million it attracts annually in research income. Its fundamental mission, with its partner NHS Trusts, and other partner organisations such as CRUK, is to ensure that that the best possible clinical service is underpinned by the very latest developments in scientific and clinical teaching, training and research.
Source: Alex Fernandes
Queen Mary, University of London
The team investigated the role of PLCОі1 in cell invasion and metastasis using different approaches to modulate its expression in highly invasive cancer cell lines. Their results showed that PLCОі1 is required for breast cancer cell invasion and activation of the protein Rac1. They revealed a functional link between PLCОі1 and Rac1 that provides insight into processes regulating cell invasion.
Professor Falasca explained: "Consistent with these data we detected an increase in PLC1 expression in metastases compared to primary tumours in breast cancer patients. Therefore PLCОі1 is critical for metastasis formation, and development and inhibition of this enzyme has a therapeutic potential in the treatment of metastasis dissemination."
"This is an exciting discovery. He has shown that turning off this molecule prevents metastasis. The simple fact is that if you stop metastasis, you stop cancer from killing people. We now need to focus on developing drugs that can block PLCОі1."
'Phospholipase CОі1 is Required for Metastasis Development and Progression' is published in Cancer Research.
The research was supported by The Association for International Cancer Research and by the European Commission FP6 program Apotherapy.
Notes:
Barts and The London School of Medicine and Dentistry
Barts and The London School of Medicine and Dentistry - at Queen Mary, University of London - offers international levels of excellence in research and teaching while serving a population of unrivalled diversity amongst which cases of diabetes, hypertension, heart disease, TB, oral disease and cancers are prevalent, within east London and the wider Thames Gateway. Through partnership with our linked trusts, notably Barts and The London NHS Trust, and our associated University Hospital trusts - Homerton, Newham, Whipps Cross and Queen's - the School's research and teaching is informed by an exceptionally wide ranging and stimulating clinical environment.
At the heart of the School's mission lies world class research, the result of a focused programme of recruitment of leading research groups from the UK and abroad and a ВЈ100 million investment in state-of-the-art facilities. Research is focused on translational research, cancer, cardiology, clinical pharmacology, inflammation, infectious diseases, stem cells, dermatology, gastroenterology, haematology, diabetes, neuroscience, surgery and dentistry.
The School is nationally and internationally recognised for research in these areas, reflected in the ВЈ40 million it attracts annually in research income. Its fundamental mission, with its partner NHS Trusts, and other partner organisations such as CRUK, is to ensure that that the best possible clinical service is underpinned by the very latest developments in scientific and clinical teaching, training and research.
Source: Alex Fernandes
Queen Mary, University of London
воскресенье, 5 июня 2011 г.
In 'Biopsy' Tests Wireless Microgrippers Grab Living Cells
In experiments that pave the way for tiny mobile surgical tools activated by heat or chemicals, Johns Hopkins researchers have invented dust-particle-size devices that can be used to grab and remove living cells from hard-to-reach places without the need for electrical wires, tubes or batteries. Instead, the devices are actuated by thermal or biochemical signals.
The mass-producible microgrippers each measure approximately one-tenth of a millimeter in diameter. In lab tests, they have been used to perform a biopsy-like procedure on animal tissue placed at the end of a narrow tube. Experiments using the devices were reported in the online Early Edition of Proceedings of the National Academy of Sciences for the week of Jan. 12-16.
Although the devices will require further refinement before they can be used in humans, David H. Gracias, who supervised the project, said these thermobiochemically responsive, functional micro-tools represent a paradigm shift in engineering. "We've demonstrated tiny inexpensive tools that can be triggered en masse by nontoxic biochemicals," said Gracias, an assistant professor of chemical and biomolecular engineering in Johns Hopkins' Whiting School of Engineering. "This is an important first step toward creating a new set of biochemically responsive and perhaps even autonomous micro- and nanoscale surgical tools that could help doctors diagnose illnesses and administer treatment in a more efficient, less invasive way."
Today, doctors who wish to collect cells or manipulate a bit of tissue inside a patient's body often use tethered microgrippers connected to thin wires or tubes. But these tethers can make it difficult navigate the tool through tortuous or hard-to-reach locations. To eliminate this problem, the untethered grippers devised by Gracias' team contain gold-plated nickel, allowing them to be steered by magnets outside the body. "With this method, we were able to remotely move the microgrippers a relatively long distance over tissue without getting stuck, he said. "Additionally, the microgrippers are triggered to close and extricate cells from tissue when exposed to certain biochemicals or biologically relevant temperatures."
The microgripper design -- six three-jointed digits extended from a central "palm" -- resembles a crab. (In fact, the joint design was inspired by that of arthropod animals.) To fabricate the microgrippers in their initial flat position with all digits fully extended, the researchers employ photolithography, the same process used to make computer chips. When the tiny devices are inserted in the body and moved magnetically, the gold-plated nickel in the palm and digits will allow doctors to see and guide the grippers with medical imaging units such as an MRI or CT.
The microgrippers' grasping ability is rooted in the chemical composition of the joints embedded in the finger-like digits. These joints contain thin layers of chromium and copper with stress characteristics that would normally cause the digits to curl themselves closed like fingers clasping a baseball. But the researchers added a polymer resin, giving the joints rigidity to keep the fingers from closing.
When the microgrippers arrive at their destination, however, the researchers raise the temperature to 40 degrees C (or 104 degrees F, equivalent to a moderate fever in humans). This heat softens the polymer in the joints, causing the fingers to flex shut. The researchers also found an alternative method: Some nontoxic biological solutions can also weaken the polymer and cause the grippers to clamp down on their target.
