A soluble, oligomeric beta-sheet-rich conformational variant of recombinant full-length prion protein, PrP beta, was generated that aggregates into amyloid fibrils, PrP betaf. These fibrils have physico-chemical and structural properties closely similar to those of pathogenic PrP Sc in scrapie-associated fibrils and prion rods, including a closely similar proteinase K digestion pattern and Congo red birefringence. The conformational transition from PrP C to PrP beta occurs at pH 5.0 in bicellar solutions containing equimolar mixtures of dihexanoyl-phosphocholine and dimyristoyl-phospholipids, and a small percentage of negatively charged dimyristoyl-phosphoserine. The same protocol was applicable to human, cow, elk, pig, dog and mouse PrP. Comparison of full-length hPrP 23-230 with the N-terminally truncated human PrP fragments hPrP 90-230, hPrP 96-230, hPrP 105-230 and hPrP 121-230 showed that the flexible peptide segment 105-120 must be present for the generation of PrP beta. Dimerization of ...
Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major prion protein, prion-related protein, CJD, GSS, ASCR, KURU, PRIP, PrPc, CD230, AltPrP, p27-30, PrP27-30, and ...
Prion protein (PrP) is a membrane glycosylphosphatidylinositol (GPI)-anchored glycoprotein that is encoded by the PRNP gene and is highly conserved among mammals. PrP contains an unstable region consisting of five octapeptide repeats; mutations in this region are associated with Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru (a type of transmissible spongiform encephalopathy, TSE). The function of PrP is not clear, although it is known to bind copper ions. PrP exists as a normal cellular isoform (PrPC) that can undergo refolding to a conformational isoform known as scrapie isoform (PrPSc). PrPSc forms compact aggregates that are highly resistant to proteolysis. The conversion of PrPC to PrPSc is postulated to be the mechanism involved in transmission of TSEs. PrP is also known as prion protein (p27-30); major prion protein, prion-related protein, CJD, GSS, ASCR, KURU, PRIP, PrPc, CD230, AltPrP, p27-30, PrP27-30, and ...
Prion rods, i.e. insoluble infectious aggregates of the N-terminally truncated form of the prion protein, PrP 27-30, and the corresponding recombinant protein, rPrP(90-231), were autoclaved in water, bovine lipid or lipid-water mixtures for 20 min at temperatures from 100 to 170 °C. A protocol was developed for the quantitative precipitation of small amounts of protein from large excesses of lipid. PrP remaining undegraded after autoclaving was quantified by Western blot and degradation factors were calculated. The Arrhenius plot of the rate of degradation vs temperature yielded linear relationships for prion rods in water or lipid-water as well as for rPrP(90-231) in lipid-water. The presence of lipids increased the heat stability of prion rods, especially at lower temperatures. Prion rods had a much higher thermal stability compared to rPrP. Autoclaving of prion rods in pure lipid gave different results - not simple degradation but bands indicative of covalently linked dimers, tetramers and higher
Prion diseases are fatal and incurable neurodegenerative diseases of humans and animals. Despite years of research, no therapeutic agents have been developed that can effectively manage or reverse disease progression. Recently it has been identified that recombinant prion proteins (rPrP) expressed in bacteria can act as inhibitors of prion replication within the in vitro prion replication system Protein Misfolding Cyclic Amplification (PMCA). Here, within PMCA reactions amplifying a range of ruminant prions including distinct Prnp genotypes/host species and distinct prion strains, recombinant ovine VRQ PrP displayed consistent inhibition of prion replication and produced IC50 values of 122 and 171 nM for ovine scrapie and bovine BSE replication, respectively. These findings illustrate the therapeutic potential of rPrPs with distinct TSE diseases.. ...
Define transmissible neurodegenerative disease. transmissible neurodegenerative disease synonyms, transmissible neurodegenerative disease pronunciation, transmissible neurodegenerative disease translation, English dictionary definition of transmissible neurodegenerative disease. n. 1. An abnormal condition of a part, organ, or system of an organism resulting from various causes, such as infection, inflammation, environmental...
