title: Full moon

text: A continuing lunisolar calendar is the Hebrew calendar. Evidence of this is noted in the dates of Passover and Easter in Judaism and Christianity, respectively. Passover falls on the full moon on 15 Nisan of the Hebrew calendar. The date of the Jewish Rosh Hashana and Sukkot festivals along with all other Jewish holidays are dependent on the dates of the new moons.


title: Full moon

text: In lunisolar calendars, an intercalary month occurs seven times in the 19 years of the Metonic cycle, or on average every 2.7 years (19/7). In the Hebrew calendar this is noted with a periodic extra month of Adar in the early spring.


title: Full moon

text: In the modern system of "traditional" American full moon names tied to the solstice and equinox points, a supernumerary full moon in such a period is called a blue moon. The term "blue moon" used in this sense may date to as early as the 16th century, but it became well known in the United States due to the "Farmers' Almanac" (published since 1818).


title: Full moon

text: According to the pattern of use in the "Farmers' Almanac", a "blue moon" is the third full moon in any period between either a solstice and an equinox, or between an equinox and a solstice, (calculated using the mean tropical year), which contains four full moons. These seasons are equal in length, unlike the astronomical ones, which vary in length depending on the Earth's speed in its elliptical orbit round the Sun. To compare, in 1983 the equal-length mean-solar solar points and the "actual" astronomical (observed) dates are shown in the table below (all dates and times in GMT):


title: Full moon

text: As a consequence of checking an inadequate number of old issues of the "Farmers' Almanac", the author of an article in the March 1946 issue of "Sky & Telescope" magazine wrongly concluded that the "Farmers' Almanac" had used "blue moon" to denote "the second full moon in any month which contains two full moons".


title: Full moon

text: The mistaken rule was retracted and declared "erroneous" in a 1999 "Sky & Telescope" article, which gave the corrected rule, based on order in seasons.


title: Full moon

text: Using the original meaning, "blue moons" occur with the same average frequency of intercalary months, 7 times in 19 years; the "Farmers' Almanac" system of full moon names effectively defines a functioning luni-solar calendar. Because the Sky & Telescope definition depends on calendar months and because February is shorter than a lunar month, the will be a higher frequency of blue moons under that definition (in years in which February squeezes in between two full moons), so that blue moons occur on average about 8 times in 19 years.


title: Full moon

text: It is a rare phenomenon to see an unusual blue color of the moon (not necessarily a full moon) when viewing the moon. This phenomenon is caused by dust particles or smoke in the atmosphere, and was seen after the forest fires in Sweden and Canada in 1950 and 1951. In 1883, after the eruption of Krakatoa in Indonesia, the Moon was blue for almost two years. Other less violent volcanic explosions have been followed by blue moons. The blue Moon was also seen after the eruption of El Chichon in Mexico in 1983, Mount St. Helens in 1980, and Mount Pinatubo in 1991.


title: Air Force ranks and insignia of India

text: The Indian Air Force's rank structure is based on that of the Royal Air Force. The highest rank attainable in the Indian Air Force is Marshal of the Indian Air Force, conferred by the President of India after exceptional service during wartime. MIAF Arjan Singh was the only officer to have achieved this rank. The head of the Indian Air Force is the Chief of the Air Staff, who holds the rank of Air Chief Marshal. The current Chief of the Air Staff is Air Chief Marshal Vivek Ram Chaudhari, took office on 30 September 2021.


title: Air Force ranks and insignia of India

text: The IAF rank of pilot officer is a rank in abeyance in the Air Force and is no longer in force, all officers begin as flying officers upon commissioning.


title: Air Force ranks and insignia of India

text: The rank of Pilot Officer is no longer in use; all new officers are commissioned as Flying Officers. The old warrant officer ranks and the rank of flight sergeant were replaced in 1977 by the new warrant officer ranks.


title: League of Ireland Premier Division

text: The League of Ireland Premier Division (), also known as the SSE Airtricity League Premier Division for sponsorship reasons, is the top level division in both the League of Ireland and the Republic of Ireland football league system. The division was formed in 1985 following a reorganisation of the League of Ireland. St Patrick's Athletic and Bohemians are the only current League of Ireland clubs never to have been relegated from the Premier Division. The league has been won on multiple occasions by Northern Ireland-based club Derry City, the presence of which within the league makes it a cross-border competition. Since 2003, the Premier Division has operated as a summer league.


title: League of Ireland Premier Division

text: The inaugural members of the Premier Division included the League of Ireland's traditional top four clubs – Shamrock Rovers, Shelbourne, Bohemians and Dundalk plus eight other clubs. Shamrock Rovers were the inaugural champions and then retained the title in 1986–87. This saw Rovers complete a four in a row of league titles. Dundalk were champions in 1987–88 and Derry City achieved a treble in 1988–89 by also winning the League of Ireland Cup and the FAI Cup.


title: League of Ireland Premier Division

text: The 1990s saw the re-emergence of St Patrick's Athletic following years of obscurity. During the decade St Pat's won four titles. Brian Kerr guided the club to success in 1989–90 and 1995–96 before Pat Dolan and Liam Buckley added further titles in 1997–98 and 1998–99. The 1992–93 season saw Cork City win their first title in dramatic circumstances after a series of three-way play-offs that also involved Bohemians and Shelbourne.


title: League of Ireland Premier Division

text: Dermot Keely guided Shelbourne to the title in 1999–2000 and 2001–02. Shelbourne won the title in controversial circumstances in 2001–02. They were only declared champions after St Patrick's Athletic were deducted 15 points for fielding Charles Livingstone Mbabazi while he was ineligible.


title: League of Ireland Premier Division

text: The league decided to become a summer league in 2003. Pat Fenlon added further titles in 2003, 2004 and 2006. Fenlon had also been a prominent member of the Shelbourne playing squads in 1999–2000 and 2001–02. As a manager Fenlon would also guide Bohemians to title successes in 2008 and 2009. Cork City denied Shelbourne a third league title in a row when they claimed their second title in 2005, defeating fellow challengers Derry City in a last game decider at Turners Cross.


title: League of Ireland Premier Division

text: During the second half of the decade a number of Premier Division clubs suffered financial difficulties. During the 2005 season Shamrock Rovers entered into examinership and it was revealed that the club had debts of nearly €3 million. It was also discovered that Rovers were not paying PAYE and PRSI taxes. As a result of these financial irregularities, Rovers were deducted eight points. This ultimately resulted in the club being relegated to the First Division after they lost the relegation/promotion playoff to Dublin City. This was the first time Rovers' senior team had dropped out of the top level of the Republic of Ireland football league system since the club had joined the League of Ireland in 1922–23. During the 2006 season the Revenue Commissioners took High Court action and threatened to have Shelbourne wound up after the club failed to pay more than €104,000 in outstanding taxes. Shelbourne also struggled to pay its players during the season. Despite winning the title Shelbourne were subsequently demoted to the First Division due to their financial difficulties. Midway through the season Dublin City also went out of business and withdrew from the league, unable to complete the season. During the 2008 season both Cork City and Drogheda United were deducted ten points after going into administration. Following the conclusion of the 2009 season both Derry City and Cork City were expelled from the League of Ireland. Derry City were accused of making extra payments to players using unofficial secondary contracts. This was against league rules which placed limits on the amount clubs could spend on players' wages. Cork City had been in serious financial difficulties for several seasons and its holding company was eventually wound up by the High Court. However both clubs were effectively reformed and were subsequently allowed to join the 2010 First Division.


title: League of Ireland Premier Division

text: The 2010s have been one of contrasting fortunes for Premier Division clubs. Under Michael O'Neill, Shamrock Rovers finished as Premier Division champions in 2010 and 2011. In 2011 Rovers also created history when they became the first team in League of Ireland history to qualify for the group stages of the UEFA Europa League. In 2012 Sligo Rovers won their first Premier Division title and their first top level title in thirty five years. St. Patrick's Athletic won their fifth Premier Division in 2013. Under Stephen Kenny, Dundalk emulated Shamrock Rovers, winning the title in 2014 and 2015 titles before qualifying for the group stages of the 2016–17 UEFA Europa League.


title: League of Ireland Premier Division

text: In contrast three Premier Division clubs – Sporting Fingal, Galway United and Monaghan United – all withdrew from the League of Ireland. Sporting Fingal also went out of business completely.


title: League of Ireland Premier Division

text: The top team in the Premier Division currently qualifies for the UEFA Champions League first qualifying round. The second-placed and third placed-teams and winners of the FAI Cup qualify for the UEFA Europa Conference League first qualifying round. Shamrock Rovers and Dundalk have both qualified for the group stages of the UEFA Europa League. In 2011, Rovers became the first team in League of Ireland history to reach the group stages and Dundalk repeated the feat in 2016 and 2020. In 2018, UEFA changed the structure of qualification for the Champions League; giving an extra four automatic qualification spots to the top four leagues in Europe. To compensate for that change, an extra round was added to the qualifying stages of the Champions League and the Europa League which made qualification more difficult for League of Ireland clubs. In 2021, the league will have its Europa League qualifying places revoked and replaced by Europa Conference League places as part of UEFA's restructuring of European football.


title: League of Ireland Premier Division

text: the Republic of Ireland are currently ranked 35th for the 2023 season with some potential for improvement. the country co-efficient has surpassed three points (3.125) for an individual season and the 2023 ranking score is now over 10 points (10.125) for the first time ever.Between 1998 and 2010, the league's place on the coefficient table rose 15 places, the biggest climb of any league in Europe. Its position of 29th in 2010 was also its highest since 1986. Since June 2010, the league's ranking has declined and it stood at 43rd place at the end of the 2013/2014 season, a drop of 14 places since 2010 and the league's worst ranking since 1998. In the 2000s, the Premier Division's coefficient vastly improved relative to the late 1990s, but at a cost. The introduction of full-time professional football by a number of clubs and the league's decision to become a summer league in 2003, improved the performance of Premier Division clubs in Europe. Increased fitness levels resulted from both, while full-time professionalism retained Irish players within the league, attracted foreign players to the league and generally improved the standard of football. At least one League of Ireland club has progressed to the next round of a European competition in every season from 2003 to 2014.


title: League of Ireland Premier Division

text: However, the costs associated with professional football and the pursuit of European success have been blamed for the financial difficulties suffered by Premier Division clubs. This period of improvement came to an end in 2010 with the league's ranking dropping. From 29th in 2010, it dropped to 31st in 2011, 33rd in 2012, 36th in 2013 and 43rd for the 2014 rankings. The league recovered to 40th for the 2015 rankings and finished 41st in the 2016 rankings.


