text:
Talk:G protein-coupled receptor

Signal transduction
"The transduction of the signal through the membrane by the receptor is not completely understood. It is known that the inactive G protein is bound to the receptor in its inactive state. Once the ligand is recognized, the receptor shifts conformation and thus mechanically activates the G protein, which detatches from the receptor. The receptor can now either activate another G protein, or switch back to its inactive state. "

This is actually rather at odds with the current idea of GPCR activation.

The results of many hybrid and mutant receptor experiments, as well as evidence of agonist trafficking and constituitive activation, suggest a model of conformational selection rather than the conformational alteration described above (which is basically the same as the lock-and-key hypothesis of enzyme activation).

Current thinking is generally based around the Extended Ternary Complex Model (ETCM). In this model the GPCR and the G-protein exist in a continuum of states which can all occur in the absence of a ligand. Some of these states are active, some inactive. Some have the G-protein bound to the receptor, some do not.

Unfortunately this is difficult to express without a diagram. I'll post one here when I have time to find one.

The idea is basically that the GPCR and the G-protein continually fluctuate between active and inactive, bound and unbound states, very very quickly.

The majority of a receptor/G-protein population will (in the absence of ligands) be in inactive states, with a few being in active states. The addition of an agonist to this equilibrium shifts it in favour of the active, G-protein bound form of the receptor, which in turn creates conditions favourable for the active form of the G-protein. In other words an agonist binds very well to the active, G-protein bound form of the receptor and stabilises it (without an agonist this form has a very short half-life and is therefore only represented in a very small number of receptors in a population), giving time for the G-protein to be activated. Thus, rather than passively sitting there waiting for an agonist molecule to come along, the components of the signalling pathway are in a state of constant flux.

This model is necessary to explain the two phenomena mentioned above:

1) Agonist trafficking.

This name is given to the observed phenomenon that the same receptor can often activate different G-proteins in response to different agonists. Thus different effects can be mediated by different agonists via the same receptor.

2) Constituitive activation.

This is the situation in which GPCRs stimulate a response in the absence of any agonist. A good example of this is the GABA-B receptor. These receptors are active without the ligand (gamma-amino butyric acid, GABA) and considerably less active when it is introduced. The term which was coined for this behaviour is inverse agonism.

The model originally described makes it difficult to account for these phenomena - if the inactive receptor and G-protein are always bound then in a situation where a selection of G-proteins is available a full response to each of the various agonists trafficked by the receptor in question would not be possible (unless we posit further mechanisms in which an agonist can force the GPCR to detach from its current G-protein). Obviously if activation of the G-protein is dependent entirely upon ligand binding then constituitive activation would not be possible. — Preceding unsigned comment added by 129.11.110.216 (talk) 16:04, 15 January 2003 (UTC)

Receptor page
Receptor (proteomics) now contains a list of receptors. Please list any pages you know on that list, because it's presently a bit messy. JFW | T@lk  20:22, 14 Apr 2004 (UTC)

Pictures needed
It would really help if there were some pictures on this page...--Dan 01:53, 21 January 2006 (UTC)

 * We need to get some structural detail with the alpha,beta, and gamma subunits on here. More detail on strucural rearrangements caused by GDP-GTP exchange. Does anyone know if you can use swissmol and Jmol as fair use for a picture upload of a GPCR?
 * Thanks for adding the image, however we need to label the subunits. Well done though.  (Sterichinderance 07:04, 28 April 2006 (UTC))

Move
This should be moved to G protein-coupled receptor as the proteins to which these receptors are linked are called "G proteins", not "G-proteins" (note the hyphen). As the move would require the fixing of more double redirects than I can presently manage alone, I'll just leave this note here. --David Iberri (talk) 23:21, 29 April 2006 (UTC)
 * I tend to agree. Please consider listing at Requested moves, which is meant for such non-trivial moves. User:Ceyockey ( talk to me ) 03:44, 30 April 2006 (UTC)
 * I lost track of this for a while, but had a few extra minutes to do the page move myself. --David Iberri (talk) 17:40, 19 May 2006 (UTC)

Structure
Should there not be mention of alpha, beta and gamma subunits, mention also of the Gs, Gi and Gq types? --Copperman 08:29, 29 May 2006 (UTC)
 * That's the G protein, not the GPCR --130.88.96.66 (talk) 02:00, 10 December 2007 (UTC)

Contradict
On the 7TM receptor it says that GPCRs are an important class of 7TM receptor. But here on the GPCR page, it says that 7TM receptor is a synonym for GPCR. Zargulon 10:25, 3 July 2006 (UTC)
 * I suppose the 7TM  R eceptor article is the one in a question, not the 7TM  r eceptor one. The second one serves as redirect to the G protein-coupled receptor article itself. (I would just boldly move the redirect to the 7TM Receptor name instead that G protein-coupled receptor, but I want to clarify the reason of confusion for those, who didn't find the target. -- R eo  ON   |   + + +  13:35, 10 July 2006 (UTC)

 * I am not aware of any non G protein-coupled 7TM receptor, so I made 7TM receptor and 7TM Receptor into redirects to G protein-coupled receptor. Cacycle 03:09, 11 July 2006 (UTC)

 * Look at bacteriorhodopsin as an example of a non G protein-coupled 7TM receptor. It is a photoreceptor that serves as an ion channel. — Preceding unsigned comment added by 141.214.17.5 (talk) 22:23, 21 September 2006 (UTC)

Redundant figures
There is little difference between FIG 1 and FIG2. The authors should DELETE Figure 2. — Preceding unsigned comment added by 130.199.3.130 (talk) 18:53, 11 October 2006 (UTC)

 * I think you mean Figure 2 and 3 are similar. Figure 2 should probably be deleted since it is too small to garner any detail from--141.214.17.5 20:33, 19 October 2006 (UTC)

Removal of info on new GPCR structure (2007)
Resolved I am curious as to the reasoning behind this reversion edit, which removed information supported by a citation (albeit not in proper form). The reversion was accompanied by the edit summary "reverting last addition -- please propose on talk page". I was not the person who added the passage that was removed, I merely detected it on my watchlist and it caused a raised eyebrow. Thank you for the explanation. Regards --User:Ceyockey ( talk to me ) 11:09, 4 November 2007 (UTC)
 * I think the reason for reverting the edit was that the interpretation of the new structure was highly misleading. It implied that homology models of human GPCRs based on the bovine rhodopsin structure would have large errors.  What is far more relevant than species differences are sequence differences (which implies structure differences).  If one wants to model a human GPCR that is more closely related in sequence to rhodopsin than the adrenergic receptor, it would be far better to use the bovine rhodopsin than the human adrenergic structure.  If one wants to model a GPCR (human or bovine) that is closely related in sequence to the adrenergic receptor, it would be better to use the human adrenergic structure.  Finally for GPCRs which are not close in sequence to either adrenergic receptor or rhodopsin, neither experimental template is likely to lead to a good model.  I have re-inserted the information about the new GPCR structure with a somewhat different, and I hope more accurate interpretation.  Cheers.  Boghog2 13:42, 4 November 2007 (UTC)
 * OK - It was mostly a matter of providing the newly published information with appropriate context and counterpoint so that it wouldn't be taken at face value. I've not yet read the manuscript myself, but I'm a bit more skeptical than most, I think, on the matter of sequence-structure relationship: structural similarity can appear in the face of sequence differences and vice versa (similar sequence, different structure) in the presence of differentiating post-translational modifications. --User:Ceyockey ( talk to me ) 14:04, 4 November 2007 (UTC)

Any eukaryotes genomes without G-protein-coupled receptors?
The indtroductory paragraph states that GPCRs are found only in eukaryotes, and then lists major eukaryote taxa or representatives from these known to have GPCRs (plant, animal, fungi, protists). The impression is that GPCRs are thought to be a universal feature of Eukaryota, but this is not asserted explicitly.

Does anyone know of a counter-example? i.e. a eukaryote genome apparently lacking GPCRs?

