Publications

TitleAbstractYear(sorted ascending)
Filter
PMID
Filter
aggregation and amyloid fibril formation of the prion protein is accelerated in the presence of glycogen.prion diseases like creutzfeldt-jakob disease in humans or scrapie in sheep and goats are infectious neurodegenerative diseases. their infectious agent, called prion, is composed mainly of aggregated and misfolded prion protein and non-proteinaceous components. an example of such a common non-proteinaceous secondary component of natural prions is the polysaccharide scaffold. we studied the influence of such a polysaccharide on the conformational transition of prp applying an in vitro conversion ...200818341429
vaccine approaches to prevent and treat prion infection : progress and challenges.prion diseases are transmissible neurodegenerative diseases of humans and animals. the prion agent consists of a misfolded protein, prpsc (prion protein, scrapie form), of a glycosylphosphatidylinositol-anchored host protein, prpc (prp cellular form) of unknown function. during prion replication, prpsc induces host prpc to adopt its pathogenic conformation. some prpsc may aggregate to microscopically visible, extracellular prion plaques that stain for amyloid. the development of antiprion vaccin ...200818215090
infection of metallothionein 1+2 knockout mice with rocky mountain laboratory scrapie.metallothioneins (mt) are heavy metal-binding, antioxidant proteins with relevant roles described in many pathological conditions affecting the central nervous system (cns). regarding prion diseases, a number of publications demonstrate an up-regulation of mt-1+2 in the brains of tse affected cattle, humans and experimentally inoculated rodents. since the prion protein also binds copper, and oxidative stress is one of the events presumably triggered by prpsc deposition, it seems plausible that m ...200818221736
structural and functional analysis of the hsp90aa1 gene: distribution of polymorphisms among sheep with different responses to scrapie.scrapie is a transmissible spongiform encephalopathy in sheep and goats. susceptibility to this neurodegenerative disease is mainly controlled by point mutations at the prnp locus. other genes, apart from prnp, have been reported to modulate resistance/susceptibility to scrapie. on the basis of several studies in alzheimer and different transmissible spongiform encephalopathy models, hsp90aa1 was chosen as a putative positional and functional candidate gene that might be involved in the polygeni ...200818347938
prevalence of sheep infected with classical scrapie in great britain: integrating multiple sources of surveillance data for 2002.estimates for the prevalence of sheep infected with classical scrapie are essential for assessing the efficacy of control strategies that have been implemented in great britain (gb). here a back-calculation approach was used to estimate the prevalence in the gb national flock by integrating data on reported cases and the results of abattoir and fallen stock surveys for 2002. prevalence estimates ranged from 0.33 to 2.06%, depending on the estimates used for the frequencies of prion protein (prp) ...200818348959
semen from scrapie-infected rams does not transmit prion infection to transgenic mice.scrapie is the most common transmissible spongiform encephalopathy (tse) in livestock. natural contamination in sheep flocks is presumed to occur by maternal transmission to offspring. however, horizontal prion transmission from animal to animal exists and may be significant in sustaining and spreading contagion in the field. artificial insemination is widely used in modern farming, and as large amounts of prion protein have been found in sheep sperm membrane, epididymal fluid and seminal plasma ...200818299435
a comparison of the active surveillance of scrapie in the european union.the abattoir and the fallen stock surveys constitute the active surveillance component aimed at improving the detection of scrapie across the european union. previous studies have suggested the occurrence of significant differences in the operation of the surveys across the eu. in the present study we assessed the standardisation of the surveys throughout time across the eu and identified clusters of countries with similar underlying characteristics allowing comparisons between them. in the abse ...200818307969
atypical prpsc distribution in goats naturally affected with scrapie.the brain and spinal cord of 48 goats from two greek herds in which scrapie had been reported were examined. all animals were symptomless at the time of euthanasia. notably, no lesions were observed either at the level of the obex or at other regions of the brain and spinal cord. immunohistochemical examination revealed prpsc labelling of the linear and fine punctuate types, mainly in the cerebral cortices, of 36 goats. twenty-seven of them were negative by elisa (designed to detect proteinase-r ...200818295782
sonication induced intermediate in prion protein conversion.we have observed that hamster prion protein (prp(c)) undergoes conformational changes on exposure to heat or sonication. if a sonication induced new conformer is seeded with a small amount of its abnormal pathogenic isoform (prp(sc)) it undergoes a significant conversion to a proteinase-resistant isoform. this suggests the presence of a third stable prp conformer, which may be intermediate in the conversion of prp(c) to prp(sc).200818289112
binding of 14-3-3 proteins to a single stranded oligodeoxynucleotide aptamer.a synthetic library of ca. 10(13) single stranded oligodeoxynucleotides, each comprising a randomized 40mer sequence and homogeneous 10mer flanking regions, was screened for binding to recombinant human 14-3-3gamma. a single aptamer, which showed similar affinities (k(d) approximately 10(-8)m) for six isoforms of the protein, has been shown to bind to undenatured 14-3-3 protein in the cerebral spinal fluid of scrapie infected sheep.200818279908
copper-induced structural changes in the ovine prion protein are influenced by a polymorphism at codon 112.prion diseases are associated with conformational change in the copper-binding protein prp. the copper-binding sites in prp are located in the n-terminal region of the molecule and comprise a series of tandem repeats of the sequence phgggwgq together with two histidines at residues 96 and 111 (human prp numbering). the co-ordination of copper ions within the non-octapeptide repeat metal ion-binding site involves met109 (human numbering, which corresponds with met112 in ovine prp) and the binding ...200818280261
