title: Spanish fly

text: The species and others in its family were used in traditional apothecary preparations as "Cantharides". The insect is the source of the terpenoid cantharidin, a toxic blistering agent once used as an exfoliating agent, anti-rheumatic drug and an aphrodisiac. The substance has also found culinary use in some blends of the North African spice mix "ras el hanout". Its various supposed benefits have been responsible for accidental poisonings.


title: Spanish fly

text: The generic name is from the Greek λύττα ("lytta"), meaning martial rage, raging madness, Bacchic frenzy, or rabies. The specific name is derived from Latin "vesica", blister.


title: Spanish fly

text: "Lytta vesicatoria" was formerly named "Cantharis vesicatoria", although the genus "Cantharis" is in an unrelated family, Cantharidae, the soldier beetles. It was classified there erroneously until the Danish zoologist Johan Christian Fabricius corrected its name in his "Systema entomologiae" in 1775. He reclassified the Spanish fly as the type species of the new genus "Lytta", in the family Meloidae.


title: Spanish fly

text: The adult Spanish fly is a slender, soft-bodied metallic and iridescent golden-green insect, one of the blister beetles. It is approximately wide by long.


title: Spanish fly

text: The female lays her fertilised eggs on the ground, near the nest of a ground-nesting solitary bee. The larvae are very active as soon as they hatch. They climb a flowering plant and await the arrival of a solitary bee. They hook themselves on to the bee using the three claws on their legs that give the first instar larvae their name, triungulins (from Latin "tri", three, and "ungulus", claw). The bee carries the larvae back to its nest, where they feed on bee larvae and the bees' food supplies. The larvae are thus somewhere between predators and parasites. The active larvae moult into very different, more typically scarabaeoid larvae for the remaining two or more instars, in a development type called hypermetamorphosis. The adults emerge from the bees' nest and fly to the woody plants on which they feed.


title: Spanish fly

text: The defensive chemical cantharidin, for which the beetle is known, is synthesised only by males; females obtain it from males during mating, as the spermatophore contains some. This may be a nuptial gift, increasing the value of mating to the female, and thus increasing the male's reproductive fitness. Zoologists note that the conspicuous coloration, the presence of a powerful toxin, and the adults' aggregating behaviour in full view of any predators strongly suggest aposematism among the blistering meloid beetles.


title: Spanish fly

text: The Spanish fly is found across Eurasia, though it is a mainly a southern European species, with some records from southern Great Britain and Poland.


title: Spanish fly

text: Adult beetles primarily feed on leaves of ash, lilac, amur privet, honeysuckle and white willow. It is occasionally found on plum, rose, and elm.


title: Spanish fly

text: Cantharidin, the principal active component in preparations of Spanish fly, was first isolated and named in 1810 by the French chemist Pierre Robiquet, who demonstrated that it was the principal agent responsible for the aggressively blistering properties of this insect's egg coating. It was asserted at that time that it was as toxic as the most violent poisons then known, such as strychnine.


title: Spanish fly

text: Each beetle contains some 0.2–0.7 mg of cantharidin, males having significantly more than females. The beetle secretes the agent orally, and exudes it from its joints as a milky fluid. The potency of the insect as a blistering agent has been known since antiquity and the activity has been used in various ways. This has led to its small-scale commercial preparation and sale, in a powdered form known as "cantharides" (from the plural of Greek κανθαρίς, "Kantharis", beetle), obtained from dried and ground beetles. The crushed powder is of yellow-brown to brown-olive color with iridescent reflections, is of disagreeable scent, and is bitter to taste. Cantharidin, the active agent, is a terpenoid, and is produced by some other insects, such as "Epicauta immaculata".


title: Spanish fly

text: Cantharidin is dangerously toxic, inhibiting the enzyme phosphatase 2A. It causes irritation, blistering, bleeding and discomfort. These effects can escalate to erosion and bleeding of mucosa in each system, sometimes followed by severe gastro-intestinal bleeding and acute tubular necrosis and glomerular destruction, resulting in gastro-intestinal and renal dysfunction, organ failure, and death.


title: Spanish fly

text: Preparations of Spanish fly and its active agent have been implicated in both inadvertent and intentional poisonings. Arthur Kendrick Ford was imprisoned in 1954 for the unintended deaths of two women surreptitiously given candies laced with cantharidin, which he had intended to act as an aphrodisiac. It has been suggested that George Washington was treated with Spanish fly for epiglottitis, the condition which caused his death.


title: Spanish fly

text: Currently the cantharidin in US, in the form of collodion, is used in the treatment of warts and molluscum.


title: Spanish fly

text: In Morocco and other parts of North Africa, spice blends known as "ras el hanout" sometimes included as a minor ingredient "green metallic beetles", inferred to be "L. vesicatoria", although its sale in Moroccan spice markets was banned in the 1990s. "Dawamesk", a spread or jam made in North Africa and containing hashish, almond paste, pistachio nuts, sugar, orange or tamarind peel, cloves, and other various spices, occasionally included cantharides.


title: Spanish fly

text: In ancient China, the beetles were mixed with human excrement, arsenic, and wolfsbane to make the world's first recorded stink bomb.


title: Spanish fly

text: In ancient Greece and Rome, Spanish fly was used to attempt to treat skin diseases, while in medieval Persia, Islamic medicine applied Spanish fly, named "ḏarārīḥ" (الذراح), to attempt to prevent rabies.


title: Spanish fly

text: In 19 century, Spanish fly was used externally mainly as blistering agent and local irritant; also, in chronic gonorrhoea, paralysis, lepra, ulcers therapy. "L. vesicatoria" was used internally as a diuretic stimulant and aphrodisiac.


title: Hiram Abiff

text: Hiram Abiff (also Hiram Abif or the Widow's son) is the central character of an allegory presented to all candidates during the third degree in Freemasonry.


title: Hiram Abiff

text: Hiram is presented as the chief architect of King Solomon's Temple. He is murdered inside this Temple by three ruffians, after they failed to obtain from him the Master Masons' secrets. The themes of the allegory are the importance of fidelity, and the certainty of death.


title: Hiram Abiff

text: The tale of Hiram Abiff as passed down in Masonic Lodges underpins the third degree. It starts with his arrival in Jerusalem, and his appointment by Solomon as chief architect and master of works at the construction of his temple. As the temple is nearing completion, three fellowcraft masons from the workforce ambush him as he leaves the building, demanding the secrets of a master mason. Hiram is challenged by each in turn and, at each refusal to divulge the information, his assailant strikes him with a mason's tool (differing between jurisdictions). He is injured by the first two assailants, and struck dead by the last.


title: Hiram Abiff

text: His murderers hide his body under a pile of rubble, returning at night to move the body outside the city, where they bury it in a shallow grave marked with a sprig of acacia. As the Master is missed the next day, Solomon sends out a group of fellowcraft masons to search for him. The loose acacia is accidentally discovered, and the body exhumed to be given a decent burial. The hiding place of the "three ruffians" is also discovered, and they are brought to justice. Solomon informs his workforce that the secret word of a master mason is now lost. He replaces it with a substitute word. This word is considered a secret by Masons, but for hundreds of years various "revelations" of the word have been made, usually all differing from each other. One such "revelation" is "Mach-benak" or "decay-apparently" based on gestures given and words spoken upon the discovery of Hiram's body. Such is the general legend as related in the Anglo-American jurisdictions.


title: Hiram Abiff

text: In Continental Freemasonry, the tale is slightly different: a large number of master masons (not just Hiram) are working on the Temple, and the three ruffians are seeking the passwords and signs that will give them a higher wage. The result is the same, but this time, it is master masons who find the body. The secrets are not lost, but Solomon orders them buried under the Temple, inscribed on Hiram's grave, and the same substitution is made as a mark of respect. The secrets "lost" in the other tradition are here given to new master masons as part of their ritual. In this version, Hiram is often renamed Adoniram.


title: Hiram Abiff

text: In the Hebrew Bible or Old Testament, there are three separate instances of people named Hiram that were involved in the construction of the temple of Solomon:


title: Hiram Abiff

text: Flavius Josephus in his "Antiquities of the Jews" (Chapter 8:76) refers to Hiram as τεχνίτης, artificer, craftsman. "Now Solomon sent for an artificer out of Tyre, whose name was Hiram: he was by birth of the tribe of Naphtali, on his mother's side (for she was of that tribe); but his father was Ur, of the stock of the Israelites."


title: Hiram Abiff

text: The Targum Sheni, an Aramaic commentary on the Book of Esther written sometime between the fall of Rome and the Crusades, credits Hiram with the construction of a miraculous throne for Solomon, which in Esther's time is being used by the descendants of Cyrus the Great.


title: Hiram Abiff

text: The most elaborate version of the legend occurs in Gérard de Nerval's 1851 account, "Voyage en Orient", where he relates the tale, inserting all the masonic passwords, as part of the story of Balkis, the "Queen of the Morning" and "Soliman", Prince of the Genii. This is an elaboration of the second version above, where the Master Craftsman is named Adoniram. Before his death, he undergoes mystical adventures as his tale is interwoven with that of Solomon and Balkis, the Queen of Sheba. The ruffians who kill him are under the instruction of Solomon himself. De Nerval relates the story as having been told in an Eastern coffee house over a two-week period. A similar account is given in Charles William Heckethorn's "The Secret Societies of all Ages and Countries", where Solomon plots to destroy Hiram because of the mutual love between Hiram and the Queen of Sheba. Meanwhile, in 1862, the whole adventure of Adoniram's love for Balkis and his murder by three workmen in the pay of Solomon had been set to music in Charles Gounod's opera, "La reine de Saba".


title: Hiram Abiff

text: There have been many proposals for the origin of the Masonic Hiram Abiff story, which are dismissed by most Masonic scholars. However the leading theory supported by many scholars of historical Freemasonry is advanced in the recent work of Bro. Christopher Powell, who in 2021 published a paper in QCCC that the Reverend Dr. John Theophilus Desaguliers is the likely author of the Hiram Abiff story in the early 1720s and it was he who introduced it into the 3rd degree. In his research Bro. Powell notes how Desaguliers also introduced the "lost word" aspect of the Royal Arch degree which he likely read in a book he owned titled "The Temple of Solomon, portrayed by Scripture-light." If the word was to be found, it would need to be first lost, hence the Hiram Abiff story. According to Powell, Desaguliers as a Frenchman living in England, would have known the Chanson de Geste legend (explored below), and used it as a base for the legend of Hiram Abiff. However instead of being used as a ritual since the 12th century, Powell argues that Desaguliers used this existing myth to create a central story for the newly created 3rd degree, for which there is no evidence whatsoever before 1720.


title: Hiram Abiff

text: According to authors Robert Lomas and Christopher Knight, the prototype for Hiram Abiff was the Egyptian king Seqenenre Tao II, who (they claim) died in an almost identical manner. This idea is dismissed by most Masonic scholars.


