Fish and some amphibians possess a unique sensory capability in the so-called lateral-line system. It allows them, in effect, to "touch" objects in their surroundings without direct physical contact or to "see" in the dark. Professor Leo van Hermmen and his team in the physics department of the Technische Universitaet Muenchen are exploring the fundamental basis for this sensory system. What they discover might one day, through biomimetic engineering, better equip robots to orient themselves in their environments.
With our senses we take in only a small fraction of the information that surrounds us. Infrared light, electromagnetic waves, and ultrasound are just a few examples of the external influences that we humans can grasp only with the help of technological measuring devices - whereas some other animals use special sense organs, their own biological equipment, for the purpose. One such system found in fish and some amphibians is under investigation by the research team of Professor Leo van Hemmen, chair of theoretical biophysics at TUM, the Technische Universitaet Muenchen.
Even in murky waters hardly penetrated by light, pike and pickerel can feel out their prey before making contact. The blind Mexican cave fish can perceive structures in its surroundings and can effortlessly avoid obstacles. Catfish on the hunt follow invisible tracks that lead directly to their prey. The organ that makes this possible is the lateral-line system, which registers changes in currents and even smaller disturbances, providing backup support for the sense of sight particularly in dark or muddy waters.
This remote sensing system, at first glance mysterious, rests on measurement of the pressure distribution and velocity field in the surrounding water. The lateral-line organs responsible for this are aligned along the left and right sides of the fish's body and also surround the eyes and mouth. They consist of gelatinous, flexible, flag-like units about a tenth of a millimeter long. These so-called neuromasts - which sit either directly on the animal's skin or just underneath, in channels that water can permeate through pores - are sensitive to the slightest motion of the water. Coupled to them are hair cells similar to the acoustic pressure sensors in the human inner ear. Nerves deliver signals from the hair cells for processing in the brain, which localizes and identifies possible sources of the changes detected in the water's motion.
These changes can arise from various sources: A fish swimming by produces vibrations or waves that are directly conveyed to the lateral-line organ. Schooling fishes can recognize a nearby attacker and synchronize their swimming motion so that they resemble a single large animal. The Mexican cave fish pushes a bow wave ahead of itself, which is reflected from obstacles. The catfish takes advantage of the fact that a swimming fish that beats its tail fin leaves a trail of eddies behind. This so-called "vortex street" persists for more than a minute and can betray the prey.
For the past five years, Leo van Hemmen and his team have been investigating the capabilities of the lateral-line system and assessing the potential to translate it into technology. How broad is the operating range of such a sense organ, and what details can it reveal about moving objects? Which stimuli does the lateral-line system receive from the eddy trail of another fish, and how are these stimuli processed? To get to the bottom of these questions, the scientists develop mathematical models and compare these with experimentally observed electrical nerve signals called action potentials. The biophysicists acquire the experimental data - measurements of lateral-line organ activity in clawed frogs and cave fish - through collaboration with biologists. "Biological systems follow their own laws," van Hemmen says, "but laws that are universally valid within biology and can be described mathematically - once you find the right biophysical or biological concepts, and the right formula."
The models yield surprisingly intuitive-sounding conclusions: Fish can reliably fix the positions of other fish in terms of a distance corresponding to their own body length. Each fish broadcasts definite and distinguishing information about itself into the field of currents. So if, for example, a prey fish discloses its size and form to a possible predator within the radius of its body length, the latter can decide if a pursuit is worth the effort. This is a key finding of van Hemmen's research team.
The TUM researchers have discovered another interesting formula. With this one, the angle between a fish's axis and a vortex street can be computed from the signals that a lateral-line system acquires. The peak capability of this computation matches the best that a fish's nervous system can do. The computed values for nerve signals from an animal's sensory organ agree astonishingly well with the actual measured electrical impulses from the discharge of nerve cells. "The lateral-line sense fascinated me from the start because it's fundamentally different from other senses such as vision or hearing, not just at first glance but also the second," van Hemmen says. "It's not just that it describes a different quality of reality, but also that in place of just two eyes or ears this sense is fed by many discrete lateral-line organs - from 180 in the clawed frog to several thousand in a fish, each of which in turn is composed of several neuromasts. The integration behind it is a tour de force."
The neuronal processing and integration of diverse sense impressions into a unified mapping of reality is a major focus for van Hemmen's group. They are pursuing this same fundamental investation through the study of desert snakes' infrared perception, vibration sensors in scorpions' feet, and barn owls' hearing.
"Technology has overtaken nature in some domains," van Hemmen says, "but lags far behind in the cognitive processing of received sense impressions. My dream is to endow robots with multiple sensory modalities. Instead of always building in more cameras, we should also along the way give them additional sensors for sound and touch." With a sense modeled on the lateral-line system, but which would function as well in air as under water, robots might for example move safely among crowds of people. But such a system also offers many promising applications in the water. Underwater robots could use it to orient themselves during the exploration of inaccessible cave systems and deep-sea volcanoes. Autonomous submarines could also locate obstacles in turbid water. Such an underwater vehicle is currently being developed within the framework of the EU project CILIA, in collaboration with the TUM chair for guidance and control technology.
Further research includes collaborations with the excellence cluster CoTeSys (Cognition for Technical Systems) and the newly created Leonardo da Vinci Center for Bionics at TUM, as well as with the chair for humanoid robots and the Bernstein Center for Computational Neuroscience.
Original papers:
"Hydrodynamic Object Recognition: When Multipoles Count," Andreas B. Sichert, Robert Bamler, and J. Leo van Hemmen, Physical Review Letters, 102, 058104 (2009)
Link: dx.doi/10.1103/PhysRevLett.102.058104
"Wake Tracking and the Detection of Vortex Rings by the Canal Lateral Line of Fish," Jan-Moritz P. Franosch, Hendrik J. A. Hagedorn, Julie Goulet, Jacob Engelmann, and J. Leo van Hemmen, Physical Review Letters 103, 078102 (2009)
Link: dx.doi/10.1103/PhysRevLett.103.078102
See also: "Following in the wake," Nature 460, 1061 (27 August 2009)
Link: dx.doi/10.1038/4601061a
Source:
Patrick Regan
Technische Universitaet Muenchen
понедельник, 6 июня 2011 г.
Phylonix Awarded National Science Foundation Phase II SBIR For Zebrafish Screening
Phylonix Pharmaceuticals, Inc. has announced it has received a $500,000 Phase II Small Business Innovation Grant (SBIR) from the National Science Foundation to assess potential toxic effects of chemicals on the development of human organs and tissues using a panel of assays performed in zebrafish.
"This award validates the importance of zebrafish as a predictive model for assessing toxic effects of environmental contaminants on mammalian development," commented Patricia McGrath, Phylonix President and Chief Executive Officer. "Our preliminary data show a striking correlation between results in zebrafish and results in mammals."
All essential components of vertebrate form and organ development are mimicked in the transparent zebrafish and their molecular basis is either identical or similar, underscoring the potential for use in research on human developmental toxicity. "Using our comprehensive ZETAXTM panel of assays, effects on morphology, organ development, neurons and cell death can easily be assessed in the transparent animal. Compounds are added directly to the fish water and results are assessed in 4 to 7 days. Endpoints can be quantitated using comparatively high through-put scanning image analysis or microplate formats," McGrath continued.
Currently, 85,000 industrial chemicals are manufactured each year in the United States and 2,000 to 3,000 new chemicals are registered for production. However, there is little or no toxicity data for more than 70% of these chemicals. The lack of efficient in vivo screening assays contributes to the lack of knowledge about short and long-term chemical effects on development. Pesticides are of particular concern, since they are designed to be toxic to insects and they can have deleterious effects on other species.
Historically, zebrafish have been used in a variety of applications to assess environmental toxicity, including directly monitoring water, soil and wastewater quality for ecotoxicity studies. However, a systematic analysis of effects in vivo in this model organism has not been performed.
About Phylonix
Phylonix Pharmaceuticals, Inc. (phylonix) is a Contract Research Organization developing and marketing novel in vivo zebrafish-based assays, eZ-ScreensTM, for assessing chemical and drug effects on developmental defects, cancers, central nervous system disorders, cardiovascular diseases, apoptosis, and organ toxicity. The company's business strategy is to leverage the speed and cost-effectiveness of the zebrafish model to provide services for industrial and biopharmaceutical companies.
Contact: Patricia McGrath
Phylonix
"This award validates the importance of zebrafish as a predictive model for assessing toxic effects of environmental contaminants on mammalian development," commented Patricia McGrath, Phylonix President and Chief Executive Officer. "Our preliminary data show a striking correlation between results in zebrafish and results in mammals."
All essential components of vertebrate form and organ development are mimicked in the transparent zebrafish and their molecular basis is either identical or similar, underscoring the potential for use in research on human developmental toxicity. "Using our comprehensive ZETAXTM panel of assays, effects on morphology, organ development, neurons and cell death can easily be assessed in the transparent animal. Compounds are added directly to the fish water and results are assessed in 4 to 7 days. Endpoints can be quantitated using comparatively high through-put scanning image analysis or microplate formats," McGrath continued.
Currently, 85,000 industrial chemicals are manufactured each year in the United States and 2,000 to 3,000 new chemicals are registered for production. However, there is little or no toxicity data for more than 70% of these chemicals. The lack of efficient in vivo screening assays contributes to the lack of knowledge about short and long-term chemical effects on development. Pesticides are of particular concern, since they are designed to be toxic to insects and they can have deleterious effects on other species.
Historically, zebrafish have been used in a variety of applications to assess environmental toxicity, including directly monitoring water, soil and wastewater quality for ecotoxicity studies. However, a systematic analysis of effects in vivo in this model organism has not been performed.
About Phylonix
Phylonix Pharmaceuticals, Inc. (phylonix) is a Contract Research Organization developing and marketing novel in vivo zebrafish-based assays, eZ-ScreensTM, for assessing chemical and drug effects on developmental defects, cancers, central nervous system disorders, cardiovascular diseases, apoptosis, and organ toxicity. The company's business strategy is to leverage the speed and cost-effectiveness of the zebrafish model to provide services for industrial and biopharmaceutical companies.
Contact: Patricia McGrath
Phylonix
In New Way To Manipulate Matter, Mechanics Meets Chemistry
The inventors of self-healing plastic have come up with another invention: a new way of doing chemistry.
Researchers at the University of Illinois at Urbana-Champaign have found a novel way to manipulate matter and drive chemical reactions along a desired direction. The new technique utilizes mechanical force to alter the course of chemical reactions and yield products not obtainable through conventional conditions.
Potential applications include materials that more readily repair themselves, or clearly indicate when they have been damaged.
"This is a fundamentally new way of doing chemistry," said Jeffrey Moore, a William H. and Janet Lycan Professor of Chemistry at Illinois and corresponding author of a paper that describes the technique in the March 22 issue of the journal Nature.
"By harnessing mechanical energy, we can go into molecules and pull on specific bonds to drive desired reactions," said Moore, who also is a researcher at the Frederick Seitz Materials Laboratory on campus and at the university's Beckman Institute for Advanced Science and Technology. The directionally specific nature of mechanical force makes this approach to reaction control fundamentally different from the usual chemical and physical constraints. To demonstrate the technique, Moore and colleagues placed a mechanically active molecule - called a mechanophore - at the center of a long polymer chain. The polymer chain was then stretched in opposite directions by a flow field created by the collapse of cavitating bubbles produced by ultrasound, subjecting the mechanophore to a mechanical tug of war.
"We created a situation where a chemical reaction could go down one of two pathways," Moore said. "By applying force to the mechanophore, we could bias which of those pathways the reaction chose to follow."
One potential application of the technique is as a trigger to divert mechanical energy stored in stressed polymers into chemical pathways such as self-healing reactions.
In the original self-healing concept, microcapsules of healing agent are ruptured when a crack forms in the material. Capillary action then transports the healing agent to the crack, where it mixes with a chemical catalyst, and polymerization takes place.
With new mechanical triggers, however, mechanical energy would initiate the polymerization directly, thereby skipping many steps. The cross-linking of neighboring chains would prevent further propagation of a crack and avoid additional damage.
"We have demonstrated that it is now possible to use mechanical force to steer chemical reactions along pathways that are unattainable by conventional means," Moore said. "We look forward to developing additional mechanophores whose chemical reactivity will be activated by external force."
The other authors of the paper besides Moore are graduate student and lead author Charles Hickenboth, aerospace engineering professor Scott White, materials science and engineering professor Nancy Sottos, and research chemists Scott Wilson and Jerome Baudry. White, Sottos and Moore co-invented self-healing plastic.
The work was supported by the U.S. Air Force Office of Scientific Research and the Petroleum Research Fund.
Contact: James E. Kloeppel
University of Illinois at Urbana-Champaign
Researchers at the University of Illinois at Urbana-Champaign have found a novel way to manipulate matter and drive chemical reactions along a desired direction. The new technique utilizes mechanical force to alter the course of chemical reactions and yield products not obtainable through conventional conditions.
Potential applications include materials that more readily repair themselves, or clearly indicate when they have been damaged.
"This is a fundamentally new way of doing chemistry," said Jeffrey Moore, a William H. and Janet Lycan Professor of Chemistry at Illinois and corresponding author of a paper that describes the technique in the March 22 issue of the journal Nature.
"By harnessing mechanical energy, we can go into molecules and pull on specific bonds to drive desired reactions," said Moore, who also is a researcher at the Frederick Seitz Materials Laboratory on campus and at the university's Beckman Institute for Advanced Science and Technology. The directionally specific nature of mechanical force makes this approach to reaction control fundamentally different from the usual chemical and physical constraints. To demonstrate the technique, Moore and colleagues placed a mechanically active molecule - called a mechanophore - at the center of a long polymer chain. The polymer chain was then stretched in opposite directions by a flow field created by the collapse of cavitating bubbles produced by ultrasound, subjecting the mechanophore to a mechanical tug of war.
"We created a situation where a chemical reaction could go down one of two pathways," Moore said. "By applying force to the mechanophore, we could bias which of those pathways the reaction chose to follow."
One potential application of the technique is as a trigger to divert mechanical energy stored in stressed polymers into chemical pathways such as self-healing reactions.
In the original self-healing concept, microcapsules of healing agent are ruptured when a crack forms in the material. Capillary action then transports the healing agent to the crack, where it mixes with a chemical catalyst, and polymerization takes place.
With new mechanical triggers, however, mechanical energy would initiate the polymerization directly, thereby skipping many steps. The cross-linking of neighboring chains would prevent further propagation of a crack and avoid additional damage.
"We have demonstrated that it is now possible to use mechanical force to steer chemical reactions along pathways that are unattainable by conventional means," Moore said. "We look forward to developing additional mechanophores whose chemical reactivity will be activated by external force."
The other authors of the paper besides Moore are graduate student and lead author Charles Hickenboth, aerospace engineering professor Scott White, materials science and engineering professor Nancy Sottos, and research chemists Scott Wilson and Jerome Baudry. White, Sottos and Moore co-invented self-healing plastic.
The work was supported by the U.S. Air Force Office of Scientific Research and the Petroleum Research Fund.
Contact: James E. Kloeppel
University of Illinois at Urbana-Champaign
Similar Influence Found Of Sex And Handedness On Brain In Capuchin Monkeys And Humans
Capuchin monkeys are playful, inquisitive primates known for their manual dexterity, complex social behavior, and cognitive abilities. New research now shows that just like humans, they display a fundamental sex difference in the organization of the brain, specifically in the corpus callosum, the region that connects the two cerebral lobes.
A recently published paper by Associate Professor of Psychology and Biology Kimberley A. Phillips (Hiram College), Chet C. Sherwood (George Washington University) and Alayna L. Lilak (Hiram College), reports finding both sex and handedness influences on the relative size of the corpus callosum. The researchers' contribution appears in PLoS ONE, the online, open-access journal of the Public Library of Science. The paper can be read at: plosone/doi/pone.0000792.
In the study, thirteen adult capuchins underwent magnetic resonance imaging of the brain to determine the size of their corpus callosum, which is the major white matter tract connecting the left and right cerebral hemispheres. The monkeys were later given a task to determine hand preference. The authors' results led them to conclude that, as in humans, male capuchins have a smaller relative size of the corpus callosum than females, and right-handed individuals have a smaller relative size of the corpus callosum than left-handed individuals.
As the two hemispheres show greater independence of function, the relative size of the corpus callosum is expected to be smaller. This has been documented in humans, and same pattern was found in capuchins. Phillips and her co-authors hypothesize their results are related to hemispheric specialization for complex foraging tasks that require the integration of motor actions and visuospatial information. In the wild, capuchin monkeys utilize both arboreal and terrestrial substrates and are also noted for being very adept at capturing small rapid prey, such as birds, lizards, and squirrels.
While such research frequently is associated with large research universities, Phillips says scientists at small liberal arts colleges such as Hiram often do not receive enough credit and, especially, for involving undergraduates, such as Lilak, in their work.
"It is not where you are," Phillips says. "It is the quality of the science, and scientists at small liberal arts colleges can and do conduct high-quality research. Undergraduates are an integral part of my research team - they participate in lab meetings, brainstorming, sharing ideas. They are colleagues in my lab. They just need a little more mentoring."
Disclaimer
The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.
At Hiram College, Phillips typically has six to eight students working in her laboratory. Alayna Lilak, who received her degree in psychology in May, has recently begun a job as a research technician in a Stanford University lab.