In their lab experiments, the Johns Hopkins researchers used a microgripper, guided by a magnet, to grab and transport a dyed bead from among a group of colorless beads in a water solution. Team members also captured dozens of live animal cells from a cell mass at the end of a capillary tube. The cells were still alive 72 hours later, indicating the capture process did not injure them. Also, the microgrippers captured samples from relatively tough bovine bladder tissue.
The experiments showed that the tetherless microgripper concept is viable and has great potential for medical applications, the researchers said. Gracias' team is now working to overcome some remaining hurdles. As currently designed, each biologically compatible gripper can close on a target only once and cannot be reactivated to reopen and release its contents. (A similar device from the Gracias team, aimed at industrial micro-assembly applications, can be directed to both capture and release its load, but this requires chemicals that are not safe for patients. This pick-and-place microgripper was described in a recent article in the Journal of the American Chemical Society.)
Gracias, who also is affiliated with the Institute for NanoBioTechnology at Johns Hopkins, hopes to collaborate with medical researchers who can help to move the microgrippers closer to use as practical biopsy and drug delivery tools in humans. In September, he received a $1.5 million New Innovators Award from the National Institutes of Health. He plans to use the five-year grant to develop an entire mobile, biochemically responsive micro- and nanoscale surgical tool kit.
The lead author of the PNAS microgripper article was Timothy G. Leong, who was a doctoral student supervised by Gracias. In addition to Leong and Gracias, the paper's co-authors, all students supervised by Gracias at Johns Hopkins, were Christina L. Randall, a doctoral student in the Department of Biomedical Engineering; Brian R. Benson, a junior undergraduate supported by a Provost's Undergraduate Research Award; Noy Bassik, who is enrolled in an M.D./Ph.D. program involving the School of Medicine and the Department of Chemical and Biomolecular Engineering; and George M. Stern, a master's degree student in chemical and biomolecular engineering.
The Johns Hopkins Technology Transfer staff has obtained a provisional United States patent covering the team's inventions and is seeking international patent protection.
Funding for the research was provided by the National Science Foundation, the National Institutes of Health, and the Dreyfus and Beckman foundations.
Photos, illustrations and videos may be seen online at jhu/news/home09/jan09/gracias.html.
Related links:
David Gracias' Lab Page: jhu/chembe/gracias/
Department of Chemical and Biomolecular Engineering: jhu/chembe/PNAS:
"Tetherless Thermo-biochemically Actuated Microgrippers: eurekalert/pio/tipsheetdoc.php/237/zpq6355.pdf
Journal of the American Chemical Society: "Pick-and-Place Using Chemically
Actuated Microgrippers": pubs.acs/doi/abs/10.1021/ja806961p
Source: Phil Sneiderman
Johns Hopkins University
The mass-producible microgrippers each measure approximately one-tenth of a millimeter in diameter. In lab tests, they have been used to perform a biopsy-like procedure on animal tissue placed at the end of a narrow tube. Experiments using the devices were reported in the online Early Edition of Proceedings of the National Academy of Sciences for the week of Jan. 12-16.
Although the devices will require further refinement before they can be used in humans, David H. Gracias, who supervised the project, said these thermobiochemically responsive, functional micro-tools represent a paradigm shift in engineering. "We've demonstrated tiny inexpensive tools that can be triggered en masse by nontoxic biochemicals," said Gracias, an assistant professor of chemical and biomolecular engineering in Johns Hopkins' Whiting School of Engineering. "This is an important first step toward creating a new set of biochemically responsive and perhaps even autonomous micro- and nanoscale surgical tools that could help doctors diagnose illnesses and administer treatment in a more efficient, less invasive way."
Today, doctors who wish to collect cells or manipulate a bit of tissue inside a patient's body often use tethered microgrippers connected to thin wires or tubes. But these tethers can make it difficult navigate the tool through tortuous or hard-to-reach locations. To eliminate this problem, the untethered grippers devised by Gracias' team contain gold-plated nickel, allowing them to be steered by magnets outside the body. "With this method, we were able to remotely move the microgrippers a relatively long distance over tissue without getting stuck, he said. "Additionally, the microgrippers are triggered to close and extricate cells from tissue when exposed to certain biochemicals or biologically relevant temperatures."
The microgripper design -- six three-jointed digits extended from a central "palm" -- resembles a crab. (In fact, the joint design was inspired by that of arthropod animals.) To fabricate the microgrippers in their initial flat position with all digits fully extended, the researchers employ photolithography, the same process used to make computer chips. When the tiny devices are inserted in the body and moved magnetically, the gold-plated nickel in the palm and digits will allow doctors to see and guide the grippers with medical imaging units such as an MRI or CT.
The microgrippers' grasping ability is rooted in the chemical composition of the joints embedded in the finger-like digits. These joints contain thin layers of chromium and copper with stress characteristics that would normally cause the digits to curl themselves closed like fingers clasping a baseball. But the researchers added a polymer resin, giving the joints rigidity to keep the fingers from closing.
When the microgrippers arrive at their destination, however, the researchers raise the temperature to 40 degrees C (or 104 degrees F, equivalent to a moderate fever in humans). This heat softens the polymer in the joints, causing the fingers to flex shut. The researchers also found an alternative method: Some nontoxic biological solutions can also weaken the polymer and cause the grippers to clamp down on their target.
