Category: Mad Cow Disease

 A new sporadic prion protein disease has been discovered. Variably protease-sensitive prionopathy (VPSPr), as it has been named, is the second type of complete sporadic disease to be identified since Creutzfeldt-Jakob disease (CJD) was reported in the 1920s.

The landmark finding from the National Prion Disease Pathology Surveillance Center at Case Western Reserve University is published in the August issue of Annals of Neurology.

Normally, the human prion protein gene comes in three types due to its capability to encode prion proteins that contain only the amino acid methionine, commonly identified as M, both methionine and valine, commonly identified as V, or only for the amino acid valine at position 129. Therefore, when it comes to the prion protein gene unaffected people can be identified as 129MM, 129MV or 129VV. Sporadic CJD (sCJD), which is the most common human prion disease, can affect patients who have any one of the three types of the prion protein gene.

In 2008, Pierluigi Gambetti, MD, and Wen-Quan Zou, MD, PhD, with collaborators, reported the discovery of this novel disease, which affected patients who exhibit only one of the three types of the prion protein gene. In this follow-up study, they discovered that all three genetic groups can be affected also by this novel disease which now joins sCJD in displaying this feature. However, VPSPr is associated with an abnormal prion protein that exhibits characteristics very different from those of sCJD, as well as other prion diseases, suggesting that it may be caused by a different mechanism, perhaps more akin to other neurodegenerative diseases, such as Alzheimer's disease. This finding may exemplify, for the first time, the possibility that the prion protein affects the brain with different mechanisms.

While examining cases received at the National Prion Disease Pathology Surveillance Center where he is the director, Dr. Gambetti observed that a subset of cases had clinical and pathological features quite different from those of all known types of human prion diseases. Further, after being tested for prion proteins via the Western blot — the gold standard of prion disease diagnosis — the cases were negative. Dr. Gambetti then collaborated with Dr. Zou, associate director at the center, to solve the riddle of a disease that exhibited some features of a prion disease in histopathological examination but was negative using the standard Western blot test.

Dr. Zou's lab performed a full characterization of the disease and discovered that the VPSPr-associated abnormal prion protein formed a ladder-like electrophoretic profile on Western blot. "When I obtained the first Western blot result of these cases with a different antibody against prions, I was surprised that these cases consistently exhibited this particular profile; one that I had never seen in my more than 10 years of work on human prion diseases," Dr. Zou, assistant professor of pathology at Case Western Reserve School of Medicine, recalls. This ladder-like profile is quite distinctive and very different from the profile of common prion diseases. "Discovery of this unique type of prion provides solid evidence that this novel disease may possess a pathogenesis that is different from that of the major prion diseases currently known," Dr. Zou adds.

Despite extensive research, a relatively large group of neurodegenerative diseases associated with dementia remain undefined. Before being discovered and characterized, VPSPr was one of the undefined dementing diseases. The discovery of VPSPr is chipping away at that group. In the two years since its discovery, more than 30 cases have been reported.

"If, as the current evidence indicates, the VPSPr mechanism of affecting the brain is different from that of other sporadic prion diseases, such as sCJD, the discovery of VPSPr would also provide the first example that the prion protein may spontaneously damage the brain with different mechanisms," concludes Dr. Gambetti, professor of pathology at Case Western Reserve School of Medicine. "This might apply to other dementing illnesses as well, and has implications for the strategies that need to be followed to attain a cure."

Drs. Gambetti and Zou, along with their extensive research team, plan to further characterize the abnormal prion protein associated with VPSPr as well as other important features of the protein, such as the disease's propensity for transmission upon inoculation and its replication in test tubes. These features in VPSPr will be compared with those of sCJD to obtain a complete picture of how the abnormal prion protein attacks the brain in these two diseases.

This research was supported by funding from the National Institutes of Health, Centers for Disease Control and Prevention, Britton Fund, CJD Foundation, Alliance BioSecure, and University Center on Aging and Health with the support of the McGregor Foundation, and President's Discretionary Fund (Case Western Reserve University).

