Publications
| Title | Abstract | Year(sorted descending) Filter | PMID Filter |
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| prion protein (prp) knock-out mice show altered iron metabolism: a functional role for prp in iron uptake and transport. | despite overwhelming evidence implicating the prion protein (prp) in prion disease pathogenesis, the normal function of this cell surface glycoprotein remains unclear. in previous reports we demonstrated that prp mediates cellular iron uptake and transport, and aggregation of prp to the disease causing prp-scrapie (prp(sc)) form results in imbalance of iron homeostasis in prion disease affected human and animal brains. here, we show that selective deletion of prp in transgenic mice (prp(ko)) alt ... | 2009 | 19568430 |
| human variant creutzfeldt-jakob disease and sheep scrapie prp(res) detection using seeded conversion of recombinant prion protein. | the pathological isoform of the prion protein (prp(res)) can serve as a marker for prion diseases, but more practical tests are needed for preclinical diagnosis and sensitive detection of many prion infections. previously we showed that the quaking-induced conversion (quic) assay can detect sub-femtogram levels of prp(res) in scrapie-infected hamster brain tissue and distinguish cerebral spinal fluid (csf) samples from normal and scrapie-infected hamsters. we now report the adaptation of the qui ... | 2009 | 19570812 |
| evaluating different prp genotype selection strategies for expected severity of scrapie outbreaks and genetic progress in performance in commercial sheep. | stochastic computer simulations were used for quantifying the effect of selecting on prion protein (prp) genotype on the risk of major outbreaks of classical scrapie and the rate of genetic progress in performance in commercial sheep populations already undergoing selection on performance. the risk of a major outbreak on a flock was measured by the basic reproduction ratio (r(0)). the effectiveness of different prp selection strategies for reducing the population risk was assessed by the percent ... | 2009 | 19577317 |
| sequence analysis of the prion protein gene in mongolian gazelles (procapra gutturosa). | prion diseases are a group of human and animal neurodegenerative conditions, which are caused by the deposition of an abnormal isoform prion protein (prpsc) encoded by a single copy prion protein gene (prnp). in sheep, genetic variations of prnp were found to be associated with the incubation period, susceptibility, and species barrier to the scrapie disease. we investigated the sequence and polymorphisms of the prion protein gene of mongolian gazelles (gprnp). gprnp gene sequence analysis of bl ... | 2009 | 19579063 |
| phosphorylation of prion protein at serine 43 induces prion protein conformational change. | the cause of the conformational change of normal cellular prion protein (prp) into its disease-associated form is unknown. posttranslational modifications, such as glycosylation, acetylation, s-nitrosylation, and phosphorylation, are known to induce protein conformational changes. here, we investigated whether phosphorylation could induce the conformational change of prp because prp contains several kinase motifs and has been found recently in the cytosol, in which kinases generally reside. neur ... | 2009 | 19587281 |
| prion protein detection via direct immuno-quantitative real-time pcr. | we describe a simple and robust assay for the quantitative detection of prions using immuno-quantitative real-time pcr (iq-rt-pcr) made possible by a direct conjugate of a prion-specific antibody (icsm35) and a synthetic 99-bp dna tail. the dna tail was engineered to include a single scrfi restriction site, which enabled subsequent quantification of restricted dna tails using real-time pcr. the assay was tested with scrapie prions bound to polyvinylidene difluoride membranes and to 96-well plate ... | 2009 | 19596031 |
| distinct structures of scrapie prion protein (prpsc)-seeded versus spontaneous recombinant prion protein fibrils revealed by hydrogen/deuterium exchange. | the detailed structures of prion disease-associated, partially protease-resistant forms of prion protein (e.g. prp(sc)) are largely unknown. prp(sc) appears to propagate itself by autocatalyzing the conformational conversion and oligomerization of normal prion protein (prp(c)). one manifestation of prp(sc) templating activity is its ability, in protein misfolding cyclic amplification reactions, to seed the conversion of recombinant prion protein (rprp) into aggregates that more closely resemble ... | 2009 | 19596861 |
| doxorubicin and congo red effectiveness on prion infectivity in golden syrian hamster. | the effect of doxorubicin and congo red on prion protein (prp) infectivity in experimental scrapie was studied to better understand the effect of these compounds in prion diseases and to establish whether a dose-response correlation exists for congo red. this was performed in order to test the effectiveness of compounds that may easily be used in human prion diseases. brain homogenate containing membrane bound prpsc monomers was used as inoculum and was previously incubated with doxorubicin 10(- ... | 2009 | 19596920 |
