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Mo Costandi Prions are best known as the infectious agents that cause ‘mad cow’ disease and the human versions of it, such as variant Creutzfeldt–Jakob Disease. But the proteins also have at least one known useful function, in the cells that insulate nerves, and are suspected to have more. Now researchers have provided the first direct evidence that the proteins play an important role in neurons themselves. The team reports in the Journal of Neuroscience1 that prions are involved in developmental plasticity, the process by which the structure and function of neurons in the growing brain is shaped by experience. Prions come in two main forms: the normal version and the misfolded, infectious version. The normal version, known as cellular prion protein (or PrPC), is present in every cell of the body and helps to maintain the myelin sheath in the cells that protect the nerves2. But the molecule is abundant in neurons themselves, especially during development. Because it is tethered to the membrane, it is widely assumed to be involved in signalling between nerve cells, but little direct evidence has been found for this. Neurobiologist Enrico Cherubini of the International School for Advanced Studies in Trieste, Italy, and his colleagues therefore decided to look at the effects of electrical stimulation on slices of tissue from the hippocampus of healthy 3–7-day-old mice and of animals genetically engineered to lack the gene that encodes the prion protein. They used electrodes to stimulate individual cells at the same time as the networks of young neurons showed bursts of spontaneous electrical activity, or to simultaneously stimulate pairs of cells that are connected to each other. © 2013 Nature Publishing Group

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders; Chapter 13: Memory, Learning, and Development
Link ID: 17809 - Posted: 02.16.2013

by Jessica Hamzelou COULD we stem the tide of ageing by delaying the deterioration of stem cells? A new compound that appears to do just that could help us find ways to protect our organs from age-related wear and tear, experiments in mice suggest. As we age, so do our mesenchymal stem cells (MSCs): their numbers in our bone marrow decline, and those that are left lose the ability to differentiate into the distinct cell types - such as bone, cartilage, fat and possibly muscle cells - that help in the healing process. "We think this ageing of stem cells may be linked to the onset of some age-related disorders, such as osteoporosis," says Ilaria Bellantuono at the University of Sheffield in the UK. Earlier research in mice had suggested that the prion protein expressed by MSCs might play a role in holding back stem cell ageing. Mice lacking the prion protein were less able to regenerate blood cells. The study provided more evidence that correctly folded prions serve a useful purpose in the body, despite the role that misfolded prions play in BSE and vCJD. Bellantuono and her colleagues have now found that the prion protein performs a similar function in humans - older MSCs from human bone marrow expressed less of the protein than younger ones. In a bid to find a compound that might slow MSC ageing, the team tested numerous molecules known to target prion proteins on dishes of human stem cells. One molecule emerged as a potential candidate - stem cells treated with it produced 300 times the number of cells over 250 days than untreated stem cells. The treated cells kept on dividing for longer. © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders; Chapter 7: Life-Span Development of the Brain and Behavior
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders; Chapter 13: Memory, Learning, and Development
Link ID: 17175 - Posted: 08.18.2012

By James Gallagher Health and science reporter, BBC News The tantalising prospect of treating a range of brain diseases, such as Alzheimer's and Parkinson's, all with the same drug, has been raised by UK researchers. In a study, published in Nature, they prevented brain cells dying in mice with prion disease. It is hoped the same method for preventing brain cell death could apply in other diseases. The findings are at an early stage, but have been heralded as "fascinating". Many neuro-degenerative diseases result in the build-up of proteins which are not put together correctly - known as misfolded proteins. This happens in Alzheimer's, Parkinson's and Huntington's as well as in prion diseases, such as the human form of mad cow disease. Turn off Researchers at the University of Leicester uncovered how the build-up of proteins in mice with prion disease resulted in brain cells dying. They showed that as misfolded protein levels rise in the brain, cells respond by trying to shut down the production of all new proteins. It is the same trick cells use when infected with a virus. Stopping production of proteins stops the virus spreading. However, shutting down the factory for a long period of time ends up killing the brain cells as they do not produce the proteins they actually need to function. BBC © 2012

