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AS Roma
Stadiums
Stadiums The club's first stadium was the Motovelodromo Appio, previously used by Alba-Audace. Roma only played the 1927–28 season there until they moved to Campo Testaccio. Campo Testaccio was used through 1929 to 1940 until the team then moved to the Stadio Nazionale del PNF, where they spent 13 years. In the 1953–54 season, Roma moved to the Stadio Olimpico, which it shares with Lazio. The stadium has undergone several changes over the years, with the most significant taking place in the 1989–90 season, when the stadium was mostly demolished and reconstructed for the 1990 FIFA World Cup held in Italy. During reconstruction, Roma played its home matches at Stadio Flaminio. On 30 December 2012, then-club president James Pallotta announced Stadio della Roma, a planned new stadium in the Tor di Valle area of Rome with a capacity of 52,500. Five years later, the Region of Lazio and the mayor of Rome rejected the stadium's construction proposal, before being approved soon following approval of readjustments to the stadium's design. However, in August 2017, the stadium suffered another delay, but that December, the project was again given the go-ahead and was expected to be built by 2020. This plan was completely cancelled by February 2021. In 2022, the club pivoted to a new site in Pietralata for the New AS Roma Stadium: construction is expected to start between 2025 and 2026 and is expected to conclude by 2028.
AS Roma
List of stadiums used by the club
List of stadiums used by the club 1927–1928 Motovelodromo Appio 1929–1940 Campo Testaccio 1940–1953 Stadio Nazionale del PNF 1953– Stadio Olimpico (1989–1990 Stadio Flaminio due to renovations on Olimpico)
AS Roma
Trigoria
Trigoria A sports centre located in Trigoria at kilometre 3600 in south-east of Rome was purchased on 22 July 1977 by then club president Gaetano Anzalone. It was opened on 23 July 1979 as Anzalone's final act as president. The complex had its first expansion in 1984 when the club was handled by Dino Viola and another in 1998 under the chairmanship of Franco Sensi. The centre's official name is the Fulvio Bernardini di Trigoria, named after club icon Fulvio Bernardini. On 4 September 2019, the Trigoria training ground began to serve also as a private school named 'Liceo Scientifico Sportivo A.S. Roma' exclusively educating only the team's youth players in a renovated building on the training ground premises. 80 students are currently enrolled in the school which features its own cafeteria and gym. The centre is also known for hosting the Argentina national team during the 1990 FIFA World Cup, held in Italy.
AS Roma
Supporters
Supporters thumb|left|Roma fans at the Stadio Olimpico Roma is the fifth-most supported football club in Italy – behind Juventus, Internazionale, A.C. Milan and Napoli – with approximately 7% of Italian football fans supporting the club, according to the Doxa Institute-L'Espresso's research of April 2006. Historically, the largest section of Roma supporters in the city of Rome have come from the inner-city, especially Testaccio. The traditional ultras group of the club was Commando Ultrà Curva Sud commonly abbreviated as CUCS. This group was founded by the merger of many smaller groups and was considered one of the most historic in the history of European football. However, by the mid-1990s, CUCS had been usurped by rival factions and ultimately broke up. Since that time, the Curva Sud of the Stadio Olimpico has been controlled by more right-wing groups, including A.S. Roma Ultras, Boys and Giovinezza, among others. However, the oldest group, Fedayn, is apolitical, and politics is not the main identity of Roma, just a part of their overall identity. Besides ultras groups, it is believed Roma fans support the left as opposed to Lazio supporters, which are notoriously proud of their right-wing affiliation. In November 2015, Roma's ultras and their Lazio counterparts boycotted Roma's 1–0 victory in the Derby della Capitale in protest at new safety measures imposed at the Stadio Olimpico. The measures – imposed by Rome's prefect, Franco Gabrielli – had involved plastic glass dividing walls being installed in both the Curva Sud and Curva Nord, splitting the sections behind each goal in two. Both sets of ultras continued their protests for the rest of the season, including during Roma's 4–1 victory in the return fixture. Lazio's ultras returned to the Curva Nord for Roma's 1–4 victory in December 2016, but the Roma ultras continue to boycott matches. thumb|Stadio Olimpico during a Roma match The most known club anthem is "Roma (non-si discute, si ama)", also known as "Roma Roma", by singer Antonello Venditti. The title roughly means, "Roma is not to be questioned, it is to be loved," and it is sung before each match. The song "Grazie Roma", by the same singer, is played at the end of victorious home matches. Recently, the main riff of The White Stripes' song "Seven Nation Army" has also become widely popular at matches.
AS Roma
Rivalries
Rivalries In Italian football, Roma is a club with many rivalries; first and foremost is their rivalry with Lazio, the club with whom they share the Stadio Olimpico. The derby between the two is called the Derby della Capitale, it is amongst the most heated and emotional footballing rivalries in the world. The fixture has seen some occasional instances of violence in the past, including the death of Lazio fan Vincenzo Paparelli in 1979–80 as a result of an emergency flare fired from the Curva Sud, and the abandonment of a match in March 2004 following unfounded rumours of a fatality which led to violence outside the stadium. Against Napoli, Roma also compete in the Derby del Sole, meaning the "Derby of the Sun". Nowadays, fans also consider other Juventus (a rivalry born especially in the 1980s), Milan, Atalanta (since 1984, when friendly relations between the two clubs' ultras deteriorated), and Internazionale (increased in recent years) among their rivals, as they are often competitors for the top four spots in the league table and qualification for the UEFA Champions League.
AS Roma
Hooliganism
Hooliganism Rivalries with other teams have escalated into serious violence. A group of ultras who label themselves the Fedayn — 'the devotees' — after a group of long-forgotten Iranian guerrilla fighters are regarded to be responsible for the organised hooliganism. In 2014 Daniele De Santis, a Roma ultra, was convicted of shooting Ciro Esposito and two others during clashes with Napoli fans who were in Rome for their club's Coppa Italia final against Fiorentina. Esposito died of his wounds. De Santis was sentenced to 26 years in prison, later reduced to 16 years on appeal. Roma ultras have displayed banners celebrating De Santis. There have been multiple instances of Roma ultras attacking supporters of foreign clubs when playing in Rome. These attacks have regularly featured the Roma ultras using knives, poles, flares, bottles and stones on unarmed foreign supporters, resulting in multiple hospitalisations. Home games against Liverpool in 1984 and 2001, Middlesbrough in 2006, Manchester United in 2007, Arsenal in 2009, Tottenham Hotspur in 2012, and Chelsea in 2017 have all resulted in multiple stabbings and other injuries to foreign supporters. In 2018 Roma ultras travelling to an away game at Liverpool attacked home supporters, resulting in a home supporter being critically injured.
AS Roma
Players
Players
AS Roma
Current squad
Current squad
AS Roma
Primavera squad
Primavera squad
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Out on loan
Out on loan
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Women team
Women team
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Notable players
Notable players Among the most iconic Roma players throughout its history are Attilio Ferraris IV, the club’s first captain; Fulvio Bernardini and Guido Masetti, key figures in the 1942 Scudetto win; and Amedeo Amadei, who still holds the record as the youngest Serie A goalscorer. The 1950s and 1960s saw stars like Giacomo Losi, Dino da Costa (top scorer in the Rome derby), and Pedro Manfredini. In the 1980s, Agostino Di Bartolomei, Bruno Conti, Roberto Pruzzo, and the Brazilian midfielder Falcão were central to Roma's second league title and European success. Later decades featured fan favorites such as Rudi Völler, Giuseppe Giannini, Aldair, Cafu, and Roman-born legends Francesco Totti and Daniele De Rossi.
AS Roma
Retired numbers
Retired numbers Since 2017, Roma has not issued the squad number 10 to commemorate Francesco Totti, who was retired from football since 2017. It was going to be issued to Paulo Dybala in 2022, but Dybala chose the number 21 instead of number 10. (1993–2017)
AS Roma
Management staff
Management staff
AS Roma
Chairmen history
Chairmen history Roma have had numerous chairmen ( or ) over the course of their history, some of which have been the owners and co-owners of the club, some of them were nominated by the owners. Franco Sensi was the chairman until his death in 2008, with his daughter, Roma CEO Rosella Sensi taking his place as chairman. Here is a complete list of Roma chairmen from 1927 until the present day.  NameYearsItalo Foschi1927–1928Renato Sacerdoti1928–1935Vittorio Scialoja1935–1936Igino Betti1936–1941Edgardo Bazzini1941–1944Pietro Baldassarre1944–1949Pier Carlo Restagno1949–1952Romolo Vaselli1952Renato Sacerdoti1952–1958Anacleto Gianni1958–1962Francesco Marini-Dettina1962–1965Franco Evangelisti1965–1968Francesco Ranucci1968–1969 NameYearsAlvaro Marchini1969–1971Gaetano Anzalone1971–1979Dino Viola1979–1991Flora Viola1991Giuseppe Ciarrapico1991–1993Ciro Di Martino1993Franco Sensi1993–2008Rosella Sensi2008–2011Roberto Cappelli2011Thomas R. DiBenedetto2011–2012James Pallotta2012–2020Dan Friedkin2020–present
AS Roma
Managerial history
Managerial history Roma have had many managers and trainers running the team during their history, here is a chronological list of them from 1927 onwards.  ManagerYears William Garbutt1927–29 Guido Baccani1929–30 Herbert Burgess1930–32 Lászlo Barr1932–33 Lajos Kovács1933–34 Luigi Barbesino1934–38 Guido Ara1938–39 Alfréd Schaffer1939–42 Géza Kertész1942–43 Guido Masetti1943–45 Giovanni Degni1945–47 Imre Senkey1947–48 Luigi Brunella1948–49 Fulvio Bernardini1949–50 Adolfo Baloncieri1950 Pietro Serantoni1950 Guido Masetti1950–51 Giuseppe Viani1951–53 Mario Varglien1953–54 Jesse Carver1954–56 György Sárosi1956 Guido Masetti1956–57 Alec Stock1957–58 Gunnar Nordahl1958–59 György Sarosi1959–60 ManagerYears Alfredo Foni1960–61 Luis Carniglia1961–63 Naim Kryeziu1963 Alfredo Foni1963–64 Luis Miró1964–65 Juan Carlos Lorenzo1965–66 Oronzo Pugliese1966–68 Helenio Herrera1968–70 Luciano Tessari1970 Helenio Herrera1971–72 Tonino Trebiciani1972–73 Nils Liedholm1974–77 Gustavo Giagnoni1978–79 Ferruccio Valcareggi1979–80 Nils Liedholm1980–84 Sven-Göran Eriksson1984–87 Angelo Sormani1987 Nils Liedholm1987–89 Luciano Spinosi1989 Gigi Radice1989–90 Ottavio Bianchi1990–92 Vujadin Boškov1992–93 Carlo Mazzone1993–96 Carlos Bianchi1996 Nils Liedholm1996 ManagerYears Ezio Sella1996 Zdeněk Zeman1997–99 Fabio Capello1999–04 Cesare Prandelli2004 Rudi Völler2004 Luigi Delneri2004–05 Bruno Conti2005 Luciano Spalletti2005–09 Claudio Ranieri2009–11 Vincenzo Montella2011 Luis Enrique2011–12 Zdeněk Zeman2012–13 Aurelio Andreazzoli2013 Rudi Garcia2013–16 Luciano Spalletti2016–17 Eusebio Di Francesco2017–19 Claudio Ranieri2019 Paulo Fonseca2019–21 José Mourinho2021–24 Daniele De Rossi2024 Ivan Jurić2024 Claudio Ranieri2024–25
AS Roma
Honours
Honours thumb|270px|Roma fans celebrating the Scudetto in 2001 at the Circus Maximus
AS Roma
National titles
National titles Serie A: Winners (3): 1941–42, 1982–83, 2000–01 Runners-up: (14): 1930–31, 1935–36, 1980–81, 1983–84, 1985–86, 2001–02, 2003–04, 2005–06, 2006–07, 2007–08, 2009–10, 2013–14, 2014–15, 2016–17 Coppa Italia: Winners (9): 1963–64, 1968–69, 1979–80, 1980–81, 1983–84, 1985–86, 1990–91, 2006–07, 2007–08 Runners-up: (8): 1936–37, 1940–41, 1992–93, 2002–03, 2004–05, 2005–06, 2009–10, 2012–13 Supercoppa Italiana: Winners (2): 2001, 2007
AS Roma
European titles
European titles European Cup: Runners-up (1): 1983–84 UEFA Cup / UEFA Europa League: Runners-up (2): 1990–91, 2022–23 UEFA Conference League: Winners (1): 2021–22 Inter-Cities Fairs Cup: Winners (1): 1960–61
AS Roma
Other titles
Other titles Serie B: Winners (1): 1951–52 Anglo-Italian Cup: Winners (1): 1972
AS Roma
Hall of Fame
Hall of Fame On 7 October 2012, the AS Roma Hall of Fame was announced. The Hall of Fame players were voted via the club's official website and a special Hall of Fame panel. In 2013 four players were voted in. In 2014, the third year of AS Roma Hall of Fame four more players were voted in. Added in 2012: Franco Tancredi (1977–1990) Cafu (1997–2003) Giacomo Losi (1954–1969) Aldair (1990–2003) Francesco Rocca (1972–1981) Fulvio Bernardini (1928–1939) Agostino Di Bartolomei (1972–1975; 1976–1984) Falcão (1980–1985) Bruno Conti (1973–1975; 1976–1978; 1979–1991) Roberto Pruzzo (1978–1988) Amedeo Amadei (1936–1938; 1939–1948) Added in 2013: Attilio Ferraris (1927–1934; 1938–1939) Sebastiano Nela (1981–1992) Giuseppe Giannini (1981–1996) Vincenzo Montella (1999–2009) Added in 2014: Alcides Ghiggia (1953–1961) Carlo Ancelotti (1979–1987) Rudi Völler (1987–1992) Vincent Candela (1997–2005) Added in 2015: Guido Masetti (1930–1943) Sergio Santarini (1968–1981) Damiano Tommasi (1996–2006) Gabriel Batistuta (2000–2003) Added in 2016: Giorgio Carpi (1927–1937) Toninho Cerezo (1983–1986) Giancarlo De Sisti (1960–1965; 1974–1979) Arcadio Venturi (1948–1957) Added in 2017: Francesco Totti (1992–2017) Added in 2018: Mario De Micheli (1927–1932) Giuliano Taccola (1967–1969) Rodolfo Volk (1928–1933)
AS Roma
Club records and statistics
Club records and statistics thumb|300px|Historical AS Roma positions in Serie A Francesco Totti currently holds Roma's official appearance record, having made 786 appearances in all competitions, over the course of 25 seasons from 1993 until 2017. He also holds the record for Serie A appearances with 619, as he passed Giacomo Losi on 1 March 2008 during a home match against Parma. Including all competitions, Totti is the all-time leading goalscorer for Roma with 307 goals since joining the club, 250 of which were scored in Serie A (another Roma record). Roberto Pruzzo, who was the all-time topscorer since 1988, comes in second in all competitions with 138. In 1930–31, Rodolfo Volk scored 29 goals in Serie A over the course of a single season. Not only was Volk the league's top scorer that year, he also set a Roma record for most goals scored in a season, which would later be matched by Edin Džeko in 2016–17. Its major founders Fortitudo and Alba having been relegated at the end of 1926–27 campaign, new-founded Roma had to take part to Southern First Division championship (Serie B) for its inaugural season. Nevertheless, the FIGC decided on a special enlargement of first level division re-admitting AS Roma and SSC Napoli. The first ever official matches participated in by Roma was in the National Division, the predecessor of Serie A, of 1927–28, against Livorno, a 2–0 Roma win. The biggest ever victory recorded by Roma was 9–0 against Cremonese during the 1929–30 Serie A season. The heaviest defeat Roma have ever suffered is 1–7, which has occurred five times; against Juventus in 1931–32, Torino in 1947–48, Manchester United in 2006–07, Bayern Munich in 2014–15 and Fiorentina in 2018–19.
