Publications

the impact of the genotype on the prevalence of classical scrapie at population level.	abstract: total number and genotypes of animals in holdings selected for the genotype & cull option in the compulsory scrapie flock scheme (csfs) in great britain were extracted from the national scrapie plan data warehouse. the association between various genotype-related measures and scrapie prevalence infection was tested using zero-inflated negative binomial models with the counts of positive cases as dependent variable, and country, number of flocks in the scheme, flock size, surveillance s ...	2011	21324113
prpsc spreading patterns in the brain of sheep linked to different prion types.	abstract: scrapie in sheep and goats has been known for more than 250 years and belongs nowadays to the so-called prion diseases that also include e.g. bovine spongiform encephalopathy in cattle (bse) and creutzfeldt-jakob disease in humans. according to the prion hypothesis, the pathological isoform (prpsc) of the cellular prion protein (prpc) comprises the essential, if not exclusive, component of the transmissible agent. currently, two types of scrapie disease are known - classical and atypic ...	2011	21324114
normal modes of prion proteins: from native to infectious particle.	prion proteins (prp) are the infectious agent in transmissible spongiform encephalopathies (i.e., mad cow disease). to be infectious, prion proteins must undergo a conformational change involving a decrease in a-helical content along with an increase in ß-strand content. this conformational change was evaluated by means of elastic normal modes. elastic normal modes show a diminution of two a-helices by one and two residues, as well as an extension of two ß-strands by three residues each, which c ...	2011	21338080
subcellular localization of peptidylarginine deiminase 2 and citrullinated proteins in brains of scrapie-infected mice: nuclear localization of pad2 and membrane fraction-enriched citrullinated proteins.	peptidylarginine deiminase (pad) and citrullinated proteins have emerged as key molecules in various human diseases, but detailed subcellular localizations of pad2 and citrullinated proteins are poorly mapped in brain under normal and pathologic conditions. we performed subcellular fractionation and electron microscopic analysis using brains of normal and scrapie-infected mice. peptidylarginine deiminase 2 was abundantly present in cytosol and weakly in microsomal and mitochondrial fractions and ...	2011	21343880
prion diseases of yeast: amyloid structure and biology.	prion "variants" or "strains" are prions with the identical protein sequence, but different characteristics of the prion infection: e.g. different incubation periods for scrapie strains or different phenotype intensities for yeast prion variants. we have shown that infectious amyloids of the yeast prions [psi+], [ure3] and [pin+] each have an in-register parallel ß-sheet architecture. moreover, we have pointed out that this amyloid architecture can explain how one protein can faithfully transmit ...	2011	21345375
biological effects and use of prpsc- and prp-specific antibodies generated by immunization with purified full-length native mouse prions.	the prion agent is the infectious particle causing spongiform encephalopathies in animals and humans and is thought to consist of an altered conformation (prp(sc)) of the normal and ubiquitous prion protein prp(c). the interaction of the prion agent with the immune system, particularly the humoral immune response, has remained unresolved. here we investigated the immunogenicity of full-length native and infectious prions, as well as the specific biological effects of the resulting monoclonal ant ...	2011	21345946
atypical/nor98 scrapie infectivity in sheep peripheral tissues.	atypical/nor98 scrapie was first identified in 1998 in norway. it is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (tse) cases in europe. atypical/nor98 scrapie cases were reported in arr/arr sheep, which are highly resistant to bse and other small ruminants tse agents. the biology and pathogenesis of the atypical/nor98 scrapie agent in its natural host is still poorly understood. how ...	2011	21347349
highly efficient protein misfolding cyclic amplification.	protein misfolding cyclic amplification (pmca) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research. however, the low efficiency of conversion of prp(c) into prp(sc) in pmca limits the applicability of pmca for many uses including structural studies of infectious prions. it also implies that only a small sub-fraction of prp(c) may be available for conversion. here we show that the yield, rate, and robustness of prion conversion and the sensit ...	2011	21347353
prion propagation and toxicity in vivo occur in two distinct mechanistic phases.	mammalian prions cause fatal neurodegenerative conditions including creutzfeldt-jakob disease in humans and scrapie and bovine spongiform encephalopathy in animals. prion infections are typically associated with remarkably prolonged but highly consistent incubation periods followed by a rapid clinical phase. the relationship between prion propagation, generation of neurotoxic species and clinical onset has remained obscure. prion incubation periods in experimental animals are known to vary inver ...	2011	21350487
features of follicular dendritic cells in ovine pharyngeal tonsil: an in vivo and in vitro study in the context of scrapie pathogenesis.	although the alimentary tract has been suggested as the most likely portal of entry in natural scrapie, a growing amount of data indicates that the respiratory system and more specifically the pharyngeal tonsils serve as a natural portal of entry for scrapie. this study describes for the first time the broad cell populations in the lymphoid compartment of pharyngeal tonsils and more specifically inside the lymphoid follicles where the scrapie agent accumulates during the period of latency. folli ...	2011	21353313
sc237 hamster prpsc and sc237-derived mouse prpsc generated by interspecies in vitro amplification exhibit distinct pathological and biochemical properties in tga20 transgenic mice.	prions are the infectious agents responsible for transmissible spongiform encephalopathy, and are primarily composed of the pathogenic form (prp(sc)) of the host-encoded prion protein (prp(c)). recent studies have revealed that protein misfolding cyclic amplification (pmca), a highly sensitive method for prp(sc) detection, can overcome the species barrier in several xenogeneic combinations of prp(sc) seed and prp(c) substrate. although these findings provide valuable insight into the origin and ...	2011	21362027
survival of infectious prions in class b biosolids.	this study developed a method for extracting infectious prions from class b biosolids and subsequently evaluated the survival of infectious prions under the influence of mesophilic (37-¦c) and thermophilic (60-¦c) temperatures in class b biosolids. unlike other studies, this study utilized a scrapie cell assay to determine infectivity and quantity of infectious prions. the best method for extraction was exposing the biosolids to 4 m urea at 80-¦c for 10 minutes followed by a membrane centrifugat ...	2011	21391030
