On its opening day, the London Millennium Bridge experienced unexpected large oscillations due to crowd loading. It has generally been thought this was due to pedestrians synchronising their footsteps with the bridge motion. However, this is not supported by more recent measurements on other bridges. In contrast with previous research, this study considers the basic way humans maintain balance. This gives the surprising result that pedestrians walking randomly, keeping balance as normal, can cause large bridge oscillations. This finally seems to explain the initiation of the Millennium Bridge 'wobble' and gives new insight for designing bridges to avoid vibration problems.
Proceedings of the Royal Society A: Physical Sciences
Proceedings A has an illustrious history of publishing pioneering and influential research articles across the entire range of the physical and mathematical sciences. These have included Maxwell's electromagnetic theory, the Braggs' first account of X-ray crystallography, Dirac's relativistic theory of the electron, and Watson and Crick's detailed description of the structure of DNA.
Proceedings of the Royal Society A: Physical Sciences
воскресенье, 31 июля 2011 г.
четверг, 28 июля 2011 г.
In Fat-Free Mice Liver Fat Reduced By Fat-Free Diet, Researchers Report
Researchers at UT Southwestern Medical Center have uncovered crucial clues about a paradoxical disease in which patients with no body fat develop many of the health complications usually found in obese people.
The findings in mice, appearing online today in Cell Metabolism, have led to the initiation of a National Institutes of Health-funded clinical trial to determine whether eating an extremely low-fat diet could prevent many of the metabolic complications brought on by lipodystrophy.
Lipodystrophies are metabolic disorders characterized by the selective loss of fat tissues and complications of insulin resistance. Scientists speculate that the condition could be caused by the failure of stem cells to become fat cells.
"These patients don't have fatty tissue, even inside their abdomen," said Dr. Abhimanyu Garg, professor of internal medicine at UT Southwestern and senior author of the study. "They basically lack all the fat we see in a typical person, but their livers are loaded with fat. That's a big problem because too much fat in the liver leads to liver damage.
"We cannot do anything to reverse fat loss, but our findings might lead to the development of new therapies for the metabolic complications of lipodystrophy, such as diabetes, fatty liver and high triglycerides," said Dr. Garg, an investigator in the Center for Human Nutrition.
Dr. Garg has been studying patients with lipodystrophies for more than 20 years. He and colleagues at UT Southwestern have led the way in identifying gene mutations responsible for several forms of lipodystrophy and in identifying novel therapeutic approaches for these patients.
In this study, researchers genetically engineered mice to lack a specific enzyme called AGPAT2, which is also lacking in humans with generalized lipodystrophy. Under normal conditions, AGPAT2 is involved in the production of fat in body fat cells. In 2002 Dr. Garg's lab found that the AGPAT2 gene is mutated in patients with congenital generalized lipodystrophy.
"We generated this mouse model to learn why humans with this type of lipodystrophy develop metabolic complications," Dr. Garg said.
The researchers found that mice without the AGPAT2 enzyme used a novel, previously uncharacterized pathway to synthesize fat in their liver. Dietary fat also contributed to fat accumulation in the liver. Typically, particles called chylomicrons carry dietary fat throughout the body and release it in peripheral tissues so that it can either be stored in adipose tissue for later use or immediately burned as energy by muscles. Normally, adipose tissue provides fatty acids for fat synthesis in the liver. In these lipodystrophic mice, however, the adipose tissue did not release the excess fatty acids and the dietary fat accumulated in the liver.
What is surprising about this, Dr. Garg said, is that the amount of fat stored in the liver dropped substantially when researchers put the lipodystrophic mice on a fat-free diet. "Just eliminating the dietary fat reduced liver triglycerides by approximately 50 percent," he said.
In addition to establishing a clinical trial, Dr. Garg said the next step is to study the stem cells from the mice with lipodystrophy in order to determine why their stem cells become bone and muscle but not fat.
Other UT Southwestern researchers involved in the research were Dr. Victor CortГ©s, lead author of the study and postdoctoral researcher in molecular genetics; Dr. David Curtis, surgery resident; Dr. Xinli Shao, research scientist in immunology; Dr. Vinay Parameswara, instructor of internal medicine; Dr. Jimin Ren, instructor in radiology at the Advanced Imaging Research Center; Dr. Victoria Esser, associate professor of internal medicine; Dr. Robert Hammer, professor of biochemistry; Dr. Anil Agarwal, associate professor of internal medicine; and Dr. Jay Horton, professor of internal medicine.
The research was funded by the NIH, Southwestern Medical Foundation and the Perot Foundation. Dr. CortГ©s is supported by a postdoctoral fellowship from Pontificia Universidad CatГіlica de Chile and a presidential fellowship from the Chilean government.
Source: Kristen Holland Shear
UT Southwestern Medical Center
The findings in mice, appearing online today in Cell Metabolism, have led to the initiation of a National Institutes of Health-funded clinical trial to determine whether eating an extremely low-fat diet could prevent many of the metabolic complications brought on by lipodystrophy.
Lipodystrophies are metabolic disorders characterized by the selective loss of fat tissues and complications of insulin resistance. Scientists speculate that the condition could be caused by the failure of stem cells to become fat cells.
"These patients don't have fatty tissue, even inside their abdomen," said Dr. Abhimanyu Garg, professor of internal medicine at UT Southwestern and senior author of the study. "They basically lack all the fat we see in a typical person, but their livers are loaded with fat. That's a big problem because too much fat in the liver leads to liver damage.