Prion protein is the causative agent of the transmissible spongiform encephalopathies. According to the prion hypothesis, the infectious isoform of prion protein, termed PrPSc, replicates by interacting with cellular PrPC and mediating its conformational change into the disease-causing PrPSc (19). Compared with its well-defined pathological significance, the physiological function of PrPC remains unclear. PrPC is highly expressed not only by cells in the CNS but also by follicular DCs, mature myeloid cells, and activated T cells. This distribution suggests involvement of PrPC in immune surveillance (20).. Our present study defines a novel role for PrPC as an M-cell receptor for the uptake of pathogenic bacteria. PrPC on macrophages has been reported to recognize surface-exposed Hsp60 of B. abortus and to facilitate internalization of the bacteria (13); however, Fontes et al. (21) reported a contradictory result. Using Prnp−/− mice, they showed that B. suis infection is independent of PrPC ...
1. Vaccination-induced anti-prion protein antibodies are presently regarded as a promising approach toward treatment of prion diseases. Here, we investigated the ability of five peptides corresponding to three different regions of the bovine prion protein (PrP) to elicit antibodies interfering with PrP(Sc) propagation in prion-infected cells.2. Rabbits were immunized with free nonconjugated peptides. Obtained immune sera were tested in enzyme-linked immunosorbent assay (ELISA) and immunoblot for their binding to recombinant PrP and cell-derived pathogenic isoform (PrP(Sc)) and normal prion protein (PrP(c)), respectively. Sera positive in all tests were chosen for PrP(Sc) inhibition studies in cell culture.3. All peptides induced anti-peptide antibodies, most of them reacting with recombinant PrP. Moreover, addition of the serum specific to peptide 95-123 led to a transient reduction of PrP(Sc) levels in persistently prion-infected cells.4. Thus, anti-PrP antibodies interfering with PrP(Sc) ...
Background Imbalance of iron homeostasis has been reported in sporadic Creutzfeldt-Jakob-disease (sCJD) affected human and scrapie infected animal brains, but the contribution of this phenotype to disease associated neurotoxicity is unclear. Methodology/Principal Findings Using cell models of familial prion disorders, we demonstrate that exposure of cells expressing normal prion protein (PrPC) or mutant PrP forms to a source of redox-iron induces aggregation of PrPC and specific mutant PrP forms. Initially this response is cytoprotective, but becomes increasingly toxic with time due to accumulation of PrP-ferritin aggregates. Mutant PrP forms that do not aggregate are not cytoprotective, and cells show signs of acute toxicity. Intracellular PrP-ferritin aggregates induce the expression of LC3-II, indicating stimulation of autophagy in these cells. Similar observations are noted in sCJD and scrapie infected hamster brains, lending credence to these results. Furthermore, phagocytosis of PrP-ferritin
Prions are the enigmatic etiological agents of transmissible spongiform encephalopathies (TSEs), a class of fatal neurodegenerative diseases affecting humans and other mammals. The pathogenic prion protein is a misfolded form of the host-encoded prion protein and represents the predominant, if not sole, component of the infectious agent. Environmental routes of TSE transmission are implicated in epizootics of sheep scrapie and chronic wasting disease of deer, elk, and moose. Soil is the most plausible candidate for preserving prion infectivity in the environment. We have investigated prion attachment to and detachment from inorganic and organic soil particle surfaces and examined the effect of association with specific soil constituents on disease transmission. Interaction of prions with some phyllosilicate mineral surfaces is remarkably strong. Interestingly, rather than diminishing bioavailability, attachment to such particles enhances disease transmission. This finding suggests an explanation ...
Both prion protein and the structurally homologous protein doppel are associated with neurodegenerative disease by mechanisms which remain elusive. We have prepared murine doppel, and a mutant with one of the two disulphide bonds removed, in the expectation of increasing the similarity of doppel to prion protein in terms of conformation and stability. Unfolding studies of doppel and the mutant have been performed using far-UV CD over a range of solution conditions known to favour the α→β transformation of recombinant prion protein. Only partial unfolding of doppel or the mutant occurs at elevated temperature, but both exhibit full and reversible unfolding in chemical denaturation with urea. Doppel is significantly less stable than prion protein, and this stability is further reduced by removal of the disulphide bond between residues 95-148. Both doppel and the mutant are observed to unfold by a two-state mechanism, even under the mildly acidic conditions where prion protein forms an ...