Alternatively, are there likely examples of GPCRs known from any of the more exotic branches of the eukaryote tree? —Preceding unsigned comment added by Johnfravolda (talk • contribs) 16:12, 10 July 2009 (UTC)

Phosphorylation by cAMP-dependent protein kinases
In this section it reads:

"In fact any receptor causing an increase in PKA activity will cause increased amounts of this type of desensitisation of other receptors coupled to Go (e.g., dopamine receptor D2 activation may lead to β2-adrenoceptor desensitisation of this type).[22]"

The given reference does not say this as far as I can tell, also I could find no reference to Beta-2 AR Go coupling, although Gi coupling does occur as can be seen in the reference I added two sentences earlier.Repapetilto (talk) 22:01, 22 September 2009 (UTC)
 * Also I realized that doesnt even make sense since D2s are Gi coupled and would decrease cAMP, so I'm just going to change D2 to D1, which at least makes sense... the reference is still bad though.Repapetilto (talk) 22:01, 22 September 2009 (UTC)
 * D2 does activate phosphatase pathways such as extracellular signal-regulated kinases (ERK), independent of Gi / cAMP decrease, that might very well lead to heterologous receptor phosphorylation. Please do not change receptors names arbitrarily by gut-referencing... Also, too much and too specific detail is probably not good for the article and you might want to consider to be bold and taking such parts out. Cacycle (talk) 22:17, 22 September 2009 (UTC)
 * I think it works as a hypothetical example though. Repapetilto (talk) 12:18, 24 September 2009 (UTC)

Plants
I removed the section about plants since it was based on the GPCR1 and 2 found by the group publishing the Science paper on the topic, the claim has been disputed by several bioinformaticists. If you search on psi-blast for these proteins you find that they belong to the LanC-like super family, not GPCR. http://www.sciencemag.org/cgi/content/abstract/318/5852/914c this discovery has been questioned in future editions of Science (the original publisher of the article) as well as other journals. Until there has been a less controversial GPCR found in plants, I believe it is proper that it is removed from this article. 99.31.87.33 (talk) 03:04, 18 October 2009 (UTC)

 * Right. Uniprot tells about this protein: belongs to "Golgi pH regulator (TC 1.A.38) family" . Any other plant "GPCR" ? Biophys (talk) 18:02, 22 June 2010 (UTC)

Number of drugs
I found a current article

Have no idea how to add it. It says that GPCRs make up 26.8% of current drugs, NOT half as mentioned in the article. HELP... — Preceding unsigned comment added by 64.134.221.95 (talk) 05:32, 2 March 2010 (UTC)
 * Thanks for catching this. The Overington paper does seem to be more definitive than the citation supporting the "around half" estimate.  Therefore I have changed the text to read "approximately 30%" and added the citation that you found.  Cheers. Boghog (talk) 05:57, 2 March 2010 (UTC)

Structure-Function Section
So I made that figure while filling out a study guide for comprehensive exams then cleaned it up to put it here. The text that goes along with it came from the same place, I didnt bother referencing anything at the time but its all good, just check the facts and add references, or else I'll do it later. Im kinda of busy right now though so... if someone else wants to do it that would be cool. Any questions just ask, I dont think it should be deleted though. Also if someone knows a better image format to reduce the thumbnail blur, that should also be changed...Repapetilto (talk) 05:05, 19 June 2010 (UTC)

 * I added a bunch more text, it has the same problems as mentioned above. I'll see about getting around to fixing that eventually.Repapetilto (talk) 08:29, 21 June 2010 (UTC)

What diseases and drugs ?
Intro says "G protein-coupled receptors are involved in many diseases, and are also the target of approximately 30% of all modern medicinal drugs[2][3]" but article, although large, doesn't seem to list or link to the diseases or drugs. Even Fillmore[2] only says "They account for the majority of best-selling drugs and about 40% of all prescription pharmaceuticals on the market. Notable examples include Eli Lilly’s Zyprexa, Schering-Plough’s Clarinex, GlaxoSmithKline’s Zantac, and Novartis’s Zelnorm."

Should we have a short section like Physiology about the diseases that could mention or link to the relevant drugs ? Rod57 (talk) 23:54, 1 March 2011 (UTC)

 * The challenge is that the list of drugs targeting GPCRs and the diseases these drugs treat is very diverse. The G protein-coupled receptors navbox that it is displayed at the end of the article has links to GPCR families and individual GPCRs.  Many of these article contain information about drugs and/or the conditions they treat (see for example Dopamine receptor, histamine receptor, etc.)  At the same time, it wouldn't hurt to add a short list or table of few well known GPCR drugs.  For example here is a list of the top selling drugs by world wide sales.  Starting at the top of the list, drugs that act at GPCRs include:

Cheers. Boghog (talk) 06:27, 2 March 2011 (UTC)

Not all 7 transmembrane domain receptors are 7 TransMembrane Domain Receptors...
Just found this the other day: AdipoR1 and 2 are seven transmembrane domain receptors, but are unlike GPCRs, in that they dont seem to associate with G-proteins, and are orientated oppositely to GPCRs in the membrane (ie. cytoplasmic N, extracellular C)

http://www.ncbi.nlm.nih.gov/pubmed/12802337

Worth a mention? There's also another link somewhere up this talk page for other non-GPCR seven transmembrane receptors. --Soltee (talk) 22:13, 11 June 2012 (UTC)
 * If I understand correctly, they aren't all G-protein-coupled. If that's right, I'd say yes, sure. --Tryptofish (talk) 22:17, 11 June 2012 (UTC)
 * I mentioned AdipoR1 and AdipoR2 in this edit. Please feel free to modify. Boghog (talk) 03:13, 12 June 2012 (UTC)

Merger proposal
The proposal is that G protein and Heterotrimeric G protein be both merged into G protein-coupled receptor.

On September 2010, there was a suggestion on Talk:G protein that G protein be merged into G protein-coupled receptor. I am not an expert in this field, so I cannot suggest the reason why these two articles should be merged. From what I see, it looks like G protein should be added as a subsection of G protein-coupled receptor.

In addition, there was a merge proposal for Heterotrimeric G protein to be merged into G protein in June 2011; however, this would mean that Heterotrimeric G protein should actually be merged into G protein-coupled receptor instead, making G protein-coupled receptor a more complete article. Should the articles G protein and Heterotrimeric G protein be merged into G protein-coupled receptor? Steel1943 (talk) 17:14, 4 August 2012 (UTC)

 * Oppose – GPCRs and G proteins belong to two different protein families that differ substantially in both structure and function (although the functions are inter-related). There is enough reliable sources and material to maintain both as separate articles. Boghog (talk) 18:03, 4 August 2012 (UTC)
 * Support Oppose – merging  Heterotrimeric G protein into G protein.  Sorry, but I didn't see the second proposal. Boghog (talk) 23:56, 4 August 2012 (UTC)
 * On second thought, it appears that there are G proteins that are not heterotrimeric, see G_protein, hence I now think it would make more sense to move much of the material that is specific to the heterotrimeric G proteins from G protein to Heterotrimeric G protein. Boghog (talk) 15:55, 5 August 2012 (UTC)
 * To put things in perspective, there is a hierarchy of protein complexes and families and corresponding articles:
 * G protein (≠ G protein-coupled receptor)
 * Small GTPase
 * Heterotrimeric G protein
 * G alpha subunit
 * Gi alpha subunit
 * Gs alpha subunit
 * Gq alpha subunit
 * Gt alpha subunit
 * G12/G13 alpha subunits
 * G beta-gamma complex
 * I agree with Boghog that G proteins and the receptor proteins that they modulate are two different things. Therefore, I oppose merging anything into G protein-coupled receptor. However, although it isn't exactly what is proposed here, I think it would be a good idea to merge Heterotrimeric G protein into G protein, per the June 2011 proposal. Those are the same thing, with the heterotrimer simply being the three-dimensional form into which the G proteins assemble during biological function. There's really no rationale that I can see for a separate article about the heterotrimer. --Tryptofish (talk) 19:03, 4 August 2012 (UTC)
 * In response to Boghog's further comments: oh yeah, I forgot about the small GTPases (facepalm). However, it seems to me that the heterotrimers are, nonetheless, a subset of the G proteins. But I guess if there isn't a good rationale for merging the small GTPases into the G protein article, then we don't really need to merge the heterotrimers either. I really don't feel strongly about it. In any case, the primary question here is about the receptors, and I think we agree that the receptors are completely distinct from the G proteins. --Tryptofish (talk) 21:27, 5 August 2012 (UTC)

Course assignment
— Preceding unsigned comment added by Hakkinen2013 (talk • contribs) 03:53, 19 February 2013 (UTC)

Nomenclature: Ga i/o vs Ga i/0
This page lists the former, with a letter o, while the subunit's own page uses a 0. I suggest using a 0 for both articles.