title: Hiram Abiff

text: In his book "The Sufis", the Afghan scholar Idries Shah suggested that Dhul-Nun al-Misri might have been the origin of the character Hiram Abiff in the masonic Master Mason ritual. The link, he believes, was through the Sufi sect Al-Banna ("The Builders") who built the Jami Al-Aqsa and the Dome of the Rock in Jerusalem. This fraternity could have influenced some early masonic guilds which borrowed heavily from the Oriental architecture in the creation of the Gothic style.


title: Hiram Abiff

text: The French masonic historian Paul Naudon has highlighted the similarity between the death of Hiram and the murder of Renaud de Montauban in the late 12th Century chanson de geste, "The Four Sons of Aymon". Renaud, like his prototype Saint Reinold, was killed by a hammer-blow to the head while working as a mason at Cologne Cathedral, and his body hidden by his murderers before being miraculously re-discovered.


title: Censored Eleven

text: The Censored Eleven is a group of "Looney Tunes" and "Merrie Melodies" cartoons originally produced and released by Warner Bros. that were withheld from syndication in the United States by United Artists (UA) since 1968. UA owned the distribution rights to the Associated Artists Productions library at that time, and decided to pull these 11 cartoons from broadcast because the use of ethnic stereotypes in the cartoons, specifically African stereotypes, was deemed too offensive for contemporary audiences. The ban has been continued by UA and the successive owners of the pre-August 1948 "Looney Tunes"/"Merrie Melodies". , these shorts have not been officially broadcast on television and have only been exhibited once theatrically by Warner Bros. in 2010 (see below for more details) since their withdrawal. They have turned up, however, on low-cost VHS and DVD collections.


title: Censored Eleven

text: The cartoon output of Warner Bros. during its most active period even sometimes had censorship problems more complex in some respects than those of features. Unlike feature films, which were routinely censored in the script, the animated shorts were passed upon only when completed, which made the producers exceptionally cautious as to restrictions. In 1983, director Chuck Jones commented on the television censorship of the Warner Bros. cartoons: "I don't like to see the films cut at all. [...] They make some cuts that are so arbitrary and stupid, you can't believe it." Independent stations that once ran the syndicated Warner Bros. cartoons never had the same type of censorship as first-run networks such as ABC and CBS did for the cartoons. Some stations even owned syndication rights to "a few they consider[ed] racially stereotypical", but never ran them.


title: Censored Eleven

text: When Ted Turner obtained the rights to the pre-1950 Warner Bros. library from MGM/UA Entertainment Co. in 1986, he vowed that he would not distribute or air any cartoons from the Censored Eleven. They were the only cartoons in this package not to be featured in the LaserDisc series "The Golden Age of Looney Tunes".


title: Censored Eleven

text: Friz Freleng directed the largest number of cartoons on the list with four, followed by Tex Avery with three, and Bob Clampett with only two. Rudolf Ising, like Jones, only has one cartoon on the list. "Angel Puss" is the only cartoon directed by Jones on the list, as well as the only "Looney Tunes" cartoon on the list. "Hittin' the Trail to Hallelujah Land" is the only black-and-white short on the list, and the only cartoon to star Piggy. "Goldilocks and the Jivin' Bears" is the only cartoon on this list not to be produced by Leon Schlesinger. It is also the first to be produced by an uncredited Eddie Selzer. "All This and Rabbit Stew" is the only Bugs Bunny cartoon on the list. "The Isle of Pingo Pongo" is also the only Elmer Fudd cartoon on the list. The other 8 are one-shot cartoons.


title: Censored Eleven

text: Several more cartoons have been removed from circulation since the list was created, but have not been added to the Censored Eleven list. These include numerous World War II-era cartoons involving the Japanese, such as "Bugs Bunny Nips the Nips" and "Tokio Jokio".


title: Censored Eleven

text: Some cartoons that remain in the release have been heavily edited to remove stereotypical depictions of African Americans, including the "Gone With the Wind" satire "Confederate Honey". "Fresh Hare" is often shorn of a scene in which a blackface Bugs and Elmer sing "Camptown Races". Friz Freleng's cartoon "September in the Rain" features some stereotyped black characters but is not entirely focused on them, so has occasionally reappeared without them. An early Porky Pig cartoon with stereotypical depictions of black people is "Porky's Railroad" (also 1937).


title: Censored Eleven

text: A number of shorts are rarely shown owing to stereotyping and potentially offensive characterizations of Native Americans. They include "The Hardship of Miles Standish" (1940), "Slightly Daffy" (1944), "A Feather in His Hare" (1948), "Nothing But the Tooth" (1948), "Tom Tom Tomcat" (1953), "Horse Hare" (1960), "Hocus Pocus Powwow" (1968), and "Injun Trouble" (1969). The 1946 short "Book Revue" is withdrawn from Cartoon Network and Boomerang and is omitted from its app due to the brief sequence showing various male characters suggestively reacts towards a sultry Native stripper.


title: Censored Eleven

text: As the 20th century came to a close, the Censored Eleven cartoons became better known as several animation historians drew attention to their existence. The publicity these films received from various animation discussion websites eventually led to an article in "The New York Times". This is in part due to the advent of the Internet, and the rise of YouTube has brought some of the Censored Eleven to light.


title: Censored Eleven

text: In February 2010, as part of a press release for the first annual TCM Classic Film Festival, it was announced that the Censored Eleven were to receive a special screening sourced from restored 35mm film prints. This special presentation was put together by George Feltenstein, vice president of Warner Bros.' classic film catalog. Film historian Donald Bogle, who has six books published to his credit on the subject of African American stereotypes in film, agreed to host the event for the festival. On April 24, 2010, a total of eight of the Censored Eleven were screened at the Egyptian Theater in Hollywood; the three that were not shown at the event were "Jungle Jitters", "All This and Rabbit Stew" and "Angel Puss". According to animation historian Jerry Beck, this event was a way for Warner Bros. to test the waters for a potential DVD release of these controversial films, possibly through the "Warner Archives" collection.


title: Censored Eleven

text: At the New York Comic Con in October 2010, Warner Bros. confirmed that it would be releasing the Censored Eleven completely uncut on DVD through the "Warner Archives" program sometime in 2011. On December 1, 2010, animation expert Jerry Beck announced on the Shokus Internet Radio call-in talk program "Stu's Show" that there were plans for a general traditional retail release and not via the Warner Archives. It would be a high-class release featuring all of the Censored Eleven and other rare cartoons restored, with some bonus materials. However, no further news of a DVD release has surfaced since. In 2016, Jerry Beck stated that the transfers had been done, but the DVD release had been delayed indefinitely due to declining sales of previous "Looney Tunes Platinum Collection" releases. In 2018, according to a user on Shadow and Act who spoke to Beck, the plans to release the cartoons had been scrapped due to changing cultural sensitivities, as well as the poor sales of classic cartoon DVDs.


title: Arthur Elgort

text: Arthur Elgort (born June 8, 1940) is an American fashion photographer best known for his work with "Vogue" magazine.


title: Arthur Elgort

text: Elgort was born in Brooklyn, to Sophie (née Didimamoff) and Harry Elgort (April 10, 1908 – October 23, 1998), a restaurant owner. He is of Russian-Jewish heritage. Raised in New York City, he attended Stuyvesant High School and Hunter College, where he studied painting.


title: Arthur Elgort

text: He lives in New York City with his wife, Grethe Barrett Holby, who is a producer, stage director, choreographer, and dramaturge, and three children, including actor and singer Ansel Elgort.


title: Arthur Elgort

text: Elgort began his career working as a photo assistant to Gosta "Gus" Peterson. Elgort's 1971 debut in "British Vogue" created a sensation in the Fashion Photography world where his soon-to-be iconic "snapshot" style and emphasis on movement and natural light liberated the idea of fashion photography. In September 2008, he told "Teen Vogue" that he credited "Mademoiselle" for his big break: "They were really brave and gave me a chance. It was the first time I was shooting a cover instead of a half-page here or there."


title: Arthur Elgort

text: He worked for such magazines as "International and American Vogue, Glamour, GQ, Rolling Stone, and Teen Vogue", and shooting advertising campaigns with fashion labels as Chanel, Valentino, and Yves Saint Laurent. He still works for fashion publications, as well as working on his most recent 2009 advertising campaigns with Via Spiga and Liz Claiborne with Isaac Mizrahi. His work is exhibited in the permanent collections of the International Center of Photography in New York, in the Victoria and Albert Museum in London and in the Museum of Fine Arts in Houston, Texas.


title: Arthur Elgort

text: Elgort made several films, including "Colorado Cowboy" that follows legendary cowboy, Bruce Ford, and which won the award for Best Cinematography at the Sundance Film Festival in 1994.


title: Gresham's law

text: In economics, Gresham's law is a monetary principle stating that "bad money drives out good". For example, if there are two forms of commodity money in circulation, which are accepted by law as having similar face value, the more valuable commodity will gradually disappear from circulation.


title: Gresham's law

text: The law was named in 1860 by economist Henry Dunning Macleod after Sir Thomas Gresham (1519–1579), an English financier during the Tudor dynasty. Gresham had urged Queen Elizabeth to restore confidence in then-debased English currency. The concept was thoroughly defined in medieval Europe by Nicolaus Copernicus and known centuries earlier in classical Antiquity, the Middle East and China.


title: Gresham's law

text: Under Gresham's Law, "good money" is money that shows little difference between its nominal value (the face value of the coin) and its commodity value (the value of the metal of which it is made, often precious metals, nickel, or copper).


title: Gresham's law

text: In the absence of legal-tender laws, metal coin money will freely exchange at somewhat above bullion market value. This may be observed in bullion coins such as the Canadian Gold Maple Leaf, the South African Krugerrand, the American Gold Eagle, or even the silver Maria Theresa thaler (Austria) and the Libertad (Mexico). Coins of this type are of a known purity and are in a convenient form to handle. People prefer trading in coins rather than in anonymous hunks of precious metal, so they attribute more value to coins of equal weight.


title: Gresham's law

text: The price spread between face value and commodity value when it is minted is called seigniorage. As some coins do not circulate, remaining in the possession of coin collectors, this can increase demand for coinage.


title: Gresham's law

text: On the other hand, "bad money" is money that has a commodity value considerably lower than its face value and is in circulation along with good money, where both forms are required to be accepted at equal value as legal tender.