"We cannot do anything to reverse fat loss, but our findings might lead to the development of new therapies for the metabolic complications of lipodystrophy, such as diabetes, fatty liver and high triglycerides," said Dr. Garg, an investigator in the Center for Human Nutrition.
Dr. Garg has been studying patients with lipodystrophies for more than 20 years. He and colleagues at UT Southwestern have led the way in identifying gene mutations responsible for several forms of lipodystrophy and in identifying novel therapeutic approaches for these patients.
In this study, researchers genetically engineered mice to lack a specific enzyme called AGPAT2, which is also lacking in humans with generalized lipodystrophy. Under normal conditions, AGPAT2 is involved in the production of fat in body fat cells. In 2002 Dr. Garg's lab found that the AGPAT2 gene is mutated in patients with congenital generalized lipodystrophy.
"We generated this mouse model to learn why humans with this type of lipodystrophy develop metabolic complications," Dr. Garg said.
The researchers found that mice without the AGPAT2 enzyme used a novel, previously uncharacterized pathway to synthesize fat in their liver. Dietary fat also contributed to fat accumulation in the liver. Typically, particles called chylomicrons carry dietary fat throughout the body and release it in peripheral tissues so that it can either be stored in adipose tissue for later use or immediately burned as energy by muscles. Normally, adipose tissue provides fatty acids for fat synthesis in the liver. In these lipodystrophic mice, however, the adipose tissue did not release the excess fatty acids and the dietary fat accumulated in the liver.
What is surprising about this, Dr. Garg said, is that the amount of fat stored in the liver dropped substantially when researchers put the lipodystrophic mice on a fat-free diet. "Just eliminating the dietary fat reduced liver triglycerides by approximately 50 percent," he said.
In addition to establishing a clinical trial, Dr. Garg said the next step is to study the stem cells from the mice with lipodystrophy in order to determine why their stem cells become bone and muscle but not fat.
Other UT Southwestern researchers involved in the research were Dr. Victor CortГ©s, lead author of the study and postdoctoral researcher in molecular genetics; Dr. David Curtis, surgery resident; Dr. Xinli Shao, research scientist in immunology; Dr. Vinay Parameswara, instructor of internal medicine; Dr. Jimin Ren, instructor in radiology at the Advanced Imaging Research Center; Dr. Victoria Esser, associate professor of internal medicine; Dr. Robert Hammer, professor of biochemistry; Dr. Anil Agarwal, associate professor of internal medicine; and Dr. Jay Horton, professor of internal medicine.
The research was funded by the NIH, Southwestern Medical Foundation and the Perot Foundation. Dr. CortГ©s is supported by a postdoctoral fellowship from Pontificia Universidad CatГіlica de Chile and a presidential fellowship from the Chilean government.
Source: Kristen Holland Shear
UT Southwestern Medical Center
понедельник, 25 июля 2011 г.
Gene Therapy For Brain Cancer Could Be Improved By Deathstalker Scorpion Venom
An ingredient in the venom of the "deathstalker" scorpion could help gene therapy become an effective treatment for brain cancer, scientists are reporting. The substance allows therapeutic genes - genes that treat disease - to reach more brain cancer cells than current approaches, according to the study in ACS Nano, a monthly journal.
Miqin Zhang and colleagues note that gene therapy - the delivery of therapeutic genes into diseased cells - shows promise for fighting glioma, the most common and most serious form of brain cancer. But difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients.
The scientists describe a new approach that could solve these problems. Key ingredients of their gene-delivery system are chlorotoxin, the substance in deathstalker scorpion venom that can slow the spread of brain cancer, and nanoparticles of iron oxide. Each nanoparticle is about 1/50,000th the width of a human hair. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient. "These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers," the article notes.
Article:
"Chlorotoxin Labeled Magnetic Nanovectors for Targeted Gene Delivery to Glioma"
Source:
Michael Bernstein
American Chemical Society
Miqin Zhang and colleagues note that gene therapy - the delivery of therapeutic genes into diseased cells - shows promise for fighting glioma, the most common and most serious form of brain cancer. But difficulties in getting genes to enter cancer cells and concerns over the safety and potential side effects of substances used to transport these genes have kept the approach from helping patients.
The scientists describe a new approach that could solve these problems. Key ingredients of their gene-delivery system are chlorotoxin, the substance in deathstalker scorpion venom that can slow the spread of brain cancer, and nanoparticles of iron oxide. Each nanoparticle is about 1/50,000th the width of a human hair. In tests on lab mice, the scientists demonstrated that their venom-based nanoparticles can induce nearly twice the amount of gene expression in brain cancer cells as nanoparticles that do not contain the venom ingredient. "These results indicate that this targeted gene delivery system may potentially improve treatment outcome of gene therapy for glioma and other deadly cancers," the article notes.
Article:
"Chlorotoxin Labeled Magnetic Nanovectors for Targeted Gene Delivery to Glioma"
Source:
Michael Bernstein
American Chemical Society
пятница, 22 июля 2011 г.
Slow-frozen People? Latest Research Supports Possibility Of Cyropreservation
The latest research on water - still one of the least understood of all liquids despite a century of intensive study - seems to support the possibility that cells, tissues and even the entire human body could be cyropreserved without formation of damaging ice crystals, according to University of Helsinki researcher Anatoli Bogdan, Ph.D.
He conducted the study, scheduled for the July 6 issue of the ACS Journal of Physical Chemistry B, one of 34 peer-review journals published by the American Chemical Society, the world's largest scientific society.