| failure to transmit scrapie infection by transferring preimplantation embryos from naturally infected donor sheep. | the objective of the study was to examine whether or not the preimplantation embryo can act as a carrier of classic scrapie infection. the study was carried out on quarantined premises with sheep of highly susceptible scrapie genotypes. uninfected embryos, collected from new zealand-derived suffolk ewes, were surgically transferred into recipient ewes that were also of new zealand origin. seventeen negative control lambs were born on the study premises from these embryo transfers. thirty-nine ex ... | 2009 | 19604572 |
| characterization of a us sheep scrapie isolate with short incubation time. | scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. susceptibility to the disease is partly dependent upon the genetic makeup of the host. in a previous study it was shown that sheep intracerebrally inoculated with us scrapie inoculum (no. 13-7) developed terminal disease within an average of 19 months. we have since produced an inoculum, no. x124 from pooled brains of us-origin sheep scrapie, that results in incubations nearly threefold shorter. the present stud ... | 2009 | 19605918 |
| reduction of prion infectivity and levels of scrapie prion protein by lithium aluminum hydride: implications for rna in prion diseases. | previous studies indicate that rna may be required for proteinase-resistant prion protein (prp) amplification and for infectious prion formation in vitro, suggesting that rna molecules may function as cellular cofactors for abnormal prp (prpsc) formation and become part of the structure of the infectious agent. to address this question, we used chemicals that can cleave phosphodiester bonds of rna and assessed their effects on the infectious agent. lithium aluminum hydride, a reducing agent that ... | 2009 | 19606066 |
| spatial distribution of the active surveillance of sheep scrapie in great britain: an exploratory analysis. | this paper explores the spatial distribution of sampling within the active surveillance of sheep scrapie in great britain. we investigated the geographic distribution of the birth holdings of sheep sampled for scrapie during 2002 - 2005, including samples taken in abattoir surveys (c. 83,100) and from sheep that died in the field ("fallen stock", c. 14,600). we mapped the birth holdings by county and calculated the sampling rate, defined as the proportion of the holdings in each county sampled b ... | 2009 | 19607705 |
| peptide nmhrypnq of the cellular prion protein (prp(c)) inhibits aggregation and is a potential key for understanding prion-prion interactions. | pathogenesis of transmissible spongiform encephalopathies is correlated with a conversion of the normal cellular form of the prion protein (prp(c)) into the abnormal isoform (scrapie form of prp). contact of the normal prp with its abnormal isoform, the scrapie form of prp, induces the transformation. knowledge of molecules that inhibit such contacts leads to an understanding of the mechanism of the aggregation, and these molecules may serve as leads for drugs against transmissible spongiform en ... | 2009 | 19607841 |
| reflections on a half-century in the field of transmissible spongiform encephalopathy. | the subject of transmissible spongiform encephalopathy may properly be said to have begun with the experimental transmission of scrapie by cuillé and chelle in 1936, although creutzfeldt and jakob had described the disease that bears their names in 1920-21. thirty more years passed before the human disease was also shown to be transmissible, in 1966, and the following half century has seen the field move from classical biology to molecular biology and genetics, and from 'slow virus' to host-enco ... | 2009 | 19618333 |
| establishment of a stable prp(sc) panel from brain tissues of experimental hamsters with scrapie strain 263k. | to establish a stable prp(sc) panel from brain tissues of experimental hamsters infected with scrapie agent 263k for evaluating diagnostic techniques of human and animals' prion diseases. | 2009 | 19618693 |
| [analysis of monoclonal antibody binding sites in ovine prion protein]. | binding sites of five monoclonal antibodies were obtained by reinforceable method of overlapping recombinant prion protein and synthetic peptide. overlapping peptides of prp core were expressed in escherichia coli by insertion of serial pcr amplicons of ovine prp gene fragments into pet32a. the expressed fusion peptides were then tested for the binding activity to prp monoclonal antibodies in western blotting. the binding sites of 5 monoclonal antibodies of ovine prp were located respectively as ... | 2009 | 19621573 |
| therapeutic interventions ameliorating prion disease. | of the many unresolved issues in relation to prion diseases, effective treatments remain an elusive exigency, although some progress has been made. this review describes disease-ameliorating therapeutic strategies reported to date in animal models of prion disease, as well as providing a brief overview of selected completed human treatment trials. included in vivo studies have been broadly dichotomized according to the time of introduction of the treatment in relation to animal inoculation and a ... | 2009 | 19622059 |
