document_title: List of most-viewed YouTube videos

question_text: what is the most watched music video on youtube of all time

text: List of most-viewed YouTube videos

text: Top videos

text: The following table lists the top 100 most viewed videos on YouTube, with each total rounded to the nearest 10 million views, as well as the creator and date of publication to YouTube.[A]

text:
Rank
Video name
Uploader / artist
Views (billions)
Upload date
Notes

1.
"Despacito"[8]
Luis Fonsi featuring Daddy Yankee
4.41
January 12, 2017
[B]

2.
"See You Again"[13]
Wiz Khalifa featuring Charlie Puth
3.24
April 6, 2015
[C]

3.
"Gangnam Style"[20]
Psy
3.00
July 15, 2012
[D]

4.
"Sorry"[25]
Justin Bieber
2.84
October 22, 2015

5.
"Uptown Funk"[26]
Mark Ronson featuring Bruno Mars
2.78
November 19, 2014

6.
"Shape of You"[27]
Ed Sheeran
2.77
January 30, 2017

7.
"Masha and the Bear: Recipe for Disaster"[28]
Get Movies
2.62
January 31, 2012
[E]

8.
"Shake It Off"[29]
Taylor Swift
2.45
August 18, 2014

9.
"Bailando"[30]
Enrique Iglesias featuring Descemer Bueno and Gente De Zona
2.43
April 11, 2014

10.
"Sugar"[31]
Maroon 5
2.42
January 14, 2015

11.
"Roar"[32]
Katy Perry
2.35
September 5, 2013

12.
"Lean On"[33]
Major Lazer and DJ Snake featuring MØ
2.22
March 22, 2015

13.
"Blank Space"[34]
Taylor Swift
2.22
November 10, 2014

14.
"Dark Horse"[35]
Katy Perry featuring Juicy J
2.17
February 20, 2014

15.
"All About That Bass"[36]
Meghan Trainor
2.15
June 11, 2014

16.
"Hello"[37]
Adele
2.14
October 22, 2015
[F]

17.
"Wheels on the Bus"[39]
LittleBabyBum
2.02
August 9, 2014

18.
"Counting Stars"[40]
OneRepublic
2.02
May 31, 2013

19.
"Chantaje"[41]
Shakira featuring Maluma
1.99
November 18, 2016

20.
"Closer (Lyric video)"[42]
The Chainsmokers featuring Halsey
1.95
July 29, 2016
[G]

21.
"Thinking Out Loud"[43]
Ed Sheeran
1.94
October 7, 2014

22.
"This Is What You Came For"[44]
Calvin Harris featuring Rihanna
1.85
June 16, 2016

23.
"What Do You Mean?"[45]
Justin Bieber
1.84
August 30, 2015

24.
"Baby"[46]
Justin Bieber featuring Ludacris
1.75
February 19, 2010
[H]

25.
"Work from Home"[49]
Fifth Harmony featuring Ty Dolla $ign
1.74
February 26, 2016

26.
"Chandelier"[50]
Sia
1.73
May 6, 2014

27.
"Rockabye"[51]
Clean Bandit featuring Sean Paul & Anne-Marie
1.69
October 21, 2016

28.
"Let Her Go"[52]
Passenger
1.67
July 25, 2012

29.
"Love Me Like You Do"[53]
Ellie Goulding
1.61
January 22, 2015

30.
"Waka Waka (This Time for Africa)"[54]
Shakira featuring Freshlyground
1.61
June 4, 2010

31.
"We Don't Talk Anymore"[55]
Charlie Puth featuring Selena Gomez
1.59
August 2, 2016

32.
"Worth It"[56]
Fifth Harmony featuring Kid Ink
1.50
March 28, 2015

33.
"Love the Way You Lie"[57]
Eminem featuring Rihanna
1.44
August 5, 2010

34.
"Treat You Better"[58]
Shawn Mendes
1.44
July 12, 2016

35.
"Ay Vamos"[59]
J Balvin
1.43
August 29, 2014

36.
"Watch Me (Whip/Nae Nae)"[60]
Silentó
1.41
June 25, 2015

37.
"Rude"[61]
Magic!
1.41
December 5, 2013

38.
"Wake Me Up"[62]
Avicii featuring Aloe Blacc
1.41
July 29, 2013

39.
"Faded"[63]
Alan Walker
1.40
December 3, 2015

40.
"Party Rock Anthem"[64]
LMFAO featuring Lauren Bennett and GoonRock
1.39
March 8, 2011

41.
"Mi Gente"[65]
J Balvin and Willy William
1.35
June 29, 2017

42.
"Hotline Bling"[66]
Drake
1.33
October 26, 2015

43.
"Vente Pa' Ca"[67]
Ricky Martin featuring Maluma
1.32
September 22, 2016

44.
"Johny Johny Yes Papa"[68]
ChuChu TV
1.31
November 14, 2014
[I]

