Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
scrapie genetics before the discovery of prions. 201019707236
prion protein polymorphisms and estimation of risk of scrapie in east asian sheep.allele and genotype frequency distributions of prion protein (prp) polymorphisms at three codons, 136, 154, and 171, in east asian sheep were determined by pcr-rflp analysis using 553 animals from nine local breeds of the northern group and four local breeds of the southern group. based on the genotype distribution, the risk score for scrapie was estimated. among the local breeds, arq appeared predominantly (0.7701-1), followed by arh and arr. from such a biased allele distribution, it was diffi ...201019731007
prion protein and metal interaction: physiological and pathological implications.metal induced free radicals are important mediators of neurotoxicity in several neurodegenerative conditions such as alzheimer's disease, parkinson's disease, and huntington's disease. similar evidence is now emerging for prion diseases, a group of neurodegenerative disorders of humans and animals. the main pathogenic agent in all prion disorders is prp-scrapie (prp(sc)), a beta-sheet rich isoform of a normal cell surface glycoprotein known as the prion protein (prp(c)). deposits of prp(sc) in t ...201019767653
polymorphisms in the hsp90aa1 5' flanking region are associated with scrapie incubation period in sheep.susceptibility to scrapie is mainly controlled by point mutations at the prnp locus. however, additional quantitative trait loci (qtl) have been identified across the genome including a region in oar18. the gene which encodes the inducible form of the cytoplasmic hsp90 chaperone (hsp90aa1) maps within this region and seems to be associated with the resistance/susceptibility to scrapie in sheep. here, we have analyzed several polymorphisms which were previously described in the ovine hsp90aa1 5' ...201019838832
removal of tse agents by depth or membrane filtration from plasma products.the removal of the abnormal form of prion protein i.e. prp(sc) by filtration steps in the plasma fractionation process has been investigated by immuno-western blotting. depth filtration has been shown to be capable of removing scrapie by 2-3 log from certain plasma product intermediates. these include cryoprecipitate supernatant, used for the manufacture of immunoglobulin and albumin, and albumin fraction v, by filtration using pall seitz or 3m cuno depth filters respectively. however no signifi ...201019854662
mouse vaccination with dendritic cells loaded with prion protein peptides overcomes tolerance and delays scrapie.prion diseases are presumed to be caused by the accumulation in the brain of a pathological protein called prion protein (prp) scrapie which results from the transconformation of cellular prp, a ubiquitous glycoprotein expressed in all mammals. since all isoforms of prp are perceived as self by the host immune system, a major problem in designing efficient immunoprophylaxis or immunotherapy is to overcome tolerance. the present study was aimed at investigating whether bone-marrow-derived dendrit ...201019864503
targeting of the prion protein to the cytosol: mechanisms and consequences.prion diseases are characterized by the conformational transition of the cellular prion protein (prp(c)) into an aberrant protein conformer, designated scrapie-prion protein (prp(sc)). a causal link between protein misfolding and neurodegeneration has been established for a variety of neurodegenerative disease, such as alzheimer's disease, parkinson's disease and polyglutamine diseases, but there is an ongoing debate about the nature of the neurotoxic species and how non-native conformers can da ...201019767654
the role of gpi-anchored prp c in mediating the neurotoxic effect of scrapie prions in neurons.there are two central phenomena in prion disease: prion replication and prion neurotoxicity. underlying them both is the conversion of a host-encoded ubiquitously expressed protein, prion protein (prp(c)), into a partially-protease resistant isoform, prp(sc), which accumulates in the brain. prp(sc) is associated with both pathology and infectivity. in the absence of prp(c), prp(sc) cannot be generated and prp-null mice do not propagate infectivity or develop pathology on infection with scrapie. ...201019767655
strain-specific proteolytic processing of the prion protein in prion diseases of ruminants transmitted in ovine transgenic mice.the cerebral prion protein (prp) isolated in the absence of proteinase k digestion, from ruminants prion sources transmitted to ovine transgenic mice, was studied by western blot analysis. a c2 prp fragment, showing strain-specific cleavages, similar to those observed after proteinase k or thermolysin digestion, accumulated in the brain. 'ch1641-like' scrapie was characterized by the unique accumulation of a more c-terminally cleaved prp fragment (ctf14). a similar, protease-resistant, prp produ ...201019828761
redox control of prion and disease pathogenesis.imbalance of brain metal homeostasis and associated oxidative stress by redox-active metals like iron and copper is an important trigger of neurotoxicity in several neurodegenerative conditions, including prion disorders. whereas some reports attribute this to end-stage disease, others provide evidence for specific mechanisms leading to brain metal dyshomeostasis during disease progression. in prion disorders, imbalance of brain-iron homeostasis is observed before end-stage disease and worsens w ...201019803746
changes in sympathetic activity in prion neuroinvasion.prion diseases are neurodegenerative diseases affecting humans and animals in which the infectious agent or prion is prp(res), a protease-resistant conformer of the cell protein prp. the natural transmission route of prion diseases is peripheral infection, with the lymphoreticular system (lrs) and peripheral nerves being involved in animal models of scrapie neuroinvasion and human prion diseases. to study the effects of prp neuroinvasion on sympathetic nerve function, we measured plasma catechol ...201019804827
alpha-synuclein deficiency in the c57bl/6jolahsd strain does not modify disease progression in the me7-model of prion disease.we previously detailed how intrahippocampal inoculation of c57bl/6j mice with murine modified scrapie (me7) leads to chronic neurodegeneration (cunningham c, deacon r, wells h, boche d, waters s, diniz cp, scott h, rawlins jn, perry vh (2003) eur j neurosci 17:2147-2155.). our characterization of the me7-model is based on inoculation of this murine modified scrapie agent into c57bl/6j mice from harlan laboratories. this agent in the c57bl/6j host generates a disease that spans a 24-week time cou ...201019879926
prediction of prion protein genotype and association of this genotype with lamb performance traits of suffolk sheep.the association of the prion protein (prp) gene with susceptibility to scrapie has formed the basis of selection programs aimed at eradicating the disease from sheep populations. animals are genotyped for the prp gene and those with the less susceptible genotypes are selected. the objectives of this study were to determine the effectiveness of predicting prp genotypes by using information from relatives and to investigate the association of the prp genotype with lamb performance traits in suffol ...201019897640