[active surveillance for scrapie in the netherlands: effect of a breeding programme on the prevalence of scrapie in sheep (2002-2010)?].	the susceptibility of sheep to scrapie is modulated by the prion protein (prp) genotype of the animal. an ambitious voluntary scrapie control programme was started in the netherlands in 1998, based on selection of rams with thearr/arr genotype for breeding. this programme was followed by an obligatory programme in 2004; the programme has been voluntary since 2007. we monitored the prevalence of prp genotype frequencies and the prevalence of scrapie in the dutch sheep population between 2002 and ...	2011	21404540
a study on the analytical sensitivity of 6 bse tests used by the canadian bse reference laboratory.	bovine spongiform encephalopathy (bse) surveillance programs have been employed in numerous countries to monitor bse prevalence and to protect animal and human health. since 1999, the european commission (ec) authorized the evaluation and approval of 20 molecular based tests for the rapid detection of the pathological prion protein (prp(sc)) in bse infection. the diagnostic sensitivity, convenience, and speed of these tests have made molecular diagnostics the preferred method for bse surveillanc ...	2011	21412419
hybrid lipoic acid derivatives to attack prion disease on multiple fronts.		2011	21412985
synthesis, structural characterization, formation constants and in vitro cytotoxicity of phenanthroline and imidazolidine-2-thione copper(ii) complexes.	the synthesis, crystal structures, physicochemical properties and complex formation constants of [cu(phen)(2)(l)](clo(4))(2) complexes, where phen is 1,10-ortho-phenanthroline and l is a series of substituted imidazolidine-2-thione, have been studied. single crystal x-ray diffraction revealed a distorted trigonal-bipyramidal geometry for all the molecules. the complex formation constants were determined in nonaqueous media by spectrophotometric measurements. testing copper(ii) complexes in mouse ...	2011	21421120
replication efficiency of soil-bound prions varies with soil type.	prion sorption to soil is thought to play an important role in the transmission of scrapie and chronic wasting disease (cwd) via the environment. sorption of prp to soil and soil minerals is influenced by the strain and species of prp(sc) and by soil characteristics. however, the ability of soil-bound prions to convert prp(c) to prp(sc) under these wide-ranging conditions remains poorly understood. we developed a semiquantitative protein misfolding cyclic amplification (pmca) protocol to evaluat ...	2011	21430062
blocking of fcr suppresses the intestinal invasion of scrapie agents.	prion diseases are a family of neurodegenerative zoonotic foodborne disorders. although prions can be transmitted orally, the mechanism by which prions are incorporated into the intestine remains unclear. our previous studies have shown that an abnormal isoform of prion protein (prp(sc)), which is the main component of prions, was efficiently incorporated into the intestine in suckling mice but not in weaned mice. furthermore, suckling scid mice lacking maternal antibodies showed decreased uptak ...	2011	21437246
the cellular prion protein mediates neurotoxic signalling of ß-sheet-rich conformers independent of prion replication.	formation of aberrant protein conformers is a common pathological denominator of different neurodegenerative disorders, such as alzheimer's disease or prion diseases. moreover, increasing evidence indicates that soluble oligomers are associated with early pathological alterations and that oligomeric assemblies of different disease-associated proteins may share common structural features. previous studies revealed that toxic effects of the scrapie prion protein (prp(sc)), a ß-sheet-rich isoform o ...	2011	21441896
deduction of the evaluation limit and termination timing of multi-round protein misfolding cyclic amplification from a titration curve.	in this study, the efficacy of disinfectants in reducing the partially protease-resistant isoform of prion protein was evaluated by a multi-round protein misfolding cyclic amplification (pmca) technique. hamster brains infected with scrapie-derived strain 263k were homogenized, treated under inactivating or mock conditions, and subjected to multi-round pmca. four sets of serial 10-fold dilutions of mock-treated samples were analyzed. although considerable variability was observed in the signal p ...	2011	21443616
distinct proteinase k-resistant prion protein fragment in goats with no signs of disease in a classical scrapie outbreak.	considerable efforts have been directed toward the identification of small-ruminant prion diseases, i.e., classical and atypical scrapie as well as bovine spongiform encephalopathy (bse). here we report the in-depth molecular analysis of the proteinase k-resistant prion protein core fragment (prp(res)) in a highly scrapie-affected goat flock in greece. the prp(res) profile by western immunoblotting in most animals was that of classical scrapie in sheep. however, in a series of clinically healthy ...	2011	21450953
overexpression of shadoo protein in transgenic mice does not impact the pathogenesis of scrapie.	shadoo is a glycoprotein expressed in the adult brain that is an interacting protein of prion protein; however, its function remains to be determined. to elucidate its role in prion pathogenesis, we generated transgenic mice overexpressing wild-type (wt) shadoo driven by the murine prp promoter. expression of the murine sprn transgene significantly increased brain shadoo protein levels in all three mouse lines generated. following infection with mouse-adapted scrapie strain 22l, all transgenic m ...	2011	21458534
investigation of the effects of experimental autolysis on the detection of abnormal prion protein in lymphoid and central nervous system tissues from elk and sheep using the western blotting method.	tissues unsuitable for standard immunohistochemical and histopathological examinations for chronic wasting disease (cwd) in cervids and for scrapie in sheep are frequently submitted for testing. this study investigated the effects of experimental autolysis on the detection of abnormal prion protein (prpsc) in lymphoid and central nervous system (cns) tissues from elk and sheep. the prpsc was detected using a western blotting (wb) test following prpsc enrichment using sodium phosphotungstic acid ...	2011	21461199
molecular dynamics studies on the structural stability of wild-type dog prion protein.	prion diseases such as creutzfeldt-jakob disease, variant creutzfeldt-jakob diseases, gerstmann-sträussler-scheinker syndrome, fatal familial insomnia, kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (or 'mad-cow' disease) and chronic wasting disease in cattle are invariably fatal and highly infectious neurodegenerative diseases affecting humans and animals. however, by now there have not been some effective therapeutic approaches to treat all these prion diseases. in 2008, ca ...	2011	21469747
molecular discrimination of sheep bovine spongiform encephalopathy from scrapie.	sheep ch1641-like transmissible spongiform encephalopathy isolates have shown molecular similarities to bovine spongiform encephalopathy (bse) isolates. we report that the prion protein prpsc from sheep bse is extremely resistant to denaturation. this feature, combined with the n-terminal prpsc cleavage, allowed differentiation of classical scrapie, including ch1641-like, from natural goat bse and experimental sheep bse.	2011	21470463
