title: Max Steel (film)

text: An early attempt to create a Max Steel film occurred in December 2009 when Paramount Pictures purchased the rights to the franchise. Taylor Lautner was an early choice for the starring role, although he later dropped out due to commitment to the Stretch Armstrong film. In January 2013, production was suspended when "Max Steel" was developed into a television series of the same name, airing later that year. In August 2013, plans for a new film adaptation resumed with Mattel partnering with Dolphin Entertainment to fund the film.


title: Max Steel (film)

text: In February 2014, Ben Winchell and Ana Villafañe were cast as Max McGrath and Sofia Martinez, respectively. That same month, the press officially confirmed Andy García's casting as Dr. Miles Edwards. In May 2014, Maria Bello and Mike Doyle joined the cast as Molly and Jim McGrath, Max's parents.


title: Max Steel (film)

text: Principal photography commenced on April 29, 2014, in Wilmington, North Carolina and ended on May 31, 2014.


title: Max Steel (film)

text: "Max Steel" grossed $3.8 million in the United States and Canada and $2.5 million in other countries, for a worldwide total of $6.3 million, against a production budget of $5–10 million.


title: Max Steel (film)

text: "Max Steel" opened on October 14, 2016, alongside "The Accountant" and "", and was expected to gross $5–7 million from 2,034 theaters in its opening weekend. After grossing just $637,795 on its first day the film went on to open to $2.2 million, finishing 11th at the box office. In its second weekend the film grossed $680,104 finishing 17th at the box office, making it a box office bomb.


title: Max Steel (film)

text: On Rotten Tomatoes, the film has an approval rating of based on reviews, with an average rating of . The site's critics' consensus states: "Bereft of characterization or even satisfying rock 'em sock 'em, "Max Steel" feels like futzing with an action figure without any childhood imagination." On Metacritic the film has a weighted average score 22 out of 100, based on reviews from 7 critics, indicating "generally unfavorable reviews". Audiences surveyed by CinemaScore gave the film a grade of "B" on an A+ to F scale.


title: Max Steel (film)

text: IGN critic Alex Welch gave the film a score of 4 out of 10, summarizing his review with: ""Max Steel" is one of the more forgettable and pointless attempts at a superhero franchise in the current post-MCU Hollywood market, lacking any of the originality or vibrance that could give it even a remote shot at a successful future." "Variety"s Joe Leydon gave a negative review, describing it as: "A half-baked, time-wasting curtain-raiser for a superhero franchise that is never, ever going to happen." Christy Lemire for "RogerEbert.com" gave half a star out of 4, writing: "For a movie about developing the greatest energy source in the universe, "Max Steel" is surprisingly bland" and that "a movie based on a toy should be a whole lot more fun than this." "The Hollywood Reporter" critic Frank Scheck gave an unfavorable review, writing: "Even tweens may find themselves underwhelmed by the new live-action film based on what—for many of them—may be their favorite Mattel action figure. Delivering a bland cinematic origin story which seems calculated to boost Christmas toy sales, "Max Steel" is a stillborn, would-be franchise starter, sneaked into multiplexes without advance critic screenings."


title: Max Steel (film)

text: Universal Pictures Home Entertainment released "Max Steel" on Digital HD on January 3, 2017, then released the film on Blu-ray/DVD/Digital HD combo-pack on January 10, 2017.


title: Naturalism (literature)

text: Naturalism is a literary movement beginning in the late nineteenth century, similar to literary realism in its rejection of Romanticism, but distinct in its embrace of determinism, detachment, scientific objectivism, and social commentary. Literary naturalism emphasizes observation and the scientific method in the fictional portrayal of reality. Naturalism includes detachment, in which the author maintains an impersonal tone and disinterested point of view; determinism, which is defined as the opposite of free will, in which a character's fate has been decided, even predetermined, by impersonal forces of nature beyond human control; and a sense that the universe itself is indifferent to human life. The novel would be an experiment where the author could discover and analyze the forces, or scientific laws, that influenced behavior, and these included emotion, heredity, and environment. The movement largely traces to the theories of French author Émile Zola.


title: Naturalism (literature)

text: Literary Naturalism traces back most directly to Émile Zola's "The Experimental Novel" (1880), which details Zola's concept of a naturalistic novel, which traces philosophically to Auguste Comte's positivism, but also to physiologist Claude Bernard and historian Hippolyte Taine. Comte had proposed a scientific method that “went beyond empiricism, beyond the passive and detached observation of phenomena”. The application of this method “called for a scientist to conduct controlled experiments that would either prove or disprove hypotheses regarding those phenomena”. Zola took this scientific method and argued that naturalism in literature should be like controlled experiments in which the characters function as the phenomena.


title: Naturalism (literature)

text: Naturalism began as a branch of literary realism, and realism had favored fact, logic, and impersonality over the imaginative, symbolic, and supernatural. Frank Norris, an American journalist and novelist, whose work was predominantly in the naturalist genre, “placed realism, romanticism, and naturalism in a dialectic, in which realism and romanticism were opposing forces”, and naturalism was a mixture of the two. Norris's idea of naturalism differs from Zola's in that “it does not mention materialistic determinism or any other philosophic idea”.


title: Naturalism (literature)

text: Apart from Zola and Norris, there are various literary critics who have their own separate views on the matter. As said by Paul Civello, these critics can be grouped into four broad, and often overlapping, groups: early theorists, history-of-idea critics, European influence critics, and recent theorists. The early theorists saw naturalism thematically and in terms of literary technique. The history-of-idea critics understood it as an expression of the central ideas to an era. The European influence critics viewed it in much the same way as Zola. For example, according to theorist Kornelije Kvas, naturalism presents "forms of human experience not spoken of before – the physiological aspect of human behavior, sexuality, poverty – as literary topics worthy of being dealt with." Recent theorists have either re-conceptualized naturalism as a narrative form, or denied its existence entirely.


title: Naturalism (literature)

text: Some say that naturalism is dead, or that it “may have never lived at all: even in the works of Émile Zola”, its founder. “In 1900 an obituary entitled “The Passing of Naturalism” in "The Outlook" officially declared the literary movement deceased”, and that Zola's attempt to create a scientific literature was a failure. This certainly wasn't the first time Zola's novel had been criticized however. After his novel "Thérèse Raquin" (1867) had been sharply criticized for both contents and language, in a foreword for its second edition (1868), in a mixture of pride and defiance, he wrote: "Le groupe d'écrivains naturalistes auquel j'ai l'honneur d'appartenir a assez de courage et d'activité pour produire des oeuvres fortes, portant en elles leur défense", which translates as: "The group of naturalist writers I have the honor to belong to have enough courage and activity to produce strong works, carrying within them their defense."


title: Naturalism (literature)

text: Naturalism was very popular in its time and was known in different literary traditions in Western Europe. In the Netherlands, there was Cooplandt, Couperus, Frederik van Eeden and Marcellus Emants. In Germany, the most important naturalistic writers were Gerhart Hauptmann, Arno Holz and Johannes Schlaf. In Belgium, the most important writers were Cyriel Buysse and Stijn Streuvels. In Spain, the most remarkable figure was Vicente Blasco Ibánez.


title: Naturalism (literature)

text: Naturalism in American literature traces to Frank Norris, whose theories were markedly different from Zola's, particularly to the status of naturalism within the loci of realism and Romanticism; Norris thought of naturalism as being Romantic, and thought Zola as being "a realist of realists". To Link, while American naturalism had trends, its definition had no unified critical consensus. Link's examples include Stephen Crane, Jack London, Theodore Dreiser, and Frank Norris, with William Dean Howells and Henry James being clear markers on the other side of the naturalist/realist divide.


title: Naturalism (literature)

text: The center of Crane's naturalism is recognized as "The Open Boat," which portrayed a naturalistic view of man with his depiction of a group of survivors adrift in a boat. The humans with their creation confronted the sea and the world of nature. In the experiences of these men, Crane articulated the illusion of gods and the realization of the universe's indifference.


title: Naturalism (literature)

text: William Faulkner's "A Rose for Emily," a story about a woman who killed her lover, is considered an example of a narrative within the naturalism category. This story, which also used Gothic elements, presented a tale that highlighted the extraordinary and excessive features in human nature and the social environment that influences them. The protagonist, Miss Emily, was forced to lead an isolated life, and that - combined with her mental illness - made insanity her inevitable fate. The environment in the forms of a class structure based on slavery and social change, together with heredity, represented the forces beyond her control.


title: Polish government-in-exile

text: The Polish government-in-exile, officially known as the Government of the Republic of Poland in exile (), was the government in exile of Poland formed in the aftermath of the Invasion of Poland of September 1939, and the subsequent occupation of Poland by Germany and the Soviet Union, which brought to an end the Second Polish Republic.


title: Polish government-in-exile

text: Despite the occupation of Poland by hostile powers, the government-in-exile exerted considerable influence in Poland during World War II through the structures of the Polish Underground State and its military arm, the Armia Krajowa (Home Army) resistance. Abroad, under the authority of the government-in-exile, Polish military units that had escaped the occupation fought under their own commanders as part of Allied forces in Europe, Africa, and the Middle East.


title: Polish government-in-exile

text: After the war, as the Polish territory came under the control of the communist Polish People's Republic, the government-in-exile remained in existence albeit without effective power. It lost recognition of the majority of states upon formation of the Provisional Government of National Unity on 5 July 1945 though continued to be hosted and informally supported by the United Kingdom, while the last country to withdraw its diplomatic recognition on 19 October 1972 was the Holy See (the Vatican City). However, only after the end of communist rule in Poland did the government-in-exile formally pass its responsibilities and insignia onto the government of the Third Polish Republic at a special ceremony held on 22 December 1990 at the Royal Castle in Warsaw, while the liquidation of its apparatus was declared accomplished on 31 December 1991.


title: Polish government-in-exile

text: The government-in-exile was based in France during 1939 and 1940, first in Paris and then in Angers. From 1940, following the Fall of France, the government moved to London, and remained in the United Kingdom until its dissolution in 1990.