In their lab experiments, the Johns Hopkins researchers used a microgripper, guided by a magnet, to grab and transport a dyed bead from among a group of colorless beads in a water solution. Team members also captured dozens of live animal cells from a cell mass at the end of a capillary tube. The cells were still alive 72 hours later, indicating the capture process did not injure them. Also, the microgrippers captured samples from relatively tough bovine bladder tissue.
The experiments showed that the tetherless microgripper concept is viable and has great potential for medical applications, the researchers said. Gracias' team is now working to overcome some remaining hurdles. As currently designed, each biologically compatible gripper can close on a target only once and cannot be reactivated to reopen and release its contents. (A similar device from the Gracias team, aimed at industrial micro-assembly applications, can be directed to both capture and release its load, but this requires chemicals that are not safe for patients. This pick-and-place microgripper was described in a recent article in the Journal of the American Chemical Society.)
Gracias, who also is affiliated with the Institute for NanoBioTechnology at Johns Hopkins, hopes to collaborate with medical researchers who can help to move the microgrippers closer to use as practical biopsy and drug delivery tools in humans. In September, he received a $1.5 million New Innovators Award from the National Institutes of Health. He plans to use the five-year grant to develop an entire mobile, biochemically responsive micro- and nanoscale surgical tool kit.
The lead author of the PNAS microgripper article was Timothy G. Leong, who was a doctoral student supervised by Gracias. In addition to Leong and Gracias, the paper's co-authors, all students supervised by Gracias at Johns Hopkins, were Christina L. Randall, a doctoral student in the Department of Biomedical Engineering; Brian R. Benson, a junior undergraduate supported by a Provost's Undergraduate Research Award; Noy Bassik, who is enrolled in an M.D./Ph.D. program involving the School of Medicine and the Department of Chemical and Biomolecular Engineering; and George M. Stern, a master's degree student in chemical and biomolecular engineering.
The Johns Hopkins Technology Transfer staff has obtained a provisional United States patent covering the team's inventions and is seeking international patent protection.
Funding for the research was provided by the National Science Foundation, the National Institutes of Health, and the Dreyfus and Beckman foundations.
Photos, illustrations and videos may be seen online at jhu/news/home09/jan09/gracias.html.
Related links:
David Gracias' Lab Page: jhu/chembe/gracias/
Department of Chemical and Biomolecular Engineering: jhu/chembe/PNAS:
"Tetherless Thermo-biochemically Actuated Microgrippers: eurekalert/pio/tipsheetdoc.php/237/zpq6355.pdf
Journal of the American Chemical Society: "Pick-and-Place Using Chemically
Actuated Microgrippers": pubs.acs/doi/abs/10.1021/ja806961p
Source: Phil Sneiderman
Johns Hopkins University
суббота, 4 июня 2011 г.
Magnetic Resonance Imaging Program In Small Animal Facility Furthers Research
When powerful magnets line up the body's protons before radiofrequency waves can grab their attention away, it's called spin physics.
When signals generated by the movement are mathematically transformed into dramatic images of hearts, lungs and other organs it's called a magnetic resonance image. "Protons normally would be pointing in many different directions," says Dr. Tom Hu, director of the Small Animal Imaging Program at the Medical College of Georgia. "But if you put an object in the MRI, the magnet will line up the protons and what that does is generate the original, steady state. Then, by applying different radio frequencies, pretty much like what you do with a car antenna, you can pursue radio frequencies to perturb the system and you pretty much listen to it."
When Dr. Hu, a biochemist and biophysicist, tunes in he sees how calcium moves in and out of heart cells as the heart contracts and relaxes and how that movement doesn't work so well in heart failure, a condition resulting in oversized hearts with difficulty beating.
He's looking at whether the metallic manganese ion, which can travel in the same circles as calcium, can enhance the signal and subsequent images he gets of how calcium can't get back into cells after a heart attack. "Once it's disturbed, the cells die and the myocardium dies and you have scar formation," says Dr. Hu whose ultimate goals include better ways to diagnose and treat heart failure, an increasingly common problem in the United States where improved cardiac treatment means many people are living with their heart disease. "Not only can you look at a living organ, you can also study the molecular aspects of this like the calcium ion," says Dr. Hu who came to MCG in 2005 to start the Small Imaging Program in support of research initiatives, such as his, that have clinical promise.
The MRI that is the program's centerpiece looks like the human version except the cylinder the patient lies in is obviously much smaller. However it has a stronger magnet than typical clinical grade units primarily because the organs of interest are so much smaller, says Dr. Nathan Yanasak, magnetic resonance scientist.
Many standard MRIs are 1.5 Tesla and high-end clinical units are 3 Tesla, a measure of the density and intensity of a magnetic field. MCG's small animal MRI is 7 Tesla, not the strongest magnet available for research but one that enables good quality images of small organs which are comparable to those obtained by clinical machines. "It's pretty close to clinical grade," says Dr. Yanasak. "But since you are scanning something smaller you need a larger field of strength to get the animal images to look like a human image," he says. The smallest heart they've imaged, for example, is that of a 3-gram mouse (that's a .105-ounce mouse). "It is better resolution in the sense that you have to have better resolution to see a brain this big," Dr. Yanasak says, holding his fingers very close together.
The textbook answer for why scientists need high-tech imaging studies -- "They are noninvasive, says Dr. Hu, which obviously makes them excellent clinical tools as well. "If you have an animal disease model, for pretty much any noninvasive technique, the advantage is it reduces animal use tremendously," he says.
Like physicians do with patients, basic scientists now use technology to help monitor disease progression over time and even to see if treatments work. In his own work, for example, Dr. Hu watches development of heart failure by monitoring changes in calcium dynamic and heart structure.