Journal Reference:

1. Wen-Quan Zou, Gianfranco Puoti, Xiangzhu Xiao, Jue Yuan, Liuting Qing, Ignazio Cali, Miyuki Shimoji, Jan P.M. Langeveld, Rudy Castellani, Silvio Notari, Barbara Crain, Robert E. Schmidt, Michael Geschwind, Stephen J. DeArmond, Nigel J. Cairns, Dennis Dickson, Lawrence Honig, Juan Maria Torres, James Mastrianni, Sabina Capellari, Giorgio Giaccone, Ermias D. Belay, Lawrence B. Schonberger, Mark Cohen, George Perry, Qingzhong Kong, Piero Parchi, Fabrizio Tagliavini and Pierluigi Gambetti. Variably protease-sensitive prionopathy: A new sporadic disease of the prion protein. Annals of Neurology, 2010; 68 (2): 162%u2013172 DOI: 10.1002/ana.22094

In a startling new study that involved research on both sides of the Atlantic, scientists from The Scripps Research Institute in Florida and the University College London (UCL) Institute of Neurology in England have shown for the first time that abnormal prions, bits of infectious protein devoid of DNA or RNA that can cause fatal neurodegenerative disease, can suddenly erupt from healthy brain tissue.

The catalyst in the study was the metallic surface of simple steel wires. Previous research showed that prions bind readily to these types of surfaces and can initiate infection with remarkable efficiency. Surprisingly, according to the new research, wires coated with uninfected brain homogenate could also initiate prion disease in cell culture, which was transmissible to mice.

The findings are being published in the online edition of the journal Proceedings of the National Academy of Sciences (PNAS).

"Prion diseases such as sporadic Creutzfeldt-Jakob disease in humans or atypical bovine spongiform encephalopathy, a form of mad cow disease, occur rarely and at random," said Charles Weissmann, M.D., Ph.D., chair of Scripps Florida's Department of Infectology, who led the study with John Collinge, head of the Department of Neurodegenerative Disease at UCL Institute of Neurology. "It has been proposed that these events reflect rare, spontaneous formation of prions in brain. Our study offers experimental proof that prions can in fact originate spontaneously, and shows that this event is promoted by contact with steel surfaces."

Infectious prions, which are composed solely of protein, are classified by distinct strains, originally characterized by their incubation time and the disease they cause. These toxic prions have the ability to reproduce, despite the fact that they contain no nucleic acid genome.

Mammalian cells normally produce harmless cellular prion protein (PrPC). Following prion infection, the abnormal or misfolded prion protein (PrPSc) converts PrPC into a likeness of itself, by causing it to change its conformation or shape. The end-stage consists of large aggregates of these misfolded proteins, which cause massive tissue and cell damage.

A Highly Sensitive Test

In the new study, the scientists used the Scrapie Cell Assay, a test originally created by Weissmann that is highly sensitive to minute quantities of prions.

Using the Scrapie Cell Assay to measure infectivity of prion-coated wires, the team observed several unexpected instances of infectious prions in control groups where metal wires had been exposed only to uninfected normal mouse brain tissue. In the current study, this phenomenon was investigated in rigorous and exhaustive control experiments specifically designed to exclude prion contamination. Weissmann and his colleagues in London found that when normal prion protein is coated onto steel wires and brought into contact with cultured cells, a small but significant proportion of the coated wires cause prion infection of the cells — and when transferred to mice, they continue to spawn the disease.

Weissmann noted that an alternative interpretation of the results is that infectious prions are naturally present in the brain at levels not detectable by conventional methods, and are normally destroyed at the same rate they are created. If that is the case, he noted, metal surfaces could be acting to concentrate the infectious prions to the extent that they became quantifiable by the team's testing methods.

The first author of the study, "Spontaneous Generation of Mammalian Prions," is Julie Edgeworth of the UCL Institute of Neurology. Other authors of the study include Nathalie Gros, Jack Alden, Susan Joiner, Jonathan D.F. Wadsworth, Jackie Linehan, Sebastian Brandner, and Graham S. Jackson, also of the UCL Institute of Neurology.