Citation: Phillips KA, Sherwood CC, Lilak AL (2007) Corpus Callosum Morphology in Capuchin Monkeys Is Influenced by Sex and Handedness. PLoS ONE 2(8): e792.doi:10.1371/journal.pone.0000792
Click here for a link to the published article.
Source: Steve Love
Public Library of Science
A recently published paper by Associate Professor of Psychology and Biology Kimberley A. Phillips (Hiram College), Chet C. Sherwood (George Washington University) and Alayna L. Lilak (Hiram College), reports finding both sex and handedness influences on the relative size of the corpus callosum. The researchers' contribution appears in PLoS ONE, the online, open-access journal of the Public Library of Science. The paper can be read at: plosone/doi/pone.0000792.
In the study, thirteen adult capuchins underwent magnetic resonance imaging of the brain to determine the size of their corpus callosum, which is the major white matter tract connecting the left and right cerebral hemispheres. The monkeys were later given a task to determine hand preference. The authors' results led them to conclude that, as in humans, male capuchins have a smaller relative size of the corpus callosum than females, and right-handed individuals have a smaller relative size of the corpus callosum than left-handed individuals.
As the two hemispheres show greater independence of function, the relative size of the corpus callosum is expected to be smaller. This has been documented in humans, and same pattern was found in capuchins. Phillips and her co-authors hypothesize their results are related to hemispheric specialization for complex foraging tasks that require the integration of motor actions and visuospatial information. In the wild, capuchin monkeys utilize both arboreal and terrestrial substrates and are also noted for being very adept at capturing small rapid prey, such as birds, lizards, and squirrels.
While such research frequently is associated with large research universities, Phillips says scientists at small liberal arts colleges such as Hiram often do not receive enough credit and, especially, for involving undergraduates, such as Lilak, in their work.
"It is not where you are," Phillips says. "It is the quality of the science, and scientists at small liberal arts colleges can and do conduct high-quality research. Undergraduates are an integral part of my research team - they participate in lab meetings, brainstorming, sharing ideas. They are colleagues in my lab. They just need a little more mentoring."
Disclaimer
The following press release refers to an upcoming article in PLoS ONE. The release has been provided by the article authors and/or their institutions. Any opinions expressed in this are the personal views of the contributors, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the release and article and your use of such information.
At Hiram College, Phillips typically has six to eight students working in her laboratory. Alayna Lilak, who received her degree in psychology in May, has recently begun a job as a research technician in a Stanford University lab.
Citation: Phillips KA, Sherwood CC, Lilak AL (2007) Corpus Callosum Morphology in Capuchin Monkeys Is Influenced by Sex and Handedness. PLoS ONE 2(8): e792.doi:10.1371/journal.pone.0000792
Click here for a link to the published article.
Source: Steve Love
Public Library of Science
Identification Of The Molecule That Helps The Sleep-Deprived To Mentally Rebound
Sleep experts know that the mental clarity lost because of a few sleepless nights can often be restored with a good night's rest. Now, UT Southwestern Medical Center researchers have identified a key molecular mechanism that regulates the brain's ability to mentally compensate for sleep deprivation.
Working with mice, they found that a molecule called an adenosine receptor is necessary for sleep-restricted animals to attain adequate levels of slow-wave activity in the brain once normal sleep resumes. It is this increase in slow-wave activity, or SWA, during rebound sleep that helps restore normal working memory and attention skills to the sleep-deprived, the scientists report in the Feb. 4 issue of the Journal of Neuroscience.
"Normal society pushes people to burn candles at both ends - going to bed late, getting up early, and somehow performing mentally with lack of adequate sleep," said senior author Dr. Robert Greene, professor of psychiatry at UT Southwestern. "We need to have our adenosine receptors intact to do that."
Adenosine receptors on nerve cells, including brain cells, are akin to docking points for the molecule adenosine. Adenosine levels increase in the brain with each hour of waking activity, and "docking" of the molecule with its receptor is shown in this study to help promote the slow-wave activity of sleep. Scientists have known that recovery from sleep deprivation involves not only an increase in sleep time, or rebound sleep, but also an elevation in this slow-wave activity.
To investigate how adenosine receptors and SWA might be linked, Dr. Greene and his team engineered mice that lacked a receptor to pair up with adenosine.
Sleep-restricted mice were kept awake by being placed on a moving treadmill. Researchers then electronically monitored sleep and waking activity of both normal and genetically engineered mice, including monitoring electronically the brain waves of the animals. The mice also traveled a maze with eight paths, each with a piece of chocolate at the end of it.
Electronic measurements showed that, unlike normal mice, the mice lacking the adenosine receptor could not increase the intensity of their slow-wave activity in response to the sleep deprivation. Under normal sleep conditions both the normal and mutant mice were almost error-free on the maze test. However, when sleep-deprived, the engineered mice made significantly more errors on the maze test than their normal counterparts. This type of skills test represents the human equivalent of the attention and working memory needed to multitask or build on tasks already done, such as being given a phone number, reaching for a pen to write it down and recalling the number, said Dr. Greene.
Linking the lack of functioning adenosine receptors to depressed normal SWA rebound response might aid in developing treatments for people with sleep-related cognitive deficits, he said.
The research also further explains the effects of caffeine, which also "docks" to adenosine receptors, preventing the docking of adenosine and keeping the caffeine-drinker awake. Dr. Greene compared the study mice's behavior response on the maze test to how a person drinking a "permanent cup of coffee" might behave.
"They probably won't get the regular amount of slow-wave activity or deep sleep as they normally would," Dr. Greene said. "This is not to say that coffee is bad, but drinking it all the time or in the evening could affect your mental performance the next day."
The researchers next will investigate the relationship between sleep, adenosine and energy metabolism, a biological process in which adenosine plays a key role.
Other researchers from UT Southwestern involved in the study were lead author Dr. Theresa Bjorness, postdoctoral research fellow in psychiatry, and Virginia Poffenberger, research technician in psychiatry.
The study was funded by the U.S. Department of Veterans Affairs and the National Institutes of Health.
Visit utsouthwestern/neurosciences to learn more about UT Southwestern's clinical services in the neurosciences, including psychiatry.
Source: LaKisha Ladson
UT Southwestern Medical Center
Working with mice, they found that a molecule called an adenosine receptor is necessary for sleep-restricted animals to attain adequate levels of slow-wave activity in the brain once normal sleep resumes. It is this increase in slow-wave activity, or SWA, during rebound sleep that helps restore normal working memory and attention skills to the sleep-deprived, the scientists report in the Feb. 4 issue of the Journal of Neuroscience.
"Normal society pushes people to burn candles at both ends - going to bed late, getting up early, and somehow performing mentally with lack of adequate sleep," said senior author Dr. Robert Greene, professor of psychiatry at UT Southwestern. "We need to have our adenosine receptors intact to do that."
Adenosine receptors on nerve cells, including brain cells, are akin to docking points for the molecule adenosine. Adenosine levels increase in the brain with each hour of waking activity, and "docking" of the molecule with its receptor is shown in this study to help promote the slow-wave activity of sleep. Scientists have known that recovery from sleep deprivation involves not only an increase in sleep time, or rebound sleep, but also an elevation in this slow-wave activity.
To investigate how adenosine receptors and SWA might be linked, Dr. Greene and his team engineered mice that lacked a receptor to pair up with adenosine.
Sleep-restricted mice were kept awake by being placed on a moving treadmill. Researchers then electronically monitored sleep and waking activity of both normal and genetically engineered mice, including monitoring electronically the brain waves of the animals. The mice also traveled a maze with eight paths, each with a piece of chocolate at the end of it.
Electronic measurements showed that, unlike normal mice, the mice lacking the adenosine receptor could not increase the intensity of their slow-wave activity in response to the sleep deprivation. Under normal sleep conditions both the normal and mutant mice were almost error-free on the maze test. However, when sleep-deprived, the engineered mice made significantly more errors on the maze test than their normal counterparts. This type of skills test represents the human equivalent of the attention and working memory needed to multitask or build on tasks already done, such as being given a phone number, reaching for a pen to write it down and recalling the number, said Dr. Greene.
Linking the lack of functioning adenosine receptors to depressed normal SWA rebound response might aid in developing treatments for people with sleep-related cognitive deficits, he said.
The research also further explains the effects of caffeine, which also "docks" to adenosine receptors, preventing the docking of adenosine and keeping the caffeine-drinker awake. Dr. Greene compared the study mice's behavior response on the maze test to how a person drinking a "permanent cup of coffee" might behave.
"They probably won't get the regular amount of slow-wave activity or deep sleep as they normally would," Dr. Greene said. "This is not to say that coffee is bad, but drinking it all the time or in the evening could affect your mental performance the next day."
The researchers next will investigate the relationship between sleep, adenosine and energy metabolism, a biological process in which adenosine plays a key role.
Other researchers from UT Southwestern involved in the study were lead author Dr. Theresa Bjorness, postdoctoral research fellow in psychiatry, and Virginia Poffenberger, research technician in psychiatry.
The study was funded by the U.S. Department of Veterans Affairs and the National Institutes of Health.
Visit utsouthwestern/neurosciences to learn more about UT Southwestern's clinical services in the neurosciences, including psychiatry.
Source: LaKisha Ladson
UT Southwestern Medical Center
Environmental Problems Could Be Reduced By More Recycling On The Farm
Growing environmental problems resulting from farming argue for a shift toward practices that use lower inputs of pesticides and energy and more recycling of energy and materials, according to an article published in the May 2007 issue of BioScience. The author, Craig J. Pearson of the University of Guelph, documents how semiclosed agricultural systems -- which he terms "regenerative" -- could enhance global sustainability of biological resources, curtail greenhouse gas emissions and groundwater contamination, and reduce farming's reliance on oil imports and water.
A switch to regenerative agriculture would involve a variety of changes, including reduced use of inorganic fertilizers and more on-farm energy generation from wind and fermentation of biosolids. It would also reduce overcropping and leakage from manure storage that contaminates groundwater. Yet despite similarities, Pearson's concept of regenerative agriculture is distinct from organic farming; for example, regenerative agriculture could use some chemically treated fertilizer and would exploit robotic systems.
The approach would entail more use of human labor, which is costly, and may reduce output per unit area farmed. Pearson summarizes studies of organic farming suggesting, however, that price premiums could overcome this disadvantage, and points out that social benefits could be expected. Pearson argues that existing funding programs for farmers could be modified to encourage more regenerative agriculture, and suggests that philanthropists and professional bodies could stimulate its uptake.
BioScience, which is published by the American Institute of Biological Sciences (AIBS), publishes commentary and peer-reviewed articles covering a wide range of biological fields, with a focus on "organisms from molecules to the environment." The journal has been published since 1964. AIBS is an umbrella organization for professional scientific societies and organizations that are involved with biology. It represents some 200 member societies and organizations with a combined membership of about 250,000.
Contact: Samantha Katz
American Institute of Biological Sciences
A switch to regenerative agriculture would involve a variety of changes, including reduced use of inorganic fertilizers and more on-farm energy generation from wind and fermentation of biosolids. It would also reduce overcropping and leakage from manure storage that contaminates groundwater. Yet despite similarities, Pearson's concept of regenerative agriculture is distinct from organic farming; for example, regenerative agriculture could use some chemically treated fertilizer and would exploit robotic systems.
The approach would entail more use of human labor, which is costly, and may reduce output per unit area farmed. Pearson summarizes studies of organic farming suggesting, however, that price premiums could overcome this disadvantage, and points out that social benefits could be expected. Pearson argues that existing funding programs for farmers could be modified to encourage more regenerative agriculture, and suggests that philanthropists and professional bodies could stimulate its uptake.
BioScience, which is published by the American Institute of Biological Sciences (AIBS), publishes commentary and peer-reviewed articles covering a wide range of biological fields, with a focus on "organisms from molecules to the environment." The journal has been published since 1964. AIBS is an umbrella organization for professional scientific societies and organizations that are involved with biology. It represents some 200 member societies and organizations with a combined membership of about 250,000.
Contact: Samantha Katz
American Institute of Biological Sciences
Pacific Rim researchers to collaborate on distributed bioinformatics analysis of avian flu
Researchers at the University of California, San Diego and the University of Hawaii will use bioinformatics, grid computing and networking infrastructure, as well as collaborative ties to Asian institutions to learn more about avian flu, in hopes of helping to head off a much-feared pandemic in the region of the world where the disease has already cost human lives.
"We will use modern high-throughput biology to annotate the biological structures of different subtypes of the avian influenza virus, at the same time as we study their variations," said principal investigator Peter Arzberger, director of Life Science Initiatives at UC San Diego. "We will also construct a grid infrastructure to support avian flu research - an infrastructure that could one day handle research on other infectious diseases as well."
Added Arzberger: "Fighting a pandemic will also be easier if we put in place the infrastructure to replicate data, support medical informatics, and even assist in remote diagnosis."
UC San Diego will lead the one-year project, with more than $350,000 in funding from the Telemedicine and Advanced Technology Research Center (TATRC), part of the U.S. Army Medical Research and Material Command (USAMRMC). TATRC invests in telemedicine and advanced medical technologies in order to deliver world-class health care to military personnel. The increasing frequency of biological events relevant to national security, and current disease surveillance systems in the United States (U.S.) require an integrated computational environment to support easy access to a set of universal tools, novel algorithmic approaches and tracking mechanisms for reproducibility at a global level.
Having Asian researchers involved in the TATRC-funded project lends an added dimension of urgency and depth to the U.S. research program. "Avian flu is very important to sites worldwide, but especially in Asia, where most of the known cases have occurred," said Wilfred Li, executive director of the UC San Diego-based National Biomedical Computation Resource (NBCR). "This partnership will give U.S. researchers enhanced access to new genomic information as it becomes available in the region. It will also promote global cooperation in case of a flu pandemic." Institutions in three Asian nations will leverage TATRC's investment by funding their own researchers to work with their counterparts in California and Hawaii, as part of their ongoing collaboration in the National Science Foundation-funded Pacific Rim Applications and Grid Middleware Assembly (PRAGMA).
"We could not be successful in this project without the substantial prior investment in partnerships with our friends and colleagues across the Pacific," said Arzberger, who directs the five-year-old PRAGMA initiative. "We will be able to hit the ground running thanks to the shared expertise, interconnected cyberinfrastructure, grid-enabled software tools and student exchange programs that have emerged out of PRAGMA."
Pacific Rim institutions collaborate in PRAGMA to develop grid-enabled applications and coordinate deployment of the needed infrastructure throughout the Pacific region to allow data, computing, and other resource sharing. The announcement of the TATRC award coincided with PRAGMA 12, which ran March 20-22 in Bangkok, Thailand. The meeting was hosted by Thailand's National Electronics and Computer Technology Center (NECTEC), and the Thai National Grid Center (TGNC).
Five non-U.S. partners have pledged to fund collaboration on the avian flu virus project: Japan's National Institute for Advanced Industrial Science and Technology (AIST); China's Jilin University (JLU) and Computer Network Information Center (CNIC); as well as the Korea Institute for Science and Technology Information (KISTI) and Konkuk University (KU). Significantly, Malaysia's Universiti Sains Malaysia (USM) has pledged new funding for the collaborative project at the PRAGMA 12 workshop.
Flu vaccines are usually developed using attenuated viruses, but the new focus is on the use of reverse genetics techniques to combat emerging bird flu pandemic threats. To that end, researchers intend to:
* Characterize the function of the influenza viruses using a structure-based approach;
* Develop simulations of the molecular dynamics involving interactions among major factors that may determine the virulence of a virus; and
* Test whether the multinational collaboration can establish a successful, large-scale, distributed computational data grid.
Scientists at UC San Diego, the California Institute for Telecommunications and Information Technology (Calit2) and San Diego Supercomputer Center (SDSC) will use bioinformatics software, including the integrated Genome Analysis Pipeline (iGAP), to analyze avian flu genomes. (The iGAP suite of bioinformatics applications are designed specifically for protein structural homology recognition and functional annotation.) The San Diego-based researchers will also develop a robust production environment for routine computational analysis, using PRAGMA member-developed tools, including Grid Datafarm (Gfarm) and Community Scheduler Framework (CSF4), while making any new software publicly available through open-source licenses.
The funding to the University of Hawaii will allow it to become a node in the computational grid - allowing it to access data for molecular-dynamics simulations using high-performance computing. "We need a better way to gain insight into the interactions among factors determining how virulent a particular type of flu might be, and this will require a lot of raw computing power," said Maqsudul Alam, director at the Advance Studies in Genomics, Proteomics and Bioinformatics, College of Natural Sciences, University of Hawaii. "This will allow us to analyze the biosynthetic pathways of viruses as well as the signal transduction pathways for clues to understanding how avian flu interferes with human metabolism."
The Asian institutions - all members of PRAGMA - will host some U.S. students and researchers, while taking responsibility for specific tasks:
* JLU will support the scheduling of multiple clusters (CSF4) to distribute jobs transparently at multiple sites around the region;
* AIST will support the deployment of Gfarm in conjunction with researchers at the University of Tsukuba;
* KISTI in conjunction with researchers at KU in Korea will create an integrated portal environment for the computational pipeline using results of Korea National e-Science Project by the Korean Ministry of Science and Technology (MOST); and
* CNIC will develop a transparent web service layer for data access.
* USM will contribute its natural compound database for use in virtual screening for new inhibitors and drug discovery.
