Mayo Clinic researchers have discovered an inherited structural mechanism that can make drugs for some diseases toxic for some patients. The mechanism decreases a protein and in turn causes certain individuals to metabolize thiopurine drugs differently. Thiopurine therapies are used to treat patients with childhood leukemia, autoimmune diseases and organ transplants. The Mayo researchers say their finding advances the field of pharmacogenomics, which tailors medicine to a patient's personal genetic makeup.
In the current issue of the Proceedings of the National Academy of Sciences, (pnas/cgi/content/abstract/102/26/9394) Mayo researchers report that under certain genetic conditions, key proteins are not formed properly -- they are "misfolded." When misfolding happens, the quality-control process in the cell detects the misfolded proteins and tags them for immediate destruction or quarantines them in a "cellular trash can" known as an aggresome (last syllable rhymes with "foam"). Whether destroyed or aggregated into the aggresome, the effect is the same: the patient's body suffers a protein deficit that disrupts the enzyme that metabolizes thiopurine.
"Our finding is surprising because the aggresome is a new kind of mechanism to study to explain this. It's quite different from what we were thinking even a few years ago," says Liewei Wang, M.D., Ph.D., lead Mayo researcher in the study. "People are still debating what its function really is, but it appears to play a role here by receiving misfolded proteins."
Significance of the Research
"Nobody has shown before that the aggresome plays a role in thiopurine metabolism, and it's a significant contribution," says Richard Weinshilboum, M.D., the Mayo Clinic researcher who first described the genetically variable response to thiopurine drugs over 20 years ago. "From a clinical point of view, the genetic test we developed at Mayo to predict response to thiopurine drugs has been invaluable to pharmacogenomic medicine -- and now this finding is taking us in promising new directions because we believe our findings can be generalized to apply to many instances in the field."
The finding helps explain what goes wrong under certain genetic conditions -- and suggests mechanisms which might help predict which genetic changes could alter the effect of drugs. Prior efforts to explain the mystery of thiopurine metabolism had focused on biochemical mechanisms -- not changes in protein levels.
Background
Researchers have known for decades that 1 in 300 patients of Caucasian European genetic background has two copies of the variant gene -- specifically, a switch in 2 out of 245 amino acids -- that results in the absence of the protein needed to properly metabolize thiopurine drugs. In patients with the genetic defect, instead of helping heal, a standard dose of thiopurine drugs can cause fatal bone marrow destruction. Though Mayo Clinic researchers described this genetically variable response and the danger it presents over 20 years ago, no one had been able to explain the cellular mechanism behind it.
Mayo Clinic
mayo
пятница, 29 июля 2011 г.
вторник, 26 июля 2011 г.
Secrets Of A Life-Giving Amino Acid Revealed By Yale Researchers
Selenium is a trace element crucial to life - too little or too much of it is fatal. In the July 17 issue of the journal Science, researchers at Yale University and University of Illinois at Chicago detail the molecular mechanisms that govern its metabolism in the human body.
"It must require an intricately regulated uptake system," said Dieter Söll, co-senior author of the paper, Sterling Professor of Molecular Biophysics and Biochemistry at Yale. "There are 25 human selenoproteins, and most of them are probably essential for life."
Selenium is thought to offer protection from diverse human ailments including adverse mood states, cardiovascular disease, viral infections and cancer.
Selenocysteine is the most active metabolite of selenium in humans. It is unique among amino acids because it is the only one synthesized directly on a transfer RNA (tRNA) molecule, which shuttles the amino acids to the protein-making machinery within cells. Proteins that contain selenocysteine are responsible for recycling protective antioxidants such as vitamin C and coenzyme Q10.
Söll's team for the first time captured images of how selenocysteine is created on a super-sized tRNA molecule, which seems to have a highly specialized role in nature. The 20 other amino acids and their associated tRNAs use the same protein vehicle, called an elongation factor, for transport to the ribosome. However, nature has provided this large tRNA molecule with a specialized elongation factor that chauffeurs only selenocysteine to the ribosome.
"This structure reveals most aspects of the mechanism for the formation of selenocysteine and provides an answer to 20 years of biochemical work in the field," said Sotiria Palioura, lead author of the study and an M.D./Ph.D. candidate at Yale.
The findings may lead to greater understanding of autoimmune liver disease. The tRNA complex described in the Science paper is the target of antibodies in patients with Type 1 autoimmune hepatitis. "The region that the antibody is supposed to recognize is at the business end of this molecule, where we see the reaction happening," Palioura said.
"Selenocysteine has been found to be a critical component of enzymes involved in a number of normal and disease processes," said Michael Bender of the National Institutes of Health's National Institute of General Medical Sciences. "This basic study, which has shed light on selenocysteine's unique biosynthetic pathway, could ultimately have an impact on many aspects of human health, including the immune response, neurodegeneration, cardiovascular disease, and cancer."
Other Yale authors on the paper were R. Lynn Sherrer and Thomas A. Steitz. Senior co-author on the paper was Miljan Simonovic of the University of Illinois at Chicago.
Funding for the research was provided by the National Institute for General Medical Sciences, the Department of Energy, and the Howard Hughes Medical Institute at Yale University.
Citation: Science, July 17
Source
Yale University
"It must require an intricately regulated uptake system," said Dieter Söll, co-senior author of the paper, Sterling Professor of Molecular Biophysics and Biochemistry at Yale. "There are 25 human selenoproteins, and most of them are probably essential for life."
Selenium is thought to offer protection from diverse human ailments including adverse mood states, cardiovascular disease, viral infections and cancer.
Selenocysteine is the most active metabolite of selenium in humans. It is unique among amino acids because it is the only one synthesized directly on a transfer RNA (tRNA) molecule, which shuttles the amino acids to the protein-making machinery within cells. Proteins that contain selenocysteine are responsible for recycling protective antioxidants such as vitamin C and coenzyme Q10.
Söll's team for the first time captured images of how selenocysteine is created on a super-sized tRNA molecule, which seems to have a highly specialized role in nature. The 20 other amino acids and their associated tRNAs use the same protein vehicle, called an elongation factor, for transport to the ribosome. However, nature has provided this large tRNA molecule with a specialized elongation factor that chauffeurs only selenocysteine to the ribosome.
"This structure reveals most aspects of the mechanism for the formation of selenocysteine and provides an answer to 20 years of biochemical work in the field," said Sotiria Palioura, lead author of the study and an M.D./Ph.D. candidate at Yale.
The findings may lead to greater understanding of autoimmune liver disease. The tRNA complex described in the Science paper is the target of antibodies in patients with Type 1 autoimmune hepatitis. "The region that the antibody is supposed to recognize is at the business end of this molecule, where we see the reaction happening," Palioura said.