45.
"Propuesta Indecente"[70]
Romeo Santos
1.30
September 9, 2013

46.
"Love Yourself"[71]
Justin Bieber
1.27
November 14, 2015

47.
"Starboy"[72]
The Weeknd featuring Daft Punk
1.26
September 28, 2016

48.
"Let It Go"[73]
Idina Menzel
1.25
January 30, 2014
[J]

49.
"Hasta el Amanecer"[75]
Nicky Jam
1.25
January 14, 2016

50.
"The Lazy Song"[76]
Bruno Mars
1.25
April 15, 2011

51.
"All of Me"[77]
John Legend
1.24
October 2, 2013

52.
"Rolling in the Deep"[78]
Adele
1.22
November 30, 2010

53.
"Side to Side"[79]
Ariana Grande featuring Nicki Minaj
1.20
August 29, 2016

54.
"Burn"[80]
Ellie Goulding
1.19
July 7, 2013

55.
"Reggaetón Lento (Bailemos)"[81]
CNCO
1.18
October 7, 2016

56.
"Summer"[82]
Calvin Harris
1.18
April 6, 2014

57.
"How Deep Is Your Love"[83]
Calvin Harris featuring Disciples
1.18
August 6, 2015

58.
"Felices los 4"[84]
Maluma
1.17
April 21, 2017

59.
"Picky"[85]
Joey Montana
1.16
June 29, 2015

60.
"Hey Mama"[86]
David Guetta featuring Nicki Minaj, Bebe Rexha and Afrojack
1.16
May 19, 2015

61.
"Bad Blood"[87]
Taylor Swift featuring Kendrick Lamar
1.16
May 17, 2015

62.
"The Hills"[88]
The Weeknd
1.15
May 27, 2015

63.
"On the Floor"[89]
Jennifer Lopez featuring Pitbull
1.15
March 3, 2011

64.
"Stressed Out"[90]
Twenty One Pilots
1.14
April 27, 2015

65.
"The Gummy Bear Song"[91]
icanrockyourworld
1.14
October 9, 2007
[K]

66.
"Thrift Shop"[92]
Macklemore & Ryan Lewis featuring Wanz
1.14
August 29, 2012

67.
"Gentleman"[93]
Psy
1.13
April 13, 2013

68.
"Diamonds"[94]
Rihanna
1.11
November 8, 2012

69.
"Shaky Shaky"[95]
Daddy Yankee
1.10
July 14, 2016

70.
"Animals"[96]
Martin Garrix
1.09
June 17, 2013

71.
"El Perdón"[97]
Nicky Jam featuring Enrique Iglesias
1.09
March 23, 2015

72.
"Andas en Mi Cabeza"[98]
Chino & Nacho featuring Daddy Yankee
1.08
April 20, 2016

73.
"El Perdedor"[99]
Maluma
1.08
April 22, 2016

74.
"Problem"[100]
Ariana Grande featuring Iggy Azalea
1.07
May 30, 2014

75.
"Firework"[101]
Katy Perry
1.07
October 28, 2010

76.
"La Bicicleta"[102]
Carlos Vives and Shakira
1.07
July 8, 2016

77.
"That's What I Like"[103]
Bruno Mars
1.06
March 2, 2017

78.
"El Pollito Pio"[104]
pulcinopiotv
1.06
November 29, 2012

79.
"Bang Bang"[105]
Jessie J, Ariana Grande and Nicki Minaj
1.05
August 25, 2014

80.
"Last Friday Night (T.G.I.F.)"[106]
Katy Perry
1.04
June 12, 2011

81.
"Not Afraid"[107]
Eminem
1.03
June 4, 2010

82.
"Just the Way You Are"[108]
Bruno Mars
1.02
September 8, 2010

83.
"Call Me Maybe"[109]
Carly Rae Jepsen
1.01
March 1, 2012

84.
"La Gozadera"[110]
Gente de Zona featuring Marc Anthony
1.01
June 5, 2015

85.
"La Mordidita"[111]
Ricky Martin featuring Yotuel
1.01
June 12, 2015

86.
"Huge Eggs Surprise Toys Challenge"[112]
Ryan ToysReview
1.00
April 13, 2016

87.
"Ahora Dice"[113]
Chris Jeday featuring J Balvin, Ozuna and Arcángel
1.00
March 19, 2017