| the toxicity of prion protein fragment prp(106-126) is not mediated by membrane permeabilization as shown by a m112w substitution. | prion diseases result from a post-translational modification of the physiological prion protein (prp(c)) into a scrapie isoform (prp(sc)). the prp(106-126) fragment is conserved among various abnormal variants and shows prp(sc) pathogenic properties. it has been proposed that the prp(106-126) fragment may exhibit its toxic effects through membrane pore formation. our previous studies showed that prp(106-126) does not interact with membranes under physiological conditions. in the present study, p ... | 2009 | 19301918 |
| the number of octapeptide repeat affects the expression and conversion of prion protein. | the human prion protein (prp) has five copies of an octapeptide repeat (or). the mutant prp with 6-14 or causes the genetic form of creutzfeldt-jakob disease (cjd). to determine the influence of or on the conversion of prp, we examined the conversion efficiency of mouse mutant prp molecules with 1-16 or in scrapie-infected cells. the expression level of mutant prp and the glycoform ratio of the abnormal isoform of prp (prp(sc)) were affected by the number of or. the conversion efficiency was alm ... | 2009 | 19318088 |
| doppel induces autophagic stress in prion protein-deficient purkinje cells. | the ectopic expression of the prion protein homologue doppel (dpl) in brain neurons causes progressive cerebellar purkinje cell death in prion protein-deficient ngsk mice (np0/0). the neurotoxicity caused by dpl involves bax-dependent apoptotic pathways as well as other yet to be characterized cell death mechanisms in the np0/0 purkinje cells. these neurons display increased amounts of several autophagy-related molecules such as the scrapie-responsive gene one (scrg1), lc3b-ii and p62 without sh ... | 2009 | 19320049 |
| scrapie-infected transgenic mice expressing a laminin receptor decoy mutant reveal a prolonged incubation time associated with low levels of prpres. | the 37-kda/67-kda laminin receptor (lrp/lr) was identified as a cell surface receptor for prion proteins. the laminin receptor mutant lrp102-295::flag interfered with prp(sc) propagation in murine neuronal cells presumably acting as a decoy in a transdominant negative fashion by trapping prp molecules in the extracellular matrix. here, we generated hemizygous transgenic mice expressing lrp102-295::flag in the brain. scrapie-infected transgenic mice exhibit a significantly prolonged incubation ti ... | 2009 | 19324055 |
| 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 ... | 2009 | 19327845 |
| 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 ... | 2009 | 19330284 |
| immunohistochemical study of prp(sc) distribution in neural and extraneural tissues of two cats with feline spongiform encephalopathy. | two domestic shorthair cats presenting with progressive hind-limb ataxia and increased aggressiveness were necropsied and a post mortem diagnosis of feline spongiform encephalopathy (fse) was made. a wide spectrum of tissue samples was collected and evaluated histologically and immunohistologically for the presence of prpsc. | 2009 | 19335885 |
| effect of enzymatic deimination on the conformation of recombinant prion protein. | deimination is the post-translational conversion of arginine residues to citrulline. it has been implicated as a causative factor in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis and more recently, as a marker of neurodegeneration. we have investigated the effect of the post-translational modification of arginine residues on the structure of recombinant ovine prion protein. deiminated prion protein exhibited biophysical properties characteristic of the scrapie-associate ... | 2009 | 19341825 |
| failure to detect the presence of prions in the uterine and gestational tissues from a gravida with creutzfeldt-jakob disease. | the vertical transmission of a prion disease from infected mothers to their offspring is believed to be one of the routes for the natural spread of animal prion diseases. supporting this notion is the observation that prion infectivity occurs in the placenta of infected ewes. furthermore, the prion protein (prp), both in its cellular form (prp(c)) and its pathological isoform (prp(sc)), has been observed at the fetal-maternal interface of scrapie-infected sheep. however, whether these features o ... | 2009 | 19349373 |
| prevalence of sheep infected with classical scrapie in great britain, 1993-2007. | extensive surveillance for classical scrapie has been carried out in great britain since 1993, the results of which can be used for monitoring the effect of control measures introduced since 2001. a back-calculation approach was used to estimate the prevalence of sheep infected with classical scrapie, which integrates data on reported clinical cases (1993-2007) and the results of fallen stock and abattoir surveys (2002-2007). the prevalence of classical scrapie in gb was fairly constant until 20 ... | 2009 | 19351431 |