"Selenocysteine has been found to be a critical component of enzymes involved in a number of normal and disease processes," said Michael Bender of the National Institutes of Health's National Institute of General Medical Sciences. "This basic study, which has shed light on selenocysteine's unique biosynthetic pathway, could ultimately have an impact on many aspects of human health, including the immune response, neurodegeneration, cardiovascular disease, and cancer."
Other Yale authors on the paper were R. Lynn Sherrer and Thomas A. Steitz. Senior co-author on the paper was Miljan Simonovic of the University of Illinois at Chicago.
Funding for the research was provided by the National Institute for General Medical Sciences, the Department of Energy, and the Howard Hughes Medical Institute at Yale University.
Citation: Science, July 17
Source
Yale University
суббота, 23 июля 2011 г.
Jet-Propelled Imaging For An Ultrafast Light Source
John Spence, a physicist at Arizona State University, is a longtime user of the Advanced Light Source at Lawrence Berkeley National Laboratory, where he has contributed to major advances in lensless imaging. It's a particularly apt propensity for someone who works with x-rays, since they can't be focused with ordinary lenses.
As new light sources evolve to produce brighter x-rays in faster pulses, lensless imaging becomes ever more critical for science. Among the promises of superbright, ultrafast x-ray pulses is the ability to solve the structure of the complicated molecules from which our bodies are made. All living things are made of proteins and nucleic acids, but relatively few of the atomic structures of the thousands, perhaps millions, of varieties of proteins are known.
The Linac Coherent Light Source (LCLS) will soon begin operation at the SLAC National Accelerator Laboratory in Palo Alto, California, using energetic electrons from a linear accelerator to produce coherent x-rays with an instrument called a free electron laser (FEL). The x-rays will be delivered 120 times a second in pulses only a tenth of a trillionth of a second long - about the time it takes light to travel the width of a human hair. These brief, bright pulses offer a novel approach to the problem of protein structure.
Unfolding the origami
Proteins begin as strings of amino acids that fold themselves into an amazing variety of origami-like structures, whose bumps and crannies and distribution of electrical charges determine how they act individually or fit together to form complex molecular machines. Simple organisms like viruses often consist of a few proteins fitted together to enclose a thread of DNA or RNA.
Proteins are usually large molecules containing many thousands of atoms. Drug molecules are much smaller, and do their work by attaching themselves to the larger protein molecules. A knowledge of the arrangement of a protein's atoms is therefore a great help to drug designers, who like to understand how a drug molecule will dock with a protein to promote or inhibit its activity, or cripple the organism of which it is a part.
Until now, the best way to solve the structure of a protein or virus has been with x ray crystallography. The crystal consists of many copies of the protein or virus arranged in regular order. As the crystal rotates in the x-ray beam, x-rays scatter off the atoms and reveal - once these complex diffraction patterns have been converted into a 3-D image by computers - how the electrons, and thus the atoms, are arranged.
But many proteins can't be crystallized at all, and others are so difficult to crystallize it's virtually impossible to obtain crystals large enough to use in today's light sources.
Ultrafast, ultrabright x-rays offer a way past this dilemma. The idea is that a quick pulse of tightly focused x-rays can be diffracted from a microcrystal or even a single protein or virus in solution. The pulse is so brief that it comes and goes before any of the atoms can move, freezing their orientation like a strobe light. Just as important, a sufficiently brief pulse may terminate before radiation damage effects can start. In this way it can outrun radiation damage, always one of the fundamental limitations to imaging in biology.
Another quick pulse could be diffracted from another copy of the protein in a different orientation. As the process is repeated, diffractions from different angles give the overlapping views needed for the computer to construct a 3-D image of the structure.
It's a great idea, but as Spence notes, there are a few problems. "So as not to scatter, the x-ray beam has to be in a high vacuum, but a protein or virus in its natural state is usually wet. As in T. S. Eliot's Wasteland, water is life. How do we maintain the protein or virus in an aqueous environment inside the vacuum?"
Shot from a microcannon
The answer was what Spence calls a "particle gun, like an ink-jet printer," designed to inject a beam of water droplets across the tightly focused x-ray beam in single file, each droplet so small it contains only a single protein or virus. He and colleagues Bruce Doak and Uwe Weierstall of ASU designed a nozzle that can fire liquid droplets, each less than a millionth of a meter in diameter (one micrometer), faster than hundreds of thousands of times a second. The sample jet is designed to shoot droplets right through a pulsed beam of x-rays a billion times brighter than any ever created in a light source before.
It wasn't easy. Nozzles made of solid material like glass invariably clog up, limiting droplets to at best 20 micrometers across. What Spence and his colleagues wanted was a jet of particles less than a micrometer in size. ASU postdoc Dan DePonte has done most of the recent hard work needed to make it all function.
Back in 1878 Lord Rayleigh, a professor of experimental physics at Cambridge University, discovered that a smooth, cylindrical jet of liquid emerging from an orifice spontaneously breaks up to form a train of spherical droplets. In the late 1990s, physicist Alfonso GaГ±ГЎn-Calvo of the University of Seville found a way to surround the streaming liquid with pressurized gas to make a co-flowing liquid sheath. By adjusting gas and liquid pressure and other parameters, he was able to create a "virtual nozzle" that could shrink the diameter of the liquid jet to a thread so small it would not clog the physical aperture of the tube. In effect, the gas sheath acts to focus the liquid stream.
Spence and his colleagues needed a true microthread of liquid, however, one that produced droplets sized a millionth of a meter or less. In their nozzle, liquid flows through a narrow capillary inside the tube through which the gas flows; the liquid issues from the capillary some distance from the opening in the outer tube, so the gas surrounds it, then increases speed and pressure as it approaches the opening, squeezing and accelerating the thin stream of liquid until it is so small that the proteins or viruses dissolved in the liquid can only fit into the droplets one at a time.
And the nozzle won't clog, because even a particle bigger than the sample protein or virus - bigger than the stream of liquid itself - can still fly through the glass nozzle without hitting the walls and getting stuck.
The frequency at which the droplets emerge can be controlled by an oscillator the researchers call an "acoustic trigger." Tuning the acoustic trigger adjusts the frequency so that each droplet containing a protein or virus meets an incoming pulse of x-rays.
The entire device - which the researchers call a gas dynamic virtual nozzle (GDVN) - is only about a millimeter in diameter (not counting feed lines and cables) and fits to the side of the beamline's vacuum chamber. After passing through the beam, the liquid droplets and the gas (typically carbon dioxide) freeze in a trap opposite the injection point, without significantly reducing the vacuum.