title: Gresham's law

text: In Gresham's day, bad money included any coin that had been debased. Debasement was often done by the issuing body, where less than the officially specified amount of precious metal was contained in an issue of coinage, usually by alloying it with a base metal. The public could also debase coins, usually by clipping or scraping off small portions of the precious metal, also known as "stemming" (reeded edges on coins were intended to make clipping evident). Other examples of bad money include counterfeit coins made from base metal. Today virtually all circulating coins are made from base metals, known as fiat money. While virtually all contemporary coinage is composed solely of base metals, during certain contemporary, 21st century years in which copper values were relatively high, at least one common coin (the U.S. nickel) still maintained "good money" status (largely depending on market rates).


title: Gresham's law

text: In the case of clipped, scraped, or counterfeit coins, the commodity value was reduced by fraud, as the face value remains at the previous higher level. On the other hand, with a coinage debased by a government issuer, the commodity value of the coinage was often reduced quite openly, while the face value of the debased coins was held at the higher level by legal tender laws.


title: Gresham's law

text: Silver coins were widely circulated in Canada (until 1968) and in the United States (until 1964 for dimes and quarters and 1970 for half-dollars) when the Coinage Act of 1965 was passed. These countries debased their coins by switching to cheaper metals, thereby inflating the new debased currency in relation to the supply of the former silver coins. The silver coins disappeared from circulation as citizens retained them both for their collector value and to capture the steady current and future intrinsic value of the metal content over the newly inflated and therefore devalued coins, using the newer coins in daily transactions.


title: Gresham's law

text: The same process occurs today with the copper content of coins such as the pre-1997 Canadian penny, the pre-1982 United States penny and the pre-1992 UK bronze pennies and two pence. This also occurred even with coins made of less expensive metals such as steel in India.


title: Gresham's law

text: The law states that any circulating currency consisting of both "good" and "bad" money (both forms required to be accepted at equal value under legal tender law) quickly becomes dominated by the "bad" money. This is because people spending money will hand over the "bad" coins rather than the "good" ones, keeping the "good" ones for themselves.


title: Gresham's law

text: Legal tender laws act as a form of price control. In such a case, the intrinsically less valuable money is preferred in exchange, because people prefer to save the intrinsically more valuable money.


title: Gresham's law

text: Consider a customer purchasing an item which costs five pence, who possesses several silver sixpence coins. Some of these coins are more debased, while others are less so – but legally, they are all mandated to be of equal value. The customer would prefer to retain the better coins, and so offers the shopkeeper the most debased one. In turn, the shopkeeper must give one penny in change, and has every reason to give the most debased penny. Thus, the coins that circulate in the transaction will tend to be of the most debased sort available to the parties.


title: Gresham's law

text: If "good" coins have a face value below that of their metallic content, individuals may be motivated to melt them down and sell the metal for its higher intrinsic value, even if such destruction is illegal. As an example, consider the 1965 United States half-dollar coins, which contained 40% silver. In previous years, these coins were 90% silver. With the release of the 1965 half-dollar, which was legally required to be accepted at the same value as the earlier 90% halves, the older 90% silver coinage quickly disappeared from circulation, while the newer debased coins remained in use. As the value of the dollar (Federal Reserve notes) continued to decline, resulting in the value of the silver content exceeding the face value of the coins, many of the older half dollars were melted down or removed from circulation and into private collections and hoards. Beginning in 1971, the U.S. government abandoned including any silver in half dollars, as the metal value of the 40% silver coins began to exceed their face value, which resulted in a repeat of the previous event, as the 40% silver coins also began to vanish from circulation and into coin hoards.


title: Gresham's law

text: A similar situation occurred in 2007, in the United States with the rising price of copper, zinc, and nickel, which led the U.S. government to ban the melting or mass exportation of one-cent and five-cent coins.


title: Gresham's law

text: In addition to being melted down for its bullion value, money that is considered to be "good" tends to leave an economy through international trade. International traders are not bound by legal tender laws as citizens of the issuing country are, so they will offer higher value for good coins than bad ones. The good coins may leave their country of origin to become part of international trade, escaping that country's legal tender laws and leaving the "bad" money behind. This occurred in Britain during the period of the gold standard.


title: Gresham's law

text: Gresham was not the first to state the law which took his name. The phenomenon had been noted by Aristophanes in his play "The Frogs", which dates from around the end of the 5th century BC. The referenced passage from "The Frogs" is as follows (usually dated at 405 BC):


title: Gresham's law

text: According to Ben Tamari, the currency devaluation phenomenon was already recognized in ancient sources. He brings some examples which include the Machpela Cave transaction and the building of the Temple from the Bible and the Mishna in tractate Bava Metzia () from the Talmud.


title: Gresham's law

text: In China, Yuan dynasty economic authors Yeh Shih and Yuan Hsieh (c. 1223) were aware of the same phenomenon.


title: Gresham's law

text: Notably this passage mentions only the flight of good money abroad and says nothing of its disappearance due to hoarding or melting. Palestinian economist Adel Zagha also attributes a similar concept to medieval Islamic thinker Al-Maqrizi, who offered, claims Zagha, a close approximation to what would become known as Gresham's law centuries later.


title: Gresham's law

text: In the 14th century it was noted by Nicole Oresme , in his treatise "On the Origin, Nature, Law, and Alterations of Money", and by jurist and historian Al-Maqrizi (1364–1442) in the Mamluk Empire.


title: Gresham's law

text: Johannes de Strigys, an agent of Ludovico III Gonzaga, Marquis of Mantua in Venice, wrote in a June 1472 report ("that the bad money will chase out the good").


title: Gresham's law

text: In the year that Gresham was born, 1519, it was described by Nicolaus Copernicus in a treatise called : "bad (debased) coinage drives good (un-debased) coinage out of circulation". Copernicus was aware of the practice of exchanging bad coins for good ones and melting down the latter or sending them abroad, and he seems to have drawn up some notes on this subject while he was at Olsztyn in 1519. He made them the basis of a report which he presented to the Prussian Diet held in 1522, attending the session with his friend Tiedemann Giese to represent his chapter. Copernicus's was an enlarged, Latin version of that report, setting forth a general theory of money for the 1528 diet. He also formulated a version of the quantity theory of money. For this reason, it is occasionally known as the Gresham–Copernicus law.


title: Gresham's law

text: Sir Thomas Gresham, a 16th century financial agent of the English Crown in the city of Antwerp, was one in a long series of proponents of the law, which he did to explain to Queen Elizabeth I what was happening to the English shilling. Her father, Henry VIII, had replaced 40% of the silver in the coin with base metals, to increase the government's income without raising taxes. Astute English merchants and ordinary subjects saved the good shillings from pure silver and circulated the bad ones. Hence, the bad money would be used whenever possible, and the good coinage would be saved and disappear from circulation.


title: Gresham's law

text: Gresham made his observations of good and bad money while in the service of Queen Elizabeth, with respect only to the observed poor quality of British coinage. Earlier monarchs, Henry VIII and Edward VI, had forced the people to accept debased coinage by means of legal tender laws. Gresham also made his comparison of good and bad money where the precious metal in the money was the same metal, but of different weight. He did not compare silver to gold, or gold to paper.


title: Gresham's law

text: In his "Gresham's Law" article, Selgin also offers the following comments regarding the origin of the name:


title: Gresham's law

text: In an influential theoretical article, Rolnick and Weber (1986) argued that bad money would drive good money to a premium, rather than driving it out of circulation. Their research did not take into account the context in which Gresham had made his observation. Rolnick and Weber ignored the influence of legal tender legislation, which requires people to accept both good and bad money as if they were of equal value. They also focused mainly on the interaction between different metallic monies, comparing the relative "goodness" of silver to that of gold, which is not what Gresham was speaking of.


title: Gresham's law

text: The experiences of dollarization in countries with weak economies and currencies (such as Israel in the 1980s, Eastern Europe and countries in the period immediately after the collapse of the Soviet bloc, or Ecuador throughout the late 20th and early 21st century) may be seen as Gresham's law operating in its reverse form (Guidotti & Rodriguez, 1992) because in general, the dollar has not been legal tender in such situations, and in some cases, its use has been illegal.


title: Gresham's law

text: Adam Fergusson and Costantino Bresciani-Turroni (in his book , published in 1931) pointed out that, during the great inflation in the Weimar Republic in 1923, as the official money became so worthless that virtually nobody would take it, people simply stopped accepting the currency in exchange for goods. That was particularly serious because farmers began to hoard food. Accordingly, any currency backed by any sort of value became a circulating medium of exchange. In 2009, hyperinflation in Zimbabwe began to show similar characteristics.


title: Gresham's law

text: Those examples show that in the absence of effective legal tender laws, Gresham's Law works in reverse. If given the choice of what money to accept, people will transact with money they believe to be of highest long-term value. If not given the choice and required to accept all money, good and bad, they will tend to keep the money of greater perceived value in their own possession, and pass the bad money to others.


title: Gresham's law

text: In short, in the absence of legal tender laws, the seller will not accept anything but money of certain value (good money), but the existence of legal tender laws will cause the buyer to offer only money with the lowest commodity value (bad money), as the creditor must accept such money at face value.


title: Gresham's law

text: Nobel Prize winner Robert Mundell believes that Gresham's Law could be more accurately rendered, taking care of the reverse, if it were expressed as: "Bad money drives out good "if they exchange for the same price"."


title: Gresham's law

text: The reverse of Gresham's Law, that good money drives out bad money whenever the bad money becomes nearly worthless, has been named "Thiers' law" by economist Peter Bernholz in honor of French politician and historian Adolphe Thiers. "Thiers' Law will only operate later [in the inflation] when the increase of the new flexible exchange rate and of the rate of inflation lower the real demand for the inflating money."


title: Gresham's law

text: The principles of Gresham's law can sometimes be applied to different fields of study. Gresham's law may be generally applied to any circumstance in which the true value of something is markedly different from the value people are required to accept, due to factors such as lack of information or governmental decree.


title: Gresham's law

text: Vice President Spiro Agnew used Gresham's law in describing American news media, stating that "Bad news drives out good news", although his argument was closer to that of a race to the bottom for higher ratings rather than over- and under-valuing certain kinds of news.


title: Gresham's law

text: Gregory Bateson postulated an analogue to Gresham's law operating in cultural evolution, in which "the oversimplified ideas will always displace the sophisticated and the vulgar and hateful will always displace the beautiful. And yet the beautiful persists."


title: Gresham's law

text: Cory Doctorow wrote that a similar effect to Gresham's law occurred in carbon offset trading. The alleged information asymmetry is that people find it difficult to distinguish just how effective credits purchased are, but can easily tell the price. As a result, cheap credits that are ineffective can displace expensive but worthwhile carbon credits. The example given was The Nature Conservancy offering cheap, yet "meaningless", carbon credits by purchasing cheap land unlikely to be logged anyway, rather than expensive and valuable land at risk of logging.