Following intracerebral or peripheral inoculation of mice with scrapie prions, infectivity accumulates first in the spleen and only later in the brain. In the spleen of scrapie-infected mice, prions were found in association with T and B lymphocytes and to a somewhat lesser degree with the stroma, which contains the follicular dendritic cells (FDCs) but not with non-B, non-T cells; strikingly, no infectivity was found in lymphocytes from blood of the same mice. Transgenic PrP knockout mice expressing PrP restricted to either B or T lymphocytes show no prion replication in the lymphoreticular system. Therefore, splenic lymphocytes either acquire prions from another source or replicate them in dependency on other PrP-expressing cells. The essential role of FDCs in prion replication in spleen was shown by treating mice with soluble lymphotoxin-β receptor, which led to disappearance of mature FDCs from the spleen and concomitantly abolished splenic prion accumulation and retarded neuroinvasion ...
Conformational intermediates of the human prion protein huPrPC were characterized by a combination of hydrostatic pressure (up to 200 MPa) with two-dimensional NMR spectroscopy. All pressure effects showed to be reversible and there is virtually no difference in the overall pressure response between the folded core of the N-terminal truncated huPrPC(121-230) and the full-length huPrPC(23-230). The only significant differences in the pressure response of full-length and truncated PrP suggest that E168, H187, T192, E207, E211 and Y226 are involved in a transient interaction with the unfolded N-terminus. High-pressure NMR spectroscopy indicates that the folded core of the human prion protein occurs in two structural states N1and N2 in solution associated with rather small differences in free enthalpies (3.0 kJ/mol). At atmospheric pressure approximately 29% of the protein are already in the pressure favored conformation N2. There is a second process representing two possible folding intermediates ...
Single nucleotide polymorphisms (SNPs) and haplotype alleles within the prion gene (PRNP) coding sequence of domestic sheep (Ovis aries) are associated with genetic predisposition to scrapie, a transmissible spongiform encephalopathy disease of sheep. This report describes regions of linkage disequilibrium (LD) throughout the PRNP gene region in U.S. sheep and provides a genetic framework for identifying additional PRNP determinants associated with scrapie resistance. Four sequence tagged sites (i.e., STS or amplicons) totaling 3869 bp and spanning 20 kbp of genomic PRNP sequence were sequenced in a diverse panel of 90 sires representing ten popular U.S. breeds of sheep. Analysis of these sequences identified 36 previously unreported polymorphisms. In combination with two previously characterized STS, 62 polymorphisms were analyzed in a 20-kbp PRNP region in this panel of U.S. sheep. Two regions of strong LD and ten common haplotypes were identified. The haplotype encoding amino acid residues A, R, and
Conversion of prion protein (PrP) to an altered conformer, the scrapie PrP (PrPSc), is a critical step in the development of transmissible spongiform encephalopathies. Both Cu(II) and nucleic acid molecules have been implicated in this conversion. Full-length PrP can bind up to six copper ions; four Cu(II) binding sites are located in the octarepeat domain (residues 60-91), and His-96 and His-111 coordinate two additional copper ions. Experimental evidence shows that PrP binds different molecules, resulting in diverse cellular signaling events. However, there is little information about the interaction of macromolecular ligands with Cu(II)-bound PrP. Both RNA and DNA sequences can bind PrP, and this interaction results in reciprocal conformational changes. Here, we investigated the interaction of Cu(II) and nucleic acids with amyloidogenic non-octarepeat PrP peptide models (comprising human PrP residues 106-126 and hamster PrP residues 109-149) that retain His-111 as the copper-anchoring residue. The
Zanusso, G; Liu, D; Ferrari, S; Hegyi, I; Yin, X; Aguzzi, A; Hornemann, S; Liemann, S; Glockshuber, R; Manson, J C; Brown, P; Petersen, R B; Gambetti, P; Sy, M S (1998). Prion protein expression in different species: analysis with a panel of new mAbs. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 95(15):8812-8816.. Raeber, A J; Race, R E; Brandner, S; Priola, S A; Sailer, A; Bessen, R A; Mucke, L; Manson, J C; Aguzzi, A; Oldstone, M B; Weissmann, C; Chesebro, B (1997). Astrocyte-specific expression of hamster prion protein (PrP) renders PrP knockout mice susceptible to hamster scrapie. EMBO Journal, 16(20):6057-6065.. ...
