Prion Diseases: A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)PrPSc Proteins: Abnormal isoform of prion proteins (PRIONS) resulting from a posttranslational modification of the cellular prion protein (PRPC PROTEINS). PrPSc are disease-specific proteins seen in certain human and animal neurodegenerative diseases (PRION DISEASES).Scrapie: A fatal disease of the nervous system in sheep and goats, characterized by pruritus, debility, and locomotor incoordination. It is caused by proteinaceous infectious particles called PRIONS.Peptide Termination Factors: Proteins that are involved in the peptide chain termination reaction (PEPTIDE CHAIN TERMINATION, TRANSLATIONAL) on RIBOSOMES. They include codon-specific class-I release factors, which recognize stop signals (TERMINATOR CODON) in the MESSENGER RNA; and codon-nonspecific class-II release factors.Wasting Disease, Chronic: A transmissible spongiform encephalopathy (prion disease) of DEER and elk characterized by chronic weight loss leading to death. It is thought to spread by direct contact between animals or through environmental contamination with the prion protein (PRIONS).PrPC Proteins: Normal cellular isoform of prion proteins (PRIONS) encoded by a chromosomal gene and found in normal and scrapie-infected brain tissue, and other normal tissue. PrPC are protease-sensitive proteins whose function is unknown. Posttranslational modification of PrPC into PrPSC leads to infectivity.Creutzfeldt-Jakob Syndrome: A rare transmissible encephalopathy most prevalent between the ages of 50 and 70 years. Affected individuals may present with sleep disturbances, personality changes, ATAXIA; APHASIA, visual loss, weakness, muscle atrophy, MYOCLONUS, progressive dementia, and death within one year of disease onset. A familial form exhibiting autosomal dominant inheritance and a new variant CJD (potentially associated with ENCEPHALOPATHY, BOVINE SPONGIFORM) have been described. Pathological features include prominent cerebellar and cerebral cortical spongiform degeneration and the presence of PRIONS. (From N Engl J Med, 1998 Dec 31;339(27))Podospora: A genus of ascomycete FUNGI in the order SORDARIALES, which is found on SOIL and herbivore dung (FECES).Encephalopathy, Bovine Spongiform: A transmissible spongiform encephalopathy of cattle associated with abnormal prion proteins in the brain. Affected animals develop excitability and salivation followed by ATAXIA. This disorder has been associated with consumption of SCRAPIE infected ruminant derived protein. This condition may be transmitted to humans, where it is referred to as variant or new variant CREUTZFELDT-JAKOB SYNDROME. (Vet Rec 1998 Jul 25;143(41):101-5)Amyloid: A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.Deer: The family Cervidae of 17 genera and 45 species occurring nearly throughout North America, South America, and Eurasia, on most associated continental islands, and in northern Africa. Wild populations of deer have been established through introduction by people in Cuba, New Guinea, Australia, New Zealand, and other places where the family does not naturally occur. They are slim, long-legged and best characterized by the presence of antlers. Their habitat is forests, swamps, brush country, deserts, and arctic tundra. They are usually good swimmers; some migrate seasonally. (Walker's Mammals of the World, 5th ed, p1362)Mesocricetus: A genus of the family Muridae having three species. The present domesticated strains were developed from individuals brought from Syria. They are widely used in biomedical research.Infectious Disease Incubation Period: The amount time between exposure to an infectious agent and becoming symptomatic.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Bentonite: A colloidal, hydrated aluminum silicate that swells 12 times its dry size when added to water.Endopeptidase K: An enzyme that catalyzes the hydrolysis of keratin, and of other proteins with subtilisin-like specificity. It hydrolyses peptide amides. Endopeptidase K is from the mold Tritirachium album Limber. (Enzyme Nomenclature, 1992) EC 3.4.21.64.Phosphotungstic Acid: Tungsten hydroxide oxide phosphate. A white or slightly yellowish-green, slightly efflorescent crystal or crystalline powder. It is used as a reagent for alkaloids and many other nitrogen bases, for phenols, albumin, peptone, amino acids, uric acid, urea, blood, and carbohydrates. (From Merck Index, 11th ed)Saccharomyces cerevisiae Proteins: Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Ruminants: A suborder of the order ARTIODACTYLA whose members have the distinguishing feature of a four-chambered stomach, including the capacious RUMEN. Horns or antlers are usually present, at least in males.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Saccharomyces cerevisiae: A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.Swainsonine: An indolizidine alkaloid from the plant Swainsona canescens that is a potent alpha-mannosidase inhibitor. Swainsonine also exhibits antimetastatic, antiproliferative, and immunomodulatory activity.Kuru: A prion disease found exclusively among the Fore linguistic group natives of the highlands of NEW GUINEA. The illness is primarily restricted to adult females and children of both sexes. It is marked by the subacute onset of tremor and ataxia followed by motor weakness and incontinence. Death occurs within 3-6 months of disease onset. The condition is associated with ritual cannibalism, and has become rare since this practice has been discontinued. Pathologic features include a noninflammatory loss of neurons that is most prominent in the cerebellum, glial proliferation, and amyloid plaques. (From Adams et al., Principles of Neurology, 6th ed, p773)Biological Assay: A method of measuring the effects of a biologically active substance using an intermediate in vivo or in vitro tissue or cell model under controlled conditions. It includes virulence studies in animal fetuses in utero, mouse convulsion bioassay of insulin, quantitation of tumor-initiator systems in mouse skin, calculation of potentiating effects of a hormonal factor in an isolated strip of contracting stomach muscle, etc.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Brain Chemistry: Changes in the amounts of various chemicals (neurotransmitters, receptors, enzymes, and other metabolites) specific to the area of the central nervous system contained within the head. These are monitored over time, during sensory stimulation, or under different disease states.Sordariales: An order of fungi in the phylum ASCOMYCOTA that includes many valuable experimental organisms. There are eight families and very few anamorphic forms.Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions.Soil: The unconsolidated mineral or organic matter on the surface of the earth that serves as a natural medium for the growth of land plants.Dendritic Cells, Follicular: Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation.Disease Transmission, Infectious: The transmission of infectious disease or pathogens. When transmission is within the same species, the mode can be horizontal or vertical (INFECTIOUS DISEASE TRANSMISSION, VERTICAL).Gerstmann-Straussler-Scheinker Disease: An autosomal dominant familial prion disease with a wide spectrum of clinical presentations including ATAXIA, spastic paraparesis, extrapyramidal signs, and DEMENTIA. Clinical onset is in the third to sixth decade of life and the mean duration of illness prior to death is five years. Several kindreds with variable clinical and pathologic features have been described. Pathologic features include cerebral prion protein amyloidosis, and spongiform or neurofibrillary degeneration. (From Brain Pathol 1998 Jul;8(3):499-513; Brain Pathol 1995 Jan;5(1):61-75)Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.HSP40 Heat-Shock Proteins: A family of heat-shock proteins that contain a 70 amino-acid consensus sequence known as the J domain. The J domain of HSP40 heat shock proteins interacts with HSP70 HEAT-SHOCK PROTEINS. HSP40 heat-shock proteins play a role in regulating the ADENOSINE TRIPHOSPHATASES activity of HSP70 heat-shock proteins.Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or CHEMICAL WARFARE AGENTS, from a person or object.Fungal Proteins: Proteins found in any species of fungus.Disinfection: Rendering pathogens harmless through the use of heat, antiseptics, antibacterial agents, etc.Quinacrine: An acridine derivative formerly widely used as an antimalarial but superseded by chloroquine in recent years. It has also been used as an anthelmintic and in the treatment of giardiasis and malignant effusions. It is used in cell biological experiments as an inhibitor of phospholipase A2.Aluminum Silicates: Any of the numerous types of clay which contain varying proportions of Al2O3 and SiO2. They are made synthetically by heating aluminum fluoride at 1000-2000 degrees C with silica and water vapor. (From Hawley's Condensed Chemical Dictionary, 11th ed)Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are SACCHAROMYCES CEREVISIAE; therapeutic dried yeast is YEAST, DRIED.Amyloidogenic Proteins: Proteins that form the core of amyloid fibrils. For example, the core of amyloid A is formed from amyloid A protein, also known as serum amyloid A protein or SAA protein.Proteostasis Deficiencies: Disorders caused by imbalances in the protein homeostasis network - synthesis, folding, and transport of proteins; post-translational modifications; and degradation or clearance of misfolded proteins.Tissue Extracts: Preparations made from animal tissues or organs (ANIMAL STRUCTURES). They usually contain many components, any one of which may be pharmacologically or physiologically active. Tissue extracts may contain specific, but uncharacterized factors or proteins with specific actions.Plaque, Amyloid: Accumulations of extracellularly deposited AMYLOID FIBRILS within tissues.Crows: Common name for the largest birds in the order PASSERIFORMES, family Corvidae. These omnivorous black birds comprise most of the species in the genus Corvus, along with ravens and jackdaws (which are often also referred to as crows).Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.Guanidine: A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Sodium Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry.HSP70 Heat-Shock Proteins: A class of MOLECULAR CHAPERONES found in both prokaryotes and in several compartments of eukaryotic cells. These proteins can interact with polypeptides during a variety of assembly processes in such a way as to prevent the formation of nonfunctional structures.Lymphatic System: A system of organs and tissues that process and transport immune cells and LYMPH.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Protein Structure, Secondary: The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.PrP 27-30 Protein: Protease-resistant core of PrPSC, the abnormal isoform of prion proteins (PRIONS). PrP 27-30 is produced by limited proteolysis of the N-terminus of PrPSc.Iatrogenic Disease: Any adverse condition in a patient occurring as the result of treatment by a physician, surgeon, or other health professional, especially infections acquired by a patient during the course of treatment.Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Arvicolinae: A subfamily of MURIDAE found nearly world-wide and consisting of about 20 genera. Voles, lemmings, and muskrats are members.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Zoonoses: Diseases of non-human animals that may be transmitted to HUMANS or may be transmitted from humans to non-human animals.Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures.Phthalimides: The imide of phthalic acids.Surgical Instruments: Hand-held tools or implements used by health professionals for the performance of surgical tasks.Animals, Wild: Animals considered to be wild or feral or not adapted for domestic use. It does not include wild animals in zoos for which ANIMALS, ZOO is available.Host Specificity: The properties of a pathogen that makes it capable of infecting one or more specific hosts. The pathogen can include PARASITES as well as VIRUSES; BACTERIA; FUNGI; or PLANTS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Sonication: The application of high intensity ultrasound to liquids.Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Lymphotoxin beta Receptor: A member of the tumor necrosis factor receptor superfamily. It has specificity for LYMPHOTOXIN ALPHA1, BETA2 HETEROTRIMER and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 14. The receptor plays a role in regulating lymphoid ORGANOGENESIS and the differentiation of certain subsets of NATURAL KILLER T-CELLS. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Adsorption: The adhesion of gases, liquids, or dissolved solids onto a surface. It includes adsorptive phenomena of bacteria and viruses onto surfaces as well. ABSORPTION into the substance may follow but not necessarily.Peptide Hydrolases: Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.Mice, Inbred C57BLMink: Carnivores of genus Mustela of the family MUSTELIDAE. The European mink, which has white upper and lower lips, was widely trapped for commercial purposes and is classified as endangered. The American mink, lacking a white upper lip, is farmed commercially.Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Saliva: The clear, viscous fluid secreted by the SALIVARY GLANDS and mucous glands of the mouth. It contains MUCINS, water, organic salts, and ptylin.Temperature: The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Lymphoid Tissue: Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.Genes, Fungal: The functional hereditary units of FUNGI.Sheep Diseases: Diseases of domestic and mountain sheep of the genus Ovis.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Mammals: Warm-blooded vertebrate animals belonging to the class Mammalia, including all that possess hair and suckle their young.Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.Disinfectants: Substances used on inanimate objects that destroy harmful microorganisms or inhibit their activity. Disinfectants are classed as complete, destroying SPORES as well as vegetative forms of microorganisms, or incomplete, destroying only vegetative forms of the organisms. They are distinguished from ANTISEPTICS, which are local anti-infective agents used on humans and other animals. (From Hawley's Condensed Chemical Dictionary, 11th ed)Disease Reservoirs: Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (DISEASE VECTORS) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Food Contamination: The presence in food of harmful, unpalatable, or otherwise objectionable foreign substances, e.g. chemicals, microorganisms or diluents, before, during, or after processing or storage.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Endpoint Determination: Establishment of the level of a quantifiable effect indicative of a biologic process. The evaluation is frequently to detect the degree of toxic or therapeutic effect.Glycosylphosphatidylinositols: Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.Neuroblastoma: A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51)Nucleic Acids: High molecular weight polymers containing a mixture of purine and pyrimidine nucleotides chained together by ribose or deoxyribose linkages.Asymptomatic Diseases: Diseases that do not exhibit symptoms.Spleen: An encapsulated lymphatic organ through which venous blood filters.Microscopy, Electron, Transmission: Electron microscopy in which the ELECTRONS or their reaction products that pass down through the specimen are imaged below the plane of the specimen.Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium.Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.Salivary Proteins and Peptides: Proteins and peptides found in SALIVA and the SALIVARY GLANDS. Some salivary proteins such as ALPHA-AMYLASES are enzymes, but their composition varies in different individuals.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., BIOPOLYMERS; PLASTICS).Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.Green Fluorescent Proteins: Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.Gene Expression Regulation, Fungal: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi.Protein Multimerization: The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Silicon Dioxide: Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, QUARTZ, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Transgenes: Genes that are introduced into an organism using GENE TRANSFER TECHNIQUES.Feces: Excrement from the INTESTINES, containing unabsorbed solids, waste products, secretions, and BACTERIA of the DIGESTIVE SYSTEM.Nerve Degeneration: Loss of functional activity and trophic degeneration of nerve axons and their terminal arborizations following the destruction of their cells of origin or interruption of their continuity with these cells. The pathology is characteristic of neurodegenerative diseases. Often the process of nerve degeneration is studied in research on neuroanatomical localization and correlation of the neurophysiology of neural pathways.Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Microscopy, Atomic Force: A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.ThiazolesGenotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.Transformation, Genetic: Change brought about to an organisms genetic composition by unidirectional transfer (TRANSFECTION; TRANSDUCTION, GENETIC; CONJUGATION, GENETIC, etc.) and incorporation of foreign DNA into prokaryotic or eukaryotic cells by recombination of part or all of that DNA into the cell's genome.Epigenesis, Genetic: A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.Luminescent Measurements: Techniques used for determining the values of photometric parameters of light resulting from LUMINESCENCE.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Amyloid beta-Peptides: Peptides generated from AMYLOID BETA-PEPTIDES PRECURSOR. An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). The peptide is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Solubility: The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Cell-Free System: A fractionated cell extract that maintains a biological function. A subcellular fraction isolated by ultracentrifugation or other separation techniques must first be isolated so that a process can be studied free from all of the complex side reactions that occur in a cell. The cell-free system is therefore widely used in cell biology. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p166)Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Kinetics: The rate dynamics in chemical or physical systems.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.Genetic Variation: Genotypic differences observed among individuals in a population.Nerve Tissue ProteinsSelection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Alzheimer Disease: A degenerative disease of the BRAIN characterized by the insidious onset of DEMENTIA. Impairment of MEMORY, judgment, attention span, and problem solving skills are followed by severe APRAXIAS and a global loss of cognitive abilities. The condition primarily occurs after age 60, and is marked pathologically by severe cortical atrophy and the triad of SENILE PLAQUES; NEUROFIBRILLARY TANGLES; and NEUROPIL THREADS. (From Adams et al., Principles of Neurology, 6th ed, pp1049-57)Sequence Alignment: The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Enzyme-Linked Immunosorbent Assay: An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.

