Talk:Prion: Difference between revisions
→Heavy metal poisoning hypothesis: "Scrapie" should be more frequent in this article. Epidemiology at Pub Med (3 concerning Iceland and Britain) iz inconclusive, and Purdey's book did not post much in the way of numbers and graphs. |
→Heavy metal poisoning hypothesis: I am glad that Pub Med includes a journal az inclusive as Medical Hypotheses. |
||
Line 110: | Line 110: | ||
== Heavy metal poisoning hypothesis == |
== Heavy metal poisoning hypothesis == |
||
Ash of [[Hamster]] transmits encephalopathy.<ref name="pmid10716712">{{cite journal |author=Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC |title=New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=97 |issue=7 |pages=3418–21 |year=2000 |month=March |pmid=10716712 |pmc=16254 |doi=10.1073/pnas.050566797 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10716712 |accessdate=2010-02-28}}</ref><ref>{{cite pmid|15575075}}</ref><ref>{{cite pmid|9000112}}</ref> Two of those suggest neither protein nor [[DNA|D.N.A.]] as an agent of disease, and allow an inorganic material such as [[Manganism|Manganese]] to cause scrapie. It also agrees with Manganese polymerizing normal prion,<ref>{{cite pmid|22007749}}</ref> which is therefore proteinase resistant. Manganism readily allows spongiform encephalopathy to cross the species barrier.<ref>{{cite pmid|21908269}}</ref> |
Ash of [[Hamster]] transmits encephalopathy.<ref name="pmid10716712">{{cite journal |author=Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC |title=New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=97 |issue=7 |pages=3418–21 |year=2000 |month=March |pmid=10716712 |pmc=16254 |doi=10.1073/pnas.050566797 |url=http://www.pnas.org/cgi/pmidlookup?view=long&pmid=10716712 |accessdate=2010-02-28}}</ref><ref>{{cite pmid|15575075}}</ref><ref>{{cite pmid|9000112}}</ref> Two of those suggest neither protein nor [[DNA|D.N.A.]] as an agent of disease, and allow an inorganic material such as [[Manganism|Manganese]] to cause scrapie. This agrees with epidemiology in which Manganese concentrations at scrapie-affected sites were 2.5 times those of adjoining areas.<ref>{{cite pmid|10790765}}</ref> It also agrees with Manganese polymerizing normal prion,<ref>{{cite pmid|22007749}}</ref> which is therefore proteinase resistant. Manganism readily allows spongiform encephalopathy to cross the species barrier.<ref>{{cite pmid|21908269}}</ref> |
||
{{reflist}} |
{{reflist}} |
Revision as of 08:03, 12 March 2012
![]() | Prion has been listed as one of the Natural sciences good articles under the good article criteria. If you can improve it further, please do so. If it no longer meets these criteria, you can reassess it. | |||||||||||||||
| ||||||||||||||||
Current status: Good article |
![]() | This article is of interest to the following WikiProjects: | ||||||||||||||||||||||||||
Template:Wikiproject MCB
Please add the quality rating to the {{WikiProject banner shell}} template instead of this project banner. See WP:PIQA for details.
Please add the quality rating to the {{WikiProject banner shell}} template instead of this project banner. See WP:PIQA for details.
|
![]() | This article has been mentioned by a media organization:
|
![]() | This article was reviewed by Nature on December 14, 2005. Comments: It was found to have 7 errors. For more information about external reviews of Wikipedia articles and about this review in particular, see this page. |
Pronunciation
I'm not sure if we should specify only one pronunciation in the article. As much as some people are absolutely sure about this, IMHO it shouldn't be the same as that for "preon". Further, "when two vowels go walking, the first does the talking"; a little ditty which English-speaking folk should remember from grade-school. Also, the "pry'-on" pronunciation was in use years ago already, so I have a hard time believing it is wrong even if it has to share the choice of pronunciations in a dictionary. - KitchM (talk) 05:09, 3 February 2010 (UTC)
- I've seen Stanley Prusiner make a point about the pronunciation before, so I'd suggest keeping the "one true pronunciation." --Dpryan (talk) 00:31, 4 February 2010 (UTC)
GA Reassessment
- This discussion is transcluded from Talk:Prion/GA1. The edit link for this section can be used to add comments to the reassessment.