The other article: https://en.wikipedia.org/wiki/Gi_alpha_subunit

(167.206.17.113 (talk) 15:16, 9 September 2015 (UTC))

Lede looks spammy
Since I'm new to this article, I thought I would just mention it instead of deleting the offending passages myself, but this sounds too Gee Wiz and not encyclopedic:

"G protein–coupled receptors are involved in many diseases, and are also the target of approximately 40% of all modern medicinal drugs.[4][5] Two of the United States's top five selling drugs (Hydrocodone and Lisinopril) act by targeting a G protein–coupled receptor.[6] The 2012 Nobel Prize in Chemistry was awarded to Brian Kobilka and Robert Lefkowitz for their work that was "crucial for understanding how G protein–coupled receptors function.".[7] There have been at least seven other Nobel Prizes awarded for some aspect of G protein–mediated signaling." Zyxwv99 (talk) 01:19, 8 October 2015 (UTC)

 * I think the fact that GPCRs are the target of a large percentage of drugs is significant snd should be mentioned in the lead. I would agree that the rest of the material that you have highlighted is not appropriate for the lead and I have moved it to an new "history and significance" section. Boghog (talk) 05:26, 8 October 2015 (UTC)
 * Thanks. Zyxwv99 (talk) 02:13, 9 October 2015 (UTC)

800 GPCRs?
The page contains the text: "The exact size of the GPCR superfamily is unknown, but nearly 800 different human genes (or ~ 4% of the entire protein-coding genome) have been predicted to code for them from genome sequence analysis.[10]". Although I acknowledge that larger numbers are more awe-inspiring (and are frequently cited), I don't think a conjecture should be so prominently featured on this wiki page. I don't have a suggested modification or replacement, and I don't have any scientific objections to the predictions made in this cited article. I am simply suggesting that it would be better to stick to known facts rather than 12-year-old conjectures (even if those conjectures are data and model driven). I took a look and could not find anything better for a general replacement citation for a summary of the number of GPCRs (besides perhaps this annotated 200+ conjecture: https://www.ncbi.nlm.nih.gov/pubmed/15914470, also from 2005). — Preceding unsigned comment added by 69.254.135.248 (talk) 07:04, 22 July 2017 (UTC)

Why you have chosen this article to evaluate?
G-Protein coupled receptors really interest me as numerous physiological processes and cellular responses are based upon GPCR interactions with various signaling molecules. Not to mention my current research focuses on GPCRs and I want to learn as much as possible. GPCRs are important because according to the article the ligands or signaling molecules that interact with the receptors are related to light-sensitivity, odors, pheromones, neurotransmitters, hormones and more, reflecting the idea that GPCRs are involved in numerous processes/actions within living organisms, particularly eukaryotes. As for my preliminary impression of the article, it appears to be well organized by initially providing an overview of what is known about GPCRs regarding its structure and role, also incorporating details regarding its history. Then moving onto more specifics related to the mechanism of function, signaling, the individual cAMP and PIP2 pathways and so on. The paper also appears to be greatly detailed providing a well-rounded overview of details and images reflecting the concepts being discussed. Additionally, the sources provided are vast and reputable, further aiding in the reliability of the information being reported within the article.

Evaluate the article
When reading the lead section, the article clearly describes the topic of discussion: GPCRs. It further goes onto briefly but accurately describing the articles major sections of discussion including ligands that interact with the GPCRs, the two distinct pathways involved within the signal transduction, the various signaling subunits involved within the process and more. However, receptor regulation is not clearly outlined within the lead section and would benefit the article if some note regarding it was made within the lead. In addition, the lead discusses applications of GPCRs as important drug targets and the applications within drug development, this is not discussed within later portions or the article in greater detail thus it would be beneficial for the readers to be provided additional details. Overall, the lead section provides enough detail to gain an overview of the article and its topics without overwhelming the reader with specific details but does lack noting an overview of GPCR regulation and includes details that are not later detailed regarding drug applications of GPCRs.

As for the content of the article, information is evenly distributed among the topics of discussion without placing too much emphasis on one compared to another. This is considering what is known and understood about each of the topics discussed, yes some sections provide more information compared to others, but this is to reflect what is known and unknown, despite this the length/details of sections do not take away from other portions of the discussion. As for the relevance of the content it is critical to understand the functions of GPCRs in addition to their structure and mechanism of function, without it GPCRs as a class of receptors will not be clearly understood, this would be a limitation to their study and the study of cellular processes/disease related. Additionally, the content related to signaling and regulation contributes to the overall understanding of GPCRs. As mentioned above, the applications of GPCRs as drug targets and drug development is something that needs to be further discussed within the article and is currently lacking. Moreover, most details within the article appear to be up-to-date utilizing sources within the 2000's and the oldest source dating back to 1987. However, there is discussion surrounding the signal transduction aspect discussed within this article that contrasts with current ideas of the transduction pathway involving a conformational selections, the author of the page should look more into this.

The tone of the article appears neutral as it doesn't focus on one point of view rather provides a wide outlook to the information and understanding regarding GPCRs. Additionally, there are no claims related to the understanding that appears heavily biased towards a particular point of view. However, the claims related to the importance of GPCRs as drug targets and their pharmaceutical applications appear underrepresented and should be provided more attention. Ultimately, the article is well written and does not take any bias towards discussing any side or detail.

When examining the sources used the links appear to work upon randomly selecting many and are readily available for viewing, and many of the ones listed supports the overall claims made within the article regarding understandings, in particular for GPCR structure/function relationships as well as mechanism of action. Additionally, the facts reported are all referenced appropriately with reliable secondary sources. And for the most part the sources are within the past 20 years, which may lend to the idea that there may be new studies on GPCRs that can contribute to this paper, despite this the sources listed do come from a diverse set of authors and publications lending to the neutral tone of the writing. Upon searching for additional sources that may contribute to this article "GPCR Signaling Regulation: The role of GRKs and Arrestins" by Vsevolod V. Gurevich and Eugenia V. Gurevich is one that may further or support the discussion regarding GPCR regulation. As for the limited discussion surrounding GPCRs as drug targets "G Protein-Coupled Receptors as Targets for Approved Drugs: How Many Targets and How Many Drugs?" by Krishna Sriram and Paul A. Insel, may provide useful details for the author of this page.

Again, the details and discussion are clearly organized, and the writing is concise, easy to read and understand. As for the images used, nothing that was used was distracting but contributed to the understanding of the topics and discussion points. While the images contribute to the readings understanding they are not as well-captioned as expected, some of the captions lack some details regarding the topic that an images is intended to reflect, for example the image captioned "G-protein-coupled receptor mechanism" the image focuses on that topic and it is understood, but readers may be confused as to what is happening in the figure, so a general overview may be helpful.

When viewing the talk-page discussions, as mentioned above there is a discussion surrounding the signal transduction mechanism where the article discusses a conformational change, but current discussions may support the idea of a conformational selection rather than a change. Other discussions surround article formatting and placement of figures/images in the article, and some related to the references used. And further discussions relate to details presented within the article that may be confusing or can be further developed for the readers’ understanding. The paper is rated as a level-5 vital article in Biology and is involved in Wiki projects for Molecular Biology / MCB, Neuroscience, and Biophysics. When reading the article, Wikipedia discusses the topic in a way that it does not command an extensive background knowledge from the reader, rather presents the information in a way that everyone can understand at a college level of education. Compared to class discussions, which may require a level of background knowledge especially knowing at least what a GPCR is, and the different words used to describe processes and applications, and how we can draw comparisons between GPCRs and other cellular processes.

Overall, the article is clearly written and concise and easy to understand and well-developed, those are its strengths. Despite this, the above-mentioned comments should be taken into consideration to improve the quality of the content and understanding. To further the discussion surrounding GPCRs, I ask what impact might mutations on GPCRs have on cellular response, i.e those that involve neurotransmitters behaving as ligands? All in all, I enjoyed reading the article and look forward to any additions/edits to the page.

Abidur.rafi24 (talk) 00:53, 5 December 2022 (UTC)

x.y amino acid residue numbering superscipt
It would be nice if someone could append info on the x.y amino acid residue numbering superscript system (e.g., Asp2.68). I sometimes see this in publications. Where I work, people speculated that "2" refers to maybe transcript ID or maybe extracellular loop number or maybe transmembrane domain. Similarly, they speculate "68" must be an amino acid position, albeit that is also ambiguous to someone who does not know the rules. IUPAC nomenclature rules does not mention such a system. Since this relates to a GPCR, could it be a GPCR specific counting system and how does it work? Where is it documented? 130.238.224.66 (talk) 10:38, 10 February 2023 (UTC)

title: Talk:G protein-coupled receptor


text:
The Atomic Cafe

The Atomic Cafe is a 1982 American documentary film directed by Kevin Rafferty, Jayne Loader and Pierce Rafferty. It is a compilation of clips from newsreels, military training films, and other footage produced in the United States early in the Cold War on the subject of nuclear warfare. Without any narration, the footage is edited and presented in a manner to demonstrate how misinformation and propaganda was used by the U.S. government and popular culture to ease fears about nuclear weapons among the American public.

In 2016, the film was selected for preservation in the United States National Film Registry by the Library of Congress as being "culturally, historically, or aesthetically significant."

Synopsis
The film covers the beginnings of the era of nuclear warfare, created from a broad range of archival material from the 1940s, 1950s and early 1960s including newsreel clips, television news footage, U.S. government-produced films (including military training films), advertisements, television and radio programs. News footage reflected the prevailing understanding of the media and public. The film covers both the impact of the atomic bomb on popular culture and daily life, as well as documents the military's increasing fascination with carrying out more and more dangerous tests. The film opens with footage of the Trinity Test and concludes with a montage of stock footage simulating a nuclear attack on the United States.

Though the topic of atomic holocaust is a grave matter, much of the humor derives from the modern audience's reaction to old training films, such as the Duck and Cover film shown in schools. Another sequence involves footage of US Army training maneuvers in which soldiers are instructed to walk into a mushroom cloud as part of an exercise to study how efficiently the armed forces could kill the survivors of a nuclear bomb strike if Soviet Soldiers ever made it to US soil; prior to the beginning of the exercise, the soldiers are informed, "Viewed from a safe distance, the atomic bomb is one of the most beautiful sights ever seen by man."