Characterization of the interaction domains of Ure2p, a prion-like protein of yeast. (1/2897)

In the yeast Saccharomyces cerevisiae, the non-Mendelian inherited genetic element [URE3] behaves as a prion. A hypothesis has been put forward which states that [URE3] arises spontaneously from its cellular isoform Ure2p (the product of the URE2 gene), and propagates through interactions of the N-terminal domain of the protein, thus leading to its aggregation and loss of function. In the present study, various N- and C-terminal deletion mutants of Ure2p were constructed and their cross-interactions were tested in vitro and in vivo using affinity binding and a two-hybrid analysis. We show that the self-interaction of the protein is mediated by at least two domains, corresponding to the first third of the protein (the so-called prion-forming domain) and the C-terminal catalytic domain.  (+info)

Prion domain initiation of amyloid formation in vitro from native Ure2p. (2/2897)

The [URE3] non-Mendelian genetic element of Saccharomyces cerevisiae is an infectious protein (prion) form of Ure2p, a regulator of nitrogen catabolism. Here, synthetic Ure2p1-65 were shown to polymerize to form filaments 40 to 45 angstroms in diameter with more than 60 percent beta sheet. Ure2p1-65 specifically induced full-length native Ure2p to copolymerize under conditions where native Ure2p alone did not polymerize. Like Ure2p in extracts of [URE3] strains, these 180- to 220-angstrom-diameter filaments were protease resistant. The Ure2p1-65-Ure2p cofilaments could seed polymerization of native Ure2p to form thicker, less regular filaments. All filaments stained with Congo Red to produce the green birefringence typical of amyloid. This self-propagating amyloid formation can explain the properties of [URE3].  (+info)

A novel epitope for the specific detection of exogenous prion proteins in transgenic mice and transfected murine cell lines. (3/2897)

Prion diseases are closely linked to the conversion of host-encoded cellular prion protein (PrPC) into its pathological isoform (PrPSc). PrP conversion experiments in scrapie infected tissue culture cells, transgenic mice, and cell-free systems usually require unique epitopes and corresponding monoclonal antibodies (MAbs) for the immunological discrimination of exogenously introduced and endogenous PrP compounds (e.g., MAb 3F4, which is directed to an epitope on hamster and human but not on murine PrP). In the current work, we characterize a novel MAb designated L42 that reacts to PrP of a variety of species, including cattle, sheep, goat, dog, human, cat, mink, rabbit, and guinea pig, but does not bind to mouse, hamster, and rat PrP. Therefore, MAb L42 may allow future in vitro conversion and transgenic studies on PrPs of the former species. The MAb L42 epitope on PrPC includes a tyrosine residue at position 144, whereas mouse, rat, and hamster PrPs incorporate tryptophane at this site. To verify this observation, we generated PrP expression vectors coding for authentic or mutated murine PrPCs (i.e., codon 144 encoding tyrosine instead of tryptophan). After transfection into neuroblastoma cells, MAb L42 did not react with immunoblotted wild-type murine PrPC, whereas L42 epitope-tagged murine PrPC was strongly recognized. Immunoblot and fluorescence-activated cell sorting data revealed that tagged PrPC was correctly posttranslationally processed and translocated to the cell surface.  (+info)

