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Scripps Florida scientists devise accelerated method to determine infectious prion strainsScripps Florida scientists devise accelerated method to determine infectious prion strains
May 29, 2009Current tests to identify specific strains of infectious prions, which cause a range of transmissible diseases (such as mad cow) in animals and humans, can take anywhere from six months to a year to yield results - a time-lag that may put human populations at risk.
Now, a group of scientists from The Scripps Research Institute's Florida campus have developed a new method that cuts this critical time lag by several months.
The new research was published in the open-access journal PLoS ONE on May 29, 2009.
"Because some prion strains are pathogenic for humans and some are not, it's vital that we know the difference when we find them in the field and when we study them in the laboratory," said Corinne Lasmézas, a professor in the Department of Infectology at Scripps Florida who led the study. "Currently, the identification process for mouse-adapted strains takes between six and eight months and can take as long as a year, depending on the strain. Our accelerated method reduces that time to around four months."
The new method for distinguishing among various strains combines a transgenic mouse model with a rapid and sensitive cell-based procedure, the Cell Panel Assay developed by Scripps Florida's Charles Weissmann (chair of the Department of Infectology) and Sukhvir Mahal (senior staff scientist), also investigators on the new study.
"There are about 20 prion strains known in mouse models," Lasmézas said. "We still don't understand what determines the difference among strains even though it's very important, especially for any potential therapeutic development. Our new method should help quicken the pace of research."
The Mysteries of Prions
Prion diseases, also called spongiform encephalopathies, are a group of closely related, fatal neurodegenerative disorders that affect mammals, including cows, sheep, and deer, as well as humans. Different strains of the infectious agent, called a prion, cause mad cow disease, chronic wasting disease, and different forms of scrapie and human Creutzfeldt-Jacob disease.
Mad cow disease has had devastating consequences for bovine livestock populations, particularly in Europe, and for humans who have consumed contaminated beef products.
To date, there have been more than 200 recorded human fatalities worldwide due to mad cow disease. Creutzfeldt-Jacob disease, a low-incidence but always fatal disease, affects humans in all countries.
Prions consist mainly or entirely of an abnormal form of a normal cellular protein. They multiply by converting their normal counterparts into a likeness of themselves, which may aggregate to form deposits called amyloid. Accumulation of different kinds of amyloid plays a role in a wide range of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.
Currently, different varieties of prion strains are identified in mouse models according to incubation time, clinical symptoms, and localization of brain lesions.
Accelerated Incubation
In the new test developed by Lasmézas and Weissmann, a transgenic mouse line called Tga20 plays an important role, because it succumbs rapidly to prion disease.
"The prions primarily target the brainstem and the thalamus of this transgenic mouse, explaining why these animals have a shorter incubation time than their normal counterparts," Lasmézas said. "The prion aggregates also don't spread evenly to other brain regions, and their distribution is characteristic for different strains."
Importantly, the brain tissue can be subjected to the Cell Panel Assay, which unlike the current histological method, doesn't require time intensive examination of brain lesions and can be completed within two weeks, Lasmézas added. The test has been partially automated.
Development of the method provided the scientists with the opportunity to make the observation that there was, in some brain regions, little relationship between the amount of abnormal prion protein deposition and the amount of normal prion protein. This was something of a surprise, Lasmézas said, but not totally unexpected.
"We and others believe that the prion protein may not be the sole player in these diseases," she said. "Perhaps there is a co-factor, or perhaps the protein structure differs somewhat from one brain region to the next. We don't know. Just like we don't really know the reason for the different behavior of the various prion strains-is this cause or effect? Our new method should help accelerate the process of discovery."
Scripps Research Institute
"Because some prion strains are pathogenic for humans and some are not, it's vital that we know the difference when we find them in the field and when we study them in the laboratory," said Corinne Lasmézas, a professor in the Department of Infectology at Scripps Florida who led the study. "Currently, the identification process for mouse-adapted strains takes between six and eight months and can take as long as a year, depending on the strain. Our accelerated method reduces that time to around four months."