88.
"Happy"[114]
Pharrell Williams
0.99
November 21, 2013

89.
"Timber"[115]
Pitbull featuring Kesha
0.99
November 25, 2013

90.
"Where Are Ü Now"[116]
Jack Ü and Justin Bieber
0.99
June 29, 2015

91.
"Someone like You"[117]
Adele
0.98
September 29, 2011

92.
"Masha and the Bear: Bon appétit!"[118]
Get Movies
0.98
September 21, 2012

93.
"Somebody That I Used to Know"[119]
Gotye featuring Kimbra
0.97
July 5, 2011

94.
"Darte un Beso"[120]
Prince Royce
0.96
August 20, 2013

95.
"6 AM"[121]
J Balvin featuring Farruko
0.96
April 4, 2014

96.
"El Amante"[122]
Nicky Jam
0.96
January 15, 2017

97.
"Work"[123]
Rihanna featuring Drake
0.96
February 22, 2016

98.
"Cheap Thrills (Lyric video)"[124]
Sia featuring Sean Paul
0.96
February 11, 2016

99.
"Danza Kuduro"[125]
Don Omar featuring Lucenzo
0.95
August 11, 2010

100.
"I'm Not the Only One"[126]
Sam Smith
0.95
August 1, 2014

As of November 26, 2017

text: By year of release

text: The following table lists the current top 5 most viewed YouTube videos uploaded in each year, with each total rounded to the nearest ten million views, as well as the uploader and date of publication to YouTube.[L]

text: As of November 2017, Katy Perry has the most appearances on the list with five, while Taylor Swift and Adele have three. Only Linkin Park (2007), Gummibär/icanrockyourworld (2007) and Taylor Swift (2014) have two videos in the top 5 of a single year, with both the English and French versions of Gummibär's The Gummy Bear Song being in the top five videos of 2007.

text:
Year
Video name
Uploader
Views (billions)
Upload date
Notes

2005
[M]
"Life Goes On"[127]
fhearnoiz
0.10
September 22, 2005

"Hurt"[128]
beachbuggy
0.08
December 12, 2005

"Bohemian Rhapsody"[129]
Frozentoast
0.06
September 18, 2005

"Tarzan Boy"[130]
nailofgilead
0.06
November 2, 2005

"Me at the zoo"[131]
jawed
0.04
April 23, 2005
[N]

Combined views (2005)
0.34
[132][133]

2006
[O]
"Galinha Pintadinha - videoclip infantil animado"[134]
Galinha Pintadinha
0.46
December 28, 2006

"Ella y Yo"[135]
JosephIngma
0.32
April 27, 2006

"Evolution of Dance"[136]
Judson Laipply
0.30
April 6, 2006
[P]

"I Write Sins Not Tragedies"[137]
Fueled By Ramen
0.21
July 18, 2006

"If you are happy"[138]
Alicia Kids!
0.18
September 5, 2006

Combined views (2006)
1.47
[139][140]

2007
[Q]
"The Gummy Bear Song"[91]
icanrockyourworld
1.14
October 9, 2007

"Charlie Bit My Finger"[141]
HDCYT
0.86
May 22, 2007
[R]

"Numb"[142]
Linkin Park
0.71
March 4, 2007

"What I've Done"[143]
0.32
April 3, 2007

"Je m'appelle Funny Bear"[144]
icanrockyourworld
0.31
October 15, 2007

Combined views (2007)
3.34
[139][140]

2008
"Hot n Cold"[145]
KatyPerryVEVO
0.74
October 13, 2008

"Pintinho Amarelinho - DVD Galena Pintadinha"[146]
Galinha Pintadinha
0.49
September 15, 2008

"Viva la Vida"[147]
Coldplay Official
0.45
August 4, 2008

"Bohemian Rhapsody"[148]
Queen Official
0.45
August 1, 2008

"Colgando en tus manos"[149]
Carlos Baute
0.36
October 29, 2008

Combined views (2008)
2.49
[139]

2009
"November Rain"[150]
GunsNRosesVEVO
0.90
December 24, 2009

"Bad Romance"[151]
LadyGagaVEVO
0.88
November 23, 2009
[S]

"You Belong with Me"[152]
TaylorSwiftVEVO
0.78
June 16, 2009

"Axel F"[153]
CrazyFrogVEVO
0.77
June 16, 2009

"Chop Suey!"[154]
systemofadownVEVO
0.64
October 2, 2009

Combined views (2009)
3.97
[139]

2010
"Baby"[46]
JustinBieberVEVO
1.75
February 19, 2010
[T]

"Waka Waka (This Time for Africa)"[54]
shakiraVEVO
1.60
June 4, 2010

"Love the Way You Lie"[57]
EminemVEVO
1.43
August 5, 2010

"Rolling in the Deep"[78]
AdeleVEVO
1.21
November 30, 2010

"Firework"[101]
KatyPerryVEVO
1.07
October 28, 2010

Combined views (2010)
7.06
[139]

2011
"Party Rock Anthem"[64]
LMFAOVEVO
1.38
March 8, 2011

"The Lazy Song"[76]
Bruno Mars
1.24
April 15, 2011

"On the Floor"[89]
JenniferLopezVEVO
1.15
March 3, 2011

"Last Friday Night (T.G.I.F.)"[106]
KatyPerryVEVO
1.03
June 12, 2011

"Someone like You"[117]
AdeleVEVO
0.97
September 29, 2011

Combined views (2011)
5.77
[139]