CNIC will also become the central repository for the project's research data. The database will be distributed through the computational data grid, and accessible through web portals mirrored at partner sites. "The availability of a central repository that is built upon distributed information and data storage not only allows one to collect information more effectively, but also makes the data immediately available to researchers worldwide," said Kai Nan, director of CNIC's Network Technology and Applications Research Laboratory. "The end result is a dynamic research community response network that can meet the needs of a global response to a global threat such as the avian flu."
Much of the nitty-gritty work on the avian flu project will be done by students, at both the graduate and undergraduate level. "We'll be engaging students from the above institutions as an international research team," said NBCR's Li. "We will also send U.S. students and graduate researchers to work in the labs of our partners around Asia - giving those students an experience that will equip them to do ongoing research in this field." This activity also leverages NSF's investment in the Pacific Rim undergraduate Education (PRIME) project, an undergraduate research abroad program awarded to UCSD.
"The next step for PRAGMA is a pragmatic one - to demonstrate that international team science can address pressing challenges in a way that might not be possible in one institution or just one country," said Arzberger. "We expect that this project will engage other researchers, both in other PRAGMA sites, e.g., at USM in Malaysia, and also at the National Biomedical Computation Resource, through the complementary, ongoing Avian flu Drug Discovery project led by professors J. Andrew McCammon and Art Olson of NBCR, by sharing expertise and resources."
Related Links
TATRC tatrc
PRAGMA pragma-grid/
PRAGMA 12 pragma12.thai-research/pragma12/index.php/Main_Page
NECTEC nectec.or.th/
TGNC thaigrid.or.th/index.php
NBCR nbcr
PRIME prime.ucsd
Calit2 calit2
SDSC sdsc
UCSD ucsd
Contact: Doug Ramsey
University of California - San Diego
"We will use modern high-throughput biology to annotate the biological structures of different subtypes of the avian influenza virus, at the same time as we study their variations," said principal investigator Peter Arzberger, director of Life Science Initiatives at UC San Diego. "We will also construct a grid infrastructure to support avian flu research - an infrastructure that could one day handle research on other infectious diseases as well."
Added Arzberger: "Fighting a pandemic will also be easier if we put in place the infrastructure to replicate data, support medical informatics, and even assist in remote diagnosis."
UC San Diego will lead the one-year project, with more than $350,000 in funding from the Telemedicine and Advanced Technology Research Center (TATRC), part of the U.S. Army Medical Research and Material Command (USAMRMC). TATRC invests in telemedicine and advanced medical technologies in order to deliver world-class health care to military personnel. The increasing frequency of biological events relevant to national security, and current disease surveillance systems in the United States (U.S.) require an integrated computational environment to support easy access to a set of universal tools, novel algorithmic approaches and tracking mechanisms for reproducibility at a global level.
Having Asian researchers involved in the TATRC-funded project lends an added dimension of urgency and depth to the U.S. research program. "Avian flu is very important to sites worldwide, but especially in Asia, where most of the known cases have occurred," said Wilfred Li, executive director of the UC San Diego-based National Biomedical Computation Resource (NBCR). "This partnership will give U.S. researchers enhanced access to new genomic information as it becomes available in the region. It will also promote global cooperation in case of a flu pandemic." Institutions in three Asian nations will leverage TATRC's investment by funding their own researchers to work with their counterparts in California and Hawaii, as part of their ongoing collaboration in the National Science Foundation-funded Pacific Rim Applications and Grid Middleware Assembly (PRAGMA).
"We could not be successful in this project without the substantial prior investment in partnerships with our friends and colleagues across the Pacific," said Arzberger, who directs the five-year-old PRAGMA initiative. "We will be able to hit the ground running thanks to the shared expertise, interconnected cyberinfrastructure, grid-enabled software tools and student exchange programs that have emerged out of PRAGMA."
Pacific Rim institutions collaborate in PRAGMA to develop grid-enabled applications and coordinate deployment of the needed infrastructure throughout the Pacific region to allow data, computing, and other resource sharing. The announcement of the TATRC award coincided with PRAGMA 12, which ran March 20-22 in Bangkok, Thailand. The meeting was hosted by Thailand's National Electronics and Computer Technology Center (NECTEC), and the Thai National Grid Center (TGNC).
Five non-U.S. partners have pledged to fund collaboration on the avian flu virus project: Japan's National Institute for Advanced Industrial Science and Technology (AIST); China's Jilin University (JLU) and Computer Network Information Center (CNIC); as well as the Korea Institute for Science and Technology Information (KISTI) and Konkuk University (KU). Significantly, Malaysia's Universiti Sains Malaysia (USM) has pledged new funding for the collaborative project at the PRAGMA 12 workshop.
Flu vaccines are usually developed using attenuated viruses, but the new focus is on the use of reverse genetics techniques to combat emerging bird flu pandemic threats. To that end, researchers intend to:
* Characterize the function of the influenza viruses using a structure-based approach;
* Develop simulations of the molecular dynamics involving interactions among major factors that may determine the virulence of a virus; and
* Test whether the multinational collaboration can establish a successful, large-scale, distributed computational data grid.
Scientists at UC San Diego, the California Institute for Telecommunications and Information Technology (Calit2) and San Diego Supercomputer Center (SDSC) will use bioinformatics software, including the integrated Genome Analysis Pipeline (iGAP), to analyze avian flu genomes. (The iGAP suite of bioinformatics applications are designed specifically for protein structural homology recognition and functional annotation.) The San Diego-based researchers will also develop a robust production environment for routine computational analysis, using PRAGMA member-developed tools, including Grid Datafarm (Gfarm) and Community Scheduler Framework (CSF4), while making any new software publicly available through open-source licenses.
The funding to the University of Hawaii will allow it to become a node in the computational grid - allowing it to access data for molecular-dynamics simulations using high-performance computing. "We need a better way to gain insight into the interactions among factors determining how virulent a particular type of flu might be, and this will require a lot of raw computing power," said Maqsudul Alam, director at the Advance Studies in Genomics, Proteomics and Bioinformatics, College of Natural Sciences, University of Hawaii. "This will allow us to analyze the biosynthetic pathways of viruses as well as the signal transduction pathways for clues to understanding how avian flu interferes with human metabolism."
The Asian institutions - all members of PRAGMA - will host some U.S. students and researchers, while taking responsibility for specific tasks:
* JLU will support the scheduling of multiple clusters (CSF4) to distribute jobs transparently at multiple sites around the region;
* AIST will support the deployment of Gfarm in conjunction with researchers at the University of Tsukuba;
* KISTI in conjunction with researchers at KU in Korea will create an integrated portal environment for the computational pipeline using results of Korea National e-Science Project by the Korean Ministry of Science and Technology (MOST); and
* CNIC will develop a transparent web service layer for data access.
* USM will contribute its natural compound database for use in virtual screening for new inhibitors and drug discovery.
CNIC will also become the central repository for the project's research data. The database will be distributed through the computational data grid, and accessible through web portals mirrored at partner sites. "The availability of a central repository that is built upon distributed information and data storage not only allows one to collect information more effectively, but also makes the data immediately available to researchers worldwide," said Kai Nan, director of CNIC's Network Technology and Applications Research Laboratory. "The end result is a dynamic research community response network that can meet the needs of a global response to a global threat such as the avian flu."
Much of the nitty-gritty work on the avian flu project will be done by students, at both the graduate and undergraduate level. "We'll be engaging students from the above institutions as an international research team," said NBCR's Li. "We will also send U.S. students and graduate researchers to work in the labs of our partners around Asia - giving those students an experience that will equip them to do ongoing research in this field." This activity also leverages NSF's investment in the Pacific Rim undergraduate Education (PRIME) project, an undergraduate research abroad program awarded to UCSD.
"The next step for PRAGMA is a pragmatic one - to demonstrate that international team science can address pressing challenges in a way that might not be possible in one institution or just one country," said Arzberger. "We expect that this project will engage other researchers, both in other PRAGMA sites, e.g., at USM in Malaysia, and also at the National Biomedical Computation Resource, through the complementary, ongoing Avian flu Drug Discovery project led by professors J. Andrew McCammon and Art Olson of NBCR, by sharing expertise and resources."
Related Links
TATRC tatrc
PRAGMA pragma-grid/
PRAGMA 12 pragma12.thai-research/pragma12/index.php/Main_Page
NECTEC nectec.or.th/
TGNC thaigrid.or.th/index.php
NBCR nbcr
PRIME prime.ucsd
Calit2 calit2
SDSC sdsc
UCSD ucsd
Contact: Doug Ramsey
University of California - San Diego
Computer Key Unlocks Heritable Disorders
Danish and Belgian researchers have found a computer key that maps genes underlying heritable disorders, such as breast cancer, multiple sclerosis, and Alzheimer's disease. These results will possibly ease the discovery of new medicines and improve treatment in various disorders.
The results which are published in the current issue of Nature Biotechnology show that genes important for the development of diseases like Alzheimer's follow the same cellular rules as genes involved in fundamentally different disorders, such as heart disorders, multiple sclerosis, breast cancer, and Type 2 diabetes.
"Many disorders manifest themselves in fundamentally different ways, but the new surprising discovery is that the underlying genes play together after the same rules. Our results show that the genes that trigger diseases, regardless of the type of disease in question, are social team players who cooperate according to highly specific rules. These rules have now been mapped, and we have pointed at hundreds of new genes that are likely to be involved in disorders including multiple sclerosis, Parkinson, heart disorders, and diabetes", says Kasper Lage from Technical University of Denmark, who is the project coordinator on this work.
Heritable disorders will be easier to interpret for clinicians using the new results. Furthermore, the identification of new genes likely to be involved in disorders will help patients with defects in these genes. For example, if you are a high risk carrier of a gene that underlies a disease such as Type 2 diabetes, physicians could prevent or delay the manifestations of the disease by dietary guidance early in life.
"This is a crucial breakthrough for our understanding of heritable disorders, and a breakthrough for systems biology as a research strategy in the field genetics and disease", says SГёren Brunak leader of Center for Biological Sequence analysis at the Technical University of Denmark. "We work with genes and proteins, but also with clinical literature describing the characteristics of different disorders. Then we let the computer integrate all of these data, and extract the pattern", he adds.
The results are the product of a collaboration between the Center for Biological Sequence analysis, the Wilhelm Johannsen Center for Functional Genomics, Steno Diabetes Center in Denmark, and the SymBioSys Center for Computational Systems Biology, Katholieke Universiteit Leuven in Belgium.
TECHNICAL UNIVERSITY OF DENMARK (DTU)
Anker Engelundsvej 1
Bygning 101A
DK-2800 Kgs Lyngby
dtu.dk
The results which are published in the current issue of Nature Biotechnology show that genes important for the development of diseases like Alzheimer's follow the same cellular rules as genes involved in fundamentally different disorders, such as heart disorders, multiple sclerosis, breast cancer, and Type 2 diabetes.
"Many disorders manifest themselves in fundamentally different ways, but the new surprising discovery is that the underlying genes play together after the same rules. Our results show that the genes that trigger diseases, regardless of the type of disease in question, are social team players who cooperate according to highly specific rules. These rules have now been mapped, and we have pointed at hundreds of new genes that are likely to be involved in disorders including multiple sclerosis, Parkinson, heart disorders, and diabetes", says Kasper Lage from Technical University of Denmark, who is the project coordinator on this work.
Heritable disorders will be easier to interpret for clinicians using the new results. Furthermore, the identification of new genes likely to be involved in disorders will help patients with defects in these genes. For example, if you are a high risk carrier of a gene that underlies a disease such as Type 2 diabetes, physicians could prevent or delay the manifestations of the disease by dietary guidance early in life.
"This is a crucial breakthrough for our understanding of heritable disorders, and a breakthrough for systems biology as a research strategy in the field genetics and disease", says SГёren Brunak leader of Center for Biological Sequence analysis at the Technical University of Denmark. "We work with genes and proteins, but also with clinical literature describing the characteristics of different disorders. Then we let the computer integrate all of these data, and extract the pattern", he adds.
The results are the product of a collaboration between the Center for Biological Sequence analysis, the Wilhelm Johannsen Center for Functional Genomics, Steno Diabetes Center in Denmark, and the SymBioSys Center for Computational Systems Biology, Katholieke Universiteit Leuven in Belgium.
TECHNICAL UNIVERSITY OF DENMARK (DTU)
Anker Engelundsvej 1
Bygning 101A
DK-2800 Kgs Lyngby
dtu.dk
Predatory Bacterial Swarm Uses Rippling Motion To Reach Prey
Like something from a horror movie, the swarm of bacteria ripples purposefully toward their prey, devours it and moves on.
Researchers at the University of Iowa are studying this behavior in Myxococcus xanthus (M. xanthus), a bacterium commonly found in soil, which preys on other bacteria.
Despite its deadly role in the bacterial world, M. xanthus is harmless to humans and might one day be used beneficially to destroy harmful bacteria on surfaces or in human infections, said John Kirby, Ph.D., associate professor of microbiology in the UI Roy J. and Lucille A. Carver College of Medicine.
"It may be that we can modify this predator-prey relationship or apply it to medically relevant situations," Kirby said. "It would be amazing if we could adapt its predatory ability to get rid of harmful bacteria that reside in places we don't want them, including in hospitals or on medical implants."
M. xanthus lives in a multi-cellular unit that can change its structure and behavior in response to changing availability of prey.
This adaptive ability to control movement in response to an environmental stimulus is called chemotaxis, and the research team coined the term predataxis to describe M. xanthus behavior in response to prey.
In earlier studies, Kirby and James Berleman, Ph.D., a postdoctoral fellow in Kirby's lab, showed that the presence of prey causes M. xanthus to form parallel rippling waves that move toward and through prey bacteria. Now, how the bacteria organize to form these traveling waves in response to the presence of prey is the subject of the UI team's latest study, which was published online Oct. 24 in Proceedings of the National Academy of Sciences (PNAS) Early Edition.
"When an M. Xanthus aggregate is placed inside a colony of E. coli bacteria, the M. xanthus proceeds to eat the colony from the inside out and creates a rippling pattern as the swarm moves through the prey cells," Kirby said. "We now know that this rippling pattern is the highly organized behavior of thousands of cells working in concert to digest the prey."
Unlike the random motion M. Xanthus exhibits at low levels of prey, the study shows that during predation, individual M. Xanthus cells line up perpendicular to the axis of the ripple and move back and forth. This motion of individual cells, known as cell reversal produces an alternating pattern of high and low cell density like crests and troughs of waves, and the overall motion of the wave formation is directed toward prey.
The UI team also showed that the ripple wavelength is adaptable and dependent of how much prey is available. At high prey density, M. Xanthus forms ripples with shorter wavelengths. As prey density decreases, the ripple wavelength gets longer. Eventually, when there is no more prey, the rippling behavior dissipates.
"The rippling appears to enhance predation by keeping more M. xanthus cells in the location of the prey cells," Kirby said.
Finally, the UI study found that the bacteria use a chemotaxis-like signaling pathway to regulate multi-cellular rippling during predation.
Individual M. Xanthus cells move by shooting rope-like projections called pili from either end of the cell. These pili attach to surfaces allowing cells to pull themselves forward or backward in a "spiderman" type motion known as cell reversal. The genes that regulate this cell reversal process are chemotaxis-like genes.
The UI team mutated two genes in this pathway to study their effect on the predatory ability of the bacterium. One mutant strain rippled continuously even in the absence of prey, and individual cells exhibited a hyper-reversing action. Conversely, the second mutation produced bacteria that were not able to ripple at all.
v
Both mutants were unable to respond to changes in the amount of available prey and both mutant strains were deficient in predation.
"Our study really connects the stimulus to the behavioral response through this molecular machinery," Kirby said.
In addition the potential medical application of M. xanthus to destroy harmful bacteria, what Kirby learns about the molecular mechanisms used by the bacterium may also provide insights into the workings of a rarer, but potentially useful, bacterial cousin. The related bacterium, Anaeromyxobacter dehalogenans, has been found at superfund sites and it can transform soluble uranium, which can leach into the water supply, into insoluble uranium, which still is radioactive, but is stable and trapped in the soil where it can be more safely stored until the radioactivity decays.
In addition to Kirby and Berleman, the UI team included Jodie Scott and Tatiana Chumley.
The research was funded in part by the National Institutes of Health.
University of Iowa Health Sciences
Researchers at the University of Iowa are studying this behavior in Myxococcus xanthus (M. xanthus), a bacterium commonly found in soil, which preys on other bacteria.
Despite its deadly role in the bacterial world, M. xanthus is harmless to humans and might one day be used beneficially to destroy harmful bacteria on surfaces or in human infections, said John Kirby, Ph.D., associate professor of microbiology in the UI Roy J. and Lucille A. Carver College of Medicine.
"It may be that we can modify this predator-prey relationship or apply it to medically relevant situations," Kirby said. "It would be amazing if we could adapt its predatory ability to get rid of harmful bacteria that reside in places we don't want them, including in hospitals or on medical implants."
M. xanthus lives in a multi-cellular unit that can change its structure and behavior in response to changing availability of prey.
This adaptive ability to control movement in response to an environmental stimulus is called chemotaxis, and the research team coined the term predataxis to describe M. xanthus behavior in response to prey.
In earlier studies, Kirby and James Berleman, Ph.D., a postdoctoral fellow in Kirby's lab, showed that the presence of prey causes M. xanthus to form parallel rippling waves that move toward and through prey bacteria. Now, how the bacteria organize to form these traveling waves in response to the presence of prey is the subject of the UI team's latest study, which was published online Oct. 24 in Proceedings of the National Academy of Sciences (PNAS) Early Edition.