| eradicating scrapie. | 2009 | 19356264 | |
| selective presynaptic degeneration in the synaptopathy associated with me7-induced hippocampal pathology. | intrahippocampal injection of the murine modified scrapie (me7) induces a model of prion disease in vivo. animals inoculated with me7 brain homogenate were compared to controls at 8, 12 and 21 weeks. the data show that the accumulation of misfolded prion (prp(sc)) coincided with selective reduction in presynaptic protein expression early in disease. this loss is independent of a change in the number of cell bodies in ca3 that provide the major presynaptic input to the stratum radiatum. electron ... | 2009 | 19362593 |
| identification of proteins co-purifying with scrapie infectivity. | prp(c), the cellular isoform of prion protein, is widely expressed in most tissues. despite its involvement in several bioprocesses it still has no apparent physiological role. during propagation of transmissible spongiform encephalopathies, prp(c) is converted to the pathological isoform, prp(sc), in a process believed to be mediated by unknown host factors. prp(sc) has altered biochemical properties and forms amyloid aggregates that display infectious characteristics. prp(sc) is also the major ... | 2009 | 19367687 |
| role of the lymphoreticular system in prion neuroinvasion from the oral and nasal mucosa. | prion neuroinvasion from peripheral tissues involves agent replication in the lymphoreticular system (lrs) prior to entry into the nervous system. this study investigated the role of the lrs in prion neuroinvasion from the oral and nasal mucosa in wild-type and immunodeficient mice and in hamsters infected with the hy and dy strains of the transmissible mink encephalopathy (tme) agent. following inoculation at neural sites, all hosts were susceptible to prion disease and had evidence of prion in ... | 2009 | 19369351 |
| the conversion of helix h2 to beta-sheet is accelerated in the monomer and dimer of the prion protein upon t183a mutation. | the conversion of the prion protein (prp) from its cellular form, prpc, to its pathogenic scrapie form, prpsc, is a key event in neurodegenerative transmissible spongiform encephalopathies such as creutzfeldt-jakob disease (cjd). prpc is characterized by three helices (h1-h3) and a small antiparallel beta-sheet. one working hypothesis for tse causation is that oligomeric forms of prp are the proximate neurotoxic agents. because these states are transient in character, current experimental studie ... | 2009 | 19371053 |
| 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 ... | 2009 | 19373978 |
| 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 ... | 2009 | 19385058 |
| 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 ... | 2009 | 19386898 |
| 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 ... | 2009 | 19171116 |
| 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 ... | 2009 | 19179038 |
| 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 ... | 2009 | 19188908 |
| 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 ... | 2009 | 19193264 |
| 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 ... | 2009 | 19200012 |
| 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 ... | 2009 | 19200014 |
| highly sensitive, quantitative cell-based assay for prions adsorbed to solid surfaces. | prions are comprised principally of aggregates of a misfolded host protein and cause fatal transmissible neurodegenerative disorders of humans and animals, such as variant creutzfeldt-jakob disease and bovine spongiform encephalopathy. prions pose significant public health concerns, including contamination of blood products and surgical instruments; require laborious and often insensitive animal bioassay to detect; and resist conventional hospital sterilization methods. a major experimental adva ... | 2009 | 19204279 |
| 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 ... | 2009 | 19208228 |
| inoculation of scrapie with the self-assembling rada-peptide disrupts prion accumulation and extends hamster survival. | intracerebral inoculation of 263k scrapie brain homogenate (prpsc) with a self-assembling rada-peptide (rada) significantly delayed disease onset and increased hamster survival. time of survival was dependent on the dose of rada and pre-incubation with prpsc prior to inoculation. rada treatment resulted in the absence of detectable prpsc at 40 d followed by an increased rate of prpsc accumulation at 75 d up to sacrifice. in all prpsc inoculated animals, clinical symptoms were observed approximat ... | 2009 | 19212437 |
| prion protein modulates cellular iron uptake: a novel function with implications for prion disease pathogenesis. | converging evidence leaves little doubt that a change in the conformation of prion protein (prp(c)) from a mainly alpha-helical to a beta-sheet rich prp-scrapie (prp(sc)) form is the main event responsible for prion disease associated neurotoxicity. however, neither the mechanism of toxicity by prp(sc), nor the normal function of prp(c) is entirely clear. recent reports suggest that imbalance of iron homeostasis is a common feature of prion infected cells and mouse models, implicating redox-iron ... | 2009 | 19212444 |