In 2008 Spence and his colleagues, including Berkeley Lab's David Shapiro, successfully tested the GDVN on the Advanced Light Source beamline 9.0.1, managed by Berkeley Lab's Stefano Marchesini. The test was done with protein microcrystals extracted from the fluid in which researchers were attempting to grow larger crystals. These are the smallest protein nanocrystals from which diffraction patterns have ever been obtained, and the first from membrane protein nanocrystals - among the most resistant to crystallization.
Although the microcrystals weren't individual protein specimens, and while the 9.0.1's x-ray beams aren't as bright or as rapidly pulsed as SLAC's LCLS will be, the experiment demonstrated the jet technique's high potential for speeds and exposures that won't subject the samples to radiation damage. Some of the patterns the researchers obtained come from nanocrystals just a few molecules on a side, with a width of about 100 billionths of a meter (100 nanometers). At SLAC, the researchers plan to steadily reduce the nanocrystal size down to single molecules.
The corresponding reduction in scattered intensity will hasten and improve lensless imaging. The first step in lensless imaging is scattering the beam from the sample; the second step is constructing the image by interpreting and combining the data from the diffracted x-rays.
In order to merge the different views (projections) of an object, which is subsequently vaporized in this "diffract-and-destroy" mode, it is important that they all be identical. In biology, that leaves only molecules like proteins and viruses. DNA or RNA inside a virus is often packed differently in each virus, and cells are not identical at the molecular level, so cannot be studied in 3-D by this method.
Besides identical particles, successful data-merging also depends partly on knowing how the sample was oriented in the beam - easy to do with a large crystal, not so easy to do with a sample inside a drop of liquid whizzing across the beam. It may be possible to orient flying droplets by optical methods such as polarized laser beams or with specially shaped nozzles.
Perhaps simpler is to use the ever-increasing power of the computer - which for a lensless imaging system is where most of the functions of a lens reside. Computer systems have been developed that infer the orientation of the sample from the diffraction pattern itself, even when as few as four percent of the pixels in the detector light up. It does take a lot of diffraction patterns to derive an image this way - as many as 10 million - which will take the LCLS a few hours until better ways of orienting the droplets can be devised.
Nevertheless, Spence's group recently obtained excellent diffraction patterns of MS2 virus capsids at the ALS by subtracting the diffraction "noise" of the liquid jet itself. These capsids, made in Mat Francis's lab at the University of California at Berkeley, are the shells of the virus lacking its RNA genome and have the regular shape of buckyballs. Eventually the LCLS will be able to get a good diffraction pattern from a target like this with a single ultrabright pulse. In this case, however, computer processing was able to derive an excellent pattern by averaging diffraction from a series of samples.
DePonte will soon install Spence and Doak's ultrafine, ultrafast "inkjet printer," tested at the ALS, on the powerful new SLAC machine. It will be the first step into a bold new future for investigating the biological universe, one big molecule at a time.
Additional information
"X-ray imaging beyond the limits," by Henry N. Chapman, appeared in Nature Materials, April, 2009.
"Powder diffraction from a continuous microjet of submicrometer protein crystals," by D. A. Shapiro, H. N. Chapman, D. DePonte, R. B. Doak, P. Fromme, G. Hembree, M. Hunter, S. Marchesini, K. Schmidt, J. Spence, D. Starodub, and U. Weierstall, appeared in the Journal of Synchrotron Radiation, November, 2008.
"Gas dynamic virtual nozzle for generation of microscopic droplet streams," by D. P. DePonte, U. Weierstall, K. Schmidt, J. Warner, D. Starodub, J. C. H. Spence, and R. B. Doak, appeared in the Journal of Physics D: Applied Physics, 19 September, 2008.
Source:
Paul Preuss
DOE/Lawrence Berkeley National Laboratory
As new light sources evolve to produce brighter x-rays in faster pulses, lensless imaging becomes ever more critical for science. Among the promises of superbright, ultrafast x-ray pulses is the ability to solve the structure of the complicated molecules from which our bodies are made. All living things are made of proteins and nucleic acids, but relatively few of the atomic structures of the thousands, perhaps millions, of varieties of proteins are known.
The Linac Coherent Light Source (LCLS) will soon begin operation at the SLAC National Accelerator Laboratory in Palo Alto, California, using energetic electrons from a linear accelerator to produce coherent x-rays with an instrument called a free electron laser (FEL). The x-rays will be delivered 120 times a second in pulses only a tenth of a trillionth of a second long - about the time it takes light to travel the width of a human hair. These brief, bright pulses offer a novel approach to the problem of protein structure.
Unfolding the origami
Proteins begin as strings of amino acids that fold themselves into an amazing variety of origami-like structures, whose bumps and crannies and distribution of electrical charges determine how they act individually or fit together to form complex molecular machines. Simple organisms like viruses often consist of a few proteins fitted together to enclose a thread of DNA or RNA.
Proteins are usually large molecules containing many thousands of atoms. Drug molecules are much smaller, and do their work by attaching themselves to the larger protein molecules. A knowledge of the arrangement of a protein's atoms is therefore a great help to drug designers, who like to understand how a drug molecule will dock with a protein to promote or inhibit its activity, or cripple the organism of which it is a part.
Until now, the best way to solve the structure of a protein or virus has been with x ray crystallography. The crystal consists of many copies of the protein or virus arranged in regular order. As the crystal rotates in the x-ray beam, x-rays scatter off the atoms and reveal - once these complex diffraction patterns have been converted into a 3-D image by computers - how the electrons, and thus the atoms, are arranged.
But many proteins can't be crystallized at all, and others are so difficult to crystallize it's virtually impossible to obtain crystals large enough to use in today's light sources.
Ultrafast, ultrabright x-rays offer a way past this dilemma. The idea is that a quick pulse of tightly focused x-rays can be diffracted from a microcrystal or even a single protein or virus in solution. The pulse is so brief that it comes and goes before any of the atoms can move, freezing their orientation like a strobe light. Just as important, a sufficiently brief pulse may terminate before radiation damage effects can start. In this way it can outrun radiation damage, always one of the fundamental limitations to imaging in biology.
Another quick pulse could be diffracted from another copy of the protein in a different orientation. As the process is repeated, diffractions from different angles give the overlapping views needed for the computer to construct a 3-D image of the structure.
It's a great idea, but as Spence notes, there are a few problems. "So as not to scatter, the x-ray beam has to be in a high vacuum, but a protein or virus in its natural state is usually wet. As in T. S. Eliot's Wasteland, water is life. How do we maintain the protein or virus in an aqueous environment inside the vacuum?"
