If you actually care about what causes BSE and other disorders, I suggest you look up Dr. Vitaly Vodyanoy's new USA patent application #20070122799.
Within this patent application, Vodyanoy describes/defines prions in a far more detailed manner than in his previously granted patent #7138255.
He ends his patent with plans to do further experimentation on prions. Unfortunately, he will not be working with the "naturally derived" prions, but with recombinant prion produced using yeast.
Main jest of the application.... Metal PNCs are the template for protein misfolding, polymerization and aggregation.
Vodyanoy references Dr. David Brown of the UK several times, with major findings of regarding copper loading of the prion protein and manganese replacement). He also references Mark Purdey, once. Amazing!
Several definitions must be understood to review his patent application:
PNCs are "proteon nucleating centers" which consist of 1 to 2 nm nanoparticles that contain 40-300 non-ionic metal atoms. These nanoclusters have been shown to scavent proteins to form proteons; clusters of up to 100,000 protein molecules with metal centers. PNCs have tremendous potential in the diagnosis and treatment of diseases associated with misfolded proteins, including prion-related diseases, neurological diseases, blood diseases and cancer." (Office of technology transfer, and patent) - depleted uranium nanoparticles produced with the use of DU weapons, would fit this definition to a T.
"Proteons are intended protein bodies, generally on the order of a few tens of nanometers up to several microns across, having misfolded or partially misfolded proteins surrounding a PNC."
Vitaly defines PRION - "A prion is a PNC surrounded only by one or more misfolded proteins."
Some points of interest within this patent are:
"all prions are proteons, but not all proteons are prions" [0185]
"chelating agents effectively immobolize the PNCs, thus neutralizing the deleterious properties of prions or proteons" [0186]
"plasma transferred to a 4 ml glass vial with a plastic cap and a teflon liner" [0189]
"indicating that misfolded albumin and hemoglobin may be present in proteons" [0202]
"define and characterize properties of PNCs participating in misfolding, polymerization and aggregation of proeins" [0265]
"mystery remains What is the nature of the seed that catalyze the prion protein to conversion" [0276]
"According to Tutte, 2000 comments to the protein seeds of prion propagation the physical agitation and presumed consequent fragmentation of prion aggregates greatly increased their seeding activity in vitro. The idea of physical agitation and fragmentation was fully explored a few years ago, when a method of cyclic amplification of misfolded protein was introduced (Saborio at al., 2001; Soto at al., 2002, 2005; Castilla et al., 2005, 2005a; Sea at al., 2005). The amplification cycle was composed of two steps. During the first step, a sample is incubated to grow polymers. In the second step the sample is subjected to ultrasound, as authors believe, to break down the polymer, multiplying the number of nuclei." [0277] - relating work by others
"There is substantial evidence that prion protein is a Cu-binding protein. In conversion to the misfolded form this Cu binding activity is lost. Instead, the protein binds other metals such as Mn or Zn (Brown, 2004). These facts are consistent with the observation that the in vitro cyclic amplification process is weakly facilitated by divalent cations such as Mn, Zn and Ni but not Cu (Sarafoff et al., 2005). Similar findings were indicating that transition metal ions bind prion proteins." [0278]
"Type I proteons are largely presented by small particles of spherical shape of 50-250 nm. (FIGS. 1A and 1B). In the optical dark-field of the liquid samples, proteons look like fast randomly moving bright dots."[0285]
"Seeds obtained from proteons or metals known to promote a specific misfolding can be used for seeding" [0296]
" Hypothesis Metal clusters (Gonzalez-Morega, 1993; Aiken & Finke, 1999) play a role in the seeds in proteons, Metals involved in the natural folding and misfolding of proteins are not in the ion state, but rather in the clusters of metal atoms. These atoms are directly bonded to each other creating a polyatomic metallic nucleus that can exist alone or are associated with a given number of ligands." [0299]
"The most remarkable property of metal clusters is that they provide a binding template for folding and aggregation of proteins." ... "Many disorders arise from misfolding and aggregation of an underlying protein (Carrel and Lormas, 1997; Sato, 2001). The same disorders were shown to depend on metal misbalance (Bush, 2000). Copper, iron or manganese are involved in the aging and neurological disorders. Metals are involved in prion diseases." ..."The mathematical accuracy and stability of geometrical patterns and a large number of structural arrangements of metal clusters make them uniquely qualified as perfect templates for protein folding." [300]
"TEM showed that the bulk of the drived PNC-containing filtrate was amorphous, and that it contained crystalline metallic nanoparticles 1-2 nm in diameter." [0302]
"Small metal nanoclusters meet requirements to serve as nuclei for aggregation of proteins and their fragments: i.e. Small, a few nm or smaller." [0305]