The study was supported by the U.K. Medical Research Council.

Journal Reference:

1. Julie A. Edgeworth, Nathalie Gros, Jack Alden, Susan Joiner, Jonathan D. F. Wadsworth, Jackie Linehan, Sebastian Brandner, Graham S. Jackson, Charles Weissmann, and John Collinge. Spontaneous generation of mammalian prions. Proceedings of the National Academy of Sciences, 2010; DOI: 10.1073/pnas.1004036107

 A new study spearheaded by Spanish scientists demonstrates a causal relationship between the onset of Creutzfeldt-Jakob disease (CJD), caused by a protein called a prion, and general surgery.

CJD manifests itself in hereditary acquired and sporadic forms, or for unknown reasons, which accounts for the majority of cases.

"Based on the monitoring records of spongiform encephalopathy in two Nordic countries, we studied the possibility of transmission of the sporadic form of CJD through general surgery," explains Jesús de Pedro, main author of the study and head of prion monitoring in patients at the National Epidemiology Centre of the Carlos III Health Institute.

The finding, published recently in the Journal of Neurology, Neurosurgery & Psychiatry, reveals that, with a few exceptions, the risk of having contracted the sporadic form of CJD manifests itself at least 20 years after having undergone an operation.

"While we are not ruling out the idea that intraoperational transfusions may play a secondary part, the data suggest that the disease enters and spreads much more quickly within the central or peripheral nervous system," says De Pedro.

According to the authors, the fact that computer records of surgeries have been in place since the early seventies in hospitals in Sweden and Denmark enables operations on residents of those countries to be linked to cases of CJD, which "extends an extraordinary quality to the information and more credibility to the findings given the almost total absence of memory bias."

Why is the idea of transmission through surgery important?

The most interesting thing about this finding, which points to an external cause that could be prevented, is that "it may signify a shift in our understanding of the nature of neurodegenerative diseases, such as Alzheimer's or Parkinson's."

We might, therefore, ask ourselves if other types of motor neuron diseases can be transmitted through surgery and be latent for decades, such as those where risk factors, particularly physical professions and activities or certain sporting activities, for example, which are more likely to lead to surgery, have already been indicated.

"Suggesting that a disease could have been acquired during health care is a very delicate affirmation, as some relatives of patients with sporadic CJD may be tempted to seek compensation from health authorities for the alleged intraoperational transmission years previously, which would be impossible to prove in individual cases," he reasons.

Nonetheless, the most conclusive pattern that the study presents, albeit based on few cases and one that must be replicated in future studies, is that the onset of CJD occurs approximately 10 years after an operation on the retina with reused equipment.

Journal Reference:

1. J. de Pedro-Cuesta, I. Mahillo-Fernandez, A. Rabano, M. Calero, M. Cruz, A. Siden, H. Laursen, G. Falkenhorst, K. Molbak. Nosocomial transmission of sporadic Creutzfeldt-Jakob disease: results from a risk-based assessment of surgical interventions. Journal of Neurology, Neurosurgery & Psychiatry, 2010; DOI: 10.1136/jnnp.2009.188425

NewsPsychology (June 14, 2010) — Prion diseases are lethal neurodegenerative disorders that include Creutzfeldt-Jakob disease (CJD) in humans and bovine spongiform encephalopathy (BSE; commonly known as mad cow disease) in cows. A team of researchers, led by Adriano Aguzzi and Christina Sigurdson, at UniversitätsSpital Zürich, Switzerland, has generated data in mice that provides greater understanding of the factors that determine how easy it is for prion diseases to be transmitted to a new host species.

This information provides new insight into a highly important food safety issue; dietary exposure to beef contaminated with the BSE agent is believed to have caused nearly 200 cases of variant CJD in humans.