Shot from a microcannon
The answer was what Spence calls a "particle gun, like an ink-jet printer," designed to inject a beam of water droplets across the tightly focused x-ray beam in single file, each droplet so small it contains only a single protein or virus. He and colleagues Bruce Doak and Uwe Weierstall of ASU designed a nozzle that can fire liquid droplets, each less than a millionth of a meter in diameter (one micrometer), faster than hundreds of thousands of times a second. The sample jet is designed to shoot droplets right through a pulsed beam of x-rays a billion times brighter than any ever created in a light source before.
It wasn't easy. Nozzles made of solid material like glass invariably clog up, limiting droplets to at best 20 micrometers across. What Spence and his colleagues wanted was a jet of particles less than a micrometer in size. ASU postdoc Dan DePonte has done most of the recent hard work needed to make it all function.
Back in 1878 Lord Rayleigh, a professor of experimental physics at Cambridge University, discovered that a smooth, cylindrical jet of liquid emerging from an orifice spontaneously breaks up to form a train of spherical droplets. In the late 1990s, physicist Alfonso GaГ±ГЎn-Calvo of the University of Seville found a way to surround the streaming liquid with pressurized gas to make a co-flowing liquid sheath. By adjusting gas and liquid pressure and other parameters, he was able to create a "virtual nozzle" that could shrink the diameter of the liquid jet to a thread so small it would not clog the physical aperture of the tube. In effect, the gas sheath acts to focus the liquid stream.
Spence and his colleagues needed a true microthread of liquid, however, one that produced droplets sized a millionth of a meter or less. In their nozzle, liquid flows through a narrow capillary inside the tube through which the gas flows; the liquid issues from the capillary some distance from the opening in the outer tube, so the gas surrounds it, then increases speed and pressure as it approaches the opening, squeezing and accelerating the thin stream of liquid until it is so small that the proteins or viruses dissolved in the liquid can only fit into the droplets one at a time.
And the nozzle won't clog, because even a particle bigger than the sample protein or virus - bigger than the stream of liquid itself - can still fly through the glass nozzle without hitting the walls and getting stuck.
The frequency at which the droplets emerge can be controlled by an oscillator the researchers call an "acoustic trigger." Tuning the acoustic trigger adjusts the frequency so that each droplet containing a protein or virus meets an incoming pulse of x-rays.
The entire device - which the researchers call a gas dynamic virtual nozzle (GDVN) - is only about a millimeter in diameter (not counting feed lines and cables) and fits to the side of the beamline's vacuum chamber. After passing through the beam, the liquid droplets and the gas (typically carbon dioxide) freeze in a trap opposite the injection point, without significantly reducing the vacuum.
In 2008 Spence and his colleagues, including Berkeley Lab's David Shapiro, successfully tested the GDVN on the Advanced Light Source beamline 9.0.1, managed by Berkeley Lab's Stefano Marchesini. The test was done with protein microcrystals extracted from the fluid in which researchers were attempting to grow larger crystals. These are the smallest protein nanocrystals from which diffraction patterns have ever been obtained, and the first from membrane protein nanocrystals - among the most resistant to crystallization.
Although the microcrystals weren't individual protein specimens, and while the 9.0.1's x-ray beams aren't as bright or as rapidly pulsed as SLAC's LCLS will be, the experiment demonstrated the jet technique's high potential for speeds and exposures that won't subject the samples to radiation damage. Some of the patterns the researchers obtained come from nanocrystals just a few molecules on a side, with a width of about 100 billionths of a meter (100 nanometers). At SLAC, the researchers plan to steadily reduce the nanocrystal size down to single molecules.
The corresponding reduction in scattered intensity will hasten and improve lensless imaging. The first step in lensless imaging is scattering the beam from the sample; the second step is constructing the image by interpreting and combining the data from the diffracted x-rays.
In order to merge the different views (projections) of an object, which is subsequently vaporized in this "diffract-and-destroy" mode, it is important that they all be identical. In biology, that leaves only molecules like proteins and viruses. DNA or RNA inside a virus is often packed differently in each virus, and cells are not identical at the molecular level, so cannot be studied in 3-D by this method.
Besides identical particles, successful data-merging also depends partly on knowing how the sample was oriented in the beam - easy to do with a large crystal, not so easy to do with a sample inside a drop of liquid whizzing across the beam. It may be possible to orient flying droplets by optical methods such as polarized laser beams or with specially shaped nozzles.
Perhaps simpler is to use the ever-increasing power of the computer - which for a lensless imaging system is where most of the functions of a lens reside. Computer systems have been developed that infer the orientation of the sample from the diffraction pattern itself, even when as few as four percent of the pixels in the detector light up. It does take a lot of diffraction patterns to derive an image this way - as many as 10 million - which will take the LCLS a few hours until better ways of orienting the droplets can be devised.
Nevertheless, Spence's group recently obtained excellent diffraction patterns of MS2 virus capsids at the ALS by subtracting the diffraction "noise" of the liquid jet itself. These capsids, made in Mat Francis's lab at the University of California at Berkeley, are the shells of the virus lacking its RNA genome and have the regular shape of buckyballs. Eventually the LCLS will be able to get a good diffraction pattern from a target like this with a single ultrabright pulse. In this case, however, computer processing was able to derive an excellent pattern by averaging diffraction from a series of samples.
DePonte will soon install Spence and Doak's ultrafine, ultrafast "inkjet printer," tested at the ALS, on the powerful new SLAC machine. It will be the first step into a bold new future for investigating the biological universe, one big molecule at a time.
Additional information
"X-ray imaging beyond the limits," by Henry N. Chapman, appeared in Nature Materials, April, 2009.
"Powder diffraction from a continuous microjet of submicrometer protein crystals," by D. A. Shapiro, H. N. Chapman, D. DePonte, R. B. Doak, P. Fromme, G. Hembree, M. Hunter, S. Marchesini, K. Schmidt, J. Spence, D. Starodub, and U. Weierstall, appeared in the Journal of Synchrotron Radiation, November, 2008.
"Gas dynamic virtual nozzle for generation of microscopic droplet streams," by D. P. DePonte, U. Weierstall, K. Schmidt, J. Warner, D. Starodub, J. C. H. Spence, and R. B. Doak, appeared in the Journal of Physics D: Applied Physics, 19 September, 2008.
Source:
Paul Preuss
DOE/Lawrence Berkeley National Laboratory
среда, 20 июля 2011 г.
Genetic Compatibility And Hatching Success In The Sea Lamprey (Petromyzon Marinus). Is There A Better Half?
It often assumed that the quality of a potential mate in terms of how their genes affect their offspring quality is a fixed feature of each individual.
However, it is becoming increasingly apparent that this is not always the case, and that mates may vary in compatibility more than in quality. We fertilised separate batches of eggs from female sea lampreys (a parasitic fish) with sperm from several different males.