AS Roma
Divisional movements
Divisional movements SeriesYearsLastPromotionsRelegationsA922024–2545 times to Europe 1 (1951)B11951–52 1 (1952)never93 years of professional football in Italy since 1929AS Roma created in National Division in 1927
AS Roma
UEFA club coefficient ranking
UEFA club coefficient ranking Rank Club Points8 Dortmund 84.7509 Barcelona 83.25010 Roma80.50011 Benfica77.75012 Atlético 77.500
AS Roma
UEFA rankings since 2005
UEFA rankings since 2005 Season Ranking Movement Points Change2024–2510 –480.400 –20.6002023–246 +4101.000 +4.0002022–2310 +197.000 –3.0002021–2211 +2100.000 +10.0002020–2113 +490.000 +10.0002019–2017 –380.000 –1.0002018–1914 +781.000 +17.0002017–1821 +1664.000 +25.0002016–1737 +1439.000 +11.5002015–1651 –527.5002014–1546 +949.500 +13.0002013–1455 –1226.500 –14.0002012–1343 –1740.500 –17.0002011–1226 –1057.500 –15.5002010–1116 –273.000 +2.0002009–1014071.000 +5.0002008–0914 +266.000 +4.0002007–0816062.000 +5.0002006–0716 +157.000 +3.0002005–0617 –154.000 +1.000
AS Roma
Football club Elo rating
Football club Elo rating Rank Club Points17 Brentford182018 Dortmund181519 Roma180720 Bournemouth180721 Juventus 1803
AS Roma
As a company
As a company Since 1999, during Franco Sensi's period in charge, Associazione Sportiva Roma has been a listed on Borsa Italiana. From 2004 to 2011, Roma's shares are distributed between; 67.1% to Compagnia Italpetroli SpA (the Sensi family holding; Banca di Roma later acquired 49% stake on Italpetroli due to debt restructuring) and 32.9% to other public shareholders. Along with Lazio and Juventus, Roma is one of only three quotated Italian clubs. According to The Football Money League published by consultants Deloitte, in the 2010–11 season, Roma was the 15th highest-earning football club in the world with an estimated revenue of €143.5 million. In April 2008, after months of speculation, George Soros was confirmed by Rosella Sensi, CEO of Serie A club A.S. Roma, to be bidding for a takeover. The takeover bid was successively rejected by the Sensi family, who instead preferred to maintain the club's ownership. On 17 August 2008 club chairman and owner Franco Sensi died after a long illness; his place at the chairmanship of the club was successively taken by his daughter Rosella. Since the takeover in 2011, NEEP Roma Holding S.p.A. has owned all shares Sensi previously hold. NEEP, itself a joint venture, was held by DiBenedetto AS Roma LLC (later renamed to AS Roma SPV, LLC) and Unicredit in 60–40 ratio from 2011 to 2013, which the former had four real person shareholders in equal ratio, led by future Roma president Thomas R. DiBenedetto (2011–12). The takeover also activated a mandatory bid of shares from the general public, however not all minority shareholders were willing to sell their shares. The mandatory bid meant NEEP held 78.038% of shares of AS Roma (increased from 67.1% of the Sensi). On 1 August 2013, the president of Roma as well as one of the four American shareholders of AS Roma SPV, LLC, James Pallotta, bought an additional 9% shares of NEEP Roma Holding from Unicredit (through Raptor Holdco LLC), as the bank was not willing to fully participate in the capital increase of NEEP from €120,000 to €160,008,905 (excluding share premium). On 4 April 2014 Starwood Capital Group also became the fifth shareholder of AS Roma SPV, as well as forming a strategic partnership with AS Roma SpA to develop real estate around the new stadium. The private investment firm was represented by Zsolt Kohalmi in AS Roma SPV, who was appointed on 4 April as a partner and head of European acquisitions of the firm. On 11 August 2014, UniCredit sold the remain shares on NEEP (of 31%) for €33 million which meant AS Roma SPV LLC (91%) and Raptor Holdco LLC (9%) were the sole intermediate holding company of AS Roma SpA. Since re-capitalization in 2003–04, Roma had a short-lived financial self-sustainability, until the takeover in 2011. The club had set up a special amortisation fund using Articolo 18-bis Legge 91/1981 mainly for the abnormal signings prior 2002–03 season, (such as Davide Bombardini for €11 million account value in June 2002, when the flopped player exchange boosted 2001–02 season result) and the tax payment of 2002–03 was rescheduled. In 2004–05, Roma made a net profit of €10,091,689 and followed by €804,285 in 2005–06. In 2006–07 season the accounting method changed to IFRS, which meant that the 2005–06 result was reclassified as net loss of €4,051,905 and 2006–07 season was net income of €10,135,539 (€14.011 million as a group). Moreover, the special fund (€80,189,123) was removed from the asset and co-currently for the equity as scheduled, meant Roma group had a negative equity of €8.795 million on 30 June 2007. Nevertheless, the club had sold the brand to a subsidiary which boost the profit in a separate financial statement, which La Repubblica described as "doping". In 2007–08, Roma made a net income of €18,699,219. (€19 million as a group) However, 2008–09 saw the decrease of gate and TV income, co-currently with finishing sixth in Serie A, which saw Roma make a net loss of €1,894,330. (€1.56 million as a group) The gate and TV income further slipped in 2009–10 with a net loss of €21,917,292 (already boosted by the sale of Alberto Aquilani; €22 million as a group) despite sporting success (finishing in second place in 2009–10). Moreover, despite a positive equity as a separate company (€105,142,589), the AS Roma Group had a negative equity on the consolidated balance sheet, and fell from +€8.8 million to −€13.2 million. In the 2010–11 season, Roma was administered by UniCredit as the Sensi family failed to repay the bank and the club was put on the market, and were expected to have a quiet transfer window. Concurrently with no selling profit on the players, Roma's net loss rose to €30,589,137 (€30.778 million as a group) and the new owner already planned a re-capitalization after the mandatory bid on the shares. On the positive side, TV income was increased from €75,150,744 to €78,041,642, and gate income increased from €23,821,218 to €31,017,179. This was because Roma entered 2010–11 Champions League, which counter-weighed the effect of the new collective agreement of Serie A. In 2011–12, the renewal of squad and participation in 2011–12 UEFA Europa League had worsened the financial result, which the €50 million capital increase (in advance) was counter-weighted totally by the net loss. In the 2012–13 season, the participation in domestic league only, was not only not harmful to the revenue but increase in gate income as well as decrease in wage bill, however Roma still did not yet break even (€40.130 million net loss in consolidated accounts). NEEP Roma also re-capitalized AS Roma in advance for another €26,550,000 during 2012–13. A proposed capital increase by €100 million for Roma was announced on 25 June 2014; however, until 22 May 2014, NEEP already injected €108 million into the club, which depends on public subscription; more than €8 million would convert to medium-long-term loan from shareholder instead of becoming share capital. Another capital increase was carried in 2018. A joint venture of Roma, which was owned by Roma (37.5%), S.S. Lazio (37.5%) and Parma F.C.(25%), Società Diritti Sportivi S.r.l., was in the process of liquidation since 2005. The company was a joint-venture of four football clubs, including Fiorentina. After the bankruptcy of Fiorentina however, both Roma and Lazio had increased their shares ratio from 25% to 37.5%. Another subsidiary, "Soccer S.A.S. di Brand Management S.r.l.", was a special-purpose entity (SPV) that Roma sold their brand to the subsidiary in 2007. In February 2015, another SPV, "ASR Media and Sponsorship S.r.l", was set up to secure a five-year bank loan of €175 million from Goldman Sachs, for three-month Euribor (min. 0.75%) + 6.25% spread (i.e. min. 7% interests rate p.a.). In 2015, Inter and Roma were the only two Italian clubs that were sanctioned by UEFA for breaking UEFA Financial Fair Play Regulations, which they signed settlement agreements with UEFA. It was followed by Milan in 2018. Roma had compliance with the requirements and overall objective of the settlement agreement in 2018, which the club exited from settlement regime.
AS Roma
Superleague Formula
Superleague Formula AS Roma had a team in the Superleague Formula race car series where teams were sponsored by football clubs. Roma's driver was ex-IndyCar Series driver Franck Perera. The team had posted three podiums and was operated by Alan Docking Racing.
AS Roma
See also
See also Football in Italy European Club Association
AS Roma
Footnotes
Footnotes
AS Roma
References
References
AS Roma
External links
External links AS Roma at Serie A AS Roma at UEFA AS Roma at FIFA (archived 6 May 2016) Category:Football clubs in Italy Category:Football clubs in Rome Category:Association football clubs established in 1927 Category:Italian football First Division clubs Category:Publicly traded sports companies Category:Coppa Italia winning clubs Category:Serie A–winning clubs Category:Serie A clubs Category:Serie B clubs Category:1927 establishments in Italy Category:Multi-sport clubs in Italy Category:Inter-Cities Fairs Cup winning clubs Category:UEFA Conference League winning clubs Category:Companies listed on the Borsa Italiana
AS Roma
Table of Content
Short description, History, Foundation, First title victory and decline, Time of mixed fortunes from the 1970s to the 1990s, Third ''scudetto'' in the Sensi era, American ownership and Pallotta era, Friedkin era and European success, Club identity, Kit suppliers and shirt sponsors, Facilities, Stadiums, List of stadiums used by the club, Trigoria, Supporters, Rivalries, Hooliganism, Players, Current squad, Primavera squad, Out on loan, Women team, Notable players, Retired numbers, Management staff, Chairmen history, Managerial history, Honours, National titles, European titles, Other titles, Hall of Fame, Club records and statistics, Divisional movements, UEFA club coefficient ranking, UEFA rankings since 2005, Football club Elo rating, As a company, Superleague Formula, See also, Footnotes, References, External links
Abu Nidal Organization
Short description
The Abu Nidal Organization (ANO; ), officially Fatah – Revolutionary Council ( ), was a Palestinian militant group founded by Abu Nidal in 1974. It broke away from Fatah, a faction within the Palestine Liberation Organization, following the emergence of a rift between Abu Nidal and Yasser Arafat. The ANO was designated as a terrorist organization by Israel, the United States, the United Kingdom, Canada, the European Union and Japan. However, a number of Arab countries supported the group's activities; it was backed by Iraq from 1974 to 1983, by Syria from 1983 to 1987, and by Libya from 1987 to 1997. It briefly cooperated with Egypt from 1997 to 1998, but ultimately returned to Iraq in December 1998, where it continued to have the state's backing until Abu Nidal's death in August 2002. In practice, the ANO was leftist and secularist, as well as anti-Zionist and anti-Western. In theory, it was not particularly associated with any specific ideology—or at least no such foundation was declared. It was mostly linked with the pursuit of Abu Nidal's personal agendas. The ANO was established to carry on an armed struggle in pursuit of pan-Arabism and the destruction of Israel. Like other Palestinian militant groups, the ANO carried out worldwide hijackings, assassinations, kidnappings of diplomats, and attacks on synagogues. It was responsible for 90 terrorist attacks between 1974 and 1992. In 2002, Abu Nidal died under disputed circumstances in Baghdad, with Palestinian sources claiming that he was assassinated on the orders of Iraqi president Saddam Hussein.