The new method for distinguishing among various strains combines a transgenic mouse model with a rapid and sensitive cell-based procedure, the Cell Panel Assay developed by Scripps Florida's Charles Weissmann (chair of the Department of Infectology) and Sukhvir Mahal (senior staff scientist), also investigators on the new study.
"There are about 20 prion strains known in mouse models," Lasmézas said. "We still don't understand what determines the difference among strains even though it's very important, especially for any potential therapeutic development. Our new method should help quicken the pace of research."
The Mysteries of Prions
Prion diseases, also called spongiform encephalopathies, are a group of closely related, fatal neurodegenerative disorders that affect mammals, including cows, sheep, and deer, as well as humans. Different strains of the infectious agent, called a prion, cause mad cow disease, chronic wasting disease, and different forms of scrapie and human Creutzfeldt-Jacob disease.
Mad cow disease has had devastating consequences for bovine livestock populations, particularly in Europe, and for humans who have consumed contaminated beef products.
To date, there have been more than 200 recorded human fatalities worldwide due to mad cow disease. Creutzfeldt-Jacob disease, a low-incidence but always fatal disease, affects humans in all countries.
Prions consist mainly or entirely of an abnormal form of a normal cellular protein. They multiply by converting their normal counterparts into a likeness of themselves, which may aggregate to form deposits called amyloid. Accumulation of different kinds of amyloid plays a role in a wide range of neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.
Currently, different varieties of prion strains are identified in mouse models according to incubation time, clinical symptoms, and localization of brain lesions.
Accelerated Incubation
In the new test developed by Lasmézas and Weissmann, a transgenic mouse line called Tga20 plays an important role, because it succumbs rapidly to prion disease.
"The prions primarily target the brainstem and the thalamus of this transgenic mouse, explaining why these animals have a shorter incubation time than their normal counterparts," Lasmézas said. "The prion aggregates also don't spread evenly to other brain regions, and their distribution is characteristic for different strains."
Importantly, the brain tissue can be subjected to the Cell Panel Assay, which unlike the current histological method, doesn't require time intensive examination of brain lesions and can be completed within two weeks, Lasmézas added. The test has been partially automated.
Development of the method provided the scientists with the opportunity to make the observation that there was, in some brain regions, little relationship between the amount of abnormal prion protein deposition and the amount of normal prion protein. This was something of a surprise, Lasmézas said, but not totally unexpected.
"We and others believe that the prion protein may not be the sole player in these diseases," she said. "Perhaps there is a co-factor, or perhaps the protein structure differs somewhat from one brain region to the next. We don't know. Just like we don't really know the reason for the different behavior of the various prion strains-is this cause or effect? Our new method should help accelerate the process of discovery."
Scripps Research Institute
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The mysterious death of patients around the world following a routine dosage of the common blood thinner, heparin, sent researchers on a frantic search to uncover what could make the standard drug so toxic.
Prions link cholesterol to neurodegeneration
Prion infection of neurons increases the free cholesterol content in cell membranes. A new study published in the online open access journal BMC Biology suggests that disturbances in membrane cholesterol may be the mechanism by which prions cause neurodegeneration and could point to a role for cholesterol in other neurodegenerative diseases.