This revealed that the viability of offspring was mainly dependent on how compatible partners were. For female lampreys, there are no good or bad males, but there are better halves.
Royal Society Journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
Biology Letters
However, it is becoming increasingly apparent that this is not always the case, and that mates may vary in compatibility more than in quality. We fertilised separate batches of eggs from female sea lampreys (a parasitic fish) with sperm from several different males.
This revealed that the viability of offspring was mainly dependent on how compatible partners were. For female lampreys, there are no good or bad males, but there are better halves.
Royal Society Journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
Biology Letters
воскресенье, 17 июля 2011 г.
Controlling Nitric Oxide Levels Could Further Improve Effectivness Of Anticancer Therapies
Manipulating levels of nitric oxide (NO), a gas involved in many biological processes, may improve the disorganized network of blood vessels supplying tumors, potentially improving the effectiveness of radiation and chemotherapy. In an upcoming issue of the journal Nature Medicine, researchers from the Steele Laboratory of Radiation Oncology at Massachusetts General Hospital (MGH) report an experiment in which NO production was selectively suppressed in tumor cells while being maintained in blood vessels. The result was a significant improvement in the appearance and function of the tumor's blood supply.
"Our finding suggest that the creation of perivascular NO gradients - differences between the levels produced in blood vessels and those found in tumor tissue - may be able to normalize tumor vasculature," says Dai Fukumura, MD, PhD, of the Steele Laboratory, who led the study. "Combining the use of angiogenesis inhibitors, which normalize vasculature through a different mechanism, with the blockade of nonvascular NO production may produce even greater improvement in therapeutic outcomes."
The blood vessels that develop around and within tumors are leaky and disorganized, interfering with delivery of chemotherapy drugs and with radiation treatment, which requires an adequate oxygen supply. Combining angiogenesis inhibitors, drugs that suppress the growth of blood vessels, with traditional anticancer therapies has improved patient survival in some tumors. That success supports a theory developed by Rakesh K. Jain, PhD, director of the Steele Laboratory, that the agents temporarily 'normalize' blood vessels, creating a period during which other treatments can be more effective.
Since angiogenesis is one of many physiologic activities mediated by NO, the MGH research team hypothesized that restricting NO production to blood vessels also could improve tumor vasculature. Using cancer cells from human brain tumors, they suppressed the enzyme that controls NO production in nonvascular tissue. When the modified tumor cells were implanted into mice, analysis of the resulting tumors showed that NO was present primarily in blood vessels, with significant reductions in tumor cells. Vessels in the growing tumors were more evenly distributed and less distorted than those in tumors grown from untreated tissue.
"Angiogenesis inhibitors block formation of new vessels by directly or indirectly inhibiting the proliferation and survival of vascular endothelial cells. But since their overall effect is to reduce the density of blood vessels, the ability of those agents to normalize tumor vasculature may not last long," says Fukumura. "Blocking nonvascular NO production and maintaining NO levels around the vessels appears to keep endothelial cell function at the proper level." An associate professor of Radiation Oncology at Harvard Medical School, Fukumura notes that the strategy now should be investigated in other types of tumors.
The Nature Medicine report has been released online and was supported by grants from the National Cancer Institute. In addition to Fukumura and Jain, co-authors of the article are first author Satoshi Kashiwagi, MD, PhD, Kosuke Tsukada, PhD, Lei Xu, MD, PhD, Junichi Miyazaki, MD, PhD, Sergey Kozin, DSc, PhD, James Tyrrell, PhD, and Leo Gerweck, PhD, all of the Steele Lab; and William Sessa, PhD, Yale University School of Medicine.
Massachusetts General Hospital (massgeneral/), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Source: Sue McGreevey
Massachusetts General Hospital
"Our finding suggest that the creation of perivascular NO gradients - differences between the levels produced in blood vessels and those found in tumor tissue - may be able to normalize tumor vasculature," says Dai Fukumura, MD, PhD, of the Steele Laboratory, who led the study. "Combining the use of angiogenesis inhibitors, which normalize vasculature through a different mechanism, with the blockade of nonvascular NO production may produce even greater improvement in therapeutic outcomes."
The blood vessels that develop around and within tumors are leaky and disorganized, interfering with delivery of chemotherapy drugs and with radiation treatment, which requires an adequate oxygen supply. Combining angiogenesis inhibitors, drugs that suppress the growth of blood vessels, with traditional anticancer therapies has improved patient survival in some tumors. That success supports a theory developed by Rakesh K. Jain, PhD, director of the Steele Laboratory, that the agents temporarily 'normalize' blood vessels, creating a period during which other treatments can be more effective.
Since angiogenesis is one of many physiologic activities mediated by NO, the MGH research team hypothesized that restricting NO production to blood vessels also could improve tumor vasculature. Using cancer cells from human brain tumors, they suppressed the enzyme that controls NO production in nonvascular tissue. When the modified tumor cells were implanted into mice, analysis of the resulting tumors showed that NO was present primarily in blood vessels, with significant reductions in tumor cells. Vessels in the growing tumors were more evenly distributed and less distorted than those in tumors grown from untreated tissue.
"Angiogenesis inhibitors block formation of new vessels by directly or indirectly inhibiting the proliferation and survival of vascular endothelial cells. But since their overall effect is to reduce the density of blood vessels, the ability of those agents to normalize tumor vasculature may not last long," says Fukumura. "Blocking nonvascular NO production and maintaining NO levels around the vessels appears to keep endothelial cell function at the proper level." An associate professor of Radiation Oncology at Harvard Medical School, Fukumura notes that the strategy now should be investigated in other types of tumors.
The Nature Medicine report has been released online and was supported by grants from the National Cancer Institute. In addition to Fukumura and Jain, co-authors of the article are first author Satoshi Kashiwagi, MD, PhD, Kosuke Tsukada, PhD, Lei Xu, MD, PhD, Junichi Miyazaki, MD, PhD, Sergey Kozin, DSc, PhD, James Tyrrell, PhD, and Leo Gerweck, PhD, all of the Steele Lab; and William Sessa, PhD, Yale University School of Medicine.
Massachusetts General Hospital (massgeneral/), established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine.
Source: Sue McGreevey
Massachusetts General Hospital
четверг, 14 июля 2011 г.
Special Laser "Tweezers" For Medicine, Communications And Harvesting Energy
Star Trek fans will remember "tractor beams," lasers that allowed the Starship Enterprise to trap and move objects. Tel Aviv University is now turning this science fiction into science fact - on a nano scale.