the evidence of associations between prion protein genotype and production, reproduction, and health traits in sheep.the eu commission issued a regulation in 2003, which requires all member states to implement a breeding programme for resistance to transmissible spongiform encephalopathies in sheep by selecting for specific alleles of the prion protein (prp) gene. a key concern with regard to this regulation was that the intensive selection programmes, designed to increase resistance to scrapie, may have a negative impact on a range of other economically important production, reproduction, and disease traits i ...200818284907
prp genetics in ruminant transmissible spongiform encephalopathies.scrapie, bovine spongiform encephalopathy (bse), and chronic wasting disease (cwd) are prion diseases in ruminants with considerable impact on animal health and welfare. they can also pose a risk to human health and control is therefore an important issue. prion protein (prp) genetics may be used to control and eventually eradicate animal prion diseases. the prp gene in sheep and other representatives of the order artiodactyles has many polymorphisms of which several are crucial determinants of ...200818284908
blood clearance of the prion protein introduced by intravenous route in sheep is influenced by host genetic and physiopathologic factors.the risk of transmissible spongiform encephalopathy (tse) transmission by blood transfusion is dependent on the blood concentrations of the pathologic isoform of prion protein (prpsc) but may also be influenced by blood concentrations of cellular prp (prpc). these concentrations are controlled by the blood clearance of prp, which has never been evaluated.200818248567
tse pathogenesis in cattle and sheep.many studies have been undertaken in rodents to study the pathogenesis of transmissible spongiform encephalopathies (tse). only a few studies have focused on the pathogenesis of bovine spongiform encephalopathy (bse) and scrapie in their natural hosts. in this review, we summarize the most recent insights into the pathogenesis of bse and scrapie starting from the initial uptake of tse agents and crossing of the gut epithelium. following replication in the gut-associated lymphoid tissues (galt), ...200818258167
progress and limits of prp gene selection policy.classical scrapie has proved to be a notoriously difficult disease to control due to a poor understanding of its natural history. the recognition of disease risk linkage to prp genotype has offered the prospect of a disease control strategy, viz. genotyping and selective breeding, novel to veterinary medicine when first considered in the 1990s. the uk spongiform encephalopathy advisory committee recommended the exploitation of this approach in a voluntary, national programme to control classical ...200818258168
high incidence of subclinical infection of lymphoid tissues in scrapie-affected sheep flocks.prion diseases are characterized by a long incubation period. in scrapie, sheep may incubate and spread the infection for several years before clinical signs evolve. we have previously studied the occurrence of subclinical infection in the brain. now, we have studied the occurrence of subclinical infection in the brain and several lymphoid tissues in two scrapie-affected icelandic sheep flocks by immunohistochemistry for prp(sc), a molecular marker for infectivity, and correlated this with resul ...200818227967
genetic variability of the prnp gene in goat breeds from northern and southern italy.to determine the variability of the prion protein gene (prnp) in goats from northern and southern italy.200818217941
prion removal by nanofiltration under different experimental conditions.manufacturing processes used in the production of biopharmaceutical or biological products should be evaluated for their ability to remove potential contaminants, including tse agents. in the present study, we have evaluated scrapie prion protein (prp sc) removal in the presence of different starting materials, using virus removal filters of different pore sizes. following 75 nm filtration, prp sc was detected in the filtrate by western blot (wb) analysis when a "super-sonicated" microsomal frac ...200817890100
structural and functional analysis of the ovine laminin receptor gene (rpsa): possible involvement of the lrp/lr protein in scrapie response.scrapie is a prion disease affecting sheep and goats. susceptibility to this neurodegenerative disease shows polygenic variance. the involvement of the laminin receptor (lrp/lr) in the metabolism and propagation of prions has previously been demonstrated. in the present work, the ovine laminin receptor gene (rpsa) was isolated, characterized, and mapped to ovine chromosome oar19q13. real-time rt-pcr revealed a significant decrease in rpsa mrna in cerebellum after scrapie infection. conversely, n ...200818202837
gene expression profile of quinacrine-cured prion-infected mouse neuronal cells.prion diseases are transmissible fatal neurodegenerative diseases of humans and animals, characterised by the presence of an abnormal isoform (scrapie prion protein; prp(sc)) of the endogenous cellular prion protein (prp(c)). the pathological mechanisms at the basis of prion diseases remain elusive, although the accumulation of prp(sc) has been linked to neurodegeneration. different genomic approaches have been applied to carry out large-scale expression analysis in prion-infected brains and cel ...200818036195
experimental transmission of scrapie agent to susceptible sheep by intralingual or intracerebral inoculation.scrapie, a transmissible spongiform encephalopathy (tse), is a naturally occurring fatal neurodegenerative disease of sheep and goats. this study documents survival periods, pathological findings, and the presence of abnormal prion protein (prp(sc)) in genetically susceptible sheep inoculated with scrapie agent. suffolk lambs (aa/rr/qq at codons 136, 154, and 171, respectively) aged 4 mo were injected by the intralingual (il) or intracerebral (ic) route with an inoculum prepared from a pool of s ...200818214164
atypical/nor98 scrapie: properties of the agent, genetics, and epidemiology.atypical/nor98 scrapie cases in sheep were diagnosed for the first time in norway in 1998. they are now identified in small ruminants in most european countries and represent an increasingly large proportion of the scrapie cases diagnosed in europe. atypical/nor98 scrapie isolates have shown to be experimentally transmissible into transgenic mice and sheep but the properties of the tse agent involved, like its biological and biochemical features, are so clearly distinct from the agent involved i ...200818187032
experimental transmission of us scrapie agent by nasal, peritoneal, and conjunctival routes to genetically susceptible sheep.scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. this study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (prp(sc)) by immunohistochemistry in tissues of genetically susceptible sheep inoculated with us sheep scrapie agent. four-month-old suffolk lambs (qq at codon 171) were inoculated by 1 of 3 different routes (nasal, peritoneal, and conjunctival) with an inoculum (no. 13-7) consisting of a pool of scrapie-aff ...200818192568