Fatal familial insomnia: a new Austrian family. (4/2897)

We present clinical, pathological and molecular features of the first Austrian family with fatal familial insomnia. Detailed clinical data are available in five patients and autopsy in four patients. Age at onset of disease ranged between 20 and 60 years, and disease duration between 8 and 20 months. Severe loss of weight was an early symptom in all five patients. Four patients developed insomnia and/or autonomic dysfunction, and all five patients developed motor abnormalities. Analysis of the prion protein (PrP) gene revealed the codon 178 point mutation and methionine homozygosity at position 129. In all brains, neuropathology showed widespread cortical astrogliosis, widespread brainstem nuclei and tract degeneration, and olivary 'pseudohypertrophy' with vacuolated neurons, in addition to neuropathological features described previously, such as thalamic and olivary degeneration. Western blotting of one brain and immunocytochemistry in four brains revealed quantitative and regional dissociation between PrP(res)(the protease resistant form of PrP) deposition and histopathology. In the cerebellar cortex of one patient, PrP(res) deposits were prominent in the molecular layer and displayed a peculiar patchy and strip-like pattern with perpendicular orientation to the surface. In another patient, a single vacuolated neuron in the inferior olivary nuclei contained prominent intravacuolar granular PrP(res) deposits, resembling changes of brainstem neurons in bovine spongiform encephalopathy.  (+info)

Copper binding to the prion protein: structural implications of four identical cooperative binding sites. (5/2897)

Evidence is growing to support a functional role for the prion protein (PrP) in copper metabolism. Copper ions appear to bind to the protein in a highly conserved octapeptide repeat region (sequence PHGGGWGQ) near the N terminus. To delineate the site and mode of binding of Cu(II) to the PrP, the copper-binding properties of peptides of varying lengths corresponding to 2-, 3-, and 4-octarepeat sequences have been probed by using various spectroscopic techniques. A two-octarepeat peptide binds a single Cu(II) ion with Kd approximately 6 microM whereas a four-octarepeat peptide cooperatively binds four Cu(II) ions. Circular dichroism spectra indicate a distinctive structuring of the octarepeat region on Cu(II) binding. Visible absorption, visible circular dichroism, and electron spin resonance spectra suggest that the coordination sphere of the copper is identical for 2, 3, or 4 octarepeats, consisting of a square-planar geometry with three nitrogen ligands and one oxygen ligand. Consistent with the pH dependence of Cu(II) binding, proton NMR spectroscopy indicates that the histidine residues in each octarepeat are coordinated to the Cu(II) ion. Our working model for the structure of the complex shows the histidine residues in successive octarepeats bridged between two copper ions, with both the Nepsilon2 and Ndelta1 imidazole nitrogen of each histidine residue coordinated and the remaining coordination sites occupied by a backbone amide nitrogen and a water molecule. This arrangement accounts for the cooperative nature of complex formation and for the apparent evolutionary requirement for four octarepeats in the PrP.  (+info)

The yeast non-Mendelian factor [ETA+] is a variant of [PSI+], a prion-like form of release factor eRF3. (6/2897)

The yeast non-Mendelian factor [ETA+] is lethal in the presence of certain mutations in the SUP35 and SUP45 genes, which code for the translational release factors eRF3 and eRF1, respectively. One such mutation, sup35-2, is now shown to contain a UAG stop codon prior to the essential region of the gene. The non-Mendelian inheritance of [ETA+] is reminiscent of the yeast [PSI+] element, which is due to a self-propagating conformation of Sup35p. Here we show that [ETA+] and [PSI+] share many characteristics. Indeed, like [PSI+], the maintenance of [ETA+] requires the N-terminal region of Sup35p and depends on an appropriate level of the chaperone protein Hsp104. Moreover, [ETA+] can be induced de novo by excess Sup35p, and [ETA+] cells have a weak nonsense suppressor phenotype characteristic of weak [PSI+]. We conclude that [ETA+] is actually a weak, unstable variant of [PSI+]. We find that although some Sup35p aggregates in [ETA+] cells, more Sup35p remains soluble in [ETA+] cells than in isogenic strong [PSI+] cells. Our data suggest that the amount of soluble Sup35p determines the strength of translational nonsense suppression associated with different [PSI+] variants.  (+info)