title: Gresham's law

text: In the market for used cars, lemon automobiles (analogous to bad currency) will drive out the good cars. The problem is one of asymmetry of information. Sellers have a strong financial incentive to pass all used cars off as good cars, especially lemons. This makes it difficult to buy a good car at a fair price, as the buyer risks overpaying for a lemon. The result is that buyers will only pay the fair price of a lemon, so at least they reduce the risk of overpaying. High-quality cars tend to be pushed out of the market, because there is no good way to establish that they really are worth more. Certified pre-owned programs are an attempt to mitigate this problem by providing a warranty and other guarantees of quality. "The Market for Lemons" is a work that examines this problem in more detail.


title: Da Ali G Show

text: Da Ali G Show is a British satirical television series created by and starring English comedian Sacha Baron Cohen. In the series, Baron Cohen plays three unorthodox journalists: faux-streetwise poseur Ali G, Kazakh reporter Borat Sagdiyev, and gay Austrian fashion enthusiast Brüno Gehard. These characters conduct real interviews with unsuspecting people, many of whom are celebrities, high-ranking government officials, and other well-known figures, during which they are asked absurd and ridiculous questions.


title: Da Ali G Show

text: The first (2000) season originally aired on Channel 4 in the UK, and the second and third (2003–2004) seasons on HBO in the United States. The second series was known as Ali G in da USAiii in the UK and Australia. In 2005, HBO stated they had no plans to make an additional season of the show.


title: Da Ali G Show

text: Baron Cohen has gone on to make four films featuring each of his three characters from the show: "Ali G Indahouse" (2002), "Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan" (2006), "Brüno" (2009) and "Borat Subsequent Moviefilm: Delivery of Prodigious Bribe to American Regime for Make Benefit Once Glorious Nation of Kazakhstan" (2020).


title: Da Ali G Show

text: In 2014, FXX reaired the show (including episodes unaired in the United States) under the branding "Ali G: Rezurection".


title: Da Ali G Show

text: Ali G (Alistair Leslie Graham) is the main character of "Da Ali G Show". He is the self-proclaimed "voice of da yoof" and the leader of the "West Staines Massiv". His mannerisms are a mix of stereotypical and often exaggerated British African-Caribbean and hip hop cultures, with some American urban influences thrown in. He interviews unsuspecting guests; in the American version of the show, he tells them he is a British talk show host and wants to discuss the media and politics. He often asks a question, and upon receiving an answer, instantly creates a story of an event relevant to the topic, employing his neighbours and fellow "gangsters" such as Ricky C, Dangerous Dave (who refuses to speak because he is terribly embarrassed about his voice) and Rainbow Jeremy (also known as Jezzy), his girlfriend, whom he refers as "me Julie" (Jamaican slang for girlfriend) or a family member such as his grandmother or his Uncle Jamal (who is apparently secretly gay). The character was later the basis of the film "Ali G Indahouse".


title: Da Ali G Show

text: Borat Sagdiyev is another character featured frequently on the show, introduced as someone Ali G came across on obscure satellite TV "whilst waiting for the 10-minute free preview on the Fantasy Channel". He comes from a fictionalized version of Kazakhstan, and travels around the United Kingdom and United States interviewing people and engaging in their activities. Though well-intentioned, Borat often makes his guests feel uncomfortable by introducing them to "Kazakh" customs, or by making misogynistic, anti-Semitic, or other comments based on his unfamiliar culture. The culture he presents is entirely fictional, however. For example, a real-world Roma ("Gypsy") village in Romania stood in for Borat's "typical Kazakh village", while the character of Borat dislikes Gypsies and claims to have once been a "Gypsy catcher". Similarly, the foreign language Baron Cohen speaks in this role is Hebrew, but interviewees and the average audience member are led to believe the anti-Semitic Borat is speaking in Kazakh. Borat makes references to his favourite sport called "shurik", a "Kazakh" custom where dogs are shot and killed in a field. He also makes references to his dead wife, his brother Bilo, and his desire to have "sexy time" with many of his interviewees. There are two films based on the character, "Borat: Cultural Learnings of America for Make Benefit Glorious Nation of Kazakhstan", released in 2006; and the sequel "Borat Subsequent Moviefilm: Delivery of Prodigious Bribe to American Regime for Make Benefit Once Glorious Nation of Kazakhstan", released in 2020.


title: Da Ali G Show

text: Brüno Gehard is a gay Austrian fashion reporter and is the third character of "Da Ali G Show". He claims to be the voice of "Austrian gay television". He often makes others uncomfortable by flaunting his flagrant homosexuality. In one episode, Brüno performs cheers with exaggerated, limp-wristed, stereotypically gay mannerisms, along with University of Alabama cheerleaders, provoking the ire of some Crimson Tide fans during the 2002 Alabama-Mississippi State football game. He nevertheless convinces the students to say that they are gay, in Polish.


title: Da Ali G Show

text: Brüno also interviews fashion aficionados and 'party people' and exposes their extreme views of how unfashionable people should be treated and aims to show the superficiality, hypocrisy and inconsistency of the fashion world. For example, he gets them to say that they think fashion has saved more lives than doctors, that people who have bad fashion should be sent to concentration camps, that Osama Bin Laden is cool, and that if house music were around in the 1930s, it would have prevented World War II. Universal Pictures released a film about the character, "Brüno", in 2009.


title: Da Ali G Show

text: Baron Cohen's methods often caused considerable controversy. Some guests became upset upon learning they had been tricked, and various comments made on the show outraged viewers.


title: Da Ali G Show

text: In one episode, Borat went to a bar in Tucson, Arizona, where he sang an antisemitic song called "In My Country There Is Problem" with lyrics including, "Throw the Jew down the well/So my country can be free/You must grab him by his horns/Then we have a big party." Many patrons of the bar were shown responding gleefully and singing along, though a later investigation by "The Jewish Daily Forward" found that many or all of the audience members were aware that the song was a joke and that Borat was a comedian in disguise. A Jewish audience member shown laughing in the HBO clip said, "You could tell right away it was a wig he was wearing, and a fake mustache. I would say 99% of the people in here saw that, too." The Anti-Defamation League complained about this segment, to which HBO spokesman Quentin Schaffer replied, "Through his alter egos, [Cohen] delivers an obvious satire that exposes people's ignorance and prejudice in much the way "All in the Family" did years ago." Baron Cohen, who is also Jewish, said in an interview that the show's Borat segments are a "dramatic demonstration of how racism feeds on dumb conformity as much as rabid bigotry" rather than a display of racism by Baron Cohen himself.


title: Da Ali G Show

text: One upset interviewee was James Broadwater, a Republican candidate for Congress. He was interviewed by Borat, who told him that the interview would be played in Kazakhstan and other foreign countries to teach others about the American political system. Borat's questioning led Broadwater to state that Jews would go to Hell if they did not convert to Christianity. This comment upset some Jewish communities and prompted Broadwater to post a letter on his website denouncing "Da Ali G Show", demanding the Federal Communications Commission (FCC) exert greater control over the "liberal, anti-God media", and saying, "I have had a logo on my website which says, 'I am a proud friend of Israel.


title: Da Ali G Show

text: On 1 November 2013, FXX announced a deal to re-broadcast the show (including episodes unaired in America) under the branding "Ali G: Rezurection", which started on 26 February 2014. The show featured new, original introductions starring Sacha Baron Cohen as Ali G.


title: Da Ali G Show

text: The show currently is streaming under the name "Da Ali G Show Remixed" on Australian streaming service Stan.


title: Da Ali G Show

text: The show's opening sequence, conceived and directed by Garth Jennings, has become well-known. It shows a naked Ali G standing under a spotlight in a black room, with each piece of his clothing flying in one by one (complete with action-packed sound effects) until he is fully dressed.


title: Da Ali G Show

text: The intro has been parodied on "The Simpsons" and in the 2005 BBC made for TV mini-series Casanova starring David Tennant.


title: Cymbeline

text: Cymbeline , also known as The Tragedie of Cymbeline or Cymbeline, King of Britain, is a play by William Shakespeare set in Ancient Britain () and based on legends that formed part of the Matter of Britain concerning the early Celtic British King Cunobeline. Although it is listed as a tragedy in the First Folio, modern critics often classify "Cymbeline" as a romance or even a comedy. Like "Othello" and "The Winter's Tale", it deals with the themes of innocence and jealousy. While the precise date of composition remains unknown, the play was certainly produced as early as 1611.


title: Cymbeline

text: Cymbeline, the Roman Empire's vassal king of Britain, once had two sons, Guiderius and Arvirargus, but they were stolen 20 years earlier as infants by an exiled traitor named Belarius. Cymbeline discovers that his only child left, his daughter Imogen (or Innogen), has secretly married her lover Posthumus Leonatus, a member of Cymbeline's court. The lovers have exchanged jewellery as tokens: Imogen with a bracelet, and Posthumus with a ring. Cymbeline dismisses the marriage and banishes Posthumus since Imogen — as Cymbeline's only child — must produce a fully royal-blooded heir to succeed to the British throne. In the meantime, Cymbeline's Queen is conspiring to have Cloten (her cloddish and arrogant son by an earlier marriage) married to Imogen to secure her bloodline. The Queen is also plotting to murder both Imogen and Cymbeline, procuring what she believes to be deadly poison from the court doctor. The doctor, Cornelius, is suspicious and switches the poison for a harmless sleeping potion. The Queen passes the "poison" along to Pisanio, Posthumus and Imogen's loving servant — the latter is led to believe it is a medicinal drug. No longer able to be with her banished Posthumus, Imogen secludes herself in her chambers, away from Cloten's aggressive advances.


title: Cymbeline

text: Posthumus must now live in Italy, where he meets Iachimo (or Giacomo), who challenges the prideful Posthumus to a bet that he, Iachimo, can seduce Imogen, whom Posthumus has praised for her chastity, and then bring Posthumus proof of Imogen's adultery. If Iachimo wins, he will get Posthumus's token ring. If Posthumus wins, not only must Iachimo pay him but also fight Posthumus in a duel with swords. Iachimo heads to Britain where he aggressively attempts to seduce the faithful Imogen, who sends him packing. Iachimo then hides in a chest in Imogen's bedchamber and, when the princess falls asleep, emerges to steal Posthumus's bracelet from her. He also takes note of the room, as well as the mole on Imogen's partly naked body, to be able to present false evidence to Posthumus that he has seduced his bride. Returning to Italy, Iachimo convinces Posthumus that he has successfully seduced Imogen. In his wrath, Posthumus sends two letters to Britain: one to Imogen, telling her to meet him at Milford Haven, on the Welsh coast; the other to the servant Pisanio, ordering him to murder Imogen at the Haven. However, Pisanio refuses to kill Imogen and reveals to her Posthumus's plot. He has Imogen disguise herself as a boy and continue to Milford Haven to seek employment. He also gives her the Queen's "poison", believing it will alleviate her psychological distress. In the guise of a boy, Imogen adopts the name "Fidele", meaning "faithful".