title: Polish government-in-exile

text: On 17 September 1939, the President of the Polish Republic, Ignacy Mościcki, who was then in the small town of Kuty (now Ukraine) near the southern Polish border, issued a proclamation about his plan to transfer power and appointing Władysław Raczkiewicz, the Marshal of the Senate, as his successor. This was done in accordance with Article 24 of the Constitution of the Republic of Poland, adopted in April 1935. Article 24 provided as follows:


title: Polish government-in-exile

text: It was not until 29 or 30 September 1939 that Mościcki resigned. Raczkiewicz, who was already in Paris, immediately took his constitutional oath at the Polish Embassy and became President of the Republic of Poland. Raczkiewicz then appointed General Władysław Sikorski to be Prime Minister. After Edward Rydz-Śmigły stepped down, Raczkiewicz also made Sikorski Commander-in-Chief of the Polish Armed Forces.


title: Polish government-in-exile

text: Most of the Polish Navy escaped to Britain, and tens of thousands of Polish soldiers and airmen escaped through Hungary and Romania or across the Baltic Sea to continue the fight in France. Many Poles subsequently took part in Allied operations: in Norway (Narvik), in France in 1940 and in 1944, in the Battle of Britain, in the Battle of the Atlantic, in North Africa (notably Tobruk), Italy (notably at Cassino and Ancona), at Arnhem, Wilhelmshaven, and elsewhere.


title: Polish government-in-exile

text: Under the Sikorski–Mayski agreement of July 1941 Polish soldiers taken prisoner by the Soviet Union in 1939, were released to form Anders' Army, intended to fight Nazi Germany in the USSR, but instead transferred via Iran to fight with US and British forces. Berling's Army, formed in the USSR in 1944, remained there and fought under Soviet command.


title: Polish government-in-exile

text: The Polish government in exile, based first in Paris, then in Angers, France, where Władysław Raczkiewicz lived at the Château de Pignerolle near Angers from 2 December 1939 until June 1940. Escaping from France the government relocated to London, where it was recognized by all the Allied governments. Politically, it was a coalition of the Polish Peasant Party, the Polish Socialist Party, the Labour Party and the National Party, although these parties maintained only a vestigial existence in the circumstances of war.


title: Polish government-in-exile

text: When Germany launched a war against the Soviets in 1941, the Polish government in exile established diplomatic relations with the Soviet Union against Hitlerism, but also in order to help Poles persecuted by the NKVD. On 12 August 1941 the Kremlin signed a one-time amnesty, extending to thousands of Polish soldiers who had been taken prisoner in 1939 by the Red Army in eastern Poland, including many Polish civilian prisoners and deportees entrapped in Siberia. The amnesty allowed the Poles to create eight military divisions known as the Anders Army. They were evacuated to Iran and the Middle East, where they were desperately needed by the British, hard pressed by Rommel's Afrika Korps. These Polish units formed the basis for the Polish II Corps, led by General Władysław Anders, which together with other, earlier-created Polish units fought alongside the Allies.


title: Polish government-in-exile

text: During the war, especially from 1942 on, the Polish government in exile provided the Allies with some of the earliest and most accurate accounts of the ongoing Holocaust of European Jews and, through its representatives, like the Foreign Minister Count Edward Raczyński and the courier of the Polish Underground movement, Jan Karski, called for action, without success, to stop it. The note the Foreign Minister, Count Edward Raczynski, sent on 10 December 1942 to the Governments of the United Nations was the first official denunciation by any Government of the mass extermination and of the Nazi aim of total extermination of the Jewish population. It was also the first official document singling out the sufferings of European Jews as Jews and not only as citizens of their respective countries of origin. The note of 10 December 1942 and the Polish Government efforts triggered the Declaration of the Allied Nations of 17 December 1942.


title: Polish government-in-exile

text: In April 1943, the Germans announced that they had discovered at Katyn Wood, near Smolensk, Russia, mass graves of 10,000 Polish officers (the German investigation later found 4,443 bodies) who had been taken prisoner in 1939 and murdered by the Soviets. The Soviet government said that the Germans had fabricated the discovery. The other Allied governments, for diplomatic reasons, formally accepted this; the Polish government in exile refused to do so.


title: Polish government-in-exile

text: Stalin then severed relations with the Polish government in exile. Since it was clear that it would be the Soviet Union, not the western Allies, who would liberate Poland from the Germans, this breach had fateful consequences for Poland. In an unfortunate coincidence, Sikorski, widely regarded as the most capable of the Polish exile leaders, was killed in an air crash at Gibraltar in July 1943. He was succeeded as head of the Polish government in exile by Stanisław Mikołajczyk.


title: Polish government-in-exile

text: During 1943 and 1944, the Allied leaders, particularly Winston Churchill, tried to bring about a resumption of talks between Stalin and the Polish government in exile. But these efforts broke down over several matters. One was the Katyń massacre (and others at Kalinin and Kharkiv). Another was Poland's postwar borders. Stalin insisted that the territories annexed by the Soviets in 1939, which had millions of Poles in addition to mostly Ukrainian and Belarusian populations, should remain in Soviet hands, and that Poland should be compensated with lands to be annexed from Germany. Mikołajczyk, however, refused to compromise on the question of Poland's sovereignty over her prewar eastern territories. A third matter was Mikołajczyk's insistence that Stalin would not set up a Communist government in postwar Poland. Mikołajczyk and his colleagues in the Polish government-in-exile insisted on making a stand in the defense of Poland's pre-1939 eastern border (retaining its Kresy region) as a basis for the future Polish-Soviet border. However, this was a position that could not be defended in practiceStalin was in occupation of the territory in question. The government-in-exile's refusal to accept the proposed new Polish borders infuriated the Allies, particularly Churchill, making them less inclined to oppose Stalin on issues of how Poland's postwar government would be structured. In the end, the exiles lost on both issues: Stalin re-annexed the eastern territories, as well as proceded to impose the communist Polish Committee of National Liberation established on 22 July 1944 by renaming it into the Provisional Government of the Republic of Poland on 31 December 1944. However, Poland preserved its status as an independent state, despite the arguments of some influential Communists, such as Wanda Wasilewska, in favor of Poland becoming a republic of the Soviet Union. In November 1944, despite his mistrust of the Soviets, Mikołajczyk resigned to return to Poland.


title: Polish government-in-exile

text: On 28 June 1945, Mikołajczyk took office in the Provisional Government of National Unity, a new government established as a result of reshuffling the existing Provisional Government, established under the auspices of the Soviet occupation authorities, through inclusion of his fraction. This provided an excuse for the Western allies to approve tacitly the "fait accompli" of Poland becoming part of the Soviet sphere of influence, and to legitimise the Warsaw government while withdrawing their recognition of the government-in-exile; France did so on 29 June 1945, then the United States and United Kingdom on 5 July 1945 withdrew their recognition. The Polish Armed Forces in exile were disbanded in 1945, and most of their members, unable to safely return to Communist Poland, settled in other countries.


title: Polish government-in-exile

text: Many Polish exiles opposed this action, believing that this government was a façade for the establishment of Communist rule in Poland. This view was later proven correct in 1947 when the Communist-dominated Democratic Bloc won a rigged election. The Communist-dominated bloc was credited with over 80 percent of the vote, a result that was only obtained through large-scale fraud. The opposition claimed it would have won in a landslide (as much as 80 percent, by some estimates) had the election been genuine and Mikołajczyk would have likely become prime minister. In November, at a meeting with the Silesian society, Mikołajczyk was informed that he was to be arrested along with his advisor Paweł Zaleski. The arrest order was already signed. They immediately took the effort to escape. Mikołajczyk headed north, while Zaleski escaped through the southern channel. From the danger zone, Zaleski was taken away in a straw cart. His brother Jan Zaleski from Boyko helped in the escape. Paweł waited a few days with Mikołaj and his father-in-law, Aries of Kamionka in Korfantów near Głuchołazy, before a transfer was arranged. Then through the Czech Republic, Zaleski got to the west, and Mikołajczyk was taken by ship from Szczecin. This was their last stay in Poland.


title: Polish government-in-exile

text: Meanwhile, the Polish government in exile had maintained its existence. The London Poles had to vacate the Polish embassy on Portland Place and were left only with the president's private residence at 43 Eaton Place. The government in exile became largely symbolic of continued resistance to foreign occupation of Poland while retaining some important archives from prewar Poland.


title: Polish government-in-exile

text: In 1954, political differences led to a split in the ranks of the government in exile. One group, claiming to represent 80% of 500,000 anti-Communist Poles exiled since the war, was opposed to President August Zaleski's continuation in office when his seven-year term expired. It formed a Council of National Unity in July 1954, and set up a Council of Three to exercise the functions of head of state, comprising Tomasz Arciszewski, General Władysław Anders, and Edward Raczyński. Only after Zaleski's death in 1972 did the two factions reunite. Some supporters of the government in exile eventually returned to Poland, such as Prime Minister Hugon Hanke in 1955 and his predecessor Stanisław Mackiewicz in 1956. The Soviet-installed government in Warsaw campaigned for the return of the exiles, promising decent and dignified employment in communist Polish administration and forgiveness of past transgressions. The last country to withdraw its diplomatic recognition was the Holy See (the Vatican City). The Republic of Ireland, Francoist Spain and finally (on 19 October 1972) the Holy See (Vatican City) were the last countries to withdraw recognition of the government-in-exile, though the Secretary of State of the Vatican City Domenico Tardini had withdrawn diplomatic privileges from the envoy of the Polish pre-war government already in 1959.


title: Polish government-in-exile

text: Despite these setbacks, the government in exile continued in existence. When Soviet influence over Poland came to an end in 1989, there was still a president and a cabinet of eight, meeting every two weeks in London, commanding the loyalty of about 150,000 Polish veterans and their descendants living in Britain, including 35,000 in London alone.


title: Polish government-in-exile

text: Only after the end of communist rule in Poland did the government-in-exile formally pass its responsibilities and insignia onto the government of the Third Polish Republic at a special ceremony held on 22 December 1990 at the Royal Castle in Warsaw where Lech Wałęsa, the first non-Communist president of Poland since the war, received the symbols of the Polish Republic (the presidential banner, the presidential and state seals, the presidential sashes, and the original text of the 1935 Constitution) from the last president of the government in exile, Ryszard Kaczorowski. The liquidation of the London-based government apparatus was declared accomplished on 31 December 1991. In 1992, military medals and other decorations awarded by the government in exile were officially recognized in Poland. The Act on Emoluments of a Former President of the Republic of Poland adopted in 1996 which establishes the rights, privileges, remuneration and other benefits of a former President, awarded them explicitly also to the last President-in-exile.


