A definition of prion is required to further unfold these connections between the methods of transference and carrier state, by metals, yeast, podospora and the aplysia.
There are stages of this introduction into the human body. This involves metal nanoparticles from chemtrails, from hybridized proteins in foods, from freeze dried spores in insecticides.
The use of an infectious particle carrying the seeds of genetic alteration, hidden in the precursor metals and its chemical reaction along with the protein's power to cross barriers
by way of unfolding and folding in the desired design, the intermediate, crossing the biological, chemical, geological, physics barriers, to alter life itself seems to have been accomplished
by the prion. The prion is the machine's seed. =========================
PrionFor the bird, see Prion (bird). For the theoretical subatomic particle, see Preon.
Prion Diseases (TSEs)
A prion (pronounced /ˈpriː.ɒn/ (Speaker Icon.svg listen)[1]) is an infectious agent that is composed primarily of protein. To date, all such agents that have been discovered propagate by transmitting a mis-folded protein state; the protein itself does not self-replicate and the process is dependent on the presence of the polypeptide in the host organism.[2] The mis-folded form of the prion protein has been implicated in a number of diseases in a variety of mammals, including bovine spongiform encephalopathy (BSE, also known as "mad cow disease") in cattle and Creutzfeldt-Jakob disease (CJD) in humans. All known prion diseases affect the structure of the brain or other neural tissue, and all are currently untreatable and are always fatal.[3] In general usage, prion refers to the theoretical unit of infection. In scientific notation, PrPC refers to the endogenous form of prion protein (PrP), which is found in a multitude of tissues, while PrPSc refers to the misfolded form of PrP, that is responsible for the formation of amyloid plaques and neurodegeneration.
Prions are hypothesized to infect and propagate by refolding abnormally into a structure which is able to convert normal molecules of the protein into the abnormally structured form. All known prions induce the formation of an amyloid fold, in which the protein polymerises into an aggregate consisting of tightly packed beta sheets. This altered structure is extremely stable and accumulates in infected tissue, causing tissue damage and cell death.[4] This stability means that prions are resistant to denaturation by chemical and physical agents, making disposal and containment of these particles difficult.
Proteins showing prion-type behavior are also found in some fungi, which has been useful in helping to understand mammalian prions. Fungal prions, however, do not appear to cause disease in their hosts and may even confer an evolutionary advantage through a form of protein-based inheritance.[5]
The word prion is a compound word derived from the initial and final letters of the words proteinaceous and infection.[6]
en.wikipedia.org/wiki/Beta_sheet============================
This definition however, does not indicate that this disease has precursors.
Something causes the protein to misfold, that is what we will concentrate on, and
prions can go through intestinal walls, skin, and other organs. It becomes a
systemic disease, when it can break through capilllaries, nerves themselves,
and seem concentrated in neurons, which are all over the human body.
This article indicates how prions can break through the intestinal wall, causing fibers
to be excreted through the skin.
What is interesting here is the relationship of iron, ferritin to the transport of prions
across the intestinal barrier.
=========================
Foodborne transmission of bovine spongiform encephalopathy (BSE) to humans as variant Creutzfeldt-Jakob disease (CJD) has affected over 100 individuals, and probably millions of others have been exposed to BSE-contaminated food substances. Despite these obvious public health concerns, surprisingly little is known about the mechanism by which PrP-scrapie (PrPSc), the most reliable surrogate marker of infection in BSE-contaminated food, crosses the human intestinal epithelial cell barrier. Here we show that digestive enzyme (DE) treatment of sporadic CJD brain homogenate generates a C-terminal fragment similar to the proteinase K-resistant PrPSc core of 27-30 kDa implicated in prion disease transmission and pathogenesis. Notably, DE treatment results in a PrPSc-protein complex that is avidly transcytosed in vesicular structures across an in vitro model of the human intestinal epithelial cell barrier, regardless of the amount of endogenous PrPC expression. Unexpectedly, PrPSc is cotransported with ferritin, a prominent component of the DE-treated PrPSc-protein complex. The transport of PrPSc-ferritin is sensitive to low temperature, brefeldin-A, and nocodazole treatment and is inhibited by excess free ferritin, implicating a receptor- or transporter-mediated pathway. Because ferritin shares considerable homology across species, these data suggest that PrPSc-associated proteins, in particular ferritin, may facilitate PrPSc uptake in the intestine from distant species, leading to a carrier state in humans.