2012
"Gangnam Style"[20]
officialpsy
3.00
July 15, 2012
[U]

"Маша и Медведь - Маша плюс каша"[28]
Get Movies
2.61
January 31, 2012

"Let Her Go"[52]
Passenger
1.67
July 25, 2012

"Thrift Shop"[92]
Macklemore LCC
1.14
August 29, 2012

"Diamonds"[94]
RihannaVEVO
1.11
November 8, 2012

Combined views (2012)
9.53
[139]

2013
"Roar"[32]
KatyPerryVEVO
2.34
September 5, 2013

"Counting Stars"[40]
OneRepublicVEVO
2.01
May 31, 2013

"Rude"[61]
ournameismagicVEVO
1.41
December 5, 2013

"Wake Me Up"[62]
AviciiVEVO
1.40
July 29, 2013

"Propuesta Indecente"[70]
RomeoSantosVEVO
1.30
September 9, 2013

Combined views (2013)
8.46
[139]

2014
"Uptown Funk"[26]
MarkRonsonVEVO
2.76
November 19, 2014

"Shake It Off"[29]
TaylorSwiftVEVO
2.44
August 18, 2014

"Bailando"[30]
EnriqueIglesiasVEVO
2.42
April 11, 2014

"Blank Space"[34]
TaylorSwiftVEVO
2.21
November 10, 2014

"Dark Horse"[35]
KatyPerryVEVO
2.16
February 20, 2014

Combined views (2014)
11.99
[139]

2015
"See You Again"[13]
Wiz Khalifa
3.22
April 6, 2015
[V]

"Sorry"[25]
JustinBieberVEVO
2.83
October 22, 2015

"Sugar"[31]
Maroon5VEVO
2.40
January 14, 2015

"Lean On"[33]
majorlazer
2.22
March 22, 2015

"Hello"[37]
AdeleVEVO
2.12
October 22, 2015

Combined views (2015)
12.79
[139]

2016
"Chantaje"[41]
shakiraVEVO
1.97
November 18, 2016

"Closer (Lyric video)"[42]
ChainsmokersVEVO
1.94
July 29, 2016

"This Is What You Came For"[44]
CalvinHarrisVEVO
1.84
June 16, 2016

"Work from Home"[49]
FifthHarmonyVEVO
1.74
February 26, 2016

"Rockabye"[51]
Clean Bandit
1.67
October 21, 2016

Combined views (2016)
9.16
[139]

2017
"Despacito"[8]
LuisFonsiVEVO
4.40
January 12, 2017
[W]

"Shape of You"[27]
Ed Sheeran
2.76
January 30, 2017

"Mi Gente"[65]
jbalvinVEVO
1.34
June 29, 2017

"Felices los 4"[84]
MalumaVEVO
1.17
April 21, 2017

"That's What I Like"[103]
Bruno Mars
1.06
March 1, 2017

Combined views (2017)
10.73
[139]

As of November 17, 2017

text: Historical most viewed videos

text: The following table lists the last 15 videos to become YouTube's most viewed video, from October 2005 to the present.

text:
Video name
Uploader
Views*
Upload date
Date achieved
Days held
Ref(s)
Notes

"Despacito"[8]
LuisFonsiVEVO
2,993,700,000
Jan 12, 2017
Aug 4, 2017
115
[155]
[X]

"See You Again"[13]
Wiz Khalifa
2,894,000,000
Apr 6, 2015
Jul 10, 2017
25
[157]

"Gangnam Style"[20]
officialpsy
803,700,000
Jul 15, 2012
Nov 24, 2012
1,689
[21]
[Y]

"Baby"[46]
JustinBieberVEVO
245,400,000
Feb 19, 2010
Jul 16, 2010
862
[47]
[Z]

"Bad Romance"[151]
LadyGagaVEVO
178,400,000
Nov 23, 2009
Apr 14, 2010
93
[161]
[AA]

"Charlie Bit My Finger"[141]
HDCYT
128,900,000
May 22, 2007
Oct 25, 2009
171
[164]

"Evolution of Dance"[136]
Judson Laipply
118,900,000
Apr 6, 2006
May 2, 2009
176
[165]

"Girlfriend"[166][167]
RCARecords
92,600,000
Feb 27, 2007
Jul 17, 2008
289
[168]

"Evolution of Dance"[136]
Judson Laipply
78,400,000
Apr 6, 2006
Mar 15, 2008
124
[169]

"Music Is My Hot Hot Sex"[170]
CLARUSBARTEL72
76,600,000
Apr 9, 2007
Feb 29, 2008
15
[171]
[AB]

"Evolution of Dance"[136]
Judson Laipply
10,600,000
Apr 6, 2006
May 19, 2006
651
[174]
[AC]