Application of distance geometry to 3D visualization of sequence relationships. (7/2897)

SUMMARY: We describe the application of distance geometry methods to the three-dimensional visualization of sequence relationships, with examples for mumps virus SH gene cDNA and prion protein sequences. Sequence-sequence distance measures may be obtained from either a multiple sequence alignment or from sets of pairwise alignments. AVAILABILITY: C/Perl code and HTML/VRML files from http://www.nibsc.ac.uk/dg3dseq/  (+info)

Effectiveness of polyene antibiotics in treatment of transmissible spongiform encephalopathy in transgenic mice expressing Syrian hamster PrP only in neurons. (8/2897)

To date very few drugs have favorably influenced the course of transmissible spongiform encephalopathies. In previous studies, the polyene antibiotics amphotericin B (AmB) and MS-8209 prolonged the incubation time in Syrian hamsters of the 263K strain of scrapie, but AmB had no effect against other scrapie strains in Syrian hamsters. In the present experiments using transgenic mice expressing Syrian hamster PrP in neurons only, MS-8209 extended the life spans of animals infected with the 263K strain but not the DY strain. AmB was effective against both 263K and DY and prevented death in 18% of DY-infected animals. The AmB effect against strain 263K was more prominent in mice whose endogenous PrP gene had been inactivated by homologous recombination. It was unclear whether this difference was due to a change in the duration of the disease or to possible interactive effects between the mouse PrP gene and the drugs themselves. The effectiveness of treatment after intracerebral scrapie infection in transgenic mice expressing PrP only in neurons suggested that neurons are important sites of action for these drugs.  (+info)