Key words: prion infection; subclinical infection; PrP transport; new variant CJD; ferritin; epithelial cell barrier; Caco-2
www.jneurosci.org/cgi/content/full/24/50/11280?ck=nck==================================
Because ferritin shares considerable homology across species, these data suggest that PrPSc-associated proteins, in particular ferritin, may facilitate PrPSc uptake in the intestine from distant species, leading to a carrier state in humans.====================================
Migrating intestinal dendritic cells transport PrPSc from the gutBovine spongiform encephalopathy, variant Creutzfeldt–Jakob disease (vCJD) and possibly also sheep scrapie are orally acquired transmissible spongiform encephalopathies (TSEs). TSE agents usually replicate in lymphoid tissues before they spread into the central nervous system. In mouse TSE models PrPc-expressing follicular dendritic cells (FDCs) resident in lymphoid germinal centres are essential for replication, and in their absence neuroinvasion is impaired. Disease-associated forms of PrP (PrPSc), a biochemical marker for TSE infection, also accumulate on FDCs in the lymphoid tissues of patients with vCJD and sheep with natural scrapie. TSE transport mechanisms between gut lumen and germinal centres are unknown. Migratory bone marrow-derived dendritic cells (DCs), entering the intestinal wall from blood, sample antigens from the gut lumen and carry them to mesenteric lymph nodes. Here we show that DCs acquire PrPSc in vitro, and transport intestinally administered PrPSc directly into lymphoid tissues in vivo. These studies suggest that DCs are a cellular bridge between the gut lumen and the lymphoid TSE replicative machinery.
vir.sgmjournals.org/cgi/content/abstract/83/1/267===============================
In another article referencing this phenomenon, the indication that these prions can propagate is clearly portrayed.
Instead of the usually Mendelian characteristic of mutations, prions carry the changes, as indicated here. These prions from yeast( s. cerevis) fungi (podospora) become the genetic material in humans, by use of the recombinants.
============================
Prions of Yeast and Fungi
PROTEINS AS GENETIC MATERIAL*
The genetic properties of [URE3] and [PSI], two non-chromosomal genetic elements of Saccharomyces cerevisiae, indicated that they were infectious proteins (prions) (1). Subsequent studies have supported this proposal, and the genetic criteria we proposed have been used in the discovery of another new prion, [Het-s], in the filamentous fungus Podospora anserina (2). The prion hypothesis has long been an intriguing explanation of the transmissible spongiform encephalopathies, such as scrapie, Creutzfeldt-Jakob disease, and “mad cow disease” (3-5) (reviewed in Refs. 6 and 7). Studies using Saccharomyces andPodospora have provided evidence of a type not available from studies of scrapie that there can be such a thing as an infectious protein. This work also revealed that prions can be the basis for inherited traits and initiated the use of the powerful yeast system to study this phenomenon. Here we review the basis for the proposal that [URE3], [PSI], and [Het-s] are prions of the chromosomally encoded Ure2p, Sup35p, and Het-s protein, respectively. We also review the properties of [URE3] and [Het-s]. Further studies of [PSI] are reviewed by Liebman and Derkatch in the following minireview (8), and other reviews of these subjects have appeared (9-12).
www.jbc.org/content/274/2/555.full=======================
The three things that seemed to push the prion as genetic material include
the Yeast........S. cerevis.
the Podospora anisera
and the aplysia
Sup 35 forms the amyloid, while pdodspora, the prion carries the message, the aplysia protein
moves it.--------------------------
Prions in Saccharomyces and Podospora spp.: protein-based inheritanceArticle Abstract:
Protein-based inheritance and prions are discussed relative to Saccharomyces and Podospora spp. On the basis of genetic properties two non-Mendelian genetic elements of S. cerevisiae, called (URE3) and (PSI), are prposed to be prions, or infectious proteins of Ure2p and Sup35p, respectively. Topics include genetic criteria for a prion, a prion form of Ure2p affecting nitrogen catabolism, a prion form of Sup35p, a translation release factor, (Het-s)Hets prion control of vegetative incompatibility in Podospora, comparison of prion systems, and structure-based inheritance: cortical inheritance on Paramecium and other ciliates.
www.faqs.org/abstracts/Biological-sciences/Prions-in-Saccharomyces-and-Podospora-spp-protein-based-inheritance.html=====================
URE3 from s. cerevisiae=============
Prion Filament Networks in [Ure3] Cells of Saccharomyces cerevisiaeVladislav V. Speranskya, Kimberly L. Taylorb, Herman K. Edskesb, Reed B. Wicknerb, and Alasdair C. Stevena
a Laboratory of Structural Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases
b Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892
Bldg. 6, Room B2-34, 6 Center Drive, MSC 2717, National Institutes of Health, Bethesda, MD 20892-2717.(301) 480-7629(301) 496-0132
steven@calvin.niams.nih.gov
=======================
The [URE3] prion (infectious protein) of yeast is a self-propagating, altered form of Ure2p that cannot carry out its normal function in nitrogen regulation. Previous data have shown that Ure2p can form protease-resistant amyloid filaments in vitro, and that it is aggregated in cells carrying the [URE3] prion. Here we show by electron microscopy that [URE3] cells overexpressing Ure2p contain distinctive, filamentous networks in their cytoplasm, and demonstrate by immunolabeling that these networks contain Ure2p. In contrast, overexpressing wild-type cells show a variety of Ure2p distributions: usually, the protein is dispersed sparsely throughout the cytoplasm, although occasionally it is found in multiple small, focal aggregates. However, these distributions do not resemble the single, large networks seen in [URE3] cells, nor do the control cells exhibit cytoplasmic filaments. In [URE3] cell extracts, Ure2p is present in aggregates that are only partially solubilized by boiling in SDS and urea. In these aggregates, the NH2-terminal prion domain is inaccessible to antibodies, whereas the COOH-terminal nitrogen regulation domain is accessible. This finding is consistent with the proposal that the prion domains stack to form the filament backbone, which is surrounded by the COOH-terminal domains. These observations support and further specify the concept of the [URE3] prion as a self-propagating amyloid.