prions and protein-folding diseases.	abstract. norrby e (royal swedish academy of sciences, stockholm, sweden). prions and protein-folding diseases (review). j intern med 2011; doi: 10.1111/j.1365-2796.2011.02387.x prions represent a group of proteins with a unique capacity to fold into different conformations. one isoform is rich in beta-pleated sheets and can aggregate into amyloid that may be pathogenic. this abnormal form propagates itself by imposing its confirmation on the homologous normal host cell protein. pathogenic prio ...	2011	21481020
transmission of prion strains in a transgenic mouse model overexpressing human a53t mutated α-synuclein.	there is a growing interest in the potential roles of misfolded protein interactions in neurodegeneration. to investigate this issue, we inoculated 3 prion strains intracerebrally into transgenic (tgm83) mice that overexpress human a53t α-synuclein. in comparison to nontransgenic controls, there was a striking decrease in the incubation periods of scrapie, classic and h-type bovine spongiform encephalopathies(c-bse and h-bse), with conservation of the histopathologic and biochemical features cha ...	2011	21487306
palladium complexes affect the aggregation of human prion protein prp106-126.	many neurodegenerative disorders are induced by protein conformational change. prion diseases are characterized by protein conformational conversion from a normal cellular form (prp(c)) to an abnormal scrapie isoform (prp(sc)). prp106-126 is an accepted model for studying the characteristics of prp(sc) because they share many biological and physiochemical properties. to understand how metal complexes affect the property of the prion peptide, the present work investigated interactions between pd ...	2011	21504185
aromatase expression in cultured fetal sheep astrocytes after nitrosative/oxidative damage.	aromatase, the enzyme converting androgens into estrogens, is involved in many brain processes such as neural differentiation and plasticity or the prevention of cell death. we have previously observed an increase in aromatase immunoreactivity in sheep neurons exposed in vitro to the oxidant 3-nitro-l: -tyrosine. however, little is known regarding the way that sheep astrocytes cope with nitrosative stress, a condition occurring in sheep in the pathogenesis of neurodegenerative disorders such as ...	2011	21509460
gene expression profiling and association with prion-related lesions in the medulla oblongata of symptomatic natural scrapie animals.	the pathogenesis of natural scrapie and other prion diseases remains unclear. examining transcriptome variations in infected versus control animals may highlight new genes potentially involved in some of the molecular mechanisms of prion-induced pathology. the aim of this work was to identify disease-associated alterations in the gene expression profiles of the caudal medulla oblongata (mo) in sheep presenting the symptomatic phase of natural scrapie. the gene expression patterns in the mo from ...	2011	21629698
clinical, electroretinographic and histomorphometric evaluation of the retina in sheep with natural scrapie.	abstract: background: the retina is part of the diencephalon in a peripheral location and may be involved in prion diseases. retinal function and structural changes were assessed in naturally scrapie-affected red face manech ewes presenting the classical signs of the disease, and clinically healthy age-matched subjects for controls. ophthalmic examination was done prior to electroretinography (erg), which was carried out under conditions that allowed photopic and scotopic activities to be assess ...	2011	21639947
estimation of variant creutzfeldt-jakob disease infectivity titers in human blood.	background: blood of individuals with variant creutzfeldt-jakob disease (vcjd) is infectious but the titer is unknown. current estimates of possible vcjd infectivity titers in blood have largely relied on an assumption that the titers of vcjd agent in human blood are likely to be similar to those in blood of rodents infected with model transmissible spongiform encephalopathy agents, assayed by intracerebral inoculations of rodents of the same species. study design and methods: we analyzed publis ...	2011	21645006
mechanism of prp-amyloid formation in mice without transmissible spongiform encephalopathy.	gerstmann-sträussler-scheinker (gss) p102l disease is a familial form of a transmissible spongiform encephalopathy (tse) that can present with or without vacuolation of neuropil. inefficient disease transmission into 101ll transgenic mice was previously observed from gss p102l without vacuolation. however several aged, healthy mice had large plaques composed of abnormal prion protein (prp(d) ). here we perform the ultrastructural characterisation of such plaques and compare them with prp(d ) agg ...	2011	21645162
photodegradation illuminates the role of polyanions in prion infectivity.	understanding the mechanism by which prion infectivity is encoded by the misfolded protein prp (sc ) remains a high priority within the prion field. work from several groups has indicated cellular cofactors may be necessary to form infectious prions in vitro. the identity of endogenous prion conversion cofactors is currently unknown, but may include polyanions and/or lipid molecules. in a recent study, we manufactured infectious hamster prions containing purified prp (sc) , co-purified lipid, an ...	2011	21646861
quantitative detection and biological propagation of scrapie seeding activity in vitro facilitate use of prions as model pathogens for disinfection.	prions are pathogens with an unusually high tolerance to inactivation and constitute a complex challenge to the re-processing of surgical instruments. on the other hand, however, they provide an informative paradigm which has been exploited successfully for the development of novel broad-range disinfectants simultaneously active also against bacteria, viruses and fungi. here we report on the development of a methodological platform that further facilitates the use of scrapie prions as model path ...	2011	21647368
uptake dynamics of scrapie agent in the intestinal villous epithelium of suckling and weanling syrian hamsters.	in mice, the number of intestinal villous columnar epithelium cells that incorporate abnormal prion protein (prp(sc) ) decreases significantly after weaning. in this study, to investigate the dynamics of prp(sc) uptake during the growth of hamsters, scrapie 263k agent was inoculated orally into suckling and weanling syrian hamsters and the number of prp(sc) -positive villous epithelium cells was estimated immunohistochemically. the number of prp(sc) -positive cells declined significantly as the ...	2011	21668484
characterization of prnp and sprn coding regions from atypical scrapie cases diagnosed in poland.	scrapie, a fatal transmissible spongiform encephalopathy (tse) occurs in two phenotypes: classical and atypical. many authors point out that the polymorphism of three codons (136, 154, 171) of the prnp (prp gene) is associated with a sheep susceptibility to classical scrapie. until now, only one prnp gene variant coding phenylalanine at codon 141 has been found to be associated with atypical scrapie. another recently identified and interesting candidate gene for scrapie susceptibility in sheep i ...	2011	21674189