| 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 ... | 2009 | 19214206 |
| 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 ... | 2009 | 19217677 |
| 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 ... | 2009 | 19218224 |
| 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 ... | 2009 | 19218225 |
| unswitched immunoglobulin m response prolongs mouse survival in prion disease. | several studies have failed to demonstrate the presence of immune responses to infectious prions during the course of prion disease, reflecting the identical primary structure of normal and disease-associated isoforms and the widespread expression of the normal cellular form of prion protein, prp(c), leading to b- and/or t-cell tolerance of disease-associated isoforms and also possibly because antigen-presenting cells are unable to process the highly aggregated, detergent-insoluble, protease-res ... | 2009 | 19218226 |
| the propagation of hamster-adapted scrapie prpsc can be enhanced by reduced pyridine nucleotide in vitro. | transmissible spongiform encephalopathies (tses), or prion diseases, are fatal neurodegenerative disorders caused by an infectious agent termed a prion, which can convert normal cellular prion protein (prp(c)) into a pathologically misfolded isoform (prp(sc)). taking advantage of protein misfolding cyclic amplification (pmca), a series of experiments was conducted to investigate the possible influences of pyridine nucleotides on the propagation activities of hamster-adapted scrapie agents 263k a ... | 2009 | 19220459 |
| 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 ... | 2009 | 19220930 |
| 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 ... | 2009 | 19221431 |
| 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 ... | 2009 | 19223486 |
| 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 ... | 2009 | 19223590 |
| 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 ... | 2009 | 19225008 |
| 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 ... | 2009 | 19229533 |
| investigation of the effect of glycosylation on human prion protein by molecular dynamics. | prion protein conformational isomerization, prp(c)-->prp(sc), has been attributed as the cause of tse diseases such as mad-cow disease. the mechanism of such isomerization, however, is little known due the experimental difficulties in studying the scrapie form. among factors that affect prp isomerization, the role which glycosylation plays remains vague. the number of innumerous glycan species, together with their high flexibility, leads to ineffective structural characterization. in this resear ... | 2009 | 19236103 |
| doppel gene polymorphisms in portuguese sheep breeds: insights on ram fertility. | transgenic knockout of the gene encoding the prion-like protein doppel leads to male infertility in mice. the precise role of doppel in male fertility is still unclear, but sperm from doppel-deficient mice appear to be unable to undergo the normal acrosome reaction necessary to penetrate the zona pellucida of the oocyte. the objective of this study was to characterize doppel (prnd) gene polymorphisms in eight portuguese sheep breeds and to determine a possible relationship between these polymorp ... | 2009 | 19028030 |
| a dynamic deterministic model to optimize a multiple-trait selection scheme. | a mathematical approach was developed to model and optimize simultaneous selection on 2 traits, a quantitative trait with underlying polygenic variation and a monogenic trait (e.g., resistance to a disease). a deterministic model allows global optimization of the selection scheme to maximize the frequency of the desired genotype for the monogenic trait, while minimizing the loss of genetic progress on the polygenic trait. an additive qtl or gene was considered. breeding programs with overlapping ... | 2009 | 19028846 |
| photocatalytic degradation of prions using the photo-fenton reagent. | prions are proteinaceous infectious agents postulated to be the causative agents of a group of fatal neurodegenerative diseases known as transmissible spongiform encephalopathies (tses). a known iatrogenic transmission route of tses to humans occurs via prion-contaminated surgical instruments or biological materials. prions, unlike most common pathogens, exhibit an extraordinary resistance to conventional decontamination procedures. we have recently demonstrated that the application of tio(2)-ba ... | 2009 | 19013681 |
| variety of antiprion compounds discovered through an in silico screen based on cellular-form prion protein structure: correlation between antiprion activity and binding affinity. | transmissible spongiform encephalopathies are associated with the conformational conversion of the prion protein from the cellular form (prp(c)) to the scrapie form. this process could be disrupted by stabilizing the prp(c) conformation, using a specific ligand identified as a chemical chaperone. to discover such compounds, we employed an in silico screen that was based on the nuclear magnetic resonance structure of prp(c). in combination, we performed ex vivo screening using the fukuoka-1 strai ... | 2009 | 19015328 |
