User talk:Boghog

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Deleting the message is fine[edit]

Your Talk page is yours to do with as you please. Message was intended just for you, in any case. Sad that you can see only nonsense, and nothing worth your consideration, but that is the state of things. Cheers. Le Prof

Image for signaling cascade in addiction[edit]

Signaling cascade in the nucleus accumbens that results in psychostimulant addiction

This diagram depicts the signaling events in the brain's reward center that are induced by chronic high-dose exposure to psychostimulants that increase the concentration of synaptic dopamine, like amphetamine, methylphenidate, and phenethylamine, and cocaine. Following presynaptic dopamine and glutamate co-release by a drug, postsynaptic receptors for these neurotransmitters trigger internal signaling events through a cAMP pathway and calcium-dependent pathway that ultimately result in increased CREB phosphorylation.[1][2] Phosphorylated CREB increases levels of ΔFosB, which in turn represses the c-fos gene with the help of corepressors.[2] A highly stable (phosphorylated) form of ΔFosB, one that persists in neurons for one or two months, slowly accumulates following repeated exposure to stimulants through this process.[3][4] ΔFosB functions as "one of the master control proteins" that produces addiction-related structural changes in the brain, and upon sufficient accumulation, with the help of its downstream targets (e.g., nuclear factor kappa B), it induces an addictive state.[3][4]


References
  1. ^ Kanehisa Laboratories (27 February 2012). "Amphetamine – Homo sapiens (human)". KEGG Pathway. Retrieved 21 July 2014. 
  2. ^ a b Renthal W, Nestler EJ (2009). "Chromatin regulation in drug addiction and depression". Dialogues Clin. Neurosci. 11 (3): 257–268. PMC 2834246. PMID 19877494. Retrieved 21 July 2014. 
  3. ^ a b Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–637. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. "ΔFosB serves as one of the master control proteins governing this structural plasticity." 
  4. ^ a b Nestler EJ (December 2012). "Transcriptional mechanisms of drug addiction". Clin. Psychopharmacol. Neurosci. 10 (3): 136–143. doi:10.9758/cpn.2012.10.3.136. PMC 3569166. PMID 23430970. "The 35-37 kD ΔFosB isoforms accumulate with chronic drug exposure due to their extraordinarily long half-lives. ... As a result of its stability, the ΔFosB protein persists in neurons for at least several weeks after cessation of drug exposure. ... ΔFosB overexpression in nucleus accumbens induces NFκB" 
  1. ^
      Ion channel
      G-proteins & linked receptors
      (Text color) Transcription factors
Image file
The mostly complete schematic, pending your feedback and very minor cosmetic fixes; the receptor and gene product labels are temporary.

Hey Boghog. I was wondering if you'd happen to know of any any information resources (e.g., databases) that would have content on on signaling cascades / communication networks between receptors and gene transcription factors.

I'm working on an image (File:ΔFosB.svg - a DA neuron/synapse in the nucleus accumbens) for the addiction section in amphetamine at the moment to illustrate how the NDMA receptors, calcium channels, and ΔFosB are related, since it's not entirely apparent in the text. This KEGG diagram (the bottom pathway) and my molecular neuropharmacology textbook are the only 2 resources I'm working off of at the moment. Unlike the KEGG pathway, I'm just doing the synaptic cleft and postsynaptic neuron since the schematic for the presynaptic half is exactly what's shown in pharmacodynamics. I know all 5 DA receptors are present in accumbens DA neurons, so I'm planning to add the 4 other DA receptors into the KEGG schematic that I recreate in order to show their influence on the cAMP cascade. Seppi333 (Insert  | Maintained) 02:50, 17 June 2014 (UTC)

Also if you have any suggestions or feedback for me on the diagram itself, feel free to chime in. Face-smile.svg Seppi333 (Insert  | Maintained) 03:42, 17 June 2014 (UTC)
Update: I just realized that I saved a few papers on this topic on my website in a subpage that I forgot I made around 2 months ago. I unfortunately lost a large number of research papers when my laptop died, but at least I still have these signaling cascade models. In any event, I probably don't need more information resources for the model, but I'm always open to feedback! Seppi333 (Insert  | Maintained) 00:42, 18 June 2014 (UTC)
Hi Seppi. Sorry for not responding sooner. Your graphic looks great! One minor issue. Shouldn't the arrow between ΔFosB and DNA be reversed? According to the KEGG diagram, CREB regulates the expression of ΔFosB (i.e., CREB transcription factor → DNA (ΔFosB gene promoter) → ΔFosB protein). Also the transcription factor NFKB is a heterodimer of Fos and Jun. The KEGG diagram suggests that Fos (through the NFKB heterodimer) up regulates the expression of c-Fos. It appears that part of the diagram needs to be adjusted as well. Boghog (talk) 17:27, 21 June 2014 (UTC)
Ahh, alright. I'll make those tweaks when I work on the image within the next couple of days; several of the resources I used as a cross reference had a differing schematic inside the nucleus, so I wasn't really sure how to model that part. I don't expect to be done for another week or 2 since I'd like to look for additional reference models in reviews and on reactome first - assuming I can find anything relevant.
Thanks for the feedback by the way. Seppi333 (Insert  | Maintained) 11:44, 22 June 2014 (UTC)