"If PNCs were not added to the PrP solution we did not find any filamentous or fiber like structures. In the presence of PNCs after 15 minutes of the heat treatment we observed a dramatic change in the protein structure. A large number of small particles (arrow) of about 10-15 nm and filamentous structures were produced in the presence of PNCs. It appears that these particles were converted first in the thin short rodlets (40-50, nm long) and then the rodlets were interconnected into longer thin filaments. After that thin filaments were interwoven into the thicker fibril looking like a rope with fibers. Finally, large fibrils were creating a complicated system of fibrils and plaques." [0314]
" Proteons and prions share many physical and chemical properties. They both are misfolded proteins, polymorphic, have no nucleic acids, metal dependent, and very resistant. They both may be induced by seeds and be controlled by guanidine hydrochloride. They both play a certain role in a cell death. They both have the same proliferation rate at 37.degree. C. (Aguzzi and Heppner, 2002; Everbroeck, et al., 2002; Ness, et al., 2002; Bounias and Purdey, 2002; Gemer 1997, 2002). Our experiments with the recombinant human protein described in the section "Proteons from prion protein (PrP)" suggest that metal nanoclusters (PNCs) play important role in production of prion particles. We need to present experimental evidence that metal particles are indeed inside the prions particles. In order to make a statement that naturally occurring prions are proteons, that is to say, natural prion particle is the misfolded prion protein aggregated around non-organic nanoparticle that serves as a nucleating center, it would require to analyze prions obtained from the animal with the prion disease. There is substantial evidence that PrP is a Cu-binding protein. It is suggested that in conversion to the abnormal form the Cu-binding activity is switched to the binding other metals such as Mn or Zn (Brown, 2004). In this work we do not plan to work with prions obtained from animals with prion diseases. We will work with in vitro system of prion particles produced from the recombinant human PrP(23-230) protein and metal PNC and examine if these particles have acquired the ability to convert the normal form of the protein into this same abnormal (prion) form." [0317]
"Aim 1. In this portion of the experiment we will determine conditions controlling assembling and disassembling of protein particles (proteons). The main hypothesis of this aim is that the stable inorganic nuclei control misfolding and aggregation of prion-related proteins. The rationale that underlines this aim is that our preliminary results together with literature data strongly indicate that seeded polymerization and aggregation is an important mechanism of replication of prions, among other misfolded proteins. The seeds (PNCs) are very resistant to various physical and chemical factors. The process of amplification of misfolded proteins is sensitive to the microenvironment of interacting protein and PNCs. The strategy will be to characterize the influence of the microenvironment on the kinetics of replication and properties of proteons using our in vitro amplification method. The particles will be characterized by dark-field light and electron microscopy and identified by gel electrophoresis and immunoblotting. The kinetic data will be analyzed with the theoretical nucleated polymerization model and will be compared with known results of prion replication and proliferation of other protein aggregates." [0321]
"(6) Inhibitory compounds like creosote. In our preliminary experiments we observed that addition of small concentration of creosote stops the motility of proteons and make them disappear from the optical dark-field microscope image (data not shown). Creosote contains many polycyclic aromatic hydrocompounds (Nylund, et al., 1992) and was known from antiquity for preservation of wood and food products (Phillips, 1999)." [0329] - like the creosote in the canadian rail-road ties used to burn the hundreds of thousands of animals destroyed in the UK, 2001, during the foot and mouth outbreak!
"Aim 2. In this aim we define and characterize properties of nuclei (PNCs) participating in misfolding, polymerization, and aggregation of proteins. The main hypothesis is that metallic or inorganic compound acts as nucleus for misfolded proteins. The rationale that underlines this aim is discussed in the subsection "PNCs" of the Preliminary results. The essence of the concept is that the metal site works as a template for the metal/protein structure formation (Liu and Xu, 2002)." [0332]
"Chaotropic compounds are commonly used for a liquid extraction of polyvalent metals (Nash and Horowitz, 1990)" [0334]
"Experiment c: Prepare PNCs purified from plasma and artificial PNCs using information obtained in Experiment b of Aim 2; use metallic nanoparticles as model systems. We prepared purified PNCs from plasma using the same methods of separation of PNCs and proteins as described in the Experiment a (Aim 2). Metal nanoparticles can be obtained from Agronide Nanomaterials, FL" [0336]
You can find the whole patent application at the USA Patent Office. This is an "application" and you must search for it in a separate spot from the granted patents.