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders; Chapter 11: Motor Control and Plasticity
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders; Chapter 5: The Sensorimotor System
Link ID: 16759 - Posted: 05.07.2012

by Helen Thompson Reports of ‘mad cow’ disease in the United States erupted in the news this week after the US Department of Agriculture (USDA) confirmed that the remains of a California dairy cow had tested positive for bovine spongiform encephalopathy (BSE). This marks the fourth case of BSE identified in the US, and the first case in six years. In spongiform encephalopathy diseases, abnormally folded prion proteins accumulate in the brain, causing other proteins to deform as well. BSE has proved to be unusually adept at jumping between species; humans exposed to BSE can develop its human counterpart: Creutzfeldt-Jakob disease (CJD). In a statement released on 24 April, Karen Ross, Secretary of the California Department of Food and Agriculture said, “The detection of BSE shows that the surveillance program in place in California and around the country is working.” Food safety advocates such as Yonkers, New York, -based Consumers Union say it’s a warning sign that surveillance is inadequate and needs to be stepped up. Ross’s statement also makes a point of noting a key feature of this particular case: The infected cow carried what is known as ‘L-type’ BSE, a version of the disease that has not been detected before in the US and has so far not been associated with transmission through animal feed. As the policy debate over testing rumbles on, here is a short guide to what is known and not known about this rare strain and its unexpected appearance. © 2012 Nature Publishing Group,

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 16740 - Posted: 05.02.2012

By STEPHANIE STROM The Department of Agriculture announced that it had identified a case of mad cow disease, the first in six years, in a dairy cow in central California. The cow “was never presented for human consumption, so it at no time presented a risk to the food supply or human health,” John Clifford, chief veterinary officer at the department, said in a statement. Dr. Clifford noted that milk did not transmit bovine spongiform encephalopathy, the scientific name for mad cow disease. He expressed confidence in the health of the nation’s cattle and the safety of beef during a press briefing in Washington. The animal had been picked up from the farm and taken to a rendering plant, which noticed some of the signs of B.S.E., such as unsteadiness and aggression, and notified U.S.D.A. inspectors, Dr. Clifford said in a brief interview. The body will remain at the rendering facility and will be disposed of once the agency completes its investigation, probably by incineration or some other method that ensures the destruction of its tissues. It was the fourth reported case of mad cow disease, a degenerative disease that affects the brains and spinal cords of cattle, in the United States. Humans can contract the disease by eating meat from an infected cow. Only one case of mad cow disease in the United States was of the type derived from feed. That case set off a panic in 2003 when a Canadian-born cow in Washington state tested positive. © 2012 The New York Times Company

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 16708 - Posted: 04.25.2012

Bijal P. Trivedi On a frigid winter's morning in 1992, Susan Lindquist, then a biologist at the University of Chicago in Illinois, trudged through the snow to the campus's intellectual-property office to share an unconventional idea for a cancer drug. A protein that she had been working on, Hsp90, guides misfolded proteins into their proper conformation. But it also applies its talents to misfolded mutant proteins in tumour cells, activating them and helping cancer to advance. Lindquist suspected that blocking Hsp90 would thwart the disease. The intellectual-property project manager she met with disagreed, calling Lindquist's idea “ridiculous” because it stemmed from experiments in yeast. His “sneering tone”, she says, left an indelible mark. “It was actually one of the most insulting conversations I've had in my professional life.” It led her to abandon her cancer research on Hsp90 for a decade. Today, more than a dozen drug companies are developing inhibitors of the protein as cancer treatments. Lindquist seems able to shrug off such injustices, now. Her work over the past 20 years has consistently challenged standard thinking on evolution, inheritance and the humble yeast. She has helped to show how misfolded infectious proteins called prions can override the rules of inheritance in yeast, and how this can be used to model human disease. She has also proposed a mechanism by which organisms can unleash hidden variation and evolve by leaps and bounds. She was the first female director of the prestigious Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, and has received more than a dozen awards and honours in the past five years. In a paper being published this week in Nature, she and her colleagues show that in wild yeast, prions provide tangible advantages, such as survival in harsh conditions and drug resistance1. © 2012 Nature Publishing Group