"When an M. Xanthus aggregate is placed inside a colony of E. coli bacteria, the M. xanthus proceeds to eat the colony from the inside out and creates a rippling pattern as the swarm moves through the prey cells," Kirby said. "We now know that this rippling pattern is the highly organized behavior of thousands of cells working in concert to digest the prey."
Unlike the random motion M. Xanthus exhibits at low levels of prey, the study shows that during predation, individual M. Xanthus cells line up perpendicular to the axis of the ripple and move back and forth. This motion of individual cells, known as cell reversal produces an alternating pattern of high and low cell density like crests and troughs of waves, and the overall motion of the wave formation is directed toward prey.
The UI team also showed that the ripple wavelength is adaptable and dependent of how much prey is available. At high prey density, M. Xanthus forms ripples with shorter wavelengths. As prey density decreases, the ripple wavelength gets longer. Eventually, when there is no more prey, the rippling behavior dissipates.
"The rippling appears to enhance predation by keeping more M. xanthus cells in the location of the prey cells," Kirby said.
Finally, the UI study found that the bacteria use a chemotaxis-like signaling pathway to regulate multi-cellular rippling during predation.
Individual M. Xanthus cells move by shooting rope-like projections called pili from either end of the cell. These pili attach to surfaces allowing cells to pull themselves forward or backward in a "spiderman" type motion known as cell reversal. The genes that regulate this cell reversal process are chemotaxis-like genes.
The UI team mutated two genes in this pathway to study their effect on the predatory ability of the bacterium. One mutant strain rippled continuously even in the absence of prey, and individual cells exhibited a hyper-reversing action. Conversely, the second mutation produced bacteria that were not able to ripple at all.
v
Both mutants were unable to respond to changes in the amount of available prey and both mutant strains were deficient in predation.
"Our study really connects the stimulus to the behavioral response through this molecular machinery," Kirby said.
In addition the potential medical application of M. xanthus to destroy harmful bacteria, what Kirby learns about the molecular mechanisms used by the bacterium may also provide insights into the workings of a rarer, but potentially useful, bacterial cousin. The related bacterium, Anaeromyxobacter dehalogenans, has been found at superfund sites and it can transform soluble uranium, which can leach into the water supply, into insoluble uranium, which still is radioactive, but is stable and trapped in the soil where it can be more safely stored until the radioactivity decays.
In addition to Kirby and Berleman, the UI team included Jodie Scott and Tatiana Chumley.
The research was funded in part by the National Institutes of Health.
University of Iowa Health Sciences
Bat Echolocation Is Intense
If you think rock concerts are loud, you should hear the bats. An
article published in the open-access journal PLoS ONE
finds that bats emit sounds that are above the human threshold
of pain.
Researcher Annemarie Surlykke (Institute of Biology, SDU, Denmark) and
her colleague Elisabeth Kalko (University of Ulm, Germany) investigated
the patterns and behavior of echolocation in 11 species of
insect-eating tropical bats from PanamГЎ. The bats use a sonar system to
capture insect prey at night, and the researchers reconstructed these
flight paths using arrays of microphones and photographic methods.
These models were used to estimate the intensity of sound that was
emitted during the flights.
Surlykke and Kalko found that bats emit a sound that is stronger than
any other animal in air. The exceptionally loud sounds exceed 140
decibels (dB) SPL (Sound Pressure Level measured at 10 cm from the
bat's mouth). This is louder than the 115 - 120 dB that is emitted at a
loud rock concert and the 120 dB human threshold of pain.
Humans, however, cannot hear the echolocation call since the bats emit
sounds at ultrasonic frequencies. They do this in order to find the
location of small insects that would be missed using lower frequencies.
These high frequencies, though, do not travel as far in air as
low frequencies because of air's ability to attenuate the sound. The
researchers used estimates of the detection range for typical insect
prey to conclude that extremely intense, ultrasonic sounds are
necessary in order to counteract this attenuation.
Another interesting finding was that bats that emit the highest
frequencies were also the ones emitting the highest intensities. This
first comparative field study of bat echolocation sounds found a wide
variation of signal intensities and frequencies that converged on
similar detection ranges.
"Overall, our study underlines the importance of intensity
measures in the field as source level plays a crucial and so far
largely underestimated role in bat echolocation. If we want to further
understand which ecological and evolutionary factors shape echolocation
signal design, an even larger variety of call parameters need to be
considered, including sound duration and pulse interval, which may
create call-echo overlap or other masking effects," conclude the
authors.
Echolocating Bats Cry Out Loud to Detect Their Prey
Surlykke A, Kalko EKV
PLoS ONE (2008). 3(4): e2036.
doi:10.1371/journal.pone.0002036
Click
Here to View Article
About PLoS ONE
PLoS ONE is the first journal of primary research
from all areas of science to employ both pre- and post-publication peer
review to maximize the impact of every report it publishes. PLoS
ONE is published by the Public Library of Science (PLoS), the
Open-access publisher whose goal is to make the world's scientific and
medical literature a public resource.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization
of scientists and physicians committed to making the world's
scientific and medical literature a freely available public resource.
For more information, visit plos
Written by: Peter M Crosta
article published in the open-access journal PLoS ONE
finds that bats emit sounds that are above the human threshold
of pain.
Researcher Annemarie Surlykke (Institute of Biology, SDU, Denmark) and
her colleague Elisabeth Kalko (University of Ulm, Germany) investigated
the patterns and behavior of echolocation in 11 species of
insect-eating tropical bats from PanamГЎ. The bats use a sonar system to
capture insect prey at night, and the researchers reconstructed these
flight paths using arrays of microphones and photographic methods.
These models were used to estimate the intensity of sound that was
emitted during the flights.
Surlykke and Kalko found that bats emit a sound that is stronger than
any other animal in air. The exceptionally loud sounds exceed 140
decibels (dB) SPL (Sound Pressure Level measured at 10 cm from the
bat's mouth). This is louder than the 115 - 120 dB that is emitted at a
loud rock concert and the 120 dB human threshold of pain.
Humans, however, cannot hear the echolocation call since the bats emit
sounds at ultrasonic frequencies. They do this in order to find the
location of small insects that would be missed using lower frequencies.
These high frequencies, though, do not travel as far in air as
low frequencies because of air's ability to attenuate the sound. The
researchers used estimates of the detection range for typical insect
prey to conclude that extremely intense, ultrasonic sounds are
necessary in order to counteract this attenuation.
Another interesting finding was that bats that emit the highest
frequencies were also the ones emitting the highest intensities. This
first comparative field study of bat echolocation sounds found a wide
variation of signal intensities and frequencies that converged on
similar detection ranges.
"Overall, our study underlines the importance of intensity
measures in the field as source level plays a crucial and so far
largely underestimated role in bat echolocation. If we want to further
understand which ecological and evolutionary factors shape echolocation
signal design, an even larger variety of call parameters need to be
considered, including sound duration and pulse interval, which may
create call-echo overlap or other masking effects," conclude the
authors.
Echolocating Bats Cry Out Loud to Detect Their Prey
Surlykke A, Kalko EKV
PLoS ONE (2008). 3(4): e2036.
doi:10.1371/journal.pone.0002036
Click
Here to View Article
About PLoS ONE
PLoS ONE is the first journal of primary research
from all areas of science to employ both pre- and post-publication peer
review to maximize the impact of every report it publishes. PLoS
ONE is published by the Public Library of Science (PLoS), the
Open-access publisher whose goal is to make the world's scientific and
medical literature a public resource.
About the Public Library of Science
The Public Library of Science (PLoS) is a non-profit organization
of scientists and physicians committed to making the world's
scientific and medical literature a freely available public resource.
For more information, visit plos
Written by: Peter M Crosta
A Synthetic Peptide That Enhances Bone Growth Patented By Brookhaven Lab And BioSET, Inc.,
Brookhaven Science Associates, the company that operates and manages the U.S. Department of Energy's Brookhaven National Laboratory (BNL), and Biosurface Engineering Technologies, Inc. (BioSET), have been issued a U.S. patent on a synthetic peptide, called B2A.
"About 250,000 Americans undergo lumbar spine fusion surgeries each year to treat lower back pain," said Tom Rouche, BioSET President and CEO. "We have developed a novel combination medical device, called AMPLEX, that incorporates B2A osteo-inductive growth factor with an ultra-high grade ceramic bone substitute for use in this type of surgery. Preclinical studies have found that it is a safe and highly effective."
B2A enhances the effects of a tissue growth factor known as bone morphogenetic protein 2, or BMP-2. BMPs are a family of proteins in the human body responsible for the proliferation, repair and differentiation of cells in many tissues, including bone.
Brookhaven Lab scientist Louis PeГ±a developed B2A with BioSET, and he performed the initial studies at Brookhaven. "I became interested in bone growth factors after NASA built a radiation research facility at Brookhaven," PeГ±a said. "Weightlessness in space causes bone loss, and cosmic radiation can cause damage to cells, so I thought I might be able to study the interaction of the two. In setting up for that, I developed B2A and couldn't ignore its biomedical applications, so I focused on it instead. The ability to shift direction and follow promising leads is important in science, and I've had the freedom to do that at Brookhaven. I am gratified that BioSET has been able to take the B2A technology to a new level of clinical testing."
In recent preclinical studies, University of Iowa researchers used a rabbit model to evaluate AMPLEX spine fusion. They found that it enhanced the fusion, compared to a conventional surgical method that uses the rabbit's own pelvic bone to form the bone graft. Also, a team of researchers assembled by BioSET reported at a 2008 Orthopedic Research Society meeting that AMPLEX enhanced spine fusion in sheep, a large animal model that more closely resembles the human spine.
BioSET has received approval from the U.S. Food and Drug Administration to initiate a pilot study to evaluate the safety and preliminary efficacy of AMPLEX in approximately 22 patients. Also, the company received approval from Health Canada for a similar study with 24 patients in that country. Each controlled study will compare AMPLEX to an autograft from the patient's own hip bone in lumbar fusion procedures to treat degenerative disc disease.
The first patient surgery in the Canadian study was performed by a neurosurgeon at Foothills Medical Centre in Calgary, Canada. The surgeon reported that AMPLEX handled as well as other ceramic graft alternatives and the patient was recovering well after surgery. Data from all patients in the clinical studies will be evaluated at six-month intervals.
The initial research to develop B2A was funded by the U.S. Department of Energy's Office of Science, the National Institutes of Health, and BioSET. The patent on B2A (Patent # US 7,482,427 B2), titled "Positive Modulator of Bone Morphogenic Protein-2," was issued on January 27, 2009.
BioSET is a private, clinical stage company developing proprietary therapeutic peptides as medical devices to improve bone and soft tissue repair. BioSET products incorporate chemically synthetic growth factor mimetics with procedure specific biomaterials to address multiple large and clinically relevant applications. The company's lead program combines BNL/BioSET's novel B2A osteo-promotive peptide with a resorbable bone scaffold to offer substantial safety and cost benefits to currently available bone grafting alternatives.
Source: Diane Greenberg
DOE/Brookhaven National Laboratory
"About 250,000 Americans undergo lumbar spine fusion surgeries each year to treat lower back pain," said Tom Rouche, BioSET President and CEO. "We have developed a novel combination medical device, called AMPLEX, that incorporates B2A osteo-inductive growth factor with an ultra-high grade ceramic bone substitute for use in this type of surgery. Preclinical studies have found that it is a safe and highly effective."
B2A enhances the effects of a tissue growth factor known as bone morphogenetic protein 2, or BMP-2. BMPs are a family of proteins in the human body responsible for the proliferation, repair and differentiation of cells in many tissues, including bone.
Brookhaven Lab scientist Louis PeГ±a developed B2A with BioSET, and he performed the initial studies at Brookhaven. "I became interested in bone growth factors after NASA built a radiation research facility at Brookhaven," PeГ±a said. "Weightlessness in space causes bone loss, and cosmic radiation can cause damage to cells, so I thought I might be able to study the interaction of the two. In setting up for that, I developed B2A and couldn't ignore its biomedical applications, so I focused on it instead. The ability to shift direction and follow promising leads is important in science, and I've had the freedom to do that at Brookhaven. I am gratified that BioSET has been able to take the B2A technology to a new level of clinical testing."
In recent preclinical studies, University of Iowa researchers used a rabbit model to evaluate AMPLEX spine fusion. They found that it enhanced the fusion, compared to a conventional surgical method that uses the rabbit's own pelvic bone to form the bone graft. Also, a team of researchers assembled by BioSET reported at a 2008 Orthopedic Research Society meeting that AMPLEX enhanced spine fusion in sheep, a large animal model that more closely resembles the human spine.
BioSET has received approval from the U.S. Food and Drug Administration to initiate a pilot study to evaluate the safety and preliminary efficacy of AMPLEX in approximately 22 patients. Also, the company received approval from Health Canada for a similar study with 24 patients in that country. Each controlled study will compare AMPLEX to an autograft from the patient's own hip bone in lumbar fusion procedures to treat degenerative disc disease.
The first patient surgery in the Canadian study was performed by a neurosurgeon at Foothills Medical Centre in Calgary, Canada. The surgeon reported that AMPLEX handled as well as other ceramic graft alternatives and the patient was recovering well after surgery. Data from all patients in the clinical studies will be evaluated at six-month intervals.
The initial research to develop B2A was funded by the U.S. Department of Energy's Office of Science, the National Institutes of Health, and BioSET. The patent on B2A (Patent # US 7,482,427 B2), titled "Positive Modulator of Bone Morphogenic Protein-2," was issued on January 27, 2009.
BioSET is a private, clinical stage company developing proprietary therapeutic peptides as medical devices to improve bone and soft tissue repair. BioSET products incorporate chemically synthetic growth factor mimetics with procedure specific biomaterials to address multiple large and clinically relevant applications. The company's lead program combines BNL/BioSET's novel B2A osteo-promotive peptide with a resorbable bone scaffold to offer substantial safety and cost benefits to currently available bone grafting alternatives.
Source: Diane Greenberg
DOE/Brookhaven National Laboratory
Gold Nanoparticles To Be Used In Early Diagnostics And Treatment Of Cancer
By attaching gold nanoparticles like tiny balls or rods- to cancer cells, earlier detection will be possible. Using photoacoustics a combination of laser light and ultrasound-, scientists of the BMTI Institute for Biomedical Technology expect to improve diagnostics, especially in the early stage of the disease. A step further is the use of the gold particles in actual treatment of cancer. For new in vitro and preclinical tests, the scientists have received funding from the Dutch research programme IOP Photonic Devices.
Gold nanoparticles have highly interesting properties: they can be heated rapidly whenever infrared light of the right wavelength touches them. By attaching antibodies to the nanorods, which can recognize a specific cancer cell, this heating phenomenon can be used in cancer detection. Heating of the gold results in a varying pressure near the particle. This pressure change, in turn is expressed in the generation of ultrasound. In this way, light from a laser eventually results in sound. This acoustic signal gives valuable information about the presence of cancer cells.
The scientists led by prof. Ton van Leeuwen of the Biophysical Engineering Group expect better results than currently possible with imaging techniques. X-Ray and MRI, for example, both have insufficient contrast to discern cancer cells from healthy tissue in the very beginning of the disease.
Photothermal therapy
The phenomenon resulting in rapid heating of the gold particles, is called plasmon resonance: the shape of the particles determines the wavelength at which this happens. The temperature rise can be up to 100 degrees. For the scientists this is an indication for possible use in cancer treatment. Photothermal therapy would use the heated gold to destroy the tumor. Another option would be to include gold particles in capsules filled with cancer medication: the capsule attaches to the cancer cell, is heated and the medicine is released locally.
Both diagnostic and therapeutic applications will be investigated by the UT scientists together with colleagues from the Erasmus MC in Rotterdam and two companies: Esoate Europe and Luminostix. The project is financed from the innovation oriented programme IOP Photonic Devices of the Dutch Ministry of Economic Affairs. Dr. Srirang Manohar from the Biophysical Engineering group already received a VENI grant for his initial research on the applications of gold nanoparticles, and there's also been related research within the Non Invasive Molecular Tumor Imaging and Killing (NIMTIK) focus project of the BMTI Institute.
TWENTE UNIVERSITY
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Gold nanoparticles have highly interesting properties: they can be heated rapidly whenever infrared light of the right wavelength touches them. By attaching antibodies to the nanorods, which can recognize a specific cancer cell, this heating phenomenon can be used in cancer detection. Heating of the gold results in a varying pressure near the particle. This pressure change, in turn is expressed in the generation of ultrasound. In this way, light from a laser eventually results in sound. This acoustic signal gives valuable information about the presence of cancer cells.
The scientists led by prof. Ton van Leeuwen of the Biophysical Engineering Group expect better results than currently possible with imaging techniques. X-Ray and MRI, for example, both have insufficient contrast to discern cancer cells from healthy tissue in the very beginning of the disease.
Photothermal therapy
The phenomenon resulting in rapid heating of the gold particles, is called plasmon resonance: the shape of the particles determines the wavelength at which this happens. The temperature rise can be up to 100 degrees. For the scientists this is an indication for possible use in cancer treatment. Photothermal therapy would use the heated gold to destroy the tumor. Another option would be to include gold particles in capsules filled with cancer medication: the capsule attaches to the cancer cell, is heated and the medicine is released locally.