title: League of Ireland Premier Division

text: A promotion and relegation system has existed between the Premier Division and the League of Ireland First Division since 1985–86. The bottom team in the Premier Division is relegated, and the second-from-bottom plays the second-from-top of the First Division for the final spot in the Premier Division. In 1992–93 a promotion/relegation play-off was also introduced. The bottom team in the Premier Division is relegated, and the second-from-bottom plays the second-from-top of the First Division for the final spot in the Premier Division.


title: League of Ireland Premier Division

text: In 2008 Cobh Ramblers were relegated directly from the Premier Division to the 2009 A Championship after they failed to obtain a First Division license. In 2017, to even up the numbers of clubs in the Premier Division and First Division to 10 teams each, the bottom three Premier League teams were relegated and only the First Division champion were promoted.


title: League of Ireland Premier Division

text: The current League of Ireland trophy was unveiled on 31 October 2007 by the Football Association of Ireland. It stands at 91 cm (36 inches) tall with a circumference of 83 cm (33 inches). It is a Sterling Silver trophy consisting of silver and a mass of other metals including copper. The design of the trophy consists of a silver football at the top, which is encompassed by the cup itself. Drogheda United were the first team to receive the newly created trophy on 2 November 2007.


title: League of Ireland Premier Division

text: The Premier Division has been sponsored since the early 1990s. The sponsor has been able to determine the league's sponsorship name. There have been three sponsors since the league's formation.


title: League of Ireland Premier Division

text: The league had no title sponsor in 2009, but had a number of secondary sponsors including Newstalk and Electronic Arts. As well as sponsorship for the league itself, the Premier Division has a number of official partners and suppliers. The official ball supplier for the league is Umbro. The official drink for the league is Lucozade. The official radio and newspaper partners are Newstalk and "Irish Daily Star".


title: Texas Longhorns football

text: The Texas Longhorns football program is the intercollegiate team representing the University of Texas at Austin (variously Texas or UT) in the sport of American football. The Longhorns compete in the NCAA Division I Football Bowl Subdivision (formerly Division I-A) as a member of the Big 12 Conference. Their home games are played at Darrell K Royal–Texas Memorial Stadium in Austin, Texas.


title: Texas Longhorns football

text: With over 900 wins, and an all-time win–loss percentage of .705, the Longhorns rank 3rd and 7th on the all-time wins and win–loss records lists, respectively. Additionally, the iconic program claims 4 national championships, 32 conference championships, 100 First Team All-Americans (62 consensus and 25 unanimous), and 2 Heisman Trophy winners.


title: Texas Longhorns football

text: Beginning in 1893, the Texas Longhorns football program is one of the most highly regarded and historic programs of all time. From 1936 to 1946 the team was led by Hall of Fame coach Dana X. Bible, and then from 1957 to 1976 the team was led by Hall of Fame coach Darrell K Royal, who won three national championships. The first championship was in 1963 and the second was in 1969. In 2009, ESPN ranked Texas as the seventh-most prestigious college football program since 1936. In 2012, the football program was valued at $805 million, more than the calculated value of several NFL teams. Texas is known for their post-season appearances, ranking second in number of bowl game appearances (55), fourth in bowl game victories (29), most Southwest Conference football championships (27), and most Cotton Bowl Classic appearances and victories. Other NCAA records include 108 winning seasons out of 122 total seasons, 24 seasons with 10 or more wins, 9 undefeated seasons, and 26 seasons with at most one loss or tie. From 1936 to 2012, the Longhorns football teams have been in the AP or coaches' rankings 66 out of 76 seasons (86.8% of the time), finishing those seasons ranked in the top twenty-five 48 times and the top ten 28 times. Texas claims four Division I-A national championships (1963, 1969, 1970 and 2005) and 32 conference championships (3 Big 12 Conference, 27 Southwest Conference, and 2 Texas Intercollegiate Athletic Association).


title: Texas Longhorns football

text: A total of 129 (53 consensus and 22 unanimous) Texas players have been named to College Football All-America Teams, while two Longhorn players, Earl Campbell (1977) and Ricky Williams (1998), have won the Heisman Trophy, "College football's most prestigious individual honor". Seventeen Longhorns have been inducted into the College Football Hall of Fame, while four are enshrined in the Pro Football Hall of Fame.


title: Texas Longhorns football

text: In the beginning of the 2019 season, Texas' all-time record was 909–371–33 (.705), which ranked as the third-most wins at the end of the same season Texas' record was 916–375–33 (.704) losing a spot and ending up in fourth in NCAA Division I FBS history.


title: Texas Longhorns football

text: After 15 seasons as a member of the Big 12, Texas accepted an invitation to join the SEC beginning with the 2025 season. The Longhorns football team intends to continue competing in the Big 12 for the remainder of its media rights deal, which expires in June 2025.


title: Texas Longhorns football

text: Texas has been selected national champion in 9 seasons from NCAA-designated major selectors (including four from major wire-service: AP Poll and Coaches' Poll). The 1963, 1969, 1970, and 2005 championships are claimed by the school, while the remainder are not claimed.


title: Texas Longhorns football

text: Texas has won 32 conference championships, 26 outright and six shared, spanning three conferences, the Texas Intercollegiate Athletic Association, the Southwest Conference, and their current conference, the Big 12 Conference.


title: Texas Longhorns football

text: Texas has won a share of 7 Big 12 South titles, 5 of which resulted in an appearance in the Big 12 Championship Game. Texas is 3–2 in those appearances. As of 2011, the new ten-team Big 12 Conference ceased to have divisions and conference championship games.


title: Texas Longhorns football

text: At the end of the 2018 season, Texas is tied for second in all time bowl appearances in the NCAA FBS at 55, matching Georgia and trailing Alabama's 70 appearances. (Note: Some years Texas went to two bowls although they were in different seasons)


title: Texas Longhorns football

text: ^ The 2006 Rose Bowl was both the Rose Bowl Game and the sanctioned BCS National Championship Game, after that season the BCS NCG became a separate game unaffiliated with the major bowl games.


title: Texas Longhorns football

text: † The Bluebonnet Bowl in Houston was discontinued in 1988, but was replaced by the Houston Bowl (2000–2001) and the Texas Bowl (2006–current).


title: Texas Longhorns football

text: Texas has played in four Bowl Championship Series games (including two BCS National Championships) and one New Year's Six bowl. Texas also played in two Bowl Alliance games (the precursor to the BCS): the 1995 Sugar Bowl and the 1997 Fiesta Bowl.


title: Texas Longhorns football

text: There have been 31 head coaches since the inaugural team in 1893, with Steve Sarkisian being the current head coach of the Longhorns.


title: Texas Longhorns football

text: The Longhorns have played their home games in Darrell K Royal–Texas Memorial Stadium (formerly just "Memorial Stadium" and "Texas Memorial Stadium") on Campbell-Williams Field since 1924. The stadium is located on the campus of The University of Texas in Austin, Texas. The current official stadium capacity is 100,119, making it the second largest football venue in the state of Texas, the largest in the Big 12 Conference, the fifth largest on-campus stadium in the NCAA, and the seventh largest non-racing stadium in the world.


title: Texas Longhorns football

text: The stadium has been expanded several times since its original opening, and now includes 100,119 permanent seats, the nation's first high definition video display in a collegiate facility nicknamed "Godzillatron," and a newly renovated Joe Jamail Field with FieldTurf. The current DKR-Texas Memorial Stadium and Big 12 attendance record was set on September 15, 2018, against USC with 103,507 spectators.


title: Texas Longhorns football

text: The final planned phase of the stadium's expansion includes the construction of permanent seating and an upper deck in the south end zone, completely enclosing the playing field. The stadium's seating capacity is expected to reach 112,000 once the south end zone is fully enclosed, which would mean DKR-Texas Memorial Stadium would surpass Michigan Stadium as the largest football stadium in North America. However, the date of the final construction phase to fully enclose the south end zone has not been set nor have any funds been raised. Varying sources claim this phase may not take place for upwards of 10 to 15 years, though on March 11, 2014, an announcement was made that an exploratory committee has been formed regarding the expansion of the stadium in conjunction with the construction of the Dell Medical School on campus.


title: Texas Longhorns football

text: Before the Longhorns football team moved to DKR, they played their home games at Clark Field from 1887 to 1924. Clark Field was a wooden-structured stadium located on the University of Texas campus. The Longhorns last game at Clark Field before moving to brand new Memorial Stadium occurred on October 25, 1924. The Longhorns battled the Florida Gators to a 7–7 tie that day. Texas finished with a record of 135–23–3 during their time at Clark Field.


title: Texas Longhorns football

text: Texas has a long-standing rivalry with the University of Oklahoma. The football game between the University of Texas and Oklahoma is commonly known as the "Red River Rivalry" and is held annually in Dallas at the Cotton Bowl. Dallas is used as a "neutral site" since it is approximately midway between the two campuses. The stadium is split, with each team having an equal number of supporters on each side of the 50 yard line. Texas state flags fly around the Longhorn end of the stadium and Oklahoma state flags fly around the Sooner end. This border rivalry is often considered to be one of the top five current rivalries in the NCAA. The Red River Shootout originated in 1900, while Oklahoma was still a territory of the United States, and it is the longest-running college-football rivalry played on a neutral field. Since 2005, the football game has received sponsorship dollars in return for being referred to as the "SBC Red River Rivalry" (changed to AT&T Red River Rivalry in 2006 after SBC merged with AT&T), a move which has been criticized both for its commercialism and its political correctness. The University of Texas holds its annual Torchlight Parade during the week of the Red River Rivalry. In 2005, the "Dallas Morning News" did an opinion poll of the 119 Division 1A football coaches as to the nations top rivalry game in college football. The Texas-OU game was ranked third. The game typically has conference or even national significance. Since 1945, one or both of the two teams has been ranked among the top 25 teams in the nation coming into 60 out of 65 games. Twice Texas has defeated the Sooners a record eight straight times from 1940 to 1947 and 1958–1965. One of the most significant meetings was in 1963 with Oklahoma ranked No. 1 and Texas ranked No. 2, the game won by Texas 28–7 en route to their first officially recognized national championship. The series has also had its share of games that came down to the wire and comebacks most recently in 2009 when Texas cemented a 16–13 victory in the fourth quarter over OU. The game has also been the result of controversy. The meeting in 1976 was a heated affair as the Oklahoma staff was accused of spying on Texas' practices, a move later confirmed by former OU head coach Barry Switzer. In the 2008 season Texas scored 45 points over then No. 1 Oklahoma for the win, but even with the victory Texas would not go on to the Big 12 Championship game due to BCS rankings. Six of the last ten showings featured one of the participants in the BCS National Championship Game (2000, 2003–2005, 2008, 2009), including national titles won by Oklahoma in 2000 and by Texas in 2005. On October 6, 2018, the Longhorns and Sooners squared off in a Red River Rivalry game that will go down in history. After giving up a 21-point 4th Quarter lead, the Longhorns found themselves tied at 45 with the Sooners with just over two minutes left to play in the game. As the Longhorns began to systematically march down the field, time began to run out. However, a Cameron Dicker 40 yard field goal sealed a 48–45 win for the Longhorns and finally ended the 2-year drought in the Red River Rivalry.