bovine spongiform encephalopathy: is it time to relax bse-related measures in the context of international trade?	bovine spongiform encephalopathy (bse) has presented serious challenges to both the world organisation for animal health and national governments, in defining and implementing appropriate national control measures, and in agreeing trade rules that permit safe trade in cattle and bovine products. precautionary trade rules were initially necessary, based upon the science of sheep scrapie, but research into bse later enabled bse-specific trade rules to be developed. as a result, current rules on tr ...	2011	21809757
biochemical and strain properties of cjd prions: complexity versus simplicity.	prions, the agents responsible for transmissible spongiform encephalopathies, are infectious proteins consisting primarily of scrapie prion protein (prp(sc) ), a misfolded, beta-sheet enriched and aggregated form of the host-encoded cellular prion protein (prp(c) ). their propagation is based on an autocatalytic prp conversion process. despite the lack of a nucleic acid genome, different prion strains have been isolated from animal diseases. increasing evidence supports the view that strain-spec ...	2011	21790605
exosome-producing follicle associated epithelium is not involved in uptake of prpd from the gut of sheep (ovis aries): an ultrastructural study.	in natural or experimental oral scrapie infection of sheep, disease associated prion protein (prp(d)) often first accumulates in peyer's patch (pp) follicles. the route by which infectivity reaches the follicles is unknown, however, intestinal epithelial cells may participate in intestinal antigenic presentation by delivering exosomes as vehicles of luminal antigens. in a previous study using an intestinal loop model, following inoculation of scrapie brain homogenate, inoculum associated prp(d) ...	2011	21789232
cytokine antibody array analysis in brain and periphery of scrapie-infected tg338 mice.	scrapie is a prion-associated transmissible spongiform encephalopathy (tse) of sheep and goats, and frequently serves as a comparative model for other prion diseases, such as chronic wasting disease and bovine spongiform encephalopathy. tses are unique neurologic disorders that do not appear to be accompanied by robust systemic immunologic responses. mrna data suggest that cytokines are involved in scrapie progression. in this study, brain tissue, mesenteric lymph nodes, splenic tissue and serum ...	2011	21788075
allelic frequency and genotypes of prion protein at codon 136 and 171 in iranian ghezel sheep breeds.	prp genotypes at codons 136 and 171 in one hundred twenty iranian ghezel sheep breeds were studied using allele-specific pcr amplification and compared with the well-known sheep breeds in north america, the united states, and europe. the frequency of v allele and vv genotype at codon 136 of ghezel sheep breed was significantly lower than aa and av. at codon 171, the frequency of allele h was significantly lower than q and r. despite the similarities of prp genotypes at codons 136 and 171 between ...	2011	21778818
histopathological studies of "ch1641-like" scrapie sources versus classical scrapie and bse transmitted to ovine transgenic mice (tgovprp4).	the possibility of the agent causing bovine spongiform encephalopathy (bse) infecting small ruminants is of serious concern for human health. among scrapie cases, the ch1641 source in particular appears to have certain biochemical properties similar to the bse strain. in france, several natural scrapie cases were identified as "ch1641-like" natural scrapie isolates in sheep and goats. the tg(ovprp4) mouse line expressing the ovine prion protein is a sensitive model for studying and identifying s ...	2011	21765939
amyloid: little proteins, big clues.		2011	21760575
from high-throughput cell culture screening to mouse model: identification of new inhibitor classes against prion disease.	transmissible spongiform encephalopathies (tse) or prion diseases belong to a category of fatal and so far untreatable neurodegenerative conditions. all prion diseases are characterized by both degeneration in the central nervous system (cns) in humans and animals and the deposition and accumulation of proteinase k-resistant prion protein (prp(res) ). until now, no pharmaceutical product has been available to cure these diseases or to alleviate their associated symptoms. here, a cell-culture scr ...	2011	21755599
characterization of the prnp gene locus in chios dairy sheep and its association with milk production and reproduction traits.	the objective of this study was to examine the prion protein gene locus (prnp) in chios sheep. prnp is linked with scrapie resistance in small ruminants. here, its impact on milk production (test-day and total lactation yield) and reproduction (age at first lambing, conception rate at first service, and prolificacy) was assessed. genotyping at codons 136, 154 and 171 (classical scrapie) and 141 (atypical scrapie) was performed using dna from milk somatic cells and pcr-rflp analysis. a total of 1 ...	2011	21749423
steric zipper formed by hydrophobic peptide fragment of syrian hamster prion protein.	steric zippers, where the residues of two neighboring ß-sheet layers are tightly interdigitated, have been proposed as fundamental structural units of amyloid fibrils by eisenberg and co-workers. the steric zipper formed by polypeptides containing the palindromic sequence agaaaaga has a distinctive feature that the distance between two interdigitated ß-sheet layers is comparable to the interstrand distance of the individual ß-sheet. this structural motif is of great interest in the study of prio ...	2011	21749158
diphenyl-pyrazole derived compounds increase survival time of mice after prion infection.	transmissible spongiform encephalopathies (tses) represent a group of fatal neurodegenerative disorders which can be transmitted by natural infection or inoculation. tses include scrapie in sheep, bse in cattle, and creutzfeldt-jakob disease (cjd) in humans. the emergence of a variant form of cjd (vcjd) which has been associated to bse, produced strong pressure to search for effective treatments with new drugs. up to now, however, tses are incurable, although many efforts have been made in vitro ...	2011	21746938
enhancement of immunohistochemical staining of scrapie proteins and immune cells within lymph nodes of early scrapie-infected sheep.	transmissible spongiform encephalopathies (tse) are a group of fatal neurodegenerative diseases that affect animals as well as humans. the oldest of these diseases is scrapie seen in sheep. scrapie is caused by an altered form (prp(sc)), capable of inducing "self-replication" of the normal host prion protein(prp(c)). there is currently no universal standard for antigen retrieval when using immunohistochemistry to simultaneously stain the prp(c) protein and other cellular markers. the use of form ...	2011	21722647
survival of infectious prions in water.	the objective of this study was to evaluate the fate of infectious prions in water. known concentrations of infectious prions were added to deionized water, tap water, and wastewater. samples were incubated at 25-¦c, 37-¦c, and 50-¦c for 1 to 8 weeks. the standard scrapie cell assay (ssca) which includes the elispot (enzyme linked immuno-spot) reaction was performed to determine prion infectivity and quantity as a function of time. a reduction of infectious prions was observed at 25-¦c, 37-¦c, a ...	2011	21707419