────────────────────────────────────────────────────────────────────────────────────────────────────@Boghog: I've revised the image; I believe it's now consistent with the two KEGG diagrams and two literature reviews that I've listed in the description on the file page - File:ΔFosB.svg. The image legend is the same as KEGG's, with exception for the "+exp" and "-exp" terms which I use to denote gene expression and gene repression respectively. I'm hoping that I can make it more accessible to the average reader by removing all the SVG text and replacing it with annotated wikilinks in the finished version (similar to the amphetamine metabolites diagram). I'm also going to get some external feedback on the image's accessibility once I've finished drawing and annotating it. Consequently, it'll probably be at least another two weeks before I put it in an article.

In any event, you're more the expert in this area than I, so if there's anything you think I should add, edit, or remove from the current version of the image, please let me know! –Seppi333 (Insert  | Maintained) 00:07, 12 July 2014 (UTC)

It is looking even better! Two minor suggestions: Change GRIN3A → NMDAR and GRIA1 → AMPAR. GRIN3A and GRIA1 are the genes that encode subunits of NMDAR and AMPAR. The individual gene products themselves are not functional in isolation but require another subunit encoded by a distinct gene to form functional heterotetramers. Cheers. Boghog (talk) 07:48, 12 July 2014 (UTC)
@Boghog: Thanks again for the feedback. More or less done now - just need to make cosmetic tweaks (the synaptic cleft and some minor tweaks) and replace the labels with a template after I remove them from the image. I might shrink the legend too, since some of those are redundant. Anyway, is there anything you think should be modified? Seppi333 (Insert  | Maintained) 09:05, 18 July 2014 (UTC)
@Seppi333: Looks fantastic! As far as I can tell, it is technically correct. One further suggestion is to color code the function of the various proteins/factors. For example (using backgrounds instead of colored text):
  • DRD1-5, Gs, Gi/o – GPCRs and G proteins
  • ion channels
    • AMPAR and NMDAR – ligand gated ion channels
    • Cav1.2 – voltage gated ion channel
  • cAMP, CaM – second messengers
  • enzymes
    • CaMKII – kinase
    • DARPP-32. PP1, PP2B – phosphatases
    • HDAC, SIRT1 – deacetylases
  • CREB, Fos, Jun, c-Fos – transcription factors
The following tool seems like a good way to select a color pallet. Also you might want to submit the diagram as a featured picture candidate. A few examples of diagrams that have been designated feature pictures:
Cheers. Boghog (talk) 07:09, 20 July 2014 (UTC)
Ah, that's a pretty good idea. I'll work on that sometime tomorrow, There's not much room to work with listing the color descriptions on the image itself, but I can use an annotation transclude a note/reference which contains the list you just wrote with the appropriate colors and has the group parameter "Color code". Then - assuming the transcluded page has a color code references group below the refs section - it'll transclude the named ref group along with the list which will appear (hopefully) appear in a reference tooltip whenever people mouse over it, like below. Seppi333 (Insert  | Maintained) 09:20, 20 July 2014 (UTC)

────────────────────────────────────────────────────────────────────────────────────────────────────I tried a variety of color combinations with this image to see how things looked. I think I'd want to use at most 1 additional background color in the boxes (4 color groups total); it just looks too busy/complicated with more than that. Should I just identify the transcript factors, GPCRs, and ion channels, or is there a better grouping? Seppi333 (Insert  | Maintained) 01:11, 21 July 2014 (UTC)