Key Words: amyloid • yeast prion • immunoelectron microscopy • protease resistance • Ure2p
jcb.rupress.org/cgi/content/abstract/153/6/1327=========================
A SELF PROPAGATING AMYLOID, the perfect intermediate, crossing natural DNA of humans
with that of yeast by way of prion proteases, or the proteome. The network is established.
PSI? evolutionary advantage to the host?======================
Fungal prionsFungal prions provide an excellent model for the understanding of disease-forming mammalian prions. Fungal prions are naturally occurring proteins that can undergo a structural conversion that becomes self-propagating and infectious. They represent an epigenetic phenomenon in which information is not encoded in the nuclear DNA, but is structurally encoded within the protein. Several prion-forming proteins have been identified in fungi, primarily in the yeast Saccharomyces cerevisiae. Some of these are not associated with any disease state and may possibly have a beneficial role by giving an evolutionary advantage to their host[1].
en.wikipedia.org/wiki/Fungal_prions========================
Next I will concentrate on the podospora.========================
The HET-s Prion of Podospora anserinaPodospora anserina is a filamentous fungus. Genetically compatible colonies of this fungus can merge together and share cellular contents such as nutrients and cytoplasm. A natural system of protective "incompatibility" proteins exists to prevent promiscuous sharing between unrelated colonies. One such protein, called HET-S, adopts a prion-like form in order to function properly.[2] The prion form of HET-S spreads rapidly throughout the cellular network of a colony and can convert the non-prion form of the protein to a prion state after compatible colonies have merged.[3] However, when an incompatible colony tries to merge with a prion-containing colony, the prion causes the "invader" cells to die, ensuring that only related colonies obtain the benefit of sharing resources.
========================
Enter the Heat shock protein:===========================
Heat shock proteinHeat shock proteins (HSP) are a class of functionally related proteins whose expression is increased when cells are exposed to elevated temperatures or other stress.[1] This increase in expression is transcriptionally regulated. The dramatic upregulation of the heat shock proteins is a key part of the heat shock response and is induced primarily by heat shock factor (HSF).[2] HSPs are found in virtually all living organisms, from bacteria to humans.
Heat-shock proteins are named according to their molecular weight. For example, Hsp60, Hsp70 and Hsp90 (the most widely-studied HSPs) refer to families of heat shock proteins on the order of 60, 70 and 90 kilodaltons in size, respectively.[3] The small 8 kilodalton protein ubiquitin, which marks proteins for degradation, also has features of a heat shock protein.[4]
========================
It does appear that these are still infectious, according to Wickner.
=======================
Prions of Yeast
[PSI+] & [URE3]In 1965, Brian Cox, a geneticist working with the yeast Saccharomyces cerevisiae, described a genetic trait (termed [PSI+]) with an unusual pattern of inheritance. The initial discovery of [PSI+] was made in a strain auxotrophic for adenine due to a nonsense mutation.[1] Despite many years of effort, Cox could not identify a conventional mutation that was responsible for the [PSI+] trait. In 1994, yeast geneticist Reed Wickner correctly hypothesized that [PSI+] as well as another mysterious heritable trait, [URE3], resulted from prion forms of certain normal cellular proteins.[4] The names of yeast prions are frequently placed within brackets to indicate that they are non-mendelian in their passage to progeny cells, much like plasmid and mitochondrial DNA.
It was soon noticed that heat shock proteins (which help other proteins fold properly) were intimately tied to the inheritance and transmission of [PSI+] and many other yeast prions. Since then, researchers have unravelled how the proteins that code for [PSI+] and [URE3] can convert between prion and non-prion forms, as well as the consequences of having intracellular prions. When exposed to certain adverse conditions, PSI+ cells actually fare better than their prion-free siblings;[5] this finding suggests that, in some proteins, the ability to adopt a prion form may result from positive evolutionary selection.[6] It has been speculated that the ability to convert between prion infected and prion-free forms enables yeast to quickly and reversibly adapt in variable environments.
Nevertheless, Wickner maintains that URE3 and [PSI+] are diseases.
en.wikipedia.org/wiki/Heat_shock_proteinSkyship