title: Texas Longhorns football

text: In 2022, Texas shut out Oklahoma, beating them 49-0. This was the most dominant win by either side since 2003, and the first shut out since 2006.


title: Texas Longhorns football

text: Texas leads the all-time series 62–50–5 through the 2021 season. In 2023 Oklahoma will surpass Texas A&M as UT’s most played football rivalry game.


title: Texas Longhorns football

text: The first meeting between the Texas Longhorns and Texas Tech Matadors (as the team was known until 1937) was in 1928, a 12–0 win for Texas. The teams only faced each other nine times before 1960 with Texas holding an 8–1 record over Tech at the time. From 1960 to 1995, both schools played annually as members of the Southwest Conference. Since 1996, both schools have played as members of the Big 12 Conference. In 1996, the Texas Tech University System was established and the system's first chancellor, John T. Montford, a former member of the Texas State Senate, started the exchange of a traveling trophy between the two universities called the Chancellor's Spurs. The spurs are gold and silver and engraved with Texas Tech's Double T and Texas' interlocking UT logo and were first awarded to Texas after a 38–32 victory over the Red Raiders in Lubbock.


title: Texas Longhorns football

text: Old Southwest Conference rivals, Texas and Arkansas first met in 1894, a 54–0 win by Texas. In the days of the Southwest Conference, the game between the two schools usually decided which team would win the conference championship. Overall, Texas won the game about 71% of the time, which led to an incredibly fierce and intense rivalry. The two programs have met 79 times and have had many big games. The meeting in 1969 is the true Game of the Century commemorating the 100th year of college football, which led to the Longhorns' 1969 national championship. This game, which is commonly known as "Dixie's Last Stand" and The Big Shootout, still does not sit well with Razorback fans to this day. The game saw Arkansas lead throughout only to have Texas come from behind and win in the final minutes, 15–14. The game also saw former President Richard Nixon attend the game and crown the Longhorns the National Champion in the locker room. The Texas-Arkansas game has not been played annually since Arkansas's departure from the Southwest Conference to the Southeastern Conference in 1991. However, many Longhorn and Razorback fans still consider this matchup an important rivalry. Texas and Arkansas played in September 2008, with Texas winning, 52–10. Texas and Arkansas also played in the 2014 Texas Bowl, which Arkansas won, 31–7. Texas and Arkansas played in the 2021 regular season, with Arkansas winning by a score of 40-21.


title: Texas Longhorns football

text: The rivalry is known for the tension between the two programs. Almost every game between the two could have gone either way, with Texas stealing many of the victories in heartbreaking fashion.


title: Texas Longhorns football

text: The first meeting between the football squads of the University of Texas and Texas A&M was in 1894, a 38–0 win for Texas. In fact, Texas won its first seven games against the Aggies, all of them by shutout. By 1915 Texas held a 15–4–2 advantage against the Aggies. The game was a back and forth affair for the next twenty years as the home team usually took the victory in the game, however Texas still maintained the series lead. In 1940, Texas shutout the Aggies 7–0 and kept them from receiving the Rose Bowl bid that year. From that year forward Texas would go on to win 33 of the next 38 games over A&M. It was not until the mid-1980s that A&M developed a win streak over Texas and in the late 1990s and 2000s the rivalry would again go back to Longhorns. The Texas/Texas A&M rivalry has given rise to several stereotypes on both sides: Texas A&M is generally portrayed as the rural smaller school while Texas is portrayed as the urban-wealthy larger school. With the exception of the 1994 game, when A&M's probation restricted the Aggies from being televised, the annual football game with Texas A&M traditionally takes place on Thanksgiving Day or the day after each year. This iconic in-state rivalry is often considered one of the top college rivalries of all time. In July 2011, Texas A&M elected to join the Southeastern Conference beginning in 2012, which ended of the 118-year consecutive meetings between the two schools. On November 24, 2011, Texas faced Texas A&M in College Station in the final scheduled meeting of the rivalry as of January 2019. Texas defeated Texas A&M 27–25 on a last second field goal to win the final meeting. In an attempt to generate more attention for the rivalry in sports other than football, the two schools created the Lone Star Showdown in 2004. Essentially, each time the two schools meet in a sport, the winner of the matchup gets a point. At the end of the year, the school with the most points wins the series and receives the Lone Star Trophy.


title: Texas Longhorns football

text: Texas leads the series 76–37–5 through the 2021 season. The rivalry will resume when Texas moves to the Southeastern Conference in 2025.


title: Texas Longhorns football

text: Baylor and Texas have played each other 111 times, with the first game between Baylor and Texas being played in 1901. Only Oklahoma and Texas A&M have played Texas more times than Baylor. Both Baylor and Texas were founding members of the Southwest Conference and the BIG 12 Conference. Texas leads the series with Baylor 70-28-4. However, starting in 2010 this rivalry intensified as Baylor established themselves as a major contender in the BIG 12 Conference with Baylor playing for 4 BIG 12 titles and winning 3, including a head-to-head win over Texas to clinch the BIG 12 Championship in 2013, in what is now known as the "Ice Bowl" Losing the BIG 12 Title to Baylor 30-10 was Mack Brown's last regular season game as the head coach at Texas.


title: Texas Longhorns football

text: The University of Texas has had 129 Longhorns selected to the College Football All-America Team including 62 Consensus and 25 Unanimous; Texas also has 17 players and coaches that have been inducted into the College Football Hall of Fame.


title: Texas Longhorns football

text: As of 2016, the Texas Longhorns have had 570 All-Conference Player selections since 1915, including 292 in the Southwest Conference and 278 in the Big 12 where Longhorn players have been named 78 times to the first team and 65 to the second team.


title: Texas Longhorns football

text: 351 Longhorns have been drafted into the NFL, including 44 in the 1st round., the Longhorns have 26 players active on NFL rosters.


title: Texas Longhorns football

text: The 1893 team did not always wear orange. They also wore gold and white uniforms. In 1895, the Texas Athletic Association moved to orange and white colors. In 1897, the Association moved to orange and maroon to save cleaning costs. The Cactus Yearbook at the time listed the university colors as either gold or orange and white until the 1899 Cactus declared the university colors to be gold and maroon. Students at the university's medical branch in Galveston (UTMB) were in favor of royal blue. By 1899, a UT fan could have worn any of yellow, orange, white, red, maroon, or even blue.


title: Texas Longhorns football

text: The Board of Regents held an election in that year to decide the team colors. Students, faculty, staff and alumni were asked to vote. 1,111 votes were cast, with 562 in favor of orange and white. Orange and maroon received 310, royal blue 203, crimson 10, and royal blue and crimson 11. For the next 30 years, Longhorn teams wore bright orange on their uniforms, which faded to yellow by the end of the season. By the 1920s, other teams sometimes called the Longhorn squads "yellow bellies," a term that didn't sit well with the athletic department. In 1928, UT football coach Clyde Littlefield ordered uniforms in a darker shade of orange that wouldn't fade, which would later become known as "burnt orange" or "Texas orange." The dark-orange color was used until the dye became too expensive during the Great Depression, and the uniforms reverted to the bright orange for another two decades, until coach Darrell K Royal revived the burnt-orange color in the early 1960s.


title: Texas Longhorns football

text: From 1961 to 1962, the Longhorns' helmets featured the individual player's number on the side in burnt orange above the "Bevo" logo, which was also in burnt orange, with a large burnt-orange stripe down the middle of the helmet. The burnt-orange stripe was removed in 1963 and the helmet featured only the burnt-orange Bevo logo below the player's number, which was also in burnt orange. In 1967, the team abandoned the individual player's number above the logo, and moved the burnt-orange Bevo logo to the center of the helmet's side. With the exception of the 1969 season, this remained the team's helmet design until 1977. In 1969, the helmet design commemorated the 100th anniversary of the first college football game. The player's number was replaced by a large burnt-orange football above the Bevo logo. Inside the football was a white number "100" that indicated the anniversary year.


title: Texas Longhorns football

text: The University of Texas is a tradition-rich school, and many of those traditions are associated with athletics events, especially football. Some Longhorn traditions include:


title: Texas Longhorns football

text: Announced schedules as of February 13, 2020. This is subject to change based on Texas' future move to the SEC.


title: Cranial nerves

text: Cranial nerves are the nerves that emerge directly from the brain (including the brainstem), of which there are conventionally considered twelve pairs. Cranial nerves relay information between the brain and parts of the body, primarily to and from regions of the head and neck, including the special senses of vision, taste, smell, and hearing.


title: Cranial nerves

text: The cranial nerves emerge from the central nervous system above the level of the first vertebra of the vertebral column. Each cranial nerve is paired and is present on both sides. There are conventionally twelve pairs of cranial nerves, which are described with Roman numerals I–XII. Some considered there to be thirteen pairs of cranial nerves, including cranial nerve zero. The numbering of the cranial nerves is based on the order in which they emerge from the brain and brainstem, from front to back.


title: Cranial nerves

text: The terminal nerves (0), olfactory nerves (I) and optic nerves (II) emerge from the cerebrum, and the remaining ten pairs arise from the brainstem, which is the lower part of the brain.


title: Cranial nerves

text: The cranial nerves are considered components of the peripheral nervous system (PNS), although on a structural level the olfactory (I), optic (II), and trigeminal (V) nerves are more accurately considered part of the central nervous system (CNS).


title: Cranial nerves

text: Most typically, humans are considered to have twelve pairs of cranial nerves (I–XII), with the terminal nerve (0) more recently canonized. The nerves are: the olfactory nerve (I), the optic nerve (II), oculomotor nerve (III), trochlear nerve (IV), trigeminal nerve (V), abducens nerve (VI), facial nerve (VII), vestibulocochlear nerve (VIII), glossopharyngeal nerve (IX), vagus nerve (X), accessory nerve (XI), and the hypoglossal nerve (XII).