Newer technology, on loan to the facility from Xenogen Corp, part of Caliber Life Sciences Corp., has enabled the lab to throw genetic expression into the mix. The optical scanning system uses luciferase, the same enzyme fireflies use to glow, to identify gene expression.
"If you combine (luciferase) with certain genes and the genes are expressed, they glow," says Dr. Hu. "For example, after a heart attack, you can look and see if certain genes are up-regulated, such as inflammatory genes. Now we take the same animal model back to the MRI machine and track how many cells have moved to the site of injury. So, we can combine the information and say, okay, potentially those cells that have been mobilized are due to the gene expression. We can try and link cause and effect so it becomes more of a valuable image," says Dr. Hu. Right now he and Dr. Yanasak are fine-tuning how to make MRI and optical scanning work optimally together and how to also quantify gene expression.
The number of MCG scientists using the facility is significant and growing, says its director. Dr. Adviye Ergul, for example, is looking at blood flow in the brain of her diabetes model and Dr. William Hill is looking at stroke event and recovery.
"We are very open to any interesting ideas that generate interesting scientific data or grant funding opportunities," says Dr. Hu. Goals include becoming an MCG core laboratory facility and adding a small animal PET scanner and ultrasound.
Source: Toni Baker
Medical College of Georgia
When signals generated by the movement are mathematically transformed into dramatic images of hearts, lungs and other organs it's called a magnetic resonance image. "Protons normally would be pointing in many different directions," says Dr. Tom Hu, director of the Small Animal Imaging Program at the Medical College of Georgia. "But if you put an object in the MRI, the magnet will line up the protons and what that does is generate the original, steady state. Then, by applying different radio frequencies, pretty much like what you do with a car antenna, you can pursue radio frequencies to perturb the system and you pretty much listen to it."
When Dr. Hu, a biochemist and biophysicist, tunes in he sees how calcium moves in and out of heart cells as the heart contracts and relaxes and how that movement doesn't work so well in heart failure, a condition resulting in oversized hearts with difficulty beating.
He's looking at whether the metallic manganese ion, which can travel in the same circles as calcium, can enhance the signal and subsequent images he gets of how calcium can't get back into cells after a heart attack. "Once it's disturbed, the cells die and the myocardium dies and you have scar formation," says Dr. Hu whose ultimate goals include better ways to diagnose and treat heart failure, an increasingly common problem in the United States where improved cardiac treatment means many people are living with their heart disease. "Not only can you look at a living organ, you can also study the molecular aspects of this like the calcium ion," says Dr. Hu who came to MCG in 2005 to start the Small Imaging Program in support of research initiatives, such as his, that have clinical promise.
The MRI that is the program's centerpiece looks like the human version except the cylinder the patient lies in is obviously much smaller. However it has a stronger magnet than typical clinical grade units primarily because the organs of interest are so much smaller, says Dr. Nathan Yanasak, magnetic resonance scientist.
Many standard MRIs are 1.5 Tesla and high-end clinical units are 3 Tesla, a measure of the density and intensity of a magnetic field. MCG's small animal MRI is 7 Tesla, not the strongest magnet available for research but one that enables good quality images of small organs which are comparable to those obtained by clinical machines. "It's pretty close to clinical grade," says Dr. Yanasak. "But since you are scanning something smaller you need a larger field of strength to get the animal images to look like a human image," he says. The smallest heart they've imaged, for example, is that of a 3-gram mouse (that's a .105-ounce mouse). "It is better resolution in the sense that you have to have better resolution to see a brain this big," Dr. Yanasak says, holding his fingers very close together.
The textbook answer for why scientists need high-tech imaging studies -- "They are noninvasive, says Dr. Hu, which obviously makes them excellent clinical tools as well. "If you have an animal disease model, for pretty much any noninvasive technique, the advantage is it reduces animal use tremendously," he says.
Like physicians do with patients, basic scientists now use technology to help monitor disease progression over time and even to see if treatments work. In his own work, for example, Dr. Hu watches development of heart failure by monitoring changes in calcium dynamic and heart structure.
Newer technology, on loan to the facility from Xenogen Corp, part of Caliber Life Sciences Corp., has enabled the lab to throw genetic expression into the mix. The optical scanning system uses luciferase, the same enzyme fireflies use to glow, to identify gene expression.
"If you combine (luciferase) with certain genes and the genes are expressed, they glow," says Dr. Hu. "For example, after a heart attack, you can look and see if certain genes are up-regulated, such as inflammatory genes. Now we take the same animal model back to the MRI machine and track how many cells have moved to the site of injury. So, we can combine the information and say, okay, potentially those cells that have been mobilized are due to the gene expression. We can try and link cause and effect so it becomes more of a valuable image," says Dr. Hu. Right now he and Dr. Yanasak are fine-tuning how to make MRI and optical scanning work optimally together and how to also quantify gene expression.
The number of MCG scientists using the facility is significant and growing, says its director. Dr. Adviye Ergul, for example, is looking at blood flow in the brain of her diabetes model and Dr. William Hill is looking at stroke event and recovery.
"We are very open to any interesting ideas that generate interesting scientific data or grant funding opportunities," says Dr. Hu. Goals include becoming an MCG core laboratory facility and adding a small animal PET scanner and ultrasound.
Source: Toni Baker
Medical College of Georgia
пятница, 3 июня 2011 г.
Breast Cancer Stem Cells Identified And Repressed In Mouse Tissue
By manipulating highly specific gene-regulating molecules called microRNAs, scientists at Cold Spring Harbor Laboratory (CSHL) report that they have succeeded in singling out and repressing stem-like cells in mouse breast tissue - cells that are widely thought to give rise to cancer.