Starting GA reassessment as part of the GA Sweeps process. Jezhotwells (talk) 20:57, 28 February 2010 (UTC)
Checking against GA criteria
- It is reasonably well written.
- a (prose):
b (MoS):
- a (prose):
- It is factually accurate and verifiable.
- a (references):
b (citations to reliable sources):
c (OR):
There are a number of un-cited paragraphs.I think all paragraphs have reliable source links, now. -- MarcoTolo (talk) 17:23, 2 March 2010 (UTC)Done
There are a number of citation needed tags, also some verification needed tags. First half done. -- MarcoTolo (talk) 00:55, 1 March 2010 (UTC)All done, I think. -- MarcoTolo (talk) 17:23, 2 March 2010 (UTC)Done
I repaired some dead links and tagged others using WP:CHECKLINKS.Fixed. -- MarcoTolo (talk) 00:55, 1 March 2010 (UTC)Done
There are a few bare URLs in the citations, please use templates to attribute publication date, author, publishers, etc.Fixed. -- MarcoTolo (talk) 00:55, 1 March 2010 (UTC)Done
- a (references):
- It is broad in its coverage.
- a (major aspects):
b (focused):
- a (major aspects):
- It follows the neutral point of view policy.
- Fair representation without bias:
- Fair representation without bias:
- It is stable.
- No edit wars, etc.:
- No edit wars, etc.:
- It is illustrated by images, where possible and appropriate.
- a (images are tagged and non-free images have fair use rationales):
b (appropriate use with suitable captions):
- a (images are tagged and non-free images have fair use rationales):
- Overall:
- Pass/Fail:
- Overall the article is in fairly good shape. Main issue: Referencing as per above. ON hold until 7 March, major contributors and projects will be notified. Jezhotwells (talk) 21:24, 28 February 2010 (UTC)
- Thanks for your hard work, the article is much improved, I am happy to confirm GA status. Jezhotwells (talk) 18:49, 2 March 2010 (UTC)
- Pass/Fail:
The citation given (3) does not support the statement referred to.Rotlor (talk) 03:42, 2 May 2010 (UTC)
Self-Replication
How is it that prions do not self-replicate? It's not like DNA singularly reconstructs copies of itself from constituent molecules. Virtually nothing recreates itself from basic components without the aid of environmental machinery, including DNA. Under what I infer the definition of self-replicating to be from the article's usage, I conclude that only self-catalyzing RNA such as Spiegelman's Monster are actually self-replicating. Moreover, the article on self-replication lists prions as an example! —Preceding unsigned comment added by 76.173.186.135 (talk) 06:51, 22 May 2010 (UTC)
- Even the monster requires RNA replicase... —Preceding unsigned comment added by 76.173.186.135 (talk) 06:53, 22 May 2010 (UTC)
- Agreed. Every cell from microbiology to animal iz all part of one big machine, and nobody haz witnessed the creation of life. Amino acids? Yes. Nucleic Acids, even. But make them work together? Not seen. Oops. There is a blue bacterium that someone created from scratch. Whether it is compatible with life on Earth iz another question, since they put a lot of extraneous DNA into it, just because they could. 142.59.231.219 (talk) 07:01, 12 March 2012 (UTC)
Proposed new section of prion replication mechanism
Earlier I deleted one of the figures, of the heterodimer model of prion propagation, because it was not supported by the data. I think it is important to put back something more about the replication mechanism. I have written a draft of a new section, which I think would fit in very naturally between the Structure and Function sections. I included both the old figure that I deleted, and a new one. I don't know how to format figure size, could somebody please help? Also any other changes/suggestions before I insert this section into the real page.Joannamasel (talk) 17:28, 29 August 2010 (UTC)
- The "heterodimer" diagram wasn't intended to literally represent a dimer - it is just meant to be a broad representation of PrPC interacting with PrPSc or whatever the infectious form actually is. It definitely wasn't intended to mean the dimer would then split into two again. The section doesn't entirely make sense as it is - it says that the heterodimer model would require PrPSc to be an amazing catalyst, but then the fibril model described would still require PrPSc to convert PrPSc, so there's really no difference between them. I think this section is overcomplicated - it would better to have one diagram. Theres no need to mention fibrils, and it doesn't have to mention PrPSc, as you can have prion diseases without either of those being present. If you really want to go into detail, the 2 main contenders for mechanism have traditionally been template-assisted conversion and nucleation-polymerisation. Purple 23:38, 2 December 2011 (UTC)
- I think that the fact that prions require an oligomeric form is notable, and this is easier to explain by means of a contrast with an alternative model. There is a range of evidence pointing to some kind of fibril as this form. I tried to clarify the section you found confusing, and how cooperativity makes the two cases different: you can find more details in Eigen's paper. Most of the literature on nucleation-polymerisation concerns in vitro work. (Primary) nucleation is obviously not part of the process of a disease acquired a single time by infection. I think the article should focus on in vivo replication as far as is practical.Joannamasel (talk) 00:49, 3 December 2011 (UTC)