title: Cranial nerves

text: Cranial nerves are generally named according to their structure or function. For example, the olfactory nerve (I) supplies smell, and the facial nerve (VII) supplies the muscles of the face. Because Latin was the "lingua franca" of the study of anatomy when the nerves were first documented, recorded, and discussed, many nerves maintain Latin or Greek names, including the trochlear nerve (IV), named according to its structure, as it supplies a muscle that attaches to a pulley (). The trigeminal nerve (V) is named in accordance with its three components ( meaning triplets), and the vagus nerve (X) is named for its wandering course ().


title: Cranial nerves

text: Cranial nerves are numbered based on their position from front to back (rostral-caudal) of their position on the brain, as, when viewing the forebrain and brainstem from below, they are often visible in their numeric order. For example, the olfactory nerves (I) and optic nerves (II) arise from the base of the forebrain, and the other nerves, III to XII, arise from the brainstem.


title: Cranial nerves

text: Cranial nerves have paths within and outside the skull. The paths within the skull are called "intracranial" and the paths outside the skull are called "extracranial". There are many holes in the skull called "foramina" by which the nerves can exit the skull. All cranial nerves are "paired", which means they occur on both the right and left sides of the body. The muscle, skin, or additional function supplied by a nerve, on the same side of the body as the side it originates from, is an "ipsilateral" function. If the function is on the opposite side to the origin of the nerve, this is known as a "contralateral" function.


title: Cranial nerves

text: Grossly, all cranial nerves have a Nucleus. With the exception of the olfactory nerve (I) and optic nerve (II), all the nuclei are present in the brainstem.


title: Cranial nerves

text: The midbrain of the brainstem has the nuclei of the oculomotor nerve (III) and trochlear nerve (IV); the pons has the nuclei of the trigeminal nerve (V), abducens nerve (VI), facial nerve (VII) and vestibulocochlear nerve (VIII); and the medulla has the nuclei of the glossopharyngeal nerve (IX), vagus nerve (X), accessory nerve (XI) and hypoglossal nerve (XII). The olfactory nerve (I) emerges from the olfactory bulb, and depending slightly on division the optic nerve (II) is considered to emerge from the lateral geniculate nuclei.


title: Cranial nerves

text: Because each nerve may have several functions, the nerve fibres that make up the nerve may collect in more than one nucleus. For example, the trigeminal nerve (V), which has a sensory and a motor role, has at least four nuclei.


title: Cranial nerves

text: With the exception of the olfactory nerve (I) and optic nerve (II), the cranial nerves emerge from the brainstem. The oculomotor nerve (III) and trochlear nerve (IV) emerge from the midbrain, the trigeminal (V), abducens (VI), facial (VII) and vestibulocochlea (VIII) from the pons, and the glossopharyngeal (IX), vagus (X), accessory (XI) and hypoglossal (XII) emerge from the medulla.


title: Cranial nerves

text: The olfactory nerve (I) and optic nerve (II) emerge separately. The olfactory nerves emerge from the olfactory bulbs on either side of the crista galli, a bony projection below the frontal lobe, and the optic nerves (II) emerge from the lateral colliculus, swellings on either side of the temporal lobes of the brain.


title: Cranial nerves

text: The cranial nerves give rise to a number of ganglia, collections of the cell bodies of neurons in the nerves that are outside of the brain. These ganglia are both parasympathetic and sensory ganglia.


title: Cranial nerves

text: The sensory ganglia of the cranial nerves, directly correspond to the dorsal root ganglia of spinal nerves and are known as cranial nerve ganglia. Sensory ganglia exist for nerves with sensory function: V, VII, VIII, IX, X. There are also a number of parasympathetic cranial nerve ganglia. Sympathetic ganglia supplying the head and neck reside in the upper regions of the sympathetic trunk, and do not belong to the cranial nerves.


title: Cranial nerves

text: The ganglion of the sensory nerves, which are similar in structure to the dorsal root ganglion of the spinal cord, include:


title: Cranial nerves

text: Additional ganglia for nerves with parasympathetic function exist, and include the ciliary ganglion of the oculomotor nerve (III), the pterygopalatine ganglion of the maxillary nerve (V2), the submandibular ganglion of the lingual nerve, a branch of the facial nerve (VII), and the otic ganglion of the glossopharyngeal nerve (IX).


title: Cranial nerves

text: After emerging from the brain, the cranial nerves travel within the skull, and some must leave it in order to reach their destinations. Often the nerves pass through holes in the skull, called foramina, as they travel to their destinations. Other nerves pass through bony canals, longer pathways enclosed by bone. These foramina and canals may contain more than one cranial nerve and may also contain blood vessels.


title: Cranial nerves

text: The cranial nerves are formed from the contribution of two specialized embryonic cell populations, cranial neural crest and ectodermal placodes. The components of the sensory nervous system of the head are derived from the neural crest and from an embryonic cell population developing in close proximity, the cranial sensory placodes (the olfactory, lens, otic, trigeminal, epibranchial and paratympanic placodes). The dual origin cranial nerves are summarized in the following Table:


title: Cranial nerves

text: Abbreviations: CN, cranial nerve; m, purely motor nerve; mix, mixed nerve (sensory and motor); NC, neural crest; PA, pharyngeal (branchial) arch; r, rhombomere; s, purely sensory nerve. * There is no known ganglion of the accessory nerve. The cranial part of the accessory nerve sends occasional branches to the superior ganglion of the vagus nerve.


title: Cranial nerves

text: The cranial nerves provide motor and sensory supply mainly to the structures within the head and neck. The sensory supply includes both "general" sensation such as temperature and touch, and "special" senses such as taste, vision, smell, balance and hearing. The vagus nerve (X) provides sensory and autonomic (parasympathetic) supply to structures in the neck and also to most of the organs in the chest and abdomen.


title: Cranial nerves

text: The terminal nerve (0) may not have a role in humans, although it has been implicated in hormonal responses to smell, sexual response and mate selection.


title: Cranial nerves

text: Damage to the olfactory nerve (I) can cause an inability to smell (anosmia), a distortion in the sense of smell (parosmia), or a distortion or lack of taste.


title: Cranial nerves

text: Damage to the optic nerve (II) affects specific aspects of vision that depend on the location of the damage. A person may not be able to see objects on their left or right sides (homonymous hemianopsia), or may have difficulty seeing objects from their outer visual fields (bitemporal hemianopsia) if the optic chiasm is involved. Inflammation (optic neuritis) may impact the sharpness of vision or colour detection


title: Cranial nerves

text: The oculomotor nerve (III), trochlear nerve (IV) and abducens nerve (VI) coordinate eye movement. The oculomotor nerve controls all muscles of the eye except for the superior oblique muscle controlled by the trochlear nerve (IV), and the lateral rectus muscle controlled by the abducens nerve (VI). This means the ability of the eye to look down and inwards is controlled by the trochlear nerve (IV), the ability to look outwards is controlled by the abducens nerve (VI), and all other movements are controlled by the oculomotor nerve (III)


title: Cranial nerves

text: Damage to these nerves may affect the movement of the eye. Damage may result in double vision (diplopia) because the movements of the eyes are not synchronized. Abnormalities of visual movement may also be seen on examination, such as jittering (nystagmus).


title: Cranial nerves

text: Damage to the oculomotor nerve (III) can cause double vision and inability to coordinate the movements of both eyes (strabismus), also eyelid drooping (ptosis) and pupil dilation (mydriasis). Lesions may also lead to inability to open the eye due to paralysis of the levator palpebrae muscle. Individuals suffering from a lesion to the oculomotor nerve may compensate by tilting their heads to alleviate symptoms due to paralysis of one or more of the eye muscles it controls.


title: Cranial nerves

text: Damage to the trochlear nerve (IV) can also cause double vision with the eye adducted and elevated. The result will be an eye which can not move downwards properly (especially downwards when in an inward position). This is due to impairment in the superior oblique muscle.


title: Cranial nerves

text: Damage to the abducens nerve (VI) can also result in double vision. This is due to impairment in the lateral rectus muscle, supplied by the abducens nerve.


title: Cranial nerves

text: The trigeminal nerve (V) and its three main branches the ophthalmic (V1), maxillary (V2), and mandibular (V3) provide sensation to the skin of the face and also controls the muscles of chewing.


title: Cranial nerves

text: Damage to the trigeminal nerve leads to loss of sensation in an affected area. Other conditions affecting the trigeminal nerve (V) include trigeminal neuralgia, herpes zoster, sinusitis pain, presence of a dental abscess, and cluster headaches.


title: Cranial nerves

text: The facial nerve (VII) controls most muscles of facial expression, supplies the sensation of taste from the front two-thirds of the tongue, and controls the stapedius muscle. Most muscles are supplied by the cortex on the opposite side of the brain; the exception is the frontalis muscle of the forehead, in which the left and the right side of the muscle both receive inputs from both sides of the brain.


title: Cranial nerves

text: Damage to the facial nerve (VII) may cause facial palsy. This is where a person is unable to move the muscles on one or both sides of their face. The most common cause of this is Bell's palsy, the ultimate cause of which is unknown. Patients with Bell's palsy often have a drooping mouth on the affected side and often have trouble chewing because the buccinator muscle is affected. The facial nerve is also the most commonly affected cranial nerve in blunt trauma.


title: Cranial nerves

text: The vestibulocochlear nerve (VIII) supplies information relating to balance and hearing via its two branches, the vestibular and cochlear nerves. The vestibular part is responsible for supplying sensation from the vestibules and semicircular canal of the inner ear, including information about balance, and is an important component of the vestibuloocular reflex, which keeps the head stable and allows the eyes to track moving objects. The cochlear nerve transmits information from the cochlea, allowing sound to be heard.


title: Cranial nerves

text: When damaged, the vestibular nerve may give rise to the sensation of spinning and dizziness (vertigo). Function of the vestibular nerve may be tested by putting cold and warm water in the ears and watching eye movements caloric stimulation. Damage to the vestibulocochlear nerve can also present as repetitive and involuntary eye movements (nystagmus), particularly when the eye is moving horizontally. Damage to the cochlear nerve will cause partial or complete deafness in the affected ear.


title: Cranial nerves

text: The glossopharyngeal nerve (IX) supplies the stylopharyngeus muscle and provides sensation to the oropharynx and back of the tongue. The glossopharyngeal nerve also provides parasympathetic input to the parotid gland.


title: Cranial nerves

text: Damage to the nerve may cause failure of the gag reflex; a failure may also be seen in damage to the vagus nerve (X).