"If certain forms of breast cancer do indeed have their origin in wayward stem cells, as we believe to be the case, then it is critical to find ways to selectively attack that tumor-initiating population," said Gregory Hannon, Ph.D., CSHL professor and Howard Hughes Medical Institute Investigator. Hannon also is head of a lab focusing on small-RNA research at CSHL and corresponding author of a paper reporting the new research, published in the latest issue of Genes and Development.
"We have shown that a microRNA called let-7, whose expression has previously been associated with tumor suppression, can be delivered to a sample of breast-tissue cells, where it can help us to distinguish stem-like tumor-initiating cells from other, more fully developed cells in the sample. Even more exciting, we found that by expressing let-7 in the sample, we were able to attack and essentially eliminate, very specifically, just that subpopulation of potentially dangerous progenitor cells."
The study was done in collaboration with Senthil Muthuswamy Ph.D., an expert in breast cancer research who heads a CSHL lab focusing on understanding the changes in the biology of breast epithelial cells during the initiation and progression of cancer. Dr. Muthuswamy emphasized that a key ingredient that made this study successful is the use of a mouse breast-derived model cell system called COMMA-1D that not only includes differentiated cells but also stem-like progenitors, in varying stages of maturity, or differentiation.
Unexpected Impact of Conventional Chemotherapy
No therapies currently exist that target stem-like tumor-initiating cells, whose existence in diverse tissues including breast, lung, brain and colon, as well as in the blood, has been demonstrated in a line of research stretching back to 2001. In that year, John E. Dick of the University of Toronto identified cancer stem cells in the blood of leukemia patients.
The cancer stem cell hypothesis is controversial, in part, because of the challenge it represents for current cancer therapy, which regards all tumor cells as potentially capable of spreading the disease, and which seeks to reduce tumor mass and destroy the maximum possible number of tumor cells. In the cancer stem cell hypothesis, reduction of tumor volume alone will not suffice if the stem cells which originally gave rise to the cancer are not specifically targeted and destroyed.
The new Cold Spring Harbor Laboratory research not only suggests one possible way of accomplishing this therapeutic goal - the Hannon lab is initiating a demonstration study in mice - but it also demonstrated that one component of a chemotherapy cocktail currently used as first-line therapy against certain kinds of breast cancer has the potential to actually enrich the subpopulation of stem-like cells that serve as cancer progenitors.
"We found that administration of cyclophosphamide in our mouse cell sample had the effect of enriching for these cells," Hannon said, "which suggests that we need to look carefully at these therapies in model systems to see if the effects we see in cell culture are mirrored in real tumors - and then, to gauge what effect that has on metastasis and relapse following therapy."
It has been known for some time that stem and progenitor cells possess unique defenses, as compared with mature, or differentiated cells, which, unlike their stem-like "mothers" do not have the capacity to renew themselves or to generate multiple cell-types. Stem cells, for instance, are thought to be able to "pump" toxins out of their cellular domain, much as do fully differentiated tumor cells that have developed resistance to chemotherapy.
"A Role for microRNAs in Maintenance of Mouse Mammary Epithelial Progenitor Cells" appears in Genes and Development on December 15, 2007. The complete citation is as follows: Ingrid Ibarra, Yaniv Erlich, Senthil K. Muthuswamy, Ravi Sachidanandam, and Gregory Hannon. Click here to access the paper online.
Cold Spring Harbor Laboratory (CSHL) is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.
For more information, visit cshl/.
Source: Jim Bono
Cold Spring Harbor Laboratory
"If certain forms of breast cancer do indeed have their origin in wayward stem cells, as we believe to be the case, then it is critical to find ways to selectively attack that tumor-initiating population," said Gregory Hannon, Ph.D., CSHL professor and Howard Hughes Medical Institute Investigator. Hannon also is head of a lab focusing on small-RNA research at CSHL and corresponding author of a paper reporting the new research, published in the latest issue of Genes and Development.
"We have shown that a microRNA called let-7, whose expression has previously been associated with tumor suppression, can be delivered to a sample of breast-tissue cells, where it can help us to distinguish stem-like tumor-initiating cells from other, more fully developed cells in the sample. Even more exciting, we found that by expressing let-7 in the sample, we were able to attack and essentially eliminate, very specifically, just that subpopulation of potentially dangerous progenitor cells."
The study was done in collaboration with Senthil Muthuswamy Ph.D., an expert in breast cancer research who heads a CSHL lab focusing on understanding the changes in the biology of breast epithelial cells during the initiation and progression of cancer. Dr. Muthuswamy emphasized that a key ingredient that made this study successful is the use of a mouse breast-derived model cell system called COMMA-1D that not only includes differentiated cells but also stem-like progenitors, in varying stages of maturity, or differentiation.
Unexpected Impact of Conventional Chemotherapy
No therapies currently exist that target stem-like tumor-initiating cells, whose existence in diverse tissues including breast, lung, brain and colon, as well as in the blood, has been demonstrated in a line of research stretching back to 2001. In that year, John E. Dick of the University of Toronto identified cancer stem cells in the blood of leukemia patients.
The cancer stem cell hypothesis is controversial, in part, because of the challenge it represents for current cancer therapy, which regards all tumor cells as potentially capable of spreading the disease, and which seeks to reduce tumor mass and destroy the maximum possible number of tumor cells. In the cancer stem cell hypothesis, reduction of tumor volume alone will not suffice if the stem cells which originally gave rise to the cancer are not specifically targeted and destroyed.