conserved properties of human and bovine prion strains on transmission to guinea pigs.	the first transmissions of human prion diseases to rodents used guinea pigs (gps, cavia porcellus). later, transgenic mice expressing human or chimeric human/mouse prp replaced gps, but the small size of the mouse limits some investigations. to investigate the fidelity of strain-specific prion transmission to gps, we inoculated 'type 1' and 'type 2' prion strains into gps, and we measured the incubation times and determined the strain-specified size of the unglycosylated, protease-resistant (r) ...	2011	21727894
mutation directional selection sheds light on prion pathogenesis.	as mutations in the prnp gene account for human hereditary prion diseases (prds), it is crucial to elucidating how these mutations affect the central pathogenic conformational transition of normal cellular prion protein (prp(c)) to abnormal scrapie isoform (prp(sc)). many studies proposed that these pathogenic mutations may make prp more susceptible to conformational change through altering its structure stability. by evaluating the most recent observations regarding pathogenic mutations, it was ...	2011	21679685
analysis of nucleic acid chaperoning by the prion protein and its inhibition by oligonucleotides.	prion diseases are unique neurodegenerative illnesses associated with the conversion of the cellular prion protein (prp(c)) into the aggregated misfolded scrapie isoform, named prp(sc). recent studies on the physiological role of prp(c) revealed that this protein has probably multiple functions, notably in cell-cell adhesion and signal transduction, and in assisting nucleic acid folding. in fact, in vitro findings indicated that the human prp (huprp) possesses nucleic acid binding and annealing ...	2011	21737432
transcriptional profiling of peripheral lymphoid tissue reveals genes and networks linked to ssbp/1 scrapie pathology in sheep.	transmissible spongiform encephalopathies (tses) are slow and progressive neurodegenerative diseases of humans and animals. the major target organ for all tses is the brain but some tse agents are associated with prior accumulation within the peripheral lymphoid system. many studies have examined the effects of scrapie infection on the expression of central nervous system (cns) genes, but this study examines the progression of scrapie pathology in the peripheral lymphoid system and how scrapie i ...	2011	21684093
prion disease detection, pmca kinetics, and igg in urine from sheep naturally/experimentally infected with scrapie and deer with preclinical/clinical chronic wasting disease.	prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. low levels of infectious agent and limited, infrequent success of disease transmissibility and prp(sc) detection have been reported with urine from experimentally infected clinical cervids and rodents. we report the detection of prion disease-associated seeding activity (pasa) in urine from naturally and orally infected sheep with clinical scrapie agent and orally infected preclinical ...	2011	21715495
common structural traits across pathogenic mutants of the human prion protein and their implications for familial prion diseases.	human (hu) familial prion diseases are associated with about 40 point mutations of the gene coding for the prion protein (prp). most of the variants associated with these mutations are located in the globular domain of the protein. we performed 50-áns of molecular dynamics for each of these mutants to investigate their structure in aqueous solution. overall, 1.6-á++s of molecular dynamics data is presented. the calculations are based on the amber(parm99) force field, which has been shown to repr ...	2011	21689662
assessment of the genetic susceptibility of sheep to scrapie by protein misfolding cyclic amplification and comparison with experimental scrapie transmission studies.	the susceptibility of sheep to scrapie is influenced mainly by the prion protein polymorphisms a136v, r154h, and q171r/h. here we analyzed the ability of protein misfolding cyclic amplification (pmca) to model the genetic susceptibility of sheep to scrapie. for this purpose, we studied the efficiency of brain homogenates from sheep with different prp genotypes to support prp(sc) amplification by pmca using an arq/arq scrapie inoculum. the results were then compared with those obtained in vivo us ...	2011	21680531
real-time quaking-induced conversion: a highly sensitive assay for prion detection.	we recently developed a new in vitro amplification technology, designated "real-time quaking-induced conversion (rt-quic)", for detection of the abnormal form of prion protein (prpsc) in easily accessible specimens such as cerebrospinal fluid (csf). after assessment of more than 200 csf specimens from japanese and australian patients, we found no instance of a false positive, and more than 80% accuracy for the correct diagnosis of sporadic creutzfeldt-jakob disease (scjd). furthermore, the rt-qu ...	2011	21778820
Bee venom phospholipase A2 prevents prion peptide induced-cell death in neuronal cells.	Bee venom phospholipase A2 (bvPLA2) is a prototypic group-áIII enzyme which consists of unique N-terminal and C-terminal domains and a central secretory PLA2 (sPLA2) domain. This sPLA2 domain is highly homologous with human group-áIII sPLA2. Current evidence suggests that group-áIII sPLA2 may affect some neuronal functions, such as neuritogenesis, neurotransmitter release and neuronal survival. The prion diseases are neurodegenerative disorders characterized by the conversion of the normal cellu ...	2011	21701769
Accumulation and aberrant composition of cholesteryl esters in Scrapie-infected N2a cells and C57BL/6 mouse brains.	ABSTRACT:	2011	21816038
Molecular cloning and polymorphism analysis of the prion protein gene in Tan sheep of Ningxia, China.	The resistance or susceptibility of sheep to scrapie is associated with polymorphisms of the prion protein gene (PRNP), particularly, single nucleotide polymorphisms (SNPs) in amino acid positions 136, 154 and 171. The prion protein (PrP) gene sequence and the deduced amino acid alignment of prion protein in Tan sheep, a local Chinese sheep breed traditionally raised in Ningxia, northwestern China, were determined and variability of the PrP amino acids sequence was analyzed in this study. The Pr ...	2011	21722718
PRNP haplotype and genotype frequencies in Brazilian sheep: Issues for conservation and breeding programs.	Polymorphisms of PRNP gene have been strongly correlated to the susceptibility/resistance to scrapie in sheep. Variants at the coding positions 136, 154 and 171 have been the most frequently associated to susceptibility to classical scrapie. The aim of this study was to estimate PRNP haplotype and genotype frequencies in a sample of 1400 sheep from 13 different breeds that are representative of the main production regions in Brazil. A total of four different alleles (ARR, ARQ, AHQ and VRQ) and n ...	2011	21816449
isolation of prion with bse properties from farmed goat.	transmissible spongiform encephalopathies are fatal neurodegenerative diseases that include variant creutzfeldt-jakob disease in humans, scrapie in small ruminants, and bovine spongiform encephalopathy (bse) in cattle. scrapie is not considered a public health risk, but bse has been linked to variant creutzfeldt-jakob disease. small ruminants are susceptible to bse, and in 2005 bse was identified in a farmed goat in france. we confirm another bse case in a goat in which scrapie was originally di ...	2011	22172149