Both diagnostic and therapeutic applications will be investigated by the UT scientists together with colleagues from the Erasmus MC in Rotterdam and two companies: Esoate Europe and Luminostix. The project is financed from the innovation oriented programme IOP Photonic Devices of the Dutch Ministry of Economic Affairs. Dr. Srirang Manohar from the Biophysical Engineering group already received a VENI grant for his initial research on the applications of gold nanoparticles, and there's also been related research within the Non Invasive Molecular Tumor Imaging and Killing (NIMTIK) focus project of the BMTI Institute.
TWENTE UNIVERSITY
P.O. Box 217
7500 AE Enschede
utwente.nl
Protein Function And Chromatin Structure Methods Featured In Cold Spring Harbor Protocols
Two new methods for analyzing the roles played by proteins in cells are featured in the March issue of Cold Spring Harbor Protocols. Thomas J. Wandless and colleagues from Stanford University provide detailed instructions for Regulating Protein Stability in Mammalian Cells Using Small Molecules. This technique provides a rapid, reversible, and tunable method for studying the activity of a protein of interest in cells. The protein is attached to a destabilization domain, and the resulting fusion proteins are unstable and degraded, except in the presence of small ligands. The speed of small-molecule binding makes it an attractive alternative to studying gene function using RNA interference (RNAi). The method is freely accessible on the website for Cold Spring Harbor Protocols.
The second featured article for March looks at long-range chromosomal interactions and the proteins that mediate them. Stephen Baylin and colleagues from Johns Hopkins University contribute a method for the Combined 3C-ChIP-Cloning (6C) Assay: A Tool to Unravel Protein Mediated Genome Architecture. 6C technology combines multiple techniques to identify the proteins that bridge distant genomic regions, while simultaneously identifying physical proximities. The method is also useful for determining if a candidate protein might mediate long-range interactions, both in cis and in trans in the nucleus. The 6C assay advances our understanding of chromatin folding and provides an important tool to examine the role of specific proteins in nuclear organization. This method is freely accessible on the website for Cold Spring Harbor Protocols.
About Cold Spring Harbor Protocols
Cold Spring Harbor Protocols is a monthly peer-reviewed journal of methods used in a wide range of biology laboratories. It is structured to be highly interactive, with each protocol cross-linked to related methods, descriptive information panels, and illustrative material to maximize the total information available to investigators. Each protocol is clearly presented and designed for easy use at the bench-complete with reagents, equipment, and recipe lists. Life science researchers can access the entire collection via institutional site licenses, and can add their suggestions and comments to further refine the techniques.
About Cold Spring Harbor Laboratory Press
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public.
Cold Spring Harbor Laboratory Press
The second featured article for March looks at long-range chromosomal interactions and the proteins that mediate them. Stephen Baylin and colleagues from Johns Hopkins University contribute a method for the Combined 3C-ChIP-Cloning (6C) Assay: A Tool to Unravel Protein Mediated Genome Architecture. 6C technology combines multiple techniques to identify the proteins that bridge distant genomic regions, while simultaneously identifying physical proximities. The method is also useful for determining if a candidate protein might mediate long-range interactions, both in cis and in trans in the nucleus. The 6C assay advances our understanding of chromatin folding and provides an important tool to examine the role of specific proteins in nuclear organization. This method is freely accessible on the website for Cold Spring Harbor Protocols.
About Cold Spring Harbor Protocols
Cold Spring Harbor Protocols is a monthly peer-reviewed journal of methods used in a wide range of biology laboratories. It is structured to be highly interactive, with each protocol cross-linked to related methods, descriptive information panels, and illustrative material to maximize the total information available to investigators. Each protocol is clearly presented and designed for easy use at the bench-complete with reagents, equipment, and recipe lists. Life science researchers can access the entire collection via institutional site licenses, and can add their suggestions and comments to further refine the techniques.
About Cold Spring Harbor Laboratory Press
Cold Spring Harbor Laboratory Press is an internationally renowned publisher of books, journals, and electronic media, located on Long Island, New York. Since 1933, it has furthered the advance and spread of scientific knowledge in all areas of genetics and molecular biology, including cancer biology, plant science, bioinformatics, and neurobiology. It is a division of Cold Spring Harbor Laboratory, an innovator in life science research and the education of scientists, students, and the public.
Cold Spring Harbor Laboratory Press
New Genetic Biomarkers Could Predict Coronary Heart Disease
New genetic markers may be able to predict whether a person is likely to have coronary heart disease (CAD) in the future. Research carried out by Dr. M. Balasubramanyam and Dr.V.Mohan at the Madras Diabetes Research Foundation (India) shows that people who are pre-diabetic or who have Type 2 diabetes have much shorter telomeres (1) and, since these people are prone to CAD, an early test could indicate their susceptibility and help them to alter their lifestyle to avoid or delay the onset of the disease. This work will be presented by Dr Adaikala Koteswari at the Society for Experimental Biology's Annual Main Meeting on Sunday 1st April 2007.
Tests have been carried out on pre-diabetics and Type 2 diabetics which have shown that telomere shortening is greater as a person progresses from being pre-diabetic through to being type-2 diabetic. Diabetics are more susceptible to oxidation and inflammation which could be the one of the reasons for telomere shortening and so an early indication of their telomeres starting to shorten could indicate the onset of diabetes and ultimately be a predictor for CAD. In other words, telomere shortening in prediabetics could predict those predisposed subjects who are at the cross-road of developing type 2 diabetes and cardiovascular disease.
1 Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other, which would otherwise result in genomic instability. Telomeres are also thought to be the "clock" that regulates how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates. When the telomeres reach a critically short length, the cell stops dividing and ages (senesces) which may cause or contribute to age-related diseases. Telomeres are essential regulators of the cellular lifespan and chromosome integrity, however it has recently been shown that telomeres may also play a role in complex genetic disorders such as hypertension and diabetes.
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Tests have been carried out on pre-diabetics and Type 2 diabetics which have shown that telomere shortening is greater as a person progresses from being pre-diabetic through to being type-2 diabetic. Diabetics are more susceptible to oxidation and inflammation which could be the one of the reasons for telomere shortening and so an early indication of their telomeres starting to shorten could indicate the onset of diabetes and ultimately be a predictor for CAD. In other words, telomere shortening in prediabetics could predict those predisposed subjects who are at the cross-road of developing type 2 diabetes and cardiovascular disease.
1 Telomeres have been compared with the plastic tips on shoelaces because they prevent chromosome ends from fraying and sticking to each other, which would otherwise result in genomic instability. Telomeres are also thought to be the "clock" that regulates how many times an individual cell can divide. Telomeric sequences shorten each time the DNA replicates. When the telomeres reach a critically short length, the cell stops dividing and ages (senesces) which may cause or contribute to age-related diseases. Telomeres are essential regulators of the cellular lifespan and chromosome integrity, however it has recently been shown that telomeres may also play a role in complex genetic disorders such as hypertension and diabetes.
SOCIETY FOR EXPERIMENTAL BIOLOGY
Burlington House
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London
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Dissecting The Genetic Components Of Adaptation Of E. coli To The Mouse Gut
New insights into the evolutionary mechanisms that facilitate the remarkably fast adaptation of intestinal bacteria within their natural environment are provided in the January issue of PLoS Genetics by researchers from INSERM and INRA at University Paris Descartes.
Using germ-free mice - a simplified but ecologically relevant system - the authors analyzed the intestinal adaptation of a model bacterial strain, Escherichia coli MG1655. E. coli is naturally resident within the adult mammalian gut and one of the first bacteria to colonize the human intestine at birth. The mammalian intestine is therefore a privileged site to study how co-evolution between hosts and the trillions of bacteria that form the commensal flora has shaped the genome of each partner and promoted the development of mutualistic interactions.
Commensal bacteria settle on all surfaces exposed to the outside but most prominently in our intestine where they develop a high degree of interdependency with their host. Recent work has shown how these bacteria may impact on our health by modulating our metabolic functions and immune defences. Much less is known on how commensal bacteria adapt to the open and constantly changing ecosystem represented by our intestine.
Intestinal colonization of germ-free mice by E. coli was followed by the very rapid selection of bacteria carrying mutations in a master regulator that controls and coordinates the expression of over 100 target genes. The important selective advantage conferred by the mutations was related with their additive and independent effects on genes regulating bacterial motility and permeability.
These results suggest that global regulators may have evolved to coordinate physiological activities necessary for adaptation to complex environments and that mutations offer a complementary genetic mechanism to adjust the scale of the physiological regulation controlled by these regulators in distinct environments.
While this study yields an interesting model to analyze how intestinal bacteria can adapt to their host, the authors stress that it represents a simplified ecological system compared with the complexity prevailing within the human intestine. Future work will be necessary to assess how commensal bacteria can adapt to their host while simultaneously competing with hundreds of other bacterial species present in the intestinal microecological system.
Citation: Giraud A, Arous S, Gaboriau-Routhiau V, De Paepe M, Bambou JC, et al. (2008) Dissecting the genetic components of adaptation of Escherichia coli to the mouse gut. PLoS Genet 4(1): e2. doi:10.1371/journal.pgen.0040002
CONTACT INFORMATION: Antoine Giraud; INSERM, U571, UniversitГ© Paris Descartes.
Disclaimer
This press release refers to articles published in PLoS Genetics and is provided by the authors and/or journal staff. Any opinions expressed in this release or article are the personal views of the article contributors and/or journal staff, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.
About PLoS Genetics
PLoS Genetics is an open-access, peer-reviewed journal published weekly by the Public Library of Science (PLoS; plos/). PLoS Genetics (plosgenetics/) reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology. All articles published in PLoS Genetics are open access, meaning everything is immediately and freely available online throughout the world, subject only to the condition that the original authorship and source are properly attributed. The Public Library of Science uses the Creative Commons Attribution License.
Source: Mary Kohut
Public Library of Science
Using germ-free mice - a simplified but ecologically relevant system - the authors analyzed the intestinal adaptation of a model bacterial strain, Escherichia coli MG1655. E. coli is naturally resident within the adult mammalian gut and one of the first bacteria to colonize the human intestine at birth. The mammalian intestine is therefore a privileged site to study how co-evolution between hosts and the trillions of bacteria that form the commensal flora has shaped the genome of each partner and promoted the development of mutualistic interactions.
Commensal bacteria settle on all surfaces exposed to the outside but most prominently in our intestine where they develop a high degree of interdependency with their host. Recent work has shown how these bacteria may impact on our health by modulating our metabolic functions and immune defences. Much less is known on how commensal bacteria adapt to the open and constantly changing ecosystem represented by our intestine.
Intestinal colonization of germ-free mice by E. coli was followed by the very rapid selection of bacteria carrying mutations in a master regulator that controls and coordinates the expression of over 100 target genes. The important selective advantage conferred by the mutations was related with their additive and independent effects on genes regulating bacterial motility and permeability.
These results suggest that global regulators may have evolved to coordinate physiological activities necessary for adaptation to complex environments and that mutations offer a complementary genetic mechanism to adjust the scale of the physiological regulation controlled by these regulators in distinct environments.
While this study yields an interesting model to analyze how intestinal bacteria can adapt to their host, the authors stress that it represents a simplified ecological system compared with the complexity prevailing within the human intestine. Future work will be necessary to assess how commensal bacteria can adapt to their host while simultaneously competing with hundreds of other bacterial species present in the intestinal microecological system.
Citation: Giraud A, Arous S, Gaboriau-Routhiau V, De Paepe M, Bambou JC, et al. (2008) Dissecting the genetic components of adaptation of Escherichia coli to the mouse gut. PLoS Genet 4(1): e2. doi:10.1371/journal.pgen.0040002
CONTACT INFORMATION: Antoine Giraud; INSERM, U571, UniversitГ© Paris Descartes.
Disclaimer
This press release refers to articles published in PLoS Genetics and is provided by the authors and/or journal staff. Any opinions expressed in this release or article are the personal views of the article contributors and/or journal staff, and do not necessarily represent the views or policies of PLoS. PLoS expressly disclaims any and all warranties and liability in connection with the information found in the releases and articles and your use of such information.
About PLoS Genetics
PLoS Genetics is an open-access, peer-reviewed journal published weekly by the Public Library of Science (PLoS; plos/). PLoS Genetics (plosgenetics/) reflects the full breadth and interdisciplinary nature of genetics and genomics research by publishing outstanding original contributions in all areas of biology. All articles published in PLoS Genetics are open access, meaning everything is immediately and freely available online throughout the world, subject only to the condition that the original authorship and source are properly attributed. The Public Library of Science uses the Creative Commons Attribution License.
Source: Mary Kohut
Public Library of Science
Smoking May Thin The Brain
Many brain imaging studies have reported that tobacco smoking is associated with large-scale and wide-spread structural brain abnormalities.
The cerebral cortex is a specific area of the brain responsible for many important higher-order functions, including language, information processing, and memory. Reduced cortical thickness has been associated with normal aging, reduced intelligence, and impaired cognition. However, prior research had not described the impact of smoking upon cortical thickness.
A new study, published in the current issue of Biological Psychiatry, now reports concerning findings about the impact of smoking.
Researchers compared cortical thickness in volunteers, both smokers and never-smokers, who were without medical or psychiatric illnesses.
Smokers exhibited cortical thinning in the left medial orbitofrontal cortex. In addition, their cortical thickness measures negatively correlated with the amount of cigarettes smoked per day and the magnitude of lifetime exposure to tobacco smoke. In other words, heavier smoking was associated with more pronounced thinning of cortical tissue.
The orbitofrontal cortex has frequently been implicated in drug addiction. The current findings suggest that smoking-related cortical thinning may increase the risk for addictions, including smoking.
"Since the brain region in which we found the smoking-associated thinning has been related to impulse control, reward processing and decision making, this might explain how nicotine addiction comes about," explained Dr. Simone KГјhn. "In a follow-up study, we plan to explore the rehabilitative effects of quitting smoking on the brain."
"The current findings suggest that smoking may have a cumulative effect on the brain," noted John Krystal, M.D., Editor of Biological Psychiatry and Professor and Chair of Psychiatry at Yale University. "This concerning finding highlights the importance of targeting young smokers for antismoking interventions." For now, this study adds to a long and ever-growing list of reasons that smokers should consider quitting.
Sources: Elsevier, AlphaGalileo Foundation.
The cerebral cortex is a specific area of the brain responsible for many important higher-order functions, including language, information processing, and memory. Reduced cortical thickness has been associated with normal aging, reduced intelligence, and impaired cognition. However, prior research had not described the impact of smoking upon cortical thickness.
A new study, published in the current issue of Biological Psychiatry, now reports concerning findings about the impact of smoking.
Researchers compared cortical thickness in volunteers, both smokers and never-smokers, who were without medical or psychiatric illnesses.
Smokers exhibited cortical thinning in the left medial orbitofrontal cortex. In addition, their cortical thickness measures negatively correlated with the amount of cigarettes smoked per day and the magnitude of lifetime exposure to tobacco smoke. In other words, heavier smoking was associated with more pronounced thinning of cortical tissue.
The orbitofrontal cortex has frequently been implicated in drug addiction. The current findings suggest that smoking-related cortical thinning may increase the risk for addictions, including smoking.
"Since the brain region in which we found the smoking-associated thinning has been related to impulse control, reward processing and decision making, this might explain how nicotine addiction comes about," explained Dr. Simone KГјhn. "In a follow-up study, we plan to explore the rehabilitative effects of quitting smoking on the brain."
"The current findings suggest that smoking may have a cumulative effect on the brain," noted John Krystal, M.D., Editor of Biological Psychiatry and Professor and Chair of Psychiatry at Yale University. "This concerning finding highlights the importance of targeting young smokers for antismoking interventions." For now, this study adds to a long and ever-growing list of reasons that smokers should consider quitting.
Sources: Elsevier, AlphaGalileo Foundation.
Marsupial Genome Sequence To Advance Human Health Studies
Being announced this week in the journal Nature is the sequencing of the genome of the gray, short-tailed opossum, Monodelphis domestica, an animal originally developed as a model for scientific studies at Southwest Foundation for Biomedical Research (SFBR) in San Antonio and now utilized by researchers around the globe for a wide variety of research on human health and disease. The tiny Monodelphis domestica is the first marsupial to be sequenced.
SFBR Chief Scientific Officer John L. VandeBerg, who first developed the animal as a scientific model and who serves as a co-author on the Nature article, explained that the genome sequencing is poised to have a significant impact on biomedical research.
"The Monodelphis has unique properties that make it particularly useful in studies of fetal development, genetic factors related to high cholesterol and melanoma, as well as the quest to find ways to repair injured spinal cords, among other areas of research," he said. "Having the animal's genetic sequence will accelerate the rate of research developments in all these areas."
Scientists in Cambridge, Mass., at the Broad Institute Sequencing Center of the Massachusetts Institute of Technology and Harvard University led the multi-institutional project sponsored by the National Institute of Human Genome Research, part of the National Institutes of Health. Kerstin Linblad-Toh oversaw the project at the Broad Institute.
The opossum that was sequenced came from SFBR's fully pedigreed Monodelphis colony, the largest such colony in the world. SFBR scientists also contributed to the white paper nominating the Monodelphis domestica as the first marsupial to have its genome sequenced.
The scientists' reasoning was that the Monodelphis sequence would have a far-reaching impact because of the breadth of scientific research programs in which the animal is utilized. In addition, the fact that inbred strains of the animal had been developed meant it would be easier and quicker to sequence. And the fact that SFBR scientists have already developed a genetic linkage map for the Monodelphis will help researchers make better use of the full genome sequence.