title: Cranial nerves

text: The vagus nerve (X) provides sensory and parasympathetic supply to structures in the neck and also to most of the organs in the chest and abdomen.


title: Cranial nerves

text: Loss of function of the vagus nerve (X) will lead to a loss of parasympathetic supply to a very large number of structures. Major effects of damage to the vagus nerve may include a rise in blood pressure and heart rate. Isolated dysfunction of only the vagus nerve is rare, but – if the lesion is located above the point at which the vagus first branches off – can be indicated by a hoarse voice, due to dysfunction of one of its branches, the recurrent laryngeal nerve.


title: Cranial nerves

text: Damage to the accessory nerve (XI) will lead to weakness in the trapezius muscle on the same side as the damage. The trapezius lifts the shoulder when shrugging, so the affected shoulder will not be able to shrug and the shoulder blade (scapula) will protrude into a winged position. Depending on the location of the lesion there may also be weakness present in the sternocleidomastoid muscle, which acts to turn the head so that the face points to the opposite side.


title: Cranial nerves

text: The hypoglossal nerve (XII) supplies the intrinsic muscles of the tongue, controlling tongue movement. The hypoglossal nerve (XII) is unique in that it is supplied by the motor cortices of both hemispheres of the brain.


title: Cranial nerves

text: Damage to the nerve may lead to fasciculations or wasting (atrophy) of the muscles of the tongue. This will lead to weakness of tongue movement on that side. When damaged and extended, the tongue will move towards the weaker or damaged side, as shown in the image. The fasciculations of the tongue are sometimes said to look like a "bag of worms". Damage to the nerve tract or nucleus will not lead to atrophy or fasciculations, but only weakness of the muscles on the same side as the damage.


title: Cranial nerves

text: Doctors, neurologists and other medical professionals may conduct a cranial nerve examination as part of a neurological examination to examine the cranial nerves. This is a highly formalised series of steps involving specific tests for each nerve. Dysfunction of a nerve identified during testing may point to a problem with the nerve or of a part of the brain.


title: Cranial nerves

text: A cranial nerve exam starts with observation of the patient, as some cranial nerve lesions may affect the symmetry of the eyes or face. Vision may be tested by examining the visual fields, or by examining the retina with an ophthalmoscope, using a process known as funduscopy. Visual field testing may be used to pin-point structural lesions in the optic nerve, or further along the visual pathways. Eye movement is tested and abnormalities such as nystagmus are observed for. The sensation of the face is tested, and patients are asked to perform different facial movements, such as puffing out of the cheeks. Hearing is checked by voice and tuning forks. The patient's uvula is examined. After performing a shrug and head turn, the patient's tongue function is assessed by various tongue movements.


title: Cranial nerves

text: Smell is not routinely tested, but if there is suspicion of a change in the sense of smell, each nostril is tested with substances of known odors such as coffee or soap. Intensely smelling substances, for example ammonia, may lead to the activation of pain receptors of the trigeminal nerve (V) located in the nasal cavity and this can confound olfactory testing.


title: Cranial nerves

text: Nerves may be compressed because of increased intracranial pressure, a mass effect of an intracerebral haemorrhage, or tumour that presses against the nerves and interferes with the transmission of impulses along the nerve. Loss of function of a cranial nerve may sometimes be the first symptom of an intracranial or skull base cancer.


title: Cranial nerves

text: An increase in intracranial pressure may lead to impairment of the optic nerves (II) due to compression of the surrounding veins and capillaries, causing swelling of the eyeball (papilloedema). A cancer, such as an optic nerve glioma, may also impact the optic nerve (II). A pituitary tumour may compress the optic tracts or the optic chiasm of the optic nerve (II), leading to visual field loss. A pituitary tumour may also extend into the cavernous sinus, compressing the oculuomotor nerve (III), trochlear nerve (IV) and abducens nerve (VI), leading to double-vision and strabismus. These nerves may also be affected by herniation of the temporal lobes of the brain through the falx cerebri.


title: Cranial nerves

text: The cause of trigeminal neuralgia, in which one side of the face is exquisitely painful, is thought to be compression of the nerve by an artery as the nerve emerges from the brain stem. An acoustic neuroma, particularly at the junction between the pons and medulla, may compress the facial nerve (VII) and vestibulocochlear nerve (VIII), leading to hearing and sensory loss on the affected side.


title: Cranial nerves

text: Occlusion of blood vessels that supply the nerves or their nuclei, an ischemic stroke, may cause specific signs and symptoms relating to the damaged area. If there is a stroke of the midbrain, pons or medulla, various cranial nerves may be damaged, resulting in dysfunction and symptoms of . Thrombosis, such as a cavernous sinus thrombosis, refers to a clot (thrombus) affecting the venous drainage from the cavernous sinus, affects the optic (II), oculomotor (III), trochlear (IV), opthalamic branch of the trigeminal nerve (V1) and the abducens nerve (VI).


title: Cranial nerves

text: Inflammation of a cranial nerve can occur as a result of infection, such as viral causes like reactivated herpes simplex virus, or can occur spontaneously. Inflammation of the facial nerve (VII) may result in Bell's palsy.


title: Cranial nerves

text: Multiple sclerosis, an inflammatory process resulting in a loss of the myelin sheathes which surround the cranial nerves, may cause a variety of shifting symptoms affecting multiple cranial nerves. Inflammation may also affect other cranial nerves. Other rarer inflammatory causes affecting the function of multiple cranial nerves include sarcoidosis, miliary tuberculosis, and inflammation of arteries, such as granulomatosis with polyangiitis.


title: Cranial nerves

text: Trauma to the skull, disease of bone, such as Paget's disease, and injury to nerves during surgery are other causes of nerve damage.


title: Cranial nerves

text: The Graeco-Roman anatomist Galen (AD 129–210) named seven pairs of cranial nerves. Much later, in 1664, English anatomist Sir Thomas Willis suggested that there were actually 9 pairs of nerves. Finally, in 1778, German anatomist Samuel Soemmering named the 12 pairs of nerves that are generally accepted today. However, because many of the nerves emerge from the brain stem as rootlets, there is continual debate as to how many nerves there actually are, and how they should be grouped. For example, there is reason to consider both the olfactory (I) and optic (II) nerves to be brain tracts, rather than cranial nerves.


title: Cranial nerves

text: Cranial nerves are also present in other vertebrates. Other amniotes (non-amphibian tetrapods) have cranial nerves similar to those of humans. In anamniotes (fishes and amphibians), the accessory nerve (XI) and hypoglossal nerve (XII) do not exist, with the accessory nerve (XI) being an integral part of the vagus nerve (X); the hypoglossal nerve (XII) is represented by a variable number of spinal nerves emerging from vertebral segments fused into the occiput. These two nerves only became discrete nerves in the ancestors of amniotes. The very small terminal nerve (nerve N or O) exists in humans but may not be functional. In other animals, it appears to be important to sexual receptivity based on perceptions of pheromones.


title: Tempura

text: A light batter is made of iced water, eggs, and soft wheat flour (cake, pastry or all-purpose flour). Sometimes baking soda or baking powder is added to make the fritter light. Using sparkling water in the place of plain water makes a similar effect. Tempura batter is traditionally mixed in small batches using chopsticks for only a few seconds, leaving lumps in the mixture that, along with the cold batter temperature, result in the unique fluffy and crisp tempura structure when cooked. The batter is often kept cold by adding ice or placing the bowl inside a larger bowl with ice. Overmixing the batter will activate wheat gluten, which causes the flour mixture to become soft and dough-like when fried.


title: Tempura

text: Specially formulated tempura flour is available in supermarkets. This is generally light (low-gluten) flour and occasionally contains leaveners such as baking powder.


title: Tempura

text: Tempura does not use breadcrumbs (panko) in the coating. Deep-fried foods which are coated with breadcrumbs are called "furai", Japanese-invented Western-style deep fried foods, such as "tonkatsu" or "ebi furai" (fried prawn).


title: Tempura

text: No seasonings or salt is added to the batter, or the ingredients, except for some recipes recommending rinsing seafood in salt water before preparation.


title: Tempura

text: Thin slices or strips of vegetables or seafood are dipped in the batter, then briefly deep-fried in hot oil. Vegetable oil or canola oil are most common; however, tempura was traditionally cooked using sesame oil. Many specialty shops still use sesame oil or tea seed oil, and it is thought certain compounds in these oils help to produce light, crispier batter.


title: Tempura

text: The bits of batter (known as "tenkasu") are scooped out between batches of tempura so they do not burn and leave a bad flavor in the oil. A small mesh scoop ("Ami jakushi") is used for this purpose. "Tenkasu" are often reserved as ingredients in other dishes or as a topping.


title: Tempura

text: The most popular seafood tempura is probably "ebi" (shrimp) tempura. Types of seafood used in tempura include:


title: Tempura

text: Vegetables tempura is called "yasai tempura". The all-vegetable tempura might be served as a vegetarian dish. Types of vegetables include:


title: Tempura

text: Cooked pieces of tempura are either eaten with dipping sauce, salted without sauce, or used to assemble other dishes. Tempura is commonly served with grated daikon and eaten hot immediately after frying. In Japan, it is often found in bowls of soba or udon soup in the form of shrimp, shiso leaf, or fritter. The most common sauce is tentsuyu sauce (roughly three parts "dashi", one part "mirin", and one part "shōyu"). Alternatively, skim tempura may be sprinkled with sea salt before eating. Mixtures of powdered green tea and salt or "yuzu" and salt are also used.


title: Tempura

text: "" is a type of tempura made with mixed vegetable strips, such as onion, carrot, and burdock, and sometimes including shrimp or squid, which are deep fried as small round fritters.


title: Tempura

text: Tempura is also used in combination with other foods. When served over "soba" (buckwheat noodles), it is called "tempura soba" or "tensoba". Tempura is also served as a "donburi" dish where tempura shrimp and vegetables are served over steamed rice in a bowl ("tendon") and on top of "udon" soup ("tempura udon").


title: Tempura

text: Earlier Japanese deep-fried food was either simply fried without breading or batter or fried with rice flour. However, toward the end of the 16th century, the technique of fritter-cooking with a batter of flour and eggs was acquired in Nagasaki from Portuguese missionaries. It was a way to fulfill the fasting and abstinence rules for Catholics surrounding the quarterly ember days (Spanish: "").. Portuguese and Spanish, both Neo-Latin languages, inherited "Têmpora" and "Témpora" from the Latin "." Hence the etymology of the word. In those days, tempura was deep-fried in lard with a batter of flour, water, eggs, and salt; unlike today, it was eaten without dipping sauce.