title: Cymbeline

text: The treacherous Queen is now wasting away due to the disappearance of her son Cloten. Meanwhile, despairing of his life, the guilt-ridden Posthumus enlists in the Roman forces as they begin their invasion of Britain. Belarius, Guiderius, Arviragus, and Posthumus all help rescue Cymbeline from the Roman onslaught; the king does not yet recognise these four, yet takes notice of them as they go on to fight bravely and even capture the Roman commanders, Lucius and Iachimo, thus winning the day. Posthumus, allowing himself to be captured, as well as Fidele, are imprisoned alongside the true Romans, all of whom await execution. In jail, Posthumus sleeps, while the ghosts of his dead family appear to complain to Jupiter of his grim fate. Jupiter himself then appears in thunder and glory to assure the others that destiny will grant happiness to Posthumus and Britain.


title: Cymbeline

text: Cornelius arrives in the court to announce that the Queen has died suddenly, and that on her deathbed she unrepentantly confessed to villainous schemes against her husband and his throne. Both troubled and relieved at this news, Cymbeline prepares to execute his new prisoners, but pauses when he sees Fidele, whom he finds both beautiful and somehow familiar. Fidele has noticed Posthumus's ring on Iachimo's finger and abruptly demands to know from where the jewel came. A remorseful Iachimo tells of his bet, and how he could not seduce Imogen, yet tricked Posthumus into thinking he had. Posthumus then comes forward to confirm Iachimo's story, revealing his identity and acknowledging his wrongfulness in desiring Imogen killed. Ecstatic, Imogen throws herself at Posthumus, who still takes her for a boy and knocks her down. Pisanio then rushes forward to explain that Fidele is Imogen in disguise; Imogen still suspects that Pisanio conspired with the Queen to give her the poison. Pisanio sincerely claims innocence, and Cornelius reveals how the poison was a non-fatal potion all along. Insisting that his betrayal years ago was a set-up, Belarius makes his own happy confession, revealing Guiderius and Arviragus as Cymbeline's own two long-lost sons. With her brothers restored to their place in the line of inheritance, Imogen is now free to marry Posthumus. An elated Cymbeline pardons Belarius and the Roman prisoners, including Lucius and Iachimo. Lucius calls forth his soothsayer to decipher a prophecy of recent events, which ensures happiness for all. Blaming his manipulative Queen for his refusal to pay earlier, Cymbeline now agrees to pay the tribute to the Roman Emperor as a gesture of peace between Britain and Rome, and he invites everyone to a great feast.


title: Cymbeline

text: "Cymbeline" is grounded in the story of the historical British king Cunobeline, which was originally recorded in Geoffrey of Monmouth's "Historia Regum Britanniae", but which Shakespeare likely found in the 1587 edition of Raphael "Holinshed's Chronicles". Shakespeare based the setting of the play and the character Cymbeline on what he found in Holinshed's chronicles, but the plot and subplots of the play are derived from other sources. The subplot of Posthumus and Iachimo's wager derives from story II.9 of Giovanni Boccaccio's "The Decameron" and the anonymously authored "Frederyke of Jennen". These share similar characters and wager terms, and both feature Iachimo's equivalent hiding in a chest in order to gather proof in Imogen's room. Iachimo's description of Imogen's room as proof of her infidelity derives from "The Decameron", and Pisanio's reluctance to kill Imogen and his use of her bloody clothes to convince Posthumus of her death derive from "Frederyke of Jennen." In both sources, the equivalent to Posthumus's bracelet is stolen jewellery that the wife later recognises while cross-dressed. Shakespeare also drew inspiration for "Cymbeline" from a play called "The Rare Triumphs of Love and Fortune," first performed in 1582. There are many parallels between the characters of the two plays, including a king's daughter who falls for a man of unknown birth who grew up in the king's court. The subplot of Belarius and the lost princes was inspired by the story of Bomelio, an exiled nobleman in "The Rare Triumphs" who is later revealed to be the protagonist's father.


title: Cymbeline

text: The first recorded production of "Cymbeline", as noted by Simon Forman, was in April 1611. It was first published in the "First Folio" in 1623. When "Cymbeline" was actually written cannot be precisely dated.


title: Cymbeline

text: The Yale edition suggests a collaborator had a hand in the authorship, and some scenes (e.g., Act III scene 7 and Act V scene 2) may strike the reader as particularly un-Shakespearean when compared with others. The play shares notable similarities in language, situation, and plot with Beaumont and Fletcher's tragicomedy "Philaster, or Love Lies a-Bleeding" (). Both plays concern themselves with a princess who, after disobeying her father in order to marry a lowly lover, is wrongly accused of infidelity and thus ordered to be murdered, before escaping and having her faithfulness proven. Furthermore, both were written for the same theatre company and audience. Some scholars believe this supports a dating of approximately 1609, though it is not clear which play preceded the other.The editors of the Oxford and Norton Shakespeare believe the name of Imogen is a misprint for Innogen—they draw several comparisons between "Cymbeline" and "Much Ado About Nothing", in early editions of which a ghost character named Innogen was supposed to be Leonato's wife (Posthumus being also known as "Leonatus", the Latin form of the Italian name in the other play). Stanley Wells and Michael Dobson point out that Holinshed's "Chronicles", which Shakespeare used as a source, mention an Innogen and that Forman's eyewitness account of the April 1611 performance refers to "Innogen" throughout. In spite of these arguments, most editions of the play have continued to use the name Imogen.


title: Cymbeline

text: Milford Haven is not known to have been used during the period (early 1st century AD) in which "Cymbeline" is set, and it is not known why Shakespeare used it in the play. Robert Nye noted that it was the closest seaport to Shakespeare's home town of Stratford-upon-Avon: "But if you marched due west from Stratford, looking neither to left nor to right, with the idea of running away to sea in your young head, then Milford Haven is the port you'd reach," a walk of about , about six days' journey, that the young Shakespeare might well have taken, or at least dreamed of taking. Marisa R. Cull notes its possible symbolism as the landing site of Henry Tudor, when he invaded England via Milford on 7 August 1485 on his way to deposing Richard III and establishing the Tudor dynasty. It may also reflect English anxiety about the loyalty of the Welsh and the possibility of future invasions at Milford.


title: Cymbeline

text: "Cymbeline" was one of Shakespeare's more popular plays during the eighteenth century, though critics including Samuel Johnson took issue with its complex plot:


title: Cymbeline

text: By the early twentieth century, the play had lost favour. Lytton Strachey found it "difficult to resist the conclusion that [Shakespeare] was getting bored himself. Bored with people, bored with real life, bored with drama, bored, in fact, with everything except poetry and poetical dreams." Harley Granville-Barker had similar views, saying that the play shows that Shakespeare was becoming a "wearied artist".


title: Cymbeline

text: Some have argued that the play parodies its own content. Harold Bloom says "Cymbeline, in my judgment, is partly a Shakespearean self-parody; many of his prior plays and characters are mocked by it."


title: Cymbeline

text: Similarities between Cymbeline and historical accounts of the Roman Emperor Augustus have prompted critics to interpret the play as Shakespeare voicing support for the political motions of James I, who considered himself the "British Augustus." His political manoeuvres to unite Scotland with England and Wales as an empire mirror Augustus' "Pax Romana." The play reinforces the Jacobean idea that Britain is the successor to the civilised virtue of ancient Rome, portraying the parochialism and isolationism of Cloten and the Queen as villainous. Other critics have resisted the idea that "Cymbeline" endorses James I's ideas about national identity, pointing to several characters' conflicted constructions of their geographic identities. For example, although Guiderius and Arviragus are the sons of Cymbeline, a British king raised in Rome, they grew up in a Welsh cave. The brothers lament their isolation from society, a quality associated with barbarousness, but Belarius, their adoptive father, retorts that this has spared them from corrupting influences of the supposedly civilised British court.


title: Cymbeline

text: Iachimo's invasion of Imogen's bedchamber reflects concern that Britain was being maligned by Italian influence. As noted by Peter A. Parolin, "Cymbeline’s" scenes ostensibly set in ancient Rome are in fact anachronistic portrayals of sixteenth-century Italy, which was characterised by contemporary British authors as a place where vice, debauchery, and treachery had supplanted the virtue of ancient Rome. Though "Cymbeline" concludes with a peace forged between Britain and Rome, Iachimo's corruption of Posthumus and metaphorical rape of Imogen demonstrate fears that Britain's political union with other cultures might expose Britons to harmful foreign influences.


title: Cymbeline

text: Scholars have emphasised that the play attributes great political significance to Imogen's virginity and chastity. There is some debate as to whether Imogen and Posthumus's marriage is legitimate. Imogen has historically been played and received as an ideal, chaste woman maintaining qualities applauded in a patriarchal structure; however, critics argue that Imogen's actions contradict these social definitions through her defiance of her father and her cross-dressing. Yet critics including Tracey Miller-Tomlinson have emphasised the ways in which the play upholds patriarchal ideology, including in the final scene, with its panoply of male victors. Whilst Imogen and Posthumus's marriage at first upholds heterosexual norms, their separation and final reunion leave open non-heterosexual possibilities, initially exposed by Imogen's cross-dressing as Fidele. Miller-Tomlinson points out the falseness of their social significance as a "perfect example" of a public "heterosexual marriage", considering that their private relations turn out to be "homosocial, homoerotic, and hermaphroditic."


title: Cymbeline

text: Queer theory has gained traction in scholarship on "Cymbeline", building upon the work of Eve Kosofsky Sedgwick and Judith Butler. Scholarship on this topic has emphasised the play's Ovidian allusions and exploration of non-normative gender/sexuality – achieved through separation from traditional society into what Valerie Traub terms "green worlds." Amongst the most obvious and frequently cited examples of this non-normative dimension of the play is the prominence of homoeroticism, as seen in Guiderius and Arviragus's semi-sexual fascination with the disguised Imogen/Fidele. In addition to homoerotic and homosocial elements, the subjects of hermaphroditism and paternity/maternity also feature prominently in queer interpretations of "Cymbeline". Janet Adelman set the tone for the intersection of paternity and hermaphroditism in arguing that Cymbeline's lines, "oh, what am I, / A mother to the birth of three? Ne’er mother / Rejoiced deliverance more", amount a "parthenogenesis fantasy". According to Adelman and Tracey Miller-Tomlinson, in taking sole credit for the creation of his children Cymbeline acts a hermaphrodite who transforms a maternal function into a patriarchal strategy by regaining control of his male heirs and daughter, Imogen. Imogen's own experience with gender fluidity and cross-dressing has largely been interpreted through a patriarchal lens. Unlike other Shakespearean agents of onstage gender fluidity – Portia, Rosalind, Viola and Julia – Imogen is not afforded empowerment upon her transformation into Fidele. Instead, Imogen's power is inherited from her father and based upon the prospect of reproduction.