co-existence of classical scrapie and nor98 in a sheep from an italian outbreak.nor98 is an atypical scrapie strain characterized by a molecular pattern and brain distribution of the pathological prion protein (prp(sc)) different from classical scrapie. in italy, 69 atypical cases have been identified so far and all were characterized as nor98 strain. in this paper we report an unusual case in a sheep which showed immunohistochemical and molecular features of prp(sc) different from the other atypical cases. the sheep was from an outbreak where the index and the other four c ...201020031179
fast, broad-range disinfection of bacteria, fungi, viruses and prions.effective disinfectants are of key importance for the safe handling and reprocessing of surgical instruments. this study tested whether new formulations containing sds, naoh and 1-propanol (n-propanol) are simultaneously active against a broad range of pathogens including bacteria, fungi, non-enveloped viruses and prions. inactivation and disinfection were examined in suspension and on carriers, using coagulated blood or brain homogenate as an organic contaminant. coomassie blue staining was use ...201019864502
infection of cell lines with experimental and natural ovine scrapie agents.mouse bioassay remains the gold standard for determining proof of infectivity, strain type, and infectious titer estimation in prion disease research. the development of an approach using ex vivo cell-based assays remains an attractive alternative, both in order to reduce the use of mice and to hasten results. the main limitation of a cell-based approach is the scarcity of cell lines permissive to infection with natural transmissible spongiform encephalopathy strains. this study combines two adv ...201020032176
atypical scrapie: impact on eradication policies. 201019910225
identification of polymorphisms in the ovine shadow of prion protein (sprn) gene and assessment of their effect on promoter activity and susceptibility for classical scrapie.shadow of prion protein (sprn) is an interesting candidate gene thought to be involved in prion pathogenesis. in humans, an association has already been discovered between mutations in sprn and the incidence of variant and sporadic creutzfeldt-jakob disease. however, in sheep, the effect of mutations in sprn is largely unknown. therefore, we analysed the presence of mutations in the entire ovine sprn gene, their association with scrapie susceptibility and their effect on sprn promoter activity. ...201019917049
effect of scrapie on the stability of housekeeping genes.scrapie is the archetype of prion diseases, fatal neurodegenerative disorders that affect humans and animals. gene expression analysis of normal and infected sheep may provide clues to clarify the molecular mechanisms involved in the neuropathology of these diseases. real time quantitative pcr has become a powerful and accurate technique for examination of transcription patterns in different biological conditions. one of the critical steps in the comparison of transcription profiles is the selec ...201020024782
mapping of quantitative trait loci affecting classical scrapie incubation time in a population comprising several generations of scrapie-infected sheep.although susceptibility to scrapie is largely controlled by the prp gene, the role of other genes that affect scrapie resistance in sheep is now confirmed. following the detection of quantitative trait loci (qtl) on chromosomes 6 and 18 in a half-sib family with an arq/vrq susceptible prp genotype, the whole pedigree of a naturally infected flock was investigated to confirm these qtl regions in different prp genotypes. the present study has allowed us to confirm the qtl on chromosome 18, and to ...201019828762
role of gfap in morphological retention and distribution of reactive astrocytes induced by scrapie encephalopathy in mice.we have previously demonstrated that mutant mice bearing astrocytes deficient in glial fibrillary acidic protein (gfap) exhibited typical spongiform degeneration and prion plaque deposition. however, it remains to be determined whether there are astrocyte-specific alterations in the reactive response of astrocytes. herein, we analyzed morphological features of gfap(-)(/)(-) reactive astrocytes. light microscopic morphometry of mutant reactive astrocytes revealed reduced outlined cell area and sh ...201019931516
evidence for maternal transmission of scrapie in naturally affected flocks.it has been known for many years that the offspring of scrapie affected ewes are at increased risk of developing scrapie but whether this is simply the result of an increased genetic susceptibility or transmission of infection has always been unclear. to contribute to clarify this we analysed the data collected in a detailed study of scrapie occurrence in a number of naturally affected commercial sheep flocks in great britain (gb) to investigate the association between prp genotype and parental ...201019945758
the prevalence of atypical scrapie in sheep from positive flocks is not higher than in the general sheep population in 11 european countries.during the last decade, active surveillance for transmissible spongiform encephalopathies in small ruminants has been intensive in europe. in many countries this has led to the detection of cases of atypical scrapie which, unlike classical scrapie, might not be contagious. eu legislation requires, that following detection of a scrapie case, control measures including further testing take place in affected flocks, including the culling of genotype susceptible to classical scrapie. this might resu ...201020137097
autophagy and cell death of purkinje cells overexpressing doppel in ngsk prnp-deficient mice.in ngsk prion protein (prp)-deficient mice (np(0/0)), ectopic expression of prp-like protein doppel (dpl) in central neurons induces significant purkinje cell (pc) death resulting in late-onset ataxia. np(0/0) pc death is partly prevented by either knocking-out the apoptotic factor bax or overexpressing the anti-apoptotic factor bcl-2 suggesting that apoptosis is involved in dpl-induced death. in this study, western blotting and immunohistofluorescence show that both before and during significan ...201019055638
lesion profiling at primary isolation in riii mice is insufficient in distinguishing bse from classical scrapie.primary isolation of bovine spongiform encephalopathy (bse) in riii mice generates a lesion profile believed to be reproducible and distinct from that produced by classical scrapie. this profile, which is characterized by peaks at gray matter areas 1, 4 and 7 (dorsal medulla, hypothalamus and septal nuclei), is used to diagnose bse on primary isolation. the aim of this study was to investigate whether the bse agent could be present in sheep diagnosed with classical scrapie, using lesion profiles ...201019298598