In medicine, cryopreservation involves preserving organs and tissues for transplantation or other uses. Only certain kinds of cells and tissues, including sperm and embryos, currently can be frozen and successfully rewarmed. A major problem hindering wider use of cyropreservation is formation of ice crystals, which damage cell structures.
Cyropreservation may be most familiar, however, as the controversial idea that humans, stricken with incurable diseases, might be frozen and then revived years or decades later when cures are available.
Bogdan's experiments involved a form of water termed "glassy water," or low-density amorphous ice (LDA), which is produced by slowly supercooling diluted aqueous droplets. LDA melts into highly viscous water (HVW). Bogdan reports that HVW is not a new form of water, as some scientists believed.
"That HVW is not a new form of water (i.e., normal and glassy water are thermodynamically connected) may have some interesting practical implications in cryobiology, medicine, and cryonics." Bogdan said.
"It may seem fantastic, but the fact that in aqueous solution, the water component can be slowly supercooled to the glassy state and warmed back without the crystallization implies that, in principle, if the suitable cyroprotectant is created, cells in plants and living matter could withstand a large supercooling and survive," Bogdan explained. In present cyropreservation, the cells being preserved are often damaged due to freezing of water either on cooling or subsequent warming to room temperature.
"Damage of the cells occurs due to the extra-cellular and intra-cellular ice formation which leads to dehydration and separation into the ice and concentrated unfrozen solution. If we could, by slow cooling/warming, supercool and then warm the cells without the crystallization of water then the cells would be undamaged."
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.
-- Michael Woods
The online version of the research paper cited above was initially published June 20 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroomacs or calling the contact person for this release.
Contact: Michael Bernstein
American Chemical Society
He conducted the study, scheduled for the July 6 issue of the ACS Journal of Physical Chemistry B, one of 34 peer-review journals published by the American Chemical Society, the world's largest scientific society.
In medicine, cryopreservation involves preserving organs and tissues for transplantation or other uses. Only certain kinds of cells and tissues, including sperm and embryos, currently can be frozen and successfully rewarmed. A major problem hindering wider use of cyropreservation is formation of ice crystals, which damage cell structures.
Cyropreservation may be most familiar, however, as the controversial idea that humans, stricken with incurable diseases, might be frozen and then revived years or decades later when cures are available.
Bogdan's experiments involved a form of water termed "glassy water," or low-density amorphous ice (LDA), which is produced by slowly supercooling diluted aqueous droplets. LDA melts into highly viscous water (HVW). Bogdan reports that HVW is not a new form of water, as some scientists believed.
"That HVW is not a new form of water (i.e., normal and glassy water are thermodynamically connected) may have some interesting practical implications in cryobiology, medicine, and cryonics." Bogdan said.
"It may seem fantastic, but the fact that in aqueous solution, the water component can be slowly supercooled to the glassy state and warmed back without the crystallization implies that, in principle, if the suitable cyroprotectant is created, cells in plants and living matter could withstand a large supercooling and survive," Bogdan explained. In present cyropreservation, the cells being preserved are often damaged due to freezing of water either on cooling or subsequent warming to room temperature.
"Damage of the cells occurs due to the extra-cellular and intra-cellular ice formation which leads to dehydration and separation into the ice and concentrated unfrozen solution. If we could, by slow cooling/warming, supercool and then warm the cells without the crystallization of water then the cells would be undamaged."
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.
-- Michael Woods
The online version of the research paper cited above was initially published June 20 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroomacs or calling the contact person for this release.
Contact: Michael Bernstein
American Chemical Society
вторник, 19 июля 2011 г.
Stem cells turn into beating heart cells
Scientists have found a way to turn mouse embryonic stem cells into beating heart muscle cells - a result that could lead to the use of embryonic stem cells in cardiac therapy, and possibly even drugs that can prompt the body to regenerate heart cells on its own.
The research, which appears in the Feb. 18 print edition of the Journal of the American Chemical Society, a peer-reviewed journal of the world's largest scientific society, tackles a number of the obstacles thwarting practical applications of embryonic stem cells, while also pointing to a viable path around the ethical and political concerns encompassing the debate.
Because embryonic stem cells can turn into any type of cell in the body, many scientists believe they hold incredible promise for treating a variety of degenerative diseases.
Quite a few scientific hurdles, however, stand in the way of tangible therapies for such maladies as diabetes, Alzheimer's, Parkinson's and heart disease.
'We have discovered a synthetic chemical, named cardiogenol, which can selectively differentiate embryonic stem cells into beating cardiac muscle cells,' says Xu Wu, a graduate student in the lab of Peter G. Schultz, Ph.D, professor of chemistry at The Scripps Research Institute in La Jolla, Calif.
Embryonic stem cells represent a potentially unlimited source of cardiomyocytes - cells that can repair damaged heart tissue in the body - but until now scientists have been unable to control the direction of embryonic stem cells to use them in the treatment of heart disease.
Schultz and his coworkers at Scripps, including Wu and assistant professor Sheng Ding, Ph.D., screened a vast library of compounds in search of molecules with the potential to cause stem cells to grow into heart muscle cells. They found four such molecules, which they named cardiogenol A-D.
They tested the cardiogenol compounds by using embryonic stem cells from mice. After seven days growing in a tissue culture dish, the majority of the stem cells were converted into beating cardiac muscle cells.
While the tests were done only with mouse cells, the fundamental biology should transfer well to higher organisms. 'By using these molecules to understand the underlying biology, it should be possible to extend this discovery to humans,' Wu says.