Abu Nidal Organization
Formation and background
Formation and background The Abu Nidal Organization was established by Sabri Khalil al-Bannah (Abu Nidal), known by his nom de guerre Abu Nidal, a Palestinian Arab nationalist and a former Ba'ath party member. Abu Nidal long argued that PLO membership should be open to all Arabs, not just Palestinians. He also argued that Palestine must be established as an Arab state, stretching from the Jordan River in the east to the Mediterranean Sea in the west. Abu Nidal established his faction within the PLO, just prior to Black September in Jordan, and following internal disagreements within the PLO. During Fatah's Third Congress in Damascus in 1971, he emerged as the leader of a leftist alliance against Yasser Arafat. After the 1973 Yom Kippur War, many members of the mainstream Fatah movement argued that a political solution with Israel should be an option. Consequently, Abu Nidal split from Fatah in 1974 and formed his "rejectionist" front to carry on a Pan-Arabist armed struggle. Abu Nidal's first independent operation took place on September 5, 1973, when five gunmen using the name Al-Iqab ("The Punishment") seized the Saudi embassy in Paris, taking 11 hostages and threatening to blow up the building if Abu Dawud was not released from jail in Jordan, where he had been arrested in February 1973 for an attempt on King Hussein's life.Melman 1986, p. 69. Following the incident, Mahmoud Abbas of the PLO took flight to Iraq to meet Abu Nidal. In the meeting Abbas became so angry, that he stormed out of the meeting, followed by the other PLO delegates, and from that point on, the PLO regarded Abu Nidal as a mercenary.Seale 1992, p. 92. Two months later, just after the October 1973 Yom Kippur War, during discussions about convening a peace conference in Geneva, the Abu Nidal Organization (ANO) hijacked a KLM airliner, using the name of the Arab Nationalist Youth Organization. The operation was intended to send a signal to Fatah not to send representatives to any peace conference. In response, Arafat officially expelled Abu Nidal from Fatah in March 1974, and the rift between the two groups, and the two men, was complete.Melman 1986, p. 70. In June the same year, ANO formed the Rejectionist Front, a political coalition that opposed the Ten Point Program adopted by the Palestine Liberation Organization in its 12th Palestinian National Congress session.Chakhtoura, Maria, La guerre des graffiti, Beyrouth, Éditions Dar an-Nahar, 2005, page 136. Abu Nidal then moved to Ba'athist Iraq where he set up the ANO, which soon began a string of terrorist attacks aimed at Israel and Western countries. Setting himself up as a freelance contractor, Abu Nidal is believed by the United States Department of State to have ordered attacks in 20 countries, killing or injuring over 900 people."Abu Nidal Organization" , Country Reports on Terrorism, 2004. United States Department of State, 2005. The ANO group's most notorious attacks were on the El Al ticket counters at Rome and Vienna airports in December 1985, when Arab gunmen high on amphetamines opened fire on passengers in simultaneous shootings, killing 18 and wounding 120. Patrick Seale, Abu Nidal's biographer, wrote of the attacks that their "random cruelty marked them as typical Abu Nidal operations."Seale 1992, pp. 243–244.
Abu Nidal Organization
Attacks
Attacks The ANO carried out attacks in 20 countries worldwide, killing or injuring about 1,650 people. Targets include the United States, the United Kingdom, France, Israel, moderate Palestinians, the PLO, and various Arab and European countries. The group has not attacked Western targets since the late 1980s. Major attacks included the Rome and Vienna Airport Attacks in December 1985, the Neve Shalom synagogue in Istanbul and the Pan Am Flight 73 hijacking in Karachi in September 1986, and the City of Poros day-excursion ship attack in Greece in July 1988. The ANO has been especially noted for its uncompromising stance on negotiation with Israel, treating anything less than all-out military struggle against Israel as treachery. This led the group to perform numerous attacks against the PLO, which had made clear it accepted a negotiated solution to the conflict. Fatah-RC is believed to have assassinated PLO deputy chief Abu Iyad and PLO security chief Abul Hul in Tunis in January 1991. It assassinated a Jordanian diplomat in Lebanon in January 1994 and has been linked to the killing of the PLO representative there. Noted PLO moderate Issam Sartawi was killed by the Fatah-RC in 1983. In October 1974, the group also made a failed assassination attempt on the present Palestinian president and PLO chairman, Mahmoud Abbas. These attacks, and numerous others, led to the PLO issuing a death sentence in absentia against Abu Nidal. In the early 1990s, it made an attempt to gain control of a refugee camp in Lebanon, but this was thwarted by PLO organizations.
Abu Nidal Organization
Internal executions and torture
Internal executions and torture The ANO's official newspaper Filastin al-Thawra regularly carried stories announcing the execution of traitors within the movement.Abu Khalil, 2000. Each new recruit of the ANO was given several days to write down his life story and sign a paper agreeing to his execution if anything was found to be untrue. Every so often, the recruit would be asked to rewrite the whole story. Any discrepancies were taken as evidence that he was a spy and he would be made to write it out again, often after days of being beaten and nights spent forced to sleep standing up.Seale 1992, pp. 6–7. British journalist Alec Collett was killed by the ANO in Aita al-Foukhar (village in Lebanon) in 1986. He was hanged on a rope and was shot in retaliation to US air raids on Libya. By 1987, Abu Nidal used extreme torture tactics on members of the ANO who were suspected of betrayal and disloyalty. The tactics included hanging prisoners naked, whipping them until unconsciousness, using salt or chili powder to revive them, forcing them into a car tire for whipping and salt application, melting plastic on their skin, frying their genitals, and confining them in tiny cells bound hand and foot. If cells were full, prisoners could be buried alive with a steel pipe for breathing. Execution was carried out by firing a bullet down the pipe.Clarridge 1997, cited in Ledeen 2002. Also see Seale 1992, pp. 286–287. From 1987 to 1988, hundreds of members of Abu Nidal's organization were killed due to internal paranoia and terror tactics. The elderly wife of a veteran member was also killed on false charges. The killings were mostly carried out by four individuals: Mustafa Ibrahim Sanduqa, Isam Maraqa, Sulaiman Samrin, and Mustafa Awad. Decisions to kill were mostly made by Abu Nidal after he had consumed a whole bottle of whiskey at night.Seale 1992, pp. 287–289. According to ANO dissidents, the attacks made by the group were unconnected to the Palestinian cause and led to their defection. In addition, they claimed the guerrilla was the "living example of paranoia".
Abu Nidal Organization
See also
See also Abu Nidal Arab People's Movement Popular Front for the Liberation of Palestine Olivia Frank List of military units named after people
Abu Nidal Organization
References
References
Abu Nidal Organization
Citations
Citations
Abu Nidal Organization
Sources
Sources
Abu Nidal Organization
Further reading
Further reading Abu Nidal: Ruthless maverick Category:Abu Nidal Category:Anti-Israeli sentiment in Palestine Category:Arab nationalist militant groups Category:Fatah breakaway groups Category:Palestinian terrorism in Europe Category:Organisations designated as terrorist by Japan Category:Organisations designated as terrorist by the European Union Category:Organisations designated as terrorist by the United Kingdom Category:Organizations designated as terrorist by the United States Category:Organizations based in Asia designated as terrorist Category:Palestinian militant groups Category:Organizations designated as terrorist by Canada
Abu Nidal Organization
Table of Content
Short description, Formation and background, Attacks, Internal executions and torture, See also, References, Citations, Sources, Further reading
Antibody
Short description
thumb|upright=1.2|Each antibody binds to a specific antigen in a highly specific interaction analogous to a lock and key. An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that cause disease. Antibodies can recognize virtually any size antigen, able to perceive diverse chemical compositions. Each antibody recognizes one or more specific antigens. Antigen literally means "antibody generator", as it is the presence of an antigen that drives the formation of an antigen-specific antibody. Each tip of the "Y" of an antibody contains a paratope that specifically binds to one particular epitope on an antigen, allowing the two molecules to bind together with precision. Using this mechanism, antibodies can effectively "tag" a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). More narrowly, an antibody (Ab) can refer to the free (secreted) form of these proteins, as opposed to the membrane-bound form found in a B cell receptor. The term immunoglobulin can then refer to both forms. Since they are, broadly speaking, the same protein, the terms are often treated as synonymous. To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. The rest of the antibody structure is much less variable; in humans, antibodies occur in five classes, sometimes called isotypes: IgA, IgD, IgE, IgG, and IgM. Human IgG and IgA antibodies are also divided into discrete subclasses (IgG1, IgG2, IgG3, IgG4; IgA1 and IgA2). The class refers to the functions triggered by the antibody (also known as effector functions), in addition to some other structural features. Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. Between species, while classes and subclasses of antibodies may be shared (at least in name), their functions and distribution throughout the body may be different. For example, mouse IgG1 is closer to human IgG2 than human IgG1 in terms of its function. The term humoral immunity is often treated as synonymous with the antibody response, describing the function of the immune system that exists in the body's humors (fluids) in the form of soluble proteins, as distinct from cell-mediated immunity, which generally describes the responses of T cells (especially cytotoxic T cells). In general, antibodies are considered part of the adaptive immune system, though this classification can become complicated. For example, natural IgM, which are made by B-1 lineage cells that have properties more similar to innate immune cells than adaptive, refers to IgM antibodies made independently of an immune response that demonstrate polyreactivity- they recognize multiple distinct (unrelated) antigens. These can work with the complement system in the earliest phases of an immune response to help facilitate clearance of the offending antigen and delivery of the resulting immune complexes to the lymph nodes or spleen for initiation of an immune response. Hence in this capacity, the function of antibodies is more akin to that of innate immunity than adaptive. Nonetheless, in general, antibodies are regarded as part of the adaptive immune system because they demonstrate exceptional specificity (with some exceptions), are produced through genetic rearrangements (rather than being encoded directly in the germline), and are a manifestation of immunological memory. In the course of an immune response, B cells can progressively differentiate into antibody-secreting cells or into memory B cells. Antibody-secreting cells comprise plasmablasts and plasma cells, which differ mainly in the degree to which they secrete antibody, their lifespan, metabolic adaptations, and surface markers. Plasmablasts are rapidly proliferating, short-lived cells produced in the early phases of the immune response (classically described as arising extrafollicularly rather than from a germinal center) which have the potential to differentiate further into plasma cells. Occasionally plasmablasts are mis-described as short-lived plasma cells; formally this is incorrect. Plasma cells, in contrast, do not divide (they are terminally differentiated), and rely on survival niches comprising specific cell types and cytokines to persist. Plasma cells will secrete huge quantities of antibody regardless of whether or not their cognate antigen is present, ensuring that antibody levels to the antigen in question do not fall to 0, provided the plasma cell stays alive. The rate of antibody secretion, however, can be regulated, for example, by the presence of adjuvant molecules that stimulate the immune response such as TLR ligands. Long-lived plasma cells can live for potentially the entire lifetime of the organism. Classically, the survival niches that house long-lived plasma cells reside in the bone marrow, though it cannot be assumed that any given plasma cell in the bone marrow will be long-lived. However, other work indicates that survival niches can readily be established within the mucosal tissues- though the classes of antibodies involved show a different hierarchy from those in the bone marrow. B cells can also differentiate into memory B cells which can persist for decades similarly to long-lived plasma cells. These cells can be rapidly recalled in a secondary immune response, undergoing class switching, affinity maturation, and differentiating into antibody-secreting cells. Antibodies are central to the immune protection elicited by most vaccines and infections (although other components of the immune system certainly participate and for some diseases are considerably more important than antibodies in generating an immune response, e.g. in the case of herpes zoster). Durable protection from infections caused by a given microbe – that is, the ability of the microbe to enter the body and begin to replicate (not necessarily to cause disease) – depends on sustained production of large quantities of antibodies, meaning that effective vaccines ideally elicit persistent high levels of antibody, which relies on long-lived plasma cells. At the same time, many microbes of medical importance have the ability to mutate to escape antibodies elicited by prior infections, and long-lived plasma cells cannot undergo affinity maturation or class switching. This is compensated for through memory B cells: novel variants of a microbe that still retain structural features of previously encountered antigens can elicit memory B cell responses that adapt to those changes. It has been suggested that long-lived plasma cells secrete B cell receptors with higher affinity than those on the surfaces of memory B cells, but findings are not entirely consistent on this point.