the effect of metal imbalances on scrapie neurodegeneration.environmental exposure to metal appears to enhance susceptibility to transmissible spongiform encephalopathies (tses); however, published data are not conclusive. the current study focuses on assessing the effects of copper depletion and/or manganese enhancement in the diet on susceptibility to scrapie and this disease progression. the degree of spongiosis was the highest in the animals that received a copper- depleted diet. these observations suggest that this diet contributes to the scrapie le ...201019486493
[polymorphism at codons 136, 141 and 154 in the ovine prion protein gene in the state of xinjiang].scrapie is a fatal and infectious neurodegenerating disease. the polymorphism in the prion protein (prnp) gene is linked to the development of clinical signs of scrapie. the most important polymorphism appears to be at codons at 136(v/a), 154(h/r), and 171(h/q/r). in this study, we investigated the polymorphisms at these codons in 746 individuals among ten sheep breeds (i.e., aletai, bashibai, bayinbuluke, celehei, duolang, he tian, chinese merino, german merino, texel, and suffolk sheep) in xin ...201021513168
heparin binding by murine recombinant prion protein leads to transient aggregation and formation of rna-resistant species.the conversion of cellular prion protein (prp(c)) into the pathological conformer prp(sc) requires contact between both isoforms and probably also requires a cellular factor, such as a nucleic acid or a glycosaminoglycan (gag). little is known about the structural features implicit in the gag-prp interaction. in the present work, light scattering, fluorescence, circular dichroism, and nuclear magnetic resonance (nmr) spectroscopy were used to describe the chemical and physical properties of the ...201021142149
prion protein misfolding affects calcium homeostasis and sensitizes cells to endoplasmic reticulum stress.prion-related disorders (prds) are fatal neurodegenerative disorders characterized by progressive neuronal impairment as well as the accumulation of an abnormally folded and protease resistant form of the cellular prion protein, termed prp(res). altered endoplasmic reticulum (er) homeostasis is associated with the occurrence of neurodegeneration in sporadic, infectious and familial forms of prds. the er operates as a major intracellular calcium store, playing a crucial role in pathological event ...201021209925
effect of fixation on brain and lymphoreticular vcjd prions and bioassay of key positive specimens from a retrospective vcjd prevalence study.anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the uk population prevalence of asymptomatic vcjd prion infection. the retrospective study of hilton et al(j pathol 2004; 203: 733-739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. this led to an estimated uk prevalence of vcjd infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic t ...201021154694
isolation of proteinase k-sensitive prions using pronase e and phosphotungstic acid.disease-related prion protein, prp(sc), is classically distinguished from its normal cellular precursor, prp(c), by its detergent insolubility and partial resistance to proteolysis. molecular diagnosis of prion disease typically relies upon detection of protease-resistant fragments of prp(sc) using proteinase k, however it is now apparent that the majority of disease-related prp and indeed prion infectivity may be destroyed by this treatment. here we report that digestion of rml prion-infected m ...201021187933
effect of fixation on brain and lymphoreticular vcjd prions and bioassay of key positive specimens from a retrospective vcjd prevalence study.anonymous screening of lymphoreticular tissues removed during routine surgery has been applied to estimate the uk population prevalence of asymptomatic vcjd prion infection. the retrospective study of hilton et al (j pathol 2004; 203: 733-739) found accumulation of abnormal prion protein in three formalin-fixed appendix specimens. this led to an estimated uk prevalence of vcjd infection of ∼1 in 4000, which remains the key evidence supporting current risk reduction measures to reduce iatrogenic ...201021294124
sheep with scrapie and mastitis transmit infectious prions through the milk.prions are misfolded proteins that are infectious and naturally transmitted, causing a fatal neurological disease in humans and animals. prion shedding routes have been shown to be modified by inflammation in excretory organs, such as the kidney. here, we show that sheep with scrapie and lentiviral mastitis secrete prions into the milk and infect nearly 90% of naïve suckling lambs. thus, lentiviruses may enhance prion transmission, conceivably sustaining prion infections in flocks for generation ...201021084475
the effects of lysosomal and proteasomal inhibitors on abnormal forms of prion protein degradation in murine macrophages.it has been reported that macrophages degrade infectious forms of prion protein (prp(sc) ). in order to investigate the mechanisms underlying prp(sc) degradation in macrophages, the effects of lysosomal and proteasomal inhibitors on macrophage cell lines which were incubated with scrapie-affected brain homogenate were studied. prp(sc) degradation was inhibited in the presence of both proteasomal and lysosomal inhibitors. indirect fluorescence assays to determine the cellular localization of prp( ...201021223366
antigen retrieval using sodium hydroxide for prion immunohistochemistry in bovine spongiform encephalopathy and scrapie.formalin-fixed and paraffin wax-embedded (ffpe) tissue sections are usually used for histopathological and immunohistochemical analyses in prion diseases in animals and man. however, formalin fixation cross-links proteins, reducing disease-associated prion protein (prp(sc)) immunolabelling. to detect prp(sc) in animals naturally affected with bovine spongiform encephalopathy (bse) and scrapie, we applied minimal pretreatment with sodium hydroxide (naoh). this simple pretreatment, combined with e ...201021112058
crucial role for prion protein membrane anchoring in the neuroinvasion and neural spread of prion infection.in nature prion diseases are usually transmitted by extracerebral prion infection, but clinical disease results only after invasion of the central nervous system (cns). prion protein (prp), a host-encoded glycosylphosphatidylinositol (gpi)-anchored membrane glycoprotein, is necessary for prion infection and disease. here, we investigated the role of the anchoring of prp on prion neuroinvasion by studying various inoculation routes in mice expressing either anchored or anchorless prp. in control ...201021123371
nuclease resistant circular dnas copurify with infectivity in scrapie and cjd.in transmissible encephalopathies (tses), it is commonly believed that the host prion protein transforms itself into an infectious form that encodes the many distinct tse agent strains without any nucleic acid. using a ф29 polymerase and chromatography strategy, highly infectious culture and brain preparations of three different geographic tse agents all contained novel circular dnas. two circular "sphinx" sequences, of 1.8 and 2.4 kb, copurified with infectious particles in sucrose gradients an ...201021165784