@Seppi333: I agree that adding too many colors can be counter productive (both for aesthetics and clarity). Highlighting the GPCRs, G-proteins, ion channels (membrane associated) and transcription factors (nuclear) in one color and everything else (enzymes and second messengers) in another color helps. Membrane associated proteins and the transcription factors are at least on opposite sides of the diagram and therefore already spatially distinguished. Two additional suggestions: (1) Using two different shapes for DRD-1,5 (spirals) and DRD-2,3,4 (ellipses) is confusing. Wouldn't it be better to use single ellipses for DRD-2,3,4 and retain double ellipses for DRD-1,5? That way it is immediately clear that the former are monomers while the latter are dimers. (2) The shapes for the ion channels could be altered so they are a bit closer to their actual low resolution shape (see for example File:Ion channels.svg). This would make clearer the distinction between the ion conduction pore and the ligand binding sites. Boghog (talk) 05:38, 21 July 2014 (UTC)
Hey Boghog - I updated the dopamine receptors and LGIC's, although I was actually already using the voltage gated ion channel structure in the graphic for the nuclear pore (I more or less duplicated the structure of the nuclear pore and DNA from this svg derivation of your image - File:NF-κB.svg. I improvised and created a new structure that reflected the channel structure of the LGICs for the VGIC. Hope that looks ok. I recolored them for consistency and to differentiate them from the nuclear pore; I think it's completely obvious what part constitutes the ion channel now though. I figure I can just use the multicol template to indicate color relationships.
How's it look?Seppi333 (Insert  | Maintained) 23:37, 21 July 2014 (UTC)
Edit: I'm still fairly certain As is currently evident on FosB, I can transclude the color code in on an annotated reference to take advantage of the tooltip. Seppi333 (Insert  | Maintained) 23:39, 21 July 2014 (UTC)
2nd edit - I captioned the image with enough generality to hopefully make it reasonably accessible. Feel free to tweak it; the parts of the 3rd and 4th paper I used are in the quote parameter. Seppi333 (Insert  | Maintained) 02:41, 22 July 2014 (UTC)
@Seppi333: Thanks for incorporating the suggested changes above. The figure and the caption are now close to perfect. Great job! Cheers. Boghog (talk) 15:06, 22 July 2014 (UTC)
I may nominate this for EN-wiki FP soon, though I have no clue how people will respond to the annotation template. File:ΔFosB.svg doesn't exactly reflect template:psychostimulant addiction very well, even with the Commons annotations. Face-wink.svg In any event, I dropped by to ask you if you knew what the compound in the center of the synthesis diagram on Bupropion is. I've turned the file into an annotated image in order to add the compound names and fix some formatting issues with that section. Seppi333 (Insert  | Maintained) 23:49, 20 August 2014 (UTC)
A name for the compound is 2-bromo-1-(3-chlorophenyl)propan-1-one. Beyond that, the compound probably has no special significance other than it is a synthetic intermediate. I am not sure how people will respond to the template either. From a technical standpoint, I think it is excellent. But to be featured, it also has to have aesthetic appeal. File:Steroidogenesis.svg demonstrates that it is possible to get a technical diagram designated as a feature picture. It will be interesting to see how others respond to it. Cheers. Boghog (talk) 19:23, 21 August 2014 (UTC)

In reply to your talk my page also appearing immediately above[edit]

I have no clue as to who Flyer22 is in relation to the question of highlighting Talk text to make minority voices clearer, or what "refactoring" or "archiving" are, and what they have to do with highlighting. Here, brevity is your enemy; I am not chasing possible meanings down for you. This you need to clarify, significantly, to simply be understood. As for Padillah's statement, I have asked him to make clear what he wants, and when he does, I will act. As for your "protest", you can assuredly speak to what I do with your comments, but—as far as I see in the WPs, and as far as I have been counseled—not about what I do with other others' comments. I have highlighted none of your comments. I have queried all others, and will respond to their requests. It is, I understand, up to them, individually. (There is no overriding, firm policy, whatever you might think; this is what I am told.) So for now, I will await Padillah et al's replies, and yours if you care to say more. (But no action taken until.) Cheers. Le Prof

August 2014[edit]

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Minor typo in image[edit]

Hey Boghog, I noticed a small typo in an image you uploaded: File:Inverse_agonist_2.png (activty - in blue text). It's not really a big deal since the intended word is obvious, but I figured I should point it out. Best, Seppi333 (Insert  | Maintained) 18:28, 10 August 2014 (UTC)

Fixed Hi Seppi. You have sharp eyes. I have fixed the typo and created a higher quality svg version here: File:Inverse agonist 3.svg. Thanks for the heads up. Boghog (talk) 19:47, 10 August 2014 (UTC)
Looks great - noticeably sharper than the png version. Seppi333 (Insert  | Maintained) 02:14, 12 August 2014 (UTC)

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