I'll try a link:
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220070122799%22.PGNR.&OS=DN/20070122799&RS=DN/20070122799
Within this patent application, Vodyanoy describes/defines prions in a far more detailed manner than in his previously granted patent #7138255.
He ends his patent with plans to do further experimentation on prions. Unfortunately, he will not be working with the "naturally derived" prions, but with recombinant prion produced using yeast.
Main jest of the application.... Metal PNCs are the template for protein misfolding, polymerization and aggregation.
Vodyanoy references Dr. David Brown of the UK several times, with major findings of regarding copper loading of the prion protein and manganese replacement). He also references Mark Purdey, once. Amazing!
Several definitions must be understood to review his patent application:
PNCs are "proteon nucleating centers" which consist of 1 to 2 nm nanoparticles that contain 40-300 non-ionic metal atoms. These nanoclusters have been shown to scavent proteins to form proteons; clusters of up to 100,000 protein molecules with metal centers. PNCs have tremendous potential in the diagnosis and treatment of diseases associated with misfolded proteins, including prion-related diseases, neurological diseases, blood diseases and cancer." (Office of technology transfer, and patent) - depleted uranium nanoparticles produced with the use of DU weapons, would fit this definition to a T.
"Proteons are intended protein bodies, generally on the order of a few tens of nanometers up to several microns across, having misfolded or partially misfolded proteins surrounding a PNC."
Vitaly defines PRION - "A prion is a PNC surrounded only by one or more misfolded proteins."
Some points of interest within this patent are:
"all prions are proteons, but not all proteons are prions" [0185]
"chelating agents effectively immobolize the PNCs, thus neutralizing the deleterious properties of prions or proteons" [0186]
"plasma transferred to a 4 ml glass vial with a plastic cap and a teflon liner" [0189]
"indicating that misfolded albumin and hemoglobin may be present in proteons" [0202]
"define and characterize properties of PNCs participating in misfolding, polymerization and aggregation of proeins" [0265]
"mystery remains What is the nature of the seed that catalyze the prion protein to conversion" [0276]
"According to Tutte, 2000 comments to the protein seeds of prion propagation the physical agitation and presumed consequent fragmentation of prion aggregates greatly increased their seeding activity in vitro. The idea of physical agitation and fragmentation was fully explored a few years ago, when a method of cyclic amplification of misfolded protein was introduced (Saborio at al., 2001; Soto at al., 2002, 2005; Castilla et al., 2005, 2005a; Sea at al., 2005). The amplification cycle was composed of two steps. During the first step, a sample is incubated to grow polymers. In the second step the sample is subjected to ultrasound, as authors believe, to break down the polymer, multiplying the number of nuclei." [0277] - relating work by others
"There is substantial evidence that prion protein is a Cu-binding protein. In conversion to the misfolded form this Cu binding activity is lost. Instead, the protein binds other metals such as Mn or Zn (Brown, 2004). These facts are consistent with the observation that the in vitro cyclic amplification process is weakly facilitated by divalent cations such as Mn, Zn and Ni but not Cu (Sarafoff et al., 2005). Similar findings were indicating that transition metal ions bind prion proteins." [0278]
"Type I proteons are largely presented by small particles of spherical shape of 50-250 nm. (FIGS. 1A and 1B). In the optical dark-field of the liquid samples, proteons look like fast randomly moving bright dots."[0285]
"Seeds obtained from proteons or metals known to promote a specific misfolding can be used for seeding" [0296]
" Hypothesis Metal clusters (Gonzalez-Morega, 1993; Aiken & Finke, 1999) play a role in the seeds in proteons, Metals involved in the natural folding and misfolding of proteins are not in the ion state, but rather in the clusters of metal atoms. These atoms are directly bonded to each other creating a polyatomic metallic nucleus that can exist alone or are associated with a given number of ligands." [0299]
"The most remarkable property of metal clusters is that they provide a binding template for folding and aggregation of proteins." ... "Many disorders arise from misfolding and aggregation of an underlying protein (Carrel and Lormas, 1997; Sato, 2001). The same disorders were shown to depend on metal misbalance (Bush, 2000). Copper, iron or manganese are involved in the aging and neurological disorders. Metals are involved in prion diseases." ..."The mathematical accuracy and stability of geometrical patterns and a large number of structural arrangements of metal clusters make them uniquely qualified as perfect templates for protein folding." [300]
"TEM showed that the bulk of the drived PNC-containing filtrate was amorphous, and that it contained crystalline metallic nanoparticles 1-2 nm in diameter." [0302]
"Small metal nanoclusters meet requirements to serve as nuclei for aggregation of proteins and their fragments: i.e. Small, a few nm or smaller." [0305]