Antibody
Structure
Structure thumb|upright=1.2|right|Schematic structure of an antibody: two heavy chains (blue, yellow) and the two light chains (green, pink). The antigen binding site is circled. Antibodies are heavy (~150 kDa) proteins of about 10 nm in size, arranged in three globular regions that roughly form a Y shape. In humans and most other mammals, an antibody unit consists of four polypeptide chains; two identical heavy chains and two identical light chains connected by disulfide bonds. Each chain is a series of domains: somewhat similar sequences of about 110 amino acids each. These domains are usually represented in simplified schematics as rectangles. Light chains consist of one variable domain VL and one constant domain CL, while heavy chains contain one variable domain VH and three to four constant domains CH1, CH2, ... Structurally an antibody is also partitioned into two antigen-binding fragments (Fab), containing one VL, VH, CL, and CH1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. In between them is a hinge region of the heavy chains, whose flexibility allows antibodies to bind to pairs of epitopes at various distances, to form complexes (dimers, trimers, etc.), and to bind effector molecules more easily. In an electrophoresis test of blood proteins, antibodies mostly migrate to the last, gamma globulin fraction. Conversely, most gamma-globulins are antibodies, which is why the two terms were historically used as synonyms, as were the symbols Ig and γ. This variant terminology fell out of use due to the correspondence being inexact and due to confusion with γ (gamma) heavy chains which characterize the IgG class of antibodies.
Antibody
Antigen-binding site
Antigen-binding site The variable domains can also be referred to as the FV region. It is the subregion of Fab that binds to an antigen. More specifically, each variable domain contains three hypervariable regions – the amino acids seen there vary the most from antibody to antibody. When the protein folds, these regions give rise to three loops of β-strands, localized near one another on the surface of the antibody. These loops are referred to as the complementarity-determining regions (CDRs), since their shape complements that of an antigen. Three CDRs from each of the heavy and light chains together form an antibody-binding site whose shape can be anything from a pocket to which a smaller antigen binds, to a larger surface, to a protrusion that sticks out into a groove in an antigen. Typically though, only a few residues contribute to most of the binding energy. The existence of two identical antibody-binding sites allows antibody molecules to bind strongly to multivalent antigen (repeating sites such as polysaccharides in bacterial cell walls, or other sites at some distance apart), as well as to form antibody complexes and larger antigen-antibody complexes. The structures of CDRs have been clustered and classified by Chothia et al. and more recently by North et al. and Nikoloudis et al. However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities. In the framework of the immune network theory, CDRs are also called idiotypes. According to immune network theory, the adaptive immune system is regulated by interactions between idiotypes.
Antibody
Fc region
Fc region The Fc region (the trunk of the Y shape) is composed of constant domains from the heavy chains. Its role is in modulating immune cell activity: it is where effector molecules bind to, triggering various effects after the antibody Fab region binds to an antigen. Effector cells (such as macrophages or natural killer cells) bind via their Fc receptors (FcR) to the Fc region of an antibody, while the complement system is activated by binding the C1q protein complex. IgG or IgM can bind to C1q, but IgA cannot, therefore IgA does not activate the classical complement pathway. Another role of the Fc region is to selectively distribute different antibody classes across the body. In particular, the neonatal Fc receptor (FcRn) binds to the Fc region of IgG antibodies to transport it across the placenta, from the mother to the fetus. In addition to this, binding to FcRn endows IgG with an exceptionally long half-life relative to other plasma proteins of 3-4 weeks. IgG3 in most cases (depending on allotype) has mutations at the FcRn binding site which lower affinity for FcRn, which are thought to have evolved to limit the highly inflammatory effects of this subclass. Antibodies are glycoproteins, that is, they have carbohydrates (glycans) added to conserved amino acid residues. These conserved glycosylation sites occur in the Fc region and influence interactions with effector molecules.
Antibody
Protein structure
Protein structure The N-terminus of each chain is situated at the tip. Each immunoglobulin domain has a similar structure, characteristic of all the members of the immunoglobulin superfamily: it is composed of between 7 (for constant domains) and 9 (for variable domains) β-strands, forming two beta sheets in a Greek key motif. The sheets create a "sandwich" shape, the immunoglobulin fold, held together by a disulfide bond.
Antibody
Antibody complexes
Antibody complexes thumb|upright|Some antibodies form complexes that bind to multiple antigen molecules. Secreted antibodies can occur as a single Y-shaped unit, a monomer. However, some antibody classes also form dimers with two Ig units (as with IgA), tetramers with four Ig units (like teleost fish IgM), or pentamers with five Ig units (like shark IgW or mammalian IgM, which occasionally forms hexamers as well, with six units). IgG can also form hexamers, though no J chain is required. IgA tetramers and pentamers have also been reported. Antibodies also form complexes by binding to antigen: this is called an antigen-antibody complex or immune complex. Small antigens can cross-link two antibodies, also leading to the formation of antibody dimers, trimers, tetramers, etc. Multivalent antigens (e.g., cells with multiple epitopes) can form larger complexes with antibodies. An extreme example is the clumping, or agglutination, of red blood cells with antibodies in blood typing to determine blood groups: the large clumps become insoluble, leading to visually apparent precipitation.
Antibody
B cell receptors
B cell receptors The membrane-bound form of an antibody may be called a surface immunoglobulin (sIg) or a membrane immunoglobulin (mIg). It is part of the B cell receptor (BCR), which allows a B cell to detect when a specific antigen is present in the body and triggers B cell activation. The BCR is composed of surface-bound IgD or IgM antibodies and associated Ig-α and Ig-β heterodimers, which are capable of signal transduction. A typical human B cell will have 50,000 to 100,000 antibodies bound to its surface. Upon antigen binding, they cluster in large patches, which can exceed 1 micrometer in diameter, on lipid rafts that isolate the BCRs from most other cell signaling receptors. These patches may improve the efficiency of the cellular immune response. In humans, the cell surface is bare around the B cell receptors for several hundred nanometers, which further isolates the BCRs from competing influences.
Antibody
Classes
Classes Antibodies can come in different varieties known as isotypes or classes. In humans there are five antibody classes known as IgA, IgD, IgE, IgG, and IgM, which are further subdivided into subclasses such as IgA1, IgA2. The prefix "Ig" stands for immunoglobulin, while the suffix denotes the type of heavy chain the antibody contains: the heavy chain types α (alpha), γ (gamma), δ (delta), ε (epsilon), μ (mu) give rise to IgA, IgG, IgD, IgE, IgM, respectively. The distinctive features of each class are determined by the part of the heavy chain within the hinge and Fc region. The classes differ in their biological properties, functional locations and ability to deal with different antigens, as depicted in the table. For example, IgE antibodies are responsible for an allergic response consisting of histamine release from mast cells, often a sole contributor to asthma (though other pathways exist as do symptoms very similar to yet not technically asthma). The variable region of these antibodies bind to allergic antigen, for example house dust mite particles, while its Fc region (in the ε heavy chains) binds to Fc receptor ε on a mast cell, triggering its degranulation: the release of molecules stored in its granules. + Antibody isotypes of humans Class Subclasses Description IgA 2 Found in mucosal areas, such as the gut, respiratory tract and urogenital tract, and prevents colonization by pathogens. Also found in saliva, tears, and breast milk. Early clinical studies suggest that IgA isotype antibodies have potential as anti-cancer therapeutics, demonstrating the ability to reduce tumor growth. IgD 1 Functions mainly as an antigen receptor on B cells that have not been exposed to antigens. It has been shown to activate basophils and mast cells to produce antimicrobial factors. Besides, IgD has also been reported to induce the release of immunoactivity and pro-inflammatory mediators. IgE 1 IgE antibodies are the least abundant class of immunoglobulin. They can engage Fc receptors on monocytes and macrophages to activate various effector cell populations. Binds to allergens and triggers histamine release from mast cells and basophils, and is involved in allergy. Humans and other animals evolved IgE to protect against parasitic worms, though in the present, IgE is primarily related to allergies and asthma. IgG 4 In its four forms, provides the majority of antibody-based immunity against invading pathogens. The only antibody capable of crossing the placenta to give passive immunity to the fetus. IgG is the most commonly used molecular format in current antibody drugs because it neutralizes infectious agents and activates the complement system to engage immune cells. IgM 1 Expressed on the surface of B cells (monomer) and in a secreted form (pentamer) with very high avidity. Eliminates pathogens in the early stages of B cell-mediated (humoral) immunity before there is sufficient IgG. IgM also is a pro-inflammatory antibody that serves as the primary defense and effectively stimulates the complement system with specialized immune functions, including higher avidity and steric hindrance, allowing it to neutralize viruses. The antibody isotype of a B cell changes during cell development and activation. Immature B cells, which have never been exposed to an antigen, express only the IgM isotype in a cell surface bound form. The B lymphocyte, in this ready-to-respond form, is known as a "naive B lymphocyte." The naive B lymphocyte expresses both surface IgM and IgD. The co-expression of both of these immunoglobulin isotypes renders the B cell ready to respond to antigen. B cell activation follows engagement of the cell-bound antibody molecule with an antigen, causing the cell to divide and differentiate into an antibody-producing cell called a plasma cell. This requires cytokines from T helper cells, unless antigen cross-links B cell receptors. In this activated form, the B cell starts to produce antibody in a secreted form rather than a membrane-bound form. Activated B cells that encounter certain signaling molecules undergo immunoglobulin class switching, also known as isotope switching, which causes the production of antibodies to change from IgM or IgD to the other antibody isotypes, IgE, IgA, or IgG.
Antibody
Light chain types
Light chain types In mammals there are two types of immunoglobulin light chain, which are called lambda (λ) and kappa (κ). However, there is no known functional difference between them, and both can occur with any of the five major types of heavy chains. Each antibody contains two identical light chains: both κ or both λ. Proportions of κ and λ types vary by species and can be used to detect abnormal proliferation of B cell clones. Other types of light chains, such as the iota (ι) chain, are found in other vertebrates like sharks (Chondrichthyes) and bony fishes (Teleostei).
Antibody
In non-mammalian animals
In non-mammalian animals In most placental mammals, the structure of antibodies is generally the same. Jawed fish appear to be the most primitive animals that are able to make antibodies similar to those of mammals, although many features of their adaptive immunity appeared somewhat earlier. Cartilaginous fish (such as sharks) produce heavy-chain-only antibodies (i.e., lacking light chains) which moreover feature longer chain pentamers (with five constant units per molecule). Camelids (such as camels, llamas, alpacas) are also notable for producing heavy-chain-only antibodies. + Antibody classes not found in mammals Class Types Description IgY Found in birds and reptiles; related to mammalian IgG. IgW Found in sharks and skates; related to mammalian IgD. IgT/Z Found in teleost fishSalinas, I., & Parra, D. (2015). Fish mucosal immunity: Intestine. In Mucosal Health in Aquaculture. Elsevier Inc. https://doi.org/10.1016/B978-0-12-417186-2.00006-6
Antibody
Antibody–antigen interactions
Antibody–antigen interactions The antibody's paratope interacts with the antigen's epitope. An antigen usually contains different epitopes along its surface arranged discontinuously, and dominant epitopes on a given antigen are called determinants. Antibody and antigen interact by spatial complementarity (lock and key). The molecular forces involved in the Fab-epitope interaction are weak and non-specific – for example electrostatic forces, hydrogen bonds, hydrophobic interactions, and van der Waals forces. This means binding between antibody and antigen is reversible, and the antibody's affinity towards an antigen is relative rather than absolute. Relatively weak binding also means it is possible for an antibody to cross-react with different antigens of different relative affinities.
Antibody
Function
Function thumb| The main categories of antibody action include the following: Neutralisation, in which neutralizing antibodies block parts of the surface of a bacterial cell or virion to render its attack ineffective Agglutination, in which antibodies "glue together" foreign cells into clumps that are attractive targets for phagocytosis Precipitation, in which antibodies "glue together" serum-soluble antigens, forcing them to precipitate out of solution in clumps that are attractive targets for phagocytosis Complement activation (fixation), in which antibodies that are latched onto a foreign cell encourage complement to attack it with a membrane attack complex, which leads to the following: Lysis of the foreign cell Encouragement of inflammation by chemotactically attracting inflammatory cells More indirectly, an antibody can signal immune cells to present antibody fragments to T cells, or downregulate other immune cells to avoid autoimmunity. Activated B cells differentiate into either antibody-producing cells called plasma cells that secrete soluble antibody or memory cells that survive in the body for years afterward in order to allow the immune system to remember an antigen and respond faster upon future exposures. At the prenatal and neonatal stages of life, the presence of antibodies is provided by passive immunization from the mother. Early endogenous antibody production varies for different kinds of antibodies, and usually appear within the first years of life. Since antibodies exist freely in the bloodstream, they are said to be part of the humoral immune system. Circulating antibodies are produced by clonal B cells that specifically respond to only one antigen (an example is a virus capsid protein fragment). Antibodies contribute to immunity in three ways: They prevent pathogens from entering or damaging cells by binding to them; they stimulate removal of pathogens by macrophages and other cells by coating the pathogen; and they trigger destruction of pathogens by stimulating other immune responses such as the complement pathway. Antibodies will also trigger vasoactive amine degranulation to contribute to immunity against certain types of antigens (helminths, allergens). thumb|left|The secreted mammalian IgM has five Ig units. Each Ig unit (labeled 1) has two epitope binding Fab regions, so IgM is capable of binding up to 10 epitopes.
Antibody
Activation of complement
Activation of complement Antibodies that bind to surface antigens (for example, on bacteria) will attract the first component of the complement cascade with their Fc region and initiate activation of the "classical" complement system. This results in the killing of bacteria in two ways. First, the binding of the antibody and complement molecules marks the microbe for ingestion by phagocytes in a process called opsonization; these phagocytes are attracted by certain complement molecules generated in the complement cascade. Second, some complement system components form a membrane attack complex to assist antibodies to kill the bacterium directly (bacteriolysis).
