Talk:Peripherin

Non-peer review

Hey guys, it looks really great. You're probably closing in on the finished product, so I have some final suggestions:

• The last sentence in the introduction should include a reference
• You should try and find a picture that you can use for the structure. You can usually find images on PDB, but I'm not sure what the copyrights are like on those images. If you haven't looked at Wikimedia Commons yet, you should definitely do that. Also you could contact the group that is doing Cyclic nucleotide-gated ion channel, I think they were able to get a picture of the structure.
• Check your use of the "Main article" links--I think it may be more appropriate in these instances to use "See also" instead

Good luck! 136.167.123.243 (talk) 22:20, 5 December 2011 (UTC)

Thanks for the pointers! A reference has been added to the end of the introduction. That was an oversight so thank you for pointing it out! Also, we agree with the substitution of "see also" for the "main article" links. The topics discussed in this article were different enough from the main topic that this makes sense. In regards to the picture, we have searched both databases you suggested for images directly related to peripherin and type III intermediate filaments in general and have not been able to find a relevant image with regards to structure. we will keep looking however and hopefully will be able to find something. Thanks again! Kelseyfish1189 (talk) 16:46, 6 December 2011 (UTC)

Peer Review 1

This is a very well-written article. The information presented on peripherin is extensive yet clear so that the reader can understand it. I think that the introduction gives the reader a concise yet complete idea of what to expect from the rest of the article. I feel that after reading the article I have a firm grasp on peripherin’s function and big-picture significance. That being said, I do have a few minor comments to offer. I think you could add a few more hyperlinks to some of the terms throughout the article for readers who may be somewhat less informed on neuroscience topics (i.e. apoptosis and siRNA form the Potential applications section and the JAK-STAT pathway from the Regulatory mechanisms section). If possible it would be really helpful if you could add pictures to the page (I know it’s hard to find relevant ones on WikiCommons). Even if it’s a picture of NGF next to Regulatory mechanisms or a photo relating to the physical basis of ALS, I think it would really enhance your page. Finally, I think that if you could expand on the clinical significance of peripherin a little more, your article would be even better. I know that peripherin is of great importance in ALS (thanks to your article) but are there any other diseases associated with peripherin deficiency or mutation? I looked into it a little and found that peripherin staining has been used to diagnose Hirschsprung’s disease. Maybe you could add a sentence about that to your application section. Hope this helps! Great article! — Preceding unsigned comment added by Tas45 (talk • contribs) 21:31, 15 November 2011 (UTC)

Tas45: Thank you so much for your feedback! With regards to pictures, 23 have looked pretty extensively for pictures to use in this article and as of yet have not found anything directly related to this topic, but 23 will definitely keep looking. We agree completely that pictures help with clarity and always improve an article! As far as the clinical significance, the dominating topic in the research pertains to peripherin's possible significant role in ALS. However, as you were able to find some information about peripheirn staining and Hirschsprung's disease, we will be sure to look further into that and add information to the article! Thanks for the tip! Also, more links will be added as you suggested. Like pictures, this will greatly help with the clarity. Thank you for all of your feedback! Kelseyfish1189 (talk) 17:43, 16 November 2011 (UTC)

Peer Review 2

First off, this is a strong article on the protein. The introduction, structure, and function aspect of the protein is well written, which is the most important part of this article. The only thing I could think of adding to help this article was the clinical significance and the regulatory mechanism of the article. In the clinical significance section of the article, was the section all dedicated to ALS? All I can add to this is maybe you can add other diseases that is concerned with this protein. In addition, another advice I can give is maybe you can add pictures of the biochemical aspect of how NGF regulates the protein. This was truly a strong article so I have nothing else I can nit pick on.

Bcneuro (talk) 04:45, 16 November 2011 (UTC)

Bcneruro: Your feedback is greatly appreciated! As stated above, peripherin's role in ALS dominated most of the research as far as clinical significance was concerned. There is still very little known about the exact role and functions of peripherin, but the connection to ALS is by far the most explored. That being said, User Tas45 suggested a link between peripherin and Hirschsprung's disease. This will definitely be further explored and hopefully will contribute to the section! Also, the search for pictures will most certainly continue, as this would greatly enhance this article. Thanks again for your feedback! Kelseyfish1189 (talk) 17:43, 16 November 2011 (UTC)