th2-polarised prp-specific transgenic t-cells confer partial protection against murine scrapie.	several hurdles must be overcome in order to achieve efficient and safe immunotherapy against conformational neurodegenerative diseases. in prion diseases, the main difficulty is that the prion protein is tolerated as a self protein, which prevents powerful immune responses. passive antibody therapy is effective only during early, asymptomatic disease, well before diagnosis is made. if efficient immunotherapy of prion diseases is to be achieved, it is crucial to understand precisely how immune t ...	2011	21909267
ten years of bse surveillance in italy: neuropathological findings in clinically suspected cases.	between 2001 and 2010, 244 clinically suspected cases of bovine spongiform encephalopathy (bse) were reported in italy. this report summarizes the neuropathological findings in cattle displaying clinical signs consistent with a diagnosis of bse. all animal specimens were submitted for confirmatory testing; samples testing negative underwent neuropathological examination to establish the differential diagnosis. immunohistochemistry for scrapie prion protein (prpsc) at the level of frontal cortex ...	2011	22083104
effect of prp genotype and route of inoculation on the ability of discriminatory western blot to distinguish scrapie from sheep bovine spongiform encephalopathy.	procedures for discriminating scrapie from bovine spongiform encephalopathy (bse) in sheep are relevant to ascertain whether bse has entered the sheep population. this study was aimed at investigating whether the suitability of an official eu discriminative method is affected by the sheep prp genotype and route of infection.	2011	21994325
styryl-based and tricyclic compounds as potential anti-prion agents.	prion diseases currently have no effective therapy. these illnesses affect both animal and human populations, and are characterized by the conformational change of a normal self protein prp(c) (c for cellular) to a pathological and infectious conformer, prp(sc) (sc for scrapie). we used a well characterized tissue culture model of prion infection, where mouse neuroblastoma cells (n2a) were infected with 22l prp(sc), to screen compounds for anti-prion activity. in a prior study we designed a libr ...	2011	21931860
demographic characteristics of scrapie-affected holdings identified by active and passive surveillance schemes in great britain: 2002-2005.	several surveillance techniques have been used to quantify the prevalence of both classical and atypical scrapie in british sheep, namely the recording of clinical suspects (rc) and the testing of animals slaughtered at abattoir (as) or reported as fallen stock (fs). any estimate of prevalence based on a particular source is likely to have been affected by demographic differences in the populations sampled. in this study, the demographic characteristics of scrapie-affected holdings detected by e ...	2011	20056463
cellular and sub-cellular pathology of animal prion diseases: relationship between morphological changes, accumulation of abnormal prion protein and clinical disease.	the transmissible spongiform encephalopathies (tses) or prion diseases of animals are characterised by cns spongiform change, gliosis and the accumulation of disease-associated forms of prion protein (prp(d)). particularly in ruminant prion diseases, a wide range of morphological types of prp(d) depositions are found in association with neurons and glia. when light microscopic patterns of prp(d) accumulations are correlated with sub-cellular structure, intracellular prp(d) co-localises with lyso ...	2011	20532540
glypican-1 facilitates prion conversion in lipid rafts.	the conformational conversion of the cellular prion protein (prp(c)) to the infectious form (prp(sc)) is the critical step in the pathogenesis of prion diseases such as creutzfeldt-jakob disease in humans and scrapie in sheep. cholesterol-rich lipid rafts play a key role in the conversion of prp(c) to prp(sc) and other cellular components have been identified as important cofactors to trigger, enhance, or accelerate prion formation. amongst these heparan sulphate proteoglycans (hspgs) and their ...	2011	20681952
an assessment of the efficiency of prpsc detection in rectal mucosa and third-eyelid biopsies from animals infected with scrapie.	in classical scrapie, detection of prpsc on lymphoreticular system is used for the in vivo and post mortem diagnosis of the disease. however, the sensitivity of this methodology is not well characterised because the magnitude and duration of lymphoid tissue involvement can vary considerably. the aim of the present study was to evaluate the efficiency of detecting prpsc in rectal mucosa and third-eyelid biopsies. a total of 474 genetically susceptible sheep and 24 goats from three scrapie infecte ...	2011	20685048
prp gene polymorphisms in cyprus goats and their association with resistance or susceptibility to natural scrapie.	in contrast to scrapie in sheep, the genetic basis of susceptibility to scrapie in goats is not well understood. to study the association of prion protein (prp) alleles with susceptibility to scrapie in goats in cyprus, the coding sequence of the caprine prp gene was determined in 717 goats, including 218 scrapie positive animals. several novel polymorphisms were detected, such as a novel octarepeat variant and a stop codon mutation. amino acids at codons 146 and 154 were associated with suscept ...	2011	20093056
extraneural manifestations of prion infection in gpi-anchorless transgenic mice.	earlier studies indicated that transgenic (tg) mice engineered to express prion protein (prp) lacking the glycophosphatidylinositol (gpi⁻/⁻) membrane anchor formed abnormal proteinase-resistant prion (prpsc) amyloid deposits in their brains and hearts when infected with the rml strain of murine scrapie. in contrast, rml scrapie infection of normal mice with a gpi-anchored prp did not deposit amyloid with prpsc in the brain or the heart. here we report that scrapie-infected gpi⁻/⁻ prp tg mice als ...	2011	21227476
glycosylphosphatidylinositol anchor-dependent stimulation pathway required for generation of baculovirus-derived recombinant scrapie prion protein.	the pathogenic isoform (prp(sc)) of the host-encoded cellular prion protein (prp(c)) is considered to be an infectious agent of transmissible spongiform encephalopathy (tse). the detailed mechanism by which the prp(sc) seed catalyzes the structural conversion of endogenous prp(c) into nascent prp(sc) in vivo still remains unclear. recent studies reveal that bacterially derived recombinant prp (recprp) can be used as a substrate for the in vitro generation of protease-resistant recprp (recprp(res ...	2011	21228241
comparison of brain prpd distribution in ovine bse and scrapie.	scrapie and bovine spongiform encephalopathy (bse) are both prion diseases affecting ruminants, and these diseases do not share the same public health concerns. surveillance of the bse agent in small ruminants has been a great challenge, and the recent identification of diverse prion diseases in ruminants has led to the development of new methods for strain typing. in our study, using immunohistochemistry (ihc), we assessed the distribution of prp(d) in the brains of 2 experimentally bse-infecte ...	2011	21245284