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 16388 - Posted: 02.16.2012

By Rebecca Cheung The protein-based pathogens known as prions may pass between different species more easily than has been thought, a team of French researchers reports in the Jan. 27 Science. By infecting engineered mice with prions from cows and goats, scientists also have shown that the invaders readily target tissues other than the brain. “We may underestimate the threat posed by some of these diseases by focusing only on the brain,” says Pierluigi Gambetti, a prion researcher at Case Western Reserve University in Cleveland. “It adds a new element to the equation.” The research also raises the possibility that new prion strains recently identified in cattle and small rodents might be able to jump to other species, including humans. “We should, in the future, be more exhaustive when looking at the possibility of prions being passed from one species to another,” says Hubert Laude, a professor at the French National Institute for Agricultural Research in Jouy-en-Josas and a coauthor of the study. Prions closely resemble normal proteins made by a host. When prions invade a host, they propagate by forcing these normal host proteins, actually called prion proteins, to assemble improperly. When these malformed proteins accumulate in the brain, they cause mind-wasting conditions such as Creutzfeldt-Jakob disease in people and scrapie in sheep. © Society for Science & the Public 2000 - 2012

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 16304 - Posted: 01.28.2012

By Tina Hesman Saey Infectious proteins that cause brain-wasting conditions like mad cow disease appear to build up in the brain long before initiating the cascade of deterioration that leads to dementia and death, a new study of mice finds. The findings suggest that other factors besides the misshapen infectious proteins characteristic of prion diseases may control the lethality of the disease. If scientists can determine what those factors are, future treatments may be able to prevent the infectious protein diseases — which include mad cow disease, scrapie in sheep and Creutzfeldt-Jakob disease in people — from progressing to a fatal stage. “We don’t know what’s going on here, but we do know there’s something interesting,” says John Collinge, director of the United Kingdom Medical Research Council Prion Unit in London, who headed the new study. Findings reported by Collinge and his colleagues in the Feb. 24 Nature contradict the idea that infectious versions of a normal brain protein called PrP accumulate slowly, gradually twisting all of the healthy copies of the protein into a disease-causing form. Researchers have thought that the disease-causing prions slowly build up to toxic levels that spell the death of brain cells. But the new study shows that the process is anything but gradual, and that infection and toxicity are independent stages of the disease. Prions quickly build up in the brains of mice over the course of a month or two, Collinge and his colleagues found, peaking at about 100 million infectious particles per brain. © Society for Science & the Public 2000 - 2011

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 15052 - Posted: 02.26.2011

Tiffany O'Callaghan Invasive biopsy is currently the only sure way to diagnose the degenerative neurological condition Creutzfeldt–Jakob Disease (CJD). But a highly sensitive assay could change that, providing a fast, accurate alternative for early diagnosis of this rare but deadly condition. In its most common form, known as sporadic CJD, the disease affects roughly one in a million people. Beginning in the 1990s, several cases of a variation of CJD known as vCJD were reported among people who had consumed beef from cows infected with another disease, bovine spongiform encephalopathy (BSE). The findings, published online in Nature Medicine1, also suggest that the assay — developed by microbiologist Ryuichiro Atarashi of Nagasaki University, Japan, and his team — could pave the way for the screening of broad sectors of the population. CJD is a prion disease, in which an isomer of a common protein known as the prion protein (PrP) takes on an abnormal shape and becomes an infectious variant called PrPSc. This variant is thought to trigger the subsequent malformation of other PrP proteins. Unlike their normal counterparts, PrPSc prions cannot be broken down, and instead accumulate — often clustering in brain tissue. The pockets of abnormal tissue that result cause brain tissue to develop a sponge-like appearance, and because prion conditions can be spread by affected humans or animals, the diseases are often referred to as transmissible spongiform encephalopathies (TSEs). Humans can be affected by several such conditions, while in addition to BSE in cows, there are several other such disorders among animals, including a condition called scrapie in sheep and hamsters. © 2011 Nature Publishing Group,