title: Polish government-in-exile

text: "Republic in Exile" tells the story of the Polish government-in-exile in the form of five short episodes available on the YouTube channel: Polish Embassy UK


title: Sonoma County, California

text: Sonoma County () is a county located in the U.S. state of California. As of the 2020 United States Census, its population was 488,863. Its county seat and largest city is Santa Rosa. It is to the north of Marin County and the south of Mendocino County. It is west of Napa County and Lake County.


title: Sonoma County, California

text: Sonoma County comprises the Santa Rosa-Petaluma Metropolitan Statistical Area, which is part of the San Jose-San Francisco-Oakland, CA Combined Statistical Area. It is the northernmost county in the nine-county San Francisco Bay Area region.


title: Sonoma County, California

text: In California's Wine Country region, which also includes Napa, Mendocino, and Lake counties, Sonoma County is the largest producer. It has thirteen approved American Viticultural Areas and more than 350 wineries. The voters have twice approved open space initiatives that have provided funding for public acquisition of natural areas, preserving forested areas, coastal habitat, and other open space. More than 8.4 million tourists visit each year, spending more than $1 billion in 2016.


title: Sonoma County, California

text: In 2012, Sonoma County ranked as the 22nd county in the United States in agricultural production. By 1920, Sonoma County was ranked as the eighth most agriculturally productive U.S. county and a leading producer of hops, grapes, prunes, apples, as well as dairy and poultry products, largely due to the extent of available, fertile agricultural land in addition to the abundance of high-quality water for irrigation. As of 2009, agriculture was largely divided between two nearly monocultural uses: grapes and pasturage.


title: Sonoma County, California

text: The Pomo, Coast Miwok and Wappo peoples were the earliest human settlers of Sonoma County, between 8000 and 5000 BC, effectively living within the natural carrying capacity of the land. Archaeological evidence of these First people includes a number of occurrences of rock carvings, especially in southern Sonoma County; these carvings often take the form of pecked curvilinear nucleated design.


title: Sonoma County, California

text: Spaniards, Russians, and other Europeans claimed and settled in the county from the late 16th to mid-19th century, seeking timber, fur, and farmland. The Russians were the first newcomers to establish a permanent foothold in Sonoma County, with the Russian-American Company establishing Fort Ross on the Sonoma Coast in 1812. This settlement and its outlying Russian settlements came to include a population of several hundred Russian and Aleut settlers and a stockaded fort with artillery. However, the Russians abandoned it in 1841 and sold the fort to John Sutter, settler and Mexican land grantee of Sacramento.


title: Sonoma County, California

text: The Mission San Francisco Solano, founded in 1823 as the last and northernmost of 21 California missions, is in the present City of Sonoma, at the northern end of El Camino Real. El Presidio de Sonoma, or Sonoma Barracks (part of Spain's "Fourth Military District"), was established in 1836 by Comandante General Mariano Guadalupe Vallejo. His duties included keeping an eye on the Russian traders at Fort Ross, secularizing the Mission, maintaining cooperation with the Native Americans of the entire region, and doling out the lands for large estates and ranches. The City of Sonoma was the site of the Bear Flag Revolt in 1846.


title: Sonoma County, California

text: Sonoma was one of the original counties when California became a state in 1850, with its county seat originally the town (now city) of Sonoma. However, by the early 1850s, Sonoma had declined in importance in both commerce and population, its county buildings were crumbling, and it was relatively remote. As a result, elements in the newer, rapidly growing towns of Petaluma, Santa Rosa, and Healdsburg began vying to move the county seat to their towns. The dispute ultimately was between the bigger, richer commercial town of Petaluma and the more centrally located, growing agricultural center of Santa Rosa. The fate was decided following an election for the state legislature in which James Bennett of Santa Rosa defeated Joseph Hooker of Sonoma and introduced a bill that resulted in Santa Rosa being confirmed as county seat in 1854. Allegedly, several Santa Rosans, not caring to wait, decided to take action and, one night, rode down the Sonoma Valley to Sonoma, took the county seals and records, and brought them to Santa Rosa. Some of the county's land was annexed from Mendocino County between 1850 and 1860.


title: Sonoma County, California

text: Early post-1847 settlement and development focused primarily on the city of Sonoma, then the region's sole town and a common transit and resting point in overland travel between the region and Sacramento and the gold fields to the east. However, after 1850, a settlement that soon became the city of Petaluma began to grow naturally near the farthest navigable point inland up the Petaluma River. Originally a hunting camp used to obtain game to sell in other markets, by 1854 Petaluma had grown into a bustling center of trade, taking advantage of its position on the river near a region of highly productive agricultural land that was being settled. Soon, other inland towns, notably Santa Rosa and Healdsburg began to develop similarly due to their locations along riparian areas in prime agricultural flatland. However, their development initially lagged behind Petaluma which, until the arrival of railroads in the 1860s, remained the primary commercial, transit, and break-of-bulk point for people and goods in the region. After the arrival of the San Francisco and North Pacific Railroad in 1870, Santa Rosa began to boom, soon equalling and then surpassing Petaluma as the region's population and commercial center. The railroad bypassed Petaluma for southern connections to ferries of San Francisco Bay.


title: Sonoma County, California

text: Sonoma County was severely shaken by the 1906 San Francisco earthquake. The displacements along the fault averaged .


title: Sonoma County, California

text: In October 2017, the county was greatly affected by the Tubbs Fire and the Nuns Fire. In late October and early November 2019, the Kincade Fire burned , almost all in Sonoma County. In August and September 2020, the Walbridge Fire burned in the western part of the county; then in September–October the Glass fire affected the city of Santa Rosa and ultimately destroying 1,000+ buildings The county also had a wildfire in the 1870s that is compared to the Hanley fire and Tubbs fire because they burned in the same path.


title: Sonoma County, California

text: The Sonoma County Landmarks Commission recognizes nearly 200 formal historical landmarks and the Sonoma County Historical Society counts 380 landmarks recognized by several agencies.


title: Sonoma County, California

text: According to the book "California Place Names", "The name of the Indian tribe is mentioned in baptismal records of 1815 as "Chucuines" or "Sonomas", by Chamisso in 1816 as "Sonomi", and repeatedly in Mission records of the following years."


title: Sonoma County, California

text: According to the Coast Miwok and the Pomo tribes that lived in the region, Sonoma translates as "valley of the moon" or "many moons". Their legends detail this as a land where the moon nestled, hence the names Sonoma Valley and the "Valley of the Moon." This translation was first recorded in an 1850 report by General Mariano Guadalupe Vallejo to the California Legislature. Jack London popularized it in his 1913 novel "The Valley of the Moon".


title: Sonoma County, California

text: In the native languages there is also a constantly recurring ending "tso-noma", from "tso", the earth; and "noma", village; hence "tsonoma", "earth village." Other sources say Sonoma comes from the Patwin tribes west of the Sacramento River, and their Wintu word for "nose". Per "California Place Names", "the name is doubtless derived from a Patwin word for 'nose', which Padre Arroyo (Vocabularies, p. 22) gives as "sonom" (Suisun)." Spaniards may have found an Indian chief with a prominent protuberance and applied the nickname of "Chief Nose" to the village and the territory. The name may have applied originally to a nose-shaped geographic feature.


title: Sonoma County, California

text: According to the U.S. Census Bureau, the county has an area of , of which is land and (10.9%) is water.


title: Sonoma County, California

text: The county lies in the North Coast Ranges of northwestern California. Its ranges include the Mayacamas and the Sonoma Mountains, the southern peak of the latter being the prominent landform Sears Point. The highest peak in the Mayacamas within the county and the highest peak in the County is Mt. Saint Helena. It has uncommon occurrences of pygmy forest, dominated by Mendocino cypress. The highest peak of the Sonoma Mountains is Sonoma Mountain itself, which boasts two significant public access properties: Jack London State Historic Park and Fairfield Osborn Preserve.


title: Sonoma County, California

text: The county includes the City of Sonoma and the Sonoma Valley, in which the City of Sonoma is located. However, these are not synonymous. The City of Sonoma is merely one of nine incorporated cities in the county. The Sonoma Valley is just the southeastern portion of the county, which includes many other valleys and geographic zones, including the Petaluma Valley, the Santa Rosa Plains, the Russian River, the Alexander Valley, and the Dry Creek Valley.


title: Sonoma County, California

text: Distinct habitat areas within the county include oak woodland, redwood forest, northern coastal scrub, grassland, marshland, oak savanna and riparian woodland. The California oak woodland in the upper Yulupa Creek and Spring Creek watersheds in Annadel State Park is a relatively undisturbed ecosystem with considerable biodiversity. These forested areas have been characterized as some of the best examples of such woodlands. An unusual characteristic of these forests is the high content of undisturbed prehistoric bunchgrass understory, testifying to the absence of historic grazing or other agriculture.


title: Sonoma County, California

text: Trees of the oak woodland habitat include Pacific madrone, Douglas fir, coast live oak, Garry oak, and California laurel. Common understory plants are toyon, poison oak, and, at the fringes, coast silk-tassel.


title: Sonoma County, California

text: Sonoma County, as is often the case with coastal counties in California, has a great degree of climatic variation and numerous, often very different, microclimates. Key determining factors for local climate are proximity to the ocean, elevation, and the presence and elevation of hills or mountains to the east and west. This is in large part due to the fact that, as throughout California, the prevailing weather systems and wind come normally from the Pacific Ocean, blowing in from the west and southwest, so that places closer to the ocean and on the windward side of higher elevations tend to receive more rain from autumn through spring and more summer wind and fog. This itself is partly a result of the presence of high and low pressures in inland California, with persistent high summer temperatures in the Central Valley, in particular, leading to low pressures, drawing in moist air from the Pacific, cooling into damp cool breezes and fog over the cold coastal water. Those places further inland and particularly in the lee of significant elevations tend to receive less rain and less, in some cases no, fog in the summer.


title: Sonoma County, California

text: The coast itself is typically cool and moist throughout summer, often foggy, with fog generally blowing in during the late afternoon and evening until it clears in the later morning becoming sunny, before repeating. Coastal summer highs are typically in the mid to high 60s, warming to the low 70s further from the ocean.


title: Sonoma County, California

text: Certain inland areas, including the Petaluma area and the Santa Rosa Plain, are also prone to this normal fog pattern in general. However, they tend to receive the fog later in the evening, the fog tends to be more short-lived, and mid-day temperatures are significantly higher than they are on the coast, typically in the low 80s F. This is particularly true for Petaluma, Cotati, and Rohnert Park, and, only slightly less so, Santa Rosa, Windsor, and Sebastopol. In large part, this results from lower elevations and the prominent Petaluma Gap in the hills between the ocean to the west and the Petaluma Valley and Santa Rosa Plain to the east.