23284 Comment by Andrea LeBlanc: This interesting paper shows that quite a few of the disease-associated human prion mutations actually switch to the normal Doppel sequence. The doppel (i.e., doppelgaenger) gene is downstream of the PrP gene. Its protein resembles amino-terminally truncated PrP and interacts with PrP.) Doppel overexpression is neurotoxic. Therefore, the switch of PrP into a Doppel-like protein could indicate that Doppel and mutant PrP are neurotoxic through a similar mechanism. However, it remains to be seen if these mutant PrPs are neurotoxic or not.. Our work has focused on the function of normal prion protein in primary human neurons. I suspected a function for prion protein in cell death or cell survival because of some similarity between the BH2 domain of Bcl-2 proteins and the octapeptide repeat of prion protein. While we now know that PrP is not a member of the Bcl-2 family of proteins, it is, however, a strong neuroprotective agent against Bax-mediated cell death. We ...
Team:Valencia/head}} ,div id=HomeCenter> ,div id=Titulos> Regulating Mars temperature ,br> ,br> using a prion switch ,/div> ,br> ==Prions== In 1982 Stanley B. Prusiner created the term prion (or proteinacius infectious particle) to name the exclusively proteic infectious agent responsible of the transmissible spongiform encephalopathies (TSEs), a group of mammalian neurodegenerative disorders. According to the widely supported protein-only model, the prion mechanism of transmissibility arise from the ability of the prion form of the protein to promote the conformational change of the normal cellular form to the infectious prion forms (Prusiner, 1998). The infectious forms are mis-folded proteins that induce by polymerization the formation of an amyloid fold constituted by tightly packed beta sheets. These aggregates are insoluble fibrils that display resistance to proteolytic digestion and have affinity for aromatic dyes. ===Fungal prions=== In 1994 Reed Wickner proposed the prion nature ...
TY - JOUR. T1 - Structure-based view on [PSI+] prion properties. AU - Bondarev, S.A.. AU - Zhouravleva, G.A.. AU - Belousov, M.V.. AU - Kajava, A.V.. PY - 2015. Y1 - 2015. N2 - Yeast [PSI+] prion is one of the most suitable and well characterized system for the investigation of the prion phenomenon. However, until recently, the lack of data on the 3D arrangement of Sup35p prion fibrils hindered progress in this area. The recent arrival in this field of new experimental techniques led to the parallel and in-register superpleated β-structure as a consensus model for Sup35p fibrils. Here, we analyzed the effect of amino acid substitutions of the Sup35 protein through the prism of this structural model. Application of a newly developed computational approach, called ArchCandy, gives us a better understanding of the effect caused by mutations on the fibril forming potential of Sup35 protein. This bioinformatics tool can be used for the design of new mutations with desired modification of prion ...
Phenotypic heterogeneity of sCJD parallels that of animal prion diseases such as scrapie or transmissible mink encephalopathy. In these diseases, phenotypic variation has been related to both variation of the agent strain and host genetic factors-namely, thePRNP genotype.4 5 Prion strains are distinguishable by the neuropathology they produce, the regional pattern of intracerebral PrP-res accumulation, and, to some extent, by differing physicochemical properties of PrP-res, such as size and glycoform ratio of the protein.4-8 These signatures are reproducible and characteristic of a given strain when examined within syngenic hosts,4-8 but they may change after transmission to hosts with a different PRNPgenotype.5 9 Four distinct clinicopathological variants of sCJD have been recently identified in a series of 19 patients.2 The typical CJD phenotype (myoclonic variant) and the Heidenhain variant were linked to MM at codon 129 and to PrP-res type 1. The ataxic variant and the variant with kuru ...
In this study, we characterized the biochemical properties of a set of chimeric prion proteins wherein the ORD of Sup35p was replaced with that of PrP. The chimeric prion proteins were created by substituting the endogenous Sup35p ORD with the repeat domain of PrP containing five, eight, 11 and 14 oligopeptide repeats [40]. The repeat-expanded proteins show a remarkable set of properties that highlight their enhanced ability to aggregate and form amyloid fibers in vitro. These data agree with work done by others in which recombinant PrP (rPrP) with ORD expansions exhibit an enhanced ability to form amyloid fibers with increasing number of repeats [20, 46]. Our data also support previous work done with transgenic mice (Tg(PG14)) that express PrP harboring nine additional octapeptide repeats. These mice manifest a spontaneous form of prion disease [21]. Although the spontaneous form of the disease in the Tg(PG14) mice is not infectious, the protein aggregates and the animals display many of the ...
