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Post by skyship on Mar 31, 2010 12:26:03 GMT -5
aplysia.miami.edu/producing-snails.htmlHow they are used? ?? The emerging concept of functional amyloid C. P. J. Maury From the Department of Medicine, University of Helsinki, Helsinki, Finland Correspondence to Prof. C. P. J. Maury, MD, PhD, Department of Medicine, University of Helsinki, Kasarmikatu 11–13, FI-00130 Helsinki, Finland. (fax: +358 9 47188688; e-mail: peter.maury@hus.fi). Copyright © 2009 Blackwell Publishing Ltd KEYWORDS β-sheet aggregates • amyloidosis • functional amyloid • prions • protein conformation • protein-based inheritance Maury CPJ (University of Helsinki, Helsinki, Finland). The emerging concept of functional amyloid (Review). J Intern Med 2009; 265: 329–334. ABSTRACT Abstract. Although amyloid has usually been considered a pathological structure, growing evidence indicates that amyloid may also be a productive part of cell biology contributing to normal physiology. In fact, amyloid formation seems to be an intrinsic propensity of polypeptides in general and the amyloid β-fold an evolutionary highly conserved structure. Functional amyloids have been found in a wide range of organisms, from bacteria to mammals, with functions as diverse as biofilm formation, development of aerial structures, scaffolding, regulation of melanin synthesis, epigenetic control of polyamines and information transfer. Obviously, organisms have evolved taking advantage of the canonical amyloid β-sheet fold, a conformation that possesses both high resistance to proteolysis, self-replicative properties and capability to function as a molecular memory. Molecular memory? Melanin synthesis self replicative proterties www3.interscience.wiley.com/journal/122189425/abstract============= Toward a Molecular Biology of Learning-Related Synaptic Growth In Aplysiawww.cellscience.com/reviews6/Learning-related_synaptic_growth.html====================== skyship
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Post by skyship on Mar 31, 2010 12:36:42 GMT -5
Use of aplysia prion to form amyloids? One of the proteins that has been associated with the synapse stabilization process in Aplysia is called ApCPEB. Its function is somewhat unclear but, like Sup35, it also may be involved in control of protein translation. ApCPEB localizes to the synapse region, and upon repeated synaptic stimulation it forms “clusters” with different regulatory properties compared to the monomeric protein. Once formed, these clusters remain stable despite protein turn-over, even in the absence of further stimulatory signals. In yeast, ApCPEB has been shown to act as a bona fide prion, which would explain the formation of clusters and their stable properties. These findings have raised enormous interest, not only from prion specialists, but among biologists in general. Many papers have appeared in major journals discussing the data and their implications. The extent of these phenomena in the biological world is unclear: prion-based inheritance and evolution may be extremely rare, or perhaps it’s quite pervasive and we just missed it. Some scientists are already talking about “paradigm shifts” [e.g., 2], although that’s probably premature. Regardless, it certainly runs against the impression, which ID proponents are trying to project in their P.R. communiques, of a monolithic, censorial Darwinian orthodoxy bent on stifling dissent and hiding evidence inconsistent with mainstream evolutionary theory. It is hard to say at this point whether in 50 years evolutionary biology textbooks will devote prions a whole chapter, a page, or just a footnote. But prions, unlike ID, will most like be there. pandasthumb.org/archives/2005/10/of-prions-and-p.htmlskyship
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Post by skyship on Mar 31, 2010 12:43:54 GMT -5
Now, consider this: An exciting development came earlier this year with the discovery that the ability of prion particles to spread infection depends on their brittleness (Tanaka et al, 2006). Jonathan Weissman, from the Howard Hughes Medical Institute at the University of California, San Francisco, USA, and colleagues showed that the more brittle—and therefore less stable—prion particles break into smaller fragments more frequently. This creates new seeding particles that, in turn, grow into larger aggregates by recruiting new molecules of the same protein. Weissman and his colleagues conducted their studies on yeast prions; although their ability to cause infection is doubted by many researchers, they transmit their abnormal folding configuration to normal molecules in a similar way to mammalian prions. Indeed, this research has been acknowledged as an important step forwards, even by leading scientists who are uncomfortable defining yeast proteins as prions at all. "I think it is fantastic work and it makes a lot of sense," said Adriano Aguzzi, a professor of neuropathology at University Hospital Zurich, Switzerland, and a leading expert on prion diseases. "The idea that the more brittle the prion, the faster its replication, fits exactly with data we have been collecting." ...the fact that proteins can cause infection has been widely accepted by all but a few hardcore dissenters This work is just the latest chapter in a story that began with Prusiner's "protein-only" hypothesis in 1982. The belief then was that one particular protein—which Prusiner called prion-related protein, or PrP—imposes its structural conformation on others, causing them to aggregate into clumps that are generally infectious. Subsequent work showed, however, that PrP occurs widely in the cells of healthy mammals, and that infection and disease is caused