title: Sonoma County, California

text: Areas north of Santa Rosa and Windsor, with larger elevations to the west and further from the fog path, tend to receive less fog and less summer marine influence. Healdsburg, to the north of Windsor, is less foggy and much warmer, with summer highs typically in the higher 80s to about . Sonoma and the Sonoma Valley, east of Petaluma, are similar, with highs typically in the very high 70s F to . This is in part due to the presence of the Sonoma Mountains between Petaluma and Sonoma. Cloverdale, far to the north and outside of the Santa Rosa Plain, is significantly hotter than any other city in the county, with rare evening-morning fog and highs often in the 90s, reaching much more frequently than the other cities. Notably, however, the temperature differences among the different areas of the county are greatest for the highs during mid-day, with the diurnal lows much more even throughout the entire county. The lows are closely tied to the evening-morning cooling marine influence, in addition to elevation, bringing similarly cool temperatures to much of region.


title: Sonoma County, California

text: These weather patterns contribute to high diurnal temperature fluctuations in much of the county. In summer, daily lows and highs are typically 30–40 °F apart inland, with highs for Petaluma, Cotati, Rohnert Park, Santa Rosa, Windsor, and Sebastopol typically being in the very low 80s F and lows at or near . Healdsburg and the City of Sonoma, with similar lows, have even greater diurnal fluctuations due to their significantly warmer highs. On the other hand, the coast, with strong marine influence, tends to have low diurnal temperature fluctuation, with summer highs much cooler than the inland towns, typically 65–75 °F, yet lows in the high 40s to low 50s F, fairly comparable to most inland towns.


title: Sonoma County, California

text: These microclimates are evident during the rainy seasons as well, with great variation in the amount of rainfall throughout the county. Generally, all of Sonoma County receives a fair amount of rain, with much of the county receiving between about , comparable to areas such as Sonoma and Petaluma, and roughly normal for Santa Rosa. However, certain areas, particularly in the north-west portion of the county around the Russian River, receive significantly more rainfall. The Guerneville area, for example, typically receives about of rain a year, with annual rain occasionally going as high as . Nearby Cazadero typically receives about of rain a year, many times has reached over a year, and sometimes over of rain in a year. The Cazadero region is the second wettest place in California after Gasquet.


title: Sonoma County, California

text: Snow is exceedingly rare in Sonoma County, except in the higher elevations on and around the Mayacamas Mountains, particularly Mount Saint Helena, and Cobb Mountain, whose peak is in Lake County.


title: Sonoma County, California

text: Sonoma County is bounded on the west by the Pacific Ocean, and has of coastline. The major coastal hydrographic features are Bodega Bay, the mouth of the Russian River, and the mouth of the Gualala River, at the border with Mendocino County. All of the county's beaches were listed as among the cleanest in the state in 2010.


title: Sonoma County, California

text: Six of the county's nine cities, from Healdsburg south through Santa Rosa to Rohnert Park and Cotati, are in the Santa Rosa Plain. The northern Plain drains directly to the Russian River, or to a tributary; the southern Plain drains to the Russian River via the Laguna de Santa Rosa.


title: Sonoma County, California

text: Much of central and northern Sonoma County is in the watershed of the Russian River and its tributaries. The river rises in the coastal mountains of Mendocino County, north of the city of Ukiah, and flows into Lake Mendocino, a major flood control reservoir. The river flows south from the lake through Mendocino to Sonoma County, paralleled by Highway 101. It turns west at Healdsburg, receiving water from Lake Sonoma via Dry Creek, and empties into the Pacific Ocean at Jenner.


title: Sonoma County, California

text: The Laguna de Santa Rosa is the largest tributary of the Russian River. It is long, running north from Cotati to the Russian River near Forestville. Its flood plain is more than . It drains a watershed, including most of the Santa Rosa Plain.


title: Sonoma County, California

text: The Laguna de Santa Rosa is Sonoma County's richest area of wildlife habitat, and the most biologically diverse region of Sonoma County (itself the second-most biologically diverse county in California)... It is a unique ecological system covering more than and a mosaic of creeks, open water, perennial marshes, seasonal wetlands, riparian forests, oak woodlands, and grasslands... As the receiving water of a watershed where most of the county's human population lives, it is a landscape feature of critical importance to Sonoma County's water quality, flood control, and biodiversity.


title: Sonoma County, California

text: The Laguna's largest tributary is Santa Rosa Creek, which runs through Santa Rosa. Its major tributaries are Brush Creek, Mark West Creek, Matanzas Creek, Spring Creek, and Piner Creek. Santa Rosa Creek was shown to be polluted in Sonoma county first flush results.


title: Sonoma County, California

text: The boundary with Marin County runs from the mouth of the Estero Americano at Bodega Bay, up Americano Creek, then overland to San Antonio Creek and down the Petaluma River to its mouth at the northwest corner of San Pablo Bay, which adjoins San Francisco Bay. The southern edge of Sonoma County comprises the northern shore of San Pablo Bay between the Marin County border at the Petaluma River and the border with Solano County at Sonoma Creek. Sonoma County has no incorporated communities directly on the shore of San Pablo Bay. At the present, there is only a private marina with related facilities called Port Sonoma near the mouth of the Petaluma River. However, the Petaluma River, which flows into San Pablo Bay, is navigable up to the city of Petaluma.


title: Sonoma County, California

text: The Petaluma River, Tolay Creek, and Sonoma Creek enter the bay at the county's southernmost tip. The intertidal zone where they join the bay is the vast Napa Sonoma Marsh.


title: Sonoma County, California

text: Americano Creek, the Petaluma River, Tolay Creek, and Sonoma Creek are the principal streams draining the southern portion of the county. The Sonoma Valley is drained by Sonoma Creek, whose major tributaries are Yulupa Creek, Graham Creek, Calabazas Creek, Schell Creek, and Carriger Creek; Arroyo Seco Creek is tributary to Schell Creek. Other creeks include Foss, Felta, and Mill.


title: Sonoma County, California

text: Lakes and reservoirs in the county include Lake Sonoma, Tolay Lake, Lake Ilsanjo, Santa Rosa Creek Reservoir, Lake Ralphine, and Fountaingrove Lake.


title: Sonoma County, California

text: Like underwater parks, these marine protected areas help conserve ocean wildlife and marine ecosystems.


title: Sonoma County, California

text: A number of endangered plants and animals are found in Sonoma County, including the California clapper rail ("Rallus longirostris obsoletus"), salt marsh harvest mouse ("Reithrodontomys raviventris"), northern red-legged frog ("Rana aurora"), Sacramento splittail ("Pogonichthys macrolepidotus"), California freshwater shrimp ("Syncaris pacifica"), showy Indian clover ("Trifolium amoenum"), and Hickman's potentilla ("Potentilla hickmanii").


title: Sonoma County, California

text: Species of special local concern include the California tiger salamander ("Ambystoma californiense") and some endangered plants, including Burke's goldfields ("Lasthenia burkei"), Sebastopol meadowfoam ("Limnanthes vinculans"), and Sonoma sunshine or Baker's stickyseed ("Blennosperma bakeri").


title: Sonoma County, California

text: Endangered species that are endemic to Sonoma County include Sebastopol meadowfoam, Sonoma sunshine, and Pitkin Marsh lily ("Lilium pardalinum" subsp. "pitkinense").


title: Sonoma County, California

text: "The primary focus of the FEP is to enhance habitat for three salmonids: Steelhead, Chinook salmon, and Coho salmon. These three species are listed as threatened under the U.S. Endangered Species Act. The California Department of Fish and Game considers the Coho salmon endangered."


title: Sonoma County, California

text: U.S. Route 101 is the westernmost Federal highway in the U.S.A. Running north/south through the states of California, Oregon, and Washington, it generally parallels the coastline from the Mexico–US border to the Canada–US border. Highway 101 links seven of the county's nine incorporated cities: Cloverdale, Healdsburg, Windsor, Santa Rosa, Rohnert Park, Cotati, and Petaluma. It is a freeway for its entire length within the county.


title: Sonoma County, California

text: The four-lane sections of the highway have been heavily congested during peak commute hours for many years and work is being done to widen part of the highway to six lanes. The segment from north of Petaluma (at Old Redwood Highway/Petaluma Boulevard North exit) to Windsor has been fully widened, as has the segment from the Petaluma River bridge to the Marin County border. The two new inner lanes are designated for vehicles with two or more occupants during commute hours. Work is being done around Petaluma to finish the widening within Sonoma County; the widening also involves upgrading the highway to full freeway standards.


title: Sonoma County, California

text: Within Sonoma County, Highway 1 follows the coastline from the Mendocino County border, at the mouth of the Gualala River, to the Marin County border, at the Estero Americano (Americano Creek), southeast of Bodega Bay.


title: Sonoma County, California

text: Highway 12 runs eastward from its intersection with Highway 116 in Sebastopol to Santa Rosa. There it turns south through the Valley of the Moon to Sonoma, then east into Napa County. The four-lane freeway section within Santa Rosa, between Fulton Road and Farmers Lane, is called the Luther Burbank Memorial Highway. That section, especially where it crosses Highway 101, is severely congested during peak commute hours.


title: Sonoma County, California

text: The two-lane Bodega Highway runs west from the intersection of Highways 12 and 116 in Sebastopol, through the coastal hills to its intersection with Highway 1, east of Bodega Bay. East of Santa Rosa, Highway 12 is also called Sonoma Highway; and east of the City of Sonoma, Carneros Highway.


title: Sonoma County, California

text: Highway 37 connects Highway 101 at Novato, in Marin County, with Interstate 80 in Vallejo, in Solano County, at the top of San Pablo Bay. Within Sonoma County, it is also called Sears Point Road.


title: Sonoma County, California

text: Highway 116 is a winding, two-lane rural route that runs from Jenner, at the mouth of the Russian River on the coast, southeast to Arnold Drive near Sonoma. It is also called Guerneville Highway, between Guerneville and Forestville; Gravenstein Highway North, between Forestville and Sebastopol; and Gravenstein Highway South, between Sebastopol and Stony Point Road, west of Rohnert Park. East of Petaluma it is called Lakeville Highway, then Stage Gulch Road.


title: Sonoma County, California

text: Highway 121 is a two-lane rural route running from Highway 37 near Sears Point Raceway to Highway 128 in Lake Berryessa, in Napa County.