"If PNCs were not added to the PrP solution we did not find any filamentous or fiber like structures. In the presence of PNCs after 15 minutes of the heat treatment we observed a dramatic change in the protein structure. A large number of small particles (arrow) of about 10-15 nm and filamentous structures were produced in the presence of PNCs. It appears that these particles were converted first in the thin short rodlets (40-50, nm long) and then the rodlets were interconnected into longer thin filaments. After that thin filaments were interwoven into the thicker fibril looking like a rope with fibers. Finally, large fibrils were creating a complicated system of fibrils and plaques." [0314]
" Proteons and prions share many physical and chemical properties. They both are misfolded proteins, polymorphic, have no nucleic acids, metal dependent, and very resistant. They both may be induced by seeds and be controlled by guanidine hydrochloride. They both play a certain role in a cell death. They both have the same proliferation rate at 37.degree. C. (Aguzzi and Heppner, 2002; Everbroeck, et al., 2002; Ness, et al., 2002; Bounias and Purdey, 2002; Gemer 1997, 2002). Our experiments with the recombinant human protein described in the section "Proteons from prion protein (PrP)" suggest that metal nanoclusters (PNCs) play important role in production of prion particles. We need to present experimental evidence that metal particles are indeed inside the prions particles. In order to make a statement that naturally occurring prions are proteons, that is to say, natural prion particle is the misfolded prion protein aggregated around non-organic nanoparticle that serves as a nucleating center, it would require to analyze prions obtained from the animal with the prion disease. There is substantial evidence that PrP is a Cu-binding protein. It is suggested that in conversion to the abnormal form the Cu-binding activity is switched to the binding other metals such as Mn or Zn (Brown, 2004). In this work we do not plan to work with prions obtained from animals with prion diseases. We will work with in vitro system of prion particles produced from the recombinant human PrP(23-230) protein and metal PNC and examine if these particles have acquired the ability to convert the normal form of the protein into this same abnormal (prion) form." [0317]
"Aim 1. In this portion of the experiment we will determine conditions controlling assembling and disassembling of protein particles (proteons). The main hypothesis of this aim is that the stable inorganic nuclei control misfolding and aggregation of prion-related proteins. The rationale that underlines this aim is that our preliminary results together with literature data strongly indicate that seeded polymerization and aggregation is an important mechanism of replication of prions, among other misfolded proteins. The seeds (PNCs) are very resistant to various physical and chemical factors. The process of amplification of misfolded proteins is sensitive to the microenvironment of interacting protein and PNCs. The strategy will be to characterize the influence of the microenvironment on the kinetics of replication and properties of proteons using our in vitro amplification method. The particles will be characterized by dark-field light and electron microscopy and identified by gel electrophoresis and immunoblotting. The kinetic data will be analyzed with the theoretical nucleated polymerization model and will be compared with known results of prion replication and proliferation of other protein aggregates." [0321]
"(6) Inhibitory compounds like creosote. In our preliminary experiments we observed that addition of small concentration of creosote stops the motility of proteons and make them disappear from the optical dark-field microscope image (data not shown). Creosote contains many polycyclic aromatic hydrocompounds (Nylund, et al., 1992) and was known from antiquity for preservation of wood and food products (Phillips, 1999)." [0329] - like the creosote in the canadian rail-road ties used to burn the hundreds of thousands of animals destroyed in the UK, 2001, during the foot and mouth outbreak!
"Aim 2. In this aim we define and characterize properties of nuclei (PNCs) participating in misfolding, polymerization, and aggregation of proteins. The main hypothesis is that metallic or inorganic compound acts as nucleus for misfolded proteins. The rationale that underlines this aim is discussed in the subsection "PNCs" of the Preliminary results. The essence of the concept is that the metal site works as a template for the metal/protein structure formation (Liu and Xu, 2002)." [0332]
"Chaotropic compounds are commonly used for a liquid extraction of polyvalent metals (Nash and Horowitz, 1990)" [0334]
"Experiment c: Prepare PNCs purified from plasma and artificial PNCs using information obtained in Experiment b of Aim 2; use metallic nanoparticles as model systems. We prepared purified PNCs from plasma using the same methods of separation of PNCs and proteins as described in the Experiment a (Aim 2). Metal nanoparticles can be obtained from Agronide Nanomaterials, FL" [0336]
You can find the whole patent application at the USA Patent Office. This is an "application" and you must search for it in a separate spot from the granted patents.
I'll try a link:
http://appft1.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220070122799%22.PGNR.&OS=DN/20070122799&RS=DN/20070122799