People shown
The following people are shown in excerpts from speeches, interviews and news reports: Lloyd Bentsen, William H. P. Blandy, Owen Brewster, Frank Gallop, Lyndon Johnson, Maurice Joyce, Nikita Khrushchev, Brien McMahon, Seymour Melman, George Molan, Richard Nixon, Val Peterson, George Portell, George Putnam, Ronald Reagan, Ethel Rosenberg, Julius Rosenberg, Mario Salvadori, Lewis Strauss, Paul Tibbets, Harry S. Truman, James E. Van Zandt.

Historical context
The Atomic Cafe, referred to as a "compilation verite" with no "voice of God narration" or any recently shot footage, was released at the height of nostalgia and cynicism in America. By 1982, Americans lost much of their faith in their government following the Vietnam War and the Watergate scandal the previous decade, alongside the seemingly never-ending arms race with the Soviet Union. The Atomic Cafe reflects and reinforces this idea as it exposes how the atomic bomb's dangers were downplayed and how the government used films to shape public opinion. Loader, who grew up in 50s-60s Fort Worth, Texas living across the street to E.O. "Soapy" Gillam, better known as the "bomb shelter king of North Texas", while also remembering one of her friends used her family's bunker as a clubhouse/secret party spot, felt compelled to revisiting the era that formed her childhood.

The Atomic Cafe was also released during the Reagan administration's civil defense revival. Barry Posen and Stephen Van Evera explain this revival in their article "Defense Policy and the Reagan Administration: Departure from Containment" published in International Security. They argue that in 1981–82 the Reagan administration was moving from an essentially defensive grand strategy of containment to a more offensive strategy. Due to the greater demands of its more offensive strategy "the Reagan Administration ... proposed the biggest military buildup since the Korean War." Of key relevance to The Atomic Cafe, the Reagan move toward offense included the adoption of a more aggressive nuclear strategy that required a large U.S. nuclear buildup. Containment only required that U.S. strategic nuclear forces be capable of one mission: inflicting unacceptable damage on the Soviet Union even after absorbing an all-out Soviet surprise attack. To this "assured destruction" mission the Reagan administration added a second "counterforce" mission, which required the capacity to launch a nuclear first strike against Soviet strategic nuclear forces that would leave the Soviets unable to inflict unacceptable damage on the U.S. in retaliation. The U.S. had always invested in counterforce but the Reagan administration put even greater emphasis on it. The counterforce mission was far more demanding than the assured destruction mission, and required a vast expansion of U.S. nuclear forces to fulfill. Civil defense was a component of a counterforce strategy, as it reduced Soviet retaliatory capacity, hence civil defense was a candidate for more spending under Reagan's counterforce nuclear strategy. Posen and Van Evera argue that this counterforce strategy was a warrant for an open-ended U.S. nuclear buildup.

Bob Mielke, in "Rhetoric and Ideology in the Nuclear Test Documentary" (Film Quarterly) discusses the release of The Atomic Cafe: "This satire feature was released at the height of the nuclear freeze movement (which was in turn responding to the Reagan administration's surreal handling of the arms race.)"

In "Atomic Café" (Film Quarterly), Fred Glass points out that the technical and cultural background needed to create the film was not available in 1955. The film's themes, critical of government propaganda and the nuclear arms race, would have been seen as unpatriotic during the McCarthy era. And getting the necessary permits and funding to make Atomic Café can be quite difficult.

Patricia Aufderheide, in Documentary Film: A Very Short Introduction touches on the significance of The Atomic Cafe as a window into the past of government propaganda and disinformation during the years following the advent of the atomic bomb. "Propaganda, also known as disinformation, public diplomacy, and strategic communication, continues to be an important tool for governments. But stand-alone documentary is no longer an important part of public relations campaigns aimed at the general public."

It has also been known as a postmodernist film.

Production
The Atomic Cafe was produced over a five-year period through the collaborative efforts of three directors: Jayne Loader and brothers Kevin and Pierce Rafferty. For this film, the Rafferty brothers and Loader formed a production company called The Archives Project. The filmmakers opted not to use narration. Instead, they deployed carefully constructed sequences of film clips to make their points. Jayne Loader has referred to The Atomic Cafe as "compilation verite": a compilation film with no "Voice of God" narration and no new footage added by the filmmakers. The soundtrack utilizes atomic-themed songs from the Cold War era to underscore the themes of the film.

The film cost $300,000 to make. The group did receive some financial support from outside sources, including the Film Fund, a New York City based non-profit. Grants comprised a nominal amount of the team's budget, and the film was largely funded by the filmmakers themselves. Jayne Loader stated in an interview, "Had we relied on grants, we would have starved." Pierce Rafferty helped to support the team and the film financially by working as a consultant and researcher on several other documentary films including the Oscar-nominated El Salvador: Another Vietnam, the Oscar-nominated With Babies and Banners, and The Life and Times of Rosie the Riveter (which also was inducted into the National Film Registry). The Rafferty brothers had also received an inheritance that they used to support the team during the five years it took to make the film. About 75% of the film is made up of government materials that were in the public domain. Though they could use those public domain materials for free, they had to make copies of the films at their own expense. This along with the newsreel and commercial stock footage that comprises the other 25% of the film (along with the music royalties) represents the bulk of the trio's expenditures.

Release
The film was released on March 17, 1982, in New York, New York. In August 1982, a tie-in companion book of the same name, written by Kevin Rafferty, Jayne Loader and Pierce Rafferty was released by Bantam Books. A 4K digital restoration of the film, created by IndieCollect, premiered at SXSW in 2018.

Home media
The 20th Anniversary Edition of the film was released in DVD format in Region 1 on March 26, 2002, by Docudrama. A 4K restored version was released on Blu-ray on December 4, 2018, by Kino Lorber.

In 1995, Jayne Loader's Public Shelter, an educational CD-ROM and website – with clips from The Atomic Cafe, plus additional material from declassified films, audio, photographs, and text files that archive the history, technology, and culture of the Atomic Age – was released by EJL Productions, a company formed by Jayne Loader and her first husband, Eric Schwaab. Though it garnered positive national reviews and awards, the self-distributed Public Shelter CD-ROM sold only 500 copies and failed to find a national publisher. Loader and Schwaab divorced. The website folded in 1999.

Critical response
When The Atomic Cafe was released, film critic Roger Ebert discussed the style and methods the filmmakers used, writing, "The makers of The Atomic Cafe sifted through thousands of feet of Army films, newsreels, government propaganda films and old television broadcasts to come up with the material in their film, which is presented without any narration, as a record of some of the ways in which the bomb entered American folklore. There are songs, speeches by politicians, and frightening documentary footage of guinea-pig American troops shielding themselves from an atomic blast and then exposing themselves to radiation neither they nor their officers understood." He also reviewed it with Gene Siskel who saw it more as a piece of Americana and a curio.

Critic Vincent Canby of the New York Times praised the film, calling the film "a devastating collage-film that examines official and unofficial United States attitudes toward the atomic age" and a film that "deserves national attention." Canby was so taken by The Atomic Cafe that he mentioned it in a subsequent article – comparing it, favorably, to the 1981 blockbuster Porky's.

Critic Glenn Erickson discussed the editorial message of the film's producers: "The makers of The Atomic Cafe clearly have a message to get across, and to achieve that goal they use the inherent absurdity of their source material in creative ways. But they're careful to make sure they leave them essentially untransformed. When we see Nixon and J. Edgar Hoover posing with a strip of microfilm, we know we're watching a newsreel. The content isn't cheated. Except in wrapup montages, narration from one source isn't used over another. When raw footage is available, candid moments are seen of speechmakers (including President Truman) when they don't know the cameras are rolling. Caught laughing incongruously before a solemn report on an atom threat, Truman comes off as callously flip ..."

On Rotten Tomatoes the film has an approval rating of 93% based on reviews from 29 critics.

Deirdre Boyle, an Associate Professor and Academic Coordinator of the Graduate Certificate in Documentary Media Studies at The New School and an author of Subject to Change: Guerrilla Television Revisited, claimed that "By compiling propaganda or fictions denying 'nuclear-truth', The Atomic Cafe reveals the American public's lack of resistance to the fear generated by the government propaganda films and the misinformation they generated. Whether Americans of the time lacked the ability to resist or reject this misinformation about the atomic bomb is a debatable truth."

The Oxford Handbook of Science Fiction said it was, in quotes, a "mockumentary" from its editing and called it, "The most powerful satire of the official treatments of the atomic age".

Influences
In 2016, The Atomic Cafe was one of the 25 films selected for preservation in the annual United States' National Film Registry of the Library of Congress for being deemed "culturally, historically, or aesthetically significant". The press release for the Registry stated that "The influential film compilation 'Atomic Cafe' provocatively documents the post-World War II threat of nuclear war as depicted in a wide assortment of archival footage from the period ..."

Controversial documentary filmmaker Michael Moore was inspired by the film that he tweeted: "This is the movie that told me that a documentary about a deadly serious subject could be very funny. Then I asked the people who made it to teach me how to do it. They did. That movie became my first – 'Roger & Me'."