title: Sonoma County, California

text: The northernmost section of Highway 128 is a two-lane, rural route running southeast from Highway 101 at Geyserville, north of Healdsburg, through the Alexander Valley and into Napa County.


title: Sonoma County, California

text: The Charles M. Schulz - Sonoma County Airport is at 2290 Airport Boulevard, west of Highway 101, between Santa Rosa and Windsor. Its main runway is long and wide, and can accommodate planes up to maximum gross takeoff weight. It offers fuel, major maintenance, hangar space, and tie-downs for local and transient aircraft. Alaska Airlines, American Airlines, and United Airlines offer regular daily commercial flights.


title: Sonoma County, California

text: In 1864, the Petaluma and Haystack Railroad connected the city of Petaluma to a ferry landing at the head of navigation on the Petaluma River.


title: Sonoma County, California

text: In 1870, the San Francisco and North Pacific Railroad (SF&NP) connected the City of Santa Rosa to ferry connections at Donahue landing on the Petaluma River. Rail service was extended north to Healdsburg in 1871 and Cloverdale in 1872. In 1884 the railroad was extended south to an alternate ferry connection in Tiburon. This rail line serves as the primary route of Sonoma–Marin Area Rail Transit.


title: Sonoma County, California

text: The 3-foot-gauge North Pacific Coast Railroad extended northward in 1876 from a ferry connection at Sausalito through Valley Ford, Freestone, and Occidental to Monte Rio on the lower Russian River. Service was extended to Duncans Mills in 1877 and Cazadero in 1885. The standard gauge Fulton and Guerneville Railroad left the SF&NP at Fulton to reach Korbel in 1876 and Guerneville in 1877. Standard-gauge rails were extended down-river to Duncan Mills in 1909 after the Northwestern Pacific Railroad merger, and narrow-gauge service was discontinued in 1930. The standard-gauge route became River Road after tracks were removed in 1935.


title: Sonoma County, California

text: The unique Sonoma Valley Prismoidal Railway linked the city of Sonoma to bay ferries in 1876 and was replaced in 1879 by the -gauge Sonoma Valley Railroad to a ferry landing near the mouth of the Petaluma River. Service was extended from Sonoma to Glen Ellen in 1882. The southern end of the line was extended westward in 1888 to a connection with the SF&NP at Ignacio. This line was converted to standard-gauge in 1890 and remains (in 2018) as Sonoma County's connection to the national rail system at Schellville.


title: Sonoma County, California

text: Southern Pacific subsidiary Santa Rosa and Carquinez Railroad extended eastward in 1888 to link Santa Rosa with the national rail system. The portion between Sonoma and Santa Rosa was dismantled in the 1940s after interchange shifted to the former Sonoma Valley line.


title: Sonoma County, California

text: A SF&NP branch line from Santa Rosa brought rail service to Sebastopol in 1890. The Petaluma and Santa Rosa Railroad extended interurban service north from a ferry connection in Petaluma to reach Sebastopol in 1904, Santa Rosa in 1905, and Forestville in 1906. Portions of this line were converted to the Joe Rodota Trail after tracks were removed in the 1980s.


title: Sonoma County, California

text: The Sonoma–Marin Area Rail Transit commuter rail line inaugurated passenger service on August 25, 2017, utilizing the Northwestern Pacific Railroad right-of-way from Sonoma County Airport station to Larkspur Landing in Marin. The system is planned to extend to Cloverdale Depot.


title: Sonoma County, California

text: The following table includes the number of incidents reported and the rate per 1,000 persons for each type of offense in the year of 2009.


title: Sonoma County, California

text: "Note: the US Census treats Hispanic/Latino as an ethnic category. This table excludes Latinos from the racial categories and assigns them to a separate category. Hispanics/Latinos can be of any race."


title: Sonoma County, California

text: The 2010 United States census reported that Sonoma County had a population of 483,878. The racial makeup of Sonoma County was 371,412 (76.8%) White, 7,610 (1.6%) African American, 6,489 (1.3%) Native American, 18,341 (3.8%) Asian, 1,558 (0.3%) Pacific Islander, 56,966 (11.8%) from other races, and 21,502 (4.4%) from two or more races. Hispanic or Latino of any race were 120,430 persons (24.9%).


title: Sonoma County, California

text: At the 2000 United States census, there were 458,614 people, 172,403 households, and 112,406 families in Sonoma County. The population density was 291/sq mi (112/km). There were 183,153 housing units at an average density of 116/sq mi (45/km).


title: Sonoma County, California

text: Of the 172,403 households, 50.3% were married couples living together, 34.8% were non-families, and 10.4% had a female householder with no husband present. 31.9% had children under the age of 18 living with them, 25.7% were individuals, and 10.0% were 65 years of age or older living alone. The average household size was 2.60, and the average family size was 3.12.


title: Sonoma County, California

text: The median age was 38 years. 24.5% were under 18, 8.8% from 18 to 24, 29.2% from 25 to 44, 24.9% from 45 to 64, and 12.6% were 65 years of age or older. For every 100 females there were 97 males. For every 100 females age 18 and over, there were 94 males.


title: Sonoma County, California

text: The median household income was $53,076, and the median family income was $61,921. Males had a median income of $42,035, females $32,022. The per capita income for the county was $25,724. About 4.7% of families and 8.1% of the population were below the poverty line, including 8.4% of those under age 18 and 5.7% of those age 65 or over.


title: Sonoma County, California

text: The United States Office of Management and Budget has designated Sonoma County as the Santa Rosa-Petaluma, CA Metropolitan Statistical Area. The United States Census Bureau ranked the Santa Rosa-Petaluma, CA Metropolitan Statistical Area as the 105th most populous metropolitan statistical area of the United States as of July 1, 2012.


title: Sonoma County, California

text: The Office of Management and Budget has further designated the Santa Rosa-Petaluma, CA Metropolitan Statistical Area as a component of the more extensive San Jose-San Francisco-Oakland, CA Combined Statistical Area, the 5th most populous combined statistical area and primary statistical area of the United States as of July 1, 2012.


title: Sonoma County, California

text: Sonoma County's governing board and legislative body is the five-member Sonoma County Board of Supervisors. Supervisors are elected by district at the Consolidated Primary Election, and serve for four years. The Supervisors also sit as directors of several local jurisdictions, such as Sonoma Water, and the Agricultural Preservation & Open Space District.


title: Sonoma County, California

text: The County Administrator is the county's chief executive officer, reporting to the Board of Supervisors. The administrator manages the county's departments, such as the regional parks department.


title: Sonoma County, California

text: On December 15, 2009, the Board announced the appointment of Veronica Ferguson to be the first woman County Administrator. She assumed office on February 1, 2010.


title: Sonoma County, California

text: On May 1, 2014, the county launched a public utility named Sonoma Clean Power. This utility was created under the guidelines of Community Choice Aggregation.


title: Sonoma County, California

text: Sonoma County is split between California's 2nd and 5th congressional districts, represented by and , respectively.


title: Sonoma County, California

text: In the California State Assembly, Sonoma County is split between the 2nd, 4th, and 10th districts, which are held by , , and , respectively. In the California State Senate, the county is split between , and .


title: Sonoma County, California

text: The Sonoma County Sheriff's Department is the law enforcement agency for the unincorporated area of the county. It also contracts to provide the police forces of the City of Sonoma and the Town of Windsor. The department has more than 1,000 employees, including more than 275 Deputy Sheriffs, in four bureaus. More than 300 Correctional Officers and staff work in two jail facilities; Main Area Detention Facility and the North County Detention Facility, with a total daily population of nearly 1,200 inmates. Police shootings in 2007 led to calls for an independent civilian police review board; which was established in 2015.


title: Sonoma County, California

text: Agriculture has long played a critical role in Sonoma County's economy, and it makes up a major component of California's Wine Country. Just over 2% of the population works in agriculture, nearly twice the state average. Similar to other regions of the state, the county's mild climate and fertile soil allow for the cultivation of a wide variety of crops, ornamentals, and for the raising of livestock. Beyond the production of grapes, the county's agricultural heartland is primarily located in the west and southwest, and near the cities of Petaluma and Sebastopol. The renowned horticulturalist Luther Burbank, who created hundreds of new varieties of plants and crops, lived and worked in Sonoma County for much of his life.


title: Sonoma County, California

text: Similar to other Bay Area communities, Sonoma County is also home to several prominent players in the Tech Industry, such as Keysight (formerly a part of Agilent Technologies) in Santa Rosa. Although primarily known for wine, Sonoma County is home to several notable brewing and beverage companies including: Bear Republic Brewing Company, Guayakí, Lagunitas Brewing Company, and the Russian River Brewing Company. The clothing manufacturer Marmot is based in Rohnert Park.


title: Sonoma County, California

text: For most of the 20th century, Sonoma County was a Republican stronghold in presidential elections. From 1880 until 1988, the only Democrats to carry Sonoma were Winfield Scott Hancock in 1880, Grover Cleveland in 1888 and 1892, Woodrow Wilson in 1912, Franklin D. Roosevelt in 1932 and 1936, and Lyndon B. Johnson in 1964. Like the rest of the Bay Area, it has since become a Democratic stronghold.


title: Sonoma County, California

text: The last Republican to win a majority in the county was Ronald Reagan in 1984, and the last Republican to represent a significant part of the county in Congress was Representative Donald H. Clausen, who left office in January 1983.


title: Sonoma County, California

text: On November 4, 2008, Sonoma County voted 66.4% against Proposition 8 which amended the California Constitution to ban same-sex marriages.


title: Sonoma County, California

text: According to the California Secretary of State, as of February 2019, there are 277,665 registered voters in Sonoma County. Of those, 143,054 (51.5%) are registered Democratic, 49,386 (17.8%) are registered Republican, and 70,244 (25.3%) declined to state a political party. Every city, town, and the unincorporated areas of Sonoma County have more registered Democrats than Republicans.


title: Sonoma County, California

text: The educational system of Sonoma County is similar to that of other counties in California, with a large number of independent school districts.


title: Sonoma County, California

text: The Sonoma County Library system offers a central library in downtown Santa Rosa plus 10 branch libraries and two rural stations. More than half of Sonoma County's residents have library cards and borrow more than 2.5 million items per year. The library's website and catalog]receive over 200,000 visits annually. Staff answer nearly half a million reference questions annually for individuals, businesses and government agencies. During a typical school year over 750 classes, more than half the county total, either visit a library or are visited by a children's librarian. The library operates an adult literacy program, and computer terminals are made available for free Internet access.