title: Cymbeline

text: After the 1611 performance mentioned by Simon Forman, there is no record of production until 1634, when the play was revived at court for Charles I and Henrietta Maria. The Caroline production was noted as being "well likte by the kinge." In 1728 John Rich staged the play with his company at Lincoln's Inn Fields, with emphasis placed on the spectacle of the production rather than the text of the play. Theophilus Cibber revived Shakespeare's text in 1744 with a performance at the Haymarket. There is evidence that Cibber put on another performance in 1746, and another in 1758.


title: Cymbeline

text: In 1761, David Garrick edited a new version of the text. It is recognized as being close to the original Shakespeare, although there are several differences. Changes included the shortening of Imogen's burial scene and the entire fifth act, including the removal of Posthumus's dream. Garrick's text was first performed in November of that year, starring Garrick himself as Posthumus. Several scholars have indicated that Garrick's Posthumus was much liked. Valerie Wayne notes that Garrick's changes made the play more nationalistic, representing a trend in perception of "Cymbeline" during that period. Garrick's version of "Cymbeline" would prove popular; it was staged a number of times over the next few decades.


title: Cymbeline

text: The play entered the Romantic era with John Philip Kemble's company in 1801. Kemble's productions made use of lavish spectacle and scenery; one critic noted that during the bedroom scene, the bed was so large that Iachimo all but needed a ladder to view Imogen in her sleep. Kemble added a dance to Cloten's comic wooing of Imogen. In 1827, his brother Charles mounted an antiquarian production at Covent Garden; it featured costumes designed after the descriptions of the ancient British by such writers as Julius Caesar and Diodorus Siculus.


title: Cymbeline

text: William Charles Macready mounted the play several times between 1837 and 1842. At the Theatre Royal, Marylebone, an epicene production was staged with Mary Warner, Fanny Vining, Anna Cora Mowatt, and Edward Loomis Davenport.


title: Cymbeline

text: In 1859, "Cymbeline" was first performed in Sri Lanka. In the late nineteenth century, the play was produced several times in India.


title: Cymbeline

text: In 1864, as part of the celebrations of Shakespeare's birth, Samuel Phelps performed the title role at Theatre Royal, Drury Lane. Helena Faucit returned to the stage for this performance.


title: Cymbeline

text: The play was also one of Ellen Terry's last performances with Henry Irving at the Lyceum in 1896. Terry's performance was widely praised, though Irving was judged an indifferent Iachimo. Like Garrick, Irving removed the dream of Posthumus; he also curtailed Iachimo's remorse and attempted to render Cloten's character consistent. A review in the "Athenaeum" compared this trimmed version to pastoral comedies such as "As You Like It". The set design, overseen by Lawrence Alma-Tadema, was lavish and advertised as historically accurate, though the reviewer for the time complained of such anachronisms as gold crowns and printed books as props.


title: Cymbeline

text: Similarly lavish but less successful was Margaret Mather's production in New York in 1897. The sets and publicity cost $40,000, but Mather was judged too emotional and undisciplined to succeed in a fairly cerebral role.


title: Cymbeline

text: Barry Jackson staged a modern dress production for the Birmingham Rep in 1923, two years before his influential modern dress "Hamlet". Walter Nugent Monck brought his Maddermarket Theatre production to Stratford in 1946, inaugurating the post-war tradition of the play.


title: Cymbeline

text: London saw two productions in the 1956 season. Michael Benthall directed the less successful production, at The Old Vic. The set design by Audrey Cruddas was notably minimal, with only a few essential props. She relied instead on a variety of lighting effects to reinforce mood; actors seemed to come out of darkness and return to darkness. Barbara Jefford was criticised as too cold and formal for Imogen; Leon Gluckman played Posthumus, Derek Godfrey Iachimo, and Derek Francis Cymbeline. Following Victorian practice, Benthall drastically shortened the last act.


title: Cymbeline

text: By contrast, Peter Hall's production at the Shakespeare Memorial presented nearly the entire play, including the long-neglected dream scene (although a golden eagle designed for Jupiter turned out too heavy for the stage machinery and was not used). Hall presented the play as a distant fairy tale, with stylised performances. The production received favourable reviews, both for Hall's conception and, especially, for Peggy Ashcroft's Imogen. Richard Johnson played Posthumus, and Robert Harris Cymbeline. Iachimo was played by Geoffrey Keen, whose father Malcolm had played Iachimo with Ashcroft at the Old Vic in 1932.


title: Cymbeline

text: Hall's approach attempted to unify the play's diversity by means of a fairy-tale topos. The next major Royal Shakespeare Company production, in 1962, went in the opposite direction. Working on a set draped with heavy white sheets, director William Gaskill employed Brechtian alienation effects, to mixed critical reviews. The acting, however, was widely praised. Vanessa Redgrave as Imogen was often compared favourably to Ashcroft; Eric Porter was a success as Iachimo, as was Clive Swift as Cloten. Patrick Allen was Posthumus, and Tom Fleming played the title role.


title: Cymbeline

text: A decade later, John Barton's 1974 production for the RSC (with assistance from Clifford Williams) featured Sebastian Shaw in the title role, Tim Pigott-Smith as Posthumus, Ian Richardson as Iachimo, and Susan Fleetwood as Imogen. Charles Keating was Cloten. As with contemporary productions of "Pericles", this one used a narrator (Cornelius) to signal changes in mood and treatment to the audience. Robert Speaight disliked the set design, which he called too minimal, but he approved the acting.


title: Cymbeline

text: In 1980, David Jones revived the play for the RSC; the production was in general a disappointment, although Judi Dench as Imogen received reviews that rivalled Ashcroft's. Ben Kingsley played Iachimo; Roger Rees was Posthumus. In 1987, Bill Alexander directed the play in The Other Place (later transferring to the Pit in London's Barbican Centre) with Harriet Walter playing Imogen, David Bradley as Cymbeline and Nicholas Farrell as Posthumus.


title: Cymbeline

text: At the Stratford Festival, the play was directed in 1970 by Jean Gascon and in 1987 by Robin Phillips. The latter production, which was marked by much-approved scenic complexity, featured Colm Feore as Iachimo, and Martha Burns as Imogen. The play was again at Stratford in 2004, directed by David Latham. A large medieval tapestry unified the fairly simple stage design and underscored Latham's fairy-tale inspired direction.


title: Cymbeline

text: In 1994, Ajay Chowdhury directed an Anglo-Indian production of "Cymbeline" at the Rented Space Theatre Company. Set in India under British rule, the play features Iachimo, played by Rohan Kenworthy, as a British soldier and Imogen, played by Uzma Hameed, as an Indian princess.


title: Cymbeline

text: At the new Globe Theatre in 2001, a cast of six (including Abigail Thaw, Mark Rylance, and Richard Hope) used extensive doubling for the play. The cast wore identical costumes even when in disguise, allowing for particular comic effects related to doubling (as when Cloten attempts to disguise himself as Posthumus.)


title: Cymbeline

text: There have been some well-received theatrical productions including the Public Theater's 1998 production in New York City, directed by Andrei Șerban. "Cymbeline" was also performed at the Cambridge Arts Theatre in October 2007 in a production directed by Sir Trevor Nunn, and in November 2007 at the Chicago Shakespeare Theatre. The play was included in the 2013 repertory season of the Oregon Shakespeare Festival.


title: Cymbeline

text: In 2004 and 2014, the Hudson Shakespeare Company of New Jersey produced two distinct versions of the play. The 2004 production, directed by Jon Ciccarelli, embraced the fairy tale aspect of the story and produced a colourful version with wicked step-mothers, feisty princesses and a campy Iachimo. The 2014 version, directed by Rachel Alt, went in a completely opposite direction and placed the action on ranch in the American Old West. The Queen was a southern belle married to a rancher, with Imogen as a high society girl in love with the cowhand Posthumous.


title: Cymbeline

text: In 2011, the Shakespeare Theatre Company of Washington, DC, presented a version of the play that emphasised its fable and folklore elements, set as a tale within a tale, as told to a child.


title: Cymbeline

text: In 2012, Antoni Cimolino directed a production at the Stratford Festival that steered into the fairy-tale elements of the text.


title: Cymbeline

text: Also in 2012 the South Sudan Theatre Company staged "Cymbeline" in Juba Arabic for the Shakespeare's Globe "Globe to Globe" festival. It was translated by Derik Uya Alfred and directed by Joseph Abuk. Connections between the content of the play and South Sudan's own political struggle have been drawn by the production's producers, as well as some scholars. Overall, the production was well received by audiences and critics. Critic Matt Truman gave the production four out of five stars, saying "The world's youngest nation seems delighted to be here and, played with this much heart, even Shakespeare's most rambling romance becomes irresistible."


title: Cymbeline

text: In 2013, Samir Bhamra directed the play for Phizzical Productions with six actors playing multiple parts for a UK national tour. The cast included Sophie Khan Levy as Innojaan, Adam Youssefbeygi, Tony Hasnath, Liz Jadav and Robby Khela. The production was set in the souks of Dubai and the Bollywood film industry during the 1990s communal riots and received acclaim from reviewers and academics alike.


title: Cymbeline

text: Also in 2013, a folk musical adaptation of "Cymbeline" was performed at the First Folio Theatre in Oak Brook, Illinois. The setting was the American South during the Civil War, with Cymbeline as a man of high status who avoids military service. The play was performed outdoors and was accompanied by traditional Appalachian folk songs.


title: Cymbeline

text: In 2015, at Shakespeare's Globe in the Sam Wanamaker Playhouse, a production was directed by Sam Yates where the role of Innogen was played by Emily Barber and Jonjo O'Neill as Posthumus.


title: Cymbeline

text: In 2016, Melly Still directed "Cymbeline" at the Royal Shakespeare Company. This version of the play was performed at the Royal Shakespeare Theatre before moving to the Barbican in late 2016. The performance featured Bethan Cullinane as Innogen and Gillian Bevan as Cymbeline.


title: Cymbeline

text: The play was adapted by Thomas d'Urfey as "The Injured Princess, or, the Fatal Wager"; this version was produced at the Theatre Royal, Drury Lane, presumably by the united King's Company and Duke's Company, in 1682. The play changes some names and details, and adds a subplot, typical of the Restoration, in which a virtuous waiting-woman escapes the traps laid by Cloten. D'Urfey also changes Pisanio's character so that he at once believes in Imogen's (Eugenia, in D'Urfey's play) guilt. For his part, D'Urfey's Posthumus is ready to accept that his wife might have been untrue, as she is young and beautiful. Some details of this alteration survived in productions at least until the middle of the century.