The new Cold Spring Harbor Laboratory research not only suggests one possible way of accomplishing this therapeutic goal - the Hannon lab is initiating a demonstration study in mice - but it also demonstrated that one component of a chemotherapy cocktail currently used as first-line therapy against certain kinds of breast cancer has the potential to actually enrich the subpopulation of stem-like cells that serve as cancer progenitors.
"We found that administration of cyclophosphamide in our mouse cell sample had the effect of enriching for these cells," Hannon said, "which suggests that we need to look carefully at these therapies in model systems to see if the effects we see in cell culture are mirrored in real tumors - and then, to gauge what effect that has on metastasis and relapse following therapy."
It has been known for some time that stem and progenitor cells possess unique defenses, as compared with mature, or differentiated cells, which, unlike their stem-like "mothers" do not have the capacity to renew themselves or to generate multiple cell-types. Stem cells, for instance, are thought to be able to "pump" toxins out of their cellular domain, much as do fully differentiated tumor cells that have developed resistance to chemotherapy.
"A Role for microRNAs in Maintenance of Mouse Mammary Epithelial Progenitor Cells" appears in Genes and Development on December 15, 2007. The complete citation is as follows: Ingrid Ibarra, Yaniv Erlich, Senthil K. Muthuswamy, Ravi Sachidanandam, and Gregory Hannon. Click here to access the paper online.
Cold Spring Harbor Laboratory (CSHL) is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.
For more information, visit cshl/.
Source: Jim Bono
Cold Spring Harbor Laboratory
четверг, 2 июня 2011 г.
Cell Signaling Glitch Contributes To Lupus Progression
Immune cells that would normally die in healthy people accumulate in bodies of patients who have lupus and contribute to the disease, according to new Saint Louis University research published in the Feb. 15 issue of Immunity.
The finding is important because it tells us more about how lupus develops and suggests a strategy for treating the autoimmune disease, said Harris Perlman, Ph.D., associate professor of molecular microbiology and immunology at Saint Louis University and senior author of the study.
"We want to eliminate those hyperactive immune cells that lead to continuation of the disease but maintain infection-fighting white blood cells," Perlman said. "This will restore the balance of cells in the immune system, which has become very skewed in lupus patients."
It is estimated that between 1.5 and 2 million Americans have some form of lupus, which can damage the kidneys, heart, joints, skin, lungs, blood vessels, liver and nervous system.
In those who have an autoimmune disease such as lupus, the cells in the immune system become confused. Instead of attacking only infected cells or foreign bodies, they turn ultra-vigilant and attack the body's own normal cells and tissues, causing inflammation, pain and injuries.
Perlman and his team have discovered the double whammy for lupus patients. They harbor a higher than normal number of immune cells that carry too much of the pro-survival or anti-apoptotic proteins that tells them to keep living past their prime.
Normally these cells should undergo "apoptosis," a natural process by which cells die so they don't spread infection or take away nutrients from healthy cells. The signal to die can come from inside the cell itself or from outside the cell.
Perlman and his colleagues found that the communications system that tells immune cells that it's time to die gets turned off in lupus patients and causes immune cells to accumulate in the body. This failure to delete these cells allows the disease to progress, Perlman said.
Perlman's research team took blood from 14 lupus patients and 14 healthy people. Patients with lupus produced more immune cells with too much of the proteins that prolonged cell life. The more of these immune cells patient had, the more severe was his or her disease.
The team used that knowledge to create mice that had a defect in the two known "death pathways" that signal when they're supposed to die. They showed that these mice displayed high numbers of immune cells that would normally die and that all of the mice developed very severe lupus.
"We showed it in patients and reproduced the result in mice," Perlman said. "Now we can use this mouse model to do pre-clinical trials for therapies to fight lupus."
The next step, Perlman said, is to test a therapy that blocks proteins that prevent cells from dying by mimicking the action of proteins that tell immune cells it's time to die.
"We want to deliver a treatment that will target those proteins that keep these immune cells alive. This could induce a type of remission in patients," Perlman said.
"We need to tilt the balance toward the normal cells cells that don't want to attack the body but function correctly so the patient can fight infection and have a normal life. We want to kill those cells that lead to the continuation of disease."
The research was conducted in collaboration with the University of Texas- Southwestern Medical Center, University of California-San Diego and Yale University. It was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Allergy and Infectious Diseases, both divisions of the National Institutes of Health, and the autoimmune disease fund provided by Saint Louis University.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.
Saint Louis University Medical Center
St. Louis, MO 63103
United States
medschool.slu/index.phtml
The finding is important because it tells us more about how lupus develops and suggests a strategy for treating the autoimmune disease, said Harris Perlman, Ph.D., associate professor of molecular microbiology and immunology at Saint Louis University and senior author of the study.
"We want to eliminate those hyperactive immune cells that lead to continuation of the disease but maintain infection-fighting white blood cells," Perlman said. "This will restore the balance of cells in the immune system, which has become very skewed in lupus patients."
It is estimated that between 1.5 and 2 million Americans have some form of lupus, which can damage the kidneys, heart, joints, skin, lungs, blood vessels, liver and nervous system.
In those who have an autoimmune disease such as lupus, the cells in the immune system become confused. Instead of attacking only infected cells or foreign bodies, they turn ultra-vigilant and attack the body's own normal cells and tissues, causing inflammation, pain and injuries.
Perlman and his team have discovered the double whammy for lupus patients. They harbor a higher than normal number of immune cells that carry too much of the pro-survival or anti-apoptotic proteins that tells them to keep living past their prime.