A new tool developed by Tel Aviv University, Holographic Optical Tweezers (HOTs) use holographic technology to manipulate up to 300 nanoparticles at a time, such as beads of glass or polymer, that are too small and delicate to be handled with traditional laboratory instruments. The technology, also known as "optical tweezers," could form the basis for tomorrow's ultra-fast, light-powered communication devices and quantum computers, says Dr. Yael Roichman of Tel Aviv University's School of Chemistry.
She's using these tweezers to build nano structures that control beams of light, aiding in the development of anything from optical microscopes to light-fuelled computer technology, she reports.
Holding onto the light
HOTS are a new family of optical tools that use a strongly-focused light beam to trap, manipulate and transform small amounts of matter. First proposed as a scientific theory in 1986 and prototyped by a University of Chicago team in 1997, holographic optical tweezers have been lauded as indispensible for researching cutting-edge ideas in physics, chemistry, and biology.
Dr. Roichman and her team of researchers are currently pioneering the use of optical tweezers to create the next generation of photonic devices. Made out of carefully arranged particles of materials such as silicon oxide and titanium oxide, these devices have the ability to insulate light, allowing less energy to be lost in transmission.
"Our invention could increase transmission speed and save energy, important for long-life batteries in computers, for instance," says Dr. Roichman.
Photons are already used in optical fibers that bring us everyday luxuries like cable TV. But Dr. Roichman says this technology can be taken much further. In her lab at Tel Aviv University, she is advancing the previous study of photonic crystals, which control and harness light, by manipulating a variety of particles to create 3D heterogeneous structures. The ability to insulate light in a novel way, preserving its potential energy, is central to this goal.
No known material today can resist the flow of light - its energy is either absorbed by, reflected off, or passed through materials. But Dr. Roichman has devised a new layering technique using special crystals central to the creation of photonic devices. These photonic crystals are arranged to create a path along which light can travel. If they're arranged correctly, she says, the light is trapped along the path.
In Dr. Roichman's approach, different materials are added to absorb or amplify light as required. She is hopeful that the ability to build these devices will transform communications, telescopic instruments, and even medical technology, making them more efficient and powerful.
Shining a light into a bacterium's belly
One project Dr. Roichman is working on tracks the effectiveness of antibiotics. Her improvements to optical microscopy will, for the first time, allow researchers to look at the internal processes within bacteria and see how different types of antibiotics attack them. More than that, her optical tweezers can isolate the bacteria to be studied, handling them without killing them.
Dr. Roichman, whose previous research was published in the journals Applied Optics and Physics Review Letters, notes that HOTs give researchers a platform with infinite possibilities. They give science a valuable tool to reach into the microscopic world - and their building potential is endless.
Source:
George Hunka
American Friends of Tel Aviv University
A new tool developed by Tel Aviv University, Holographic Optical Tweezers (HOTs) use holographic technology to manipulate up to 300 nanoparticles at a time, such as beads of glass or polymer, that are too small and delicate to be handled with traditional laboratory instruments. The technology, also known as "optical tweezers," could form the basis for tomorrow's ultra-fast, light-powered communication devices and quantum computers, says Dr. Yael Roichman of Tel Aviv University's School of Chemistry.
She's using these tweezers to build nano structures that control beams of light, aiding in the development of anything from optical microscopes to light-fuelled computer technology, she reports.
Holding onto the light
HOTS are a new family of optical tools that use a strongly-focused light beam to trap, manipulate and transform small amounts of matter. First proposed as a scientific theory in 1986 and prototyped by a University of Chicago team in 1997, holographic optical tweezers have been lauded as indispensible for researching cutting-edge ideas in physics, chemistry, and biology.
Dr. Roichman and her team of researchers are currently pioneering the use of optical tweezers to create the next generation of photonic devices. Made out of carefully arranged particles of materials such as silicon oxide and titanium oxide, these devices have the ability to insulate light, allowing less energy to be lost in transmission.
"Our invention could increase transmission speed and save energy, important for long-life batteries in computers, for instance," says Dr. Roichman.
Photons are already used in optical fibers that bring us everyday luxuries like cable TV. But Dr. Roichman says this technology can be taken much further. In her lab at Tel Aviv University, she is advancing the previous study of photonic crystals, which control and harness light, by manipulating a variety of particles to create 3D heterogeneous structures. The ability to insulate light in a novel way, preserving its potential energy, is central to this goal.
No known material today can resist the flow of light - its energy is either absorbed by, reflected off, or passed through materials. But Dr. Roichman has devised a new layering technique using special crystals central to the creation of photonic devices. These photonic crystals are arranged to create a path along which light can travel. If they're arranged correctly, she says, the light is trapped along the path.
In Dr. Roichman's approach, different materials are added to absorb or amplify light as required. She is hopeful that the ability to build these devices will transform communications, telescopic instruments, and even medical technology, making them more efficient and powerful.
Shining a light into a bacterium's belly
One project Dr. Roichman is working on tracks the effectiveness of antibiotics. Her improvements to optical microscopy will, for the first time, allow researchers to look at the internal processes within bacteria and see how different types of antibiotics attack them. More than that, her optical tweezers can isolate the bacteria to be studied, handling them without killing them.
Dr. Roichman, whose previous research was published in the journals Applied Optics and Physics Review Letters, notes that HOTs give researchers a platform with infinite possibilities. They give science a valuable tool to reach into the microscopic world - and their building potential is endless.
Source:
George Hunka
American Friends of Tel Aviv University
понедельник, 11 июля 2011 г.
Ingredient Found In Green Tea Significantly Inhibits BreastCancer Growth In Female Mice
Green tea is high in the antioxidant EGCG (epigallocatechin-3- gallate) which helps prevent the body's cells from becoming damaged and prematurely aged. Studies have suggested that the combination of green tea and EGCG may also be beneficial by providing protection against certain types of cancers, including breast cancer. A new study conducted by researchers at the University of Mississippi researchers now finds that consuming EGCG significantly inhibits breast tumor growth in female mice. These results bring us one step closer to better understanding the disease and potentially new and naturally occurring therapies.
The study was conducted by Jian-Wei Gu, Emily Young, Jordan Covington, James Wes Johnson, and Wei Tan, all of the Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu will present his team's findings, entitled, Oral Administration of EGCG, an Antioxidant Found in Green Tea, Inhibits Tumor Angiogenesis and Growth of Breast Cancer in Female Mice, at the 121st Annual Meeting of the American Physiological Society, part of the Experimental Biology 2008 scientific conference.
The Study
Epidemiological studies suggest that green tea and its major constituent, EGCG, can provide some protection against cancer. Because these studies were very limited, the anti-cancer mechanism of green tea and EGCG was not clear. As a result, the researchers examined whether drinking EGCG (just the antioxidant infused in water) inhibited the following: expression of VEGF (vascular endothelial growth factor, which is found in a variety of breast cancer types); tumor angiogenesis (thought to help tumors expand by supplying them with nutrients); and the growth of breast cancer in female mice.