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14935 - Posted: 01.31.2011

by Debora MacKenzie You catch flu by inhaling germs – now it seems you can catch prion diseases that way too. Prions are misshapen proteins that cause brain degeneration in conditions such as mad cow disease and scrapie in animals, and Creutzfeldt–Jakob disease in humans. They can get into you if you eat infected meat or receive infected blood, but it was thought they couldn't spread through air. Now Adriano Aguzzi of the Swiss Federal Institute of Technology in Zurich reports that mice exposed for 10 minutes to aerosols containing as little as 2.5 per cent brain tissue from mice with scrapie all developed the disease within months. The prions didn't need processing by the immune system first, as some other research has suggested, but entered the brain directly through nasal nerves. "We were amazed at how efficiently they spread," says Aguzzi. He warns that this doesn't mean animals or people with prion diseases actually transmit them through the air: there have been no unexplained cases of disease transmission which suggested this. But workers in mills that process potentially infected carcasses may need more respiratory protection. Labs that test for prions routinely make 10 per cent suspensions of brain tissue, and any handling – pipetting, for example – creates aerosols. Prion labs are not required to use safety equipment that protects workers from aerosols. Aguzzi, who tested his aerosols at the highest level of protection, thinks those labs may now need to rethink safety measures. Journal reference: PLoS Pathogens, DOI: 10.1371/journal.ppat.1001257 © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14873 - Posted: 01.15.2011

A fast test to diagnose fatal brain conditions such as mad cow disease in cattle and Creutzfeldt-Jakob disease in humans could be on the horizon, according to a new study from National Institutes of Health scientists. Researchers at NIH's National Institute of Allergy and Infectious Diseases (NIAID) have developed a highly sensitive and rapid new method to detect and measure infectious agents called prions that cause these diseases. Prion diseases are primarily brain-damaging conditions also known as transmissible spongiform encephalopathies. They are difficult to diagnose, untreatable and ultimately fatal. A key physical characteristic of these diseases is dead tissue that leaves sponge-like holes in the brain. Prion diseases include mad cow disease, or bovine spongiform encephalopathy in cattle; scrapie in sheep; Creutzfeldt-Jakob disease in humans; and chronic wasting disease in deer, elk and moose. For more information about NIAID research on prion diseases, visit the NIAID Prion Diseases portal (http://www.niaid.nih.gov/topics/prion/Pages/default.aspx). Currently available diagnostic tests lack the sensitivity, speed or quantitative capabilities required for many important applications in medicine, agriculture, wildlife biology and research. Because prion infections can be present for decades before disease symptoms appear, a better test might create the possibility for early treatment to stop the spread of disease and prevent death. Now, a blending of previous test concepts by the NIAID group has led to the development of a new prion detection method, called real time quaking induced conversion assay, or RT-QuIC. This approach is described in a paper now online in the open-access journal PLoS Pathogens. Byron Caughey, Ph.D., led the study at NIAID's Rocky Mountain Laboratories in Hamilton, Mont.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14737 - Posted: 12.04.2010