Image needed
Need some 3d images of prions. --68.91.94.192 (talk) 21:54, 7 October 2011 (UTC)
See PrP. I suppose there are two articles on the same thing, because this article got too big. 137.186.47.81 (talk) 17:28, 9 March 2012 (UTC)
Alzheimers caused by prions
Research is showing alzheimers might be caused by it.--68.91.94.192 (talk) 21:54, 7 October 2011 (UTC)
- That iz not news to me. The unifying symptom iz amyloidosis.
137.186.47.81 (talk) 15:16, 4 March 2012 (UTC)
Is it alive?
Given all that it does, is it reasonable to regard the prion as alive; ie, that it is a lifeform in its own right? I'm not pushing either answer, simply looking for arguments either for or against. Old_Wombat (talk) 09:47, 24 January 2012 (UTC)
- No. I believe Gajdusek's 'Ash of Hamster' experiment proves more than he claimed in his title: The cause of scrapie iz inorganic. Even viruses need both DNA and protein, and by themselves they are dead and dormant, only to come alive when they get access to a cell with the rest of the minerals and energy needed to replicate. 142.59.231.219 (talk) 06:55, 12 March 2012 (UTC)
No such thing az PrPC iz.
No such thing az common protease resistant protein egzists. If such a thing wuz, then we would all hav Alzheimer's. This acronym iz a lie. Delete it, and replace it with "a protein that can become protease resistant", or just "a protein" or "amyloid precuror protein (APP)". 137.186.47.81 (talk) 15:06, 4 March 2012 (UTC)
- The name of the gene/protein is PrP. It doesn't matter what this originally stood for, although for the record, it stands for prion protein, not protease resistant protein, something made quite clear in the article. In any case, PrP is now its name. It is defined by its amino acid sequence, or homology thereto. You cannot change that fact on a wikipedia page. Amyloid precursor protein is a completely different protein. You cannot substitute that in. Nor can you substitute in generic reference to a protein. PrP is a particular protein, and PrPC is the accepted term for one form of that particular protein. I will revert your changes, please do not edit again without first getting consensus for this very major change on the talk page. I am also reverting changes to the heavy metal poisoning hypothesis section. No reason was given for the deletion of existing material, and the material you replaced it with is not supported by the accompanying references. Joannamasel (talk) 00:40, 5 March 2012 (UTC)
- Moreover, the amyloid precursor protein (APP) is a completely different protein (sequence and structure) from PrP. APP is (as the same suggests) the precursor protein from which the beta amyloid peptide is cleaved; the disease for which it is reasponsible – Alzheimer's – has never shown any sign of being susceptible to prion transmission. That said, we should probably look at the way the material in the 'Structure' and 'Function' sections is presented; there's a lot of material that's specific to mammalian PrP that probably shouldn't be in this more-general 'prion' article. TenOfAllTrades(talk) 02:16, 5 March 2012 (UTC)
- I am sorry that I did not believe you in the first place. It would've helped if you had noticed that someone else on this page did not realize that PrP is a different article from prion. Owing to redirections, it happens that they could be the same article. 137.186.47.81 (talk) 20:09, 9 March 2012 (UTC)
- Material on the structure haz been deleted, because it would detract from what haz become the point of the article: It contains too much dissent, and it iz too overwhelming to actually believe in an infectious protein, so drawing pictures of it became offensive. No clear evidence of an infectious protein exists, and Gajdusek offers convincing evidence that the cause of CJD iz inorganic. Alzheimer's and CJD cannot be easily distinguished. Both of them rezult in a smaller brain with holes and amyloid plaques. An old version of this article (probably with pictures) lists the other "prion diseases", including other species, Alzheimer's among them. I put my bit in here to illustrate that yes, indeed, my references support my statements. I deleted the section az it wuz, because it did not clearly support the manganism hypothesis. I can barely read it az it iz. I do not accept PrP to mean prion protein. The coroner's test of amyloidosis iz protease resistant protein, although there are probably many other tests and stains. PrP and APP are identical: See the link to amyloidosis. 137.186.47.81 (talk) 16:14, 5 March 2012 (UTC)
- Perhaps you've been confused by the suggestion (for which at least some evidence does exist) that the major prion protein PrP may be a membrane receptor for the beta amyloid peptide? As long as you're hung up on basic factual errors like equating APP and PrP you're not going to be able to understand the literature, and I'm afraid there's not a lot I can do to help you.