The key infectious agent in prion diseases is PrPSc, a highly aggregated form of the cellular prion protein (PrPC). The ease with which prions from different species can be transmitted to a new host species varies dramatically. The team found that transmission between species with the same protein building block at position 170 in PrPC was relatively easy while it was relatively difficult between those species with different building blocks at that position.

As this protein building block influences the structure of the PrPC protein, the authors suggest that local structure of PrPC affected by the protein building block at position 170 might have a triggering role in prion transmissibility between different species.

The research is published in the Journal of Clinical Investigation.

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Story Source:

The above story is reprinted (with editorial adaptations by newsPsychology staff) from materials provided by Journal of Clinical Investigation, via EurekAlert!, a service of AAAS.

Journal Reference:

1. Christina J. Sigurdson, K. Peter R. Nilsson, Simone Hornemann, Giuseppe Manco, Natalia Fernández-Borges, Petra Schwarz, Joaquín Castilla, Kurt Wüthrich, and Adriano Aguzzi. A molecular switch controls interspecies prion disease transmission in mice. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI42051

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of NewsPsychology or its staff.

A group led by Dr. Edward Hoover at Colorado State University, Fort Collins, CO have generated a mouse model of cervid chronic wasting disease.

They present these findings in the June 2010 issue of The American Journal of Pathology.

Chronic wasting disease is a fatal prion-induced disease, similar to mad cow disease, that affects cervids such as deer, elk, and moose. It is a neurodegenerative disease typified by chronic weight-loss leading to death. Prions are infectious agents composed primarily of proteins that are thought to be propagated by transmitting a mis-folded protein state. Due to the lack of an appropriate small animal model, little is known about cervid chronic wasting disease.

Using a mouse model of chronic wasting disease that expresses cervid prion protein (PrP), Seelig et al examined the susceptibility, pathogenesis, and transmission of cervid chronic wasting disease. They found that cervid PrP^C (protease-sensitive PrP) was expressed in a number of different tissues, including lymphoid, nervous, hematopoietic, endocrine, and certain epithelial tissues, in this model. Additionally, disease could be transferred by various infectious methods, including injection into the brain, blood stream, and gut. It could also be transmitted orally, although the oral route required a larger infecting dose. Furthermore, this disease could be transferred between animals without experimental intervention to uninfected mice, highlighting the suitability of this system in studying cervid transmissible spongiform encephalopathy.

Dr. Hoover's group suggests that "cervidized transgenic mice substantially recapitulate the clinical, neuropathologic, and PrP^RES tropism and transmission patterns reported in the native cervid species and [that] studies in Tg[CerPrP] mice can provide additional insights into the trafficking, shedding, and lateral transmission of [chronic wasting disease] prions."

Journal Reference:

1. Seelig DM, Mason GL, Telling GC, Hoover EA. Pathogenesis of Chronic Wasting Disease in Cervidized Transgenic Mice. American Journal Of Pathology, 2010; DOI: 10.2353/ajpath.2010.090710

National Institutes of Health (NIH) scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the sponge-like brain deterioration typically seen in prion diseases. Instead, it resembles a form of human Alzheimer's disease, cerebral amyloid angiopathy, that damages brain arteries.

The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID) in the online journal PLoS Pathogens, are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID's Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups: those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer's disease, Dr. Chesebro says.

Scientists from the Veterinary Laboratories Agency in Scotland also participated in the study.

Journal Reference:

1. Chesebro et al. Fatal Transmissible Amyloid Encephalopathy: A New Type of Prion Disease Associated with Lack of Prion Protein Membrane Anchoring. PLoS Pathogens, 2010; 6 (3): e1000800 DOI: 10.1371/journal.ppat.1000800

The fatal brain disease Creutzfeldt-Jakob in humans, BSE (bovine spongiform encephalopathy) in cattle and scrapie in sheep are so-called prion diseases, whereby one of the body's normal proteins, the prion protein PrPc misfolds into a pathogenic form: PrPSc. In spite of several years of extensive research, little is still known about what actually happens in this process.