Antibody
Activation of effector cells
Activation of effector cells To combat pathogens that replicate outside cells, antibodies bind to pathogens to link them together, causing them to agglutinate. Since an antibody has at least two paratopes, it can bind more than one antigen by binding identical epitopes carried on the surfaces of these antigens. By coating the pathogen, antibodies stimulate effector functions against the pathogen in cells that recognize their Fc region. Those cells that recognize coated pathogens have Fc receptors, which, as the name suggests, interact with the Fc region of IgA, IgG, and IgE antibodies. The engagement of a particular antibody with the Fc receptor on a particular cell triggers an effector function of that cell; phagocytes will phagocytose, mast cells and neutrophils will degranulate, natural killer cells will release cytokines and cytotoxic molecules; that will ultimately result in destruction of the invading microbe. The activation of natural killer cells by antibodies initiates a cytotoxic mechanism known as antibody-dependent cell-mediated cytotoxicity (ADCC) – this process may explain the efficacy of monoclonal antibodies used in biological therapies against cancer. The Fc receptors are isotype-specific, which gives greater flexibility to the immune system, invoking only the appropriate immune mechanisms for distinct pathogens.
Antibody
Natural antibodies
Natural antibodies Humans and higher primates also produce "natural antibodies" that are present in serum before viral infection. Natural antibodies have been defined as antibodies that are produced without any previous infection, vaccination, other foreign antigen exposure or passive immunization. These antibodies can activate the classical complement pathway leading to lysis of enveloped virus particles long before the adaptive immune response is activated. Antibodies are produced exclusively by B cells in response to antigens where initially, antibodies are formed as membrane-bound receptors, but upon activation by antigens and helper T cells, B cells differentiate to produce soluble antibodies. Many natural antibodies are directed against the disaccharide galactose α(1,3)-galactose (α-Gal), which is found as a terminal sugar on glycosylated cell surface proteins, and generated in response to production of this sugar by bacteria contained in the human gut. These antibodies undergo quality checks in the endoplasmic reticulum (ER), which contains proteins that assist in proper folding and assembly. Rejection of xenotransplantated organs is thought to be, in part, the result of natural antibodies circulating in the serum of the recipient binding to α-Gal antigens expressed on the donor tissue.
Antibody
Immunoglobulin diversity
Immunoglobulin diversity Virtually all microbes can trigger an antibody response. Successful recognition and eradication of many different types of microbes requires diversity among antibodies; their amino acid composition varies allowing them to interact with many different antigens. It has been estimated that humans generate about 10 billion different antibodies, each capable of binding a distinct epitope of an antigen. Although a huge repertoire of different antibodies is generated in a single individual, the number of genes available to make these proteins is limited by the size of the human genome. Several complex genetic mechanisms have evolved that allow vertebrate B cells to generate a diverse pool of antibodies from a relatively small number of antibody genes.
Antibody
Domain variability
Domain variability thumb|upright=1.25|The complementarity determining regions of the heavy chain are shown in red () The chromosomal region that encodes an antibody is large and contains several distinct gene loci for each domain of the antibody—the chromosome region containing heavy chain genes (IGH@) is found on chromosome 14, and the loci containing lambda and kappa light chain genes (IGL@ and IGK@) are found on chromosomes 22 and 2 in humans. One of these domains is called the variable domain, which is present in each heavy and light chain of every antibody, but can differ in different antibodies generated from distinct B cells. Differences between the variable domains are located on three loops known as hypervariable regions (HV-1, HV-2 and HV-3) or complementarity-determining regions (CDR1, CDR2 and CDR3). CDRs are supported within the variable domains by conserved framework regions. The heavy chain locus contains about 65 different variable domain genes that all differ in their CDRs. Combining these genes with an array of genes for other domains of the antibody generates a large cavalry of antibodies with a high degree of variability. This combination is called V(D)J recombination and discussed below.Peter Parham. The Immune System. 2nd ed. Garland Science: New York, 2005. pg.47–62
Antibody
V(D)J recombination
V(D)J recombination thumb|upright=1.25|Simplified overview of V(D)J recombination of immunoglobulin heavy chains Somatic recombination of immunoglobulins, also known as V(D)J recombination, involves the generation of a unique immunoglobulin variable region. The variable region of each immunoglobulin heavy or light chain is encoded in several pieces—known as gene segments (subgenes). These segments are called variable (V), diversity (D) and joining (J) segments. V, D and J segments are found in Ig heavy chains, but only V and J segments are found in Ig light chains. Multiple copies of the V, D and J gene segments exist, and are tandemly arranged in the genomes of mammals. In the bone marrow, each developing B cell will assemble an immunoglobulin variable region by randomly selecting and combining one V, one D and one J gene segment (or one V and one J segment in the light chain). As there are multiple copies of each type of gene segment, and different combinations of gene segments can be used to generate each immunoglobulin variable region, this process generates a huge number of antibodies, each with different paratopes, and thus different antigen specificities. The rearrangement of several subgenes (i.e. V2 family) for lambda light chain immunoglobulin is coupled with the activation of microRNA miR-650, which further influences biology of B-cells. RAG proteins play an important role with V(D)J recombination in cutting DNA at a particular region. Without the presence of these proteins, V(D)J recombination would not occur. After a B cell produces a functional immunoglobulin gene during V(D)J recombination, it cannot express any other variable region (a process known as allelic exclusion) thus each B cell can produce antibodies containing only one kind of variable chain.
Antibody
Somatic hypermutation and affinity maturation
Somatic hypermutation and affinity maturation Following activation with antigen, B cells begin to proliferate rapidly. In these rapidly dividing cells, the genes encoding the variable domains of the heavy and light chains undergo a high rate of point mutation, by a process called somatic hypermutation (SHM). SHM results in approximately one nucleotide change per variable gene, per cell division. As a consequence, any daughter B cells will acquire slight amino acid differences in the variable domains of their antibody chains. This serves to increase the diversity of the antibody pool and impacts the antibody's antigen-binding affinity. Some point mutations will result in the production of antibodies that have a weaker interaction (low affinity) with their antigen than the original antibody, and some mutations will generate antibodies with a stronger interaction (high affinity). B cells that express high affinity antibodies on their surface will receive a strong survival signal during interactions with other cells, whereas those with low affinity antibodies will not, and will die by apoptosis. Thus, B cells expressing antibodies with a higher affinity for the antigen will outcompete those with weaker affinities for function and survival allowing the average affinity of antibodies to increase over time. The process of generating antibodies with increased binding affinities is called affinity maturation. Affinity maturation occurs in mature B cells after V(D)J recombination, and is dependent on help from helper T cells.
Antibody
Class switching
Class switching thumb|upright=1.25|Mechanism of class switch recombination that allows isotype switching in activated B cells Isotype or class switching is a biological process occurring after activation of the B cell, which allows the cell to produce different classes of antibody (IgA, IgE, or IgG). The different classes of antibody, and thus effector functions, are defined by the constant (C) regions of the immunoglobulin heavy chain. Initially, naive B cells express only cell-surface IgM and IgD with identical antigen binding regions. Each isotype is adapted for a distinct function; therefore, after activation, an antibody with an IgG, IgA, or IgE effector function might be required to effectively eliminate an antigen. Class switching allows different daughter cells from the same activated B cell to produce antibodies of different isotypes. Only the constant region of the antibody heavy chain changes during class switching; the variable regions, and therefore antigen specificity, remain unchanged. Thus the progeny of a single B cell can produce antibodies, all specific for the same antigen, but with the ability to produce the effector function appropriate for each antigenic challenge. Class switching is triggered by cytokines; the isotype generated depends on which cytokines are present in the B cell environment. Class switching occurs in the heavy chain gene locus by a mechanism called class switch recombination (CSR). This mechanism relies on conserved nucleotide motifs, called switch (S) regions, found in DNA upstream of each constant region gene (except in the δ-chain). The DNA strand is broken by the activity of a series of enzymes at two selected S-regions. The variable domain exon is rejoined through a process called non-homologous end joining (NHEJ) to the desired constant region (γ, α or ε). This process results in an immunoglobulin gene that encodes an antibody of a different isotype.
Antibody
Specificity designations
Specificity designations An antibody can be called monospecific if it has specificity for a single antigen or epitope,p. 22 in: or bispecific if it has affinity for two different antigens or two different epitopes on the same antigen. A group of antibodies can be called polyvalent (or unspecific) if they have affinity for various antigens or microorganisms.Farlex dictionary > polyvalent Citing: The American Heritage Medical Dictionary. 2004 Intravenous immunoglobulin, if not otherwise noted, consists of a variety of different IgG (polyclonal IgG). In contrast, monoclonal antibodies are identical antibodies produced by a single B cell.
Antibody
Asymmetrical antibodies
Asymmetrical antibodies Heterodimeric antibodies, which are also asymmetrical antibodies, allow for greater flexibility and new formats for attaching a variety of drugs to the antibody arms. One of the general formats for a heterodimeric antibody is the "knobs-into-holes" format. This format is specific to the heavy chain part of the constant region in antibodies. The "knobs" part is engineered by replacing a small amino acid with a larger one. It fits into the "hole", which is engineered by replacing a large amino acid with a smaller one. What connects the "knobs" to the "holes" are the disulfide bonds between each chain. The "knobs-into-holes" shape facilitates antibody dependent cell mediated cytotoxicity. Single-chain variable fragments (scFv) are connected to the variable domain of the heavy and light chain via a short linker peptide. The linker is rich in glycine, which gives it more flexibility, and serine/threonine, which gives it specificity. Two different scFv fragments can be connected together, via a hinge region, to the constant domain of the heavy chain or the constant domain of the light chain. This gives the antibody bispecificity, allowing for the binding specificities of two different antigens. The "knobs-into-holes" format enhances heterodimer formation but does not suppress homodimer formation. To further improve the function of heterodimeric antibodies, many scientists are looking towards artificial constructs. Artificial antibodies are largely diverse protein motifs that use the functional strategy of the antibody molecule, but are not limited by the loop and framework structural constraints of the natural antibody. Being able to control the combinational design of the sequence and three-dimensional space could transcend the natural design and allow for the attachment of different combinations of drugs to the arms. Heterodimeric antibodies have a greater range in shapes they can take and the drugs that are attached to the arms do not have to be the same on each arm, allowing for different combinations of drugs to be used in cancer treatment. Pharmaceuticals are able to produce highly functional bispecific, and even multispecific, antibodies. The degree to which they can function is impressive given that such a change of shape from the natural form should lead to decreased functionality.
Antibody
Interchromosomal DNA Transposition
Interchromosomal DNA Transposition Antibody diversification typically occurs through somatic hypermutation, class switching, and affinity maturation targeting the BCR gene loci, but on occasion more unconventional forms of diversification have been documented. For example, in the case of malaria caused by Plasmodium falciparum, some antibodies from those who had been infected demonstrated an insertion from chromosome 19 containing a 98-amino acid stretch from leukocyte-associated immunoglobulin-like receptor 1, LAIR1, in the elbow joint. This represents a form of interchromosomal transposition. LAIR1 normally binds collagen, but can recognize repetitive interspersed families of polypeptides (RIFIN) family members that are highly expressed on the surface of P. falciparum-infected red blood cells. In fact, these antibodies underwent affinity maturation that enhanced affinity for RIFIN but abolished affinity for collagen. These "LAIR1-containing" antibodies have been found in 5-10% of donors from Tanzania and Mali, though not in European donors. European donors did show 100-1000 nucleotide stretches inside the elbow joints as well, however. This particular phenomenon may be specific to malaria, as infection is known to induce genomic instability.