In a different paper published recently in the Journal of the American Chemical Society, Ding and his colleagues reported the discovery of another small molecule - called reversine - that appears to convert adult cells normally programmed to create skeletal muscles back into precursor cells with similar properties as stem cells.
'This type of research may ultimately facilitate development of drugs that can stimulate tissues to regenerate themselves, without any need to harvest external stem cells,' Ding says. 'We think this represents an exciting medical opportunity.'
Much more work is required to understand the biological properties and mechanisms of reversine, but these preliminary results raise the tantalizing possibility that it may be possible to synthesize a compound that creates viable stem cells from adult tissue, Ding says.
Such cells would not be rejected by the immune system, since they come directly from the patient who needs them.
A molecule like reversine could be combined with a cardiogenol-type molecule to produce a drug that kindles regeneration of heart tissue. 'Almost every tissue has its own reserve of stem cells, so ultimately we hope we don't have to isolate those cells from the body,' Ding says.
'We can stimulate tissue to regenerate by just stimulating cells within the body.'
This type of regeneration already occurs in a number of natural processes. In lower organisms, for example, urodele amphibians can regenerate lost limbs and tails. 'In humans and other mammals, the liver can regenerate naturally,' Ding says. 'And young children can even regenerate fingertips.'
All of these processes are directed by molecular signaling. 'If people can develop small molecule therapeutics to precisely mimic and control those signals for correcting defects or repairing damaged tissues, you could eventually buy those in a pharmacy as a prescription drug,' Ding says.
Not only would this alleviate some of the ethical concerns surrounding stem cells, but also a less-frequently discussed downside to stem cell treatments: their invasiveness. Small-molecule therapies involving regenerative medicine are probably years away from clinical use.
At present, Schultz, Wu and other coworkers are focusing on understanding cardiogenol's mechanism of action, and designing future experiments to test these molecules in disease models.
The online version of the research paper cited above was initially published Jan. 22 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroomacs or calling the contact person for this release.
Contact: Michael Bernstein
m_bernsteinacs
202-872-6042
American Chemical Society
The research, which appears in the Feb. 18 print edition of the Journal of the American Chemical Society, a peer-reviewed journal of the world's largest scientific society, tackles a number of the obstacles thwarting practical applications of embryonic stem cells, while also pointing to a viable path around the ethical and political concerns encompassing the debate.
Because embryonic stem cells can turn into any type of cell in the body, many scientists believe they hold incredible promise for treating a variety of degenerative diseases.
Quite a few scientific hurdles, however, stand in the way of tangible therapies for such maladies as diabetes, Alzheimer's, Parkinson's and heart disease.
'We have discovered a synthetic chemical, named cardiogenol, which can selectively differentiate embryonic stem cells into beating cardiac muscle cells,' says Xu Wu, a graduate student in the lab of Peter G. Schultz, Ph.D, professor of chemistry at The Scripps Research Institute in La Jolla, Calif.
Embryonic stem cells represent a potentially unlimited source of cardiomyocytes - cells that can repair damaged heart tissue in the body - but until now scientists have been unable to control the direction of embryonic stem cells to use them in the treatment of heart disease.
Schultz and his coworkers at Scripps, including Wu and assistant professor Sheng Ding, Ph.D., screened a vast library of compounds in search of molecules with the potential to cause stem cells to grow into heart muscle cells. They found four such molecules, which they named cardiogenol A-D.
They tested the cardiogenol compounds by using embryonic stem cells from mice. After seven days growing in a tissue culture dish, the majority of the stem cells were converted into beating cardiac muscle cells.
While the tests were done only with mouse cells, the fundamental biology should transfer well to higher organisms. 'By using these molecules to understand the underlying biology, it should be possible to extend this discovery to humans,' Wu says.
In a different paper published recently in the Journal of the American Chemical Society, Ding and his colleagues reported the discovery of another small molecule - called reversine - that appears to convert adult cells normally programmed to create skeletal muscles back into precursor cells with similar properties as stem cells.
'This type of research may ultimately facilitate development of drugs that can stimulate tissues to regenerate themselves, without any need to harvest external stem cells,' Ding says. 'We think this represents an exciting medical opportunity.'
Much more work is required to understand the biological properties and mechanisms of reversine, but these preliminary results raise the tantalizing possibility that it may be possible to synthesize a compound that creates viable stem cells from adult tissue, Ding says.
Such cells would not be rejected by the immune system, since they come directly from the patient who needs them.
A molecule like reversine could be combined with a cardiogenol-type molecule to produce a drug that kindles regeneration of heart tissue. 'Almost every tissue has its own reserve of stem cells, so ultimately we hope we don't have to isolate those cells from the body,' Ding says.
'We can stimulate tissue to regenerate by just stimulating cells within the body.'
This type of regeneration already occurs in a number of natural processes. In lower organisms, for example, urodele amphibians can regenerate lost limbs and tails. 'In humans and other mammals, the liver can regenerate naturally,' Ding says. 'And young children can even regenerate fingertips.'
All of these processes are directed by molecular signaling. 'If people can develop small molecule therapeutics to precisely mimic and control those signals for correcting defects or repairing damaged tissues, you could eventually buy those in a pharmacy as a prescription drug,' Ding says.
Not only would this alleviate some of the ethical concerns surrounding stem cells, but also a less-frequently discussed downside to stem cell treatments: their invasiveness. Small-molecule therapies involving regenerative medicine are probably years away from clinical use.
At present, Schultz, Wu and other coworkers are focusing on understanding cardiogenol's mechanism of action, and designing future experiments to test these molecules in disease models.