- In any event, could take a little more time to proofread your posts? The chronic misspellings are extremely distracting. TenOfAllTrades(talk) 17:24, 5 March 2012 (UTC)
- My "misspellings" are literal and intentional. I am primarily a linguist. I know what schwa iz. The people who write pronunciations into wikipedia do not.
- I looked around with the question "how does anyone know that PrP and APP are different". I did find an interesting article, and it did not answer my question. http://everything2.com/title/The+prion+protein+as+a+receptor+for+amyloid-beta It wuz a whole lot easier to read than anything Prussiner writes, though. Perhaps you can find something that explains this basic understanding you have, because az far az I know, basic understandings come from wikipedia. 137.186.47.81 (talk) 17:34, 5 March 2012 (UTC)
- Meanwhile, this gets 88 hits:
http://www.ncbi.nlm.nih.gov/pubmed?term=PrP%20amyloid%20plaque
- The 'basic understanding' that APP and PrP are different proteins is readily apparent from their respective Wikipedia articles, to which I've already linked. I'm seriously concerned that your recent edits to this and other disease-related articles are not backed by a sufficient background competence in biochemistry and medicine, and your confrontational attitude (insisting that you be spoon-fed and tutored, and that other editors put up with your deliberate obfuscation of your language) disinclines me to expend the effort to deal with that deficit. TenOfAllTrades(talk) 04:42, 6 March 2012 (UTC)
- If you do not feel like doing the research, it iz nice of you to say so, and don't blame me: Do not spend more time arguing with me than with my points. Both are involved in amyloidosis. APP and PrP will both bind with copper. So, what happens in vivo? Do they fight for copper? Or iz one protein part of the other, so that some large structure, like an ionophore can decide whether a cell needs more copper? This issue is a side issue. My section on Manganism is far less obfuscatory than what iz already there. What iz there begs relevance. 137.186.47.81 (talk) 11:08, 8 March 2012 (UTC)
Heavy metal poisoning hypothesis
Ash of Hamster transmits encephalopathy.[1][2][3] Two of those suggest neither protein nor D.N.A. as an agent of disease, and allow an inorganic material such as Manganese to cause scrapie. This agrees with epidemiology in which Manganese concentrations at scrapie-affected sites were 2.5 times those of adjoining areas.[4] It also agrees with Manganese polymerizing normal prion,[5] which is therefore proteinase resistant. Manganism readily allows spongiform encephalopathy to cross the species barrier.[6]
- ^ Brown P, Rau EH, Johnson BK, Bacote AE, Gibbs CJ, Gajdusek DC (2000). "New studies on the heat resistance of hamster-adapted scrapie agent: threshold survival after ashing at 600 degrees C suggests an inorganic template of replication". Proceedings of the National Academy of Sciences of the United States of America. 97 (7): 3418–21. doi:10.1073/pnas.050566797. PMC 16254. PMID 10716712. Retrieved 2010-02-28.