Antibody
History
History The first use of the term "antibody" occurred in a text by Paul Ehrlich. The term Antikörper (the German word for antibody) appears in the conclusion of his article "Experimental Studies on Immunity", published in October 1891, which states that, "if two substances give rise to two different Antikörper, then they themselves must be different". However, the term was not accepted immediately and several other terms for antibody were proposed; these included Immunkörper, Amboceptor, Zwischenkörper, substance sensibilisatrice, copula, Desmon, philocytase, fixateur, and Immunisin. The word antibody has formal analogy to the word antitoxin and a similar concept to Immunkörper (immune body in English). As such, the original construction of the word contains a logical flaw; the antitoxin is something directed against a toxin, while the antibody is a body directed against something. thumb|left|Angel of the West (2008) by Julian Voss-Andreae is a sculpture based on the antibody structure published by E. Padlan. Created for the Florida campus of the Scripps Research Institute, the antibody is placed into a ring referencing Leonardo da Vinci's Vitruvian Man thus highlighting the similarity of the antibody and the human body. The study of antibodies began in 1890 when Emil von Behring and Kitasato Shibasaburō described antibody activity against diphtheria and tetanus toxins. Von Behring and Kitasato put forward the theory of humoral immunity, proposing that a mediator in serum could react with a foreign antigen.Emil von Behring – Biographical. NobelPrize.org. Nobel Media AB 2020. Mon. 20 January 2020. https://www.nobelprize.org/prizes/medicine/1901/behring/biographical/ His idea prompted Paul Ehrlich to propose the side-chain theory for antibody and antigen interaction in 1897, when he hypothesized that receptors (described as "side-chains") on the surface of cells could bind specifically to toxins – in a "lock-and-key" interaction – and that this binding reaction is the trigger for the production of antibodies. Other researchers believed that antibodies existed freely in the blood and, in 1904, Almroth Wright suggested that soluble antibodies coated bacteria to label them for phagocytosis and killing; a process that he named opsoninization. thumb|Michael Heidelberger In the 1920s, Michael Heidelberger and Oswald Avery observed that antigens could be precipitated by antibodies and went on to show that antibodies are made of protein. The biochemical properties of antigen-antibody-binding interactions were examined in more detail in the late 1930s by John Marrack. The next major advance was in the 1940s, when Linus Pauling confirmed the lock-and-key theory proposed by Ehrlich by showing that the interactions between antibodies and antigens depend more on their shape than their chemical composition. In 1948, Astrid Fagraeus discovered that B cells, in the form of plasma cells, were responsible for generating antibodies. Further work concentrated on characterizing the structures of the antibody proteins. A major advance in these structural studies was the discovery in the early 1960s by Gerald Edelman and Joseph Gally of the antibody light chain, and their realization that this protein is the same as the Bence-Jones protein described in 1845 by Henry Bence Jones. Edelman went on to discover that antibodies are composed of disulfide bond-linked heavy and light chains. Around the same time, antibody-binding (Fab) and antibody tail (Fc) regions of IgG were characterized by Rodney Porter. Together, these scientists deduced the structure and complete amino acid sequence of IgG, a feat for which they were jointly awarded the 1972 Nobel Prize in Physiology or Medicine. The Fv fragment was prepared and characterized by David Givol. While most of these early studies focused on IgM and IgG, other immunoglobulin isotypes were identified in the 1960s: Thomas Tomasi discovered secretory antibody (IgA); David S. Rowe and John L. Fahey discovered IgD; and Kimishige Ishizaka and Teruko Ishizaka discovered IgE and showed it was a class of antibodies involved in allergic reactions. In a landmark series of experiments beginning in 1976, Susumu Tonegawa showed that genetic material can rearrange itself to form the vast array of available antibodies.
Antibody
Medical applications
Medical applications
Antibody
Disease diagnosis
Disease diagnosis Detection of particular antibodies is a very common form of medical diagnostics, and applications such as serology depend on these methods. For example, in biochemical assays for disease diagnosis, a titer of antibodies directed against Epstein-Barr virus or Lyme disease is estimated from the blood. If those antibodies are not present, either the person is not infected or the infection occurred a very long time ago, and the B cells generating these specific antibodies have naturally decayed. In clinical immunology, levels of individual classes of immunoglobulins are measured by nephelometry (or turbidimetry) to characterize the antibody profile of patient. Elevations in different classes of immunoglobulins are sometimes useful in determining the cause of liver damage in patients for whom the diagnosis is unclear. For example, IgM levels are often elevated in patients with primary biliary cirrhosis, whereas IgA deposition along hepatic sinusoids can suggest alcoholic liver disease. Autoimmune disorders can often be traced to antibodies that bind the body's own epitopes; many can be detected through blood tests. Antibodies directed against red blood cell surface antigens in immune mediated hemolytic anemia are detected with the Coombs test. The Coombs test is also used for antibody screening in blood transfusion preparation and also for antibody screening in antenatal women. Practically, several immunodiagnostic methods based on detection of complex antigen-antibody are used to diagnose infectious diseases, for example ELISA, immunofluorescence, Western blot, immunodiffusion, immunoelectrophoresis, and magnetic immunoassay. Over-the-counter home pregnancy tests rely on human chorionic gonadotropin (hCG)-directed antibodies. New dioxaborolane chemistry enables radioactive fluoride (18F) labeling of antibodies, which allows for positron emission tomography (PET) imaging of cancer.
Antibody
Disease therapy
Disease therapy Targeted monoclonal antibody therapy is employed to treat diseases such as rheumatoid arthritis, multiple sclerosis, psoriasis, and many forms of cancer including non-Hodgkin's lymphoma, colorectal cancer, head and neck cancer and breast cancer. Some immune deficiencies, such as X-linked agammaglobulinemia and hypogammaglobulinemia, result in partial or complete lack of antibodies. These diseases are often treated by inducing a short-term form of immunity called passive immunity. Passive immunity is achieved through the transfer of ready-made antibodies in the form of human or animal serum, pooled immunoglobulin or monoclonal antibodies, into the affected individual.
Antibody
Prenatal therapy
Prenatal therapy Rh factor, also known as Rh D antigen, is an antigen found on red blood cells; individuals that are Rh-positive (Rh+) have this antigen on their red blood cells and individuals that are Rh-negative (Rh–) do not. During normal childbirth, delivery trauma or complications during pregnancy, blood from a fetus can enter the mother's system. In the case of an Rh-incompatible mother and child, consequential blood mixing may sensitize an Rh- mother to the Rh antigen on the blood cells of the Rh+ child, putting the remainder of the pregnancy, and any subsequent pregnancies, at risk for hemolytic disease of the newborn. Rho(D) immune globulin antibodies are specific for human RhD antigen. Anti-RhD antibodies are administered as part of a prenatal treatment regimen to prevent sensitization that may occur when a Rh-negative mother has a Rh-positive fetus. Treatment of a mother with Anti-RhD antibodies prior to and immediately after trauma and delivery destroys Rh antigen in the mother's system from the fetus. This occurs before the antigen can stimulate maternal B cells to "remember" Rh antigen by generating memory B cells. Therefore, her humoral immune system will not make anti-Rh antibodies, and will not attack the Rh antigens of the current or subsequent babies. Rho(D) Immune Globulin treatment prevents sensitization that can lead to Rh disease, but does not prevent or treat the underlying disease itself.
Antibody
Research applications
Research applications thumb|Immunofluorescence image of the eukaryotic cytoskeleton. Microtubules as shown in green, are marked by an antibody conjugated to a green fluorescing molecule, FITC. Specific antibodies are produced by injecting an antigen into a mammal, such as a mouse, rat, rabbit, goat, sheep, or horse for large quantities of antibody. Blood isolated from these animals contains polyclonal antibodies—multiple antibodies that bind to the same antigen—in the serum, which can now be called antiserum. Antigens are also injected into chickens for generation of polyclonal antibodies in egg yolk. To obtain antibody that is specific for a single epitope of an antigen, antibody-secreting lymphocytes are isolated from the animal and immortalized by fusing them with a cancer cell line. The fused cells are called hybridomas, and will continually grow and secrete antibody in culture. Single hybridoma cells are isolated by dilution cloning to generate cell clones that all produce the same antibody; these antibodies are called monoclonal antibodies. Polyclonal and monoclonal antibodies are often purified using Protein A/G or antigen-affinity chromatography. In research, purified antibodies are used in many applications. Antibodies for research applications can be found directly from antibody suppliers, or through use of a specialist search engine. Research antibodies are most commonly used to identify and locate intracellular and extracellular proteins. Antibodies are used in flow cytometry to differentiate cell types by the proteins they express; different types of cells express different combinations of cluster of differentiation molecules on their surface, and produce different intracellular and secretable proteins. They are also used in immunoprecipitation to separate proteins and anything bound to them (co-immunoprecipitation) from other molecules in a cell lysate, in Western blot analyses to identify proteins separated by electrophoresis, and in immunohistochemistry or immunofluorescence to examine protein expression in tissue sections or to locate proteins within cells with the assistance of a microscope. Proteins can also be detected and quantified with antibodies, using ELISA and ELISpot techniques. Antibodies used in research are some of the most powerful, yet most problematic reagents with a tremendous number of factors that must be controlled in any experiment including cross reactivity, or the antibody recognizing multiple epitopes and affinity, which can vary widely depending on experimental conditions such as pH, solvent, state of tissue etc. Multiple attempts have been made to improve both the way that researchers validate antibodies and ways in which they report on antibodies. Researchers using antibodies in their work need to record them correctly in order to allow their research to be reproducible (and therefore tested, and qualified by other researchers). Less than half of research antibodies referenced in academic papers can be easily identified. Papers published in F1000 in 2014 and 2015 provide researchers with a guide for reporting research antibody use. The RRID paper, is co-published in 4 journals that implemented the RRIDs Standard for research resource citation, which draws data from the antibodyregistry.org as the source of antibody identifiers (see also group at Force11). Antibody regions can be used to further biomedical research by acting as a guide for drugs to reach their target. Several application involve using bacterial plasmids to tag plasmids with the Fc region of the antibody such as pFUSE-Fc plasmid.
Antibody
Regulations
Regulations
Antibody
Production and testing
Production and testing There are several ways to obtain antibodies, including in vivo techniques like animal immunization and various in vitro approaches, such as the phage display method. Traditionally, most antibodies are produced by hybridoma cell lines through immortalization of antibody-producing cells by chemically induced fusion with myeloma cells. In some cases, additional fusions with other lines have created "triomas" and "quadromas". The manufacturing process should be appropriately described and validated. Validation studies should at least include: The demonstration that the process is able to produce in good quality (the process should be validated) The efficiency of the antibody purification (all impurities and virus must be eliminated) The characterization of purified antibody (physicochemical characterization, immunological properties, biological activities, contaminants, ...) Determination of the virus clearance studies
Antibody
Before clinical trials
Before clinical trials Product safety testing: Sterility (bacteria and fungi), in vitro and in vivo testing for adventitious viruses, murine retrovirus testing..., product safety data needed before the initiation of feasibility trials in serious or immediately life-threatening conditions, it serves to evaluate dangerous potential of the product. Feasibility testing: These are pilot studies whose objectives include, among others, early characterization of safety and initial proof of concept in a small specific patient population (in vitro or in vivo testing).
Antibody
Preclinical studies
Preclinical studies Testing cross-reactivity of antibody: to highlight unwanted interactions (toxicity) of antibodies with previously characterized tissues. This study can be performed in vitro (reactivity of the antibody or immunoconjugate should be determined with a quick-frozen adult tissues) or in vivo (with appropriates animal models). Preclinical pharmacology and toxicity testing: preclinical safety testing of antibody is designed to identify possible toxicity in humans, to estimate the likelihood and severity of potential adverse events in humans, and to identify a safe starting dose and dose escalation, when possible. Animal toxicity studies: Acute toxicity testing, repeat-dose toxicity testing, long-term toxicity testing Pharmacokinetics and pharmacodynamics testing: Use for determinate clinical dosages, antibody activities, evaluation of the potential clinical effects
Antibody
Structure prediction and computational antibody design
Structure prediction and computational antibody design The importance of antibodies in health care and the biotechnology industry demands knowledge of their structures at high resolution. This information is used for protein engineering, modifying the antigen binding affinity, and identifying an epitope, of a given antibody. X-ray crystallography is one commonly used method for determining antibody structures. However, crystallizing an antibody is often laborious and time-consuming. Computational approaches provide a cheaper and faster alternative to crystallography, but their results are more equivocal, since they do not produce empirical structures. Online web servers such as Web Antibody Modeling (WAM) WAM and Prediction of Immunoglobulin Structure (PIGS) Prediction of Immunoglobulin Structure (PIGS) enable computational modeling of antibody variable regions. Rosetta Antibody is a novel antibody FV region structure prediction server, which incorporates sophisticated techniques to minimize CDR loops and optimize the relative orientation of the light and heavy chains, as well as homology models that predict successful docking of antibodies with their unique antigen.RosettaAntibody However, describing an antibody's binding site using only one single static structure limits the understanding and characterization of the antibody's function and properties. To improve antibody structure prediction and to take the strongly correlated CDR loop and interface movements into account, antibody paratopes should be described as interconverting states in solution with varying probabilities. The ability to describe the antibody through binding affinity to the antigen is supplemented by information on antibody structure and amino acid sequences for the purpose of patent claims. Several methods have been presented for computational design of antibodies based on the structural bioinformatics studies of antibody CDRs. There are a variety of methods used to sequence an antibody including Edman degradation, cDNA, etc.; albeit one of the most common modern uses for peptide/protein identification is liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). High volume antibody sequencing methods require computational approaches for the data analysis, including de novo sequencing directly from tandem mass spectra and database search methods that use existing protein sequence databases. Many versions of shotgun protein sequencing are able to increase the coverage by utilizing CID/HCD/ETD fragmentation methods and other techniques, and they have achieved substantial progress in attempt to fully sequence proteins, especially antibodies. Other methods have assumed the existence of similar proteins, a known genome sequence, or combined top-down and bottom up approaches. Current technologies have the ability to assemble protein sequences with high accuracy by integrating de novo sequencing peptides, intensity, and positional confidence scores from database and homology searches.
Antibody
Antibody mimetic
Antibody mimetic Antibody mimetics are organic compounds, like antibodies, that can specifically bind antigens. They consist of artificial peptides or proteins, or aptamer-based nucleic acid molecules with a molar mass of about 3 to 20 kDa. Antibody fragments, such as Fab and nanobodies are not considered as antibody mimetics. Common advantages over antibodies are better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. Antibody mimetics have been developed and commercialized as research, diagnostic and therapeutic agents.