title: Tempura

text: In the early 17th century, around the Tokyo Bay area, tempura ingredients and preparation underwent a remarkable change as the Yatai (food cart) culture gained popularity. Making the best use of fresh seafood while preserving its delicate taste, tempura used only flour, eggs, and water as ingredients, and the batter was not flavored. As the batter was mixed minimally in cold water, it avoided the dough-like stickiness caused by the activation of wheat gluten, resulting in the crispy texture, which is now characteristic of tempura. It became customary to dip tempura quickly in a sauce mixed with grated daikon just before eating it.


title: Tempura

text: Today in Japan, the mainstream of tempura recipes originate from "Tokyo style (Edo style)" tempura, invented at the food stalls along the riverside fish market in the Edo period. The main reason tempura became popular was the abundance of seafood. In addition, as oil extraction techniques advanced, cooking oil became cheaper. Serving of deep-fried food indoors was prohibited during Edo because tempura oil was a fire hazard in Japanese buildings, which were made of paper and wood. Therefore, tempura gained popularity as fast food eaten at outdoor food stalls. It was skewered and eaten with a dipping sauce. Tempura is considered one of "the Edo Delicacies" along with soba (buckwheat noodles) and sushi, which were also food-stall take-outs.


title: Tempura

text: The modern tempura recipe was first published in 1671 in the cookbook called "料理献立抄". After the Meiji period, tempura was no longer considered a fast food item but developed as a high-class cuisine.


title: Tempura

text: The word "tempura", or the technique of dipping fish and vegetables into a batter and frying them, comes from the word , a Latin word meaning "times", "time period" used by both Spanish and Portuguese missionaries to refer to the Lenten period or Ember Days ("ad tempora quadragesima"), Fridays, and other Christian holy days. Ember Days, or ' in Latin, refer to holy days when Catholics avoid red meat and eat fish or vegetables instead. The idea that the word "tempura" may have been derived from the Portuguese noun ', meaning a condiment or seasoning of any kind, or from the verb ', meaning "to season" is also possible as the Japanese language could easily have assumed the word ' as is, without changing any vowels as the Portuguese pronunciation in this case is similar to the Japanese. There is still today a dish in Portugal very similar to tempura called "peixinhos da horta", "garden fishes", which consists of green beans dipped in a batter and fried.


title: Tempura

text: The term "tempura" is thought to have gained popularity in southern Japan; it became widely used to refer to any food prepared using hot oil, including some already existing Japanese foods. Today. Particularly in western Japan, the word "tempura" is also commonly used to refer to "satsuma-age", fried surimi fish cake which is made without batter.


title: Tempura

text: In Japan, restaurants specializing in tempura are called "tenpura-ya". Many restaurants offer tempura as part of a set meal or a "bento" (lunch box), and it is also a popular ingredient in take-out or convenience store "bento" boxes. The ingredients and styles of cooking and serving tempura vary greatly throughout the country, with importance placed on using fresh, seasonal ingredients.


title: Tempura

text: Outside Japan (as well as recently in Japan), there are many nontraditional and fusion uses of tempura. Chefs over the world include tempura dishes on their menus, and a wide variety of different batters and ingredients are used, including the nontraditional broccoli, zucchini, asparagus and chuchu. More unusual ingredients may include nori slices, dry fruit such as banana, and ice cream ("tempura"-based fried ice cream). American restaurants are known to serve tempura in the form of various types of meat, particularly chicken and cheeses, usually mozzarella. A variation is to use panko (breadcrumbs), which results in a crisper consistency than tempura batter, although in Japan this would be classified as a "furai" dish. Tempura (particularly shrimp) is often used as a filling in "makizushi". A more recent variation of tempura sushi has entire pieces of sushi dipped in batter and tempura-fried.


title: Tempura

text: In Bangladesh, the blossoms of pumpkins or marrows are often deep fried with a gram of rice flour spice mix, creating a Bengali-style tempura known as kumro ful bhaja.


title: Tempura

text: In Taiwan, tempura, as described in the preceding, is known as "tiānfùluó" () and can commonly be found on the menu in Japanese restaurants all over the island. A similar-sounding dish, "tianbula" () is usually sold at night markets. Tianbula is Japanese satsuma-age and was introduced to Taiwan under Japanese rule by people from Kyushu, where satsuma-age is commonly known as "tempura".


title: NMDA receptor

text: The "N"-methyl--aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and kainate receptors. Depending on its subunit composition, its ligands are glutamate and glycine (or -serine). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by Mg ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a “coincidence detector” and only once both of these conditions are met, the channel opens and it allows positively charged ions (cations) to flow through the cell membrane. The NMDA receptor is thought to be very important for controlling synaptic plasticity and mediating learning and memory functions.


title: NMDA receptor

text: The NMDA receptor is ionotropic, meaning it is a protein which allows the passage of ions through the cell membrane. The NMDA receptor is so named because the agonist molecule "N"-methyl--aspartate (NMDA) binds selectively to it, and not to other glutamate receptors. Activation of NMDA receptors results in the opening of the ion channel that is nonselective to cations, with a combined reversal potential near 0 mV. While the opening and closing of the ion channel is primarily gated by ligand binding, the current flow through the ion channel is voltage-dependent. Extracellular magnesium (Mg) and zinc (Zn) ions can bind to specific sites on the receptor, blocking the passage of other cations through the open ion channel. Depolarization of the cell dislodges and repels the Mg and Zn ions from the pore, thus allowing a voltage-dependent flow of sodium (Na) and calcium (Ca) ions into the cell and potassium (K) out of the cell. Ca flux through NMDA receptors in particular is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory, due to proteins which bind to and are activated by Ca ions.


title: NMDA receptor

text: Activity of the NMDA receptor is blocked by many psychoactive drugs such as phencyclidine (PCP), alcohol (ethanol) and dextromethorphan (DXM). The anaesthetic and analgesic effects of the drugs ketamine and nitrous oxide are also partially due to their effects at blocking NMDA receptor activity. In contrast, overactivation of NMDAR by NMDA agonists increases the cytosolic concentrations of calcium and zinc, which significantly contributes to neural death, an effect known to be prevented by cannabinoids, mediated by activation of the CB1 receptor, which leads HINT1 protein to counteract the toxic effects of NMDAR-mediated NO production and zinc release. As well as preventing methamphetamine-induced neurotoxicity via inhibition of nitric oxide synthase (nNOS) expression and astrocyte activation, is seen to reduce methamphetamine induced brain damage through a CB1-dependent and independent mechanisms, respectively, and inhibition of methamphetamine induced astrogliosis is likely to occur through a CB2 receptor dependent mechanism for THC. Since 1989, memantine has been recognized to be an uncompetitive antagonist of the NMDA receptor, entering the channel of the receptor after it has been activated and thereby blocking the flow of ions.


title: NMDA receptor

text: Overactivation of the receptor, causing excessive influx of Ca can lead to excitotoxicity which is implied to be involved in some neurodegenerative disorders. Blocking of NMDA receptors could therefore, in theory, be useful in treating such diseases. However, hypofunction of NMDA receptors (due to glutathione deficiency or other causes) may be involved in impairment of synaptic plasticity and could have other negative repercussions. The main problem with the utilization of NMDA receptor antagonists for neuroprotection is that the physiological actions of the NMDA receptor are essential for normal neuronal function. To be clinically useful NMDA antagonists need to block excessive activation without interfering with normal functions. Memantine has this property.


title: NMDA receptor

text: The discovery of NMDA receptors was followed by the synthesis and study of "N"-methyl--aspartic acid (NMDA) in the 1960s by Jeff Watkins and colleagues. In the early 1980s, NMDA receptors were shown to be involved in several central synaptic pathways. Receptor subunit selectivity was discovered in the early 1990s, which led to recognition of a new class of compounds that selectively inhibit the NR2B subunit. These findings led to vigorous campaign in the pharmaceutical industry. From this it was considered that NMDA receptors were associated with a variety of neurological disorders such as epilepsy, Parkinson's, Alzheimer's, Huntington's and other CNS disorders.


title: NMDA receptor

text: In 2002, it was discovered by Hilmar Bading and co-workers that the cellular consequences of NMDA receptor stimulation depend on the receptor's location on the neuronal cell surface. Synaptic NMDA receptors promote gene expression, plasticity-related events, and acquired neuroprotection. Extrasynaptic NMDA receptors promote death signaling; they cause transcriptional shut-off, mitochondrial dysfunction, and structural disintegration. This pathological triad of extrasynaptic NMDA receptor signaling represents a common conversion point in the etiology of several acute and chronic neurodegenerative conditions. The molecular basis for toxic extrasynaptic NMDA receptor signaling was uncovered by Hilmar Bading and co-workers in 2020. Extrasynaptic NMDA receptors form a death signaling complex with TRPM4. NMDAR/TRPM4 interaction interface inhibitors (also known as interface inhibitors) disrupt the NMDAR/TRPM4 complex and detoxify extrasynaptic NMDA receptors.


title: NMDA receptor

text: A fortuitous finding was made in 1968 when a woman was taking amantadine as flu medicine and experienced remarkable remission of her Parkinson's symptoms. This finding, reported by Scawab et al., was the beginning of medicinal chemistry of adamantane derivatives in the context of diseases affecting the CNS. Before this finding, memantine, another adamantane derivative, had been synthesized by Eli Lilly and Company in 1963. The purpose was to develop a hypoglycemic drug, but it showed no such efficacy. It was not until 1972 that a possible therapeutic importance of memantine for treating neurodegenerative disorders was discovered. From 1989 memantine has been recognized to be an uncompetitive antagonist of the NMDA receptor.


title: NMDA receptor

text: Functional NMDA receptors are heterotetramers composed of two GluN1 and typically two GluN2 subunits. There is one GluN1, four GluN2, and two GluN3 subunit encoding genes, and each gene may produce more than one splice variant.


title: NMDA receptor

text: The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it. The receptor is a heteromeric complex that interacts with multiple intracellular proteins by three different subunits: GluN1, GluN2 and GluN3. GluN1 has eight different isoforms due to alternative splicing of the gene GRIN1. There are four different GluN2 subunits (A-D) and two different Glun3 subunits (A and B). Six separate genes encode for GluN2 and GluN3. All the subunits share a common membrane topology that is dominated by a large extracellular N-terminus, a membrane region comprising three transmembrane segments, a re-entrant pore loop, an extracellular loop between the transmembrane segments that are structurally not well known, and an intracellular C-terminus, which are different in size depending on the subunit and provide multiple sites of interaction with many intracellular proteins. Figure 1 shows a basic structure of GluN1/GluN2 subunits that forms the binding site for memantine, Mg and ketamine.