Normally these cells should undergo "apoptosis," a natural process by which cells die so they don't spread infection or take away nutrients from healthy cells. The signal to die can come from inside the cell itself or from outside the cell.
Perlman and his colleagues found that the communications system that tells immune cells that it's time to die gets turned off in lupus patients and causes immune cells to accumulate in the body. This failure to delete these cells allows the disease to progress, Perlman said.
Perlman's research team took blood from 14 lupus patients and 14 healthy people. Patients with lupus produced more immune cells with too much of the proteins that prolonged cell life. The more of these immune cells patient had, the more severe was his or her disease.
The team used that knowledge to create mice that had a defect in the two known "death pathways" that signal when they're supposed to die. They showed that these mice displayed high numbers of immune cells that would normally die and that all of the mice developed very severe lupus.
"We showed it in patients and reproduced the result in mice," Perlman said. "Now we can use this mouse model to do pre-clinical trials for therapies to fight lupus."
The next step, Perlman said, is to test a therapy that blocks proteins that prevent cells from dying by mimicking the action of proteins that tell immune cells it's time to die.
"We want to deliver a treatment that will target those proteins that keep these immune cells alive. This could induce a type of remission in patients," Perlman said.
"We need to tilt the balance toward the normal cells cells that don't want to attack the body but function correctly so the patient can fight infection and have a normal life. We want to kill those cells that lead to the continuation of disease."
The research was conducted in collaboration with the University of Texas- Southwestern Medical Center, University of California-San Diego and Yale University. It was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and National Institute of Allergy and Infectious Diseases, both divisions of the National Institutes of Health, and the autoimmune disease fund provided by Saint Louis University.
Established in 1836, Saint Louis University School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: cancer, liver disease, heart/lung disease, aging and brain disease, and infectious disease.
Saint Louis University Medical Center
St. Louis, MO 63103
United States
medschool.slu/index.phtml
среда, 1 июня 2011 г.
Impact Of Insulin Receptor Signaling Upon Synapses And Dendrites Shown For The First Time In Living Creatures
A team of neuroscientists at Cold Spring Harbor Laboratory (CSHL) has demonstrated for the first time in living animals that insulin receptors in the brain can initiate signaling that regulates both the structure and function of neural circuits.
The finding suggests a significant role for this class of receptors and perhaps for insulin, not only in brain development, but also in cognition and in pathological processes in which cognition is impaired, as in Alzheimer's disease, for example.
Insulin receptors on the surface of cells throughout the body have long been understood to play a central role in controlling metabolism through the regulation of glucose. When a molecule of insulin, a hormone, "docks" with the receptor, a complex signaling cascade is set in motion inside a cell, culminating in the cell's uptake of insulin.
The Brain Is Not "Insulin-Insensitive" After All
Although insulin receptors are observed in certain parts of the mammalian brain, most scientists, until a few years ago, had assumed the organ was "insulin-insensitive," knowing that glucose could be taken up by brain cells without the involvement of either insulin or insulin receptors.
In recent years, however, it has been shown that the brain is indeed an insulin target, and in cell-culture experiments that insulin receptor signaling in neurons can have an impact on the formation and development of neural circuits. This had never been demonstrated in living organisms until it was shown in experiments performed in the laboratory of CSHL Professor Hollis Cline, Ph.D., and reported this week in the journal Neuron.
These experiments, in Xenopus tadpoles, show that insulin receptor signaling in neurons regulates the maintenance of synapses, contributes to the processing of sensory information and is also involved in adjusting the plasticity of brain circuits in response to experience. The latter function is particularly interesting, notes Dr. Cline, since "it is required for the incorporation of neurons into brain circuits."
Blocking the Receptor
To test the idea that insulin receptor signaling regulates the formation of brain circuits during development, the Cold Spring Harbor team used two different techniques to block the function of the receptor in neurons located in the visual pathway of tadpoles. One method "knocked down" expression of the receptors genetically, while the other left them in place but prevented them from initiating signaling cascades within the cell.
"Tadpoles are wonderful creatures for such experiments," Dr. Cline explained, "in part because they have translucent bodies, which makes it easy for us to visualize and record what happens to individual neurons as we manipulate the insulin receptors on their surface."
When insulin receptor function was blocked, neurons in the visual pathway connecting the tadpole's retina to a brain region called the tectum responded very poorly to light stimuli. The tectum is the area in which brain cells process incoming visual signals. "We showed that the insulin receptor is critical for the proper operation of this circuit, and also that defects in receptor signaling cause a reduction in the animal's visual responses," Dr. Cline said.
Time-Lapse Images of Dendritic Branching
The team went on to perform other experiments that demonstrated two remarkable facts. One is that insulin receptor signaling correlates with the density of the synapses, or neuron-to-neuron connections, in brain circuits. In more technical terms, they found that insulin receptors maintain synaptic density and that synapse density decreases when insulin receptors are removed or dysfunctional.
The team also secured time-lapse images of dendritic formations, the ethereal, branch-like structures that receive chemical signals sent from one neuron to the next. Again, they found that when insulin receptors are engaged and sending signals inside the neuron, dendritic growth is enhanced, specifically in response to visual stimulation.
In this, as in the findings about synaptic density, the team found that insulin receptor signaling regulates the form and function of brain circuits in response to incoming visual information. Another way to put this is that the receptor regulates brain circuits in response to "experience."