| concentration of disease-associated prion protein with silicon dioxide. | reagents that can precipitate the disease-associated prion protein (prp(sc)) are vital for the development of high sensitivity tests to detect low levels of this disease marker in biological material. here, a range of minerals are shown to precipitate both ovine cellular prion protein (prp(c)) and ovine scrapie prp(sc). the precipitation of prion protein with silicon dioxide is unaffected by prp(sc) strain or host species and the method can be used to precipitate bovine bse. this method can reli ... | 2009 | 19058035 |
| differential expression of prnp and sprn in scrapie infected sheep also reveals prnp genotype specific differences. | the central role for prp in the pathogenesis of the transmissible spongiform encephalopathies (tses) is illustrated by the resistance of prnp(0/0) mice to disease and by the inverse association of prnp gene dosage with incubation period. understanding the role of prp(c) in tses necessitates knowledge of expression levels of the prnp gene during the development of disease. ssbp/1 scrapie shows a defined pattern of disease progression and here we show that prnp and shadow of prp (sprn) are differe ... | 2009 | 19070601 |
| 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 ... | 2009 | 19072552 |
| strain-specific viral properties of variant creutzfeldt-jakob disease (vcjd) are encoded by the agent and not by host prion protein. | human cjd, endemic sheep scrapie, epidemic bovine spongiform encephalopathy (bse), and other transmissible spongiform encephalopathies (tses), are caused by a group of related but molecularly uncharacterized infectious agents. the uk-bse agent infected many species, including humans where it causes variant cjd (vcjd). as in most viral infections, different tse disease phenotypes are determined by both the agent strain and the host species. tse strains are most reliably classified by incubation t ... | 2009 | 19097123 |
| 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 ... | 2009 | 19098230 |
| 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 ... | 2009 | 19088298 |
| 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 ... | 2009 | 19103159 |
| 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 ... | 2009 | 19107494 |
| serial passage of sheep scrapie inoculum in suffolk sheep. | scrapie is a naturally occurring fatal neurodegenerative disease of sheep and goats. susceptibility to the disease is partly dependent upon the genetic makeup of the host. in a recent study, it was shown that sheep intracerebrally inoculated with a us scrapie agent (no. 13-7) developed scrapie and survived for an average of 19 months post inoculation. in the present study, when this scrapie inoculum was further passaged for 3 successive generations, the survival time was reduced by approximately ... | 2009 | 19112113 |
| 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 ... | 2009 | 19112116 |
| evaluation of immunohistochemical detection of prion protein in rectoanal mucosa-associated lymphoid tissue for diagnosis of scrapie in sheep. | to determine the suitability and estimate the sensitivity of an immunohistochemical (ihc) test for disease-associated prion protein (prp(sc)) in biopsy specimens of rectoanal mucosa-associated lymphoid tissue (ramalt) for diagnosis of scrapie in sheep. | 2009 | 19119950 |
| prion variants and species barriers among saccharomyces ure2 proteins. | as hamster scrapie cannot infect mice, due to sequence differences in their prp proteins, we find "species barriers" to transmission of the [ure3] prion in saccharomyces cerevisiae among ure2 proteins of s. cerevisiae, paradoxus, bayanus, cariocanus, and mikatae on the basis of differences among their ure2p prion domain sequences. the rapid variation of the n-terminal ure2p prion domains results in protection against the detrimental effects of infection by a prion, just as the prp residue 129 me ... | 2009 | 19124570 |
| within-holding prevalence of sheep classical scrapie in great britain. | data from the compulsory scrapie flocks scheme (csfs), part of the compulsory eradication measures for the control of scrapie in the eu, have been used to estimate the within-holding prevalence of classical scrapie in great britain (gb). specifically data from one of the testing routes within the csfs have been used; the initial cull (ic), whereby two options can be applied: the whole flock cull option by which the entire flock is depopulated, and the genotyping and cull of certain genotypes. | 2009 | 19133119 |
| experimental oral transmission of united states origin scrapie to neonatal sheep. | scrapie, a transmissible spongiform encephalopathy (tse), is a naturally occurring fatal neurodegenerative disease of sheep and goats. the current study documents incubation periods, pathologic findings, and distribution of abnormal prion proteins (prp(sc)) by immunohistochemistry and western blot in tissues of genetically susceptible and resistant neonatal lambs inoculated with pooled brain homogenates from 13 u.s. origin scrapie-affected ewes. nine suffolk lambs with genotypes aa/rr/qq (n = 5) ... | 2009 | 19139503 |