the elk prnp codon 132 polymorphism controls cervid and scrapie prion propagation.the elk prion protein gene (prnp) encodes either methionine (m) or leucine (l) at codon 132, the l132 allele apparently affording protection against chronic wasting disease (cwd). the corresponding human codon 129 polymorphism influences the host range of bovine spongiform encephalopathy (bse) prions. to fully address the influence of this cervid polymorphism on cwd pathogenesis, we created transgenic (tg) mice expressing cervid prpc with l at residue 132, referred to as cerprpc-l132, and compar ...200818198392
comprehensive gene expression analysis in human periodontal ligaments of the mandibular third molars performing vertical movement and the maxillary second premolars with occlusal contact.the periodontal ligament (pdl) is thought to be an important tissue in vertical movement during tooth eruption, but the precise molecular mechanism is not known. thereto, comprehensive gene expression was analyzed in human pdl of mandibular third molars performing vertical movement and maxillary second premolars with occlusal contact.200818199074
prp n-terminal domain triggers prp(sc)-like aggregation of dpl.transmissible spongiform encephalopathies are fatal neurodegenerative disorders thought to be transmitted by self-perpetuating conformational conversion of a neuronal membrane glycoprotein (prp(c), for "cellular prion protein") into an abnormal state (prp(sc), for "scrapie prion protein"). doppel (dpl) is a protein that shares significant biochemical and structural homology with prp(c). in contrast to its homologue prp(c), dpl is unable to participate in prion disease progression or to achieve a ...200817997980
pathogenesis of bovine spongiform encephalopathy in sheep.the pathogenesis of bovine spongiform encephalopathy (bse) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (prp(sc)) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with bse brain homogenate. first accumulation of prp(sc) was detected after 6 months in the tonsil and the ileal peyer's patches. at 9 months postinfection, prp(sc) accumulation involved all gut-associated lymphoid tissues and lymph nodes as well as the spleen. ...200818092124
scrapie resistance and production traits in rambouillet rams: ram performance test 2002-2006.sheep possessing alleles for the prion protein with glutamine (q) or histidine, both reported as q, at codon 171 are highly susceptible to scrapie. incidence of scrapie infection is rare when animals possess at least one allele for arginine (r) at codon 171. the current usda aphis scrapie eradication program utilizes genotyping for alleles that confer resistance to scrapie. although it has not been a criterion of registration, genotyping has been utilized in the university of wyoming ram perform ...200818093625
atypical status of bovine spongiform encephalopathy in poland: a molecular typing study.the aim of this study was to analyze molecular features of protease-resistant prion protein (prp(res)) in western blots of bse cases diagnosed in poland with respect to a possible atypical status. confirmed cases were analyzed by western blotting with several monoclonal antibodies directed at n-terminal and core epitopes of prion protein (prp). most cases showed the classical glycoprofile characterized by the dominance of the di- over the monoglycosylated prp(res) band, yielding di-/mono- ratios ...200817896076
protective effect of prion protein via the n-terminal region in mediating a protective effect on paraquat-induced oxidative injury in neuronal cells.transmissible spongiform encephalopathies are a group of neurodegenerative disorders caused by a posttranslational, conformational change in the cellular isoform of the prion protein (prp(c)) into an infectious, disease-associated form (prp(sc)). increasing evidence supports a role for prp(c) in the cellular response to oxidative stress. we investigated the effect of oxidative stress mediated by paraquat exposure on sh-sy5y neuroblastoma cells. a loss of mitochondrial membrane potential and subs ...200817896796
human prion diseases: from antibody screening to a standardized fast immunodiagnosis using automation.demonstration of pathological prion protein accumulation in the central nervous system is required to establish the diagnosis of transmissible subacute encephalopathies. in humans, this is frequently achieved using prion protein immunohistochemistry in paraffin-embedded tissue, a technique that requires multiple epitope retrieval and denaturing pretreatments. in addition to being time-consuming, this procedure induces tissue alterations that preclude accurate morphological examination. the aim o ...200818084251
cell models of prion infection.due to recent renewal of interest and concerns in prion diseases, a number of cell systems permissive to prion multiplication have been generated in the last years. these include established cell lines, neuronal stem cells and primary neuronal cultures. while most of these models are permissive to experimental, mouse-adapted strains of prions, the propagation of natural field isolates from sheep scrapie and chronic wasting disease has been recently achieved. these models have improved our knowle ...200818073097
pathologic prion protein infects cells by lipid-raft dependent macropinocytosis.transmissible spongiform encephalopathies, including variant-creutzfeldt-jakob disease (vcjd) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (prp(c)) to the infectious scrapie form (prp(sc)). however, the mechanism that exogenous prp(sc) infects cells and where pathologic conversion of prp(c) to the prp(sc) form occurs remains uncertain. here we report that similar to the mec ...200819390657
a patient with mv2 subtype of sporadic creutzfeldt-jakob disease and atypical clinical presentation.we report the case of a 71-year-old woman with progressive dementia over the course of 4 years, characterized by prominent pyramidal signs and by the lack of ataxia and other cerebellar signs. creutzfeldt-jakob disease (cjd) was not suspected during the patient's life. autopsy brain tissue showed severe spongiform encephalopathy with kuru-like, but not florid, plaques in neocortex and cerebellum. massive synaptic diffuse and plaque-like prp(sc) deposition was found in the cerebral cortex, striat ...200819130739
prions in the environment: occurrence, fate and mitigation.scrapie and cwd are horizontally transmissible, and the environment likely serves as a stable reservoir of infectious prions, facilitating a sustained incidence of cwd in free-ranging cervid populations and complicating efforts to eliminate disease in captive herds. prions will enter the environment through mortalities and/or shedding from live hosts. unfortunately, a sensitive detection method to identify prion contamination in environmental samples has not yet been developed. an environmentall ...200819242120