"Pokemon Theme Music Video"[175]
Smosh
4,300,000
Nov 28, 2005
Mar 12, 2006
68
[176]
[AD]

"Myspace - The Movie"[179]
eggtea
2,700,000
Jan 31, 2006
Feb 18, 2006
22
[180]

"Phony Photo Booth"[181]
mugenized
3,400,000
Dec 1, 2005
Jan 21, 2006
28
[182]
[AE]

"The Chronic of Narnia Rap"[183]
youtubedude
2,300,000
Dec 18, 2005
Jan 9, 2006
12
[184]

"Ronaldinho: Touch of Gold"[185]
Nikesoccer
255,000
Oct 21, 2005
Oct 31, 2005
70
[186]
[AF]

"I/O Brush"[189]
larfus
247,000
Oct 5, 2005
Oct 29, 2005
2
[190]

As of November 27, 2017

text: *The approximate number of views each video had when it became YouTube's most viewed video.

text: Timeline of Most Viewed Videos (Oct 2005 - Nov 2017)

text: № 1 Most Viewed Video (Oct 2005 - Jun 2006)

text: № 1 Most Viewed Video (Apr 2006 - Jan 2010)

text: № 1 Most Viewed Video (Oct 2009 - Jan 2013)

text: № 1 Most Viewed Video (Jan 2012 - Nov 2017)


document_title: One Day at a Time (2017 TV series)

question_text: who plays the dad on one day at a time

question_tokens: who plays the dad on one day at a time

root

text: One Day at a Time (2017 TV series)

text: Premise[edit]

text: The show depicts the everyday life of a Cuban-American family with each character finding their own journey. Following the story of Penelope Alvarez (Justina Machado) a United States Army Nurse Corps[3] veteran, facing her return to civilian life with a lot of unresolved issues from her time in the Army. She works as a nurse in the office of Dr. Leslie Berkowitz (Stephen Tobolowsky). After her husband's alcoholism due to post-traumatic stress disorder from his time in the Army made it, in Penelope's words, 'unsafe to be in the house', she separates from Victor (James Martínez), taking the children with her. With the help of her Mother, Lydia (Rita Moreno), a refugee who left Cuba as a teen following Fidel Castro's rise to power, she is raising her two children: Elena (Isabella Gómez) and Alex (Marcel Ruiz). Apart from planning her daughter's quinceañera, Penelope starts dating and finds a love interest. Elena, resistant to have a quinces, starts dating a teenager from her class; to later realize that she is a lesbian. After struggling in ways to tell her family about her sexuality she finds the right time to come out. Alex starts working in a school project about Cuba with the help of Schneider (Todd Grinnell) and Lydia. Lydia talks about leaving Cuba escaping from Castro's dictatorship and how she fell in love with her late husband Berto (Tony Plana).

tag: p

text: Each episode of the series focuses on important issues that face the Hispanic community and families in general. It has dealt with topics such as veterans' struggles with PTSD, depression, and anxiety, as well as sexuality, gender identity, sexism, and religion, amongst others.

text: Cast and characters[edit]

text: Main[edit]

text:
Justina Machado as Penelope Riera Alvarez, a United States Army Nurse Corps and mother of Alex and Elena. She works as a nurse for Dr. Leslie Berkowitz. After coming back from army service, she joins a therapy group to help her with her depression and anxiety. In the first season she separates from her husband Victor and starts dating Ben. Later she breaks up with Ben after Victor's visit for Elena's quinceañera. In season two Penelope decides to go back to school to become a nurse practitioner. She begins dating an Army Veteran, now EMT Max Ferraro, but breaks up with him after finding out he wanted children of his own, and decides to let him find that chance with someone else, as she believes that she is too old for another child, and has two children of her own.
Rita Moreno as Lydia Margarita del Carmen Inclán Maribona Leyte-Vidal de Riera, a faithful Cuban, Penelope's mother and grandmother of Elena and Alex. She fled Cuba after Castro seized power. She was a dancer and a performer back in the day. Over the course of the season, she develops a relationship with Dr. Berkowitz.
Isabella Gomez as Elena Maria Alvarez Riera Calderón Leyte-Vidal Inclán, the activist and feminist teenage daughter of Penelope. After dating Josh, a classmate, and watching gay porn, she discovers that she is a lesbian and comes out to her family. The news doesn't sit well with her father, which upsets Elena. In season two she finds a love interest and founds a Gay-Straight Alliance club at her Catholic School.
Marcel Ruiz as Alejandro "Alex" Alberto Alvarez Riera Calderon Leyte-Vidal Inclán, the son of Penelope. He wants to gain popularity at school and is part of the baseball team. He starts a school project about Cuba. In season two he begins working during the summer at Dr. Berkowitz's office.
Todd Grinnell as Dwayne Schneider, the rich landlord of the building. He is a close friend of the family and Penelope's best friend. Schneider is frequently having one-night stands with different women. Often in the series he talks about having multiple stepmothers and how dysfunctional his family was, while also occasionally discussing his history of addictions. He is Canadian and after years of having a green card decides to become a US citizen.
Stephen Tobolowsky as Dr. Leslie Berkowitz, Penelope's boss and Lydia's love interest.