The online version of the research paper cited above was initially published Jan. 22 on the journal's Web site. Journalists can arrange access to this site by sending an e-mail to newsroomacs or calling the contact person for this release.
Contact: Michael Bernstein
m_bernsteinacs
202-872-6042
American Chemical Society
суббота, 16 июля 2011 г.
Shedding Light On The Evolution Of The Human Diet
Diet - and how it has shaped our genome - occupies much of an evolutionary scientist's time. Anne Stone, associate professor of anthropology in Arizona State University's School of Human Evolution and Social Change, will discuss how diet holds keys to understanding who we are, how we live and form societies, and how we evolved from hunter-gatherers to agriculturists, all the way to modern urban dwellers, at the American Association for the Advancement of Science annual meeting. Her seminar - "Genetic Perspectives on the Evolution of Human Diets" - will be presented at 8:30 a.m. Feb. 13.
Researchers like Stone look to our closest relatives - the chimpanzee and other primates - for comparisons to humans in order to understand the unique development of the human body and how it is impacted by diseases and the environment.
"One area we look at is starch consumption, something prominent in both agriculturalists and hunter-gatherers," says Stone. A study she and graduate student George "P.J." Perry led on the amalyse gene (AMY1) copy number variation - the gene responsible for starch hydrolysis - produced one of the first examples of positive selection on a copy number variable gene in the human genome. The results show how different levels of AMY1 copy number differentiation is unusual in a population, and that individuals with high starch diets have more copies than those with traditionally low starch diets. Digestion of starches is critically important for energy absorption - especially during episodes of diarrhea. This research gives insight into why certain populations may weather diarrheal diseases better than others.
"To gain an even better understanding of this process in humans, we analyzed patterns of AMY1 copy number variation in chimpanzees and bonobos. We discovered that the average human has about three times more AMY1 copies than chimpanzees, which eat mostly fruit and far less starch than humans. And bonobos may not have any," says Stone. "This human-specific increase may have occurred with a dietary shift early in hominin evolutionary history. We know that starch-rich root plants were a critical food for early hominins, and may even have facilitated the initial spread of Homo erectus out of Africa."
Other genetic research on copy number variants in humans and primates includes examining the TAS2R gene family, the gene responsible for taste sensitivity to the bitter compound phynylthiocarbamide (PTC). "Sensitivity to bitter taste is an important means for animals to interact with their environment. These variants may be very significant from an evolutionary perspective, and they're important to study and understand," says Perry. "We talk about genetic diseases and cures, but first you have to find out what genetic differences are there so you can study what they're involved with and what they mean from a morphological variation and disease standpoint."
Identifying unusual patterns between species, such as copy number differences between humans and chimpanzees, can lead to identifying those that were involved in producing the evolution of human-specific traits. "This research not only illustrates the importance of studying genetic variation in other primates to understand our own genome better, but also sheds light on the diversity and adaptations of our nearest relatives," adds Stone.
Stone is one of the senior researchers, along with Charles Lee of Harvard Medical School's Brigham and Women's Hospital, on studies funded through the National Institute of Health and the National Science Foundation. She received her doctorate in anthropology from Pennsylvania State where she wrote her dissertation on the genetic and mortuary analyses of a prehistoric Native American community. Her undergraduate work in archaeology and biology was at the University of Virginia. Stone's interdisciplinary work in Arizona State University's College of Liberal Arts and Sciences primarily focuses on anthropological genetics - applying genetics to questions concerning the origins, population history and evolution of humans and the great apes. Her research has been featured on the covers of Nature (April 13, 2006) and Genome Research (Nov. 2, 2008), and in the Proceedings of the National Academy of Sciences (PNAS, May 23, 2006).
Source:Jodi Guyot
Arizona State University
Researchers like Stone look to our closest relatives - the chimpanzee and other primates - for comparisons to humans in order to understand the unique development of the human body and how it is impacted by diseases and the environment.
"One area we look at is starch consumption, something prominent in both agriculturalists and hunter-gatherers," says Stone. A study she and graduate student George "P.J." Perry led on the amalyse gene (AMY1) copy number variation - the gene responsible for starch hydrolysis - produced one of the first examples of positive selection on a copy number variable gene in the human genome. The results show how different levels of AMY1 copy number differentiation is unusual in a population, and that individuals with high starch diets have more copies than those with traditionally low starch diets. Digestion of starches is critically important for energy absorption - especially during episodes of diarrhea. This research gives insight into why certain populations may weather diarrheal diseases better than others.
"To gain an even better understanding of this process in humans, we analyzed patterns of AMY1 copy number variation in chimpanzees and bonobos. We discovered that the average human has about three times more AMY1 copies than chimpanzees, which eat mostly fruit and far less starch than humans. And bonobos may not have any," says Stone. "This human-specific increase may have occurred with a dietary shift early in hominin evolutionary history. We know that starch-rich root plants were a critical food for early hominins, and may even have facilitated the initial spread of Homo erectus out of Africa."
Other genetic research on copy number variants in humans and primates includes examining the TAS2R gene family, the gene responsible for taste sensitivity to the bitter compound phynylthiocarbamide (PTC). "Sensitivity to bitter taste is an important means for animals to interact with their environment. These variants may be very significant from an evolutionary perspective, and they're important to study and understand," says Perry. "We talk about genetic diseases and cures, but first you have to find out what genetic differences are there so you can study what they're involved with and what they mean from a morphological variation and disease standpoint."