[establishment of a prion disease prp(sc) panel from the brain tissues of experimental hamsters infected with scrapie agent 263k].to establish a prion disease prp(sc) panel from the brain tissues of experimental hamsters and to address the stability of the panel conserved under the specific condition, for evaluating the diagnostic techniques of human and animal's prion diseases.200819469162
urinary alpha1-antichymotrypsin: a biomarker of prion infection.the occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. however, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. sensitive biomarkers may help meeting this need. here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. we found that alpha(1)-antichymotrypsin (alpha(1)-act) was highly upregulated in brains ...200819057641
accelerated prion replication in, but prolonged survival times of, prion-infected cxcr3-/- mice.prion diseases have a significant inflammatory component. glia activation, which is associated with increased production of cytokines and chemokines, may play an important role in disease development. among the chemokines upregulated highly and early upregulated during scrapie infections are ligands of cxcr3. to gain more insight into the role of cxcr3 in a prion model, cxcr3-deficient (cxcr3(-/-)) mice were infected intracerebrally with scrapie strain 139a and characterized in comparison to sim ...200818842729
assessing the presence of bse and scrapie in slaughterhouse wastewater.this paper describes a procedure for evaluating the presence and the stability of the proteinase k-resistant form of the prion protein (prp(res)) in slaughterhouse wastewater.200819146499
kuru likened to scrapie: the story remembered. 200818849258
reduction of prion infectivity in packed red blood cells.the link between a new variant form of creutzfeldt-jakob disease (vcjd) and the consumption of prion contaminated cattle meat as well as recent findings showing that vcjd can be transmitted by blood transfusion have raised public health concerns. currently, a reliable test to identify prions in blood samples is not available. the purpose of this study was to evaluate the possibility to remove scrapie prion protein (prp(sc)) and infectivity from red blood cell (rbc) suspensions by a simple washin ...200818851948
prion propagation in vitro: are we there yet?prion diseases are caused by proteinaceous pathogens termed prions. although the details of the mechanism of prion propagation are not fully understood, conformational conversion of cellular prion protein (prp(c)) to misfolded, disease-associated scrapie prion protein (prp(sc)) is considered the essential biochemical event for prion replication. currently, studying prion replication in vitro is difficult due to the lack of a system which fully recapitulates the in vivo phenomenon. over the last ...200819015743
a mirna signature of prion induced neurodegeneration.micrornas (mirnas) are small, non-coding rna molecules which are emerging as key regulators of numerous cellular processes. compelling evidence links mirnas to the control of neuronal development and differentiation, however, little is known about their role in neurodegeneration. we used microarrays and rt-pcr to profile mirna expression changes in the brains of mice infected with mouse-adapted scrapie. we determined 15 mirnas were de-regulated during the disease processes; mir-342-3p, mir-320, ...200818987751
transmissible spongiform encephalopathies. 200819046027
the effect of fenton reaction on protease-resistant prion protein (prpsc) degradation and scrapie infectivity.in prion diseases, metal imbalances in brain and/or metal substitutions for copper in prion protein suggest that metal-catalyzed oxidation (mco) and oxidative stress may affect cellular function and accumulation of protease-resistant prion protein (prp(sc)). we examined the effect of metal-induced oxidative stress by fenton reaction on prion protein with regard to its degradation, insolubility, and infectivity. precipitation and insolubility of prion protein were induced by fenton reaction in sc ...200818771660
[establishment of prp(sc) conversion based on serial pmca in vitro].in order to establish an amplification system in vitro with which the prp(sc) is able to convert prp(c) into proteinase k-resistant isoform infinitely and whether this system is more efficient than conventional protein misfolding cyclic amplification (pmca), scrapie strain 263k-infected hamster's brain homogenate and homologous normal brain homogenate were prepared, respectively. a new methodology, namely serial pmca, was utilized to reveal the continuous propagation ability of prp(sc). totally ...200818780631
accumulation of citrullinated proteins by up-regulated peptidylarginine deiminase 2 in brains of scrapie-infected mice: a possible role in pathogenesis.peptidylarginine deiminases (pads), which are a group of posttranslational modification enzymes, are involved in protein citrullination (deimination) by the conversion of peptidylarginine to peptidylcitrulline in a calcium concentration-dependent manner. among the pads, pad2 is widely distributed in various tissues and is the only type that is expressed in brain. to elucidate the involvement of protein citrullination by pad2 in the pathogenesis of brain-specific prion diseases, we examined the p ...200818787103
quantitative recovery of scrapie agent with minimal protein from highly infectious cultures.there are few reports on the isolation, quantitative recovery, and relative purification of infectious particles that cause scrapie, creutzfeldt-jakob disease (cjd) and epidemic bovine spongiform encephalopathy (bse). because pure prion protein (prp) has failed to show significant infectivity, it is critical to find other molecules that are integral agent components. only complex diseased tissues such as degenerating brain have been fractionated, and agent recoveries have been quite low in conce ...200818788938
neuroinvasion of the 263k scrapie strain after intranasal administration occurs through olfactory-unrelated pathways.the olfactory system has been implicated in the pathogenesis of transmissible spongiform encephalopathies (tses). to examine this issue and identify the pattern of tse agent spread after intranasal administration, we inoculated a high-infectious dose of neurotropic scrapie strain 263k into the nasal cavity of syrian hamsters. all animals allowed to survive became symptomatic with a mean incubation period of 162.4 days. analysis at different time points revealed deposition of the pathological pri ...200919107494
accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host.in order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the vrq allele of the prp gene were infected by the oral route. infection occurred in all lambs with a remarkably short and highly consistent incubation period of approximately 6 months. challenge of lambs at approximately eight months of age resulted in disease in all animals, but with more variable incubation periods aver ...200919243608
detection of pathologic prion protein in the olfactory bulb of natural and experimental bovine spongiform encephalopathy affected cattle in great britain.to investigate the relative involvement of the olfactory region in classical bovine spongiform encephalopathy (bse), immunohistochemical labeling of prion protein scrapie (prp(sc)) was scored in the brainstem, frontal cerebral cortex, and olfactory bulb of cattle with natural and experimental clinical cases of bse in great britain. the intensity of immunolabeling was greatest in the brainstem, but prp(sc) was also detected in the olfactory bulb and the cerebral cortex. a diffuse, nonparticulate ...200919112116
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
ovine prnp untranslated region and promoter haplotype diversity.the diversity and possible contribution of non-coding regions of the prion protein (prp) gene (prnp) to transmissible spongiform encephalopathy susceptibility and prp regulation are not fully known. this study defined ten ovine prnp promoters and five untranslated region (utr) haplotypes found in atypical and classical scrapie cases and healthy control sheep. a greater diversity of promoter and utr haplotypes was observed in conjunction with the arq prp allele (seven promoter and four utr haplot ...200919264598
transmission of scrapie and sheep-passaged bovine spongiform encephalopathy prions to transgenic mice expressing elk prion protein.chronic wasting disease (cwd) is a transmissible, fatal prion disease of cervids and is largely confined to north america. the origin of cwd continues to pose a conundrum: does the disease arise spontaneously or result from some other naturally occurring reservoir? to address whether prions from sheep might be able to cause disease in cervids, we inoculated mice expressing the elk prion protein (prp) transgene [tg(elkprp) mice] with two scrapie prion isolates. the ssbp/1 scrapie isolate transmit ...200919264659
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
a new genotyping strategy for efficient scoring of closely positioned snps in the ovine prion protein gene.amino-acid polymorphisms of the ovine prion protein have been known to influence susceptibility to scrapie for many years. recently, a role in both classical and atypical scrapie was assigned to new mutations, increasing the overall number of polymorphisms of interest for breeding plans. besides, the high number and density of polymorphisms in the prion protein gene (prp) and the presence of unusual mutations in some breeds hampers genotyping methods, making multiplexing difficult and sometimes ...200919272344
[research progress on genetic diversity of sheep prnp and resistance breeding].prion protein (prp) is a pathogeny identified in recent years, which infects both mankind and other mammals. it has been proved that prp is a sole protein able to duplicate and propagate with itself. prp can express in many tissues and has important physiological functions in many species of animals. the conformation change of prp is the origin of transmissible spongiform encephalopathies (tses). it has been proved that the sheep genetic diversity of prion protein gene (prnp) is significantly as ...200919273420
cells expressing anchorless prion protein are resistant to scrapie infection.the hallmark of transmissible spongiform encephalopathies (tses or prion diseases) is the accumulation of an abnormally folded, partially protease-resistant form (prp-res) of the normal protease-sensitive prion protein (prp-sen). prp-sen is attached to the cell membrane by a glycosylphosphatidylinositol (gpi) anchor. in vitro, the anchor and the local membrane environment are important for the conversion of prp-sen to prp-res. in vivo, however, the anchor is not necessary because transgenic mice ...200919225008
integrity of h1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of h1 and its s1 flank.in the template-assistance model, normal prion protein (prpc), the pathogenic cause of prion diseases such as creutzfeldt-jakob in human, bovine spongiform encephalopathy in cow, and scrapie in sheep, converts to infectious prion (prpsc) through an autocatalytic process triggered by a transient interaction between prpc and prpsc. conventional studies suggest the s1-h1-s2 region in prpc to be the template of s1-s2 beta-sheet in prpsc, and the conformational conversion of prpc into prpsc may invol ...200919229533
detection of typical and atypical bovine spongiform encephalopathy and scrapie prion strains by prion protein motif-grafted antibodies.to evaluate further the reactivity of prion-specific monoclonal antibodies containing the 89-112 or 136-158 prion protein (prp) polypeptides, immunoprecipitations were performed on brain extracts from italian bovines, sheep and goats with transmissible spongiform encephalopathies. no binding of igg 89-112 or igg 136-158 to prp in normal brain extracts was detected. conversely, both reagents immunoprecipitated prp from bovine and bovine amyloidotic spongiform encephalopathies, and from typical an ...200919223486
scrapie-resistant sheep show certain coat colour characteristics.susceptibility to scrapie is known to be associated with polymorphisms at the prion protein (prp) gene, and this association is the basis of current selective programmes implemented to control scrapie in many countries. however, these programmes might have unintended consequences for other traits that might be associated with prp genotype. the objective of this study was to investigate the relationship between prp genotype and coat colour characteristics in two uk native sheep breeds valued for ...200919220930
atypical scrapie in sheep from a uk research flock which is free from classical scrapie.in the wake of the epidemic of bovine spongiform encephalopathy the british government established a flock of sheep from which scrapie-free animals are supplied to laboratories for research. three breeds of sheep carrying a variety of different genotypes associated with scrapie susceptibility/resistance were imported in 1998 and 2001 from new zealand, a country regarded as free from scrapie. they are kept in a purpose-built sheep unit under strict disease security and are monitored clinically an ...200919208228