tag: ul

text: Recurring[edit]

text:
Fiona Gubelmann as Lori (season 1): Penelope's co-worker.
Ariela Barer as Carmen (season 1): Elena's best friend. She spent nights with Elena in her bedroom after her parents were deported back to Mexico, but Penelope finds out. She later moves to Austin, Texas to live with her brothers.
Froy Gutierrez as Josh Flores (season 1)
Eric Nenninger as Scott (season 1–present): Penelope's co-worker.
Haneefah Wood as Jill Riley (season 1–present): Penelope's friend.
Mackenzie Phillips as Pam Valentine (season 1–present): the leader of Penelope's female veteran therapy group.
Judy Reyes as Ramona (season 1–present): Penelope's friend from the therapy group.
Tony Plana as Berto Riera (season 1–present): Lydia's late husband.
James Martínez as Victor Alvarez (season 1–present): Penelope's ex-husband.
Ed Quinn as Max Ferraro (season 2): a military veteran, EMT, and Penelope's ex-boyfriend[15]
Sheridan Pierce as Syd (season 2–present): Elena's girlfriend who is non-binary.[16][17]
Raúl Castillo as Mateo (season 3): Penelope's friend from school who is also a parent[18]

text: Guest[edit]

text:
Cedric Yarbrough as Jerry
Jay Hayden as Ben
Gabrielle Elyse as Dani
Jolie Jenkins as Nikki
Ivonne Coll as Esme
Emiliano Díez as Padre Jose
Georgia Engel as Sister Barbara
Tim Bagley as Henry
Mindy Sterling as Delia
Timm Sharp as Nurse Wally

text: Episodes[edit]

text: SeasonEpisodesOriginally released113January 6, 2017 (2017-01-06)213January 26, 2018 (2018-01-26)313[19]2019 (2019)[19]

tag: table

text: Production[edit]

text: This section needs expansion. You can help by adding to it. (April 2018)

text: Music[edit]

text: The theme song for the original One Day at a Time series, “This is It", was re-recorded for the newer version of the series, with a new arrangement by Emilio Estefan featuring Cuban instrumentation and lead vocals by Gloria Estefan. The song was composed by husband-and-wife songwriters Jeff Barry and Nancy Barry. Recording artist Polly Cutter sang the original version of the theme song.[20]

text: Reception[edit]

text:
Season

Critical response

Rotten Tomatoes

Metacritic

1

97% (29 reviews)

79 (23 reviews)

2

100% (14 reviews)

88 (6 reviews)

text: Critical response[edit]

text: On the review aggregator Rotten Tomatoes, the first season has an approval rating of 97% based on 30 reviews with an average rating of 7.62/10. The site's critical consensus reads, "One Day at a Time breathes fresh life into the classic Norman Lear original with a lively, sharp, and proudly old-school sitcom bolstered by a surfeit of heart and terrific performances from Rita Moreno and Justina Machado."[21]

text: Robert Lloyd of the Los Angeles Times found the first season to be "lively without being rushed" thanks to the full 30 minute run time.[22] "The show is nicely written ... and the performances [especially Moreno's] are almost universally engaging," according to David Wiegand of the San Francisco Chronicle.[23] The Newsday review by Verne Gay particularly praises Machado as "flat-out terrific" and calls the first season "congenial, good-hearted, easy going, sentimental, old-fashioned and surprisingly new-fashioned. There’s also a deep emotional core here which refuses to be devalued by the typical (or tired) beat of a multicamera sitcom."[24]

text: A USA Today review by Kelly Lawler noted that Elena's coming-out arc in the first season has drawn special praise from LGBT critics for its "unique, realistic and refreshing take on the subject... the depiction of a young, happy Latinx lesbian comes as a hopeful sign for many."[25] Autostraddle senior editor Yvonne Marquez called the arc "mind-blowing"[25] and the show revolutionary because "it centers the family’s brownness and provides ample social commentary to deliver a fantastic modern-day sitcom."[26]

text: Awards and nominations[edit]

text:
Year

Award

Category

Nominees

Result

Ref.