only by particles that are folded in a specific way. The normal form of the protein was then called PrPC, with the C referring to cellular, whereas the infectious form was called PrPSc, with the Sc referring to scrapie. Since 1982, research has focused on PrP as the only known infectious protein occurring natively in its normal form, but recently a few other candidates have emerged, notably among the amyloids. These are fibrillar deposits comprising a fibril protein and additional molecules (Fig 1), which can cause disease and have been shown to be transmissible through a seeding mechanism similar to that of PrPSc. The most common form of amyloid disease in humans is AA amyloidosis, so called because it involves deposits of fibrils comprising the serum amyloid A (AA) protein, produced predominantly by hepatocytes. These proteins are converted into their amyloid form as the result of chronic inflammation. There are several theories as to how this transformation occurs, although several lines of research have indicated that it results from specific interactions between AA and heparan sulphate, a component of the extracellular matrix. Amyloidoses are often inherited; the relevant alleles have point mutations that encourage the parts of the amyloid prone to aggregation to split off and form new 'seeds'. www.nature.com/embor/journal/v7/n12/full/7400863.htmlMore generally, the concept of a protein existing in two or more states—one of which is dominant and can spread its conformation through a process akin to infection—is gaining support, with a small number of likely candidates turning up in humans. One of the most exciting discoveries was made by Eric Kandel at Columbia University (New York, NY, USA), who shared the 2000 Nobel Prize in Physiology or Medicine for his research on signal transduction in the nervous system. This research led to a study of cytoplasmic polyadenylation element binding (CPEB) protein, which regulates mRNA translation in neurons. Kandel found that CPEB has properties similar to yeast prions (Si et al, 2003) and hypothesized that structural conversion of CPEB occurs during the formation and maintenance of memories. Having switched to the dominant prion state, CPEB retains this configuration, thus providing the stability required for long-term memory storage. Kandel and colleagues are now drafting a follow-up paper on CPEB in Aplysia, a marine snail, which shows that the protein has prion properties in nerve cells. This all lends credence to Aguzzi's belief that prions were bound to be invented because of their unique properties as vectors of conformational information. Recent research now suggests that many more examples of their advantageous roles will be discovered. It might be that the pathological aspect of prions is an aberration and that their main biological role is in the storage and transmission of information between cells. www.nature.com/embor/journal/v7/n12/full/7400863.htmlskyship
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Post by skyship on Mar 31, 2010 13:27:18 GMT -5
Where do prions come from in the first place? they are found in nature, ........ fungus, as well, the snail, etc. what fungus carries prions? wonder if there is a connection between uracil and prions and amyloids? ========================== Isolation of uracil auxotrophic mutants of Trichoderma harzianum and their transformation with heterologous vectors LászlóManczingerx*ZsuzsannaAntalLajosFerenczy 1 Department of Microbiology, Attila József University, PO Box 533, H-6701 Szeged, Hungary *Corresponding author. Fax: + 36 (432) 488. Copyright 1995 Federation of European Microbiological Societies KEYWORDS Trichoderma harzianum • Uracil auxotrophic mutants • Genetic transformation • Heterologous vectors ABSTRACT AbstractNine uracil auxotrophic mutants were isolated from a mycoparasitic strain of Trichoderma harzianum. One of these could be transformed with the pKIM7 cosmid, which contained the pyr-4 gene of Neurospora crassa. Another uracil-requiring mutant was transformed with heterologous vectors containing the orotate pyrophosphoribosyl transferase genes of Podospora anserina and Trichoderma reesei. The transformation frequencies varied between 150 and 1000 μg−1 plasmid DNA. Hybridization analysis of the transformants revealed distinct locations of integrated vectors in the genomes, but in some transformants freely replicating plasmids could also be detected. www3.interscience.wiley.com/journal/119249269/abstractWhere did Uracil come from? and how did it get in human genome? ====================== Abstract Uracil is a natural base of RNA but may appear in DNA through two different pathways including cytosine deamination or misincorporation of deoxyuridine 5'-triphosphate nucleotide (dUTP) during DNA replication and constitutes one of the most frequent DNA lesions. In cellular organisms, such lesions are faithfully cleared out through several universal DNA repair mechanisms, thus preventing genome injury. However, several recent studies have brought some pieces of evidence that introduction of uracil bases in viral genomic DNA intermediates during genome replication might be a way of innate immune defence against some viruses. As part of countermeasures, numerous viruses have developed powerful strategies to prevent emergence of uracilated viral genomes and/or to eliminate uracils already incorporated into DNA. This review will present the current knowledge about the cellular and viral countermeasures against uracils in DNA and the implications of these uracils as weapons against viruses. www.retrovirology.com/content/5/1/45wow, so uracil causing problems? replaces thymine? skyship
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