Peer Review 3

I found your article to be very informative. As an English major, I have a few copyedits, as well as recommendations for improving your article. First off, maybe it’s just because I don’t understand, but I was wondering if you could expand on what “homopolymeric filamentous networks” are as opposed to coexisting with neurofilaments in your introduction. To me these need to be distinguished a bit more clearly so that the reader understands the unique property of peripherin as opposed to the other proteins you name. I also wonder if you might want to explain the different types of intermediate filaments a tad, particularly as two different types (III and IV, I believe) come into significant play later on in the article. Next, this sentence needs to be fixed: “The rod also contains specific placement of alternating acidic and basic residues, many of which are spaced 4 aa apart”. Amino acid should be written out completely. Also, there should be a comma after ionic salt bridges in this fragment: “ionic salt bridges which serve to stabilize”. After that, I think that this sentence should be broken up into two sentences after squiggles because it becomes a bit run-on: “These states include nonfilamentous particles which combine to firm short IFs, or squiggles, which come together to form long IFs that make up cytoskeletal networks”. The dash after kinesin should be removed in the Structures and properties section. There should be a comma after manner in this fragment: “manner and as spreading continues, the particles polymerize into intermediate filaments”. There is a tense shift in this sentence: “These two alternatives were both made by alternative splicing”. Were should be switched to are. I was confused in the section on the different types of peripherin. Given that you never mention that Per 57 is the main peripherin prior to the end of the Structures and properties section, this came a bit out of the blue. I think you should add an earlier sentence mentioning the 57 version as the dominant form. That said, I was also confused by this sentence: “Per 56 is made by a receptor on exon 9 of the peripherin gene transcript which induces a frameshift and replacement of C-terminal 21 amino acids with a new 8 amino acid sequence”. Are you saying that 21 amino acids in the C-terminal are replaced with 8 different ones? Also, since you haven’t mentioned the structure of the C-terminal prior to this, I find this sentence hard to follow. Maybe it would be better to say something like: The frameshift mutation leads to the replacement of a sequence of 21 amino acids in the C-terminal found on the dominant 57 form with a new sequence of 8 amino acids. (Or something to that effect – I realize that wasn’t the cleanest English). Also, C-terminal should not be linked here, you have already linked it earlier in the article. Next, there should be a comma before whereas: “Per 57 and 56 are normally co-expressed whereas Per 61 is not found in normal peripherin expression in adult motor neurons”. Also, if Per 56 is co-expressed with 57, how is 57 the main form? Furthermore, since they are co-expressed, they should follow each other in the article, instead of treating 57, then 61, then 56. Is there anything significant about the fact that 57 and 56 are normally co-expressed? Moreover, if Per 61 is not found in normal adult motor neurons, then where is it found? What, if any, is its significance as a variant? Next, this is a run-on sentence; there should be a semi-colon before however: “Post transcriptional mechanisms reduce detectable peripehrin to only the small sized cells, however crushing of the peripheral processes in dorsal root ganglion neurons lead to mRNA and detectable peripherin in the large sized cells”. Moreover, I think you should link JAK-STAT at the instance where the JAK-STAT pathway comes up. Or, if there is no link (though there should be, I would think), then I might explain it a tad. In the Function section, I would explain (if you can, I know my topic had precious little information) why it is important for the type III to transition to type IV to “attain normal velocities of action potentials”. What would happen if this transition did not take place? Finally, given peripherin’s potential role in ALS, I wonder if there is any information on treatment of ALS by targeting peripherin. Since you note that a knockout seems to cause no issues, could a treatment in which the mutated form of peripherin is knocked down potentially serve as a treatment for ALS? Is there any information on this at all? If so, I would definitely include a section on what treatments involving peripherin are being looked into. Also, if you have any more information on future research directions (that is, the research going on at the moment), I would either add more of that to the section Potential applications or create a new section titled Research directions. Sorry this is a monstrous comment, I was just taking notes as I went through. Good luck with the rest, I definitely feel far more informed! Fowlerta (talk) 14:46, 16 November 2011 (UTC)

Fowlerta: Thank you for your very thorough commentary! The grammar edits throughout were extremely helpful, as those tend to get lost with a large amount of text. Your comment about the confusion between coexisting and homopolymerizing were justified. What makes peripherin special is that it can heteropolymerize with other types of IFs, so this has been changed in the introduction. We hope this adds clarity. The confusion with the gene variants is also understandable. Unfortunately, there is little information regarding the causes and effects of such variation outside of what was presented. Per61, as stated in the article, has so far been found in mice only. Hopefully many of these questions regarding the significance of the variants will be explored in future research. Along those lines, current research so far has not indicated any peripherin related therapy in ALS treatment. Currently, its potential involvement in the disease is more the target of research investigation. Hopefully this clears a few things up. Again, thank you very much for the grammar edits. They, along with some additional hyperlinks, have been added. Kelseyfish1189 (talk) 18:31, 5 December 2011 (UTC)