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The Pathological Protein: Mad Cow, Chronic Wasting, and Other Deadly Prion Diseases by Philip Yam (Author) In 1996, British doctors were horrified to discover that mad cow disease (BSE), an affliction that had been plaguing British cattle for ten years, had jumped the species barrier and was appearing in humans as variant Creutzfeldt-Jakob disease (vCJD). Not unlike the mad cows, victims of vCJD suffer from a degenerative neurological disease that peppers the brain with microscopic holes, causing dementia, loss of motor control, and certain death. What alarms researchers and public health officials worldwide is that the incubation period for vCJD may be as long as 10 or even 15 years, and during this period those infected are symptom-free. And because the disease is so far undetectable except by autopsy, there is no way of knowing with certainty how many people have already been infected. In... |
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Deadly Feasts: The "Prion" Controversy and the Public's Health by Richard Rhodes (Author) In this brilliant and gripping medical detective story. Richard Rhodes follows virus hunters on three continents as they track the emergence of a deadly new brain disease that first kills cannibals in New Guinea, then cattle and young people in Britain and France -- and that has already been traced to food animals in the United States. In a new Afterword for the paperback, Rhodes reports the latest U.S. and worldwide developments of a burgeoning global threat. |
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Prion Biology and Diseases, Second Edition (Cold Spring Harbor Monograph Series) by Stanley B. Prusiner (Author), Stanley B. Prusiner (Editor) A new edition of the most authoritative book in its field, first published in 1999 and edited by the Nobel Prize–winning founder of the field. This edition is expanded and completely updated, and includes chapters on therapeutics, and diagnostic methods and approaches. |
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The Family That Couldn't Sleep: A Medical Mystery by D.T. Max (Author) For two hundred years a noble Venetian family has suffered from an inherited disease that strikes their members in middle age, stealing their sleep, eating holes in their brains, and ending their lives in a matter of months. In Papua New Guinea, a primitive tribe is nearly obliterated by a sickness whose chief symptom is uncontrollable laughter. Across Europe, millions of sheep rub their fleeces raw before collapsing. In England, cows attack their owners in the milking parlors, while in the American West, thousands of deer starve to death in fields full of grass. What these strange conditions–including fatal familial insomnia, kuru, scrapie, and mad cow disease–share is their cause: prions. Prions are ordinary proteins that sometimes go wrong, resulting in neurological... |
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thirtytwo Men's Prion Snowboard Boot,Black/Grey,10.5 M US by thirtytwo The ThirtyTwo Mens Prion Snowboard Boot provides the performance you need without making you forgo that new jacket you've been eyeing. The Prions forgiving flex along with its heel-holding moldable liner and cushioning footbeds enable seasoned freestylers and progressing riders alike to up their games. Product FeaturesMaterial: [Upper] PU-coated synthetic & textile; [Sole] rubberLacing System: Traditional with speed hooks on cuffs Flex: Medium-soft (4 on ThirtyTwos 10-point scale) Removable Liner: Yes, thermo-moldableRecommended Use: Freestyle, all-mountain snowboardingManufacturer Warranty: 1 Year |
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thirtytwo Men's Prion Snowboard Boot,Black/Grey,7 M US by thirtytwo The ThirtyTwo Mens Prion Snowboard Boot provides the performance you need without making you forgo that new jacket you've been eyeing. The Prions forgiving flex along with its heel-holding moldable liner and cushioning footbeds enable seasoned freestylers and progressing riders alike to up their games. Product FeaturesMaterial: [Upper] PU-coated synthetic & textile; [Sole] rubberLacing System: Traditional with speed hooks on cuffs Flex: Medium-soft (4 on ThirtyTwos 10-point scale) Removable Liner: Yes, thermo-moldableRecommended Use: Freestyle, all-mountain snowboardingManufacturer Warranty: 1 Year |
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Prions: The New Biology of Proteins by Claudio Soto (Author) The current interest in prion diseases has been fueled by the panic that originated from the appearance of a new variant of Creutzfeldt-Jakob disease and the evidence linking it to human exposure to the bovine spongiform encephalopathy (BSE) agent. Peer-reviewed to assure accuracy, this book describes the science, concepts, hypothesis, and mechanisms of prion disease transmission. It covers human and animal prion diseases, their incidence, prevalence, origin, and clinical and neuropathologic characteristics. The author provides scientific facts and a clear explanation of the relevance and implications of the findings for science in general. |
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Time of Plagues Prion (Performer) Tracks include: Senseless Miseries, To the Abyss of Hell, Envy & Hate, The Plagues, Executed, Beyond the Period, Armenia, The Opposite, and Instrumental. Argentinian metal. |
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