monitoring immune cells trafficking fluorescent prion rods hours after intraperitoneal infection.presence of an abnormal form a host-encoded prion protein (prpc) that is protease resistant, pathologic and infectious characterizes prion diseases such as chronic wasting disease (cwd) of cervids and scrapie in sheep. the prion hypothesis asserts that this abnormal conformer constitutes most or all of the infectious prion. the role of the immune system in early events in peripheral prion pathogenesis has been convincingly demonstrated for cwd and scrapie. transgenic and pharmacologic studies in ...201021113122
enhanced enteric invasion of scrapie agents into the villous columnar epithelium via maternal immunoglobulin.transmissible spongiform encephalopathies (tse) are caused by dietary oral exposure to infectious prion proteins (prpsc); however, the mechanism behind the uptake of prpsc in the intestines is poorly understood. in addition, epidemiological studies of bse showed that most cattle are exposed to the agents in the first 6 months of life, during the suckling and weaning periods. in the present study, to elucidate the enteric invasion mechanism of prions and to investigate the age-dependent transmiss ...201021042778
ovine serum biomarkers of early and late phase scrapie.transmissible spongiform encephalopathies are fatal neurodegenerative disease occurring in animals and humans for which no ante-mortem diagnostic test in biological fluids is available. in such pathologies, detection of the pathological form of the prion protein (i.e., the causative factor) in blood is difficult and therefore identification of new biomarkers implicated in the pathway of prion infection is relevant.201021044301
marked influence of the route of infection on prion strain apparent phenotype in a scrapie transgenic mouse model.prion strains yield specific neuropathological features including spongiform degeneration and deposition patterns of pathological prion protein. their invariant regional distribution, following variations in the infection route, has led to the proposal that prions replicate preferentially in defined neuro-anatomical areas. the molecular mechanisms underlying this apparent strain-specific neuronal tropism are currently unknown. however, a possible explanation may be that prion replication is rela ...201020875860
differentiation of ruminant transmissible spongiform encephalopathy isolate types, including bovine spongiform encephalopathy and ch1641 scrapie.with increased awareness of the diversity of transmissible spongiform encephalopathy (tse) strains in the ruminant population, comes an appreciation of the need for improved methods of differential diagnosis. exposure to bovine spongiform encephalopathy (bse) has been associated with the human tse, variant creutzfeldt-jakob disease, emphasizing the necessity in distinguishing low-risk tse types from bse. tse type discrimination in ruminants such as cattle, sheep, goats and deer, requires the app ...201020943889
atypical scrapie/nor98 in a sheep from new zealand.in a consignment of sheep brains from new zealand, to be used in europe as negative control material in scrapie rapid screening test evaluations, brain samples from 1 sheep (no. 1512) gave the following initially confusing results in various screening tests: the brainstem repeatedly produced negative results in 2 very similar screening kits (enzyme-linked immunosorbent assay [elisa]-1, elisa-2), a macerate made from brainstem and cerebellum returned a clearly positive result in elisa-2, and the ...201021088169
intraspecies prion transmission results in selection of sheep scrapie strains.sheep scrapie is caused by multiple prion strains, which have been classified on the basis of their biological characteristics in inbred mice. the heterogeneity of natural scrapie prions in individual sheep and in sheep flocks has not been clearly defined.201021103326
neuropathological changes correlate temporally but not spatially with selected neuromodulatory responses in natural scrapie.aim: neuropathological changes classically associated with sheep scrapie do not always correlate with clinical disease. we aimed to determine if selected neuromodulatory responses were altered during the course of the infection as it has been described in creutzfeldt-jakob disease and experimental bovine spongiform encephalopathy. methods: hemibrains from healthy sheep and natural scrapie cases at two stages of infection were examined for biochemical alterations related to the expression of type ...201021114681
high hydrophobic amino acid exposure is responsible of the neurotoxic effects induced by e200k or d202n disease-related mutations of the human prion protein.mutations in prion protein are thought to be causative of inherited prion diseases favoring the spontaneous conversion of the normal prion protein into the scrapie-like pathological prion protein. we previously reported that, by controlled thermal denaturation, human prion protein fragment 90-231 acquires neurotoxic properties when transformed in a β-rich conformation, resembling the scrapie-like conformation. in this study we generated prion protein fragment 90-231 bearing mutations identified ...201021094273
molecular interactions between prions as seeds and recombinant prion proteins as substrates resemble the biological interspecies barrier in vitro.prion diseases like creutzfeldt-jakob disease in humans, scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. prion diseases are transmissible between different species, however, with a variable species barrier. the key event of prion amplification is the conversion of the cellular isoform of the prion protein (prp(c)) into the pathogenic isoform (prp(sc)). we developed a sodiumdodecylsulfate-based prp ...201021151607
sex and prnp genotype determination in preimplantation caprine embryos.the objective of this study was to test the accuracy of genotype diagnosis after whole amplification of dna extracted from biopsies obtained by trimming goat embryos and to evaluate the viability of biopsied embryos after vitrification/warming and transfer. whole genome amplification (wga) was performed using multiple displacement amplification (mda). sex and prion protein (prnp) genotypes were determined. sex diagnosis was carried out by pcr amplification of zfx/zfy and y chromosome-specific se ...201021121967
increased susceptibility of human-prp transgenic mice to bovine spongiform encephalopathy infection following passage in sheep.the risk of the transmission of ruminant transmissible spongiform encephalopathy (tse) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human tse. however, a single tse agent strain has been shown to cause both bovine spongiform encephalopathy (bse) and human vcjd, indicating that some ruminant tses are transmissible to humans. while the transmission of cattle bse to humans in transgenic mouse models has been inefficient, indicating the pr ...201021084466
immunomodulation for prion and prion-related diseases.prion diseases are a unique category of illness, affecting both animals and humans, where the underlying pathogenesis is related to a conformational change of a normal self protein called cellular prion protein to a pathological and infectious conformer known as scrapie prion protein (prp(sc)). currently, all prion diseases lack effective treatment and are universally fatal. past experiences with bovine spongiform encephalopathy and variant creutzfeldt-jakob disease mainly in europe, as well as ...201021105779