In spite of the fact that PrP is one of most intensely studied proteins in the human genome, its physiological function is still unknown. The pathogenic variant PrPSc arises as a result of changes in the structural folding of PrPc.

We need to know more about how PrPc is expressed and treated in cells in order to understand how the misfolding of PrPc occurs and why cells die as a result. In the course of the work connected with his PhD, Christoffer Lund has therefore carried out detailed studies of cell cultures of normal PrP in sheep. By means of green fluorescent protein (GFP) cloned into PrP, PrP in cell cultures can be studied under a microscope. In addition, genetically manipulated variants of PrP have been made in order to uncover important factors regarding the localisation of PrP in cells and the enzymatic cutting of PrP.

PrP is normally cut into fragments in the course of its cellular lifespan. Lund has studied one of these cutting processes, the α-cut. Where the PrP α-cut occurs in the cell, and to what purpose, is unknown. Through his studies, Lund has shown that PrP is cut in the same place, even when the amino acid composition at the place of cutting is changed. PrP is also cut at the same place, irrespective of whether it is joined to the outside of the cell membrane or whether it is localised in the cell cytoplasm. Lund's findings indicate that the cutting occurs at the same place in PrP, but that the cutting is caused by different mechanisms, depending on where the PrP is localised in the cell.

A phenomenon associated with PrP's localisation in cells that is still poorly understood is that in some types of cells, PrP is positioned in the cell's cytoplasm instead of on the cell membrane, where it most likely fulfils its function. A predominant theory on why proteins may be found in the cytoplasm instead of on the cell membrane is that the cell in question is in a state of stress. Furthermore, PrP has been shown to have an inefficient signal sequence compared to other proteins and may therefore be less efficient at following its natural route out onto the cell membrane, even under normal cellular conditions.

Lund's work reveals that a completely different mechanism related to the actual translation of PrP may also be the reason why a proportion of the PrP molecules end up in the cytoplasm. By studying different mutated variants of PrP, Lund has demonstrated that a cytoplasmic variant of PrP can emerge after PrP molecules have been synthetised from a downstream start codon in the PrP gene. The result of this translation is a shortened form of PrP which lacks large portions of the signal sequence and therefore ends up in the cytoplasm of the cell.

Lund has carried out a detailed characterisation of an antibody (3F4), which is frequently used in prion research. He has shown that the criteria that are necessary for the antibody to bind with PrP are different to those previously assumed necessary. This new knowledge is of great significance when it comes to the interpretation of data where 3F4 has been used. Taken as a whole, the results of this work lead to a greater understanding of fundamental processes related to PrP and new insight into the utility value of fluorescently tagged PrP for studying PrP in cell cultures. Lund's work also highlights other challenges facing studies of proteins in cell cultures.

Christoffer Lund presented his doctoral thesis on 3re December 2009 at The Norwegian School of Veterinary Science. The thesis is entitled: "Studies on fluorescently tagged prion protein in cell culture."

 Prions are a special class of proteins best known as the source for mad cow and other neurodegenerative diseases. Despite this negative reputation, according to a new report in the February 5th issue of the journal Cell, a Cell Press publication, a prion may also have important and very positive roles in brain function. The researchers suggest that a prion-like protein may participate in memory in higher eukaryotes, from sea slugs on up.

"The persistence of memory is a fundamental problem," said Kausik Si of Stowers Institute for Medical Research. "Experiences are temporal; they happen once, but somehow must lead to changes [in the brain] that are somewhat permanent."

Those changes must be mediated by molecules, including proteins. "The question is: how can you maintain a stable state with unstable biological molecules," Si said.

And now, research conducted by Si in collaboration with Nobel laureate Eric Kandel, suggests that prions may be one solution to that problem. Prions are distinguished by their ability to assume at least two distinct conformational states, one of which is dominant and self-perpetuating. That means that once a protein switches to its "prion state" it has the ability to convert other "non-prion" proteins to that state as well. Therefore, once engaged, the "prion state" is self-renewing and stable.