VandeBerg, who previously worked with captive colonies of large marsupials such as kangaroos and wallabies in Australia, began developing the Monodelphis as a research model in 1979, realizing that its small size made it a more practical laboratory animal.
"Since marsupials have very different characteristics from eutherian, or placental mammals, particularly in their early stage of birth, my thinking was that any marsupial that could be produced in large numbers in the laboratory would become extraordinarily valuable for research on early mammalian development," he said.
VandeBerg brought 27 animals with him to San Antonio when he joined SFBR in 1980 and soon developed a colony that became a worldwide resource. Today SFBR's Monodelphis colony numbers about 2,400 animals, all fully pedigreed. It produces 6,000 progeny a year totaling about 80,000 animals over 30 generations. SFBR has supplied many of these animals to others laboratories that have established their own colonies.
All this has been possible because of several years of NIH funding in the 1980s followed by strong and consistent grant support from the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation to sustain and enhance the SFBR colony since 1990.
Particularly beneficial characteristics and resulting research programs with the Monodelphis domestica include:
-- It is the only mammal known to develop melanoma skin cancer solely from exposure to ultraviolet light, the cause of melanoma in most human cases.
-- With NIH funding, VandeBerg's team of scientists at SFBR has developed the Monodelphis for research on dietary-induced hypercholesterolemia (high blood cholesterol), a major contributor to heart disease. Some animals are genetically predisposed to high blood cholesterol that is only manifested when the animal is fed a human-style high-cholesterol diet. The SFBR team has been working to identify genes that cause some animals to be susceptible to that type of diet and others to be resistant.
-- The Monodelphis offers insight into fetal development, because the animal is born at a stage that would be the equivalent of about a six-week human fetus and continues its development outside the uterus, where it can easily be monitored without any invasive procedures.
-- Because the baby Monodelphis can regenerate a severed or crushed spinal cord, up to about one week of age, this species offers insight into therapies for spinal cord injury, an area of research where SFBR researchers are collaborating with others. They are studying the expression of genes that make this healing possible, and what genetic or physiological changes occur that cause the animal to lose this ability as it matures. Identifying and understanding those changes could lead to new ideas for treatment of human spinal cord injuries.
Speeding up the pace of scientific research
VandeBerg is encouraged by the sequencing of the Monodelphis genome, which he expects to dramatically speed the pace of genetic research investigations with this unique animal model. "Trying to find these genes has been extremely difficult without having the sequence of the animal," he said. "But now that the sequence is available, I expect it to eliminate as much as one to three years of preliminary work required before a researcher can zero in on a gene or set of genes that appears to play a role in a certain disease or illness."
He explained, "Now, when we identify a Monodelphis gene that we suspect influences a physiologic process, we can go straight to the Monodelphis genome and find out the exact sequence of that gene without doing the incredibly painstaking lab work it once required. Instead, we can now go straight to this database and in an hour or two learn what we want to learn, match it up with the human database, find out where that gene is located on a human chromosome and what genes are surrounding it on a human chromosome, go back and see if the same genes are around it on the Monodelphis chromosome, and then launch straight into experiments on the function of the gene. In the past, it would take one year, two years, or even three years, to go from the idea of having one or more candidate genes for a process to where you could actually do functional experiments."
He cited the example of the search for genes that make some more susceptible to a high-cholesterol diet.
"For years we've been doing genome scans, that is, tracking marker genes through generations, together with physiologic characters such as high blood cholesterol," VandeBerg said. "We get signals on particular chromosomes where we know there must be a gene, let's say chromosome 8, that influences blood cholesterol. So we know there's a gene in one segment of chromosome 8 that controls blood cholesterol.
"The narrowest we can get through that technology is maybe 200 genes or 300 genes. In the past, we never even knew what genes were in that segment. It was so hard to go from there to finding the gene that we were interested in. Now we'll be able to go to the Monodelphis gene map, find all the genes that are in that chromosomal segment of Monodelphis, get some ideas of function of those genes from research with humans, mice and so on, and be able to target the ones that we want to investigate. Before, we had this pool of 200 or 300 genes with no efficient way to get a handle on which ones we might want to look at."
The availability of this genome sequence will contribute greatly to the collage of animals needed for biomedical research to progress.
"The opossum does not displace any other laboratory animal, but it has brought to the table some new capabilities, particularly in developmental biology," he said.
The Monodelphis domestica is found in the wild in Brazil, Bolivia, and Guyana. An adult weighs three to four ounces and is about twice the size of a mouse, and usually lives no longer than two years in the wild.
Southwest Foundation for Biomedical Research (SFBR)
P.O. Box 760549
San Antonio, TX 78245-0549
United States
sfbr
SFBR Chief Scientific Officer John L. VandeBerg, who first developed the animal as a scientific model and who serves as a co-author on the Nature article, explained that the genome sequencing is poised to have a significant impact on biomedical research.
"The Monodelphis has unique properties that make it particularly useful in studies of fetal development, genetic factors related to high cholesterol and melanoma, as well as the quest to find ways to repair injured spinal cords, among other areas of research," he said. "Having the animal's genetic sequence will accelerate the rate of research developments in all these areas."
Scientists in Cambridge, Mass., at the Broad Institute Sequencing Center of the Massachusetts Institute of Technology and Harvard University led the multi-institutional project sponsored by the National Institute of Human Genome Research, part of the National Institutes of Health. Kerstin Linblad-Toh oversaw the project at the Broad Institute.
The opossum that was sequenced came from SFBR's fully pedigreed Monodelphis colony, the largest such colony in the world. SFBR scientists also contributed to the white paper nominating the Monodelphis domestica as the first marsupial to have its genome sequenced.
The scientists' reasoning was that the Monodelphis sequence would have a far-reaching impact because of the breadth of scientific research programs in which the animal is utilized. In addition, the fact that inbred strains of the animal had been developed meant it would be easier and quicker to sequence. And the fact that SFBR scientists have already developed a genetic linkage map for the Monodelphis will help researchers make better use of the full genome sequence.
VandeBerg, who previously worked with captive colonies of large marsupials such as kangaroos and wallabies in Australia, began developing the Monodelphis as a research model in 1979, realizing that its small size made it a more practical laboratory animal.
"Since marsupials have very different characteristics from eutherian, or placental mammals, particularly in their early stage of birth, my thinking was that any marsupial that could be produced in large numbers in the laboratory would become extraordinarily valuable for research on early mammalian development," he said.
VandeBerg brought 27 animals with him to San Antonio when he joined SFBR in 1980 and soon developed a colony that became a worldwide resource. Today SFBR's Monodelphis colony numbers about 2,400 animals, all fully pedigreed. It produces 6,000 progeny a year totaling about 80,000 animals over 30 generations. SFBR has supplied many of these animals to others laboratories that have established their own colonies.
All this has been possible because of several years of NIH funding in the 1980s followed by strong and consistent grant support from the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation to sustain and enhance the SFBR colony since 1990.
Particularly beneficial characteristics and resulting research programs with the Monodelphis domestica include:
-- It is the only mammal known to develop melanoma skin cancer solely from exposure to ultraviolet light, the cause of melanoma in most human cases.
-- With NIH funding, VandeBerg's team of scientists at SFBR has developed the Monodelphis for research on dietary-induced hypercholesterolemia (high blood cholesterol), a major contributor to heart disease. Some animals are genetically predisposed to high blood cholesterol that is only manifested when the animal is fed a human-style high-cholesterol diet. The SFBR team has been working to identify genes that cause some animals to be susceptible to that type of diet and others to be resistant.
-- The Monodelphis offers insight into fetal development, because the animal is born at a stage that would be the equivalent of about a six-week human fetus and continues its development outside the uterus, where it can easily be monitored without any invasive procedures.
-- Because the baby Monodelphis can regenerate a severed or crushed spinal cord, up to about one week of age, this species offers insight into therapies for spinal cord injury, an area of research where SFBR researchers are collaborating with others. They are studying the expression of genes that make this healing possible, and what genetic or physiological changes occur that cause the animal to lose this ability as it matures. Identifying and understanding those changes could lead to new ideas for treatment of human spinal cord injuries.
Speeding up the pace of scientific research
VandeBerg is encouraged by the sequencing of the Monodelphis genome, which he expects to dramatically speed the pace of genetic research investigations with this unique animal model. "Trying to find these genes has been extremely difficult without having the sequence of the animal," he said. "But now that the sequence is available, I expect it to eliminate as much as one to three years of preliminary work required before a researcher can zero in on a gene or set of genes that appears to play a role in a certain disease or illness."
He explained, "Now, when we identify a Monodelphis gene that we suspect influences a physiologic process, we can go straight to the Monodelphis genome and find out the exact sequence of that gene without doing the incredibly painstaking lab work it once required. Instead, we can now go straight to this database and in an hour or two learn what we want to learn, match it up with the human database, find out where that gene is located on a human chromosome and what genes are surrounding it on a human chromosome, go back and see if the same genes are around it on the Monodelphis chromosome, and then launch straight into experiments on the function of the gene. In the past, it would take one year, two years, or even three years, to go from the idea of having one or more candidate genes for a process to where you could actually do functional experiments."
He cited the example of the search for genes that make some more susceptible to a high-cholesterol diet.
"For years we've been doing genome scans, that is, tracking marker genes through generations, together with physiologic characters such as high blood cholesterol," VandeBerg said. "We get signals on particular chromosomes where we know there must be a gene, let's say chromosome 8, that influences blood cholesterol. So we know there's a gene in one segment of chromosome 8 that controls blood cholesterol.
"The narrowest we can get through that technology is maybe 200 genes or 300 genes. In the past, we never even knew what genes were in that segment. It was so hard to go from there to finding the gene that we were interested in. Now we'll be able to go to the Monodelphis gene map, find all the genes that are in that chromosomal segment of Monodelphis, get some ideas of function of those genes from research with humans, mice and so on, and be able to target the ones that we want to investigate. Before, we had this pool of 200 or 300 genes with no efficient way to get a handle on which ones we might want to look at."
The availability of this genome sequence will contribute greatly to the collage of animals needed for biomedical research to progress.
"The opossum does not displace any other laboratory animal, but it has brought to the table some new capabilities, particularly in developmental biology," he said.
The Monodelphis domestica is found in the wild in Brazil, Bolivia, and Guyana. An adult weighs three to four ounces and is about twice the size of a mouse, and usually lives no longer than two years in the wild.
Southwest Foundation for Biomedical Research (SFBR)
P.O. Box 760549
San Antonio, TX 78245-0549
United States
sfbr
Testing For Drug Safety Using Insects
Insects, such as some moths and fruit flies, react to microbial infection in the same way as mammals and so can be used to test the efficiency of new drugs, thereby reducing the need for animal testing. Dr Kevin Kavanagh from the National University of Ireland - Maynooth, presented his research findings at the Society for General Microbiology's meeting at Heriot Watt University, Edinburgh, today (8 September).
Neutrophils, which are a type of white blood cell and part of the mammalian immune system, and haematocytes, which are cells that carry out a similar function in insects, react in the same way to infecting microbes. Both the insect and mammalian cells produce chemicals with a similar structure which move to the surface of the cells to kill the invading microbe. The immune cells then enclose the microbe and release enzymes to break it down.
Insects such as fruit flies (Drosophila), Greater Wax Moths (Galleria) and a type of Hawkmoth (Manduca) can be used to test the efficacy of new antimicrobial drugs or to judge how virulent fungal pathogens are. It is now routine practice to use insect larvae to perform initial testing of new drugs and then to use mice for confirmation tests. As well as reducing by up to 90% the number of mice required, this method of testing is quicker as tests with insects yield results in 48 hours whereas tests with mice usually take 4-6 weeks.
"We will continue to explore the similarities between insect and mammalian immune responses so that insects can be used as models to study different disease states in humans," said Dr Kavanagh.
"In addition we have shown that immune cells in insects and mammals are structurally and functionally similar despite being separated by over 400 million years of evolution."
Source:
Dianne Stilwell
Society for General Microbiology
Neutrophils, which are a type of white blood cell and part of the mammalian immune system, and haematocytes, which are cells that carry out a similar function in insects, react in the same way to infecting microbes. Both the insect and mammalian cells produce chemicals with a similar structure which move to the surface of the cells to kill the invading microbe. The immune cells then enclose the microbe and release enzymes to break it down.
Insects such as fruit flies (Drosophila), Greater Wax Moths (Galleria) and a type of Hawkmoth (Manduca) can be used to test the efficacy of new antimicrobial drugs or to judge how virulent fungal pathogens are. It is now routine practice to use insect larvae to perform initial testing of new drugs and then to use mice for confirmation tests. As well as reducing by up to 90% the number of mice required, this method of testing is quicker as tests with insects yield results in 48 hours whereas tests with mice usually take 4-6 weeks.
"We will continue to explore the similarities between insect and mammalian immune responses so that insects can be used as models to study different disease states in humans," said Dr Kavanagh.
"In addition we have shown that immune cells in insects and mammals are structurally and functionally similar despite being separated by over 400 million years of evolution."
Source:
Dianne Stilwell
Society for General Microbiology
How Mitochondria Get Their Membranes Bent
Mitochondria are the powerhouses of cells. Underneath their smooth surface they harbor an elaborately folded inner membrane. It holds a multitude of bottleneck like invaginations, which expand into elongated cavities (cristae). The narrow shape of the entrance or pore to the cristae ('crista junction') allows separation of the intracristal space and storage of molecules. Cytochrome c, for example, an important signaling protein in programmed cell death (apoptosis), is stored in this compartment. When apoptosis is triggered, the pores enlarge and cytochrome c is released into the cytosol. Thus, understanding of how the pore diameter and the shape of the inner membrane are regulated on a molecular basis is of great relevance to a better understanding of mitochondrial function in general. Recently, in cooperation with other research teams, the group of Prof. Andreas Reichert, who has been appointed as professor for Mitochondrial Biology to the Goethe University within the Cluster of Excellence Macromolecular Complexes in 2007, has identified two proteins linked in an antagonistic manner that are relevant for governing inner membrane structure.
In the current issue of the the Journal of Cell Biology Rabl, Soubannier et al. report on their quest of slow-growing bakers yeast mutants harboring deformed mitochondria. Thereby, they discovered the protein Fcj1 ("Formation of criasta junction protein 1"), which is embedded in the inner membrane and accumulates at crista junctions. Upon increased expression of Fcj1 the number of cristae junctions goes up. Without the protein, however, crista junctions are lacking and the inner cristae membrane forms internal parallel stacks of vesicles.
On the other hand, the researchers found that regular assemblies (supercomplexes) of the F1FO-ATPase, a protein complex required for supplying the cell's energy, accumulated at the cristae tips but were less abundant at crista junctions. In addition, Fcj1 and the F1FO-ATPase appear to have opposing functions. In fact, Fcj1 reduces the formation of F1FO-supercomplexes. "We hypothesize, Fcj1 makes sure that the membrane can adopt a negative curvature, while the F1FO-ATPase supercomplex induces positive bending", Andreas Reichert interprets the results. "This is highly exciting, as we have for the first time found out how mitochondrial ultrastructure is regulated and which components determine the structure of crista junctions at all."
Original publication: Rabl, R.*, Soubannier, V.*, Scholz, R., Vogel, F., Mendl, N., Vasiljev-Neumeyer, A., Körner, C., Jagasia, R., Keil, T., Baumeister, W., Cyrklaff, M., Neupert, W., and Reichert, A.S. (2009). Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g. J Cell Biol, 2009; ePub 15th June 2009. *equally contributed
Source:
Dr. Andreas Reichert
Goethe University Frankfurt
In the current issue of the the Journal of Cell Biology Rabl, Soubannier et al. report on their quest of slow-growing bakers yeast mutants harboring deformed mitochondria. Thereby, they discovered the protein Fcj1 ("Formation of criasta junction protein 1"), which is embedded in the inner membrane and accumulates at crista junctions. Upon increased expression of Fcj1 the number of cristae junctions goes up. Without the protein, however, crista junctions are lacking and the inner cristae membrane forms internal parallel stacks of vesicles.
On the other hand, the researchers found that regular assemblies (supercomplexes) of the F1FO-ATPase, a protein complex required for supplying the cell's energy, accumulated at the cristae tips but were less abundant at crista junctions. In addition, Fcj1 and the F1FO-ATPase appear to have opposing functions. In fact, Fcj1 reduces the formation of F1FO-supercomplexes. "We hypothesize, Fcj1 makes sure that the membrane can adopt a negative curvature, while the F1FO-ATPase supercomplex induces positive bending", Andreas Reichert interprets the results. "This is highly exciting, as we have for the first time found out how mitochondrial ultrastructure is regulated and which components determine the structure of crista junctions at all."
Original publication: Rabl, R.*, Soubannier, V.*, Scholz, R., Vogel, F., Mendl, N., Vasiljev-Neumeyer, A., Körner, C., Jagasia, R., Keil, T., Baumeister, W., Cyrklaff, M., Neupert, W., and Reichert, A.S. (2009). Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g. J Cell Biol, 2009; ePub 15th June 2009. *equally contributed
Source:
Dr. Andreas Reichert
Goethe University Frankfurt
Zymes LLC Obtains GRAS Status For Its New Water-Soluble Coenzyme Q10, HQO(TM)
The U.S. Food and Drug
Administration (FDA) has acknowledged that Zymes' PTS technology is
Generally Recognized as Safe (GRAS) as a solubilizer for coenzyme Q10. PTS
is the lead compound of Ubisol-Aqua(TM), Zymes' delivery system technology.