Peer Review 4

Hey guys! This article is very good overall. I really liked how you got the box on the upper right that is able to categorize everything and link to the databases, that is very useful. There are a couple things that can be improved. The first line of the introduction states that the PRPH gene encodes Periperin in the human genome. I feel that the first line of the intro should emphasize the 'function' of the protein rather than where it is encoded. It is an important fact, but not the most vial piece of information for someone looking this up. You also blend history and the introduction together. This is more of a group thing, but perhaps you guys could make that a different subsection. The function and structure parts are well-researched, very good job on that. What needs expanded the most though is the potential application/clinical sections. Is ALS the only disease implicated with this protein? It says in potential applications that there is possible involvement in other neurodegenerative diseases. Mentioning those would be a good addition. Also, could you guys not find anything about the link between Periperin, or did you find an article saying it hasn’t been discovered yet? Because talking more about the direct link would be great. Hopefully these questions and suggestions will help you out, great job guys! Ayman S. Bodair (talk) 19:36, 16 November 2011 (UTC)BCayman1992

BCayman1992: Thanks for your feedback! You were not alone in suggesting the reorganization of the introduction, so that has been changed, and we think it helps greatly with the clarity and flow of the article. Thanks! What was presented in the clinical section is largely what has been found thus far. Some connections between peripherin and other diseases have been discussed, and have been added to the clinical section! The dominating disease discussed in the research is ALS and the possible role of peripherin in this disease. Your question about a direct link with peripherin was slightly confusing...did you mean a direct link between peripherin and ALS? If so, there has not as of yet been a cause for ALS directly linked to peripherin. What has been presented in the research as well as in the article is that there have been peripherin related changes found in some ALS cases. The exact role and significance of these peripherin variants is not completely understood and is under further investigation. We hope this clarifies your question! Thank you again for your contributions, they were greatly appreciated! Kelseyfish1189 (talk) 18:52, 5 December 2011 (UTC)

Peer Review 5

Hey Peripherin group!

First off, I think your article is one of the best at including very scientific research that professionals can understand, but straightforward enough to read so that students can also understand the concepts being described. Your writing definitely does not lose itself in a myriad of letters and numbers of proteins and molecular structures. On that note, I also have a few pointers to give:

I think you should start the definition with your second sentence, and then add the first sentence as the second, so it reads something like “Peripherin is a type III Intermediate filament (IF) protein expressed mainly in neurons of the peripheral nervous system. In humans, peripherin is encoded by the PRPH gene. It is also found…”

Could you also explain or link an article to the term “homopolymeric filamentous networks”? I’m not sure everyone will understand what this means off the top of their head.

Can you double check the dates in these sentences? I’m not sure if you mean 1890, instead of 1990: “Peripherin, first named such in 1984, was also known as 57 kDa neuronal intermediate filament prior to 1990. In 1987, a second distinct peripherally located retinal rod protein was also given the name peripherin.”

Can you find a structure or computer-animated image of the peripherin protein? It would be a nice addition to the “structure and properties” section. Or maybe even just a general type II IF protein image, if possible? Otherwise, your structure and properties section is extremely thorough and well-written. The writing is technical, yet a lot easier to read then some of the articles I read through. You did a good job balancing those aspects. From this section on, the writing was very tight and clearly written – definitely one of the more manageable articles to read from our class’s Wiki topics. I think you did a wonderful job explaining the possible links of peripherin to ALS, the experimental results of mutating the protein, and the current research with other neurodegenerative diseases. Your group did a really superb job! Awesome!