title: Cymbeline

text: William Hawkins revised the play again in 1759. His was among the last of the heavy revisions designed to bring the play in line with classical unities. He cut the Queen, reduced the action to two places (the court and a forest in Wales). The dirge "With fairest flowers..." was set to music by Thomas Arne.


title: Cymbeline

text: Nearer the end of the century, Henry Brooke wrote an adaptation which was apparently never staged. His version eliminates the brothers altogether as part of a notable enhancement of Posthumus's role in the play.


title: Cymbeline

text: George Bernard Shaw, who criticised the play perhaps more harshly than he did any of Shakespeare's other works, took aim at what he saw as the defects of the final act in his 1937 "Cymbeline Refinished"; as early as 1896, he had complained about the absurdities of the play to Ellen Terry, then preparing to act Imogen. He called it "stagey trash of the lowest melodramatic order". He later changed his view, saying it was "one of the finest of Shakespeare's later plays", but he remained convinced that it "goes to pieces in the final act". Accordingly, in "Cymbeline Refinished" he rewrote the last act, cutting many of the numerous revelations and expositions, while also making Imogen a much more assertive figure in line with his feminist views.


title: Cymbeline

text: There have been a number of radio adaptations of "Cymbeline" between the 1930s and the 2000s. The BBC broadcast productions of "Cymbeline" in the United Kingdom in 1934, 1951, 1957, 1986, 1996, and 2006. NBC broadcast a production of the play in the United States in 1938. In October 1951 the BBC aired a production of George Bernard Shaw's "Cymbeline Refinished", as well as Shaw's foreword to the play.


title: Cymbeline

text: Lucius J. Henderson directed the first screen adaptation of "Cymbeline" in 1913. The film was produced by the Thanhouser Company and starred Florence La Badie as Imogen, James Cruze as Posthumus, William Garwood as Iachimo, William Russell as Cymbeline, and Jean Darnell as the Queen.


title: Cymbeline

text: In 1937 the BBC broadcast several scenes of André van Gyseghem's production of the play, which opened 16 November the same year, on television. The scenes that comprised the broadcast were pulled exclusively from Acts I and II of the play, and included the 'trunk scene' from Act II Scene 2. In 1956 the BBC produced a similar television program, this time airing scenes from Michael Benthall's theatrical production, which opened 11 September 1956. Like the 1937 program, the 1956 broadcast ran for roughly half an hour and presented several scenes from "Cymbeline," including the trunk scene.


title: Cymbeline

text: In 1968 Jerzy Jarocki directed an adaptation of the play for Polish television, starring Wiktor Sadecki as Cymbeline and Ewa Lassek as Imogen.


title: Cymbeline

text: Elijah Moshinsky directed the BBC Television Shakespeare adaptation in 1982, ignoring the ancient British period setting in favour of a more timeless and snow-laden atmosphere inspired by Rembrandt and his contemporary Dutch painters. Richard Johnson, Claire Bloom, Helen Mirren, and Robert Lindsay play Cymbeline, his Queen, Imogen, and Iachimo, respectively, with Michael Pennington as Posthumus.


title: Cymbeline

text: In 2014, Ethan Hawke and director Michael Almereyda, who previously collaborated on the 2000 film "Hamlet", re-teamed for the film "Cymbeline", in which Hawke plays Iachimo. The film is set in the context of urban gang warfare. Ed Harris takes the title role. Penn Badgley plays the orphan Posthumus; Milla Jovovich plays the role of the Queen; Anton Yelchin is Cloten; and Dakota Johnson plays the role of Imogen.


title: Cymbeline

text: Prior to operatic adaptations only incidental music was composed. The first operatic adaption seems to be composed by Edmond Missa in 1894, under the title "Dinah"; American composer Christopher Berg composed another one, of which scenes were performed in 2009.


title: Cymbeline

text: In Beethoven’s one opera Fidelio, the loyal wife Leonore, disguising herself as a man, takes on the name Fidelio, as a probable reference to Imogen’s cross-dressing as Fidele.


title: Cymbeline

text: Perhaps the most famous verses in the play come from the funeral song of Act IV, Scene 2, which begins:


title: Cymbeline

text: The first two lines are quoted by Virginia Woolf in "Mrs. Dalloway" by the two main characters Clarissa and Septimus Smith. The lines, which turn Mrs. Dalloway's thoughts to the trauma of the First World War, are at once an elegiac dirge and a profoundly dignified declaration of endurance. The song provides a major organisational motif for the novel. The final couplet also appears in the Anton Myrer novel, "The Last Convertible".


title: Cymbeline

text: The last two lines appear to have inspired T. S. Eliot in "Lines to a Yorkshire Terrier" (in "Five-Finger Exercises"). He writes:


title: Cymbeline

text: The song was set to music by Roger Quilter as "Fear No More the Heat o' the Sun," No. 1 of Five Shakespeare Songs, Op. 23 (1921). It was also set by Gerald Finzi as part of his song cycle on texts by Shakespeare "Let Us Garlands Bring" (1942). The text is sung by Cleo Laine to music by John Dankworth on her 1964 album "Shakespeare and All That Jazz".


title: Cymbeline

text: At the end of Stephen Sondheim's "The Frogs", William Shakespeare is competing against George Bernard Shaw for the title of best playwright, deciding which of them is to be brought back from the dead in order to improve the world. Shakespeare sings the funeral song of Act IV, Scene 2, when asked about his view of death (the song is titled "Fear No More").


title: Cymbeline

text: "Fear no more the heat of the sun" is the line that Winnie and her husband are trying to remember in Samuel Beckett's "Happy Days" as they sit exposed to the elements.


title: Cymbeline

text: In the Epilogue of the novel "Appointment with Death" by Agatha Christie, the first four lines of the verse are quoted by the character Ginevra Boynton as she reflects on the life of her deceased mother Mrs Boynton.


title: Cymbeline

text: In "The Scent of Water" (1963) by Elizabeth Goudge, the central character, Mary Lindsay, feels struck by lightning when she realises she has fallen in love with Paul Randall, an author and Royal Air Force pilot, blinded in the last days of World War II, and married. "Fear no more the lightning-flash", Mary suddenly thinks, along with the rest of that stanza, ending "All lovers young, all lovers must /Consign to thee, and come to dust", knowing she must hide her love, and recognising that, already fifty, she is growing old (Chapter IX, Part 1, p 164).


title: NF-κB

text: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.


title: NF-κB

text: NF-κB was discovered by Ranjan Sen in the lab of Nobel laureate David Baltimore via its interaction with an 11-base pair sequence in the immunoglobulin light-chain enhancer in B cells. Later work by Alexander Poltorak and Bruno Lemaitre in mice and "Drosophila" fruit flies established Toll-like receptors as universally conserved activators of NF-κB signalling. These works ultimately contributed to awarding of Nobel laureates to Bruce Beutler and Jules A. Hoffmann, who were the principal investigators of those studies.


title: NF-κB

text: All proteins of the NF-κB family share a Rel homology domain in their N-terminus. A subfamily of NF-κB proteins, including RelA, RelB, and c-Rel, have a transactivation domain in their C-termini. In contrast, the NF-κB1 and NF-κB2 proteins are synthesized as large precursors, p105 and p100, which undergo processing to generate the mature p50 and p52 subunits, respectively. The processing of p105 and p100 is mediated by the ubiquitin/proteasome pathway and involves selective degradation of their C-terminal region containing ankyrin repeats. Whereas the generation of p52 from p100 is a tightly regulated process, p50 is produced from constitutive processing of p105. The p50 and p52 proteins have no intrinsic ability to activate transcription and thus have been proposed to act as transcriptional repressors when binding κB elements as homodimers. Indeed, this confounds the interpretation of p105-knockout studies, where the genetic manipulation is removing an IκB (full-length p105) and a likely repressor (p50 homodimers) in addition to a transcriptional activator (the RelA-p50 heterodimer).


title: NF-κB

text: NF-κB family members share structural homology with the retroviral oncoprotein v-Rel, resulting in their classification as NF-κB/Rel proteins.


title: NF-κB

text: In addition to mammals, NF-κB is found in a number of simple animals as well. These include cnidarians (such as sea anemones, coral and hydra), porifera (sponges), single-celled eukaryotes including "Capsaspora owczarzaki" and choanoflagellates, and insects (such as moths, mosquitoes and fruitflies). The sequencing of the genomes of the mosquitoes "A. aegypti" and "A. gambiae", and the fruitfly "D. melanogaster" has allowed comparative genetic and evolutionary studies on NF-κB. In those insect species, activation of NF-κB is triggered by the Toll pathway (which evolved independently in insects and mammals) and by the Imd (immune deficiency) pathway.


title: NF-κB

text: NF-κB is important in regulating cellular responses because it belongs to the category of "rapid-acting" primary transcription factors, i.e., transcription factors that are present in cells in an inactive state and do not require new protein synthesis in order to become activated (other members of this family include transcription factors such as c-Jun, STATs, and nuclear hormone receptors). This allows NF-κB to be a first responder to harmful cellular stimuli. Known inducers of NF-κB activity are highly variable and include reactive oxygen species (ROS), tumor necrosis factor alpha (TNFα), interleukin 1-beta (IL-1β), bacterial lipopolysaccharides (LPS), isoproterenol, cocaine, endothelin-1 and ionizing radiation.


title: NF-κB

text: NF-κB suppression of tumor necrosis factor cytotoxicity (apoptosis) is due to induction of antioxidant enzymes and sustained suppression of c-Jun N-terminal kinases (JNKs).


title: NF-κB

text: Receptor activator of NF-κB (RANK), which is a type of TNFR, is a central activator of NF-κB. Osteoprotegerin (OPG), which is a decoy receptor homolog for RANK ligand (RANKL), inhibits RANK by binding to RANKL, and, thus, osteoprotegerin is tightly involved in regulating NF-κB activation.


title: NF-κB

text: Many bacterial products and stimulation of a wide variety of cell-surface receptors lead to NF-κB activation and fairly rapid changes in gene expression. The identification of Toll-like receptors (TLRs) as specific pattern recognition molecules and the finding that stimulation of TLRs leads to activation of NF-κB improved our understanding of how different pathogens activate NF-κB. For example, studies have identified TLR4 as the receptor for the LPS component of Gram-negative bacteria. TLRs are key regulators of both innate and adaptive immune responses.


title: NF-κB

text: Unlike RelA, RelB, and c-Rel, the p50 and p52 NF-κB subunits do not contain transactivation domains in their C terminal halves. Nevertheless, the p50 and p52 NF-κB members play critical roles in modulating the specificity of NF-κB function. Although homodimers of p50 and p52 are, in general, repressors of κB site transcription, both p50 and p52 participate in target gene transactivation by forming heterodimers with RelA, RelB, or c-Rel. In addition, p50 and p52 homodimers also bind to the nuclear protein Bcl-3, and such complexes can function as transcriptional activators.