generalized cerebral atrophy seen on mri in a naturally exposed animal model for creutzfeldt-jakob disease.magnetic resonance imaging has been used in the diagnosis of human prion diseases such as scjd and vcjd, but patients are scanned only when clinical signs appear, often at the late stage of disease. this study attempts to answer the questions "could mri detect prion diseases before clinical symptoms appear?, and if so, with what confidence?"201021108848
relevance of oral experimental challenge with classical scrapie in sheep.oral inoculation is currently considered as the best approach to mimic natural tse contamination in ruminants. in this study, we compared the timing of abnormal prion protein (prp(sc)) dissemination and accumulation in the organism of susceptible sheep either orally inoculated or naturally infected with classical scrapie. both animal groups shared a similar prp(sc) dissemination scheme and accumulation dynamics in lymphoid tissues. however, orally challenged animals displayed an earlier neuro-in ...201020444991
a bayesian hierarchical analysis to compare classical and atypical scrapie surveillance data; wales 2002-2006.we describe the application of bayesian hierarchical models (bhm) to the analysis of risk of sheep scrapie using data from multiple surveillance sources. more specifically, we analysed data from the test results of three surveillance sources on classical and atypical scrapie in wales for the period 2002-2006. for each form of scrapie, a bhm was fitted to assess the occurrence of spatial patterns of risk shared by the multiple surveillance sources and the association between covariates and diseas ...201021040987
[interaction between various 14-3-3beta segments and prp in vitro].objective to study the potential interaction between prp protein.201021186515
identification and structural analysis of c-terminally truncated collapsin response mediator protein-2 in a murine model of prion diseases.abstract:201020961402
membrane interactions and conformational preferences of human and avian prion n-terminal tandem repeats: the role of copper(ii) ions, ph, and membrane mimicking environments.the flexible n-terminal domain of the prion protein (prp(c)) is believed to play a pivotal role in both trafficking of the protein through the cell membrane and its pathogenic conversion into the β sheet-rich scrapie isoform (prp(sc)). unlike mammalian prp(c), avian prion proteins are not known to undergo any pathogenic conformational conversions. consequently, some critical advances in our understanding of the molecular mechanisms underlying prion pathogenesis are expected from comparative stud ...201020936829
a novel class of potential prion drugs: preliminary in vitro and in vivo data for multilayer coated gold nanoparticles.gold nanoparticles coated with oppositely charged polyelectrolytes, such as polyallylamine hydrochloride and polystyrenesulfonate, were examined for potential inhibition of prion protein aggregation and prion (prpsc) conversion and replication. different coatings, finishing with a positive or negative layer, were tested, and different numbers of layers were investigated for their ability to interact and reduce the accumulation of prpsc in scrapie prion infected scgt1 and scn2a cells. the particl ...201020944860
prion transmission: prion excretion and occurrence in the environment.prion diseases range from being highly infectious, for example scrapie and cwd, which show facile transmission between susceptible individuals, to showing negligible horizontal transmission, such as bse and cjd, which are spread via food or iatrogenically, respectively. scrapie and cwd display considerable in vivo dissemination, with prp(sc) and infectivity being found in a range of peripheral tissues. this in vivo dissemination appears to facilitate the recently reported excretion of prion thro ...201020948292
solution structure and dynamics of the i214v mutant of the rabbit prion protein.the conformational conversion of the host-derived cellular prion protein (prp(c)) into the disease-associated scrapie isoform (prp(sc)) is responsible for the pathogenesis of transmissible spongiform encephalopathies (tses). various single-point mutations in prp(c)s could cause structural changes and thereby distinctly influence the conformational conversion. elucidation of the differences between the wild-type rabbit prp(c) (raprp(c)) and various mutants would be of great help to understand the ...201020949107
sulfated dextrans enhance in vitro amplification of bovine spongiform encephalopathy prp(sc) and enable ultrasensitive detection of bovine prp(sc).prions, infectious agents associated with prion diseases such as creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse) in cattle, and scrapie in sheep and goats, are primarily comprised of prp(sc), a protease-resistant misfolded isoform of the cellular prion protein prp(c). protein misfolding cyclic amplification (pmca) is a highly sensitive technique used to detect minute amounts of scrapie prp(sc). however, the current pmca technique has been unsuccessful in achieving goo ...201020957174
the interaction of ruminant prp(sc) with soils is influenced by prion source and soil type.the persistence of prions within the environment is implicated in the horizontal transmission of ovine scrapie and cervid chronic wasting disease. description of the interaction of prion strains derived from their natural hosts with a range of soil types is imperative in understanding how prions persist in the environment and, therefore, the characteristics of prion transmission. here, we demonstrate that all detectable ovine scrapie and bovine bse prp(sc) bind to a range of soil types within 24 ...201020968294
capacity of the manufacturing process of flebogamma(®) dif, a new human high purity intravenous immunoglobulin, to remove a tse model-agent.the variant creutfeldt-jakob disease (vcjd) is a transmissible spongiform encephalopathy (tse) associated with the ingestion of cattle derived products affected with bovine spongiform encephalopathy. vcjd emerged in the uk, where most of the cases occurred (170 of 217 cases worldwide). manufacturers of biological products must investigate the ability of their production processes to remove tse agents. two manufacturing steps (polyethylene glycol-peg precipitation and nanofiltration down to 20 nm ...201020863716
prion genotypes of scrapie-infected canadian sheep 1998-2008.this report describes the genetics of the prion protein gene (prnp) at codons 136, 154, and 171 for sheep diagnosed with naturally acquired classical scrapie in canada between 1998 and 2008. genotyping analysis was performed on 249 sheep with confirmed classical scrapie infection representing 98 flocks from 6 provinces. a further case-control analysis of 3 of these flocks compared the genotypes between infected sheep (n = 72) and those of their healthy flockmates (n = 1990). the incidence of cla ...201020885849