title: Sonoma County, California

text: At the time of its formation, the county comprised four civil townships. It was restructured several times, and by 1880 was made up of 14 townships:


title: Sonoma County, California

text: Due to the varied scenery in Sonoma County and proximity to the city of San Francisco, a large number of movies have been filmed using venues within the county. Some of the earliest U.S. filmmaking occurred in Sonoma County, including "Salomy Jane" (1914) and one of Broncho Billy Anderson's 1915 Westerns.


title: Sonoma County, California

text: Other films include the 1947 film "The Farmer's Daughter" (starring Joseph Cotten and Loretta Young) as well as two Alfred Hitchcock films, "Shadow of a Doubt" of 1943, filmed and set in Santa Rosa, and "The Birds" of 1963, filmed largely in Bodega Bay and Bodega. "American Graffiti" was filmed largely in Petaluma.


title: Sonoma County, California

text: "Bliss", the default computer wallpaper of Microsoft's Windows XP operating system, is a photograph of a green hill and blue sky with clouds in Sonoma County. Taken in 1996 by Charles O'Rear, it is the most viewed photo in the world.


title: Pitch Perfect (franchise)

text: Pitch Perfect is an American musical comedy media franchise created by Kay Cannon, loosely based on the non-fiction book "Pitch Perfect: The Quest for Collegiate a Cappella Glory" by Mickey Rapkin. Jason Moore directed the first film, Elizabeth Banks directed the second, and Trish Sie directed the third. Paul Brooks, Max Handelman, and Banks produced the films. The film series features an ensemble cast, including Anna Kendrick, Rebel Wilson, Anna Camp, Brittany Snow, Skylar Astin, Adam DeVine, Ben Platt, Alexis Knapp, Hana Mae Lee, Ester Dean, Hailee Steinfeld, Chrissie Fit, John Michael Higgins, and Banks; while the television series stars DeVine. The series is distributed by Universal Pictures.


title: Pitch Perfect (franchise)

text: The first film was a sleeper hit. It received positive reviews and was financially successful, grossing over $115 million against a $17 million budget. A sequel was made and released in 2015, to greater financial success, grossing over $287 million against a $29 million budget. The series has since gained a cult following, grossing $565 million worldwide, and the second film is the highest grossing musical comedy film of all time, beating "School of Rock"s record.


title: Pitch Perfect (franchise)

text: Beca Mitchell (Anna Kendrick), a rebellious and unwilling freshman at Barden University, joins a disgraced all-female a cappella group, The Barden Bellas, directed by uptight senior student Aubrey Posen (Anna Camp). The film follows the unlikely new formation of The Barden Bellas which has to struggle to win at the collegiate a cappella competition.


title: Pitch Perfect (franchise)

text: Set three years after the first film, The Bellas are the leading a cappella group with Beca as the leader until Fat Amy (Rebel Wilson) accidentally rips her pants during a performance, effectively suspending the group. They could be reinstated if they win an international a cappella competition, where no American team has ever won. With new members, tough competition, and doubts everywhere from almost everyone, they try to regain their glory, only to find it harder than it looks with their focus being split up and losing their harmony along the way.


title: Pitch Perfect (franchise)

text: Two years after the second film, the now graduated Bellas find themselves split apart and struggling with their real life jobs. However, after a brief reunion, Aubrey comes up with an idea to perform for the USO tour, which will reunite them for a series of shows. The Bellas go overseas for the USO where they find out that they are actually competing with other bands on tour to be the opening act for DJ Khaled.


title: Pitch Perfect (franchise)

text: In September 2021, it was announced that a television series based on the film series had been ordered at Peacock for a 2022 release, with Adam DeVine reprising his role as Bumper Allen. It will be written by Megan Amram, who will also serve as executive producer and showrunner and Elizabeth Banks serve as executive producer. In March 2022, Sarah Hyland, Jameela Jamil and Lera Abova were announced to be joining the cast alongside Flula Borg, who is reprising his role as Piëter Krämer from the second film.


title: Pitch Perfect (franchise)

text: The film is based on Mickey Rapkin's non-fiction book "Pitch Perfect: The Quest for Collegiate a Cappella Glory". Rapkin, senior editor at "GQ" magazine, spent a season covering competitive collegiate a cappella. He followed the Tufts University Beelzebubs, the University of Oregon Divisi (the loose inspiration for the Bellas), and the University of Virginia Hullabahoos, who have a cameo in the film. Rapkin's book mainly covers the singing, groupies, partying and rivalries. Two members of the a cappella community, Deke Sharon, who founded the International Championship of College A Cappella, and Ed Boyer, both in Rapkin's book, were brought on board to arrange songs, produce vocals and act as on-site music directors, where they ran a month-long "a cappella boot camp". The film was shot throughout campus and inside buildings at Louisiana State University in Baton Rouge, Louisiana. Elizabeth Banks is a co-producer and a co-star in the film.


title: Pitch Perfect (franchise)

text: The casting department included Justin Coulter, Rich Delia, Allison Estrin, and Michael Roth. One of the producers, Paul Brooks, stated "First and foremost, we were looking for actors who had comedic instincts and thought we'd get lucky with terrific actors who happened to be funny and can actually dance and maybe sing. It turns out we did get lucky with our cast!" According to producer Elizabeth Banks, "The character Beca required someone who was grounded, who has a strong point of view on the world, who is funny and empathetic and someone who we can all relate to and root for." Of Kendrick she said, "Anna is all those things, and there was no other choice." Fellow producer Brooks said "I saw Anna in "Up in the Air" and thought it was the most exquisite, elegant, balanced, sublime performance. Anna was our first choice for the role of Beca."


title: Pitch Perfect (franchise)

text: When casting the character of Jesse, Max Handelman said "We were looking for a young John Cusack-type guy. We needed to find someone who was kind of awkward but not a geek, but not so cool that you're not rooting for him." Skylar Astin was chosen for the role. Of Astin's audition, Banks said the chemistry between Skylar and Anna when they read together prior to shooting was "clear and they were able to riff off each other."


title: Pitch Perfect (franchise)

text: Rebel Wilson was recognized for her performance in the comedy film "Bridesmaids" upon auditioning for the role of Fat Amy, which she won instantly. Moore recalled Wilson singing Lady Gaga's "The Edge of Glory" while beating "on her chest with her fists." He said, "I didn't even hear the end of the song because I was laughing so hard. There's this beautiful openness to the way Rebel approaches everything, and that's what works great for the character. She's fearless." Adam DeVine was personally chosen by Banks and Handelman for the role of Bumper after they saw him on the television series "Workaholics". Banks said that she and her husband are "big "Workaholics" fans," and after watching one night during the film's casting, they saw DeVine and "immediately thought" he would be a good choice for Bumper. He initially declined because he was not a singer. DeVine eventually surprised Banks and Handelman with his vocal skills. Anna Camp was chosen for the role of Aubrey. Producer Max Handelman said, "Elizabeth and I were huge fans of Anna's from "True Blood". Aubrey is set up as the antagonist for Beca, and Beca's already a bit hard-edged, so it was so important to find an actress who could play Aubrey as someone who could marshal the crazy but also was sympathetic." Kelley Jakle was brought in as a "ringer" due to her past experience as a two-time ICCA champion with the SoCal VoCals and had also appeared on two seasons of The Sing-Off.


title: RNA interference

text: RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including "co-suppression", "post-transcriptional gene silencing" (PTGS), and "quelling". The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm "Caenorhabditis elegans", which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.


title: RNA interference

text: Two types of small ribonucleic acid (RNA) molecules, microRNA (miRNA) and small interfering RNA (siRNA), are central to components to the RNAi pathway. Once mRNA is degraded, post-transcriptional silencing occurs as protein translation is prevented. Transcription can be inhibited via the pre-transcriptional silencing mechanism of RNAi, through which an enzyme complex catalyzes DNA methylation at genomic positions complementary to complexed siRNA or miRNA. RNAi has an important role in defending cells against parasitic nucleotide sequences (e.g., viruses or transposons) and also influences development of organisms.


title: RNA interference

text: The RNAi pathway is a naturally occurring process found in many eukaryotes and animal cells. It is initiated by the enzyme Dicer, which cleaves long double-stranded RNA (dsRNA) molecules into short double-stranded fragments of approximately 21 to 23 nucleotide siRNAs. Each siRNA is unwound into two single-stranded RNAs (ssRNAs), the passenger (sense) strand and the guide (antisense) strand. The passenger strand is then cleaved by the protein Argonaute 2 (Ago2). The passenger strand is degraded and the guide strand is incorporated into the RNA-induced silencing complex (RISC). The RISC assembly then binds and degrades the target mRNA. Specifically, this is accomplished when the guide strand pairs with a complementary sequence in a mRNA molecule and induces cleavage by Ago2, a catalytic component of the RISC. In some organisms, this process spreads systemically, despite the initially limited molar concentrations of siRNA.


title: RNA interference

text: RNAi is a valuable research tool, both in cell culture and in living organisms, because synthetic dsRNA introduced into cells can selectively and robustly induce suppression of specific genes of interest. RNAi may be used for large-scale screens that systematically shut down each gene (and the subsequent proteins it codes for) in the cell, which can help to identify the components necessary for a particular cellular process or an event such as cell division. The pathway is also used as a practical tool for food, medicine and insecticides.


title: RNA interference

text: RNAi is an RNA-dependent gene silencing process that is controlled by RISC and is initiated by short double-stranded RNA molecules in a cell's cytoplasm, where they interact with the catalytic RISC component argonaute. When the dsRNA is exogenous (coming from infection by a virus with an RNA genome or laboratory manipulations), the RNA is imported directly into the cytoplasm and cleaved to short fragments by Dicer. The initiating dsRNA can also be endogenous (originating in the cell), as in pre-microRNAs expressed from RNA-coding genes in the genome. The primary transcripts from such genes are first processed to form the characteristic stem-loop structure of pre-miRNA in the nucleus, then exported to the cytoplasm. Thus, the two dsRNA pathways, exogenous and endogenous, converge at the RISC.