-A. Alexander Alexanae (talk) 14:45, 16 November 2011 (UTC)

Alexanae: Thank you very much for your comments! We agree that the first sentence should be relocated. It was actually later on in our article and an outside editor came in after the original due date and placed it in there. We re-inserted it back into the body of the opening paragraph so that it flows better. We also added a comment on the homopolymeric filamentous networks with a link to clear up any confusion. I double checked the dates from the original source and while I agree that they do sound confusing, they are the correct dates and attached to the right information. We are also, as many people have suggested, on the hunt for more pictures but wiki commons and the protein databank are failing us right now. Thanks again for your helpful commentary. Melnickk (talk) 14:22, 6 December 2011 (UTC)

Peer Review 6

Hi guys,

It was a very well written article and extremely informative! I think maybe you guys should reexamine the organization of your article. I think it can be better organized. You introductory paragraph should include the basic outline of the information that you are going to present. Maybe it is better if you place the history section under a different subtitle. You should also probably expand on it if you chose to do so. I think the overall order your content should be like so: 1. Gene 2. Structure 3. Function 4. Tissue Distribution 5. Clinical Significance 6. Potential Applications In the “Gene” section, you can easily group gene structure and the paragraph about structure and properties from “alternative splicing” can also be moved here. You can also place the information about regulation of gene expression here. That should not be under “Structure”. I thought the section about the structure of the gene was really informative. However, I was a little confused. I think a picture would illustrate your information better. You should not put “tissue distribution” and “Regulatory mechanisms” under structure. The regulatory mechanisms should be under “function”. Other than organization, here are the few other things that you guys can change. Since you mentioned peripherin II, maybe you should include a different section on it. That way, you guys can discuss the differences between I and II. Under structure, you guys can link “ vimentin, GFAP and desmin” so your readers can have an easier time understanding your article. For “function” you should first state that the function is unknown, because that is the most important point. Also maybe you can expand a little more about α-internexin. I wasn’t very clear on how that came into the function of peripherin.

- Angi G. Angiguo644 (talk 20:10, 16 November 2011 (UTC)

Angiguo644: Thank you very much for your helpful review. We placed the history in its own section to help with organization. We agree with your order of content, however we left the gene section after the structure and function because we felt that those sections were more important and should come first. We also left the alternative splicing under the section covering ALS because while it does have to do with genes it is in the article in reference to its pathology regarding ALS. We did move the regulatory mechanisms section under the title "gene" because that definitely makes more sense. Vimentin, GFAP and desmin are referenced and linked in the opening paragraph. Peripherin 2 is a completely different protein. We linked it and gave some background information regarding its function so as to differentiate between the two. The fact that the function is unknown is important, but we believe its placement is ok because the first paragraph talks about the function of all type III IFs in summary as opposed to peripherin's specific role. THe first paragraph is background information before peripherin is talked about. I hope we clarified up any misunderstanding. Once again thank you very much for your commentary, we really appreciate it. Melnickk (talk) 14:32, 6 December 2011 (UTC)

Peer Review 7

This article actually seems really well written and organized. I think organization is pretty important in wikipedia articles and the headings and subheadings seem pretty well organized in general although there always can be some improvements. There is good enough information about it in the beginning section and the other sections seem to have the right amount of info as well. In the end part, it might be good to add a further research heading that explains where or in which areas about the topic is being investigated and things like that. Oh and if there are any diseases or sicknesses that can be caused by this protein, adding information about that can be informative as well. In general and overall however, great job and the image added is also a plus to the article. --Smiley4rang (talk) 02:05, 17 November 2011 (UTC)

Smiley4rang: Thank you very much for your comments! We are definitely adding more information as to how peripherin relates to ALS and even type II diabetes mellitus. We are also going to add information on its role in identifying Hirschsprung’s disease. Hopefully this will enhance our section involving diseases and further research. Thanks again for the advice, we really appreciate it. Melnickk (talk) 14:37, 6 December 2011 (UTC)

Peer Review 8

Very extensive and informative. This is especially true for the "Structure and Properties" section , although an image of the actual protein may help the reader visualize all of this. If no image is available, even just an image of a neuron's dendrites or a cytoskeleton may help better understand peripherin's role in dendrite elongation. Also, in the section entitled "Tissue distribution," this sentence was unclear to me: "This higher expression is due to the presence of peripherin in the tuberomammillary neurons of the mouse hypothalamus "--reword? Under "Clinical Significance" it would help to explain what exactly protein aggregates are and how they lead to diseases. Choino (talk) —Preceding undated comment added 05:40, 17 November 2011 (UTC).

Choino: Thank you very much for your review! We are currently still looking for a relevant image to add to the article. We also added the word "posterior" into the sentence to hopefully clarify how the tuberomammillary proteins increase expression of peripherin in the posterior hypothalamus. Finally, we are expanding our clinical significance section to clarify its role in the disease. Thanks again for the input we really appreciate it. Melnickk (talk) 14:40, 6 December 2011 (UTC)