Accolades

 * Wins
 * Boston Society of Film Critics: BSFC Award, Best Documentary; 1983.

 * Nomination
 * British Academy Film Awards: Flaherty Documentary Award, Kevin Rafferty, Jayne Loader and Pierce Rafferty; 1983.

Soundtrack
Atomic Cafe: Radioactive Rock 'n Roll, Blues, Country & Gospel is the soundtrack to the 1982 film The Atomic Cafe. A vinyl LP record was released in 1982 by Rounder Records. Some of the credits for the record include: co-produced by Charles Wolfe, The Archives Project (Jayne Loader, Kevin Rafferty and Pierce Rafferty), album cover artwork by Dennis Pohl, cover design by Mel Green, and booklet text by Charles Wolfe.

Track listing
Featured in the film but not the soundtrack were "13 Women" by Bill Haley and His Comets, Glenn Miller's version of "Flying Home", a couple of themes from Miklos Rozsa, Arthur Fiedler's take on Franz Liszt's Hungarian Rhapsody No. 2, Charles Mackerras's interpretation of "The Old Castle" from Pictures at an Exhibition and Floyd Tillman's original 1948 version of "This Cold War with You" that was heard during the credits.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/

title: The Atomic Cafe


text:
Talk:Sequence alignment

Pre-2004 adds
Sorry. I rather forged ahead and added a lot of content to this page without suggesting it first. I hope you can forgive me - I was just rather eager to add something on a topic that I know about.

I have taken pains not to remove anything, so if you don't want what I've added it should be easy enough to get rid of my new stuff.

MockAE.

Needs massive software listing update
The software listing is horribly out of date. I'm currently working on benchmarking such aligment packages, and the ones listed here are fast but awful in quality. T-Coffee, Di-Align, MUSCLE, and others merit mention. Davidstrauss

Reverted reference conversion
Tooto helpfully refconverted this page, and I temporarily reverted that change. I meant to put a comment in the article asking people not to change the references, but I figured, what are the odds of someone converting this exact page in the next week or two?

I'm actively working on this article and find it much easier to add the references in the old style first and then use refconvert at the end, so that the reference text isn't interspersed with the article text. So I'll re-convert the references after the text is more complete. Opabinia regalis 03:38, 24 June 2006 (UTC)

old external links section
I removed the external links section from the main article pending their merger with sequence alignment software. For the time being I'm storing them here for easy reference. Opabinia regalis 04:40, 4 July 2006 (UTC)

 * Blast Server at the NCBI

 * Local alignment tools:
 * Smith-Waterman (online): Emboss::WATER (full memory dynamic programming matrix) - SSEARCH - STRETCHER (optimized dynamic programming matrix) - SEQALN
 * Suffix_tree based (fast): REPuter
 * Seed based (online): FASTA - BLAST family - human BLAT
 * Spaced seed based (more accurate): PatternHunter - human BLASTZ - YASS
 * Global alignment tools:
 * Needleman-Wunsch (online): Emboss::Needle (full memory dynamic programming matrix) - Emboss::Matcher (optimized dynamic programming matrix)
 * Suffix_tree based (fast): MUMmer
 * Multiple alignment tools (online): DIALIGN-T - Clustal - Dialign - MAFFT - Multalin - MAVID - Multi-LAGAN - Muscle - POA - ProbCons - T-Coffee

 * An excellent article at the NCBI web site on the methodology of the BLAST algorithm and the statistical significance of sequence alignments in general.
 * JAligner is an open source Java implementation of the dynamic programming algorithm Smith-Waterman for biological pairwise local sequence alignment.

 * Alignment of Genomes with Rearrangement: Mauve - Mulan - Shuffle-LAGAN (pairwise only)

 * Visualisation tools for alignments
 * VISTA genome browser http://pipeline.lbl.gov
 * Mauve visualization system http://gel.ahabs.wisc.edu/mauve
 * STRAP - 3D-alignments and sequence alignments http://3d-alignment.eu
 * Open content directory of sequence alignment resources (BioDirectory)
 * Sequence Alignment

Grammar Suggestion
I'd suggest rearranging this sentence to improve readability: "If two sequences in an alignment share a common ancestor, mismatches can be interpreted as point mutations and gaps as indels (that is, insertion or deletion mutations) introduced in one or both lineages in the time since they diverged from one another." GravityIsForSuckers 22:09, 28 August 2006 (UTC)
 * Do you have a suggested rewording? Perhaps removing the parenthetical explanation of indels? It sounds fine to me, but it should, since I wrote that sentence in the first place :) Opabinia regalis 05:03, 29 August 2006 (UTC)
 * It would be easier for me to be more specific (or I would have just changed it myself) if I knew this particular subject matter. Perhaps someone else will have an opinion on this. GravityIsForSuckers 05:29, 29 August 2006 (UTC)
 * How about - The differences in the aligned sequences correspond to mutations that have occurred in one or both lineages since their time of divergence.If two sequences share a common ancestor, mismatches and gaps in the aligned sequences can be interpreted as point mutations or insertion/deletion mutations (indels), respectively. Gribskov 04:04, 20 September 2007 (UTC)

Wording of the lead
The lead has gone through a few changes since this hit the main page. Theuser, I take your point about arranging residues rather than sequences, but the deficiency of the "residues" wording is that it implies that the order of the residues in the sequence is altered, which is more ambiguous than the alternative "arranging primary sequences". Also, the removal of the word "may" or its equivalent in the statement about emphasizing similarity is much too strong. Spurious similarity happens and there shouldn't be an implication that the results are more definitive than they are. Opabinia regalis 00:37, 29 August 2006 (UTC)

 * I'm also confused by the wording "historically similar". Certainly sequence-alignment algorithms don't have any information about history, but just operate on sequences?  Biologists may use sequence-alignment results to make inferences about history, but sequence-alignment itself doesn't look for things that are "historically similar"; rather, it finds things that are similar by some algorithmic metric. --Delirium 01:24, 29 August 2006 (UTC)
 * You're right, I reworded it closer to the original. The algorithms themselves are usually ignorant of history (except some that can use an independently-derived phylogenetic tree as input), but the results are usually interpreted as reflecting evolutionary change. Opabinia regalis 01:33, 29 August 2006 (UTC)
 * Looks better now; thanks! --Delirium 20:05, 31 August 2006 (UTC)

Assessment of significance
I think this section is unnecessarily vague (even for a non-technical audience). I could add a few details here. Also, the discussion of convergence, IMO, makes it sound much more likely than it really is. Patterson (I think) made a compelling argument in a paper sometime in the 80s (again, I think). I could dig this up, or reconstruct it. Gribskov 04:10, 20 September 2007 (UTC)

"Bioinformatics sequence alignment"
I think "bioinformatics sequence alignment" is a horrible name for this page. It showed up on my watchlist and my immediate reaction was "what's that?". If it absolutely has to move, it should go to "Protein and nucleic acid sequence alignment" or something like that. I think the article should stay at "sequence alignment" though. --Aranae 22:26, 24 October 2007 (UTC)
 * Fully agree. The move should at least have been discussed, especially since it is a featured article. Have moved it back to the original name. Shyamal 01:06, 25 October 2007 (UTC)
 * Me three. Thanks, Shyamal. I don't see a compelling reason for this at all; there's no outstanding ambiguity that needs to be resolved by a longer and less intuitive title. Opabinia regalis 02:38, 25 October 2007 (UTC)

Editing
"Semi-conserved": Is that term really defined? It may be specific to how a user sets up the software. I found an article on the internet saying it means having similar shape, so I added that to the first figure's key. Perhaps the idea should be removed from the article & figure.

"Conservation of base pairing" is mentioned. I find no mention in Wikipedia of that, though the internet has around 250 references to it. I suspect that conservation of bases, rather than base pairing, is meant, so I changed base pairing to base pairs.

The distinction between global and local alignments is not spelled out.--Christopher King (talk) 16:45, 8 January 2009 (UTC)

Links only with uppercase "S"
Links to this page only work if the "S" in "sequence" is capitalized. This should be changed so that links work with letters in either upper or lower case. I believe you change the page title to accomplish this. ask123 (talk) 17:02, 5 May 2009 (UTC)

bug in local alignment example
The local alignment example is clearly wrong, since

FTFTALILLAVAV

--FTAL-LLA-AV

will have a higher score with any substitution matrix or gap costs.