Ubisol-Aqua(TM) provides superior platforms for solubilizing coenzyme Q10
and other water-insoluble compounds for foods, beverages, nutritional
supplements and pharmaceuticals. Zymes' new water-soluble formulation of
coenzyme Q10, HQO(TM), is a major breakthrough for the many industries
looking to supplement their products with coenzyme Q10.
Zymes' new HQO(TM) has an average particle size in water of 22
nanometers, 10 times smaller than those commercially available. It offers
improved solubility, enhanced bioavailability, higher concentration and is
available for licensing.
"Obtaining GRAS status for our water-soluble coenzyme Q10, HQO(TM),
creates unlimited opportunities in food, beverage and nutritional markets
around the world," said Benjamin D. Mamola, Co-founder and Executive Vice
President of Global Business Development at Zymes. "Our new breakthrough
technology finally makes it possible to deliver coenzyme Q10 in everyday
products like water, soft drinks, juices and many other types of foods,
beverages and nutritional supplements."
Zymes also offers its delivery system technology, Ubisol-Aqua(TM) to
industry partners seeking more efficient ways of making their insoluble or
lipophilic ingredients water-soluble.
"The scientific data presented within our GRAS application indicates
that PTS can safely provide solubility benefits," said Randi Fain, MD,
Co-founder and Executive Vice President of Clinical and Scientific Affairs.
"Receiving the FDA's positive response to our GRAS application is very
important to our research efforts and validates the delivery system's
14-year development process."
About Zymes:
Zymes LLC is a bio-science company that combines science,
technology and nature to create products that improve the quality of life.
It is dedicated to contributing to the well-being of individuals by
developing high-quality products that provide significant,
clinically-proven health and beauty benefits to consumers. Based in
Hasbrouck Heights, NJ, Zymes holds substantial intellectual property
ranging from production of CoQ10 to pharmaceutical drug delivery systems.
For more information, visit zymesllc.
Zymes LLC
zymesllc
Administration (FDA) has acknowledged that Zymes' PTS technology is
Generally Recognized as Safe (GRAS) as a solubilizer for coenzyme Q10. PTS
is the lead compound of Ubisol-Aqua(TM), Zymes' delivery system technology.
Ubisol-Aqua(TM) provides superior platforms for solubilizing coenzyme Q10
and other water-insoluble compounds for foods, beverages, nutritional
supplements and pharmaceuticals. Zymes' new water-soluble formulation of
coenzyme Q10, HQO(TM), is a major breakthrough for the many industries
looking to supplement their products with coenzyme Q10.
Zymes' new HQO(TM) has an average particle size in water of 22
nanometers, 10 times smaller than those commercially available. It offers
improved solubility, enhanced bioavailability, higher concentration and is
available for licensing.
"Obtaining GRAS status for our water-soluble coenzyme Q10, HQO(TM),
creates unlimited opportunities in food, beverage and nutritional markets
around the world," said Benjamin D. Mamola, Co-founder and Executive Vice
President of Global Business Development at Zymes. "Our new breakthrough
technology finally makes it possible to deliver coenzyme Q10 in everyday
products like water, soft drinks, juices and many other types of foods,
beverages and nutritional supplements."
Zymes also offers its delivery system technology, Ubisol-Aqua(TM) to
industry partners seeking more efficient ways of making their insoluble or
lipophilic ingredients water-soluble.
"The scientific data presented within our GRAS application indicates
that PTS can safely provide solubility benefits," said Randi Fain, MD,
Co-founder and Executive Vice President of Clinical and Scientific Affairs.
"Receiving the FDA's positive response to our GRAS application is very
important to our research efforts and validates the delivery system's
14-year development process."
About Zymes:
Zymes LLC is a bio-science company that combines science,
technology and nature to create products that improve the quality of life.
It is dedicated to contributing to the well-being of individuals by
developing high-quality products that provide significant,
clinically-proven health and beauty benefits to consumers. Based in
Hasbrouck Heights, NJ, Zymes holds substantial intellectual property
ranging from production of CoQ10 to pharmaceutical drug delivery systems.
For more information, visit zymesllc.
Zymes LLC
zymesllc
Fish Odour Triggers Conspecific Attraction Behavior In An Aquatic Invertebrate
Group living has evolved as an adaptation to predation in many animal species. In a multitude of vertebrates, the tendency to aggregate varies with the risk of predation, but experimental evidence for this is less well known in invertebrates.
Here, we examine the tendency to aggregate in the freshwater amphipod Gammarus pulex in the absence and presence of predator fish odour.
Without fish odours, the gammarids showed no significant tendency to aggregate.
In contrast to this, in fish-conditioned water they significantly preferred to stay close to conspecifics.
Predation risk can, thus, influences gammarids social behavior.
Royal Society journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
publishing.royalsociety/biologyletters
Here, we examine the tendency to aggregate in the freshwater amphipod Gammarus pulex in the absence and presence of predator fish odour.
Without fish odours, the gammarids showed no significant tendency to aggregate.
In contrast to this, in fish-conditioned water they significantly preferred to stay close to conspecifics.
Predation risk can, thus, influences gammarids social behavior.
Royal Society journal Biology Letters
Biology Letters publishes short, innovative and cutting-edge research articles and opinion pieces accessible to scientists from across the biological sciences. The journal is characterised by stringent peer-review, rapid publication and broad dissemination of succinct high-quality research communications.
publishing.royalsociety/biologyletters
Alzheimer's disease a new hypothesis
A group of scientists at The Scripps Research Institute has proposed a new theory about the cause of Alzheimer's disease, the progressive neurodegenerative disorder that currently afflicts some 4.5 million Americans.
According to the hypothesis, the disease arises as a consequence of inflammation, which creates abnormal metabolites out of normal brain molecules.
These abnormal metabolites then modify 'amyloid beta' proteins in the brain and cause them to misfold. Misfolded amyloid beta proteins are thought to be a major player in Alzheimer's disease, because they can accumulate into the fibrils and plaques that autopsies reveal in the brains of patients with the disease. These fibrils and plaques and their precursors are implicated in neuronal loss.
The inflammation process that creates these metabolites can be triggered by numerous stimuli, including infections that precede the onset of Alzheimer's disease by a significant amount of time -- perhaps years.
'If a certain inflammatory metabolite or family of metabolites confers risk later in life, then we need to know this, and we need to attack the problem,' says Scripps Research Professor Jeffery W. Kelly, who is the Lita Annenberg Hazen Professor of Chemistry in The Skaggs Institute for Chemical Biology and vice president of academic affairs at Scripps Research.
Kelly and his Scripps Research colleagues present their new theory in an article that will be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences.
A Progressive, Incurable Disease
Alzheimer's is a progressive neurodegenerative disease marked by memory loss, loss of language ability, loss of the ability to mentally manipulate visual information, poor judgment, confusion, restlessness, and mood swings.
According to the Alzheimer's Disease Education and Referral Center, a service of the National Institute on Aging, Alzheimer's disease is now believed to inflict some 4.5 million people and is the most common form of dementia among older people in the United States. Currently, there is no cure for Alzheimer's and no way to slow the progression of the disease.
German doctor Alois Alzheimer discovered the disease in 1906, when he examined a post-mortem patient who had died with an unusual mental illness.
Alzheimer found unusual clumps of protein or plaques in her brain. These plaquesmade up of aggregated proteins called amyloid betaare a clear sign of the disease, and the aggregation of amyloid beta protein is an accepted primary pathological marker for Alzheimer's.
But scientists have not been sure whether these fibrils are causing the disease or are simply a marker of it. By analogy, a tidal wave may cause massive destruction to a coastal area, but the tidal wave itself may have been caused by a distant earthquake undetected in that coastal area.
Kelly and his colleagues have studied the basic biology of Alzheimer's and related diseases for many years, looking for new treatment approaches. Now, they think they may have taken a significant step along this path by identifying the distant earthquake that causes Alzheimer's.
Basic Science Brings it All Together
Amyloid diseases are caused by the misfolding of proteins into structures that lead them to cluster together, forming microscopic fibril or plaques, which deposit in internal organs and interfere with normal function, sometimes lethally. In the case of Alzheimer's, these fibrils kill nerve cells in areas of the brain that are crucial for memory.
These diseases include Alzheimer's, Parkinson's, and a peripheral nervous system disease called familial amyloid polyneuropathy (FAP)a collection of more than 80 rare amyloid diseases caused by the misfolding of the protein transthyretin (TTR), which the liver secretes into the bloodstream to carry thyroid hormone and vitamin A.
In the FAP diseases, mutations in the TTR protein are known to play a direct role in causing the disease. Basically, these mutations change the amino acid sequence of TTR, and these changes alter protein folding in such a way as to predispose the proteins to misfold and accumulate into microscopic fibrils, which can then grow into the protein plaques characteristic of FAP and other amyloid diseases.
However, in Alzheimer's disease, the cause of misfolding is not so obvious. A number of mutations are associated with rare forms of familial Alzheimer's, but not with most common cases (about 95 percent of the cases). This suggests there must be a more common cause of Alzheimer's disease, and Kelly has combined efforts with several of his colleagues at Scripps Research to find it.
A few years ago, Kelly started to think about traumatic head injuries, which are a major risk factor for later developing Alzheimer's disease. The body responds to such injuries with inflammatory reactions that cause the release of components of lipid membranes, such as cholesterol.
Kelly began to discuss this with his colleagues in The Skaggs Institute for Chemical Biology, Scripps Research President Richard A. Lerner, M.D., and Scripps Research Associate Professor Paul Wentworth, Jr., Ph.D. Lerner and Wentworth had recently discovered how inflammation can lead to the production of reactive oxygen species such as ozone, which can trigger pathological changes in other molecules in the body, like cholesterol.
In a paper last year, Lerner, Wentworth, and several colleagues described how ozone reacts with normal metabolites to produce toxic compounds during inflammatory processes taking place in the body. The scientists describe two such compounds, which they call the 'atheronals.'
The scientists suggest these newly identified products are critical to the pathogenesis of the disease atherosclerosis because these atheronals were found in atherosclerotic plaques that were surgically removed from patients with atherosclerosis. (Atherosclerosis is a common vascular disease that increases the risk of heart attacks and strokes and is characterized by a hardening of the arteries over time due to deposits of fibrous tissue, calcium, fat, cholesterol, proteins, cells, and other materials on the inner 'endothelial' walls of an artery).
This discovery made Kelly sit up straight when he first heard it because inflammation is increasingly seen as playing a role in neurodegenerative diseases. Also, there are a fair number of risk factors in common between the two diseases, including hypercholesterolemia and inflammation.
In their new study, Kelly and his colleagues suggest that inflammation in the brain could create a perfect storm in which cholesterol and lipids react with ozone and other inflammatory chemicals to produce abnormal reactive metabolites, which, in turn, modify the folding of normal amyloid beta protein.
These modified amyloid beta proteins can catalyze misfolding in other unmodified amyloid beta proteins, starting an avalanche of misfolding that results -- perhaps years or decades later -- in Alzheimer's disease.
A New Way of Thinking About Disease in General
To examine the hypothesis that these metabolites may be the root cause of Alzheimer's, Kelly and his colleagues examined the post-mortem brains of Alzheimer's patients and compared these to age-matched controls.
They found evidence of atheronals in the brains of both the Alzheimer's patients and the control subjects. The levels of atheronals in the brains of the Alzheimer's patients were not significantly elevated, but this is not necessarily surprising.
According to the new theory, the propagation of misfolding and the buildup of fibrils inside the brain does not depend upon continuous exposure to metabolite-modified proteins, but to exposure during a precipitating event that may occur a decade or more earlier. The creation of these metabolite-linked misfolding proteins is only the initiator of the fibril plaques.
Kelly and colleagues also performed experiments in the test tube and found that atheronals and lipid oxidation products have the ability to dramatically accelerate the misfolding of amyloid beta and to reduce the concentration of the protein needed for misfolding to take place to concentrations found in the brain.
This is an entirely new way of thinking about not only Alzheimer's disease, but disease in general. Historically, science has regarded disease as based on the up or down regulation of gene expression or protein function.
But this theory suggests a new sort of pathology -- the creation of a reactive metabolite by inflammatory stress, leading to the modification of a protein, the aggregation of that protein over time, and the degeneration of function in the brain or whichever internal organ hosts the aggregation.
The inflammatory metabolite theory of Alzheimer's will be difficult to prove, admits Kelly, because the presence of these abnormal metabolites are hard to detect years after they initiated the aggregation. There is, so far, no smoking gun.
'Is [this theory] right? Time will tell,' says Kelly. 'That's how science works.'
The article, 'Metabolite-initiated protein misfolding may trigger Alzheimer's disease' was authored by Qinghai Zhang, Evan T. Powers, Jorge Nieva, Mary E. Huff, Maria A. Dendle, Jan Bieschke, Charles G. Glabe, Albert Eschenmoser, Paul Wentworth, Jr., Richard A. Lerner, and Jeffery W. Kelly and appears in the online edition of the journal Proceedings of the National Academy of Sciences the week of March 15-19, 2004. The article will appear in print later this year. See: pnas/cgi/doi/10.1073/pnas.0400924101.
This work was supported by The Skaggs Institute for Chemical Biology and the Lita Annenberg Hazen Foundation.
About The Scripps Research Institute
The Scripps Research Institute in La Jolla, California, is one of the world's largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.
Contact: Jason Bardi
jasonbscripps
858-784-9254
Scripps Research Institute
According to the hypothesis, the disease arises as a consequence of inflammation, which creates abnormal metabolites out of normal brain molecules.
These abnormal metabolites then modify 'amyloid beta' proteins in the brain and cause them to misfold. Misfolded amyloid beta proteins are thought to be a major player in Alzheimer's disease, because they can accumulate into the fibrils and plaques that autopsies reveal in the brains of patients with the disease. These fibrils and plaques and their precursors are implicated in neuronal loss.
The inflammation process that creates these metabolites can be triggered by numerous stimuli, including infections that precede the onset of Alzheimer's disease by a significant amount of time -- perhaps years.
'If a certain inflammatory metabolite or family of metabolites confers risk later in life, then we need to know this, and we need to attack the problem,' says Scripps Research Professor Jeffery W. Kelly, who is the Lita Annenberg Hazen Professor of Chemistry in The Skaggs Institute for Chemical Biology and vice president of academic affairs at Scripps Research.
Kelly and his Scripps Research colleagues present their new theory in an article that will be published in an upcoming issue of the journal Proceedings of the National Academy of Sciences.
A Progressive, Incurable Disease
Alzheimer's is a progressive neurodegenerative disease marked by memory loss, loss of language ability, loss of the ability to mentally manipulate visual information, poor judgment, confusion, restlessness, and mood swings.
According to the Alzheimer's Disease Education and Referral Center, a service of the National Institute on Aging, Alzheimer's disease is now believed to inflict some 4.5 million people and is the most common form of dementia among older people in the United States. Currently, there is no cure for Alzheimer's and no way to slow the progression of the disease.
German doctor Alois Alzheimer discovered the disease in 1906, when he examined a post-mortem patient who had died with an unusual mental illness.
Alzheimer found unusual clumps of protein or plaques in her brain. These plaquesmade up of aggregated proteins called amyloid betaare a clear sign of the disease, and the aggregation of amyloid beta protein is an accepted primary pathological marker for Alzheimer's.
But scientists have not been sure whether these fibrils are causing the disease or are simply a marker of it. By analogy, a tidal wave may cause massive destruction to a coastal area, but the tidal wave itself may have been caused by a distant earthquake undetected in that coastal area.
Kelly and his colleagues have studied the basic biology of Alzheimer's and related diseases for many years, looking for new treatment approaches. Now, they think they may have taken a significant step along this path by identifying the distant earthquake that causes Alzheimer's.
Basic Science Brings it All Together
Amyloid diseases are caused by the misfolding of proteins into structures that lead them to cluster together, forming microscopic fibril or plaques, which deposit in internal organs and interfere with normal function, sometimes lethally. In the case of Alzheimer's, these fibrils kill nerve cells in areas of the brain that are crucial for memory.
These diseases include Alzheimer's, Parkinson's, and a peripheral nervous system disease called familial amyloid polyneuropathy (FAP)a collection of more than 80 rare amyloid diseases caused by the misfolding of the protein transthyretin (TTR), which the liver secretes into the bloodstream to carry thyroid hormone and vitamin A.
In the FAP diseases, mutations in the TTR protein are known to play a direct role in causing the disease. Basically, these mutations change the amino acid sequence of TTR, and these changes alter protein folding in such a way as to predispose the proteins to misfold and accumulate into microscopic fibrils, which can then grow into the protein plaques characteristic of FAP and other amyloid diseases.
However, in Alzheimer's disease, the cause of misfolding is not so obvious. A number of mutations are associated with rare forms of familial Alzheimer's, but not with most common cases (about 95 percent of the cases). This suggests there must be a more common cause of Alzheimer's disease, and Kelly has combined efforts with several of his colleagues at Scripps Research to find it.
A few years ago, Kelly started to think about traumatic head injuries, which are a major risk factor for later developing Alzheimer's disease. The body responds to such injuries with inflammatory reactions that cause the release of components of lipid membranes, such as cholesterol.