| field performance of two rapid screening tests in active surveillance of transmissible spongiform encephalopathies in small ruminants. | recently, screening tests for monitoring the prevalence of transmissible spongiform encephalopathies specifically in sheep and goats became available. although most countries require comprehensive test validation prior to approval, little is known about their performance under normal operating conditions. switzerland was one of the first countries to implement 2 of these tests, an enzyme-linked immunosorbent assay (elisa) and a western blot, in a 1-year active surveillance program. slaughtered a ... | 2009 | 19139507 |
| scrapie pathogenesis: the role of complement c1q in scrapie agent uptake by conventional dendritic cells. | mice lacking complement components show delayed development of prion disease following peripheral inoculation. the delay could relate to reduced scrapie prion protein (prp(sc)) accumulation on follicular dendritic cells (dcs). however conventional dcs (cdcs) play a crucial role in the early pathogenesis of prion diseases and complement deficiency could result in decreased prp(sc) uptake by cdcs in the periphery. to explore this possibility, we cultured murine splenic or gut-associated lymph node ... | 2009 | 19155476 |
| 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 ... | 2009 | 19157728 |
| 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 ... | 2009 | 19158242 |
| 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 ... | 2009 | 19162101 |
| transmission dynamics and mechanisms of endemicity of scrapie in the uk sheep population. | summaryscrapie is a fatal neurological disease of sheep which is endemic in the united kingdom. it is one of the family of transmissible spongiform encephalopathies (tses) that includes bse. in this paper, we developed a micro-simulation model for scrapie in the uk sheep population, incorporating the genetic and structural diversity of the population and infectious contact between flocks through trading. the simulation was fitted to epidemiological data from a range of sources. we found a detect ... | 2009 | 18687155 |
| control of scrapie in the uk sheep population. | scrapie is a fatal transmissible spongiform encephalopathy (tse) of sheep, endemic in the uk for centuries. interest in the disease has been heightened over the last decade by the possibility of the related bse being transmissible to and between sheep and a range of control interventions has been proposed and implemented. in this paper, we examined the effect of these policies and their components on observed case rate, susceptible allele frequency and r0 within the framework of a large simulati ... | 2009 | 18687157 |
| production of prnp -/- goats by gene targeting in adult fibroblasts. | homozygous mice devoid of functional prnp are resistant to scrapie and prion propagation, but heterozygous mice for prnp disruption still suffer from prion disease and prion deposition. we have previously generated heterozygous cloned goats with one allele of prnp functional disruption. to obtain goats with both alleles of prnp be disrupted which would be resistant to scrapie completely, a second-round gene targeting was applied to disrupt the wild type allele of prnp in the heterozygous goats. ... | 2009 | 18821027 |
| 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 ... | 2009 | 18824519 |
| 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 ... | 2009 | 18828985 |
| 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 ... | 2009 | 18834644 |
| [newly discovered forms of prion diseases in ruminants]. | transmissible spongiform encephalopathies (tses), are fatal neurodegenerative diseases caused by unconventional agents, the prions. they are characterised by the accumulation in infected tissues of an abnormally folded form of the host-encoded prion protein (prp). this pathological form is partially resistant to protease digestion, leading to the production of so-called prp(res) fragments. different isolates from the same host species may show different eletrophoretic profiles, reflecting the ex ... | 2009 | 18848406 |
| 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- ... | 2009 | 18973796 |
| 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 ... | 2009 | 19000036 |
| repetitive immunization enhances the susceptibility of mice to peripherally administered prions. | the susceptibility of humans and animals to prion infections is determined by the virulence of the infectious agent, by genetic modifiers, and by hitherto unknown host and environmental risk factors. while little is known about the latter two, the activation state of the immune system was surmised to influence prion susceptibility. here we administered prions to mice that were repeatedly immunized by two initial injections of cpg oligodeoxynucleotides followed by repeated injections of bovine se ... | 2009 | 19779609 |