  • Yeast [PSI+] prion is one of the most suitable and well characterized system for the investigation of the prion phenomenon. (spbu.ru)
  • Collectively, these findings suggest that cPLA 2 plays a vital role in the action of HuPrP106-126 and that the colocalisation of p-cPLA 2 with beta III tubulin could be central to the progress of neurodegeneration caused by prion peptides. (beds.ac.uk)
  • However, until recently, the lack of data on the 3D arrangement of Sup35p prion fibrils hindered progress in this area. (spbu.ru)
  • On the basis of the transmission features in conventional mice (incubation periods, distribution of the lesions in the brain), early transmission experiments described a considerable diversity of the scrapie agents with up to 20 prion strains reportedly identified 8 . (nature.com)
  • Despite converging evidence that scrapie is caused by a variety of prion strains, there is at this stage no comprehensive description of their diversity. (nature.com)
  • The investigators concluded that these results suggest that the new filter can be used to remove different strains of infectious prions, including vCJD. (news-medical.net)
  • To confirm the findings and to explore the issue of evolution of drug resistance, Weissmann and his colleagues used the drug swainsonine or swa, which is found in plants and fungi, and has been shown to inhibit certain prion strains. (scripps.edu)
  • Nevertheless, in standard lab conditions [ PSI + ] strains containing prions seem to grow just as well as [ psi − ] strains that lack them ( T rue and L indquist 2000 ). (genetics.org)
  • When prions are exposed to temperature changes and/or chemicals, they adapt to the exposures by shapeshifting to create new strains. (abovetopsecret.com)
  • So if a vat held a contaminated batch of milk 50 years ago, it's still spewing out prions - probably a whole collection of different strains. (abovetopsecret.com)
  • Any study of prions in milk would need to look for a huge variety of different strains - not just the standard BSE's and TSE's. (abovetopsecret.com)
  • Our National Prion Clinic (NPC)'s multidisciplinary team comprises consultant neurologists, clinical research fellows and clinical nurse specialists. (uclh.nhs.uk)
  • Two other cases -- identified after death and reported two years ago -- were previously identified among 66 people who got blood transfusions from donors who subsequently developed vCJD, according to Stephen Wroe, M.D., of the National Prion Clinic at the National Hospital for Neurology and Neurosurgery in London. (medpagetoday.com)
  • Prion aggregates are extremely stable and accumulate in infected tissue, causing tissue damage and cell death. (wikipedia.org)
  • In earlier studies, transgenic (Tg) mice expressing low levels of PrP(ΔGPI) did not develop signs of spontaneous neurologic illness, but harbored large amyloidogenic PrP(ΔGPI) aggregates in the brain after exposure to prions ( 6 , 7 ). (pnas.org)
  • Prion aggregates renew themselves by continually recruiting newly made soluble prions into the aggregates. (eurekalert.org)
  • 2014. Role of the goat K222-PrPC polymorphic variant in prion infection resistance . (wur.nl)
  • O prion celular (PrPc) é uma glicoproteína ligada à membrana plasmática por uma âncora de GPI (glycosylphosphatidylinositol). (usp.br)
  • Prions are different because they do not infect and replicate in the same way that viruses do. (answers.com)
  • Prions have neither machinery to replicate themselves, nor code to hijack the machinery of the cell. (creation.com)
  • There is still a veil of mystery around prions and exactly how they replicate, cross the blood-brain barrier and cross the species barrier - i.e. infect different species of host. (scienceinschool.org)
  • Now we know that the abnormal prions replicate, and create variants, perhaps at a low level initially. (scripps.edu)
  • The summary table below, of what the two new anti-prion antibodies immuno-precipitate, is based on the highly compressed text, gel legends, illegible fax images, faulty memory of citation content, and guesswork. (mad-cow.org)
  • So, with respect to anti-prion pills, any prions that happen to become part of the diet can be destroyed before they reach the brain. (halfbakery.com)
  • Using this method, the scientists were able to detect more than a billion-fold dilution of prions using an anti-prion antibody. (nih.gov)
  • The researchers considered three explanations for the exacerbation of amyloid pathology by the prions. (alzforum.org)
  • They have treated diseased brain tissue with detergents and centrifuges and harvested the encrusted, suspect prion. (encyclopedia.com)
  • This result suggests that interactions between PrP C and polyanions found naturally in the brain may contribute to spontaneous prion formation. (nih.gov)
  • The BSE prions concentrate in an animal's brain and spinal cord, but they been detected only in sheep blood at low concentrations. (rense.com)
  • It's caused by eating human brain tissue contaminated with infectious prions. (hopkinsmedicine.org)
  • Most prion infections begin when the normal shape, for reasons unknown, spontaneously changes into the infectious form that kills brain cells. (innovations-report.com)
  • Possibly those enzymes can also circulate in the blood and eliminate prions in the brain, too. (halfbakery.com)
  • When living wheat grass leaves were sprayed with a 1% hamster brain homogenate, prions could attach to the leaves and be detected for 49 days. (virology.ws)
  • To determine if prions in plants could infect animals, plants were exposed to brain homogenates, washed thoroughly, and then fed to hamsters. (virology.ws)
  • Barley grass plants were grown on soil that had been mixed with hamster brain homogenate, and then 1-3 weeks later, stem and leaves were assayed for the presence of prions. (virology.ws)
  • While the presence of Aβ did not seem to affect the extent of prion-driven spongiform degeneration, it did increase the levels of prions that could be measured in brain tissue. (alzforum.org)
  • Likewise, the presence of prions increased brain inflammation and Aβ deposition. (alzforum.org)
  • It has been proposed that these events reflect rare, spontaneous formation of prions in brain. (thaindian.com)
  • Weissmann noted that an alternative interpretation of the results is that infectious prions are naturally present in the brain at levels not detectable by conventional methods, and are normally destroyed at the same rate they are created. (thaindian.com)
  • Used to analyze the CJD patient eyes, the assay detected abnormal prions in multiple ocular tissues, with the highest seed levels-which in some cases were not much lower than those in the brain-found in the retina. (genengnews.com)