by Amber Angelle For nearly 30 years, researchers have gathered evidence that a group of bizarre, fatal brain diseases—including mad cow and its human equivalent, Creutzfeldt-Jakob disease—are caused not by a virus or bacterium but by an abnormal form of a protein, called a prion. New studies lend the strongest support yet to this once-controversial idea and are also starting to reveal the beneficial natural functions these proteins perform before they go bad. Molecular biochemist Jiyan Ma at Ohio State University and colleagues were able to transform a normal protein produced by E. coli bacteria into a prion whose properties match those of the infectious version: It forms clumps, resists being cut by enzymes, and converts other normal proteins into the aberrant form. When the prion was injected into the brains of mice, the brains became spongy and riddled with holes, the telltale signs of prion disease. “Next we plan to take a closer look at the system we used to create infectious prions to identify the molecular mechanisms behind the change,” Ma says. In a separate experiment, researchers in the United States and Austria used a prion protein generated by E. coli to infect hamsters with a transmissible brain disease. The disease progressed very gradually, just as it does in humans, suggesting that the hamsters could provide a useful animal model system. Copyright © 2010, Kalmbach Publishing Co.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14523 - Posted: 10.05.2010

by Roger Highfield Before winning his Nobel prize, Stanley Prusiner was ridiculed for suggesting that something he called a prion caused spongiform brain diseases WHEN the evidence suggested that the baffling "spongiform" brain disorders Creutzfeldt-Jakob disease (CJD), kuru and scrapie could not be transmitted by a virus or bacterium, the neurologist Stanley Prusiner put forward a novel type of infectious agent as the cause: a rogue protein. It was an idea considered so outrageous that Prusiner was ridiculed. Prusiner first began to study these diseases in 1972, after one of his patients at the University of California, San Francisco, died of CJD. A decade later, in the journal Science (vol 216, p 136), he suggested that these diseases were caused by a "proteinaceous infectious particle", or prion. The idea built on the findings of British researchers. In 1967, Tikvah Alper of the Medical Research Council's Radiopathology Unit showed that whatever it was that caused CJD was unscathed by levels of ultraviolet radiation that would destroy any genetic material (Nature, vol 214, p 764). Shortly afterwards, mathematician John Stanley Griffith of Bedford College in London devised a protein-only hypothesis for scrapie propagation. His 1967 Nature paper (vol 215, p 1043) states there was no reason to fear that the idea "would cause the whole theoretical structure of molecular biology to come tumbling down". © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14464 - Posted: 09.18.2010

By Caroline Parkinson A new form of brain disease, similar to Creutzfeld-Jakob Disease, could affect more people than previously thought, researchers in the US say. It had been thought that only people with one genetic profile were vulnerable to the prion disease VPSPr. But in an Annals of Neurology study, Case Western Reserve University experts found people with all three possible gene patterns are affected by VPSPr. They say the findings could help with the treatment of prion diseases. Although it is a prion disease like vCJD, VPSPr is not linked to eating infected meat. However, like CJD, the new condition happens sporadically. It was first identified because of the fast-advancing form of dementia seen in those affected. They were also unable to speak or move. But tests for CJD proved negative. Further molecular examination showed VPSPr was a prion disease, but one which looked very different to those already known. The human prion protein gene comes in three variants, depending on which amino acid the prion proteins contain - valine (V) or methionine (M). People can be VV, MM or MV. The first clutch of cases identified all had the VV variant. However, these latest cases included people with the other variants too. Despite extensive research, a relatively large group of neurodegenerative diseases associated with dementia remain undefined. (C)BBC

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14359 - Posted: 08.14.2010

Daniel Cressey After an epic series of experiments, a group of researchers has observed and reproduced what could be the spontaneous generation of prions — rogue misfolded proteins that have been implicated in the destruction of the central nervous system. These misfolded proteins, the culprits in Creutzfeldt–Jakob disease and scrapie, are highly infectious. Although famously transmitted by the ingestion of infected meats, prions are also thought to arise spontaneously in a tiny fraction of humans and other animals. Such de novo prion generation has previously been achieved with animal cells using a method called 'protein misfolding cyclic amplification' (PMCA), which involves repeated rounds of ultrasound and incubation. Now, a London-based team reports observing prions appearing from healthy mouse brain tissue1. (Human samples have traditionally proved less amenable to PMCA, and the misfolding of prion proteins is believed to occur at a much lower rate in humans than in mice.) "What we were doing was trying to develop a very sensitive assay for prion detection on a metal surface, so we could use that in prion decontamination," says co-author John Collinge, who heads up the Department of Neurodegenerative Disease at University College London. "It took a while before we could convince ourselves this was a real phenomenon." © 2010 Nature Publishing Group