title: RNA interference

text: Exogenous dsRNA initiates RNAi by activating the ribonuclease protein Dicer, which binds and cleaves dsRNAs in plants, or short hairpin RNAs (shRNAs) in humans, to produce double-stranded fragments of 20–25 base pairs with a 2-nucleotide overhang at the 3′ end. Bioinformatics studies on the genomes of multiple organisms suggest this length maximizes target-gene specificity and minimizes non-specific effects. These short double-stranded fragments are called siRNAs. These siRNAs are then separated into single strands and integrated into an active RISC, by RISC-Loading Complex (RLC). RLC includes Dicer-2 and R2D2, and is crucial to unite Ago2 and RISC. TATA-binding protein-associated factor 11 (TAF11) assembles the RLC by facilitating Dcr-2-R2D2 tetramerization, which increases the binding affinity to siRNA by 10-fold. Association with TAF11 would convert the R2-D2-Initiator (RDI) complex into the RLC. R2D2 carries tandem double-stranded RNA-binding domains to recognize the thermodynamically stable terminus of siRNA duplexes, whereas Dicer-2 the other less stable extremity. Loading is asymmetric: the MID domain of Ago2 recognizes the thermodynamically stable end of the siRNA. Therefore, the "passenger" (sense) strand whose 5′ end is discarded by MID is ejected, while the saved "guide" (antisense) strand cooperates with AGO to form the RISC.


title: RNA interference

text: After integration into the RISC, siRNAs base-pair to their target mRNA and cleave it, thereby preventing it from being used as a translation template. Differently from siRNA, a miRNA-loaded RISC complex scans cytoplasmic mRNAs for potential complementarity. Instead of destructive cleavage (by Ago2), miRNAs rather target the 3′ untranslated region (UTR) regions of mRNAs where they typically bind with imperfect complementarity, thus blocking the access of ribosomes for translation.


title: RNA interference

text: Exogenous dsRNA is detected and bound by an effector protein, known as RDE-4 in "C. elegans" and R2D2 in "Drosophila", that stimulates dicer activity. The mechanism producing this length specificity is unknown and this protein only binds long dsRNAs.


title: RNA interference

text: In "C. elegans" this initiation response is amplified through the synthesis of a population of 'secondary' siRNAs during which the dicer-produced initiating or 'primary' siRNAs are used as templates. These 'secondary' siRNAs are structurally distinct from dicer-produced siRNAs and appear to be produced by an RNA-dependent RNA polymerase (RdRP).


title: RNA interference

text: MicroRNAs (miRNAs) are genomically encoded non-coding RNAs that help regulate gene expression, particularly during development. The phenomenon of RNAi, broadly defined, includes the endogenously induced gene silencing effects of miRNAs as well as silencing triggered by foreign dsRNA. Mature miRNAs are structurally similar to siRNAs produced from exogenous dsRNA, but before reaching maturity, miRNAs must first undergo extensive post-transcriptional modification. A miRNA is expressed from a much longer RNA-coding gene as a primary transcript known as a "pri-miRNA" which is processed, in the cell nucleus, to a 70-nucleotide stem-loop structure called a "pre-miRNA" by the microprocessor complex. This complex consists of an RNase III enzyme called Drosha and a dsRNA-binding protein DGCR8. The dsRNA portion of this pre-miRNA is bound and cleaved by Dicer to produce the mature miRNA molecule that can be integrated into the RISC complex; thus, miRNA and siRNA share the same downstream cellular machinery. First, viral encoded miRNA was described in Epstein–Barr virus (EBV). Thereafter, an increasing number of microRNAs have been described in viruses. VIRmiRNA is a comprehensive catalogue covering viral microRNA, their targets and anti-viral miRNAs (see also VIRmiRNA resource: http://crdd.osdd.net/servers/virmirna/).


title: RNA interference

text: siRNAs derived from long dsRNA precursors differ from miRNAs in that miRNAs, especially those in animals, typically have incomplete base pairing to a target and inhibit the translation of many different mRNAs with similar sequences. In contrast, siRNAs typically base-pair perfectly and induce mRNA cleavage only in a single, specific target. In "Drosophila" and "C. elegans", miRNA and siRNA are processed by distinct argonaute proteins and dicer enzymes.


title: RNA interference

text: Three prime untranslated regions (3′UTRs) of mRNAs often contain regulatory sequences that post-transcriptionally cause RNAi. Such 3′-UTRs often contain both binding sites for miRNAs as well as for regulatory proteins. By binding to specific sites within the 3′-UTR, miRNAs can decrease gene expression of various mRNAs by either inhibiting translation or directly causing degradation of the transcript. The 3′-UTR also may have silencer regions that bind repressor proteins that inhibit the expression of a mRNA.


title: RNA interference

text: The 3′-UTR often contains microRNA response elements (MREs). MREs are sequences to which miRNAs bind. These are prevalent motifs within 3′-UTRs. Among all regulatory motifs within the 3′-UTRs (e.g. including silencer regions), MREs make up about half of the motifs.


title: RNA interference

text: As of 2014, the miRBase web site, an archive of miRNA sequences and annotations, listed 28,645 entries in 233 biologic species. Of these, 1,881 miRNAs were in annotated human miRNA loci. miRNAs were predicted to have an average of about four hundred target mRNAs (affecting expression of several hundred genes). Friedman et al. estimate that >45,000 miRNA target sites within human mRNA 3′UTRs are conserved above background levels, and >60% of human protein-coding genes have been under selective pressure to maintain pairing to miRNAs.


title: RNA interference

text: Direct experiments show that a single miRNA can reduce the stability of hundreds of unique mRNAs. Other experiments show that a single miRNA may repress the production of hundreds of proteins, but that this repression often is relatively mild (less than 2-fold).


title: RNA interference

text: The effects of miRNA dysregulation of gene expression seem to be important in cancer. For instance, in gastrointestinal cancers, nine miRNAs have been identified as epigenetically altered and effective in down regulating DNA repair enzymes.


title: RNA interference

text: The effects of miRNA dysregulation of gene expression also seem to be important in neuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depression, Parkinson's disease, Alzheimer's disease and autism spectrum disorders.


title: RNA interference

text: Exogenous dsRNA is detected and bound by an effector protein, known as RDE-4 in "C. elegans" and R2D2 in "Drosophila", that stimulates dicer activity. This protein only binds long dsRNAs, but the mechanism producing this length specificity is unknown. This RNA-binding protein then facilitates the transfer of cleaved siRNAs to the RISC complex.


title: RNA interference

text: The active components of an RNA-induced silencing complex (RISC) are endonucleases called argonaute proteins, which cleave the target mRNA strand complementary to their bound siRNA. As the fragments produced by dicer are double-stranded, they could each in theory produce a functional siRNA. However, only one of the two strands, which is known as the "guide strand", binds the argonaute protein and directs gene silencing. The other "anti-guide strand" or "passenger strand" is degraded during RISC activation. Although it was first believed that an ATP-dependent helicase separated these two strands, the process proved to be ATP-independent and performed directly by the protein components of RISC. However, an "in vitro" kinetic analysis of RNAi in the presence and absence of ATP showed that ATP may be required to unwind and remove the cleaved mRNA strand from the RISC complex after catalysis. The guide strand tends to be the one whose 5′ end is less stably paired to its complement, but strand selection is unaffected by the direction in which dicer cleaves the dsRNA before RISC incorporation. Instead, the R2D2 protein may serve as the differentiating factor by binding the more-stable 5′ end of the passenger strand.


title: RNA interference

text: The structural basis for binding of RNA to the argonaute protein was examined by X-ray crystallography of the binding domain of an RNA-bound argonaute protein. Here, the phosphorylated 5′ end of the RNA strand enters a conserved basic surface pocket and makes contacts through a divalent cation (an atom with two positive charges) such as magnesium and by aromatic stacking (a process that allows more than one atom to share an electron by passing it back and forth) between the 5′ nucleotide in the siRNA and a conserved tyrosine residue. This site is thought to form a nucleation site for the binding of the siRNA to its mRNA target. Analysis of the inhibitory effect of mismatches in either the 5’ or 3’ end of the guide strand has demonstrated that the 5’ end of the guide strand is likely responsible for matching and binding the target mRNA, while the 3’ end is responsible for physically arranging target mRNA into a cleavage-favorable RISC region.


title: RNA interference

text: It is not understood how the activated RISC complex locates complementary mRNAs within the cell. Although the cleavage process has been proposed to be linked to translation, translation of the mRNA target is not essential for RNAi-mediated degradation. Indeed, RNAi may be more effective against mRNA targets that are not translated. Argonaute proteins are localized to specific regions in the cytoplasm called P-bodies (also cytoplasmic bodies or GW bodies), which are regions with high rates of mRNA decay; miRNA activity is also clustered in P-bodies. Disruption of P-bodies decreases the efficiency of RNAi, suggesting that they are a critical site in the RNAi process.


title: RNA interference

text: Components of the RNAi pathway are used in many eukaryotes in the maintenance of the organization and structure of their genomes. Modification of histones and associated induction of heterochromatin formation serves to downregulate genes pre-transcriptionally; this process is referred to as RNA-induced transcriptional silencing (RITS), and is carried out by a complex of proteins called the RITS complex. In fission yeast this complex contains argonaute, a chromodomain protein Chp1, and a protein called Tas3 of unknown function. As a consequence, the induction and spread of heterochromatic regions requires the argonaute and RdRP proteins. Indeed, deletion of these genes in the fission yeast "S. pombe" disrupts histone methylation and centromere formation, causing slow or stalled anaphase during cell division. In some cases, similar processes associated with histone modification have been observed to transcriptionally upregulate genes.


title: RNA interference

text: The mechanism by which the RITS complex induces heterochromatin formation and organization is not well understood. Most studies have focused on the mating-type region in fission yeast, which may not be representative of activities in other genomic regions/organisms. In maintenance of existing heterochromatin regions, RITS forms a complex with siRNAs complementary to the local genes and stably binds local methylated histones, acting co-transcriptionally to degrade any nascent pre-mRNA transcripts that are initiated by RNA polymerase. The formation of such a heterochromatin region, though not its maintenance, is dicer-dependent, presumably because dicer is required to generate the initial complement of siRNAs that target subsequent transcripts. Heterochromatin maintenance has been suggested to function as a self-reinforcing feedback loop, as new siRNAs are formed from the occasional nascent transcripts by RdRP for incorporation into local RITS complexes. The relevance of observations from fission yeast mating-type regions and centromeres to mammals is not clear, as heterochromatin maintenance in mammalian cells may be independent of the components of the RNAi pathway.