development of antibody fragments for immunotherapy of prion diseases.prions are infectious proteins responsible for a group of fatal neurodegenerative diseases called tses (transmissible spongiform encephalopathies) or prion diseases. in mammals, prions reproduce themselves by recruiting the normal cellular protein prp(c) and inducing its conversion into the disease-causing isoform denominated prp(sc). recently, anti-prion antibodies have been shown to permanently cure prion-infected cells. however, the inability of full-length antibodies and proteins to cross th ...200919000036
hectd2 is associated with susceptibility to mouse and human prion disease.prion diseases are fatal transmissible neurodegenerative disorders, which include scrapie, bovine spongiform encephalopathy (bse), creutzfeldt-jakob disease (cjd), and kuru. they are characterised by a prolonged clinically silent incubation period, variation in which is determined by many factors, including genetic background. we have used a heterogeneous stock of mice to identify hectd2, an e3 ubiquitin ligase, as a quantitative trait gene for prion disease incubation time in mice. further, we ...200919214206
poisson sampling: a sampling strategy for concurrently establishing freedom from disease and estimating population characteristics.surveys of animal populations are often designed to either demonstrate freedom from disease or to estimate parameters that describe the population, such as disease prevalence, proportion of vaccinated animals, or average animal weight and value. targeted surveillance is a sampling approach where animals are selected for testing based on the presence of characteristics that indicate a higher probability of disease. this approach can substantially reduce the sample size that is required to demonst ...200919217677
three serial passages of bovine spongiform encephalopathy in sheep do not significantly affect discriminatory test results.during the 1980s, bovine spongiform encephalopathy (bse)-contaminated meat and bonemeal were probably fed to sheep, raising concerns that bse may have been transmitted to sheep in the uk. the human disease, variant creutzfeldt-jakob disease, arose during the bse epidemic, and oral exposure of humans to bse-infected tissues has been implicated in its aetiology. the concern is that sheep bse could provide another source of bse exposure to humans via sheep products. two immunological techniques, we ...200919218224
identification of seven haplotypes of the caprine prp gene at codons 127, 142, 154, 211, 222 and 240 in french alpine and saanen breeds and their association with classical scrapie.in sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the prp gene. in goats, there are to date few data related to scrapie susceptibility association with prp gene polymorphisms. in this study, we first investigated prp gene polymorphisms of the french alpine and saanen breeds. based on prp gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. however, only seven haplo ...200919218225
increased neurogenesis in brains of scrapie-infected mice.persistent neurogenesis occurs in the adult brain throughout the life of all mammals. recent studies have shown that neurogenesis was increased in adult gerbil and rat brains after ischemia. neurogenesis has not been examined during neurodegenerative diseases such as scrapie. to investigate the regeneration of neurons after scrapie-infection, we infused 5-bromo-2'-deoxyuridine (brdu), a dna replication indicator, into both control and scrapie-infected mice. mice were sacrificed at 150 days post- ...200918973796
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
opposing effects of erk and p38-jnk map kinase pathways on formation of prions in gt1-1 cells.brain-derived neurotrophic factor, which activates the extracellular regulated kinase (erk) pathway, increases formation of prions in scrapie-infected gonadotropin-releasing hormone (gt1-1) cells. this indicates that conversion of the cellular prion protein prp(c) to its pathogenic isoform, prp(sc), can be regulated by physiological stimuli acting on specific signal transduction pathways. in the present study, we examined the involvement of different mitogen-activated protein (map) kinase cascad ...200918824519
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
olfactory system involvement in natural scrapie disease.the olfactory system (os) is involved in many infectious and neurodegenerative diseases, both human and animal, and it has recently been investigated in regard to transmissible spongiform encephalopathies. previous assessments of nasal mucosa infection by prions following intracerebral challenge suggested a potential centrifugal spread along the olfactory nerve fibers of the pathological prion protein (prp(sc)). whether the nasal cavity may be a route for centripetal prion infection to the brain ...200919158242
faecal shedding, alimentary clearance and intestinal spread of prions in hamsters fed with scrapie.shedding of prions via faeces may be involved in the transmission of contagious prion diseases. here, we fed hamsters 10mg of 263k scrapie brain homogenate and examined the faecal excretion of disease-associated prion protein (prp(tse)) during the course of infection. the intestinal fate of ingested prp(tse) was further investigated by monitoring the deposition of the protein in components of the gut wall using immunohistochemistry and paraffin-embedded tissue (pet) blotting. western blotting of ...200918828985
immunolocalisation of prpsc in scrapie-infected n2a mouse neuroblastoma cells by light and electron microscopy.the causative agent of transmissible spongiform encephalopathies (tse) is prpsc, an infectious, misfolded isoform of the cellular prion protein (prpc). the localisation and trafficking of prpsc and sites of conversion from prpc to prpsc are under debate, particularly since most published work did not discriminate between prpc and prpsc. here we describe the localisation of prpc and prpsc in a scrapie-infected neuroblastoma cell line, scn2a, by light and electron microscopic immunolocalisation. a ...200918834644
protective effect of the at137rq and arqk176 prp allele against classical scrapie in sarda breed sheep.the susceptibility of sheep to scrapie is under the control of the host's prion protein (prp gene and is also influenced by the strain of the agent. prp polymorphisms at codons 136 (a/v), 15 (r/h) and 171 (q/r/h) are the main determinants of susceptibility/resistance of sheep to classical scrapie. they are combined in four main variants of the wild-type arq allele: vrq, ahq, arh and arr. breeding programmes have been undertaken on this basis in the european union and th usa to increase the frequ ...200919171116
increased gh secretion in scrapie, a prion-associated neurodegenerative disease, is not due to suppressed igf-1 negative feedback.gh secretion is increased in scrapie-diseased sheep. although the role of the somatotropic axis as a neurotrophic and neuroprotective factor is well documented, no studies have been carried out on the mechanisms and functional significance of somatotropic perturbation in the pathophysiology of prion-associated neurodegenerative disease. the goal of this study was to test the hypothesis that increased gh secretion observed in a natural animal prion disease, scrapie, might reflect a general lack o ...200919179038