2017

Teen Choice Awards

Choice TV Show: Comedy

One Day at a Time

Nominated

[27]

Imagen Foundation Awards

Best Primetime Television Program – Comedy

Won

[28][29]

Best Actress – Television

Justina Machado

Won

Best Supporting Actress – Television

Rita Moreno

Nominated

Isabella Gomez

Won

Best Young Actor – Television

Marcel Ruiz

Won

IGN Summer Awards

Best Comedic TV Performance

Rita Moreno

Nominated

[30]

Primetime Emmy Awards

Outstanding Multi-Camera Picture Editing for a Comedy Series

Pat Barnett

Nominated

[31]

Online Film & Television Association Awards

Best Comedy Series

One Day at a Time

Nominated

[32]

Best Actress in a Comedy Series

Justina Machado

Nominated

Best Supporting Actress in a Comedy Series

Rita Moreno

Nominated

Best Ensemble in a Comedy Series

One Day at a Time

Nominated

Best Direction in a Comedy Series

Nominated

Gold Derby Awards

Best Comedy Supporting Actress

Rita Moreno

Nominated

[33]

2018

Critics' Choice Television Awards

Best Supporting Actress in a Comedy Series

Nominated

[34]

TVLine Awards

Performer of the Week

Justina Machado

Won

[35]

GLAAD Media Awards

Outstanding Comedy Series

One Day at a Time

Nominated

[36]

Television Academy Honors

Television with a Conscience

Won

[37]

TCA Awards

Outstanding Achievement in Comedy

Pending

[38]

Imagen Foundation Awards

Best Primetime Television Program – Comedy

Pending

[39]

Best Actress – Television

Justina Machado

Pending

Rita Moreno

Pending

Isabella Gomez

Pending

Best Young Actor – Television

Marcel Ruiz

Pending


document_title: Progesterone

question_text: where does the progesterone that helps maintain the pregnancy come from

text: Progesterone

text: Biological activity[edit]

text: Progesterone is the most important progestogen in the body, the result of its action as a potent agonist of the nuclear progesterone receptor (nPR) (with an affinity of KD = 1 nM).[13][11] In addition, progesterone is an agonist of the more recently discovered membrane progesterone receptors (mPRs),[14] as well as a ligand of the PGRMC1 (progesterone receptor membrane component 1).[15] Moreover, progesterone is also known to be an antagonist of the sigma σ1 receptor,[16][17] a negative allosteric modulator of nicotinic acetylcholine receptors,[12] and a potent antagonist of the mineralocorticoid receptor (MR).[18] Progesterone prevents MR activation by binding to this receptor with an affinity exceeding even those of aldosterone and glucocorticoids such as cortisol and corticosterone,[18] and produces antimineralocorticoid effects, such as natriuresis, at physiological concentrations.[19] In addition, progesterone binds to and behaves as a partial agonist of the glucocorticoid receptor (GR), albeit with very low potency (EC50 >100-fold less relative to cortisol).[20][21]

text: Progesterone, through its neurosteroid active metabolites such as 5α-dihydroprogesterone and allopregnanolone, acts indirectly as a positive allosteric modulator of the GABAA receptor.[22]

text: Progesterone and some of its metabolites, such as 5β-dihydroprogesterone, are agonists of the pregnane X receptor (PXR),[23] albeit weakly so (EC50 >10 µM).[24] In accordance, progesterone induces several hepatic cytochrome P450 enzymes,[25] such as CYP3A4,[26][27] especially during pregnancy when concentrations are much higher than usual.[28] Perimenopausal women have been found to have greater CYP3A4 activity relative to men and postmenopausal women, and it has been inferred that this may be due to the higher progesterone levels present in perimenopausal women.[26]

text: Progesterone modulates the activity of CatSper (cation channels of sperm) voltage-gated Ca2+ channels. Since eggs release progesterone, sperm may use progesterone as a homing signal to swim toward eggs (chemotaxis). As a result, it has been suggested that substances that block the progesterone binding site on CatSper channels could potentially be used in male contraception.[29][30]

text: Biological function[edit]

text: Hormonal interactions[edit]

text: Progesterone has a number of physiological effects that are amplified in the presence of estrogens. Estrogens through estrogen receptors (ERs) induce or upregulate the expression of the PR.[31] One example of this is in breast tissue, where estrogens allow progesterone to mediate lobuloalveolar development.[32][33][34]

text: Elevated levels of progesterone potently reduce the sodium-retaining activity of aldosterone, resulting in natriuresis and a reduction in extracellular fluid volume. Progesterone withdrawal, on the other hand, is associated with a temporary increase in sodium retention (reduced natriuresis, with an increase in extracellular fluid volume) due to the compensatory increase in aldosterone production, which combats the blockade of the mineralocorticoid receptor by the previously elevated level of progesterone.[35]

text: Reproductive system[edit]

text: Progesterone has key effects via non-genomic signalling on human sperm as they migrate through the female tract before fertilization occurs, though the receptor(s) as yet remain unidentified.[36] Detailed characterisation of the events occurring in sperm in response to progesterone has elucidated certain events including intracellular calcium transients and maintained changes,[37] slow calcium oscillations,[38] now thought to possibly regulate motility.[39] It is produced by the ovaries.[40] Interestingly, progesterone has also been shown to demonstrate effects on octopus spermatozoa.[41]