early embryonic gene expression profiling of zebrafish prion protein (prp2) morphants.the prion protein (prnp/prp) plays a crucial role in transmissible spongiform encephalopathies (tses) like creutzfeldt-jakob disease (cjd), scrapie and mad cow disease. notwithstanding the importance in human and animal disease, fundamental aspects of prnp/prp function and transmission remains unaccounted for.201021042590
prion replication in the hematopoietic compartment is not required for neuroinvasion in scrapie mouse model.fatal neurodegenerative prion diseases are caused by the transmissible prp(sc) prion agent whose initial replication after peripheral inoculation takes place in follicular dendritic cells present in germinal centers of lymphoid organs. however, prion replication also occurs in lymphoid cells. to assess the role of the hematopoietic compartment in neuroinvasion and prion replication, we generated chimeric mice, on a uniform congenic c57/bl6j background, by bone marrow replacement with hematopoiet ...201020957200
rapid end-point quantitation of prion seeding activity with sensitivity comparable to bioassays.a major problem for the effective diagnosis and management of prion diseases is the lack of rapid high-throughput assays to measure low levels of prions. such measurements have typically required prolonged bioassays in animals. highly sensitive, but generally non-quantitative, prion detection methods have been developed based on prions' ability to seed the conversion of normally soluble protease-sensitive forms of prion protein to protease-resistant and/or amyloid fibrillar forms. here we descri ...201021152012
comparison studies of the structural stability of rabbit prion protein with human and mouse prion proteins.prion diseases are fatal and infectious neurodegenerative diseases affecting humans and animals. rabbits are one of the few mammalian species reported to be resistant to infection from prion diseases isolated from other species (i. vorberg et al., journal of virology 77 (3) (2003) 2003-2009). thus the study of rabbit prion protein structure to obtain insight into the immunity of rabbits to prion diseases is very important.201020970434
molecular characterization of the full-length coding sequence of the caprine laminin receptor gene (rpsa).scrapie is a prion disease in sheep and goats. ribosomal protein sa (rpsa), also called 37 kda laminin receptor precursor/67 kda laminin receptor has been demonstrated to be a putative cell surface receptor for prion. to investigate the caprine rpsa, we cloned the full-length coding sequence of the gene of goat and submitted it to genbank. the length of the open reading frame is 888 bp, encoding 295 amino acids. the putative amino acid sequence is highly similar to that of other mammals. the cap ...201020839046
a "shotgun" method for tracing the birth locations of sheep from flock tags, applied to scrapie surveillance in great britain.movement records are often used to identify animal sample provenance by retracing the movements of individuals. here we present an alternative method, which uses the same identity tags and movement records as are used to retrace movements, but ignores individual movement paths. the first step uses a simple query to identify the most likely birth holding for every identity tag included in a database recording departures from agricultural holdings. the second step rejects a proportion of the birth ...201020692059
transcytosis of murine-adapted bovine spongiform encephalopathy agents in an in vitro bovine m cell model.transmissible spongiform encephalopathies (tse), including bovine spongiform encephalopathy (bse), are fatal neurodegenerative disorders in humans and animals. bse appears to have spread to cattle through the consumption of feed contaminated with bse/scrapie agents. in the case of an oral infection, the agents have to cross the gut-epithelial barrier. we recently established a bovine intestinal epithelial cell line (bie cells) that can differentiate into the m cell type in vitro after lymphocyti ...201020861256
cartilaginous metaplasia in the sclera of suffolk sheep.scleral cartilaginous metaplasia was detected by routine histologic examination of globes from 5 suffolk sheep from a scrapie pathogenesis study. the extent of the metaplasia varied among the sheep but was always posterior to the tapetal fundus. the matrix surrounding chondrocytes stained intensely with alcian blue and was immunopositive for type ii collagen. retrospective evaluation of additional eyes from suffolk and cheviot sheep used in various scrapie pathogenesis studies at the authors' fa ...201020861498
amyloid structure and assembly: insights from scanning transmission electron microscopy.amyloid fibrils are filamentous protein aggregates implicated in several common diseases such as alzheimer's disease and type ii diabetes. similar structures are also the molecular principle of the infectious spongiform encephalopathies such as creutzfeldt-jakob disease in humans, scrapie in sheep, and of the so-called yeast prions, inherited non-chromosomal elements found in yeast and fungi. scanning transmission electron microscopy (stem) is often used to delineate the assembly mechanism and s ...201020868754
prion protein self-interactions: a gateway to novel therapeutic strategies?transmissible spongiform encephalopathies (tses) or prion diseases are fatal neurodegenerative disorders and include among others creutzfeldt-jakob disease in humans, bovine spongiform encephalopathy (bse) in cattle, and scrapie in sheep. the central event in disease development in tses is the refolding of the normal host-encoded cellular prion protein (prp) into abnormal and disease associated prion protein. the agent is thought to consist mainly or exclusively of these pathologically folded pr ...201020932496
bse infectivity in the absence of detectable prp(sc) accumulation in the tongue and nasal mucosa of terminally diseased cattle.the pathogenesis of bovine spongiform encephalopathy (bse) infections in cattle has been studied in recent years by using highly sensitive transgenic-mouse bioassays. it has been shown that in this species, the bse agent amplifies almost exclusively in the central and peripheral nervous system. even in animals that were killed in the clinical end stage of the disease, the lymphoreticular system was shown to be free of the infectious agent. no other animal species investigated to date exhibits su ...201020943888
digestion and transportation of bovine spongiform encephalopathy-derived prion protein in the sheep intestine.bovine spongiform encephalopathy (bse) is acquired orally and the mechanisms involved in the absorption and transportation of infectivity across the gut wall are therefore critical. isolated gut loops were created in lambs, massaged to remove intestinal contents (flushed) or left non-flushed, inoculated with cattle bse homogenate and excised at different time-points. gut loops were examined by immunohistochemistry (ihc) for disease-associated prion protein (prp(d)), and the contents were analyse ...201020826616