Prion protein 2 (dublet), also known as PRND, or Doppel protein, is a protein which in humans is encoded by the PRND gene. This gene is found on chromosome 20, approximately 20 kbp downstream of the gene encoding cellular prion protein, to which it is biochemically and structurally similar. The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that is found predominantly in testis. Mutations in this gene may lead to neurological disorders. GRCh38: Ensembl release 89: ENSG00000171864 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000098754 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Entrez Gene: PRND prion protein 2 (dublet). Moore RC, Lee IY, Silverman GL, et al. (1999). Ataxia in prion protein (PrP)-deficient mice is associated with upregulation of the novel PrP-like protein doppel. J. Mol. Biol. 292 (4): 797-817. doi:10.1006/jmbi.1999.3108. PMID 10525406. Weissmann C, Aguzzi A (1999). Perspectives: ...
The role of carcinine in signaling at the Drosophila photoreceptor synapse. Gavin BA, Arruda SE, Dolph PJ. PLoS Genet. 2007 Dec;3(12):e206. PMID: 18069895 [PubMed - indexed for MEDLINE]. Accelerated accumulation of misfolded prion protein and spongiform degeneration in a Drosophila model of Gerstmann-Sträussler-Scheinker syndrome. Gavin BA, Dolph MJ, Deleault NR, Geoghegan JC, Khurana V, Feany MB, Dolph PJ, Supattapone S. J Neurosci. 2006 Nov 29;26(48):12408-14. PMID: 17135402 [PubMed - indexed for MEDLINE]. An essential role for endocytosis of rhodopsin through interaction of visual arrestin with the AP-2 adaptor. Orem NR, Xia L, Dolph PJ. J Cell Sci. 2006 Aug 1;119(Pt 15):3141-8. Epub 2006 Jul 11. PMID: 16835270 [PubMed - indexed for MEDLINE]. Molecular cloning of the pawn locus from Drosophila melanogaster. Arruda SE, Dolph PJ. Gene. 2003 May 22;310:169-73. PMID: 12801644 [PubMed - indexed for MEDLINE]. Post-transcriptional suppression of pathogenic prion protein expression in Drosophila ...
Egg candling gadget made by the BE department. An egg candling gadget is used to identify infertile eggs and monitor the development of embryos. Chicken embryos were used for tick research in the yolk sac method ...
The NMR structures of the recombinant human prion protein, hPrP(23-230), and two C-terminal fragments, hPrP(90-230) and hPrP(121-230), include a globular domain extending from residues 125-228, for which a detailed structure was obtained, and an N-terminal flexibly disordered tail. The globular domain contains three alpha-helices comprising the residues 144-154, 173-194, and 200-228 and a short anti-parallel beta-sheet comprising the residues 128-131 and 161-164. Within the globular domain, three polypeptide segments show increased structural disorder: i.e., a loop of residues 167-171, the residues 187-194 at the end of helix 2, and the residues 219-228 in the C-terminal part of helix 3. The local conformational state of the polypeptide segments 187-193 in helix 2 and 219-226 in helix 3 is measurably influenced by the length of the N-terminal tail, with the helical states being most highly populated in hPrP(23-230). When compared with the previously reported structures of the murine and Syrian ...
In the central nervous system, cellular prion proteins are found in astrocytes and neurons. There has been evidence showing that they prolong the survival9 as well as affect the differentiation of these structures. Scientists have found that cellular prions interact with NCAM, neuronal cell adhesion molecules, in astrocytes and this causes neurogenesis. Another role that the cellular prions might be involved in is the differentiation process of neurons. Scientists have found that when the ligand, STI1 (secreted from astrocytes) binds a receptor on the cellular prion glycoprotein membrane, the neurons differentiate. There were much lower levels of neurogenesis in neuron-astrocyte co-cultures, when they did not express the Prnp gene. Furthermore, they suggested that the interaction between cellular prion proteins and STI1 may play a role in protecting against apoptosis, as they have seen in neurons located in the hippocampus and the retina8 . It is likely that there are other molecular factors in ...