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 14298 - Posted: 07.27.2010

By Laura Sanders Prion protein, notorious for causing the brain-wasting mad cow and Creutzfeldt-Jakob diseases, may also be a coconspirator in Alzheimer’s disease, a new study in mice suggests. In mad cow and Creutzfeldt-Jakob diseases, misshapen prion proteins do the damage. But the new paper, appearing February 26 in Nature, offers evidence that the harmless version of the prion protein assists the amyloid-beta protein responsible for brain cell death in Alzheimer’s disease. “It’s pretty sensational,” comments Adriano Aguzzi, a neuropathologist at the University of Zurich. “What’s tremendously electrifying is that prion protein may be a genetic sensor for extremely toxic, small concentrations of A-beta.” A-beta proteins can travel alone or in groups in the brain. On their own, A-beta proteins are harmless. Massive, insoluble clumps of A-beta, known as plaques, are probably harmless, too, says study coauthor Stephen Strittmatter, a neuroscientist at Yale University. These plaques may be a gravestone marker of dead brain cells but are probably not the killer. Instead, smaller, soluble clumps of 50 to 100 A-beta proteins, known as oligomers, are the most likely suspect, Strittmatter says. Earlier studies have shown that mice with A-beta oligomers can’t remember how to get through a maze as quickly as mice without A-beta oligomers. Such oligomers prevent cross-talk between certain brain cells in the hippocampus of mice, which helps explain the loss of learning and memory functions in Alzheimer’s disease. © Society for Science & the Public 2000 - 2009

Related chapters from BP7e: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 13: Memory, Learning, and Development; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 12594 - Posted: 06.24.2010

The US has found its second case of mad cow disease in a cow suspected, but cleared, of having BSE in November 2004. Although meat from the cow did not enter the food chain, the finding calls into question the accuracy of the country’s BSE surveillance programme. The cow might also be the first case born in the US. The first US case was in a cow imported from Canada in 2003. In 2004 the country started testing “high-risk” cattle - those that show neurological symptoms, are found dead or are “downers” (unable to stand). Since then it has tested 375,000 cattle. None were declared positive. In contrast, Canada has tested 30,000 cattle and found three positives. The rate at which the tests uncover positive cattle depends on the sample size, stresses Marcus Doherr of the University of Bern in Switzerland, who helped develop Swiss BSE surveillance. This means either that BSE is less evenly distributed in North America than thought, or that the US is missing cases. Unlike Canada, which uses the rapid “western blot” test, the US uses a test called ELISA, which is more prone to false positives. In 2004 the ELISA test detected three BSE positive cattle in the US. When these brains were re-tested, the ELISA was negative. Then they were subjected to immunohistochemistry (IHC) testing - a thin slice of brain is stained with antibodies for the prion protein that causes BSE. All were negative, and the cattle were declared BSE-free. “But if the prion is diffuse enough in the brain tissue, you can get a weak signal with the ELISA, and a negative with IHC,” says Doherr. Another test is needed to be certain, he says. © Copyright Reed Business Information Ltd