Seven week old female mice were given EGCG (25 mg/50 ml) in drinking water for five weeks (approximately 50-100 mg/kg/day.) The control mice received regular drinking water. In the second week of the study mouse breast cancer cells were injected in the left fourth mammary glands of the mice. Tumor size was monitored by measuring the tumor cross section area (TCSA). Tumors were eventually isolated and measured for tumor weight, intratumoral microvessel (IM) density (using staining), and VEGF protein levels (using ELISA).
At the end of the five week period the researchers found that oral consumption of EGCG caused significant decreases in TCSA (66%), tumor weight (68%), IM density 155В±6 vs.111В±20 IM#mm^2) and VEGF protein levels (59.0В±3.7 vs. 45.7В±1.4 pg/mg) in the breast tumors vs. the control mice, respectively (N=8; P
The study was conducted by Jian-Wei Gu, Emily Young, Jordan Covington, James Wes Johnson, and Wei Tan, all of the Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS. Dr. Gu will present his team's findings, entitled, Oral Administration of EGCG, an Antioxidant Found in Green Tea, Inhibits Tumor Angiogenesis and Growth of Breast Cancer in Female Mice, at the 121st Annual Meeting of the American Physiological Society, part of the Experimental Biology 2008 scientific conference.
The Study
Epidemiological studies suggest that green tea and its major constituent, EGCG, can provide some protection against cancer. Because these studies were very limited, the anti-cancer mechanism of green tea and EGCG was not clear. As a result, the researchers examined whether drinking EGCG (just the antioxidant infused in water) inhibited the following: expression of VEGF (vascular endothelial growth factor, which is found in a variety of breast cancer types); tumor angiogenesis (thought to help tumors expand by supplying them with nutrients); and the growth of breast cancer in female mice.
Seven week old female mice were given EGCG (25 mg/50 ml) in drinking water for five weeks (approximately 50-100 mg/kg/day.) The control mice received regular drinking water. In the second week of the study mouse breast cancer cells were injected in the left fourth mammary glands of the mice. Tumor size was monitored by measuring the tumor cross section area (TCSA). Tumors were eventually isolated and measured for tumor weight, intratumoral microvessel (IM) density (using staining), and VEGF protein levels (using ELISA).
At the end of the five week period the researchers found that oral consumption of EGCG caused significant decreases in TCSA (66%), tumor weight (68%), IM density 155В±6 vs.111В±20 IM#mm^2) and VEGF protein levels (59.0В±3.7 vs. 45.7В±1.4 pg/mg) in the breast tumors vs. the control mice, respectively (N=8; P
пятница, 8 июля 2011 г.
Timing Precision In Population Coding Of Natural Scenes In The Early Visual System
The timing of spiking activity across neurons is a fundamental aspect of the neural population code. Individual neurons in the retina, thalamus, and
cortex can have very precise and repeatable responses but exhibit degraded temporal precision in response to suboptimal stimuli.
To investigate the
functional implications for neural populations in natural conditions, the authors recorded in vivo the simultaneous responses, to movies of natural
scenes, of multiple thalamic neurons likely converging to a common neuronal target in primary visual cortex. They show that the response of individual
neurons is less precise at lower contrast, but that spike timing precision across neurons is relatively insensitive to global changes in visual
contrast.
Overall, spike timing precision within and across cells is on the order of 10 ms. Since closely timed spikes are more efficient in inducing
a spike in downstream cortical neurons, and since fine temporal precision is necessary to represent the more slowly varying natural environment, we
argue that preserving relative spike timing at a;10-ms resolution is a crucial property of the neural code entering cortex.
Citation:
"Timing precision in population coding of natural scenes in the early visual system."
Desbordes G, Jin J, Weng C, Lesica NA, Stanley GB, et al. (2008)
PLoS Biol 6(12): e324. doi:10.1371/journal.pbio.0060324
Click here to view article online.
JOURNAL PLoS BIOLOGY
plosbiology
cortex can have very precise and repeatable responses but exhibit degraded temporal precision in response to suboptimal stimuli.
To investigate the
functional implications for neural populations in natural conditions, the authors recorded in vivo the simultaneous responses, to movies of natural
scenes, of multiple thalamic neurons likely converging to a common neuronal target in primary visual cortex. They show that the response of individual
neurons is less precise at lower contrast, but that spike timing precision across neurons is relatively insensitive to global changes in visual
contrast.
Overall, spike timing precision within and across cells is on the order of 10 ms. Since closely timed spikes are more efficient in inducing
a spike in downstream cortical neurons, and since fine temporal precision is necessary to represent the more slowly varying natural environment, we
argue that preserving relative spike timing at a;10-ms resolution is a crucial property of the neural code entering cortex.
Citation:
"Timing precision in population coding of natural scenes in the early visual system."
Desbordes G, Jin J, Weng C, Lesica NA, Stanley GB, et al. (2008)
PLoS Biol 6(12): e324. doi:10.1371/journal.pbio.0060324
Click here to view article online.
JOURNAL PLoS BIOLOGY
plosbiology
вторник, 5 июля 2011 г.
Mirus Bio Announces Efficient New Genetic Immunization Method To Produce Antibodies
Scientists at Mirus Bio
Corporation have developed a genetic immunization technique for making
high-quality antibodies faster and more cheaply than by conventional methods.
This proprietary process is described in the February issue of the journal
BioTechniques. It involves an innovative new method of intravenously
injecting DNA into animals, whose immune systems respond by producing
antibodies that can be harvested for subsequent use.
Antibodies are part of the body's immune system. Because they can bind to
and neutralize specific antigens, such as proteins, viruses, and cancer cells,
they have become useful tools in medical diagnosis and scientific research.
Antibodies are also used for the targeted treatment of diseases, such as
cancer.
Conventional methods of generating antibodies require the slow process of
identifying, isolating, and purifying the protein which serves as the target
antigen. The resulting protein is then injected into animals to elicit an
antibody response, after which the antibodies are harvested and used for their
intended purpose. However, due to the processes employed, such purified
proteins may not be identical to the natural antigenic protein, and therefore
may not be as potent at eliciting an immune response. They can also be very
difficult to manufacture. The cost and uncertainty of this process, both in
dollars and time, represent significant hurdles. The new technique developed
at Mirus Bio bypasses these hurdles and enables research animals to naturally
produce antigenic proteins that elicit a potent antibody response. This
offers a higher quality antibody in less time at reduced cost.