Kelly began to discuss this with his colleagues in The Skaggs Institute for Chemical Biology, Scripps Research President Richard A. Lerner, M.D., and Scripps Research Associate Professor Paul Wentworth, Jr., Ph.D. Lerner and Wentworth had recently discovered how inflammation can lead to the production of reactive oxygen species such as ozone, which can trigger pathological changes in other molecules in the body, like cholesterol.
In a paper last year, Lerner, Wentworth, and several colleagues described how ozone reacts with normal metabolites to produce toxic compounds during inflammatory processes taking place in the body. The scientists describe two such compounds, which they call the 'atheronals.'
The scientists suggest these newly identified products are critical to the pathogenesis of the disease atherosclerosis because these atheronals were found in atherosclerotic plaques that were surgically removed from patients with atherosclerosis. (Atherosclerosis is a common vascular disease that increases the risk of heart attacks and strokes and is characterized by a hardening of the arteries over time due to deposits of fibrous tissue, calcium, fat, cholesterol, proteins, cells, and other materials on the inner 'endothelial' walls of an artery).
This discovery made Kelly sit up straight when he first heard it because inflammation is increasingly seen as playing a role in neurodegenerative diseases. Also, there are a fair number of risk factors in common between the two diseases, including hypercholesterolemia and inflammation.
In their new study, Kelly and his colleagues suggest that inflammation in the brain could create a perfect storm in which cholesterol and lipids react with ozone and other inflammatory chemicals to produce abnormal reactive metabolites, which, in turn, modify the folding of normal amyloid beta protein.
These modified amyloid beta proteins can catalyze misfolding in other unmodified amyloid beta proteins, starting an avalanche of misfolding that results -- perhaps years or decades later -- in Alzheimer's disease.
A New Way of Thinking About Disease in General
To examine the hypothesis that these metabolites may be the root cause of Alzheimer's, Kelly and his colleagues examined the post-mortem brains of Alzheimer's patients and compared these to age-matched controls.
They found evidence of atheronals in the brains of both the Alzheimer's patients and the control subjects. The levels of atheronals in the brains of the Alzheimer's patients were not significantly elevated, but this is not necessarily surprising.
According to the new theory, the propagation of misfolding and the buildup of fibrils inside the brain does not depend upon continuous exposure to metabolite-modified proteins, but to exposure during a precipitating event that may occur a decade or more earlier. The creation of these metabolite-linked misfolding proteins is only the initiator of the fibril plaques.
Kelly and colleagues also performed experiments in the test tube and found that atheronals and lipid oxidation products have the ability to dramatically accelerate the misfolding of amyloid beta and to reduce the concentration of the protein needed for misfolding to take place to concentrations found in the brain.
This is an entirely new way of thinking about not only Alzheimer's disease, but disease in general. Historically, science has regarded disease as based on the up or down regulation of gene expression or protein function.
But this theory suggests a new sort of pathology -- the creation of a reactive metabolite by inflammatory stress, leading to the modification of a protein, the aggregation of that protein over time, and the degeneration of function in the brain or whichever internal organ hosts the aggregation.
The inflammatory metabolite theory of Alzheimer's will be difficult to prove, admits Kelly, because the presence of these abnormal metabolites are hard to detect years after they initiated the aggregation. There is, so far, no smoking gun.
'Is [this theory] right? Time will tell,' says Kelly. 'That's how science works.'
The article, 'Metabolite-initiated protein misfolding may trigger Alzheimer's disease' was authored by Qinghai Zhang, Evan T. Powers, Jorge Nieva, Mary E. Huff, Maria A. Dendle, Jan Bieschke, Charles G. Glabe, Albert Eschenmoser, Paul Wentworth, Jr., Richard A. Lerner, and Jeffery W. Kelly and appears in the online edition of the journal Proceedings of the National Academy of Sciences the week of March 15-19, 2004. The article will appear in print later this year. See: pnas/cgi/doi/10.1073/pnas.0400924101.
This work was supported by The Skaggs Institute for Chemical Biology and the Lita Annenberg Hazen Foundation.
About The Scripps Research Institute
The Scripps Research Institute in La Jolla, California, is one of the world's largest, private, non-profit biomedical research organizations. It stands at the forefront of basic biomedical science that seeks to comprehend the most fundamental processes of life. Scripps Research is internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases and synthetic vaccine development.
Contact: Jason Bardi
jasonbscripps
858-784-9254
Scripps Research Institute
Synthesis-Dependent Strand Annealing In Meiosis
In organisms that reproduce sexually, sex cells (gametes) are produced by the specialized cell division called meiosis, which halves the number of
chromosomes from two sets (diploid) to one (haploid). During meiosis, homologous DNA molecules exchange genetic material (in a process called
homologous recombination), thereby contributing to genetic diversity. In addition, a subset of recombinants, called crossovers, creates connections
between chromosomes that are required for those chromosomes to be accurately segregated.
Accurate segregation ensures that gametes contain one and
only one copy of each chromosome. Recombination is initiated by chromosome breakage. A regulatory process then selects a subset of breaks to be healed
by a mechanism that forms crossover recombinants. Many of the remaining breaks are healed to form so-called "noncrossover" recombinants (also
referred to as "gene conversions"). Until recently it was thought that both crossovers and noncrossovers were formed by nearly identical pathways;
which form arose was thought to depend on how the last enzyme in the pathway attacked the last DNA intermediate.
However, more recent observations
suggested noncrossover recombinants might arise by a mechanism involving less stable intermediates than those required to make crossovers. In this
week's issue of PLoS Biology Dr. Douglas Bishop, Dr. Melissa McMahill, and Dr. Caroline Sham show how a yeast strain was constructed that allowed
detection of a genetic signature of such unstable recombination intermediates. This strain provided evidence that meiotic crossovers and
non-crossovers do indeed form by quite different mechanisms.
Citation: McMahill MS, Sham CW, Bishop DK (2007) Synthesis-dependent strand annealing in meiosis. PLoS Biol 5(11): e299.
doi:10.1371/journal.pbio.0050299
Please click here
plosbiology
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
chromosomes from two sets (diploid) to one (haploid). During meiosis, homologous DNA molecules exchange genetic material (in a process called
homologous recombination), thereby contributing to genetic diversity. In addition, a subset of recombinants, called crossovers, creates connections
between chromosomes that are required for those chromosomes to be accurately segregated.
Accurate segregation ensures that gametes contain one and
only one copy of each chromosome. Recombination is initiated by chromosome breakage. A regulatory process then selects a subset of breaks to be healed
by a mechanism that forms crossover recombinants. Many of the remaining breaks are healed to form so-called "noncrossover" recombinants (also
referred to as "gene conversions"). Until recently it was thought that both crossovers and noncrossovers were formed by nearly identical pathways;
which form arose was thought to depend on how the last enzyme in the pathway attacked the last DNA intermediate.
However, more recent observations
suggested noncrossover recombinants might arise by a mechanism involving less stable intermediates than those required to make crossovers. In this
week's issue of PLoS Biology Dr. Douglas Bishop, Dr. Melissa McMahill, and Dr. Caroline Sham show how a yeast strain was constructed that allowed
detection of a genetic signature of such unstable recombination intermediates. This strain provided evidence that meiotic crossovers and
non-crossovers do indeed form by quite different mechanisms.
Citation: McMahill MS, Sham CW, Bishop DK (2007) Synthesis-dependent strand annealing in meiosis. PLoS Biol 5(11): e299.
doi:10.1371/journal.pbio.0050299
Please click here
plosbiology
Public Library of Science
185 Berry Street, Suite 3100
San Francisco, CA 94107
USA
Two Innovative University Of Texas At Austin Biologists Become HHMI Early Career Scientists
Two University of Texas at Austin biologists join 50 of the nation's best early career science faculty to focus on their boldest and potentially transformative research ideas with support from a new initiative from the Howard Hughes Medical Institute (HHMI).
As Early Career Scientists, Dr. Dan Bolnick and Dr. John Wallingford will receive a six-year appointment to HHMI and, along with it, the freedom to explore their best ideas without worrying about where to find the money to fund those experiments.
Bolnick, an assistant professor of integrative biology, studies how species evolve using threespine stickleback fish on Vancouver Island, British Columbia. Thousands of lakes and streams that were created when the giant glaciers melted at the end of the last Ice Age were colonized by the stickleback's marine ancestors, which were remarkably successful in adapting to various niches in their new habitats.
Today, the environmental variations among the lakes make them the perfect setting for Bolnick to explore how the fish coevolve with other organisms. He wants to determine why each lake harbors a distinctive community of parasites. He will then measure how sticklebacks' immune systems have evolved to fight off the parasites found in any given lake. Sorting out these responses may improve understanding of chronic parasite-borne diseases that affect humans.
John Wallingford, an associate professor of molecular cell and developmental biology, studies morphogenesis - how tissues, organs and organisms develop their shapes. His interest in this field began as an undergraduate when he manipulated frog embryos and watched them develop in a dish of pond water. He later found that activating a single gene in the embryos triggers a series of shape-shifting events that curl a flat sheet of cells into a closed neural tube.
This tube later develops into the spinal cord and brain. Improper closure of the neural tube leads to birth defects, such as spina bifida. Wallingford is expanding his research program to use frogs and mice to study how genetic information is translated into the forces that move tissues during development.
HHMI will provide Wallingford and Bolnick with a full salary, benefits and a research budget of $1.5 million over their six-year appointment. The institute will also cover other expenses, including research space and the purchase of critical equipment.
The institute established its Early Career Scientist program in 2008 as a way to provide much-needed support to the United States' best faculty as they pursue innovative ideas in the early stages of their careers.
"These scientists are at the early stage of their careers, when they are full of energy and not afraid to try something new," said Jack Dixon, HHMI vice president and chief scientific officer. "They have already demonstrated that they are not apt to play it safe - and we hope they will continue to do something really original."
Last year, Dr. Tanya Paull, an associate professor of molecular genetics and microbiology, became the first faculty member at The University of Texas at Austin to be named an HHMI Investigator. This highly prestigious and coveted award is funded by a different support program at HHMI that gives established faculty the funding and flexibility to tackle their most ambitious, risky research plans.
Source:
Lee Clippard
University of Texas at Austin
As Early Career Scientists, Dr. Dan Bolnick and Dr. John Wallingford will receive a six-year appointment to HHMI and, along with it, the freedom to explore their best ideas without worrying about where to find the money to fund those experiments.
Bolnick, an assistant professor of integrative biology, studies how species evolve using threespine stickleback fish on Vancouver Island, British Columbia. Thousands of lakes and streams that were created when the giant glaciers melted at the end of the last Ice Age were colonized by the stickleback's marine ancestors, which were remarkably successful in adapting to various niches in their new habitats.
Today, the environmental variations among the lakes make them the perfect setting for Bolnick to explore how the fish coevolve with other organisms. He wants to determine why each lake harbors a distinctive community of parasites. He will then measure how sticklebacks' immune systems have evolved to fight off the parasites found in any given lake. Sorting out these responses may improve understanding of chronic parasite-borne diseases that affect humans.
John Wallingford, an associate professor of molecular cell and developmental biology, studies morphogenesis - how tissues, organs and organisms develop their shapes. His interest in this field began as an undergraduate when he manipulated frog embryos and watched them develop in a dish of pond water. He later found that activating a single gene in the embryos triggers a series of shape-shifting events that curl a flat sheet of cells into a closed neural tube.
This tube later develops into the spinal cord and brain. Improper closure of the neural tube leads to birth defects, such as spina bifida. Wallingford is expanding his research program to use frogs and mice to study how genetic information is translated into the forces that move tissues during development.
HHMI will provide Wallingford and Bolnick with a full salary, benefits and a research budget of $1.5 million over their six-year appointment. The institute will also cover other expenses, including research space and the purchase of critical equipment.
The institute established its Early Career Scientist program in 2008 as a way to provide much-needed support to the United States' best faculty as they pursue innovative ideas in the early stages of their careers.
"These scientists are at the early stage of their careers, when they are full of energy and not afraid to try something new," said Jack Dixon, HHMI vice president and chief scientific officer. "They have already demonstrated that they are not apt to play it safe - and we hope they will continue to do something really original."
Last year, Dr. Tanya Paull, an associate professor of molecular genetics and microbiology, became the first faculty member at The University of Texas at Austin to be named an HHMI Investigator. This highly prestigious and coveted award is funded by a different support program at HHMI that gives established faculty the funding and flexibility to tackle their most ambitious, risky research plans.
Source:
Lee Clippard
University of Texas at Austin
Researchers Could Use Plant's Light Switch To Control Cells
Chandra Tucker shines a blue light on yeast and mammalian cells in her Duke University lab and the edges of them start to glow. The effect is the result of a light-activated switch from a plant that has been inserted into the cell.
Researchers could use this novel "on-off switch" to control cell growth or death, grow new tissue or deliver doses of medication directly to diseased cells, said Tucker, an assistant research professor in the biology department at Duke.
She and colleagues created the switch by genetically inserting two proteins from a mustard plant, Arabidopsis thaliana, into yeast cells, kidney cells and cultured rodent brain tissue. The two proteins interact under light to provide the control over cell functions.
The switch is similar to one described last year where researchers genetically inserted a different light-receptive plant protein and its interacting protein partner from Arabidopsis into mammalian cells. In response to red light, these proteins interacted to cause mammalian cells to change shape, moving in the direction of the light.
Tucker's switch uses Arabidopsis proteins that respond to blue light. Unlike the red-light activated proteins, which need an added cofactor, a chemical that is required for the light response, the blue-light switch doesn't need any additional chemicals to work because it uses a cofactor that naturally exists in non-plant organisms.
"It's hard to deliver a chemical to a fly or to individual cells. This new approach, with one of the molecules already in the mammalian or yeast cells, makes building a light-controlled switch a lot easier," Tucker said. Her team describes the switch in the Oct. 31 Nature Methods.
To test the switch, the team fused one of the light-sensitive Arabidopsis proteins to a red fluorescent protein and the other to a green fluorescent protein, which was in turn attached to the cell membrane. When the researchers flashed blue light on the cell, the plant proteins interacted, causing the red fluorescent protein to rapidly move to the cell membrane, which then glowed yellow due to the merging of the red and green fluorescing proteins. The team found that this interaction was reversible and could be triggered repeatedly with light exposure.
The switch is one among several that have been designed to give researchers better control of different functions of the cell. The next step in developing the switch will be to make the interacting proteins more effective, Tucker said. The approach is expected to be applicable not only for studies in cultured cells and yeast, but also worms, fruit flies, mice and other model organisms. Eventually this method could allow researchers to test how cells in a tissue affect neighboring cells in a tissue, to guide axon growth in neurons to repair brain tissue, or even to kill cancer cells.
Tucker's new approach will be a "major boon" to those who wish to apply light activation to their own experimental systems, said Klaus Hahn, a pharmacologist at the University of North Carolina at Chapel Hill, whose lab reported on another blue-light responsive protein to control movement of mammalian cells last year.
Hahn said the "elegant work will likely see broad use, in many fields and for applications that will surprise us," and it is already going to be applied to important areas of research, such as control of gene expression.
Source:
Ashley Yeager
Duke University
Researchers could use this novel "on-off switch" to control cell growth or death, grow new tissue or deliver doses of medication directly to diseased cells, said Tucker, an assistant research professor in the biology department at Duke.
She and colleagues created the switch by genetically inserting two proteins from a mustard plant, Arabidopsis thaliana, into yeast cells, kidney cells and cultured rodent brain tissue. The two proteins interact under light to provide the control over cell functions.
The switch is similar to one described last year where researchers genetically inserted a different light-receptive plant protein and its interacting protein partner from Arabidopsis into mammalian cells. In response to red light, these proteins interacted to cause mammalian cells to change shape, moving in the direction of the light.
Tucker's switch uses Arabidopsis proteins that respond to blue light. Unlike the red-light activated proteins, which need an added cofactor, a chemical that is required for the light response, the blue-light switch doesn't need any additional chemicals to work because it uses a cofactor that naturally exists in non-plant organisms.
"It's hard to deliver a chemical to a fly or to individual cells. This new approach, with one of the molecules already in the mammalian or yeast cells, makes building a light-controlled switch a lot easier," Tucker said. Her team describes the switch in the Oct. 31 Nature Methods.
To test the switch, the team fused one of the light-sensitive Arabidopsis proteins to a red fluorescent protein and the other to a green fluorescent protein, which was in turn attached to the cell membrane. When the researchers flashed blue light on the cell, the plant proteins interacted, causing the red fluorescent protein to rapidly move to the cell membrane, which then glowed yellow due to the merging of the red and green fluorescing proteins. The team found that this interaction was reversible and could be triggered repeatedly with light exposure.
The switch is one among several that have been designed to give researchers better control of different functions of the cell. The next step in developing the switch will be to make the interacting proteins more effective, Tucker said. The approach is expected to be applicable not only for studies in cultured cells and yeast, but also worms, fruit flies, mice and other model organisms. Eventually this method could allow researchers to test how cells in a tissue affect neighboring cells in a tissue, to guide axon growth in neurons to repair brain tissue, or even to kill cancer cells.
Tucker's new approach will be a "major boon" to those who wish to apply light activation to their own experimental systems, said Klaus Hahn, a pharmacologist at the University of North Carolina at Chapel Hill, whose lab reported on another blue-light responsive protein to control movement of mammalian cells last year.
Hahn said the "elegant work will likely see broad use, in many fields and for applications that will surprise us," and it is already going to be applied to important areas of research, such as control of gene expression.
Source:
Ashley Yeager
Duke University
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