{{cite journal}}
: Unknown parameter|month=
ignored (help)CS1 maint: multiple names: authors list (link) - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 15575075, please use {{cite journal}} with
|pmid=15575075
instead. - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 9000112, please use {{cite journal}} with
|pmid=9000112
instead. - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 10790765, please use {{cite journal}} with
|pmid=10790765
instead. - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 22007749, please use {{cite journal}} with
|pmid=22007749
instead. - ^ Attention: This template ({{cite pmid}}) is deprecated. To cite the publication identified by PMID 21908269, please use {{cite journal}} with
|pmid=21908269
instead.
The Gajdusek paper you cite is certainly a provocative and controversial one, but it does not claim to eliminate protein as a vector. Incineration to 600C massively reduced infectivity, even though it did not eliminate it altogether. The authors hypothesize that the core fact about a prion is its shape. While it is NORMALLY A PROTEIN that takes this shape, they hypothesized that it is also possible for inorganic ash to retain an imprint of the shape that a protein previously held, and so act as an inefficient template for future protein conversion to restore the presence of prions. I would be happy to see this paper covered in the prion article, but your text is not consistent with the authors' claims. In contrast, manganism is a fringe theory, and does not belong on this page at all. Joannamasel (talk) 16:05, 8 March 2012 (UTC)
- You hav two peer-reviewed, pubmed-listed articles to classify as fringe theory. This is one: http://www.ncbi.nlm.nih.gov/pubmed/8912903 The other one is about manganese-catalyzed polymerization. 137.186.47.81 (talk) 15:01, 9 March 2012 (UTC)
- The article you link to here does not mention prions, and so does not support your point.Joannamasel (talk) 19:29, 9 March 2012 (UTC)
- That does not follow. It mentions amyloidosis. The reason someone thinks that prions can deform prions is because proteinase resistant protein is involved in amyloidosis. 137.186.47.81 (talk) 19:56, 9 March 2012 (UTC)
- Plenty of articles relevant to prions that do not mention prions can be found on Pub Med with a search for scrapie: http://www.ncbi.nlm.nih.gov/pubmed?term=(scrapie)%20NOT%20prion 142.59.231.219 (talk) 03:31, 11 March 2012 (UTC)
- Two transmissions at 600C is a containment failure, and the dose of 0.03mL iz too small. I would like to see the experiment done with oral feeding, too. I've read that it was done before 2000, and I just don't know the right search terms.
- It is unfortunate that the authors chose so many words, and a conservative estimate of what their evidence means in their title. It is also unfortunate that Gajdusek said anything about "hamster-adapted scrapie agent" before he said anything about "inorganic". It is easy to explain 600C, and I do wish they had used lower temperatures and longer periods of incineration. When Wood Ash is burned at 600C, many of the trace metals vaporize. When you add all of my citations together, Manganism iz not a theory, and the remaining text in that section is still not related to a heavy metal poisoning hypothesis. Ash of Hamster transmits encephalopathy. It does not contain carbon. I wish the authors had analyzed their ash for protein molecules. At the temperatures they were using (six times boiling), I would not believe complete molecules of any protein, and it would not hurt to be sure. 137.186.47.81 (talk) 11:45, 9 March 2012 (UTC)
How differs APP from prion?
Please put your answer here 137.186.47.81 (talk) 17:12, 9 March 2012 (UTC)
- It's very simple. A protein is defined by its amino acid sequence. APP and PrP are the names for two proteins, that have totally different amino acid sequences. Joannamasel (talk) 15:59, 8 March 2012 (UTC)
- Maybe I can believe you, and I can't believe the guy who is trying to tell me that prions and PrP are different. They are different articles; different aspects of the same thing. That was my biggest problem. I did not follow a link to PrP, because I thot it was a redirection to prion. 137.186.47.81 (talk) 20:04, 9 March 2012 (UTC)
- Wikipedia good articles
- Natural sciences good articles
- Old requests for peer review
- GA-Class neuroscience articles
- High-importance neuroscience articles
- GA-Class medicine articles
- High-importance medicine articles
- All WikiProject Medicine pages
- Wikipedia pages referenced by the press
- Externally peer reviewed articles
- Externally peer reviewed articles by Nature