Possible Links to Disease
This suggests that insulin receptors in the brain may play a key role not only in the brain's development early in life, but also in disease processes that usually occur late in life. People with advanced diabetes suffer memory loss and cognitive deficits, possibly because insulin receptor signaling in the brain is disrupted, synaptic connections are lost and brain circuits don't work optimally.
In addition, other researchers have found a correlation between diminished insulin receptor signaling and Alzheimer's disease. Results of the Cold Spring Harbor team's research raise the question of whether deficits in learning and memory associated with Alzheimer's might be linked causally to decreased synaptic density as a consequence of lowered insulin receptor signaling. "We are a long way from knowing this for sure, but it's the direction in which our work now takes us," Dr. Cline said.
"Insulin Receptor Signaling Regulates Synapse Number, Dendritic Plasticity, and Circuit Function In Vivo" appeared in Neuron on June 11, 2008. The complete citation is as follows: Shu-Ling Chiu, Chih-Ming Chen and Hollis T. Cline. Click here to access the paper online.
Cold Spring Harbor Laboratory (CSHL) is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering.
For more information, visit cshl/.
Source: Jim Bono
Cold Spring Harbor Laboratory
The finding suggests a significant role for this class of receptors and perhaps for insulin, not only in brain development, but also in cognition and in pathological processes in which cognition is impaired, as in Alzheimer's disease, for example.
Insulin receptors on the surface of cells throughout the body have long been understood to play a central role in controlling metabolism through the regulation of glucose. When a molecule of insulin, a hormone, "docks" with the receptor, a complex signaling cascade is set in motion inside a cell, culminating in the cell's uptake of insulin.
The Brain Is Not "Insulin-Insensitive" After All
Although insulin receptors are observed in certain parts of the mammalian brain, most scientists, until a few years ago, had assumed the organ was "insulin-insensitive," knowing that glucose could be taken up by brain cells without the involvement of either insulin or insulin receptors.
In recent years, however, it has been shown that the brain is indeed an insulin target, and in cell-culture experiments that insulin receptor signaling in neurons can have an impact on the formation and development of neural circuits. This had never been demonstrated in living organisms until it was shown in experiments performed in the laboratory of CSHL Professor Hollis Cline, Ph.D., and reported this week in the journal Neuron.
These experiments, in Xenopus tadpoles, show that insulin receptor signaling in neurons regulates the maintenance of synapses, contributes to the processing of sensory information and is also involved in adjusting the plasticity of brain circuits in response to experience. The latter function is particularly interesting, notes Dr. Cline, since "it is required for the incorporation of neurons into brain circuits."
Blocking the Receptor
To test the idea that insulin receptor signaling regulates the formation of brain circuits during development, the Cold Spring Harbor team used two different techniques to block the function of the receptor in neurons located in the visual pathway of tadpoles. One method "knocked down" expression of the receptors genetically, while the other left them in place but prevented them from initiating signaling cascades within the cell.
"Tadpoles are wonderful creatures for such experiments," Dr. Cline explained, "in part because they have translucent bodies, which makes it easy for us to visualize and record what happens to individual neurons as we manipulate the insulin receptors on their surface."
When insulin receptor function was blocked, neurons in the visual pathway connecting the tadpole's retina to a brain region called the tectum responded very poorly to light stimuli. The tectum is the area in which brain cells process incoming visual signals. "We showed that the insulin receptor is critical for the proper operation of this circuit, and also that defects in receptor signaling cause a reduction in the animal's visual responses," Dr. Cline said.
Time-Lapse Images of Dendritic Branching
The team went on to perform other experiments that demonstrated two remarkable facts. One is that insulin receptor signaling correlates with the density of the synapses, or neuron-to-neuron connections, in brain circuits. In more technical terms, they found that insulin receptors maintain synaptic density and that synapse density decreases when insulin receptors are removed or dysfunctional.
The team also secured time-lapse images of dendritic formations, the ethereal, branch-like structures that receive chemical signals sent from one neuron to the next. Again, they found that when insulin receptors are engaged and sending signals inside the neuron, dendritic growth is enhanced, specifically in response to visual stimulation.
In this, as in the findings about synaptic density, the team found that insulin receptor signaling regulates the form and function of brain circuits in response to incoming visual information. Another way to put this is that the receptor regulates brain circuits in response to "experience."
Possible Links to Disease
This suggests that insulin receptors in the brain may play a key role not only in the brain's development early in life, but also in disease processes that usually occur late in life. People with advanced diabetes suffer memory loss and cognitive deficits, possibly because insulin receptor signaling in the brain is disrupted, synaptic connections are lost and brain circuits don't work optimally.
In addition, other researchers have found a correlation between diminished insulin receptor signaling and Alzheimer's disease. Results of the Cold Spring Harbor team's research raise the question of whether deficits in learning and memory associated with Alzheimer's might be linked causally to decreased synaptic density as a consequence of lowered insulin receptor signaling. "We are a long way from knowing this for sure, but it's the direction in which our work now takes us," Dr. Cline said.
"Insulin Receptor Signaling Regulates Synapse Number, Dendritic Plasticity, and Circuit Function In Vivo" appeared in Neuron on June 11, 2008. The complete citation is as follows: Shu-Ling Chiu, Chih-Ming Chen and Hollis T. Cline. Click here to access the paper online.
Cold Spring Harbor Laboratory (CSHL) is a private, nonprofit research and education institution dedicated to exploring molecular biology and genetics to advance the understanding and ability to diagnose and treat cancers, neurological diseases and other causes of human suffering.
For more information, visit cshl/.
Source: Jim Bono
Cold Spring Harbor Laboratory
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