aerosols transmit prions to immunocompetent and immunodeficient mice.	prions, the agents causing transmissible spongiform encephalopathies, colonize the brain of hosts after oral, parenteral, intralingual, or even transdermal uptake. however, prions are not generally considered to be airborne. here we report that inbred and crossbred wild-type mice, as well as tga20 transgenic mice overexpressing prp(c), efficiently develop scrapie upon exposure to aerosolized prions. nse-prp transgenic mice, which express prp(c) selectively in neurons, were also susceptible to ai ...	2011	21249178
comparative performance of three tse rapid tests for surveillance in healthy sheep affected by scrapie.	rapid tests specific for sheep and goats became part of european union-wide active scrapie surveillance in 2006. performance of three approved tse rapid tests for the detection of sheep infected with scrapie in field cases in the pre-clinical stage of the disease was compared. the medulla oblongata of 969 asymptomatic sheep of various genotype and breed aged over 18 months from 23 italian flocks affected with scrapie, were tested by the bio-rad tesee sheep/goat (a), the idexx herdchek bse-scrapi ...	2011	21256871
emergence of multiple prion strains from single isolates of ovine scrapie.	the infectious agent associated with prion diseases such as ovine scrapie shows strain diversity. ovine prion strains have typically been identified by their transmission properties in wild-type mice. however, strain typing of ovine scrapie isolates in wild-type mice may not reveal properties of the infectious prion agent as they exist in the original host. this could be circumvented if ovine scrapie isolates are passaged in ovine prion protein (prp)-transgenic mice. this study used incubation t ...	2011	21270287
fundamentals of prions and their inactivation (review).	prion is an infectious particle composed of an abnormal isoform of the prion protein (prpsc) and causes prion diseases such as bovine spongiform encephalopathy (bse), creutzfeldt-jakob disease (cjd) and scrapie. host cells express cellular prion protein (prpc), which plays roles in normal functions such as anti-oxidative stress. prpsc is derived from prpc and produced by conformational conversion. prion is notorious as a resistant pathogen, being difficult to inactivate with conventional sterili ...	2011	21271212
sparse prp(sc) accumulation in the placentas of goats with naturally acquired scrapie.	domestic goats (capra hircus) are a natural and experimental host of scrapie and bovine spongiform encephalopathy, the transmissible spongiform encephalopathies (tse) of sheep and cattle. goats are also susceptible to experimental infection with the agents of tses of deer and elk (chronic wasting disease) and humans (creutzfeldt jakob disease). distribution of prpsc, the abnormal prion protein, is similar in the tissues of scrapie-infected sheep and goats but no data are available on the potenti ...	2011	21284878
utility of mass spectrometry in the diagnosis of prion diseases.	we developed a sensitive mass spectrometry-based method of quantitating the prions present in a variety of mammalian species. calibration curves relating the area ratios of the integrated mrm signals from selected analyte peptides and their oxidized analogues to their homologous stable isotope labeled internal standards were prepared. the limit of detection (lod) and limit of quantitation (loq) for the synthetic peptides from human, sheep, deer, cow, and mouse prp were determined to be below 100 ...	2011	21288014
transmission of classical scrapie to wild-type mice: the influence of the ovine prp sequence on lesion profiles.	susceptibility of sheep to classical scrapie is determined by polymorphisms in the coding region of the prion protein gene (prnp), mainly at codons 136, 154 and 171. it has recently been shown that lesion profiles from classical field scrapie isolates that transmitted to riii mice can be classified into different groups. there was also strong, but not absolute, association between the different groups and codon 136. here, we examine the hypothesis that additional polymorphisms in the open readin ...	2011	21293966
molecular typing of protease-resistant prion protein in transmissible spongiform encephalopathies of small ruminants, france, 2002-2009.	the agent that causes bovine spongiform encephalopathy (bse) may be infecting small ruminants, which could have serious implications for human health. to distinguish bse from scrapie and to examine the molecular characteristics of the protease-resistant prion protein (prp(res)), we used a specifically designed western blot method to test isolates from 648 sheep and 53 goats. during 2002-2009, classical non-nor98 transmissible spongiform encephalopathy had been confirmed among ≈1.7 million small ...	2011	21192855
understanding the neurospecificity of prion protein signaling.	the cellular prion protein prp(c) is the normal counterpart of the scrapie prion protein prp(sc), the main component of the infectious agent of transmissible spongiform encephalopathies (tses). it is a ubiquitous cell-surface glycoprotein, abundantly expressed in neurons, which constitute the targets of tse pathogenesis. the presence of prp(c) at the surface of neurons is an absolute requirement for the development of prion diseases and corruption of prp(c) function(s) within an infectious conte ...	2011	21196165
biological properties of the prp-like shadoo protein.	the sprn gene encodes the shadoo glycoprotein (sho), a central nervous system-expressed member of the prion protein superfamily. sho has similarity to two features within prpc's natively unstructured n-terminus, a hydrophobic domain and tandem repeats with positively charged residues. indeed, scrutiny of sho's biochemical properties in uninfected cells has revealed overlaps with the properties of prpc, these including shared protein binding partners. sprn is conserved in mammals, as is the prion ...	2011	21196244
spiroplasma found in the eyes of scrapie affected sheep.	scrapie, a transmissible spongiform encephalopathy (tse) occurring naturally in sheep, characteristically shows a severe retinopathy that is well developed in the terminal phases of the disease. in this study, we set out to demonstrate similar retinal changes in our ruminant spiroplasmosis tse model.	2011	21199275
alimentary prion infections: touchdown in the intestine.	neurodegenerative diseases are caused by proteinaceous aggregates, usually consisting of misfolded proteins which are often typified by a high proportion of β-sheets, which accumulate in the central nervous system. these diseases, including morbus alzheimer, parkinson disease and transmissible spongiform encephalopathies (tses)--also termed prion disorders--afflict a substantial proportion of the human population and as such the etiology and pathogenesis of these diseases has been the focus of m ...	2011	21150306
pruritus in familial creutzfeldt-jakob disease: a common symptom associated with central nervous system pathology.	pruritus, a common feature of animal prion diseases such as scrapie, is rarely reported in humans with creutzfeldt-jakob disease (cjd), and its anatomical background is not well defined. the present study was undertaken to carry out a methodical prospective search for the prevalence of pruritus in cjd patients and investigate its anatomical substrate by mri. the study group included consecutive familial and sporadic cjd patients carrying the e200k prnp mutation followed up in a longitudinal pros ...	2011	20725737