Kevin k (talk) 03:17, 17 September 2009 (UTC)

Wish List
I wish there was a clearer distinguishing here between local and global alignment methods. Briancady413 (talk) 14:25, 18 February 2010 (UTC)

Consensus symbols error
There was a little mistake in Consensus symbols definition - "." (semi-conserved substitutions) and ":" (=conserved substitutions) were inverted. But the picture is still wrong and I have no time (and don't know how) to fix it. 80.188.178.177 (talk) 13:56, 19 June 2010 (UTC)

Text representations - CIGAR, VULGAR etc.
I noticed a CIGAR-shaped hole around here, but I'm not sure how to fill it. I made CIGAR string and linked from Cigar (disambiguation). I doubt there is enough material for a whole article, so I made it a redirect. I'm reluctant to edit this article because it was featured (should I be?). -- Silicosaurus (talk) 15:24, 18 April 2012 (UTC)

I'm not an expert, but the leads I have are
 * CIGAR string format
 * is emitted by the Exonerate aligner
 * is used in an extended form by Ensembl
 * There are several specifications, but I was told recently that the SAMtools format has the nearest to a superset of features.
 * Accuracy of the expansion is in doubt, compare Compact Idiosyncratic Gapped Alignment Report, concise idiosyncratic gapped alignment report — Preceding unsigned comment added by Silicosaurus (talk • contribs) 15:38, 18 April 2012 (UTC)
 * VULGAR format is a variation
 * It is used in GFF3

I think if CIGAR string redirects here, then the article should at least mention CIGAR strings. I just searched Wikipedia and was confused by this discrepancy; I thought I must be missing something in the article. Currently this article seems to focus on pairwise alignment (of comparable strings) and multiple sequence alignment, so CIGAR strings are not very relevant. The only representations of alignments discussed in the article currently are those where both sequences are written out. Common methods of representing an alignment to a reference genome are not mentioned.

I feel that this article would benefit from an "Alignment to a reference genome" section which could briefly mention SAM/BAM/CRAM representations and link to the SAM format specification, which covers CIGAR strings. Happy to have a go at this if there is some agreement. Currently I think that there is no description of the SAM/BAM/CRAM file formats on Wikipedia (?), even though there is a SAMtools article, and there are pages on some other bio formats such as GFF or FASTQ. 59.167.191.34 (talk) 03:16, 16 January 2015 (UTC)

Audio Recording
Hi, I created an audio recording for this article. But I wasn't sure how to pronounce some words/acronyms and just made a good guess. I'd appreciate any corrections.

 * MUM
 * Needleman–Wunsch
 * indel
 * Genewise
 * FASTA
 * EMBL FASTA
 * NCBI BLAST
 * BAliBASE
 * SSAP

Thanks. --Mangst (talk) 00:50, 6 June 2012 (UTC)

Shorter paragraphs
This is mostly just so that I'll remember later. I'm in a rush at the moment, but: this article really needs to be split into shorter paragraphs. Risc64 (talk) 03:41, 11 December 2015 (UTC)

External links modified
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title: Talk:Sequence alignment


text:
User:MockAE

I'm a postdoc working in David Jones's group at UCL.

As I recently remembered the password to this account I've been adding some stuff to various pages on bioinformatics, particularly SCOP and CATH. Time permitting I shall add more to other bioinformatics pages as the need becomes apparent.

title: User:MockAE


text:
History of the Riksdag

The Riksdag is the national legislature of Sweden. However, when it was founded in 1866 Sweden did not have a parliamentary system of government.

The national legislatures of Estonia and Finland are also called Riksdag in Swedish.

The Old Riksdag
The precursor to the modern Riksdag was the Riksdag of the Estates (Ståndsriksdagen). Of ancient origin in the Viking Things, the 1435 meeting in the city of Arboga is considered the first Riksdag, however only three of the estates were probably present the nobility, the clergy and the burghers. This informal representation was formalized in 1527 by King Gustav I of Sweden to include representatives of all the four estates, which historically reflected the lines of division in Swedish society: the nobility, the clergy, the burghers and the peasantry. Under the Instrument of Government of 1809 the Riksdag shared the powers of government with the King.

The New Riksdag
On the basis of the 1863 electoral reform bill the Estates voted in 1866 to dissolve the Riksdag of the Estates and establish a new Riksdag. The new Riksdag was a political assembly with two chambers where the members were chosen in national elections.

The revolution was that citizens could participate and vote in the elections without regard to which Estate they had hitherto belonged; instead there were new requirements on income or wealth, i.e. census suffrage. Despite the fundamental change in the principles of representation, the social composition of the Riksdag did not alter by much, and the system of government had not changed. Under the Constitution of 1809 the Riksdag still divided the powers of government with the King.

Democracy emerges
From the second half of the 19th century, when the Riksdag was founded, until the early 20th century, Swedish society underwent a number of fundamental changes that impacted on the political system. Political demands, but also sheer economic progress, increased the size of the electorate and the degree of political mobilization. This in turn also sponsored the emergence and growth of political parties. As such, the legislature became more assertive against royal authority, successfully asserting responsible government; a parliamentary system thus became de facto established; the King could not (or at least would not dare) keep a government in office against parliamentary objections.

The last time the king attempted to assert himself in opposition to the Riksdag was the Courtyard Crisis of 1914, where King Gustav V delivered a partisan speech which precipitated the resignation of Prime Minister Karl Staaff and his government. Though the outbreak of World War I kept the King’s conservative government in office, in the face of popular unrest and a clear majority for the opposition Social Democrats and Liberals at the 1917 general election, the King reluctantly resolved to appoint a cabinet from the reform-minded majority in the Riksdag. The new government's main task was to present bills on constitutional reform.

The franchise had been extended to all adult men in 1907; women’s suffrage first came in the 1921 general election.

Constitutional reform
In the 1960s, debates intensified over constitutional reform in Sweden. The fundamental question was over the system of government. Even though a de facto parliamentary system was firmly established, somewhat similar to the situation in the United Kingdom, there were demands for a more democratic constitution. One of the main issues was whether the monarchy would survive constitutional reform and this blocked the issue for a long time.

Effective from 1970, a reform of the Riksdag had been agreed upon. Though not technically part of the constitution it showed that the parties in the Riksdag were able to agree upon fundamental changes of the political system, which transformed the Riksdag from a bicameral legislature into a unicameral one. This would have 350 seats, all of which would be filled by direct election. However, the second general election to the unicameral Riksdag only gave the government support from 175 members, while the opposition could mobilize an equal force of 175 members, resulting in what became known as the "lottery Riksdag", in which the Speaker had to draw lots to resolve deadlocked votes. In 1974, it was decided that the number of seats from 1977 were to be reduced to 349.

Present
In 1974, a new Instrument of Government was established as a vital part of the Constitution and for the system of government. The monarchy was retained, whereas the monarch lost all formal political influence and became only a symbolic head of state. Several of the traditional head-of-state functions have instead been transferred to the Speaker of the Riksdag.

title: History of the Riksdag


text:
Talk:Force (disambiguation)

Needs to be edited for better structure.

I doubt anyone will be looking for "Force" as it relates to the game R-Type, likely they will search for the title of the game itself. Removed as it adds clutter to an already huge disambiguation page.--Slike 09:51, 24 Dec 2004 (UTC)

The kitchen tool.
I can't find info on that in Wiktionary, OR this page. Where is the info about the kitchen tool? I mean the kitchen tool that's related to knifes and spoons.
 * Nevermind, I found out I misspelled fork. TheBlazikenMaster 13:12, 12 August 2007 (UTC)

Lead item
MOS:DAB is clear "Rather than including a dictionary definition of a word, create a cross-link to our sister project, Wiktionary" DAB pages are to help a reader navigate to the required article from a group that have the same of a similar title and which could therfore be confused (my wording). I suggest you read MOS:DAB it has lots of suggestions as to the way a dab page should be constructed and it is quite clear that the primary article should be the one in the lead position. Abtract (talk) 01:15, 12 March 2008 (UTC)

Reverting the whole page seems a rather blunt tool. I will seek help from DAB page specialists. Abtract (talk) 09:20, 12 March 2008 (UTC)
 * Thanks to JHunterJ for assisting. Abtract (talk) 11:20, 12 March 2008 (UTC)

george lucas
what about his "force" LOL 84.16.123.194 (talk) 16:21, 15 April 2008 (UTC)
 * What about it? Lord Sesshomaru (talk • edits) 19:08, 15 April 2008 (UTC)

a couple of uses that would be handy to add
1) Radiative forcing

2) no good link, but
 * Orchestra: "The so-called "standard complement" of double winds and brass in the orchestra from the first half of the 19th century is generally attributed to the forces called for by Ludwig van Beethoven."
 * Orchestra: "... Mahler pushes the furthest boundaries of orchestral size, employing huge forces."

Milkunderwood (talk) 00:22, 2 November 2011 (UTC)
 * I've now added both a link at See also to Forcing (disambiguation), and a redlink to Forces (music), just as a heads-up - hopefully a musician will come along and fix this one. Milkunderwood (talk) 02:55, 2 November 2011 (UTC)

Merge The Force
I am proposing merging The Force (disambiguation) into this article. The two things are very similar and in some cases it is unclear which page an item belongs on. This has led to a number of inconsistencies. For instance "police force" appears on both pages. Ipswich Force is on this page while Western Force is on "The Force" page, despite both teams being referred to as "the Force". It would be entirely simpler to have both of these on one page. SpinningSpark 13:55, 29 January 2023 (UTC)

 * Can't you just fix those few errors, instead of combining the two already reasonably long lists, making them overall more difficult to navigate? --Joy (talk) 10:09, 30 January 2023 (UTC)
 * Because, as I said, they are not straightforward errors. It is ambiguous in a number of cases which page they do belong on. SpinningSpark 17:45, 9 February 2023 (UTC)
 * Oppose, as the terms are sufficiently distinct. It seems fine to leave some of those duplicates, as they seem to rightly be listed in two places. For example, The Force is a colloquial term for the Police force around here ... Klbrain (talk) 23:14, 6 April 2023 (UTC)
 * Closing, given the objections, no support, and stale discussion. Klbrain (talk) 10:38, 16 September 2023 (UTC)

title: Talk:Force (disambiguation)


text:
User talk:MockAE

Hello! Nice work on Sequence alignment. Don't be afraid to just jump in without discussion... one of the wikipedia commandments is to Be_bold_in_updating_pages. If people have issues, they'll bring them up, and that's when discussion is appropriate.