Antibody
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Binding antibody unit BAU (binding antibody unit, often as BAU/mL) is a measurement unit defined by the WHO for the comparison of assays detecting the same class of immunoglobulins with the same specificity. (68 pages)
Antibody
See also
See also Affimer Anti-mitochondrial antibodies Anti-nuclear antibodies Antibody mimetic Aptamer Colostrum ELISA Humoral immunity Immunology Immunosuppressive drug Intravenous immunoglobulin (IVIg) Magnetic immunoassay Microantibody Monoclonal antibody Neutralizing antibody Optimer Ligand Secondary antibodies Single-domain antibody Slope spectroscopy Surrobody Synthetic antibody Western blot normalization
Antibody
References
References
Antibody
External links
External links Mike's Immunoglobulin Structure/Function Page at University of Cambridge Antibodies as the PDB molecule of the month Discussion of the structure of antibodies at RCSB Protein Data Bank A hundred years of antibody therapy History and applications of antibodies in the treatment of disease at University of Oxford How Lymphocytes Produce Antibody from Cells Alive! Category:Glycoproteins Category:Immunology Category:Reagents for biochemistry
Antibody
Table of Content
Short description, Structure, Antigen-binding site, Fc region, Protein structure, Antibody complexes, B cell receptors, Classes, Light chain types, In non-mammalian animals, Antibody–antigen interactions, Function, Activation of complement, Activation of effector cells, Natural antibodies, Immunoglobulin diversity, Domain variability, V(D)J recombination, Somatic hypermutation and affinity maturation, Class switching, Specificity designations, Asymmetrical antibodies, Interchromosomal DNA Transposition, History, Medical applications, Disease diagnosis, Disease therapy, Prenatal therapy, Research applications, Regulations, Production and testing, Before clinical trials, Preclinical studies, Structure prediction and computational antibody design, Antibody mimetic, {{anchor, See also, References, External links
Alessandro Scarlatti
Short description
Pietro Alessandro Gaspare Scarlatti (2 May 1660 – 22 October 1725) was an Italian Baroque composer, known especially for his operas and chamber cantatas. He is considered the most important representative of the Neapolitan school of opera. Nicknamed by his contemporaries "the Italian Orpheus", he divided his career between Naples and Rome; a significant part of his works was composed for the papal city. He is often considered the founder of the Neapolitan school, although he has only been its most illustrious representative: his contribution, his originality and his influence were essential, as well as lasting, both in Italy and in Europe. Particularly known for his operas, he brought the Italian dramatic tradition to its maximum development, begun by Monteverdi at the beginning of 17th century and continued by Cesti, Cavalli, Carissimi, Legrenzi and Stradella, designing the final form of the Da capo aria, imitated throughout Europe. He was also the inventor of the Italian overture in three movements (which was of the highest importance in the development of the symphony), of the four-part sonata (progenitor of the modern string quartet),Dirk Kruse: Alessandro Scarlatti: Größter Erneuerer der Musik auf: BR-Klassik vom 19. Februar 2017. and of the technique of motivic development./ encyclopedia / alessandro-scarlatti_% 28Biographical-dictionary% 29 / SCARLATTI, Alessandro in "Biographical Dictionary" He was a model for the musical theater of his time, as evoked by Händel's Italian works, deeply influenced by his theatrical music. Eclectic, Scarlatti also worked on all the other common genres of his time, from the sonata to the concerto grosso, from the motet to the mass, from the oratorio to the cantata, the latter being a genre in which he was an undisputed master. He was the father of two other composers, Domenico Scarlatti and Pietro Filippo Scarlatti.
Alessandro Scarlatti
Life
Life Scarlatti was born in Palermo (or in TrapaniAlfred Music, Anthology of Italian Songs (17th & 18th Century), Volume I: Vocal Collection), then part of the Kingdom of Sicily. He received his first musical education in his family in Palermo. thumb|left|upright|Portrait of Scarlatti, adolescent He is generally said to have been a pupil of Giacomo Carissimi in Rome, and some theorize that he had some connection with northern Italy because his early works seem to show the influence of Stradella and Legrenzi. The production at Rome of his opera Gli equivoci nel sembiante (1679) gained him the support of Queen Christina of Sweden (who at the time was living in Rome), and he became her maestro di cappella. In February 1684 he became maestro di cappella to the viceroy of Naples, perhaps through the influence of his sister, an opera singer, who might have been the mistress of an influential Neapolitan noble. Here he produced a long series of operas, remarkable chiefly for their fluency and expressiveness, as well as other music for state occasions. In 1702 Scarlatti left Naples and did not return until the Spanish domination had been superseded by that of the Austrians. In the interval he enjoyed the patronage of Ferdinando de' Medici, for whose private theatre near Florence he composed operas, and of Cardinal Ottoboni, who made him his maestro di cappella, and procured him a similar post at the Basilica di Santa Maria Maggiore in Rome in 1703. After visiting Venice and Urbino in 1707, Scarlatti took up his duties in Naples again in 1708, and remained there until 1717. By this time Naples seems to have become tired of his music; the Romans, however, appreciated it better, and it was at the Teatro Capranica in Rome that he produced some of his finest operas (Telemaco, 1718; Marco Attilio Regolò, 1719; La Griselda, 1721), as well as some noble specimens of church music, including a Messa di Santa Cecilia for chorus and orchestra, composed in honor of Saint Cecilia for Cardinal Francesco Acquaviva in 1721. His last work on a large scale appears to have been the unfinished Erminia serenata for the marriage of the prince of Stigliano in 1723. He died in Naples in 1725 and is entombed there at the church of Santa Maria di Montesanto.
Alessandro Scarlatti
Music
Music thumb|Scarlatti as a young man, attributed to Lorenzo Vaccaro (c1770)Portrait of Alessandro Scarlatti, attributed to Lorenzo Vaccaro (c1770). Grove Music Online. Retrieved 19 Nov. 2023, from https://www.oxfordmusiconline.com/grovemusic/view/10.1093/gmo/9781561592630.001.0001/omo-9781561592630-e-8000923029 . Scarlatti's music forms an important link between the early Baroque Italian vocal styles of the 17th century, with their centers in Florence, Venice and Rome, and the classical school of the 18th century. Scarlatti's style, however, is more than a transitional element in Western music; like most of his Naples colleagues he shows an almost modern understanding of the psychology of modulation and also frequently makes use of the ever-changing phrase lengths so typical of the Napoli school. His early operas—Gli equivoci nel sembiante 1679; L'honestà negli amori 1680, containing the famous aria "Già il sole dal Gange"; Il Pompeo 1683, containing the well-known airs "O cessate di piagarmi" and "Toglietemi la vita ancor," and others down to about 1685—retain the older cadences in their recitatives, and a considerable variety of neatly constructed forms in their charming little arias, accompanied sometimes by the string quartet, treated with careful elaboration, sometimes with the continuo alone. By 1686, he had definitely established the "Italian overture" form (second edition of Dal male il bene), and had abandoned the ground bass and the binary form air in two stanzas in favour of the ternary form or da capo type of air. His best operas of this period are La Rosaura (1690, printed by the Gesellschaft für Musikforschung), and Pirro e Demetrio (1694), in which occur the arias "Le Violette", and "Ben ti sta, traditor". From about 1697 onwards (La caduta del Decemviri), influenced partly perhaps by the style of Giovanni Bononcini and probably more by the taste of the viceregal court, his opera arias become more conventional and commonplace in rhythm, while his scoring is hasty and crude, yet not without brilliance (L'Eraclea, 1700), the oboes and trumpets being frequently used, and the violins often playing in unison. The operas composed for Ferdinando de' Medici are lost; they might have given a more favourable idea of his style as his correspondence with the prince shows that they were composed with a very sincere sense of inspiration. thumb|left|An autograph manuscript of Scarlatti's Griselda Mitridate Eupatore, accounted his masterpiece, composed for Venice in 1707, contains music far in advance of anything that Scarlatti had written for Naples, both in technique and in intellectual power. The later Neapolitan operas (L'amor volubile e tiranno 1709; La principessa fedele 1710; Tigrane, 1714, &c.) are showy and effective rather than profoundly emotional; the instrumentation marks a great advance on previous work, since the main duty of accompanying the voice is thrown upon the string quartet, the harpsichord being reserved exclusively for the noisy instrumental ritornelli. In his opera Teodora (1697) he originated the use of the orchestral ritornello. His last group of operas, composed for Rome, exhibit a deeper poetic feeling, a broad and dignified style of melody, a strong dramatic sense, especially in accompanied recitatives, a device which he himself had been the first to use as early as 1686 (Olimpia vendicata) and a much more modern style of orchestration, the horns appearing for the first time, and being treated with striking effect. Besides the operas, oratorios (Agar et Ismaele esiliati, 1684; La Maddalena, 1685; La Giuditta, 1693; Humanita e Lucifero, 1704; Christmas Oratorio, c. 1705; Cain, 1707; S. Filippo Neri, 1714; and others) and serenatas, which all exhibit a similar style, Scarlatti composed upwards of five hundred chamber-cantatas for solo voice. These represent the most intellectual type of chamber-music of their period, and it is to be regretted that they have remained almost entirely in manuscript, since a careful study of them is indispensable to anyone who wishes to form an adequate idea of Scarlatti's development. His few remaining Masses and church music in general are comparatively unimportant, except the great Saint Cecilia Mass (1721), which is one of the first attempts at the style which reached its height in the great Masses of Johann Sebastian Bach and Ludwig van Beethoven. His instrumental music, though not without interest, is curiously antiquated as compared with his vocal works.
Alessandro Scarlatti
Operas
Operas
Alessandro Scarlatti
Recordings
Recordings Philharmonia Baroque Orchestra, Nicholas McGegan. (2016). La Gloria di Primavera. Philharmonia Baroque Orchestra. Diana Moore, Suzana Ograjensek, Nicholas Phan, Clint van der Linde, Douglas Williams, Philharmonia Chorale. Akademie für alte Musik Berlin, René Jacobs. (2007). Griselda. Harmonia Mundi HMC 901805.07. Dorothea Röschmann, Lawrence Zazzo, Veronica Cangemi, Bernarda Fink, Silvia Tro Santafé, Kobie van Rensburg. Le Consert de l'Hostel Dieu. (2006). Il martirio di Sant'Orsola. Ligia digital: 0202176–07 Le parlement de musique. (2005). La Giuditta. Ambronay editions: AMY004 Ensemble Europa Galante. (2004). Oratorio per la Santissima Trinità. Virgin Classics: 5 45666 2 Academia Bizantina. (2004). Il Giardino di Rose. Decca: 470 650-2 DSA. Orqestra barocca di Sevilla . (2003). Colpa, Pentimento e Grazia. Harmonia Mundi: HMI 987045.46 Seattle Baroque. (2001). Agar et Ismaele Esiliati. Centaur: CRC 2664 Sedecia, re di Gerusalemme. 2000 . Gérard Lesne, Philippe Jaroussky, Virginie Pouchon, Mark Padmore, Peter Harvey, Il Seminario musicale. Virgin veritas, Erato Capella Palatina. (2000). Davidis pugna et victoria. Agora: AG 249.1 Akademie für alte Musik Berlin, René Jacobs. (1998). Il Primo Omicidio. Harmonia Mundi Fr. Dorothea Röschmann, Graciela Oddone, Richard Croft, René Jacobs, Bernarda Fink, Antonio Abete Ensemble Europa Galante. (1995). Humanita e Lucifero. Opus 111: OPS 30–129 Ensemble Europa Galante. (1993). La Maddalena. Opus 111: OPS 30–96 Allesandro Stradella Consort. (1992). Cantata natalizia Abramo, il tuo sembiante. Nuova era: 7117 I Musici. (1991). Concerto Grosso. Philips Classics Productions: 434 160–2 I Musici. William Bennett (Flute), Lenore Smith (Flute), Bernard Soustrot (Trumpet), Hans Elhorst (Oboe). (1961). 12 Sinfonie di concerto grosso Philips Box 6769 066 [9500 959 & 9500 960 – 2 vinyl discs] Emma Kirkby, soprano and Daniel Taylor, countertenor, with the Theatre of Early Music. (2005). Stabat Mater. ATMA Classique: ACD2 2237 Francis Colpron, recorder, with Les Boréades. (2007). Concertos for flute. ATMA Classique: ACD2 2521 Nederlands Kamerkoor, with Harry van der Kamp, conductor. (2008). Vespro della Beata Vergine for 5 voices and continuo. ATMA Classique: ACD2 2533
Alessandro Scarlatti
See also
See also Messa di Santa Cecilia Il Martirio di Santa Cecilia
Alessandro Scarlatti
References
References
Alessandro Scarlatti
External links
External links Associazione Domenico Scarlatti. Italian language (some material in English). Free scores by Alessandro Scarlatti at the International Music Score Library Project The Madrigals of Alessandro Scarlatti: A lecture/recital by Garrick Comeaux and Consortium Carissimi, with Kelley Harness, 12 February 2009. University of Minnesota Institute for Advanced Studies. Audio and video available. The partimenti of Alessandro Scarlatti (D-Hs M/A 251) Category:1660 births Category:1725 deaths Category:17th-century Italian educators Category:18th-century Italian educators Category:18th-century Italian male musicians Category:Catholic liturgical composers Category:Italian classical composers of church music Category:Italian Baroque composers Category:Italian opera composers Category:Italian classical musicians Category:Italian male opera composers Category:Neapolitan school composers Category:Italian string quartet composers Category:17th-century Italian composers Category:18th-century Italian composers Category:Composers from Sicily Category:Musicians from Palermo 01 Category:17th-century Italian male musicians Alessandro
Alessandro Scarlatti
Table of Content
Short description, Life, Music, Operas, Recordings, See also, References, External links
Aston Martin
Short description
Aston Martin Lagonda Global Holdings PLC () is a British manufacturer of luxury sports cars and grand tourers. Its predecessor was founded in 1913 by Lionel Martin and Robert Bamford. Headed from 1947 by David Brown, it became associated with expensive grand touring cars in the 1950s and 1960s, and with the fictional character James Bond following his use of a DB5 model in the 1964 film Goldfinger. Their grand tourers and sports cars are regarded as a British cultural icon. Aston Martin has held a royal warrant as purveyor of motorcars to Charles III (as Prince of Wales and later as King) since 1982, and has over 160 car dealerships in 53 countries, making it a global automobile brand. The company is traded on the London Stock Exchange and is a constituent of the FTSE 250 Index. In 2003 it received the Queen's Award for Enterprise for outstanding contribution to international trade. The company has survived seven bankruptcies throughout its history. The headquarters and main production of its sports cars and grand tourers are in a facility in Gaydon, Warwickshire, England, on the former site of RAF Gaydon, adjacent to the Jaguar Land Rover Gaydon Centre. The old facility in Newport Pagnell, Buckinghamshire, is the present home of the Aston Martin Works classic car department, which focuses on heritage sales, service, spares and restoration operations. The factory in St Athan, Wales, features three converted 'super-hangars' from MOD St Athan, and serves as the production site of Aston Martin's SUV, the DBX. Aston Martin has been involved in motorsport at various points in its history, mainly in sports car racing, and also in Formula One. The Aston Martin brand is increasingly being used, mostly through licensing, on other products including a submarine, real estate development, and aircraft.