Identifying unusual patterns between species, such as copy number differences between humans and chimpanzees, can lead to identifying those that were involved in producing the evolution of human-specific traits. "This research not only illustrates the importance of studying genetic variation in other primates to understand our own genome better, but also sheds light on the diversity and adaptations of our nearest relatives," adds Stone.
Stone is one of the senior researchers, along with Charles Lee of Harvard Medical School's Brigham and Women's Hospital, on studies funded through the National Institute of Health and the National Science Foundation. She received her doctorate in anthropology from Pennsylvania State where she wrote her dissertation on the genetic and mortuary analyses of a prehistoric Native American community. Her undergraduate work in archaeology and biology was at the University of Virginia. Stone's interdisciplinary work in Arizona State University's College of Liberal Arts and Sciences primarily focuses on anthropological genetics - applying genetics to questions concerning the origins, population history and evolution of humans and the great apes. Her research has been featured on the covers of Nature (April 13, 2006) and Genome Research (Nov. 2, 2008), and in the Proceedings of the National Academy of Sciences (PNAS, May 23, 2006).
Source:Jodi Guyot
Arizona State University
среда, 13 июля 2011 г.
Progression Of Parkinson's Disease May Be Prevented By Widely Used Cholesterol-Lowering Drug
Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease.
"Statins are one of the most widely used cholesterol-lowering drugs throughout the world," said study author Kalipada Pahan, PhD, professor of neurological sciences at Rush University Medical Center. "This may be a safer approach to halt the disease progression in Parkinson's patients."
Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center in Omaha published these findings in the October 28 issue of the Journal of Neurosciences.
The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.
"Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson's," said Pahan. "If we are able to replicate these results in Parkinson's patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease."
The study was supported by grants from National Institutes of Health and Michael J. Fox Foundation for Parkinson's Research.
Parkinson's is a slowly progressive disease that affects a small area of cells within the mid-brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in dopamine, which is a vital chemical neurotransmitter. The decrease in dopamine results in one or more of the classic signs of Parkinson's disease that includes, resting tremor on one side of the body, generalized slowness of movement, stiffness of limbs, and gait or balance problems. The cause of Parkinson's disease is unknown. Both environmental and genetic causes of the disease have been postulated.
Parkinson's disease affects about 1.2 million patients in the United States and Canada. Although 15 percent of patients are diagnosed before age 50, it is generally considered a disease that targets older adults, affecting one of every 100 persons over the age of 60. This disease appears to be slightly more common in men than women.
Source: Deborah Song
Rush University Medical Center
"Statins are one of the most widely used cholesterol-lowering drugs throughout the world," said study author Kalipada Pahan, PhD, professor of neurological sciences at Rush University Medical Center. "This may be a safer approach to halt the disease progression in Parkinson's patients."
Pahan and colleagues from Rush, along with researchers at the University of Nebraska Medical Center in Omaha published these findings in the October 28 issue of the Journal of Neurosciences.
The authors have shown that the activity of one protein called p21Ras is increased very early in the midbrain of mice with Parkinson's pathology. Simvastatin enters into the brain and blocks the activity of the p21Ras protein and other associated toxic molecules, and goes on to protect the neurons, normalize neurotransmitter levels, and improves the motor functions in the mice with Parkinson's.
"Understanding how the disease works is important to developing effective drugs that protect the brain and stop the progression of Parkinson's," said Pahan. "If we are able to replicate these results in Parkinson's patients in the clinical setting, it would be a remarkable advance in the treatment of this devastating neurodegenerative disease."
The study was supported by grants from National Institutes of Health and Michael J. Fox Foundation for Parkinson's Research.
Parkinson's is a slowly progressive disease that affects a small area of cells within the mid-brain known as the substantia nigra. Gradual degeneration of these cells causes a reduction in dopamine, which is a vital chemical neurotransmitter. The decrease in dopamine results in one or more of the classic signs of Parkinson's disease that includes, resting tremor on one side of the body, generalized slowness of movement, stiffness of limbs, and gait or balance problems. The cause of Parkinson's disease is unknown. Both environmental and genetic causes of the disease have been postulated.
Parkinson's disease affects about 1.2 million patients in the United States and Canada. Although 15 percent of patients are diagnosed before age 50, it is generally considered a disease that targets older adults, affecting one of every 100 persons over the age of 60. This disease appears to be slightly more common in men than women.
Source: Deborah Song
Rush University Medical Center
воскресенье, 10 июля 2011 г.
Directionality In The Evolution Of Influenza A Hemagglutinin
Hemagglutinin is an important influenza virus antigen whose fast rate of evolution allows the virus to evade the human antibody response.
This phenomenon is called antigenic drift. Several key amino acid positions in hemagglutinin have been previously identified as evolving especially rapidly, presumably under pressure from the human immune system, but the identities of the selectively favored amino acids at those positions remained unknown. In this paper, we identify those specific amino acid substitutions at rapidly as well as slowly evolving sites that occurred in hemagglutinin unusually often over the past 40 years.
These amino acid substitutions are likely to have been adaptive. Our findings shed light on how the influenza A antigenic drift proceeds and may have implications for vaccine development.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
This phenomenon is called antigenic drift. Several key amino acid positions in hemagglutinin have been previously identified as evolving especially rapidly, presumably under pressure from the human immune system, but the identities of the selectively favored amino acids at those positions remained unknown. In this paper, we identify those specific amino acid substitutions at rapidly as well as slowly evolving sites that occurred in hemagglutinin unusually often over the past 40 years.
These amino acid substitutions are likely to have been adaptive. Our findings shed light on how the influenza A antigenic drift proceeds and may have implications for vaccine development.