The findings suggest that memory traces may depend on a fairly unique mechanism involving a prion-like protein known as CPEB, Si said, adding to a growing body of evidence that proteins with the characteristics ascribed to disease-causing prions may have a broader role in biology.

Scientists have known for some time that plenty of prion-like proteins are found in relatively simple organisms such as yeast, some of which have known functions. A report by another group in Cell last year suggested that prions in yeast may serve as an important source of variation in nature.

Si's team made its discovery in studies of the sea slug Aplysia, which has served as an elemental model for learning and memory for decades. When you touch the animals' gills, they withdraw. When the slugs are trained by touching their gill and delivering a shock, that withdrawal reaction becomes stronger for up to a month.

Scientists long ago traced that simple learned behavior to a specific set of sensory and motor neurons, which are stimulated by the nerve messenger serotonin. But Si wanted to better understand the underlying molecular details. In a survey of proteins made at the synapse when serotonin is applied, he turned up CPEB. Upon closer examination of the protein's sequence, Si had what he calls his "aha moment." He realized CPEB looked a lot like the prions others had found in yeast.

He earlier reported evidence that the slug protein does display prion-like properties when inserted into yeast. They now provide evidence that those characteristics hold when the protein is expressed in its usual spot — Aplysia sensory neurons. The proteins switch to their prion state and clump together (as prions typically do) in the presence of serotonin. An antibody that targets the clumped prion protein blocks the persistence of neural connections that are the cellular basis for learning and memory.

"These results are consistent with the idea that ApCPEB can act as a self-sustaining prion-like protein in the nervous system and thereby might allow the activity-dependent change in synaptic efficacy to persist for long periods of time," the researchers conclude. Si cautions, however, that they haven't yet proven that blocking CPEB's ability to self-perpetuate also blocks memory. For that, he says they would need to see whether a slug with a mutant version of the protein would learn but then quickly forget.

"Persistence of memory is a difficult problem," Si said. The new evidence offers "at least an idea" for how this may happen and he suspects the prion-like protein's apparent role in memory may turn out to be a more general phenomenon. His group is following up on their findings by investigating the role of the fly version of CPEB, and Si notes that humans do have a similar protein.

The researchers include Kausik Si, Stowers Institute for Medical Research, Kansas City, MO, University of Kansas Medical Center, Kansas City, KS; Yun-Beom Choi, New York State Psychiatric Institute, New York, NY; New York State Psychiatric Institute, New York, NY; Erica White-Grindley, Stowers Institute for Medical Research, Kansas City, MO; Amitabha Majumdar, Stowers Institute for Medical Research, Kansas City, MO; and Eric R. Kandel, Howard Hughes Medical Institute, New York State Psychiatric Institute, New York, NY.

 We are watching television together less and less often. "We are becoming more and more individualistic also in our choice of TV programs," says Jakob Bjur in a new dissertation from University of Gothenburg in Sweden.

In his dissertation work at the Department of Journalism, Media, and Communication, Jakob Bjur studied so-called social viewing.

In the past, watching TV was a social activity that brought people together. The whole family watched the same program on the same TV set, and when people went to work the next day they could be fairly sure that most other people had also seen the same program. This is no longer the case. What once brought us together is now a source of fragmentation. Most families have several TVs, and they sit in different rooms and view different programs — if they watch TV at all. What's more, the channel offerings have become so large and varied that few programs qualify as shared topics in the lunchroom at work.

"In 1999 social viewing, watching together, accounted for 45 percent, and in 2008 it was down to 37 percent. We are becoming more and more individualistic also in our TV choices, and I'm convinced that this trend will continue. We can no longer speak of TV as a social adhesive, a unifying force," says Jakob Bjur.

There still are programs that attract really large audiences: the European Song Contest and games featuring the national soccer team, for example. But the TV landscape is different from what it was just a decade ago, with more players, more distribution channels, more ways of viewing, all in stiffening competition. Competition for viewers has prompted TV companies to seek out niche channels rather than finding programs to attract a huge audience. TV 4, for example, started out with a single channel, but today they have some 30 channels throughout the Nordic countries.