Aston Martin
History
History
Aston Martin
Founding
Founding Aston Martin was founded in 1913 by Lionel Martin and Robert Bamford. The two had joined forces as Bamford & Martin the previous year to sell cars made by Singer from premises in Callow Street, London where they also serviced GWK and Calthorpe vehicles. Martin raced specials at Aston Hill near Aston Clinton, and the pair decided to make their own vehicles. The first car to be named Aston Martin was created by Martin by fitting a four-cylinder Coventry-Simplex engine to the chassis of a 1908 Isotta Fraschini. They acquired premises at Henniker Mews in Kensington and produced their first car in March 1915. Production could not start because of the outbreak of the First World War, when Martin joined the Admiralty and Bamford joined the Army Service Corps.
Aston Martin
1918–1939: Interwar years
1918–1939: Interwar years thumb|1923 Razor Blade Team car thumb|1924 tourer thumb|1937 2-Litre open 2/4-seater Speed model, Kop Hill 2010 After the war they found new premises at Abingdon Road, Kensington and designed a new car. Bamford left in 1920 and Bamford & Martin was revitalised with funding from Louis Zborowski. In 1922, Bamford & Martin produced cars to compete in the French Grand Prix, which went on to set world speed and endurance records at Brooklands. Three works Team Cars with 16-valve twin cam engines were built for racing and record-breaking: chassis number 1914, later developed as the Green Pea; chassis number 1915, the Razor Blade record car; and chassis number 1916, later developed as the Halford Special.The AM Halford Special, The First Five Years, AM Quarterly, Volume 19 Number 77, Summer 1981. Approximately 55 cars were built for sale in two configurations; long chassis and short chassis. Bamford & Martin went bankrupt in 1924 and was bought by Dorothea, Lady Charnwood, who put her son John Benson on the board. Bamford & Martin got into financial difficulty again in 1925 and Martin was forced to sell the company (Bamford had already left it in 1920). Later that year, Bill Renwick, Augustus (Bert) Bertelli and investors including Lady Charnwood took control of the business. They renamed it Aston Martin Motors and moved it to the former Whitehead Aircraft Limited Hanworth works in Feltham. Renwick and Bertelli had been in partnership some years and had developed an overhead-cam four-cylinder engine using Renwick's patented combustion chamber design, which they had tested in an Enfield-Allday chassis. The only "Renwick and Bertelli" motor car made, it was known as "Buzzbox" and still survives. The pair had planned to sell their engine to motor manufacturers, but having heard that Aston Martin was no longer in production realised they could capitalise on its reputation to jump-start the production of a completely new car. Between 1926 and 1937 Bertelli was both technical director and designer of all new Aston Martins, since known as "Bertelli cars". They included the 1½-litre "T-type", "International", "Le Mans", "MKII" and its racing derivative, the "Ulster", and the 2-litre 15/98 and its racing derivative, the "Speed Model". Most were open two-seater sports cars bodied by Bert Bertelli's brother Enrico (Harry), with a small number of long-chassis four-seater tourers, dropheads and saloons also produced. Bertelli was a competent driver keen to race his cars, one of few owner/manufacturer/drivers. The "LM" team cars were very successful in national and international motor racing including at Le Mans. Financial problems reappeared in 1932. Aston Martin was rescued for a year by Lance Prideaux Brune before passing it on to Sir Arthur Sutherland. In 1936, Aston Martin decided to concentrate on road cars, producing just 700 until World War II halted work. Production shifted to aircraft components during the war.
Aston Martin
1947–1972: David Brown
1947–1972: David Brown thumb|1958 Aston Martin DB Mark III In 1947, old-established (1860) privately owned Huddersfield gear and machine tools manufacturer David Brown Limited bought Aston Martin, putting it under control of its Tractor Group. David Brown became Aston Martin's latest saviour.The David Brown Corporation Limited (Incorporated under the Companies Act. 1948.) The Times, Monday, 12 March 1951; p. 9; issue 51947. He also acquired Lagonda,The New Lagonda Car. The Times, Saturday, 20 September 1947; p. 3; issue 50871. without its factory, for its 2.6-litre W. O. Bentley-designed engine. Lagonda moved operations to Newport Pagnell and shared engines, resources and workshops. Aston Martin began to build the classic "DB" series of cars. In April 1950, they announced planned production of their Le Mans prototype to be called the DB2,The 2½-Litre Aston-Martin. The Times, Tuesday, 25 April 1950; p. 3; issue 51674. followed by the DB2/4 in 1953, the DB2/4 MkII in 1955, the DB Mark III in 1957 and the Italian-styled 3.7 L DB4 in 1958. While these models helped Aston Martin establish a good racing pedigree, the DB4 stood out and yielded the famous DB5 in 1963. Aston stayed true to its grand touring style with the DB6 (1965–70), and DBS (1967–1972). The six-cylinder engines of these cars from 1954 up to 1965 were designed by Tadek Marek.Classic Cars: The World's Greatest Marques p. 29
Aston Martin
1972–1975: William Willson
1972–1975: William Willson thumb|The Tadek Marek-designed V8 engine was a mainstay of the Aston Martin lineup for decades, and was built from 1969 until 2000. Aston Martin was often financially troubled. In 1972, David Brown paid off all its debts, said to be £5 million or more, and handed it for £101 to Company Developments, a Birmingham-based investment bank consortium chaired by accountant William Willson. More detail on this period may be read at Willson's biography. The worldwide recession, lack of working capital and the difficulties of developing an engine to meet California's exhaust emission requirements – it stopped the company's US sales – again pulled Aston Martin into receivership at the end of 1974. The company had employed 460 workers when the manufacturing plant closed.Receiver is called in at Jensen Motors. The Times, Tuesday, 16 September 1975; p. 17; issue 59502.
Aston Martin
1975–1981: Sprague and Curtis
1975–1981: Sprague and Curtis The receiver sold the business in April 1975 for £1.05 million to North American businessman Peter Sprague of National Semiconductor, Toronto hotelier George Minden, and Jeremy Turner, a London businessman,Aston Martin bid final, consortium says. The Times, Friday, 4 April 1975; p. 19; issue 59361. who insisted to reporters that Aston Martin remained a British controlled business. Sprague later claimed he had fallen in love with the factory, not the cars, the workforce's craftsmanship dedication and intelligence. At this point, he and Minden had brought in investor Alan Curtis, a British office property developer, together with George Flather, a retired Sheffield steel magnate.Lagonda sets out on a new course. The Times, Monday, 24 April 1978; p. 18; issue 60284. Six months later, in September 1975, the factory – shut down the previous December – re-opened under its new owner as Aston Martin Lagonda Limited with 100 employees, and planned to lift staff to 250 by the end of 1975. In January 1976, AML revealed that it now held orders for 150 cars for the US, 100 for other markets and another 80 from a Japanese importing agency.Aston Martin Revival. The Times, Saturday, 10 January 1976; p. 17; issue 59598. At the Geneva Motor Show, Fred Hartley, managing director and sales director for 13 years before that, announced he had resigned over "differences in marketing policy".On the Move. The Times, Wednesday, 16 March 1977; p. 21; issue 59953. The new owners pushed Aston Martin into modernising its line, introducing the V8 Vantage in 1977, the convertible Volante in 1978, and the one-off Bulldog styled by William Towns in 1980. Towns also styled the futuristic new Lagonda saloon, based on the V8 model. Curtis, who had a 42% stake in Aston Martin,Consortium puts in its bid for MG. The Times, Friday, 25 January 1980; p. 17; issue 60533. also brought about a change in direction from the usual customers who were Aston Martin fans, to successful young married businessmen. Prices had been increased by 25%. There was speculation that AML was about to buy Italian automobile manufacturer Lamborghini.August car sales may hit peak. The Times, Friday, 18 August 1978; p. 16; issue 60383. At the end of the 1970s, there was widespread debate about running MG into the Aston Martin consortium. 85 Conservative MPs formed themselves into a pressure group to get British Leyland to release their grip and hand it over.Sell MG to Aston Martin, MPs say. The Times, Tuesday, 27 November 1979; p. 16; issue 60485. CH Industrials plc (car components) bought a 10% share in AML. But in July 1980, blaming a recession, AML cut back their workforce of 450 by more than 20%, making those people redundant.The Times, Tuesday, 1 July 1980; p. 17; issue 60665.
Aston Martin
1981–1987: Victor Gauntlett
1981–1987: Victor Gauntlett In January 1981, there having been no satisfactory revival partners, Alan Curtis and Peter Sprague announced they had never intended to maintain a long-term financial stake in Aston Martin Lagonda and it was to be sold to Pace Petroleum's Victor Gauntlett. Sprague and Curtis pointed out that under their ownership AML finances had improved to where an offer for MG might have been feasible.Petrol chief takes over Aston Martin. The Times, Monday, 5 January 1981; p. 15; issue 60817. Gauntlett bought a 12.5% stake in Aston Martin for £500,000 via Pace Petroleum in 1980, with Tim Hearley of CH Industrials taking a similar share. Pace and CHI took over as joint 50/50 owners at the beginning of 1981, with Gauntlett as executive chairman. Gauntlett also led the sales team, and after some development and publicity when the Lagonda became the world's fastest four-seater production car, was able to sell the car in Oman, Kuwait, and Qatar. In 1982, Aston Martin was granted a Royal Warrant of Appointment by the Prince of Wales. Understanding that it would take some time to develop new Aston Martin products, they created an engineering service subsidiary to develop automotive products for other companies. It was decided to use a trade name of Salmons & Son, their in-house coachbuilder, Tickford, which Aston Martin had bought in 1955. Tickford's name had been long associated with expensive high-quality carriages and cars along with their folding roofs. New products included a Tickford Austin Metro, a Tickford Ford Capri and even Tickford train interiors, particularly on the Jaguar XJS. Pace continued sponsoring racing events, and now sponsored all Aston Martin Owners Club events, taking a Tickford-engined Nimrod Group C car owned by AMOC President Viscount Downe, which came third in the Manufacturers Championship in both 1982 and 1983. It also finished seventh in the 1982 24 Hours of Le Mans race. However, sales of production cars were now at an all-time low of 30 cars produced in 1982. right|thumb|Aston Martin V8 Vantage from The Living Daylights As trading became tighter in the petroleum market, and Aston Martin was requiring more time and money, Gauntlett agreed to sell Hays/Pace to the Kuwait Investment Office in September 1983. As Aston Martin required greater investment, he also agreed to sell his share holding to American importer and Greek shipping tycoon Peter Livanos, who invested via his joint venture with Nick and John Papanicolaou, ALL Inc. Gauntlett remained chairman of AML, 55% of the stake was owned by ALL, with Tickford a 50/50 venture between ALL and CHI. The uneasy relationship was ended when ALL exercised options to buy a larger share in AML; CHI's residual shares were exchanged for CHI's complete ownership of Tickford, which retained the development of existing Aston Martin projects. In 1984, Papanicolaou's Titan shipping business was in trouble so Livanos's father George bought out the Papanicolaou's shares in ALL, while Gauntlett again became a shareholder with a 25% holding in AML. The deal valued Aston Martin/AML at £2 million, the year it built its 10,000th car. Although as a result Aston Martin had to make 60 members of the workforce redundant, Gauntlett bought a stake in Italian styling house Zagato, and resurrected its collaboration with Aston Martin. In 1986, Gauntlett negotiated the return of the fictional British secret agent James Bond to Aston Martin. Cubby Broccoli had chosen to recast the character using actor Timothy Dalton, in an attempt to re-root the Bond-brand back to a more Sean Connery-like feel. Gauntlett supplied his personal pre-production Vantage for use in the filming of The Living Daylights, and sold a Volante to Broccoli for use at his home in America. Gauntlett turned down the role of a KGB colonel in the film, however: "I would have loved to have done it but really could not afford the time."