Welcome to wikipedia, and i hope we see more of your writing! Graft

Thanks for the info about ALICE & ELIZA. --Koyaanis Qatsi

title: User talk:MockAE


text:
Pleasure

Pleasure is experience that feels good, that involves the enjoyment of something. It contrasts with pain or suffering, which are forms of feeling bad. It is closely related to value, desire and action: humans and other conscious animals find pleasure enjoyable, positive or worthy of seeking. A great variety of activities may be experienced as pleasurable, like eating, having sex, listening to music or playing games. Pleasure is part of various other mental states such as ecstasy, euphoria and flow. Happiness and well-being are closely related to pleasure but not identical with it. There is no general agreement as to whether pleasure should be understood as a sensation, a quality of experiences, an attitude to experiences or otherwise. Pleasure plays a central role in the family of philosophical theories known as hedonism.

Overview
"Pleasure" refers to experience that feels good, that involves the enjoyment of something. The term is primarily used in association with sensory pleasures like the enjoyment of sex or food. But in its most general sense, it includes all types of positive or pleasant experiences including the enjoyment of sports, seeing a beautiful sunset or engaging in an intellectually satisfying activity. Pleasure contrasts with pain or suffering, which are forms of feeling bad. Both pleasure and pain come in degrees and have been thought of as a dimension going from positive degrees through a neutral point to negative degrees. This assumption is important for the possibility of comparing and aggregating the degrees of pleasure of different experiences, for example, in order to perform the Utilitarian calculus.

The concept of pleasure is similar but not identical to the concepts of well-being and of happiness. These terms are used in overlapping ways, but their meanings tend to come apart in technical contexts like philosophy or psychology. Pleasure refers to a certain type of experience while well-being is about what is good for a person. Many philosophers agree that pleasure is good for a person and therefore is a form of well-being. But there may be other things besides or instead of pleasure that constitute well-being, like health, virtue, knowledge or the fulfillment of desires. On some conceptions, happiness is identified with "the individual's balance of pleasant over unpleasant experience". Life satisfaction theories, on the other hand, hold that happiness involves having the right attitude towards one's life as a whole. Pleasure may have a role to play in this attitude, but it is not identical to happiness.

Pleasure is closely related to value, desire, motivation and right action. There is broad agreement that pleasure is valuable in some sense. Axiological hedonists hold that pleasure is the only thing that has intrinsic value. Many desires are concerned with pleasure. Psychological hedonism is the thesis that all our actions aim at increasing pleasure and avoiding pain. Freud's pleasure principle ties pleasure to motivation and action by holding that there is a strong psychological tendency to seek pleasure and to avoid pain. Classical utilitarianism connects pleasure to ethics in stating that whether an action is right depends on the pleasure it produces: it should maximize the sum-total of pleasure.

Sources and types of pleasure
Many pleasurable experiences are associated with satisfying basic biological drives, such as eating, exercise, hygiene, sleep, and sex. The appreciation of cultural artifacts and activities such as art, music, dancing, and literature is often pleasurable. Pleasure is sometimes subdivided into fundamental pleasures that are closely related to survival (food, sex, and social belonging) and higher-order pleasures (e.g., viewing art and altruism). Bentham listed 14 kinds of pleasure; sense, wealth, skill, amity, a good name, power, piety, benevolence, malevolence, memory, imagination, expectation, pleasures dependent on association, and the pleasures of relief. Some commentators see 'complex pleasures' including wit and sudden realisation, and some see a wide range of pleasurable feelings.

Theories of pleasure
Pleasure comes in various forms, for example, in the enjoyment of food, sex, sports, seeing a beautiful sunset or engaging in an intellectually satisfying activity. Theories of pleasure try to determine what all these pleasurable experiences have in common, what is essential to them. They are traditionally divided into quality theories and attitude theories. An alternative terminology refers to these theories as phenomenalism and intentionalism. Quality theories hold that pleasure is a quality of pleasurable experiences themselves while attitude theories state that pleasure is in some sense external to the experience since it depends on the subject's attitude to the experience. More recently, dispositional theories have been proposed that incorporate elements of both traditional approaches.

Quality theories
In everyday language, the term "pleasure" is primarily associated with sensory pleasures like the enjoyment of food or sex. One traditionally important quality-theory closely follows this association by holding that pleasure is a sensation. On the simplest version of the sensation theory, whenever we experience pleasure there is a distinctive pleasure-sensation present. So a pleasurable experience of eating chocolate involves a sensation of the taste of chocolate together with a pleasure-sensation. An obvious shortcoming of this theory is that many impressions may be present at the same time. For example, there may be an itching sensation as well while eating the chocolate. But this account cannot explain why the enjoyment is linked to the taste of the chocolate and not to the itch. Another problem is due to the fact that sensations are usually thought of as localized somewhere in the body. But considering the pleasure of seeing a beautiful sunset, there seems to be no specific region in the body at which we experience this pleasure.

These problems can be avoided by felt-quality-theories, which see pleasure not as a sensation but as an aspect qualifying sensations or other mental phenomena. As an aspect, pleasure is dependent on the mental phenomenon it qualifies, it cannot be present on its own. Since the link to the enjoyed phenomenon is already built into the pleasure, it solves the problem faced by sensation theories to explain how this link comes about. It also captures the intuition that pleasure is usually pleasure of something: enjoyment of drinking a milkshake or of playing chess but not just pure or object-less enjoyment. According to this approach, pleasurable experiences differ in content (drinking a milkshake, playing chess) but agree in feeling or hedonic tone. Pleasure can be localized, but only to the extent that the impression it qualifies is localized.

One objection to both the sensation theory and the felt-quality theory is that there is no one quality shared by all pleasure-experiences. The force of this objection comes from the intuition that the variety of pleasure-experiences is just too wide to point out one quality shared by all, for example, the quality shared by enjoying a milkshake and enjoying a chess game. One way for quality theorists to respond to this objection is by pointing out that the hedonic tone of pleasure-experiences is not a regular quality but a higher-order quality. As an analogy, a vividly green thing and a vividly red thing do not share a regular color property but they share "vividness" as a higher-order property.

Attitude theories
Attitude theories propose to analyze pleasure in terms of attitudes to experiences. So to enjoy the taste of chocolate it is not sufficient to have the corresponding experience of the taste. Instead, the subject has to have the right attitude to this taste for pleasure to arise. This approach captures the intuition that a second person may have exactly the same taste-experience but not enjoy it since the relevant attitude is lacking. Various attitudes have been proposed for the type of attitude responsible for pleasure, but historically the most influential version assigns this role to desires. On this account, pleasure is linked to experiences that fulfill a desire had by the experiencer. So the difference between the first and the second person in the example above is that only the first person has a corresponding desire directed at the taste of chocolate.

One important argument against this version is that while it is often the case that we desire something first and then enjoy it, this cannot always be the case. In fact, often the opposite seems to be true: we have to learn first that something is enjoyable before we start to desire it. This objection can be partially avoided by holding that it does not matter whether the desire was there before the experience but that it only matters what we desire while the experience is happening. This variant, originally held by Henry Sidgwick, has recently been defended by Chris Heathwood, who holds that an experience is pleasurable if the subject of the experience wants the experience to occur for its own sake while it is occurring. But this version faces a related problem akin to the Euthyphro dilemma: it seems that we usually desire things because they are enjoyable, not the other way round. So desire theories would be mistaken about the direction of explanation. Another argument against desire theories is that desire and pleasure can come apart: we can have a desire for things that are not enjoyable and we can enjoy things without desiring to do so.

Dispositional theories
Dispositional theories try to account for pleasure in terms of dispositions, often by including insights from both the quality theories and the attitude theories. One way to combine these elements is to hold that pleasure consists in being disposed to desire an experience in virtue of the qualities of this experience. Some of the problems of the regular desire theory can be avoided this way since the disposition does not need to be realized for there to be pleasure, thereby taking into account that desire and pleasure can come apart.

Philosophy
Pleasure plays a central role in theories from various areas of philosophy. Such theories are usually grouped together under the label "hedonism".