Proceedings of the Royal Society B: Biological Sciences
Proceedings B is the Royal Society's flagship biological research journal, dedicated to the rapid publication and broad dissemination of high-quality research papers, reviews and comment and reply papers. The scope of journal is diverse and is especially strong in organismal biology.
publishing.royalsociety/proceedingsb
четверг, 7 июля 2011 г.
'Moving' Theory Behind Bacterial Decision-Making Presented By Scientists
Biochemists at North Carolina State University have answered a fundamental question of how important bacterial proteins make life-and-death decisions that allow them to function, a finding that could provide a new target for drugs to disrupt bacterial decision-making processes and related diseases.
In a study published this month in the journal Structure, the NC State scientists show for the first time that the specific movements of these important bacterial proteins, called transition-state regulators, guide how the proteins bind with DNA and thus control a variety of functions. These rare proteins are like army generals sizing up a battlefield; while they all look the same and have the same rank, their highly specialized "wiggles" allow them to figure out how to bind to different parts of DNA, triggering defense capabilities, for example, or commands to set up camp and chow down.
"For the first time, we've shown that proteins with identical shapes have different movements, and these movements allow proteins to select proper DNA targets that lead to tens or hundreds of processes," says Dr. John Cavanagh, William Neal Reynolds Distinguished Professor of Molecular and Structural Biochemistry at NC State and the corresponding author of the paper. "Motion is really important. If the proteins didn't move, they wouldn't be able to bind to DNA and therefore to function."
Cavanagh and NC State senior biochemistry researcher Dr. Benjamin Bobay, a paper co-author, say that the findings present a new way of thinking about stopping bacteria. If a drug or antibiotic can stymie the motion of the transition-state regulators, the thinking goes, bacteria won't be able to figure out where to bind to DNA, effectively shutting the bacteria down. Killing a general, therefore, would stop the infantry from taking the battlefield.
Besides the fundamental knowledge about bacterial protein movement and DNA binding, the Structure paper also sheds light on the specific bacterial protein responsible for producing anthrax toxins.
One of the transition-state regulators studied by the NC State biochemists, called AbrB, helps control the production of the three toxins in anthrax: lethal factor, edema factor and protective antigen. Production of all three of these toxins is necessary to make anthrax lethal.
Cavanagh and Bobay say that knowledge of AbrB's function could make it a likely target for a drug that would knock out its function. That would prevent anthrax from "going lethal."
"We now know more about the protein that causes you to die from anthrax poisoning and a brand new way of understanding how important proteins bind to targets," Cavanagh said. "This presents a whole new paradigm for drug design in the arms race against harmful bacteria and disease."
The National Institutes of Health, the Kenan Institute for Engineering, Technology & Science and the National Institute of Environmental Health Sciences supported the study.
Note: An abstract of the paper follows.
"Insights into the Nature of DNA Binding of AbrB-like Transcription Factors"
Authors: Daniel M. Sullivan, Benjamin G. Bobay, Richele J. Thompson and John Cavanagh, North Carolina State University; Douglas Kojetin and Mark Rance, University of Cincinnati; Mark Strauch, University of Maryland at Baltimore
Published: Nov. 11, 2008, in Structure
Abstract: Understanding the DNA recognition and binding by the AbrB-like family of transcriptional regulators is of significant interest since these proteins enable bacteria to elicit the appropriate response to diverse environmental stimuli. Although these ''transition-state regulator'' proteins have been well characterized at the genetic level, the general and specific mechanisms of DNA binding remain elusive. We present RDC-refined NMR solution structures and dynamic properties of the DNA-binding domains of three Bacillus subtilis transition-state regulators: AbrB, Abh, and SpoVT. We combined previously investigated DNase I footprinting, DNA methylation, gel-shift assays, and mutagenic and NMR studies to generate a structural model of the complex between AbrBN55 and its cognate promoter, abrB8. These investigations have enabled us to generate a model for the specific nature of the transition-state regulator-DNA interaction, a structure that has remained elusive thus far.
Source: Dr. John Cavanagh
North Carolina State University
In a study published this month in the journal Structure, the NC State scientists show for the first time that the specific movements of these important bacterial proteins, called transition-state regulators, guide how the proteins bind with DNA and thus control a variety of functions. These rare proteins are like army generals sizing up a battlefield; while they all look the same and have the same rank, their highly specialized "wiggles" allow them to figure out how to bind to different parts of DNA, triggering defense capabilities, for example, or commands to set up camp and chow down.
"For the first time, we've shown that proteins with identical shapes have different movements, and these movements allow proteins to select proper DNA targets that lead to tens or hundreds of processes," says Dr. John Cavanagh, William Neal Reynolds Distinguished Professor of Molecular and Structural Biochemistry at NC State and the corresponding author of the paper. "Motion is really important. If the proteins didn't move, they wouldn't be able to bind to DNA and therefore to function."
Cavanagh and NC State senior biochemistry researcher Dr. Benjamin Bobay, a paper co-author, say that the findings present a new way of thinking about stopping bacteria. If a drug or antibiotic can stymie the motion of the transition-state regulators, the thinking goes, bacteria won't be able to figure out where to bind to DNA, effectively shutting the bacteria down. Killing a general, therefore, would stop the infantry from taking the battlefield.
Besides the fundamental knowledge about bacterial protein movement and DNA binding, the Structure paper also sheds light on the specific bacterial protein responsible for producing anthrax toxins.