prion strain interactions are highly selective.various misfolded and aggregated neuronal proteins commonly coexist in neurodegenerative disease, but whether the proteins coaggregate and alter the disease pathogenesis is unclear. here, we used mixtures of distinct prion strains, which are believed to differ in conformation, to test the hypothesis that two different aggregates interact and change the disease in vivo. we tracked two prion strains in mice histopathologically and biochemically, as well as by spectral analysis of plaque-bound ptaa ...201020826672
environmental sources of scrapie prions.ovine scrapie and cervine chronic wasting disease show considerable horizontal transmission. here we report that a scrapie-affected sheep farm has a widespread environmental contamination with prions. prions were amplified by protein-misfolding cyclic amplification (spmca) from seven of nine environmental swab samples taken, including those from metal, plastic, and wooden surfaces. sheep had been removed from the areas from which the swabs were taken up to 20 days prior to sampling, indicating t ...201020739536
synthesis and anti-prion activity evaluation of aminoquinoline analogues.transmissible spongiform encephalopathies form a group of neurodegenerative diseases that affect humans and other mammals. they occur when the native prion protein is converted into an infectious isoform, the scrapie prp, which aggregates, leading to neurodegeneration. although several compounds were evaluated for their ability to inhibit this conversion, there is no effective therapy for such diseases. previous studies have shown that antimalarial compounds, such as quinolines, possess anti-scr ...201020797807
detection of prp(sc) in formalin-fixed, paraffin-embedded tissue by western blot differentiates classical scrapie, nor98 scrapie, and bovine spongiform encephalopathy.transmissible, spongiform encephalopathies including bovine spongiform encephalopathy (bse) and scrapie are fatal neurodegenerative disorders associated with the presence of an infectious abnormal isoform of normal mammalian proteins called prions. identification of the prion protein associated with scrapie (prp(sc)) in the central nervous system is typically based upon immunoassays including immunohistochemistry (ihc) using formalin-fixed tissues or western blot (wb) assays using fresh and/or f ...201020807921
sequence-dependent prion protein misfolding and neurotoxicity.prion diseases are neurodegenerative disorders caused by misfolding of the normal prion protein (prp) into a pathogenic "scrapie" conformation. to better understand the cellular and molecular mechanisms that govern the conformational changes (conversion) of prp, we compared the dynamics of prp from mammals susceptible (hamster and mouse) and resistant (rabbit) to prion diseases in transgenic flies. we recently showed that hamster prp induces spongiform degeneration and accumulates into highly ag ...201020817727
a drosophila model of gss syndrome suggests defects in active zones are responsible for pathogenesis of gss syndrome.we have established a drosophila model of gerstmann-sträussler-scheinker (gss) syndrome by expressing mouse prion protein (prp) having leucine substitution at residue 101 (moprp(p101l)). flies expressing moprp(p101l), but not wild-type moprp (moprp(3f4)), showed severe defects in climbing ability and early death. expressed moprp(p101l) in drosophila was differentially glycosylated, localized at the synaptic terminals and mainly present as deposits in adult brains. we found that behavioral defect ...201020829230
early noninvasive diagnosis of neurodegenerative diseases.this paper reviews the contemporary trends in the pathobiochemistry of neurodegenerative disorders with respect to their early predictive diagnosis and possible treatment interventions. if we consider the current epidemiological data related to neurodegenerative disorders, medicine is going to face in the near future latent pandemic situations. the introduction puts an emphasis on the emerging importance of one major cluster of neurodegenerative disorders: diseases of the abnormal protein beta-c ...201020836391
the h187r mutation of the human prion protein induces conversion of recombinant prion protein to the prp(sc)-like form.prion diseases are associated with a conformational switch in the prion protein (prp) from its normal cellular form (denoted prp(c)) to a disease-associated "scrapie" form (prp(sc)). a number of prp(sc)-like conformations can be generated by incubating recombinant prp(c) at low ph, indicating that protonation of key residues is likely to destabilize prp(c), facilitating its conversion to prp(sc). here, we examine the stability of human prp(c) with ph and find that prp(c) fold stability is signif ...201020718410
peg-interspersed nitrilotriacetic acid-functionalized quantum dots for site-specific labeling of prion proteins expressed on cell surfaces.a strategy has been put forward to fabricate peg-interspersed nitrilotriacetic acid (nta)-functionalized qds by one-step self-assembly using a mixture of self-synthesized nta-terminated amphiphilic polymer and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-n-[carboxy(polyethylene glycol)2000] (dspe-peg-cooh). the process was highly reproducible for facile functionalization of qds via simultaneous self-assembly of biocompatible peg molecules onto their surface. an optimized molar ratio of nta-te ...201020723972
iatrogenic concerns of the twentieth century: post-vaccinal encephalitis and spongiform encephalopathy.throughout the twentieth century, iatrogenic disease constituted an enduring problem in western medical discourse and practice. a survey of the medical literature, investigative reports, and archival material indicates that iatrogenic concerns persisted throughout the century. two groups of case studies are presented: one associated with post-vaccinal encephalitis; the other, with the iatrogenically transmitted spongiform encephalopathies, scrapie and creutzfeldt-jakob disease. kuru, a similar d ...201021553697
glycosylation-related gene expression profiling in the brain and spleen of scrapie-affected mouse.a central event in the formation of infectious prions is the conformational change of a host-encoded glycoprotein, prp(c), into a pathogenic isoform, prp(sc). the molecular requirements for efficient prp conversion remain unknown. altered glycosylation has been linked to various pathologies and the n-glycans harbored by two prion protein isoforms are different. in order to search for glycosylation-related genes that could mark prion infection, we used a glycosylation-dedicated microarray that al ...200919386898
prion protein genotypes of italian sheep breeds with lysine-171 and phenylalanine-141 detection.amino acid polymorphisms of the prion protein gene influence sheep susceptibility to classical and atypical scrapie. substitutions at codons 136, 154 and 171 play an important role in classical scrapie. codon 141 leucine to phenylalanine mutation (afrq) has been recognized as an increased risk factor for atypical scrapie. in addition a rare allele with lysine at codon 171 (ark) has been detected in mediterranean sheep breeds. the presence of ark poses two problems: the determination of its frequ ...200919157728