Ethics
Pleasure is related not just to how we actually act, but also to how we ought to act, which belongs to the field of ethics. Ethical hedonism takes the strongest position on this relation in stating that considerations of increasing pleasure and decreasing pain fully determine what we should do or which action is right. Ethical hedonist theories can be classified in relation to whose pleasure should be increased. According to the egoist version, each agent should only aim at maximizing her own pleasure. This position is usually not held in very high esteem. Utilitarianism, on the other hand, is a family of altruist theories that are more respectable in the philosophical community. Within this family, classical utilitarianism draws the closest connection between pleasure and right action by holding that the agent should maximize the sum-total of everyone's happiness. This sum-total includes the agent's pleasure as well, but only as one factor among many.

Value
Pleasure is intimately connected to value as something that is desirable and worth seeking. According to axiological hedonism, it is the only thing that has intrinsic value or is good in itself. This position entails that things other than pleasure, like knowledge, virtue or money, only have instrumental value: they are valuable because or to the extent that they produce pleasure but lack value otherwise. Within the scope of axiological hedonism, there are two competing theories about the exact relation between pleasure and value: quantitative hedonism and qualitative hedonism. Quantitative hedonists, following Jeremy Bentham, hold that the specific content or quality of a pleasure-experience is not relevant to its value, which only depends on its quantitative features: intensity and duration. On this account, an experience of intense pleasure of indulging in food and sex is worth more than an experience of subtle pleasure of looking at fine art or of engaging in a stimulating intellectual conversation. Qualitative hedonists, following John Stuart Mill, object to this version on the grounds that it threatens to turn axiological hedonism into a "philosophy of swine". Instead, they argue that the quality is another factor relevant to the value of a pleasure-experience, for example, that the lower pleasures of the body are less valuable than the higher pleasures of the mind.

Beauty
A very common element in many conceptions of beauty is its relation to pleasure. Aesthetic hedonism makes this relation part of the definition of beauty by holding that there is a necessary connection between pleasure and beauty, e.g. that for an object to be beautiful is for it to cause pleasure or that the experience of beauty is always accompanied by pleasure. The pleasure due to beauty does not need to be pure, i.e. exclude all unpleasant elements. Instead, beauty can involve mixed pleasure, for example, in the case of a beautifully tragic story. We take pleasure from many things that are not beautiful, which is why beauty is usually defined in terms of a special type of pleasure: aesthetic or disinterested pleasure. A pleasure is disinterested if it is indifferent to the existence of the beautiful object. For example, the joy of looking at a beautiful landscape would still be valuable if it turned out that this experience was an illusion, which would not be true if this joy was due to seeing the landscape as a valuable real estate opportunity. Opponents of aesthetic hedonism have pointed out that despite commonly occurring together, there are cases of beauty without pleasure. For example, a cold jaded critic may still be a good judge of beauty due to her years of experience but lack the joy that initially accompanied her work. A further question for hedonists is how to explain the relation between beauty and pleasure. This problem is akin to the Euthyphro dilemma: is something beautiful because we enjoy it or do we enjoy it because it is beautiful? Identity theorists solve this problem by denying that there is a difference between beauty and pleasure: they identify beauty, or the appearance of it, with the experience of aesthetic pleasure.

Hellenistic philosophy
The ancient Cyrenaics posited pleasure as the universal aim for all people. Later, Epicurus defined the highest pleasure as aponia (the absence of pain), and pleasure as "freedom from pain in the body and freedom from turmoil in the soul". According to Cicero (or rather his character Torquatus) Epicurus also believed that pleasure was the chief good and pain the chief evil. The Pyrrhonist philosopher Aenesidemus claimed that following Pyrrhonism's prescriptions for philosophical skepticism produced pleasure.

Medieval philosophy
In the 12th century, Razi's Treatise of the Self and the Spirit (Kitab al Nafs Wa’l Ruh) analyzed different types of pleasure- sensuous and intellectual, and explained their relations with one another. He concludes that human needs and desires are endless, and "their satisfaction is by definition impossible."

Schopenhauer
The 19th-century German philosopher Arthur Schopenhauer understood pleasure as a negative sensation, one that negates the usual existential condition of suffering.

Psychology
Pleasure is often regarded as a bipolar construct, meaning that the two ends of the spectrum from pleasure to suffering are mutually exclusive. That is part of the circumplex model of affect. Yet, some lines of research suggest that people do experience pleasure and suffering at the same time, giving rise to so-called mixed feelings. Pleasure is considered one of the core dimensions of emotion. It can be described as the positive evaluation that forms the basis for several more elaborate evaluations such as "agreeable" or "nice". As such, pleasure is an affect and not an emotion, as it forms one component of several different emotions. The clinical condition of being unable to experience pleasure from usually enjoyable activities is called anhedonia. An active aversion to obtaining pleasure is called hedonophobia.

Pleasure and belief
The degree to which something or someone is experienced as pleasurable not only depends on its objective attributes (appearance, sound, taste, texture, etc.), but on beliefs about its history, about the circumstances of its creation, about its rarity, fame, or price, and on other non-intrinsic attributes, such as the social status or identity it conveys. For example, a sweater that has been worn by a celebrity is more desired than an otherwise identical sweater that has not, though considerably less so if it has been washed.

Motivation and behavior
Pleasure-seeking behavior is a common phenomenon and may indeed dominate our conduct at times. The thesis of psychological hedonism generalizes this insight by holding that all our actions aim at increasing pleasure and avoiding pain. This is usually understood in combination with egoism, i.e. that each person only aims at her own happiness. Our actions rely on beliefs about what causes pleasure. False beliefs may mislead us and thus our actions may fail to result in pleasure, but even failed actions are motivated by considerations of pleasure, according to psychological hedonism. The paradox of hedonism states that pleasure-seeking behavior commonly fails also in another way. It asserts that being motivated by pleasure is self-defeating in the sense that it leads to less actual pleasure than following other motives.

Sigmund Freud formulated his pleasure principle in order to account for the effect pleasure has on our behavior. It states that there is a strong, inborn tendency of our mental life to seek immediate gratification whenever an opportunity presents itself. This tendency is opposed by the reality principle, which constitutes a learned capacity to delay immediate gratification in order to take the real consequences of our actions into account. Freud also described the pleasure principle as a positive feedback mechanism that motivates the organism to recreate the situation it has just found pleasurable, and to avoid past situations that caused pain.

Cognitive biases
A cognitive bias is a systematic tendency of thinking and judging in a way that deviates from a normative criterion, especially from the demands of rationality. Cognitive biases in regard to pleasure include the peak–end rule, the focusing illusion, the nearness bias and the future bias.

The peak–end rule affects how we remember the pleasantness or unpleasantness of experiences. It states that our overall impression of past events is determined for the most part not by the total pleasure and suffering it contained but by how it felt at its peaks and at its end. For example, the memory of a painful colonoscopy is improved if the examination is extended by three minutes in which the scope is still inside but not moved anymore, resulting in a moderately uncomfortable sensation. This extended colonoscopy, despite involving more pain overall, is remembered less negatively due to the reduced pain at the end. This even increases the likelihood for the patient to return for subsequent procedures. Daniel Kahneman explains this distortion in terms of the difference between two selves: the experiencing self, which is aware of pleasure and pain as they are happening, and the remembering self, which shows the aggregate pleasure and pain over an extended period of time. The distortions due to the peak–end rule happen on the level of the remembering self. Our tendency to rely on the remembering self can often lead us to pursue courses of action that are not in our best self-interest.

A closely related bias is the focusing illusion. The "illusion" occurs when people consider the impact of one specific factor on their overall happiness. They tend to greatly exaggerate the importance of that factor, while overlooking the numerous other factors that would in most cases have a greater impact.

The nearness bias and the future bias are two different forms of violating the principle of temporal neutrality. This principle states that the temporal location of a benefit or a harm is not important for its normative significance: a rational agent should care to the same extent about all parts of their life. The nearness bias, also discussed under the labels "present bias" or "temporal discounting", refers to our tendency to violate temporal neutrality in regards to temporal distance from the present. On the positive side, we prefer pleasurable experiences to be near rather than distant. On the negative side, we prefer painful experiences to be distant rather than near. The future bias refers to our tendency to violate temporal neutrality in regards to the direction of time. On the positive side, we prefer pleasurable experiences to be in the future rather than in the past. On the negative side, we prefer painful experiences to be in the past rather than in the future.

Motivation
While all pleasurable stimuli can be seen as rewards, some rewards do not evoke pleasure. Based upon the incentive salience model of reward – the attractive and motivational property of a stimulus that induces approach behavior and consummatory behavior – an intrinsic reward has two components: a "wanting" or desire component that is reflected in approach behavior, and a "liking" or pleasure component that is reflected in consummatory behavior. Some research indicates that similar mesocorticolimbic circuitry is activated by quite diverse pleasures, suggesting a common neural currency. Some commentators opine that our current understanding of how pleasure happens within us remains poor, but that scientific advance gives optimism for future progress.

Animal pleasure
In the past, there has been debate as to whether pleasure is experienced by other animals rather than being an exclusive property of humankind; however, it is now known that animals do experience pleasure, as measured by objective behavioral and neural hedonic responses to pleasurable stimuli.

title: Pleasure