Cellular prion protein (PrpC) is a glycoprotein usually associated with membranes via its glycosylphosphatidylinositol (GPI) anchor. The trans-conformational form of this protein (PrpSC) is the suggested agent responsible for transmissible neurodegenerative spongiform encephalopathies. This protein has been shown on sperm and in the reproductive fluids of males. Antibodies directed against the C-terminal sequence near the GPI-anchor site, an N-terminal sequence, and against the whole protein showed that the Prp isoforms were compartmentalized within the reproductive tract of the ram. Immunoblotting with the three antibodies showed that the complete protein and both N- and C-terminally truncated and glycosylated isoforms are present within cauda epididymal fluid and seminal plasma. Moreover, we demonstrate that in these fluids, the PrpC isoforms are both in a soluble state as well as associated with small membranous vesicles (epididymosomes). We also report that only one major glycosylated 25 kDa ...
Cellular prion protein, a membrane protein, is expressed in all mammals. Prion protein is also found in human blood as an anchorless protein, and this protein form is one of the many potential sources of misfolded prion protein replication during transmission. Many studies have suggested that β-amyloid1-42 oligomer causes neurotoxicity associated with Alzheimers disease, which is mediated by the prion protein that acts as a receptor and regulates the hippocampal potentiation. The prevention of the binding of these proteins has been proposed as a possible preventative treatment for Alzheimers disease; therefore, a greater understanding of the binding hot-spots between the two molecules is necessary. In this study, the epitope mapping immunoassay was employed to characterize binding epitopes within the prion protein and complementary epitopes in β-amyloid. Residues 23-39 and 93-119 in the prion protein were involved in binding to β-amyloid1-40 and 1-42, and monomers of this protein interacted ...
1B10: Solution structure of a 142-residue recombinant prion protein corresponding to the infectious fragment of the scrapie isoform.
Elastic and Plastic Strain Properties of Sand. This paper describes the results of tests using conventional triaxial apparatus with loading and unloading, on samples of medium sand with two different unit weights. The method is used to study the elastic and plastic volumetric and axial strains under the conditions of hydrostatic and deviator stress. It is shown that under hydrostatic compression, the elastic volumetric strain of medium sand is always greater than its plastic volumetric strain. The ratio of elastic volumetric strain to plastic volumetric strain may decrease as the hydrostatic pressure increases. Other conclusions are also described.
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Protein-only (prion) epigenetic elements confer unique phenotypes by adopting alternate conformations that specify new traits. Given the conformational flexibility of prion proteins, protein-only inheritance requires efficient self-replication of the underlying conformation. To explore the cellular …
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Huntingtons and Parkinsons diseases are neurodegenerative disorders associated with unusual protein interactions. Although the origin and evolution of these diseases are completely different, characteristic deposits of protein aggregates (huntingti
Activation of phospholipase A2 (PLA2) and the subsequent metabolism of arachidonic acid (AA) to prostaglandins have been shown to play an important role in neuronal death in neurodegenerative disease. Here we report the effects of the prion peptide fragment HuPrP106-126 on the PLA2 cascade in primary cortical neurons and translocation of cPLA2 to neurites. Exposure of primary cortical neurons to HuPrP106-126 increased the levels of phosphorylated cPLA2 and caused phosphorylated cPLA2 to relocate from the cell body to the cellular neurite in a PrP-dependent manner, a previously unreported observation. HuPrP106-126 also induced significant AA release, an indicator of cPLA2 activation; this preceded synapse damage and subsequent cellular death. The novel translocation of p-cPLA2 postulated the potential for exposure to HuPrP106-126 to result in a re-arrangement of the cellular cytoskeleton. However p-cPLA2 did not colocalise significantly with F-actin, intermediate filaments, or microtubule-associated
A proposal by Dr. Harlan Caldwell at the Rocky Mountain Laboratories (RML) involving the deliberate transfer of a tetracycline resistance trait to non-ocular strains of Chlamydia trachomatis has been submitted to the NIH Office of Biotechnology Activities (OBA). The introduction of tetracycline...