title: RNA interference

text: The type of RNA editing that is most prevalent in higher eukaryotes converts adenosine nucleotides into inosine in dsRNAs via the enzyme adenosine deaminase (ADAR). It was originally proposed in 2000 that the RNAi and A→I RNA editing pathways might compete for a common dsRNA substrate. Some pre-miRNAs do undergo A→I RNA editing and this mechanism may regulate the processing and expression of mature miRNAs. Furthermore, at least one mammalian ADAR can sequester siRNAs from RNAi pathway components. Further support for this model comes from studies on ADAR-null "C. elegans" strains indicating that A→I RNA editing may counteract RNAi silencing of endogenous genes and transgenes.


title: RNA interference

text: Organisms vary in their ability to take up foreign dsRNA and use it in the RNAi pathway. The effects of RNAi can be both systemic and heritable in plants and "C. elegans", although not in "Drosophila" or mammals. In plants, RNAi is thought to propagate by the transfer of siRNAs between cells through plasmodesmata (channels in the cell walls that enable communication and transport). Heritability comes from methylation of promoters targeted by RNAi; the new methylation pattern is copied in each new generation of the cell. A broad general distinction between plants and animals lies in the targeting of endogenously produced miRNAs; in plants, miRNAs are usually perfectly or nearly perfectly complementary to their target genes and induce direct mRNA cleavage by RISC, while animals' miRNAs tend to be more divergent in sequence and induce translational repression. This translational effect may be produced by inhibiting the interactions of translation initiation factors with the mRNA's polyadenine tail.


title: RNA interference

text: Some eukaryotic protozoa such as "Leishmania major" and "Trypanosoma cruzi" lack the RNAi pathway entirely. Most or all of the components are also missing in some fungi, most notably the model organism "Saccharomyces cerevisiae". The presence of RNAi in other budding yeast species such as "Saccharomyces castellii" and "Candida albicans", further demonstrates that inducing two RNAi-related proteins from "S. castellii" facilitates RNAi in "S. cerevisiae". That certain ascomycetes and basidiomycetes are missing RNAi pathways indicates that proteins required for RNA silencing have been lost independently from many fungal lineages, possibly due to the evolution of a novel pathway with similar function, or to the lack of selective advantage in certain niches.


title: RNA interference

text: Gene expression in prokaryotes is influenced by an RNA-based system similar in some respects to RNAi. Here, RNA-encoding genes control mRNA abundance or translation by producing a complementary RNA that anneals to an mRNA. However these regulatory RNAs are not generally considered to be analogous to miRNAs because the dicer enzyme is not involved. It has been suggested that CRISPR interference systems in prokaryotes are analogous to eukaryotic RNAi systems, although none of the protein components are orthologous.


title: RNA interference

text: RNAi is a vital part of the immune response to viruses and other foreign genetic material, especially in plants where it may also prevent the self-propagation of transposons. Plants such as "Arabidopsis thaliana" express multiple dicer homologs that are specialized to react differently when the plant is exposed to different viruses. Even before the RNAi pathway was fully understood, it was known that induced gene silencing in plants could spread throughout the plant in a systemic effect and could be transferred from stock to scion plants via grafting. This phenomenon has since been recognized as a feature of the plant immune system which allows the entire plant to respond to a virus after an initial localized encounter. In response, many plant viruses have evolved elaborate mechanisms to suppress the RNAi response. These include viral proteins that bind short double-stranded RNA fragments with single-stranded overhang ends, such as those produced by dicer. Some plant genomes also express endogenous siRNAs in response to infection by specific types of bacteria. These effects may be part of a generalized response to pathogens that downregulates any metabolic process in the host that aids the infection process.


title: RNA interference

text: Although animals generally express fewer variants of the dicer enzyme than plants, RNAi in some animals produces an antiviral response. In both juvenile and adult "Drosophila", RNAi is important in antiviral innate immunity and is active against pathogens such as Drosophila X virus. A similar role in immunity may operate in "C. elegans", as argonaute proteins are upregulated in response to viruses and worms that overexpress components of the RNAi pathway are resistant to viral infection.


title: RNA interference

text: The role of RNAi in mammalian innate immunity is poorly understood, and relatively little data is available. However, the existence of viruses that encode genes able to suppress the RNAi response in mammalian cells may be evidence in favour of an RNAi-dependent mammalian immune response, although this hypothesis has been challenged as poorly substantiated.


title: RNA interference

text: Evidence for the existence of a functional antiviral RNAi pathway in mammalian cells has been presented.


title: RNA interference

text: Other functions for RNAi in mammalian viruses also exist, such as miRNAs expressed by the herpes virus that may act as heterochromatin organization triggers to mediate viral latency.


title: RNA interference

text: Endogenously expressed miRNAs, including both intronic and intergenic miRNAs, are most important in translational repression and in the regulation of development, especially on the timing of morphogenesis and the maintenance of undifferentiated or incompletely differentiated cell types such as stem cells. The role of endogenously expressed miRNA in downregulating gene expression was first described in "C. elegans" in 1993. In plants this function was discovered when the "JAW microRNA" of "Arabidopsis" was shown to be involved in the regulation of several genes that control plant shape. In plants, the majority of genes regulated by miRNAs are transcription factors; thus miRNA activity is particularly wide-ranging and regulates entire gene networks during development by modulating the expression of key regulatory genes, including transcription factors as well as F-box proteins. In many organisms, including humans, miRNAs are linked to the formation of tumors and dysregulation of the cell cycle. Here, miRNAs can function as both oncogenes and tumor suppressors.


title: RNA interference

text: Based on parsimony-based phylogenetic analysis, the most recent common ancestor of all eukaryotes most likely already possessed an early RNAi pathway; the absence of the pathway in certain eukaryotes is thought to be a derived characteristic. This ancestral RNAi system probably contained at least one dicer-like protein, one argonaute, one PIWI protein, and an RNA-dependent RNA polymerase that may also have played other cellular roles. A large-scale comparative genomics study likewise indicates that the eukaryotic crown group already possessed these components, which may then have had closer functional associations with generalized RNA degradation systems such as the exosome. This study also suggests that the RNA-binding argonaute protein family, which is shared among eukaryotes, most archaea, and at least some bacteria (such as "Aquifex aeolicus"), is homologous to and originally evolved from components of the translation initiation system.


title: RNA interference

text: Gene knockdown is a method used to reduce the expression of an organism’s specific genes. This is accomplished by using the naturally occurring process of RNAi. This gene knockdown technique uses a double-stranded siRNA molecule that is synthesized with a sequence complementary to the gene of interest. The RNAi cascade begins once the Dicer enzyme starts to process siRNA. The end result of the process leads to degradation of mRNA and destroys any instructions needed to build certain proteins. Using this method, researchers are able to decrease (but not completely eliminate) the expression of a targeted gene. Studying the effects of this decrease in expression may show the physiological role or impact of the targeted gene products.


title: RNA interference

text: Extensive efforts in computational biology have been directed toward the design of successful dsRNA reagents that maximize gene knockdown but minimize "off-target" effects. Off-target effects arise when an introduced RNA has a base sequence that can pair with and thus reduce the expression of multiple genes. Such problems occur more frequently when the dsRNA contains repetitive sequences. It has been estimated from studying the genomes of humans, "C. elegans" and "S. pombe" that about 10% of possible siRNAs have substantial off-target effects. A multitude of software tools have been developed implementing algorithms for the design of general mammal-specific, and virus-specific siRNAs that are automatically checked for possible cross-reactivity.


title: RNA interference

text: Depending on the organism and experimental system, the exogenous RNA may be a long strand designed to be cleaved by dicer, or short RNAs designed to serve as siRNA substrates. In most mammalian cells, shorter RNAs are used because long double-stranded RNA molecules induce the mammalian interferon response, a form of innate immunity that reacts nonspecifically to foreign genetic material. Mouse oocytes and cells from early mouse embryos lack this reaction to exogenous dsRNA and are therefore a common model system for studying mammalian gene-knockdown effects. Specialized laboratory techniques have also been developed to improve the utility of RNAi in mammalian systems by avoiding the direct introduction of siRNA, for example, by stable transfection with a plasmid encoding the appropriate sequence from which siRNAs can be transcribed, or by more elaborate lentiviral vector systems allowing the inducible activation or deactivation of transcription, known as "conditional RNAi".


title: RNA interference

text: The technique of knocking down genes using RNAi therapeutics has demonstrated success in randomized controlled clinical studies. These medications are a growing class of siRNA-based drugs that decrease the expression of proteins encoded by certain genes. To date, four RNAi medications have been approved by regulatory authorities in the US and Europe: patisiran (2018), givosiran (2019), lumasiran (2020), inclisiran (2020 in Europe with anticipated US approval in 2021).


title: RNA interference

text: While all of the current regulatory body approved RNAi therapeutics focus on diseases that originate in the liver, additional medications under investigation target a host of disease areas including cardiovascular diseases, bleeding disorders, alcohol use disorders, cystic fibrosis, gout, carcinoma, and eye disorders.


title: RNA interference

text: Patisiran is the first double stranded siRNA-based medication approved in 2018 and developed by Alnylam Pharmaceuticals. Patisiran uses the RNAi cascade to suppress the gene that codes for TTR (transthryetin). Mutations in this gene may cause the misfolding of a protein responsible for hereditary ATTR amyloidosis. To achieve therapeutic response, patirisan is encased by a lipid nanoparticle membrane that facilitates crossover into the cytoplasm. Once inside the cell, the siRNA begins processing by the enzyme Dicer. Patirisan is administered by a healthcare professional through an intravenous infusion with dosing based on body weight. Warnings and precautions include risk of infusion-related reactions and reduced vitamin A levels (serum).


title: RNA interference

text: In 2019, the FDA and EMA approved givosiran for the treatment of adults with acute hepatic porphyria (AHP). The FDA also granted givosiran a breakthrough therapy designation, priority review designation, and orphan drug designation for the treatment of acute hepatic porphyria (AHP) in November 2019. By 2020, givosiran received EMA approval. Givosiran is an siRNA that breaks down aminolevulinic acid synthase 1 (ALAS1) mRNA in the liver. Breaking down ALAS1 mRNA prevents toxins (responsible for neurovisceral attacks and AHP disease) such as aminolevulinic acid (ALA) and porphobilinogen (PBG) from accumulating. To facilitate entry into the cytoplasm, givosiran uses GalNAc ligands and enters into liver cells. The medication is administered subcutaneously by a healthcare professional with dosing based on body weight. Warnings and precautions include risk of anaphylactic reactions, hepatic toxicity, renal toxicity and injection site reactions.