One of the transition-state regulators studied by the NC State biochemists, called AbrB, helps control the production of the three toxins in anthrax: lethal factor, edema factor and protective antigen. Production of all three of these toxins is necessary to make anthrax lethal.
Cavanagh and Bobay say that knowledge of AbrB's function could make it a likely target for a drug that would knock out its function. That would prevent anthrax from "going lethal."
"We now know more about the protein that causes you to die from anthrax poisoning and a brand new way of understanding how important proteins bind to targets," Cavanagh said. "This presents a whole new paradigm for drug design in the arms race against harmful bacteria and disease."
The National Institutes of Health, the Kenan Institute for Engineering, Technology & Science and the National Institute of Environmental Health Sciences supported the study.
Note: An abstract of the paper follows.
"Insights into the Nature of DNA Binding of AbrB-like Transcription Factors"
Authors: Daniel M. Sullivan, Benjamin G. Bobay, Richele J. Thompson and John Cavanagh, North Carolina State University; Douglas Kojetin and Mark Rance, University of Cincinnati; Mark Strauch, University of Maryland at Baltimore
Published: Nov. 11, 2008, in Structure
Abstract: Understanding the DNA recognition and binding by the AbrB-like family of transcriptional regulators is of significant interest since these proteins enable bacteria to elicit the appropriate response to diverse environmental stimuli. Although these ''transition-state regulator'' proteins have been well characterized at the genetic level, the general and specific mechanisms of DNA binding remain elusive. We present RDC-refined NMR solution structures and dynamic properties of the DNA-binding domains of three Bacillus subtilis transition-state regulators: AbrB, Abh, and SpoVT. We combined previously investigated DNase I footprinting, DNA methylation, gel-shift assays, and mutagenic and NMR studies to generate a structural model of the complex between AbrBN55 and its cognate promoter, abrB8. These investigations have enabled us to generate a model for the specific nature of the transition-state regulator-DNA interaction, a structure that has remained elusive thus far.
Source: Dr. John Cavanagh
North Carolina State University
понедельник, 4 июля 2011 г.
Indresh Srivastava, Ph.D., To Give A Featured Presentation At The 5th Biological Therapeutics Conference Oct 20-22, San Francisco, CA
Indresh Srivastava, Ph.D., Head of Protein Biology, Novartis, will give a featured presentation at the 5th Biological Therapeutics Research and Development Conference to be held in San Francisco, CA on Oct. 20-22, 2010 by GTCbio as part of the 6th Annual Modern Drug Discovery and Development Summit. The conference provides its participants with a current look at biologics and projects into its future with discussions regarding developments and challenges in immunogenicity, humanization, drug delivery techniques for biologics, modern vaccine development, antibodies, and novel protein and peptide delivery. Overcoming the issue of the role of biologics in drug discovery and how to improve upon the length of time a drug remains effective in the body, without losing money, will be addressed.
Also presenting at the 5th Biological Therapeutics Conference are prestigious organizations including Abbott, Amgen, Albany Medical Center, Auburn University, Facet Biotech, subsidiary of Abbott Labs, Genentech, Novartis, NCI, NIH, MedImmune, UCSF, Transgene, Micromet, Amunix, Nektar, Bayhill Therapeutics, and other leaders in the industry.
Author:
GTCbio
Source:
GTCbio
434 W. Foothill Blvd. Monrovia, CA 91016
Tel: (626) 256-6405
fax: (626) 256-6460
email: infogtcbiogtcbio
Company Website
Event Website
Also presenting at the 5th Biological Therapeutics Conference are prestigious organizations including Abbott, Amgen, Albany Medical Center, Auburn University, Facet Biotech, subsidiary of Abbott Labs, Genentech, Novartis, NCI, NIH, MedImmune, UCSF, Transgene, Micromet, Amunix, Nektar, Bayhill Therapeutics, and other leaders in the industry.
Author:
GTCbio
Source:
GTCbio
434 W. Foothill Blvd. Monrovia, CA 91016
Tel: (626) 256-6405
fax: (626) 256-6460
email: infogtcbiogtcbio
Company Website
Event Website
пятница, 1 июля 2011 г.
A Simple Modification Of The Hodgkin & Huxley Equations Explains Type 3 Excitability In Squid Giant Axons
This paper describes an unusual finding from a well known preparation in neuroscience - squid giant axons.
Specifically, the cell fires once and only once in response to a sustained depolarizing current pulse, a result Alan Hodgkin referred to as Type 3 in a classic paper on crustacean axons published in 1948.
Surprisingly, squid giant axons also exhibit this behavior even though the classic Hodgkin and Huxley (1952) model for squid axons fires repetitively for these conditions - Type 2 behavior.
A simple modification in the K+ conductance system in their equations is sufficient to mimic this result.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fourth in JCR's multidisciplinary category.
publishing.royalsociety/interface
Specifically, the cell fires once and only once in response to a sustained depolarizing current pulse, a result Alan Hodgkin referred to as Type 3 in a classic paper on crustacean axons published in 1948.
Surprisingly, squid giant axons also exhibit this behavior even though the classic Hodgkin and Huxley (1952) model for squid axons fires repetitively for these conditions - Type 2 behavior.
A simple modification in the K+ conductance system in their equations is sufficient to mimic this result.
Journal of the Royal Society Interface
Journal of the Royal Society Interface is the Society's cross-disciplinary publication promoting research at the interface between the physical and life sciences. It offers rapidity, visibility and high-quality peer review and is ranked fourth in JCR's multidisciplinary category.
publishing.royalsociety/interface
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