"People still gab," says Jakob Bjur. "But the discussion is on the Net instead, in specific groups, not least for TV series. "

This fragmented/niched audience is moreover economically attractive: advertisers can zero in on the exact target group for their message. It's easy to find parents of small children, those interested in construction, or fashionistas.

A community in Papua New Guinea that suffered a major epidemic of a CJD-like fatal brain disease called kuru has developed strong genetic resistance to the disease, according to new research by Medical Research Council (MRC) scientists.

Kuru is a fatal prion disease, similar to CJD in humans and BSE in animals, and is geographically unique to an area in Papua New Guinea. In the mid 20th Century, an epidemic of kuru devastated a population in the Eastern Highlands of Papua New Guinea. The infection was passed on at mortuary feasts, where mainly women and children consumed their deceased relatives as a mark of respect and mourning. This practice was banned and ceased in the late 1950s.

Scientists from the MRC Prion Unit, a national centre of excellence in prion diseases, assessed over 3000 people from the affected and surrounding Eastern Highland populations, including 709 who had participated in cannibalistic mortuary feasts, 152 of whom subsequently died of kuru. They discovered a novel and unique variation in the prion protein gene called G127V in people from the Purosa valley region where kuru was most rife.

This gene mutation, which is found nowhere else in the world, seems to offer high or even complete protection against the development of kuru and has become frequent in this area through natural selection over recent history, in direct response to the epidemic. This is thought be perhaps the strongest example yet of recent natural selection in humans.

Lead author Professor John Collinge, Director of the MRC Prion Unit said: "It's absolutely fascinating to see Darwinian principles at work here. This community of people has developed their own biologically unique response to a truly terrible epidemic. The fact that this genetic evolution has happened in a matter of decades is remarkable. Kuru comes from the same disease family as CJD so the discovery of this powerful resistance factor opens up new areas for research taking us closer to understanding, treating and hopefully preventing a range of prion diseases."

The study, which began in 1996, is published in the New England Journal of Medicine.

Background

Prion diseases or transmissible spongiform encephalopathies (TSEs) belong to group of progressive conditions that affect the nervous system in humans and animals. In humans, prion diseases impair brain function, causing memory changes, personality changes, a decline in intellectual function (dementia), and problems with movement that worsen over time. They are fatal conditions. Familial prion diseases of humans include classic Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) fatal insomnia (FI) and Kuru.

Kuru was restricted to the Fore linguistic groups and their immediate neighbours which whom they intermarried. It was the practice in the Fore society for kinship groups to consume deceased relatives at mortuary feasts, a practice that resulted in human-to-human prion transmission. On the whole, men and children over 8 years of age did not participate in the feast, with the result that kuru at its peak predominantly affected women and children. As recorded in oral history the first cases appeared in the early 20th century and thereafter the number of cases increased in incidence. A peak annual mortality of more than 2% was recorded in some villages. Some villages became largely devoid of young women. More information on the Papua New Guinea Institute of Medical Research is available at www.pngimr.org.pg.

The study was lead by the Medical Research Council Prion Unit, and involved scientists from the University College London Institute of Neurology; Papua New Guinea Institute of Medical Research; and Curtin University Australia. Other institutions participating; the Genome Centre, Barts the London Queen Mary's School of Medicine and Dentistry; London School of Hygiene and Tropical Medicine.

Journal Reference:

1. Mead, Simon, Whitfield, Jerome, Poulter, Mark, Shah, Paresh, Uphill, James, Campbell, Tracy, Al-Dujaily, Huda, Hummerich, Holger, Beck, Jon, Mein, Charles A., Verzilli, Claudio, Whittaker, John, Alpers, Michael P., Collinge, John. A Novel Protective Prion Protein Variant that Colocalizes with Kuru Exposure. New England Journal of Medicine, 2009; 361 (21): 2056 DOI: 10.1056/NEJMoa0809716