bacterial colitis increases susceptibility to oral prion disease.dietary exposure to prion-contaminated materials has caused kuru and variant creutzfeldt-jakob disease in humans and transmissible spongiform encephalopathies (tses) in cattle, mink, and felines. the epidemiology of dietary prion infections suggests that host genetic modifiers and possibly exogenous cofactors may play a decisive role in determining disease susceptibility. however, few cofactors influencing susceptibility to prion infection have been identified. in the present study, we investiga ...200919072552
prnp haplotype distribution in moroccan goats.susceptibility/resistance to scrapie in sheep and goats is influenced by host prion protein gene (prnp) genotype. in this study, we report the analysis of prion protein gene polymorphisms in 137 goats of two moroccan populations: d'man and chaouni. we found seven previously described amino acid polymorphisms at codons 37, 127, 137, 142, 154, 222 and 240, as well as three known silent mutations. in addition, we identified three new allelic variants: 101r and 139s in d'man goats and 145d in d'man ...200919397523
distinct spatial activation of intrinsic and extrinsic apoptosis pathways in natural scrapie: association with prion-related lesions.neurodegeneration and gliosis are the main neuropathological features of prion diseases. however, the molecular mechanisms involved in these processes remain unclear. several studies have demonstrated changes in the expression of apoptotic factors and inflammatory cytokines in animals with experimental infection. here we present the expression profiles of 15 genes implicated in the intrinsic and extrinsic apoptotic pathways in the central nervous systems of sheep naturally infected with scrapie. ...200919401142
a case-control study on the origin of atypical scrapie in sheep, france.a matched case-control study (95 cases and 220 controls) was designed to study risk factors for atypical scrapie in sheep in france. we analyzed contacts with animals from other flocks, lambing and feeding practices, and exposure to toxic substances. data on the prnp genotype were collected for some case and control animals and included in a complementary analysis. sheep dairy farms had a higher risk for scrapie (odds ratio [or] 15.1, 95% confidence interval [ci] 3.3-69.7). lower risk was associ ...200919402956
comparison of strategies for substantiating freedom from scrapie in a sheep flock.the public health threat represented by a potential circulation of bovine spongiform encephalopathy agent in sheep population has led european animal health authorities to launch large screening and genetic selection programmes. if demonstrated, such a circulation would have dramatic economic consequences for sheep breeding sector. in this context, it is important to evaluate the feasibility of qualification procedures that would allow sheep breeders demonstrating their flock is free from scrapi ...200919405956
blood chimerism confounds genetic relative susceptibility testing for classical scrapie in sheep.classical scrapie disease is a transmissible spongiform encephalopathy of sheep that is enzootic in the united states. susceptibility of sheep to classical scrapie is linked to single nucleotide polymorphisms in the prion protein gene (prnp), forming the basis for genetic testing strategies used by national efforts to eradicate scrapie. such efforts are occasionally hampered by inconclusive results stemming from the detection of "complex" genotypes. naturally occurring cases of ovine chimerism a ...200919407081
cryptic peptides of the kringle domains preferentially bind to disease-associated prion protein.prion diseases are a group of fatal neurodegenerative disorders characterized by the accumulation of a misfolded form (prp(sc)) of the cellular prion protein (prp(c)) in the brains of affected individuals. the conversion of prp(c) to prp(sc) is thought to involve a change in protein conformation from a normal, primarily alpha-helical structure into a beta-sheet conformer. few proteins have been identified that differentially interact with the two forms of prp. it has been reported that plasminog ...200919221431
on the question of proportionality of the count of observed scrapie cases and the size of holding.the present paper investigates the question of a suitable basic model for the number of scrapie cases in a holding and applications of this knowledge to the estimation of scrapie-affected holding population sizes and adequacy of control measures within holding. is the number of scrapie cases proportional to the size of the holding in which case it should be incorporated into the parameter of the error distribution for the scrapie counts? or, is there a different - potentially more complex - rela ...200919419538
surface charge of polyoxometalates modulates polymerization of the scrapie prion protein.prions are composed solely of an alternatively folded isoform of the prion protein (prp), designated prp(sc). n-terminally truncated prp(sc), denoted prp 27-30, retains infectivity and polymerizes into rods with the ultrastructural and tinctorial properties of amyloid. we report here that some polyoxometalates (poms) favor polymerization of prp 27-30 into prion rods, whereas other poms promote assembly of the protein into 2d crystals. antibodies reacting with epitopes in denatured prp 27-30 also ...200919223590
microinjection of lentiviral vectors expressing small interfering rnas directed against laminin receptor precursor mrna prolongs the pre-clinical phase in scrapie-infected mice.we examined therapeutic in vitro and in vivo approaches using lentivirus-based packaging of small interfering rnas (sirnas) targeting the non-integrin laminin receptor mrna for treatment and prevention of prion disorders. transfection of n2asc(+) cells with recombinant plasmids expressing three different sirnas, significantly reduced both the lrp (laminin receptor precursor) and prp(sc) levels by approximately 40-60 %. stereotactic intracerebral microinjection of recombinant lentiviral vectors l ...200919088298
surround optical fiber immunoassay (sofia): an ultra-sensitive assay for prion protein detection.we describe the development of a new technology (sofia) and demonstrate its utility by establishing a sensitive and specific assay for prp(sc). sofia is a surround optical fiber immunoassay which is comprised of a set of specific monoclonal antibodies and comprehensive capture of high energy fluorescence emission. in its current format, this system is capable of detecting less than 10 attogram (ag) of hamster, sheep and deer recombinant prp. approximately 10 ag of prp(sc) from 263 k-infected ham ...200919442839