  • The abnormal prions then clump together, which researchers believe may lead to neuron loss and brain damage. (sixwise.com)
  • In the first part of the study, Weissmann and his colleagues transferred prion populations from infected brain cells to culture cells. (scripps.edu)
  • When transplanted, cell-adapted prions developed and out-competed their brain-adapted counterparts, confirming prions' ability to adapt to new surroundings, a hallmark of Darwinian evolution. (scripps.edu)
  • When returned to brain, brain-adapted prions again took over the population. (scripps.edu)
  • It will be interesting for the authors to follow up their EM studies on PrP to define the ultrastructural site(s) of PrP accumulation with the onset of prion pathology. (alzforum.org)
  • Because of that, Soto said, there will be more interest in looking at prion pathology in AD going forward. (alzforum.org)
  • 15B3 specifically precipitates bovine, murine or human rogue, but not normal conformer, suggesting that it recognizes an epitope common to rogue prions from different species. (mad-cow.org)
  • Researchers at the Whitehead Institute in Cambridge, Massachusetts, US, have now found that adult stem cells in bone marrow gradually lose their ability to regenerate without their normal complement of membrane-bound prions. (newscientist.com)
  • This new rogue prion joins in the game of "tag," by forcing another normal prion into the abnormal form. (innovations-report.com)
  • The new filter also has an affinity to all types of prions including aggregated, denatured and normal. (news-medical.net)
  • Apparently some prions are normal, and actually play a role in protecting our nervous system, though. (virology.ws)
  • The finding that prion null mice do not have a significant overt phenotype suggests that the normal function of PrP is of minor importance. (nih.gov)
  • Normal prions occur naturally in the body and are harmless. (sixwise.com)
  • But when a prion takes on a different folded shape than its normal counterparts, it becomes infectious. (sixwise.com)
  • The prion theory was controversial at first, since other known infectious agents - bacteria, viruses, parasites and fungi - contain their own genetic information (DNA or RNA). (sourcewatch.org)
  • Prions are so small that they are even smaller than viruses and can only be seen through an electron microscope when they have aggregated and formed a cluster. (news-medical.net)
  • Prions, bacteria, and viruses are all kind of blurred together and known generically as the same thing. (brightkite.com)
  • The three that I will be discussing are bacteria, viruses, and prions. (brightkite.com)
  • 810 words - 4 pages Viruses, bacteria, and prions are all major topics in biology. (brightkite.com)
  • Bacteria and viruses are more similar with each other than a prion with either one. (brightkite.com)
  • Are Viruses, Prions And Viriods Alive? (brightkite.com)
  • 1023 words - 5 pages Prions, bacteria, and viruses are all kind of blurred together and known generically as the same thing. (brightkite.com)
  • 1323 words - 5 pages Many people get viruses, prions, and bacteria confused in multiple ways. (brightkite.com)
  • Prions are very different from infectious organisms like bacteria and viruses. (sixwise.com)
  • On the face of it, you have exactly the same process of mutation and adaptive change in prions as you see in viruses," said Charles Weissmann, the head of Scripps Florida's Department of Infectology, who led the study. (scripps.edu)
  • Mammary gland infections are common in dairy cows - they're not considered transmissible to humans, so the cows are just shot up with antibiotics and their milk is shipped along with the rest - laced with antibiotics, viruses, and possibly prions. (abovetopsecret.com)
  • The occurrence of vCJD has provided significant evidence to show that the transmission barrier does not constitute an absolute protection against the zoonotic risk of prions that circulate in animal populations. (nature.com)
  • The study, presented today at the annual meeting of the AABB, found that a new filtration technology from Pall Corporation reduces infectious vCJD prions from red blood cell concentrates, the most commonly transfused blood component. (news-medical.net)
  • The study, conducted at a leading prion research institute in Europe, found that the Pall Leukotrap® Affinity Prion Reduction Filter reduces infectious vCJD prions from red blood cell concentrates below the limit of detection of the Western blot assay. (news-medical.net)
  • The concentration of infectious vCJD prions in the red cell concentrates was measured before and after filtration with the Pall Leukotrap Prion Affinity Reduction Filter using a Western blot assay. (news-medical.net)
  • The scientists next tested whether the technique could be used to detect prions in blood samples from 14 people with vCJD and 153 controls. (nih.gov)
  • Keeping cervids out of grazing or growing fields should be considered as a way to manage the risk of prions entering the human food chain. (virology.ws)
  • This updated review focuses primarily on chemicalbased treatments in light of developments in diagnostic technologies, including results from recent clinical trials, and proposes some promising new targets for prion therapy. (ingentaconnect.com)
  • however the presence of prions in such wastes is uncertain (EPA 2001). (rense.com)
  • The authors conclude that the presence of prions leads to a dramatic acceleration in the misfolding, aggregation, and cerebral accumulation of Aβ, and vice versa. (alzforum.org)
  • A research team at Dartmouth Medical School led by Dr. Surachai Supattapone reported in the June 5, 2007, issue of Proceedings of the National Academy of Sciences that they came upon a way to generate infectious prions spontaneously from noninfectious components. (nih.gov)
  • Prions can form spontaneously as well, though this is fairly rare. (bigthink.com)
  • Scientists who deal with prions] are not going to speak out, especially with the political repercussions in science. (rense.com)
  • In the new study, the scientists used the Scrapie Cell Assay, a test originally created by Weissmann that is highly sensitive to minute quantities of prions. (thaindian.com)
  • The causative agents of TSEs are believed to be prions. (cdc.gov)
  • However, even the best efforts to purify prions have been plagued by contaminants, so it's been difficult for researchers to exclude the possibility that something else might really be causing TSEs. (nih.gov)
  • Importantly, their data, which appeared in the August 6 Journal of Neuroscience, show that a pool of prions exists in the neuronal cytosol, supporting a recent hypothesis that minute amounts of misfolded, cytosolic prion may be sufficient to cripple neurons. (alzforum.org)