title: NMDA receptor

text: Mg blocks the NMDA receptor channel in a voltage-dependent manner. The channels are also highly permeable to Ca. Activation of the receptor depends on glutamate binding, -serine or glycine binding at its GluN1-linked binding site and  AMPA receptor-mediated depolarization of the postsynaptic membrane, which relieves the voltage-dependent channel block by Mg. Activation and opening of the receptor channel thus allows the flow of K, Na and Ca ions, and the influx of Ca triggers intracellular signaling pathways. Allosteric receptor binding sites for zinc, proteins and the polyamines spermidine and spermine are also modulators for the NMDA receptor channels.


title: NMDA receptor

text: The GluN2B subunit has been involved in modulating activity such as learning, memory, processing and feeding behaviors, as well as being implicated in number of human derangements. The basic structure and functions associated with the NMDA receptor can be attributed to the GluN2B subunit. For example, the glutamate binding site and the control of the Mg block are formed by the GluN2B subunit. The high affinity sites for glycine antagonist are also exclusively displayed by the GluN1/GluN2B receptor.


title: NMDA receptor

text: GluN1/GluN2B transmembrane segments are considered to be the part of the receptor that forms the binding pockets for uncompetitive NMDA receptor antagonists, but the transmembrane segments structures are not fully known as stated above. It is claimed that three binding sites within the receptor, A644 on the GluNB subunit and A645 and N616 on the GluN1 subunit, are important for binding of memantine and related compounds as seen in figure 2.


title: NMDA receptor

text: The NMDA receptor forms a heterotetramer between two GluN1 and two GluN2 subunits (the subunits were previously denoted as GluN1 and GluN2), two obligatory GluN1 subunits and two regionally localized GluN2 subunits. A related gene family of GluN3 A and B subunits have an inhibitory effect on receptor activity. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the GluN1 transcripts and differential expression of the GluN2 subunits.


title: NMDA receptor

text: Each receptor subunit has modular design and each structural module, also represents a functional unit:


title: NMDA receptor

text: The glycine-binding modules of the GluN1 and GluN3 subunits and the glutamate-binding module of the GluN2A subunit have been expressed as soluble proteins, and their three-dimensional structure has been solved at atomic resolution by x-ray crystallography. This has revealed a common fold with amino acid-binding bacterial proteins and with the glutamate-binding module of AMPA-receptors and kainate-receptors.


title: NMDA receptor

text: NMDA receptors are a crucial part of the development of the central nervous system. The processes of learning, memory, and neuroplasticity rely on the mechanism of NMDA receptors. NMDA receptors are glutamate-gated cation channels that allow for an increase of calcium permeability. Channel activation of NMDA receptors is a result of the binding of two co agonists, glycine and glutamate.


title: NMDA receptor

text: Overactivation of NMDA receptors, causing excessive influx of Ca can lead to excitotoxicity. Excitotoxicity is implied to be involved in some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Blocking of NMDA receptors could therefore, in theory, be useful in treating such diseases. It is, however, important to preserve physiological NMDA receptor activity while trying to block its excessive, excitotoxic activity. This can possibly be achieved by uncompetitive antagonists, blocking the receptors ion channel when excessively open.


title: NMDA receptor

text: Uncompetitive NMDA receptor antagonists, or channel blockers, enter the channel of the NMDA receptor after it has been activated and thereby block the flow of ions. MK-801, ketamine, amantadine and memantine are examples of such antagonists, see figure 1. The off-rate of an antagonist from the receptors channel is an important factor as too slow off-rate can interfere with normal function of the receptor and too fast off-rate may give ineffective blockade of an excessively open receptor.


title: NMDA receptor

text: Memantine is an example of an uncompetitive channel blocker of the NMDA receptor, with a relatively rapid off-rate and low affinity. At physiological pH its amine group is positively charged and its receptor antagonism is voltage-dependent. It thereby mimics the physiological function of Mg as channel blocker. Memantine only blocks NMDA receptor associated channels during prolonged activation of the receptor, as it occurs under excitotoxic conditions, by replacing magnesium at the binding site. During normal receptor activity the channels only stay open for several milliseconds and under those circumstances memantine is unable to bind within the channels and therefore doesn't interfere with normal synaptic activity.


title: NMDA receptor

text: While a single GluN2 subunit is found in invertebrate organisms, four distinct isoforms of the GluN2 subunit are expressed in vertebrates and are referred to with the nomenclature GluN2A through GluN2D (encoded by GRIN2A, GRIN2B, GRIN2C, GRIN2D). Strong evidence shows that the genes encoding the GluN2 subunits in vertebrates have undergone at least two rounds of gene duplication. They contain the binding-site for glutamate. More importantly, each GluN2 subunit has a different intracellular C-terminal domain that can interact with different sets of signalling molecules. Unlike GluN1 subunits, GluN2 subunits are expressed differentially across various cell types and developmental timepoints and control the electrophysiological properties of the NMDA receptor. In classic circuits, GluN2B is mainly present in immature neurons and in extrasynaptic locations such as growth cones, and contains the binding-site for the selective inhibitor ifenprodil. However, in pyramidal cell synapses in the newly evolved primate dorsolateral prefrontal cortex, GluN2B are exclusively within the postsynaptic density, and mediate higher cognitive operations such as working memory. This is consistent with the expansion in GluN2B actions and expression across the cortical hierarchy in monkeys and humans and across primate cortex evolution.


title: NMDA receptor

text: While GluN2B is predominant in the early postnatal brain, the number of GluN2A subunits increases during early development; eventually, GluN2A subunits become more numerous than GluN2B. This is called the GluN2B-GluN2A developmental switch, and is notable because of the different kinetics each GluN2 subunit contributes to receptor function. For instance, greater ratios of the GluN2B subunit leads to NMDA receptors which remain open longer compared to those with more GluN2A. This may in part account for greater memory abilities in the immediate postnatal period compared to late in life, which is the principle behind genetically altered 'doogie mice'.


title: NMDA receptor

text: The detailed time course of this switch in the human cerebellum has been estimated using expression microarray and RNA seq and is shown in the figure on the right.


title: NMDA receptor

text: The GluN2B and GluN2A subunits also have differential roles in mediating excitotoxic neuronal death. The developmental switch in subunit composition is thought to explain the developmental changes in NMDA neurotoxicity. Homozygous disruption of the gene for GluN2B in mice causes perinatal lethality, whereas disruption of the GluN2A gene produces viable mice, although with impaired hippocampal plasticity. One study suggests that reelin may play a role in the NMDA receptor maturation by increasing the GluN2B subunit mobility.


title: NMDA receptor

text: Granule cell precursors (GCPs) of the cerebellum, after undergoing symmetric cell division in the external granule-cell layer (EGL), migrate into the internal granule-cell layer (IGL) where they down-regulate GluN2B and activate GluN2C, a process that is independent of neuregulin beta signaling through ErbB2 and ErbB4 receptors.


title: NMDA receptor

text: NMDA receptors have been implicated by a number of studies to be strongly involved with excitotoxicity. Because NMDA receptors play an important role in the health and function of neurons, there has been much discussion on how these receptors can affect both cell survival and cell death. Recent evidence supports the hypothesis that overstimulation of extrasynaptic NMDA receptors has more to do with excitotoxicity than stimulation of their synaptic counterparts. In addition, while stimulation of extrasynaptic NMDA receptors appear to contribute to cell death, there is evidence to suggest that stimulation of synaptic NMDA receptors contributes to the health and longevity of the cell. There is ample evidence to support the dual nature of NMDA receptors based on location, and the hypothesis explaining the two differing mechanisms is known as the "localization hypothesis".


title: NMDA receptor

text: In order to support the localization hypothesis, it would be necessary to show differing cellular signaling pathways are activated by NMDA receptors based on its location within the cell membrane. Experiments have been designed to stimulate either synaptic or non-synaptic NMDA receptors exclusively. These types of experiments have shown that different pathways are being activated or regulated depending on the location of the signal origin. Many of these pathways use the same protein signals, but are regulated oppositely by NMDARs depending on its location. For example, synaptic NMDA excitation caused a decrease in the intracellular concentration of p38 mitogen-activated protein kinase (p38MAPK). Extrasynaptic stimulation NMDARs regulated p38MAPK in the opposite fashion, causing an increase in intracellular concentration. Experiments of this type have since been repeated with the results indicating these differences stretch across many pathways linked to cell survival and excitotoxicity.


title: NMDA receptor

text: Two specific proteins have been identified as a major pathway responsible for these different cellular responses ERK1/2, and Jacob. ERK1/2 is responsible for phosphorylation of Jacob when excited by synaptic NMDARs. This information is then transported to the nucleus. Phosphorylation of Jacob does not take place with extrasynaptic NMDA stimulation. This allows the transcription factors in the nucleus to respond differently based in the phosphorylation state of Jacob.


title: NMDA receptor

text: NMDA receptors (NMDARs) critically influence the induction of synaptic plasticity. NMDARs trigger both long-term potentiation (LTP) and long-term depression (LTD) via fast synaptic transmission. Experimental data suggest that extrasynaptic NMDA receptors inhibit LTP while producing LTD. Inhibition of LTP can be prevented with the introduction of a NMDA antagonist. A theta burst stimulation that usually induces LTP with synaptic NMDARs, when applied selectively to extrasynaptic NMDARs produces a LTD. Experimentation also indicates that extrasynaptic activity is not required for the formation of LTP. In addition, both synaptic and extrasynaptic activity are involved in expressing a full LTD.


title: NMDA receptor

text: Another factor that seems to affect NMDAR induced toxicity is the observed variation in subunit makeup. NMDA receptors are heterotetramers with two GluN1 subunits and two variable subunits. Two of these variable subunits, GluN2A and GluN2B, have been shown to preferentially lead to cell survival and cell death cascades respectively. Although both subunits are found in synaptic and extrasynaptic NMDARs there is some evidence to suggest that the GluN2B subunit occurs more frequently in extrasynaptic receptors. This observation could help explain the dualistic role that NMDA receptors play in excitotoxicity.


title: NMDA receptor

text: Despite the compelling evidence and the relative simplicity of these two theories working in tandem, there is still disagreement about the significance of these claims. Some problems in proving these theories arise with the difficulty of using pharmacological means to determine the subtypes of specific NMDARs. In addition, the theory of subunit variation does not explain how this effect might predominate, as it is widely held that the most common tetramer, made from two GluN1 subunits and one of each subunit GluN2A and GluN2B, makes up a high percentage of the NMDARs.