Here, we report the development and further characterisation of a novel PrP-specific monoclonal antibody: 2A11. By Western blot analysis, 2A11 reacts with PrPC from a variety of species including cow, sheep, pig, hamster, rabbit, cat, dog, deer and mouse but fails to react with human, chicken and turtle PrP. Reactivity to PrPC in Western blot was found to be dependent on the redox state of the protein since binding of mAb 2A11 to its epitope was more effective in reducing conditions. 2A11 binding site was mapped within a region comprised by residues 171-179 (six octarepeats bovine PrP notation; 163-171 for the ovine PrP notation). Interestingly, in immunohistochemistry (IHC) analysis, immunoreactivity was greatly enhanced after proteinase K (PK) sample treatment, while little or no reaction was observed in non-PK-treated BSE samples and samples from healthy animals. Quantitative differences in reactivity to BSE prions after PK treatment were also observed, to a lesser extent, by Western blot ...
Inserting genes from psychrophilic, or cold-loving, bacteria, into bacterial pathogens could prove a cool new way for developing vaccines, according to microbiologist Francis Nano at the University of Victoria, British Columbia, Canada, and his collaborators there and at the Rocky Mountain Laboratories in Hamilton, Mont. Under control of genes from psychrophiles, the pathogens grow only at relatively low temperatures but not at 37°C. Thus, the modified bacteria
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
While prions can be thought of like a disease, that is not a good description. Prions are just misfolded proteins, that can make similar proteins misfold as well.. To understand what this means, proteins can be compared to hundreds of springs attached together in a large blanket of springs. Some of the springs are extension springs, and some are contraction springs. To execute its function, a protein will fold up this blanket of springs into a ball.. And it will fold up exactly the same way every time.. But a prion is a mistake in the folding up process. If it folds up incorrectly, the protein does not work. And to make matters worse, it can tell other proteins of its type to fold up incorrectly as well.. Importantly, priors happen constantly in our bodies, and just as constantly, they are destroyed by our bodies. But infectious prions are not *recognized* as prions by our bodies, so they are not destroyed, and can try to tell all the other proteins like them to misfold as well. And once you ...
Fingerprint Dive into the research topics of A dominant-negative mutant inhibits multiple prion variants through a common mechanism. Together they form a unique fingerprint. ...
The properties of this strain that contribute to its usefulness as a cloning strain are described below. The genotypes underlying these properties appear in parentheses.
The properties of this strain that contribute to its usefulness as a cloning strain are described below. The genotypes underlying these properties appear in parentheses.
WEDNESDAY, MAY 17, 2017 CWD, TSE, PRION, Cattle, Pigs, Sheep, and Humans aka Mad Cow Disease http://chronic-wasting-disease.blogspot.com/2017/05/cwd-tse-prion-cattle-pigs-sheep-and.html kind regards, terry
The demonstration of prion secretion in sheep in a variety of matrices including milk (Maddison et al. (2009) J. Virol. 83:8293-8296), saliva (Maddison et al. (2010) J. Inf. Dis. 201:1672-1676.) and faeces (Terry et al. (2011) Vet. Res. 42:65). Excretion/secretion occurs through long asymptomatic periods of disease development and from sheep with a range of PRNP genotypes, including those with limited lymphoreticular involvement in prion replication (Gough et al. (2011) J. Virol. 86:566-571 ...
Mechanism of PrP-mediated myopathy. Accumulation of an N-terminal truncated PrP C1 fragment in muscle activates p53 resulting in the induction of p53-regulated
Abskharon, R. N. N., G. Giachin, A. Wohlkonig, S. H. Soror, E. Pardon, G. Legname, and J. Steyaert, Probing the N-terminal β-sheet conversion in the crystal structure of the human prion protein bound to a nanobody., J Am Chem Soc, vol. 136, issue 3, pp. 937-44, 2014 Jan 22. ...
For example, people use terms like ввdirectionality,вв ввblobbiness,вв ввrandomness,вв and so on. System suitability в resolution minimum of 5.
View Prnp/Prnp Tg(Prnp*D177N*M128V)A21Rchi/Tg(Prnp*D177N*M128V)A21Rchi involves: 129S7/SvEvBrd * C57BL/6 * CBA: phenotypes, images, diseases, and references.
In a new study NYU School of Medicine researchers report that they have found several chemical compounds, including an antidepressant, that have powerful effects against brain-destroying prion infections in mice, opening ...