title: NF-κB

text: In unstimulated cells, the NF-κB dimers are sequestered in the cytoplasm by a family of inhibitors, called IκBs (Inhibitor of κB), which are proteins that contain multiple copies of a sequence called ankyrin repeats. By virtue of their ankyrin repeat domains, the IκB proteins mask the nuclear localization signals (NLS) of NF-κB proteins and keep them sequestered in an inactive state in the cytoplasm.


title: NF-κB

text: IκBs are a family of related proteins that have an N-terminal regulatory domain, followed by six or more ankyrin repeats and a PEST domain near their C terminus. Although the IκB family consists of IκBα, IκBβ, IκBε, and Bcl-3, the best-studied and major IκB protein is IκBα. Due to the presence of ankyrin repeats in their C-terminal halves, p105 and p100 also function as IκB proteins. The c-terminal half of p100, that is often referred to as IκBδ, also functions as an inhibitor. IκBδ degradation in response to developmental stimuli, such as those transduced through LTβR, potentiate NF-κB dimer activation in a NIK dependent non-canonical pathway.


title: NF-κB

text: Activation of the NF-κB is initiated by the signal-induced degradation of IκB proteins. This occurs primarily via activation of a kinase called the IκB kinase (IKK). IKK is composed of a heterodimer of the catalytic IKKα and IKKβ subunits and a "master" regulatory protein termed NEMO (NF-κB essential modulator) or IKKγ. When activated by signals, usually coming from the outside of the cell, the IκB kinase phosphorylates two serine residues located in an IκB regulatory domain. When phosphorylated on these serines (e.g., serines 32 and 36 in human IκBα), the IκB proteins are modified by a process called ubiquitination, which then leads them to be degraded by a cell structure called the proteasome.


title: NF-κB

text: With the degradation of IκB, the NF-κB complex is then freed to enter the nucleus where it can 'turn on' the expression of specific genes that have DNA-binding sites for NF-κB nearby. The activation of these genes by NF-κB then leads to the given physiological response, for example, an inflammatory or immune response, a cell survival response, or cellular proliferation. Translocation of NF-κB to nucleus can be detected immunocytochemically and measured by laser scanning cytometry. NF-κB turns on expression of its own repressor, IκBα. The newly synthesized IκBα then re-inhibits NF-κB and, thus, forms an auto feedback loop, which results in oscillating levels of NF-κB activity. In addition, several viruses, including the AIDS virus HIV, have binding sites for NF-κB that controls the expression of viral genes, which in turn contribute to viral replication or viral pathogenicity. In the case of HIV-1, activation of NF-κB may, at least in part, be involved in activation of the virus from a latent, inactive state. YopP is a factor secreted by "Yersinia pestis", the causative agent of plague, that prevents the ubiquitination of IκB. This causes this pathogen to effectively inhibit the NF-κB pathway and thus block the immune response of a human infected with Yersinia.


title: NF-κB

text: Concerning known protein inhibitors of NF-κB activity, one of them is IFRD1, which represses the activity of NF-κB p65 by enhancing the HDAC-mediated deacetylation of the p65 subunit at lysine 310, by favoring the recruitment of HDAC3 to p65. In fact IFRD1 forms trimolecular complexes with p65 and HDAC3.


title: NF-κB

text: The NAD-dependent protein deacetylase and longevity factor SIRT1 inhibits NF-κB gene expression by deacetylating the RelA/p65 subunit of NF-κB at lysine 310.


title: NF-κB

text: A select set of cell-differentiating or developmental stimuli, such as lymphotoxin β-receptor (LTβR), BAFF or RANKL, activate the non-canonical NF-κB pathway to induce NF-κB/RelB:p52 dimer in the nucleus. In this pathway, activation of the NF-κB inducing kinase (NIK) upon receptor ligation led to the phosphorylation and subsequent proteasomal processing of the NF-κB2 precursor protein p100 into mature p52 subunit in an IKK1/IKKa dependent manner. Then p52 dimerizes with RelB to appear as a nuclear RelB:p52 DNA binding activity. RelB:p52 regulates the expression of homeostatic lymphokines, which instructs lymphoid organogenesis and lymphocyte trafficking in the secondary lymphoid organs. In contrast to the canonical signaling that relies on NEMO-IKK2 mediated degradation of IκBα, -β, -ε, non-canonical signaling depends on NIK mediated processing of p100 into p52. Given their distinct regulations, these two pathways were thought to be independent of each other. However, it was found that syntheses of the constituents of the non-canonical pathway, viz RelB and p52, are controlled by canonical IKK2-IκB-RelA:p50 signaling. Moreover, generation of the canonical and non-canonical dimers, viz RelA:p50 and RelB:p52, within the cellular milieu are mechanistically interlinked. These analyses suggest that an integrated NF-κB system network underlies activation of both RelA and RelB containing dimer and that a malfunctioning canonical pathway will lead to an aberrant cellular response also through the non-canonical pathway. Most intriguingly, a recent study identified that TNF-induced canonical signalling subverts non-canonical RelB:p52 activity in the inflamed lymphoid tissues limiting lymphocyte ingress. Mechanistically, TNF inactivated NIK in LTβR‐stimulated cells and induced the synthesis of "Nfkb2" mRNA encoding p100; these together potently accumulated unprocessed p100, which attenuated the RelB activity. A role of p100/"Nfkb2" in dictating lymphocyte ingress in the inflamed lymphoid tissue may have broad physiological implications.


title: NF-κB

text: In addition to its traditional role in lymphoid organogenesis, the non-canonical NF-κB pathway also directly reinforces inflammatory immune responses to microbial pathogens by modulating canonical NF-κB signalling. It was shown that p100/"Nfkb2" mediates stimulus-selective and cell-type-specific crosstalk between the two NF-κB pathways and that "Nfkb2"-mediated crosstalk protects mice from gut pathogens. On the other hand, a lack of p100-mediated regulations repositions RelB under the control of TNF-induced canonical signalling. In fact, mutational inactivation of p100/"Nfkb2" in multiple myeloma enabled TNF to induce a long-lasting RelB activity, which imparted resistance in myeloma cells to chemotherapeutic drug.


title: NF-κB

text: NF-κB is a major transcription factor that regulates genes responsible for both the innate and adaptive immune response. Upon activation of either the T- or B-cell receptor, NF-κB becomes activated through distinct signaling components. Upon ligation of the T-cell receptor, protein kinase Lck is recruited and phosphorylates the ITAMs of the CD3 cytoplasmic tail. ZAP70 is then recruited to the phosphorylated ITAMs and helps recruit LAT and PLC-γ, which causes activation of PKC. Through a cascade of phosphorylation events, the kinase complex is activated and NF-κB is able to enter the nucleus to upregulate genes involved in T-cell development, maturation, and proliferation.


title: NF-κB

text: In addition to roles in mediating cell survival, studies by Mark Mattson and others have shown that NF-κB has diverse functions in the nervous system including roles in plasticity, learning, and memory. In addition to stimuli that activate NF-κB in other tissues, NF-κB in the nervous system can be activated by Growth Factors (BDNF, NGF) and synaptic transmission such as glutamate. These activators of NF-κB in the nervous system all converge upon the IKK complex and the canonical pathway.


title: NF-κB

text: Recently there has been a great deal of interest in the role of NF-κB in the nervous system. Current studies suggest that NF-κB is important for learning and memory in multiple organisms including crabs, fruit flies, and mice. NF-κB may regulate learning and memory in part by modulating synaptic plasticity, synapse function, as well as by regulating the growth of dendrites and dendritic spines.


title: NF-κB

text: Genes that have NF-κB binding sites are shown to have increased expression following learning, suggesting that the transcriptional targets of NF-κB in the nervous system are important for plasticity. Many NF-κB target genes that may be important for plasticity and learning include growth factors (BDNF, NGF) cytokines (TNF-alpha, TNFR) and kinases (PKAc).


title: NF-κB

text: Despite the functional evidence for a role for Rel-family transcription factors in the nervous system, it is still not clear that the neurological effects of NF-κB reflect transcriptional activation in neurons. Most manipulations and assays are performed in the mixed-cell environments found in vivo, in "neuronal" cell cultures that contain significant numbers of glia, or in tumor-derived "neuronal" cell lines. When transfections or other manipulations have been targeted specifically at neurons, the endpoints measured are typically electrophysiology or other parameters far removed from gene transcription. Careful tests of NF-κB-dependent transcription in highly purified cultures of neurons generally show little to no NF-κB activity.


title: NF-κB

text: Some of the reports of NF-κB in neurons appear to have been an artifact of antibody nonspecificity. Of course, artifacts of cell culture—e.g., removal of neurons from the influence of glia—could create spurious results as well. But this has been addressed in at least two co-culture approaches. Moerman et al. used a coculture format whereby neurons and glia could be separated after treatment for EMSA analysis, and they found that the NF-κB induced by glutamatergic stimuli was restricted to glia (and, intriguingly, only glia that had been in the presence of neurons for 48 hours). The same investigators explored the issue in another approach, utilizing neurons from an NF-κB reporter transgenic mouse cultured with wild-type glia; glutamatergic stimuli again failed to activate in neurons. Some of the DNA-binding activity noted under certain conditions (particularly that reported as constitutive) appears to result from Sp3 and Sp4 binding to a subset of κB enhancer sequences in neurons. This activity is actually inhibited by glutamate and other conditions that elevate intraneuronal calcium. In the final analysis, the role of NF-κB in neurons remains opaque due to the difficulty of measuring transcription in cells that are simultaneously identified for type. Certainly, learning and memory could be influenced by transcriptional changes in astrocytes and other glial elements. And it should be considered that there could be mechanistic effects of NF-κB aside from direct transactivation of genes.


title: NF-κB

text: NF-κB is widely used by eukaryotic cells as a regulator of genes that control cell proliferation and cell survival. As such, many different types of human tumors have misregulated NF-κB: that is, NF-κB is constitutively active. Active NF-κB turns on the expression of genes that keep the cell proliferating and protect the cell from conditions that would otherwise cause it to die via apoptosis. In cancer, proteins that control NF-κB signaling are mutated or aberrantly expressed, leading to defective coordination between the malignant cell and the rest of the organism. This is evident both in metastasis, as well as in the inefficient eradication of the tumor by the immune system.


title: NF-κB

text: Normal cells can die when removed from the tissue they belong to, or when their genome cannot operate in harmony with tissue function: these events depend on feedback regulation of NF-κB, and fail in cancer.


title: NF-κB

text: Defects in NF-κB results in increased susceptibility to apoptosis leading to increased cell death. This is because NF-κB regulates anti-apoptotic genes especially the TRAF1 and TRAF2 and therefore abrogates the activities of the caspase family of enzymes, which are central to most apoptotic processes.