polymorphism of prion protein gene in sheep of inner mongolian, china.	susceptibility to natural scrapie in sheep is associated with polymorphisms at codons 136, 154 and 171 of the prion protein (prp) gene. to assess the risk of scrapie in sheep raised in china, dna from 30 sheep of two breeds was isolated, amplified and sequenced for the prp gene. the ovine prp gene was found to be highly homogenous. the genotype associated with high susceptibility to scrapie (vrq) was absent, whereas that associated with the resistance (arr) was present in 6.7% of sheep examined. ...	2011	21063762
hsp70 binds to prpc in the process of prpc release via exosomes from thp-1 monocytes.	prpc (cellular prion protein) is a gpi (glycophosphatidylinositol)-anchored protein present on the surface of a number of peripheral blood cells. prpc must be present for the generation and propagation of pathogenic conformer [prpsc (scrapie prion protein)], which is a conformational conversion form of prpc and has a central role in transmissible spongiform encephalopathies. it is important to determine the transportation mechanism of normal prpc between cells. exosomes are membrane vesicles rel ...	2011	20964628
expression and knockdown of cellular prion protein (prpc) in differentiating mouse embryonic stem cells.	the mammalian cellular prion protein (prp(c)) is a highly conserved glycoprotein that may undergo conversion into a conformationally altered isoform (scrapie prion protein or prp(sc)), widely believed to be the pathogenic agent of transmissible spongiform encephalopathies (tses). although much is known about pathogenic prp conversion and its role in tses, the normal function of prp(c) is poorly understood. given the abundant expression of prp(c) in the developing mammalian cns and the spatial as ...	2011	20926176
cytosolic prp induces apoptosis of cell by disrupting microtubule assembly.	prion protein (prp) is able to bind with tubulin and to interfere with the formation of microtubule. to investigate the influence of accumulation of cytosolic prp in cytoplasm on microtubule, plasmid pcdna3.1-prp23-230 expressing human prp23-230 was introduced into hela cells. immunoprecipitation assays identified the molecular interaction between cytosolic prp and cellular tubulin. confocal microscopy showed the co-localization of the expressed cytosolic prp with tubulin in cytoplasm. immunoflu ...	2011	20838930
gene expression analysis in distinct regions of the central nervous system during the development of ssbp/1 sheep scrapie.	rodent scrapie models have been exploited to define the molecular basis for the progression of neuropathological changes in tse diseases. we aim to assess whether cns gene expression changes consistently observed in mouse models are of generic relevance, for example to natural tse diseases, or are tse strain, host species or brain region specific. six genes, representing distinct physiological pathways and showing consistent changes in expression levels with disease progression in murine scrapie ...	2011	20576367
a partially folded state of ovalbumin at low ph tends to aggregate.	at ph 2, ovalbumin retains native-like secondary structure as seen by far-uv cd and ftir, but lacks well-defined tertiary structure as seen by the fluorescence and near-uv cd spectra. addition of 20 mm trifluoroacetic acid (tfa) or 30 mm trichloroacetic acid (tca) on acid-induced state results in protein aggregation. this aggregated state possesses extensive β-sheet structure as revealed by far-uv cd and ftir spectroscopy. furthermore, the aggregates exhibit decreased ans fluorescence and increa ...	2011	20703954
Frequency distribution of PRNP polymorphisms in the Pakistani population.	Prion diseases are neurodegenerative conditions caused by misfolding of a normal host-encoded prion protein (PrP(C)) into pathogenic scrapie prion protein (PrP(Sc)). In human prion diseases, the M129V prion protein polymorphism is known to confer susceptibility to the disease, determines PrP(Sc) conformation and alters clinicopathological phenotypes. To date, all clinicopathologically confirmed cases of a variant form of Cruetzfeldt-Jacob disease (vCJD) have been 129MM homozygotes. There is also ...	2012	22062631
historical overview of prion diseases: a view from afar.	the transmissible spongiform encephalopathies (tses), or prion diseases, are a group of neurodegenerative disorders which include kuru, creutzfeldt-jakob disease (cjd), gerstmann-sträussler-scheinker (gss) syndrome, and fatal familial insomnia in men, natural scrapie in sheep, goats and mufflons, transmissible mink encephalopathy in ranch-reared mink, chronic wasting disease of mule deer and elk, bovine spongiform encephalopathy or "mad cow disease" and its analogues in several exotic species of ...	2012	22505359
heat shock protein 70 selectively mediates the degradation of cytosolic prps and restores the cytosolic prp-induced cytotoxicity via a molecular interaction.	although the aggregation of prpsc is thought to be crucial for the neuropathology of prion diseases, there is evidence in cultured cells and transgenic mice that neuronal death can be triggered by the accumulation of cytosolic prps, leading to the hypothesis that the accumulation of prps in the cytosol of neurons may be a primary neurotoxic culprit. hsp70, a molecular chaperone involved in protein folding/refolding and degradation in the cytoplasm, has a protective effect in some models of neuro ...	2012	23216755
acetone precipitation of the scrapie agent results in successful recovery of prp(sc) but decreased infectivity.	bioassay is considered the most sensitive method for evaluating prion inactivation procedures. because prions are resistant to methods effective at inactivating conventional microorganisms, prion inactivation research has focused on relatively harsh alternatives, such as concentrated sodium hypochlorite or sodium hydroxide. often, bioassay for residual infectivity in these studies requires dilution or biochemical alteration of the treated sample in order to maintain subject health and survival. ...	2012	22519670
the effects of host age on the transport of complement-bound complexes to the spleen and the pathogenesis of intravenous scrapie infection.	infections with variant creutzfeldt-jakob disease (vcjd) have almost exclusively occurred in young patients, but the reasons for this age distribution are uncertain. our data suggest that the pathogenesis of many peripherally acquired transmissible spongiform encephalopathy (tse) agents is less efficient in aged individuals. four vcjd cases linked to transfusion of vcjd-contaminated blood or blood products have been described. three cases occurred in elderly patients, implying that intravenous e ...	2012	22031932
the oral secretion of infectious scrapie prions occurs in preclinical sheep with a range of prnp genotypes.	preclinical sheep with the highly scrapie-susceptible vrq/vrq prnp genotype secrete prions from the oral cavity. in order to further understand the significance of orally available prions, buccal swabs were taken from sheep with a range of prnp genotypes and analyzed by serial protein misfolding cyclic amplification (spmca). prions were detected in buccal swabs from scrapie-exposed sheep of genotypes linked to high (vrq/vrq and arq/vrq) and low (arr/vrq and ahq/vrq) lymphoreticular system involv ...	2012	22013047