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 7487 - Posted: 06.24.2010

Jim Schnabel Of all the ways that proteins can go bad, becoming an amyloid is surely one of the worst. In this state, sticky elements within proteins emerge and seed the growth of sometimes deadly fibrils. Amyloids riddle the brain in Alzheimer's disease and Creutzfeldt–Jakob disease. But until recently it has seemed that this corrupt state could threaten only a tiny fraction of proteins. Research is now hinting at a more unsettling picture. In work reported in February, a team led by David Eisenberg at the University of California, Los Angeles, sifted through tens of thousands of proteins looking for segments with the peculiar stickiness needed to form amyloid1. They found, says Eisenberg, that "effectively all complex proteins have these short segments that, if exposed and flexible enough, are capable of triggering amyloid formation". Not all proteins form amyloids, however. The 'amylome', as Eisenberg calls it, is restricted because most proteins hide these sticky segments out of harm's way or otherwise keep their stickiness under control. His results and other work suggest that evolution treats amyloids as a fundamental threat. Amyloids have been found in some of the most common age-related diseases, and there is evidence that ageing itself makes some amyloid accumulation inevitable. It now seems as though the human body is perched precariously above an amyloidal abyss. "The amyloid state is more like the default state of a protein, and in the absence of specific protective mechanisms, many of our proteins could fall into it," says Chris Dobson, a structural biologist at the University of Cambridge, UK. © 2010 Nature Publishing Group,

Related chapters from BP7e: Chapter 7: Life-Span Development of the Brain and Behavior; Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 13: Memory, Learning, and Development; Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 13964 - Posted: 06.24.2010

Prions, the mis-folded proteins best known for causing diseases such as bovine spongiform encephalopathy in cows, scrapie in sheep and Creutzfeldt–Jakob disease in humans, could also help yeast survival, according to a study in the journal Cell1. "We think prions are really important," says co-author Simon Alberti of the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. "When environmental conditions are harsh, they might allow a species to survive." The work, led by Susan Lindquist of the Whitehead Institute, bolsters the theory that prions might confer an evolutionary advantage, says Alberti. Lindquist first broached that idea nine years ago, after finding that a prion called PSI+ in the yeast Saccharomyces cerevisiae triggered heritable changes that could provide a way of adapting to fluctuating environments2. More recent work also suggests prions might play a role in memory in sea slugs and smell in mice. In the new work, a scan of the S. cerevisiae genome yielded 24 potential prion-forming proteins. Only five prions were known to exist in yeast before this study. The team focused on a protein called Mot3 and found that it can twist into a prion form. When in its normal shape, Mot3 suppresses yeast genes involved in building the cellular wall. But when Mot3 kinks into a prion, it loses this function and the wall-building genes activate. Hence, yeast carrying the Mot3 prions grew thicker, more robust cell walls. © 2009 Nature Publishing Group,

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 12716 - Posted: 06.24.2010

Debora McKenzie Viruses, not prions, may be at the root of diseases such as scrapie, BSE and variant Creutzfeldt-Jakob disease (vCJD), researchers say. If true, the new theory could revolutionise our understanding of these so-called transmissible spongiform encephalopathies (TSEs), and potentially lead to new ways of treating them. The widely accepted theory of what causes infectious prion diseases – such as vCJD, scrapie and “mad cow disease” – is that deformed proteins called prions corrupt other brain proteins, eventually clogging and destroying brain cells. However, this theory has not been definitively proven. Laura Manuelidis at Yale University in New Haven, Connecticut, US, has insisted for years that tiny virus-like particles observed in TSE-infected brains may be the culprits. But such brains are degenerating, so the particles had been dismissed as general debris. When Manuelidis studied cultures of neural cells infected with two particular strains of scrapie and CJD, she found that these virus-like particles were clustered in regular arrays within the cells – in a pattern that viruses regularly form in cells – and she saw no apparent prions in the cells. © Copyright Reed Business Information Ltd.

Related chapters from BP7e: Chapter 16: Psychopathology: Biological Basis of Behavior Disorders
Related chapters from MM:Chapter 12: Psychopathology: The Biology of Behavioral Disorders
Link ID: 9956 - Posted: 06.24.2010