title: NMDA receptor

text: Excitotoxicity has been thought to play a role in the degenerative properties of neurodegenerative conditions since the late 1950s. NMDA receptors seem to play an important role in many of these degenerative diseases affecting the brain. Most notably, excitotoxic events involving NMDA receptors have been linked to Alzheimer's disease and Huntington's disease, as well as with other medical conditions such as strokes and epilepsy. Treating these conditions with one of the many known NMDA receptor antagonists, however, leads to a variety of unwanted side effects, some of which can be severe. These side effects are, in part, observed because the NMDA receptors do not just signal for cell death but also play an important role in its vitality. Treatment for these conditions might be found in blocking NMDA receptors not found at the synapse. One class of excitotoxicity in disease includes gain-of-function mutations in GRIN2B and GRIN1 associated with cortical malformations, such as polymicrogyria.


title: NMDA receptor

text: Activation of NMDA receptors requires binding of glutamate or aspartate (aspartate does not stimulate the receptors as strongly). In addition, NMDARs also require the binding of the co-agonist glycine for the efficient opening of the ion channel, which is a part of this receptor.


title: NMDA receptor

text: -Serine has also been found to co-agonize the NMDA receptor with even greater potency than glycine. It is produced by serine racemase, and is enriched in the same areas as NMDA receptors. Removal of -serine can block NMDA-mediated excitatory neurotransmission in many areas. Recently, it has been shown that -serine can be released both by neurons and astrocytes to regulate NMDA receptors.


title: NMDA receptor

text: NMDA receptor (NMDAR)-mediated currents are directly related to membrane depolarization. NMDA agonists therefore exhibit fast Mg unbinding kinetics, increasing channel open probability with depolarization. This property is fundamental to the role of the NMDA receptor in memory and learning, and it has been suggested that this channel is a biochemical substrate of Hebbian learning, where it can act as a coincidence detector for membrane depolarization and synaptic transmission.


title: NMDA receptor

text: An example of memantine derivative is neramexane which was discovered by studying number of aminoalkyl cyclohexanes, with memantine as the template, as NMDA receptor antagonists. Neramexane binds to the same site as memantine within the NMDA receptor associated channel and with comparable affinity. It does also show very similar bioavailability and blocking kinetics in vivo as memantine. Neramexane went to clinical trials for four indications, including Alzheimer's disease.


title: NMDA receptor

text: "N"-Methyl--aspartic acid (NMDA), which the NMDA receptor was named after, is a partial agonist of the active or glutamate recognition site.


title: NMDA receptor

text: 3,5-Dibromo--phenylalanine, a naturally occurring halogenated derivative of -phenylalanine, is a weak partial NMDA receptor agonist acting on the glycine site. 3,5-Dibromo--phenylalanine has been proposed a novel therapeutic drug candidate for treatment of neuropsychiatric disorders and diseases such as schizophrenia, and neurological disorders such as ischemic stroke and epileptic seizures.


title: NMDA receptor

text: Other partial agonists of the NMDA receptor acting on novel sites such as rapastinel (GLYX-13) and apimostinel (NRX-1074) are now viewed for the development of new drugs with antidepressant and analgesic effects without obvious psychotomimetic activities.


title: NMDA receptor

text: Antagonists of the NMDA receptor are used as anesthetics for animals and sometimes humans, and are often used as recreational drugs due to their hallucinogenic properties, in addition to their unique effects at elevated dosages such as dissociation. When certain NMDA receptor antagonists are given to rodents in large doses, they can cause a form of brain damage called Olney's lesions. NMDA receptor antagonists that have been shown to induce Olney's lesions include ketamine, phencyclidine, and dextrorphan (a metabolite of dextromethorphan), as well as some NMDA receptor antagonists used only in research environments. So far, the published research on Olney's lesions is inconclusive in its occurrence upon human or monkey brain tissues with respect to an increase in the presence of NMDA receptor antagonists.


title: NMDA receptor

text: Most NMDAR antagonists are uncompetitive or noncompetitive blockers of the channel pore or are antagonists of the glycine co-regulatory site rather than antagonists of the active/glutamate site.


title: NMDA receptor

text: Some common agents in which weak NMDA receptor antagonism is a secondary or additional action include:


title: NMDA receptor

text: The NMDA receptor is regulated via nitrosylation and aminoadamantane can be used as a target-directed shuttle to bring nitrogen oxide (NO) close to the site within the NMDA receptor where it can nitrosylate and regulate the ion channel conductivity. A NO donor that can be used to decrease NMDA receptor activity is the alkyl nitrate nitroglycerin. Unlike many other NO donors, alkyl nitrates do not have potential NO associated neurotoxic effects. Alkyl nitrates donate NO in the form of a nitro group as seen in figure 7, -NO-, which is a safe donor that avoids neurotoxicity. The nitro group must be targeted to the NMDA receptor, otherwise other effects of NO such as dilatation of blood vessels and consequent hypotension could result.


title: NMDA receptor

text: Nitromemantine is a second-generation derivative of memantine, it reduces excitotoxicity mediated by overactivation of the glutamatergic system by blocking NMDA receptor without sacrificing safety. Provisional studies in animal models show that nitromemantines are more effective than memantine as neuroprotectants, both in vitro and in vivo. Memantine and newer derivatives could become very important weapons in the fight against neuronal damage.


title: NMDA receptor

text: The main problem with the development of NMDA antagonists for neuroprotection is that physiological NMDA receptor activity is essential for normal neuronal function. Complete blockade of all NMDA receptor activity results in side effects such as hallucinations, agitation and anesthesia. To be clinically relevant, an NMDA receptor antagonist must limit its action to blockade of excessive activation, without limiting normal function of the receptor.


title: NMDA receptor

text: Competitive NMDA receptor antagonists, which were developed first, are not a good option because they compete and bind to the same site (NR2 subunit) on the receptor as the agonist, glutamate, and therefore block normal function also. They will block healthy areas of the brain prior to having an impact on pathological areas, because healthy areas contain lower levels of agonist than pathological areas. These antagonists can be displaced from the receptor by high concentration of glutamate which can exist under excitotoxic circumstances.


title: NMDA receptor

text: Uncompetitive NMDA receptor antagonists block within the ion channel at the Mg site (pore region) and prevent excessive influx of Ca. Noncompetitive antagonism refers to a type of block that an increased concentration of glutamate cannot overcome, and is dependent upon prior activation of the receptor by the agonist, i.e. it only enters the channel when it is opened by agonist.


title: NMDA receptor

text: Because of these adverse side effects of high affinity blockers, the search for clinically successful NMDA receptor antagonists for neurodegenerative diseases continued and focused on developing low affinity blockers. However the affinity could not be too low and dwell time not too short (as seen with Mg) where membrane depolarization relieves the block. The discovery was thereby development of uncompetitive antagonist with longer dwell time than Mg in the channel but shorter than MK-801. That way the drug obtained would only block excessively open NMDA receptor associated channels but not normal neurotransmission. Memantine is that drug. It is a derivative of amantadine which was first an anti-influenza agent but was later discovered by coincidence to have efficacy in Parkinson's disease. Chemical structures of memantine and amantadine can be seen in figure 5. The compound was first thought to be dopaminergic or anticholinergic but was later found to be an NMDA receptor antagonist.


title: NMDA receptor

text: Memantine is the first drug approved for treatment of severe and more advanced Alzheimer's disease, which for example anticholinergic drugs do not do much good for. It helps recovery of synaptic function and in that way improves impaired memory and learning. In 2015 memantine is also in trials for therapeutic importance in additional neurological disorders.


title: NMDA receptor

text: Many second-generation memantine derivatives have been in development that may show even better neuroprotective effects, where the main thought is to use other safe but effective modulatory sites on the NMDA receptor in addition to its associated ion channel.


title: NMDA receptor

text: Memantine (1-amino-3,5-dimethyladamantane) is an aminoalkyl cyclohexane derivative and an atypical drug compound with non-planar, three dimensional tricyclic structure. Figure 8 shows SAR for aminoalkyl cyclohexane derivative. Memantine has several important features in its structure for its effectiveness:


title: NMDA receptor

text: Despite the small structural difference between memantine and amantadine, two adamantane derivatives, the affinity for the binding site of NR1/NR2B subunit is much greater for memantine. In patch-clamp measurements memantine has an IC of (2.3+0.3) μM while amantadine has an IC of (71.0+11.1) μM.


title: NMDA receptor

text: The binding site with the highest affinity is called the dominant binding site. It involves a connection between the amine group of memantine and the NR1-N161 binding pocket of the NR1/NR2B subunit. The methyl side groups play an important role in increasing the affinity to the open NMDA receptor channels and making it a much better neuroprotective drug than amantadine. The binding pockets for the methyl groups are considered to be at the NR1-A645 and NR2B-A644 of the NR1/NR2B. The binding pockets are shown in figure 2.


title: NMDA receptor

text: Memantine binds at or near to the Mg site inside the NMDA receptor associated channel. The -NH group on memantine, which is protonated under physiological pH of the body, represents the region that binds at or near to the Mg site. Adding two methyl groups to the -N on the memantine structure has shown to decrease affinity, giving an IC value of (28.4+1.4) μM.


title: NMDA receptor

text: Several derivatives of Nitromemantine, a second-generation derivative of memantine, have been synthesized in order to perform a detailed structure activity relationship (SAR) of these novel drugs. One class, containing a nitro (NO) group opposite to the bridgehead amine (NH), showed a promising outcome. Nitromemantine utilizes memantine binding site on the NMDA receptor to target the NO (X= 1 or 2) group for interaction with the S- nitrosylation/redox site external to the memantine binding site. Lengthening the side chains of memantine compensates for the worse drug affinity in the channel associated with the addition of the –ONO group


title: NMDA receptor

text: Excitotoxicity is implied to be involved in some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. Blocking of NMDA receptors could therefore, in theory, be useful in treating such diseases. It is, however, important to preserve physiological NMDA receptor activity while trying to block its excessive, excitotoxic activity. This can possibly be achieved by uncompetitive antagonists, blocking the receptors ion channel when excessively open


title: NMDA receptor

text: Memantine is an example of uncompetitive NMDA receptor antagonist that has approved indication for the neurodegenerative disease Alzheimer's disease. In 2015 memantine is still in clinical trials for additional neurological diseases.