"This represents yet another breakthrough application of our nucleic acid
delivery portfolio," notes Jon A. Wolff, M.D., Mirus Bio's Chief Scientific
Officer. This research was conducted by Mary Kay Bates, Hans Herweijer,
Ph.D., and their colleagues at Mirus Bio and the University of
Wisconsin-Madison.
This research tool is available for licensing for those who wish to use it
within the biotechnology and pharmaceutical industry, either for internal
research or as part of a commercial antibody production service.
About Mirus Bio Corporation
Mirus Bio Corporation is a leader in the emerging fields of gene therapy
and RNA interference, based upon its expertise in nucleic acid chemistry and
delivery. The company currently markets state-of-the-art DNA and siRNA
transfection and labeling products to researchers worldwide. In addition, the
company is developing novel human therapeutics enabled by its proprietary
Pathway IV(TM) delivery platform. The company's lead therapeutic is a
treatment for Muscular Dystrophy, which is being developed collaboratively
with Transgene S.A. of Strasbourg, France.
Mirus Bio Corporation
mirusbio
Corporation have developed a genetic immunization technique for making
high-quality antibodies faster and more cheaply than by conventional methods.
This proprietary process is described in the February issue of the journal
BioTechniques. It involves an innovative new method of intravenously
injecting DNA into animals, whose immune systems respond by producing
antibodies that can be harvested for subsequent use.
Antibodies are part of the body's immune system. Because they can bind to
and neutralize specific antigens, such as proteins, viruses, and cancer cells,
they have become useful tools in medical diagnosis and scientific research.
Antibodies are also used for the targeted treatment of diseases, such as
cancer.
Conventional methods of generating antibodies require the slow process of
identifying, isolating, and purifying the protein which serves as the target
antigen. The resulting protein is then injected into animals to elicit an
antibody response, after which the antibodies are harvested and used for their
intended purpose. However, due to the processes employed, such purified
proteins may not be identical to the natural antigenic protein, and therefore
may not be as potent at eliciting an immune response. They can also be very
difficult to manufacture. The cost and uncertainty of this process, both in
dollars and time, represent significant hurdles. The new technique developed
at Mirus Bio bypasses these hurdles and enables research animals to naturally
produce antigenic proteins that elicit a potent antibody response. This
offers a higher quality antibody in less time at reduced cost.
"This represents yet another breakthrough application of our nucleic acid
delivery portfolio," notes Jon A. Wolff, M.D., Mirus Bio's Chief Scientific
Officer. This research was conducted by Mary Kay Bates, Hans Herweijer,
Ph.D., and their colleagues at Mirus Bio and the University of
Wisconsin-Madison.
This research tool is available for licensing for those who wish to use it
within the biotechnology and pharmaceutical industry, either for internal
research or as part of a commercial antibody production service.
About Mirus Bio Corporation
Mirus Bio Corporation is a leader in the emerging fields of gene therapy
and RNA interference, based upon its expertise in nucleic acid chemistry and
delivery. The company currently markets state-of-the-art DNA and siRNA
transfection and labeling products to researchers worldwide. In addition, the
company is developing novel human therapeutics enabled by its proprietary
Pathway IV(TM) delivery platform. The company's lead therapeutic is a
treatment for Muscular Dystrophy, which is being developed collaboratively
with Transgene S.A. of Strasbourg, France.
Mirus Bio Corporation
mirusbio
суббота, 2 июля 2011 г.
In Schizophrenia And Bipolar Disorder, Life Is Not Black And White
Schizophrenia and bipolar disorder affect tens of millions of individuals around the world. These disorders have a typical onset in the early twenties and in most cases have a chronic or recurring course. Neither disorder has an objective biological marker than can be used to make diagnoses or to guide treatment.
Findings in Biological Psychiatry, published by Elsevier suggest that electroretinography (ERG), a specialized measure of retinal function might be a useful biomarker of risk for these disorders, and retinal deficits may contribute to the perceptual problems associated with schizophrenia and bipolar disorder.
Over the past several years, research has suggested that cognitive impairments in schizophrenia might be linked to early stages of visual perception. This work is now drawing attention to the function of the retina, the component of the eye that detects light. Within the retina, rods are light sensors that respond to black and white, but not to color. Rods are particularly important for maintaining vision under conditions of low light and for detecting stimuli at the periphery of vision. Cones are light sensors that detect color and perceive stimuli at the center of vision.
Using ERG, Canadian researchers Marc HГ©bert, Michel Maziade and their colleagues observed that the ability of light to activate rods was significantly reduced in currently healthy individuals who descended from multigenerational families that had members diagnosed with either schizophrenia or bipolar disorder. In contrast, the response of their cones to light was normal.
"We take for granted that other people experience the world in the same way that we do. It is important to appreciate that for schizophrenia and bipolar disorder, as for colorblindness or selective hearing loss, people who appear to perceive the world normally may actually have subtle but important problems with perception, which may contribute to other adaptive impairments," comments Dr. John Krystal, Editor of Biological Psychiatry.
Scientists are still searching for a valid biomarker for the heritable risk for schizophrenia and bipolar disorder. Although the current data are interesting, extensive testing is still needed before the utility of this measure as a risk biomarker can be evaluated.
Source: Elsevier
Findings in Biological Psychiatry, published by Elsevier suggest that electroretinography (ERG), a specialized measure of retinal function might be a useful biomarker of risk for these disorders, and retinal deficits may contribute to the perceptual problems associated with schizophrenia and bipolar disorder.
Over the past several years, research has suggested that cognitive impairments in schizophrenia might be linked to early stages of visual perception. This work is now drawing attention to the function of the retina, the component of the eye that detects light. Within the retina, rods are light sensors that respond to black and white, but not to color. Rods are particularly important for maintaining vision under conditions of low light and for detecting stimuli at the periphery of vision. Cones are light sensors that detect color and perceive stimuli at the center of vision.
Using ERG, Canadian researchers Marc HГ©bert, Michel Maziade and their colleagues observed that the ability of light to activate rods was significantly reduced in currently healthy individuals who descended from multigenerational families that had members diagnosed with either schizophrenia or bipolar disorder. In contrast, the response of their cones to light was normal.
"We take for granted that other people experience the world in the same way that we do. It is important to appreciate that for schizophrenia and bipolar disorder, as for colorblindness or selective hearing loss, people who appear to perceive the world normally may actually have subtle but important problems with perception, which may contribute to other adaptive impairments," comments Dr. John Krystal, Editor of Biological Psychiatry.
Scientists are still searching for a valid biomarker for the heritable risk for schizophrenia and bipolar disorder. Although the current data are interesting, extensive testing is still needed before the utility of this measure as a risk biomarker can be evaluated.
Source: Elsevier
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