| prp genotype: a flock-level risk factor for scrapie? | previous epidemiological studies of risk factors for classical scrapie at flock level have identified a variety of management and purchase related variables, along with increased flock size and, in some cases, breed effects. although known as a risk factor at the individual animal level, prp genotype frequencies at flock level have not yet been studied. in an unmatched case-control study, three measures of flock-level prion protein (prp) frequency estimates were investigated with respect to the ... | 2009 | 19783057 |
| the effects of host age on follicular dendritic cell status dramatically impair scrapie agent neuroinvasion in aged mice. | following peripheral exposure, many transmissible spongiform encephalopathy (tse) agents accumulate first in lymphoid tissues before spreading to the cns (termed neuroinvasion) where they cause neurodegeneration. early tse agent accumulation upon follicular dendritic cells (fdcs) in lymphoid follicles appears critical for efficient neuroinvasion. most clinical cases of variant creutzfeldt-jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptib ... | 2009 | 19786551 |
| the role of the prion protein membrane anchor in prion infection. | normal cellular and abnormal disease-associated forms of prion protein (prp) contain a c-terminal glycophosphatidyl-inositol (gpi) membrane anchor. the importance of the gpi membrane anchor in prion diseases is unclear but there are data to suggest that it both is and is not required for abnormal prion protein formation and prion infection. utilizing an in vitro model of prion infection we have recently demonstrated that, while the gpi anchor is not essential for the formation of abnormal prion ... | 2009 | 19786843 |
| visual pathology in animal prion diseases. | prion diseases, also known as the transmissible spongiform encephalopathies (tses), are a group of slowly developing neurodegenerations occurring in human and animals. prion diseases can be transferred between animals, humans, from humans to animals, and from animals to humans. as a result, the central nervous system is attacked, resulting in microglia activation, astrocytosis, prion plaque deposition, and neuronal degeneration. prion also targets on the eye and brain visual system. in scrapie-i ... | 2009 | 19795355 |
| co-existence of scrapie prion protein types 1 and 2 in sporadic creutzfeldt-jakob disease: its effect on the phenotype and prion-type characteristics. | five phenotypically distinct subtypes have been identified in sporadic creutzfeldt-jakob disease (scjd), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (prp) gene and the presence of either one of the two protease k-resistant scrapie prion protein (prp(sc)) types identified as 1 and 2. the infrequent co-existence of both prp(sc) types in the same case has been known for a long time. recently, it has been reported, using type-specific antibodies, that the pr ... | 2009 | 19734292 |
| classical sheep scrapie in great britain: spatial analysis and identification of environmental and farm-related risk factors. | previous studies suggest that the spatial distribution of classical sheep scrapie in great britain is uneven and that certain flock characteristics may be associated with occurrence of the disease. however, the existence of areas of high and low disease-risk may also result from differences in the spatial distribution of environmental characteristics. in this study we explored the spatial pattern of classical scrapie in great britain between 2002 and 2005 and investigated the association between ... | 2009 | 19737376 |
| two adjacent nuclear factor-binding domains activate expression from the human prnp promoter. | the transmissible spongiform encephalopathies (tses) comprise a group of fatal degenerative neurological diseases in humans and other mammals. after infection, the cellular prion protein isoform prpc is converted to the pathological prpsc scrapie isoform. the continued conversion of prpc to prpsc requires de novo endogenous prp synthesis for disease progression. the human prion protein gene (prnp) promoter was therefore investigated to identify regulatory elements that could serve as targets for ... | 2009 | 19740434 |
| detection of prpsc in blood from sheep infected with the scrapie and bovine spongiform encephalopathy agents. | the role of blood in the iatrogenic transmission of transmissible spongiform encephalopathy (tse) or prion disease has become an increasing concern since the reports of variant creutzfeldt-jakob disease (vcjd) transmission through blood transfusion from humans with subclinical infection. the development of highly sensitive rapid assays to screen for prion infection in blood is of high priority in order to facilitate the prevention of transmission via blood and blood products. in the present stud ... | 2009 | 19740979 |
| asymptomatic deer excrete infectious prions in faeces. | infectious prion diseases-scrapie of sheep and chronic wasting disease (cwd) of several species in the deer family-are transmitted naturally within affected host populations. although several possible sources of contagion have been identified in excretions and secretions from symptomatic animals, the biological importance of these sources in sustaining epidemics remains unclear. here we show that asymptomatic cwd-infected mule deer (odocoileus hemionus) excrete cwd prions in their faeces long be ... | 2009 | 19741608 |