prp(sc) of scrapie 263k propagates efficiently in spleen and muscle tissues with protein misfolding cyclic amplification.transmissible spongiform encephalopathies (tses), or prion diseases, are transmissible neurodegenerative disorders of protein conformation. this group of diseases is caused by infectious agents, termed prions, which can convert normal conformation (prp(c)) into misfolded protein (prp(sc)). the infectivity of non-neuronal tissues has been wildly addressed, but the propagating features and the biochemical properties of prion generated from these tissues are only partially settled. in this study, u ...200919162101
comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone.identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, res ...200919535908
neuroinvasion in sheep transmissible spongiform encephalopathies: the role of the haematogenous route.it is generally believed that after oral exposure to transmissible spongiform encephalopathy (tse) agents, neuroinvasion occurs via the enteric nervous system (ens) and the autonomic nervous system. as a result, the dorsal motor nucleus of the vagus nerve is the initial point of disease-associated prion protein (prp(d)) accumulation in the brain. hypothesis and aim: if direct ens invasion following oral infection results in an early and specific brain targeting for prp(d) accumulation, such topo ...200919473292
burrowing: a sensitive behavioural assay, tested in five species of laboratory rodents.in the burrowing test, mice or rats spontaneously empty a tube filled with food pellets, gravel or other substances. the test is extremely simple to perform, the apparatus is inexpensive and readily constructed. it exploits a natural rodent behaviour, provides quantitative data under controlled laboratory conditions, and has proved extremely sensitive to prion disease in mice (mus musculus), cytokines in rats (rattus norvegicus), lipopolysaccharide in mice and rats, strain differences and brain ...200919373978
anti-prp mab 6d11 suppresses prp(sc) replication in prion infected myeloid precursor line fdc-p1/22l and in the lymphoreticular system in vivo.the pathogenesis of prion diseases is related to conformational transformation of cellular prion protein (prp(c)) into a toxic, infectious, and self-replicating conformer termed prp(sc). following extracerebral inoculation, the replication of prp(sc) is confined for months to years to the lymporeticular system (lrs) before the secondary cns involvement results in occurrence of neurological symptoms. therefore, replication of prp(sc), in the early stage of infection can be targeted by therapeutic ...200919385058
abnormal prion protein is associated with changes of plasma membranes and endocytosis in bovine spongiform encephalopathy (bse)-affected cattle brains.transmissible spongiform encephalopathies (tses) or prion diseases are fatal neurodegenerative diseases of man and animals characterized by vacuolation and gliosis of neuropil and the accumulation of abnormal isoforms of a host protein known as prion protein (prp). it is widely assumed that the abnormal isoforms of prp (prp(d), disease-specific form of prp) are the proximate cause of neurodegeneration.200919473293
rapid folding of the prion protein captured by pressure-jump.the conversion of the cellular form of the prion protein (prp(c)) to an altered disease state, generally denoted as scrapie isoform (prp(sc)), appears to be a crucial molecular event in prion diseases. the details of this conformational transition are not fully understood, but it is perceived that they are associated with misfolding of prp or its incapacity to maintain the native fold during its cell cycle. here we present a tryptophan mutant of prp (f198w), which has enhanced fluorescence sensi ...200919255752
frequency and distribution of nerves in scrapie-affected and unaffected peyer's patches and lymph nodes.transmission of sheep scrapie and some other prion diseases, including variant creutzfeldt-jakob disease of man, probably occurs via the oral route. a disease-associated variant of the host-coded prion protein (prp(d)) accumulates in germinal center follicles of lymphoid tissues, including peyer's patches of the gut, where it can be detected before its accumulation in the central nervous system. to investigate the potential role of lymphoid tissue nerves in neuroinvasion, we used immunohistochem ...200919261634
use of epidemiologic information in targeted surveillance for population inference.epidemiologic information, including animal characteristics (e.g., observable risk factors or clinical signs) predisposing to animal disease, is frequently used for design of targeted surveillance systems, but this information is infrequently used for population inference. in this study, we report the evaluation of use of epidemiologic information for population inference in targeted surveillance in three animal disease scenarios. we adapted sampling theory using monte carlo methods to determine ...200919269705
characteristics of 263k scrapie agent in multiple hamster species.transmissible spongiform encephalopathy (tse) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood. to better understand these changes, we infected 6 hamster species with 263k hamster scrapie strain and, after each of 3 successive passages in the new species, analyzed abnormal proteinase k (pk)-resistant prion protein (prpres) glycoform ratios, prpres pk sensitivity, incubation periods, and lesion profiles ...200919193264
core structure of amyloid fibrils formed by residues 106-126 of the human prion protein.peptides comprising residues 106-126 of the human prion protein (prp) exhibit many features of the full-length protein. prp(106-126) induces apoptosis in neurons, forms fibrillar aggregates, and can mediate the conversion of native cellular prp (prp(c)) to the scrapie form (prp(sc)). despite a wide range of biochemical and biophysical studies on this peptide, including investigation of its propensity for aggregation, interactions with cell membranes, and prp-like toxicity, the structure of amylo ...200919278656
ovine progressive pneumonia provirus levels are unaffected by the prion 171r allele in an idaho sheep flock.selective breeding of sheep for arginine (r) at prion gene (prnp) codon 171 confers resistance to classical scrapie. however, other effects of 171r selection are uncertain. ovine progressive pneumonia/maedi-visna virus (oppv) may infect up to 66% of a flock thus any affect of 171r selection on oppv susceptibility or disease progression could have major impact on the sheep industry. hypotheses that the prnp 171r allele is 1) associated with the presence of oppv provirus and 2) associated with hig ...200919284685
dendritic cell-mediated-immunization with xenogenic prp and adenoviral vectors breaks tolerance and prolongs mice survival against experimental scrapie.in prion diseases, prp(c), a widely expressed protein, is transformed into a pathogenic form called prp(sc), which is in itself infectious. antibodies directed against prp(c) have been shown to inhibit prp(c) to prp(sc) conversion in vitro and protect in vivo from disease. other effectors with potential to eliminate prpsc-producing cells are cytotoxic t cells directed against prp-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. the natural ...200919295917
Refresh
firstprev
12345678910...
nextlast
Displaying items 301 - 400 of 4534