interlaboratory trial on tse rapid tests for the control of the italian scrapie surveillance network.scrapie, a neurodegenerative disease of sheep and goats and one of several transmissible spongiform encephalopathies (tses) has been subject to mandatory active surveillance in eu through rapid testing since 2002. regulation ec/999/2001 on tse surveillance requires that each member state's national reference laboratory for tse periodically verifies diagnostic standards and methods by comparative testing. in 2007 the italian reference centre carried out the first ring trial for classical scrapie ...200919457624
frequency of genotypes in the prp prion protein gene locus in the polish sheep population.scrapie is an invariably fatal transmissible neurodegenerative disease of sheep, goats and moufflons, characterised by ataxia, lower body weight and changes in behaviour. the aim of this study was to determine the genotype distribution at codons 136, 154 and 171 of the prp locus in sheep bred in poland. the genotypes of 801 sheep representing 10 different breeds and crossbreds were analysed using real-time pcr allele discrimination method. the combination of point mutations of the three codons ( ...200919457772
alkaline hydrolysis of mouse-adapted scrapie for inactivation and disposal of prion-positive material.prion diseases such as bovine spongiform encephalopathy, chronic wasting disease, and scrapie pose serious risks to human and animal health due to a host of disease-specific factors, including the resistance of infectious prions (prp(sc)) to natural degradation and to most commercial inactivation procedures. in an attempt to address this concern, a mouse model was used to compare the efficacy of an alkaline hydrolysis process with a simulated continuous-flow rendering treatment for disposal of p ...200919098230
prp106-126 peptide disrupts lipid membranes: influence of c-terminal amidation.prp106-126 is located within the important domain concerning membrane related conformational conversion of human prion protein (from cellular isoform prp(c) to scrapie isoform prp(sc)). recent advances reveal that the pathological and physicochemical properties of prp106-126 peptide are very sensitive to its n-terminal amidation, however, the detailed mechanism remains unclear. in this work, we studied the interactions of the prp106-126 isoforms (prp106-126(conh2) and prp106-126(cooh)) with the ...200919103159
species and strain glycosylation patterns of prpsc.a key event in transmissible spongiform encephalopathies (tses) is the conversion of the soluble, protease-sensitive glycosylated prion protein (prp(c)) to an abnormally structured, aggregated and partially protease-resistant isoform (prp(sc)). both prp isoforms bear two potential glycosylation sites and thus in a typical western blot with an anti-prp antibody three distinct bands appear, corresponding to the di-, mono- or unglycosylated forms of the protein. the relative intensity and electroph ...200919461968
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
feasibility of infectious prion digestion using mild conditions and commercial subtilisin.two serine protease enzymes, subtilisin 309 and subtilisin 309-v, were used to digest brain homogenates containing high levels of prion infectivity using mildly alkaline conditions to investigate prion decontamination methods. to establish that prp(res) infectivity was eliminated, we utilized the rocky mountain laboratory (rml) mouse-adapted scrapie model system for bioassay. only one digestion condition (subtilisin 309 at 138mau/ml, 55 degrees c and 14h digestion time ph 7.9) was considered to ...200919467265
rapid diagnosis of human prion disease using streptomycin with tonsil and brain tissues.the use of streptomycin in the pathological prion protein (prp(sc)) detection procedures represents a new and attractive way for diagnostic purpose. with this agent, western blot readily detected prp(sc) in 263k scrapie hamster and c57bl/6 wild-type mice challenged with c506m3 scrapie strain. our aim was to evaluate this new diagnosis procedure in the field of human transmissible spongiform encephalopathies (tses). first, we had confirmed the ability of streptomycin to precipitate prp(res) from ...200919188908
tetracyclines and prion infectivity.in the last decade information has accumulated on the potential anti-prion activity of polycyclic compounds. initially we showed that the antitumoral idodoxorubicin reduced the infectivity in experimental scrapie. on the basis of the chemical homology with anthracyclines, we rapidly moved to tetracyclines, compounds that are safer and widely used as antibiotics in clinical practice. the tetracyclines, essentially doxycycline and minocycline, were characterized as a therapeutical tool in transmis ...200919200012
inhibition of prion amplification by expression of dominant inhibitory mutants--a systematic insertion mutagenesis study.until now it is still not clear which structural elements of the prion protein (prp) are involved in its conversion process. characterisation of these essential regions would help to understand the conversion process itself and might help to develop specific therapeutic approaches to inhibit prp(res) formation by dominant inhibitory mutations. to address this important question 33 evenly spaced insertion mutants were generated spanning the entire sequence of the murine 3f4-tagged prp. the mutant ...200919200014
cd21 b cell populations are altered following subcutaneous scrapie inoculation in sheep.in order to gain a better understanding of the pathogenesis of scrapie in sheep an experimental model was developed to characterise immune system cells in the minutes following inoculation with scrapie-brain homogenate. four 1-year-old susceptible (arq/arq) sheep were inoculated via the subcutaneous route at four different peripheral lymph node (lns) drainage sites, at specific time points, prior to euthanasia of the sheep. the lns were removed post-mortem at 30, 90, 180 and 300min after inocula ...200919327845
ileal tract and peyer's patch innervation in scrapie-free versus scrapie-affected ovines.ileal peyer's patches (pps) are involved early during sheep scrapie infection. this study qualitatively and semi-quantitatively evaluated ileal tract and pp innervation in 29 sarda ovines of different age, prp genotype and scrapie status. a prominent network of fibres was detected within pps, mainly located in interfollicular lymphoid and stromal components. intrafollicular fibres were rarely observed, with no apparent differences between scrapie-free and scrapie-affected animals, or among ovine ...200919330284
Refresh
firstprev
...31323334353637383940...
nextlast
Displaying items 3901 - 4000 of 4534