text: Progesterone is sometimes called the "hormone of pregnancy",[42] and it has many roles relating to the development of the fetus:

text:
Progesterone converts the endometrium to its secretory stage to prepare the uterus for implantation. At the same time progesterone affects the vaginal epithelium and cervical mucus, making it thick and impenetrable to sperm. Progesterone is anti-mitogenic in endometrial epithelial cells, and as such, mitigates the tropic effects of estrogen.[43] If pregnancy does not occur, progesterone levels will decrease, leading, in the human, to menstruation. Normal menstrual bleeding is progesterone-withdrawal bleeding. If ovulation does not occur and the corpus luteum does not develop, levels of progesterone may be low, leading to anovulatory dysfunctional uterine bleeding.
During implantation and gestation, progesterone appears to decrease the maternal immune response to allow for the acceptance of the pregnancy.
Progesterone decreases contractility of the uterine smooth muscle.[42]
In addition progesterone inhibits lactation during pregnancy. The fall in progesterone levels following delivery is one of the triggers for milk production.
A drop in progesterone levels is possibly one step that facilitates the onset of labor.

text: The fetus metabolizes placental progesterone in the production of adrenal steroids.

text: Breasts[edit]

text: Lobuloalveolar development[edit]

text: Progesterone plays an important role in breast development in women. In conjunction with prolactin, it mediates lobuloalveolar maturation of the mammary glands during pregnancy to allow for milk production and thus lactation and breastfeeding of offspring following parturition (childbirth).[44] Estrogen induces expression of the PR in breast tissue and hence progesterone is dependent on estrogen to mediate lobuloalveolar development.[32][33][34] It has been found that RANKL is a critical downstream mediator of progesterone-induced lobuloalveolar maturation.[45] RANKL knockout mice show an almost identical mammary phenotype to PR knockout mice, including normal mammary ductal development but complete failure of the development of lobuloalveolar structures.[45]

text: Ductal development[edit]

text: Though to a far lesser extent than estrogen, which is the major mediator of mammary ductal development (via the ERα),[46][47] progesterone has been found to be involved in ductal development of the mammary glands to some extent as well.[48] PR knockout mice or mice treated with the PR antagonist mifepristone show delayed although otherwise normal mammary ductal development at puberty.[48] In addition, mice modified to have overexpression of PRA display ductal hyperplasia,[45] and progesterone induces ductal growth in the mouse mammary gland.[48] Progesterone mediates ductal development mainly via induction of the expression of amphiregulin, the same growth factor that estrogen primarily induces the expression of to mediate ductal development.[48] These animal findings suggest that, while not essential for full mammary ductal development, progesterone seems to play a potentiating or accelerating role in estrogen-mediated mammary ductal development.[48]

text: Breast cancer risk[edit]

text: Progesterone also appears to be involved in the pathophysiology of breast cancer, though its role, and whether it is a promoter or inhibitor of breast cancer risk, has not been fully elucidated.[49] In any case, while most synthetic progestins like medroxyprogesterone acetate have been found to significantly increase the risk of breast cancer in postmenopausal women in combination with estrogen as a component of hormone replacement therapy, the combination of natural progesterone (or the atypical progestin dydrogesterone) with estrogen has been found not to do so.[50][51]

text: Skin health[edit]

text: The estrogen receptor, as well as the progesterone receptor, have been detected in the skin, including in keratinocytes and fibroblasts.[52][53] At menopause and thereafter, decreased levels of female sex hormones result in atrophy, thinning, and increased wrinkling of the skin and a reduction in skin elasticity, firmness, and strength.[52][53] These skin changes constitute an acceleration in skin aging and are the result of decreased collagen content, irregularities in the morphology of epidermal skin cells, decreased ground substance between skin fibers, and reduced capillaries and blood flow.[52][53] The skin also becomes more dry during menopause, which is due to reduced skin hydration and surface lipids (sebum production).[52] Along with chronological aging and photoaging, estrogen deficiency in menopause is one of the three main factors that predominantly influences skin aging.[52]

text: HRT, consisting of systemic treatment with estrogen alone or in combination with a progestogen, has well-documented and considerable beneficial effects on the skin of postmenopausal women.[52][53] These benefits include increased skin collagen content, skin thickness and elasticity, and skin hydration and surface lipids.[52][53] Topical estrogen has been found to have similar beneficial effects on the skin.[52] In addition, a study has found that topical 2% progesterone cream significantly increases skin elasticity and firmness and observably decreases wrinkles in peri- and postmenopausal women.[53] Skin hydration and surface lipids, on the other hand, did not significantly change with topical progesterone.[53] These findings suggest that progesterone, like estrogen, also has beneficial effects on the skin, and may be independently protective against skin aging.[53]

text: Sexuality[edit]

text: Sex drive[edit]

text: Progesterone and its neurosteroid active metabolite allopregnanolone appear to be importantly involved in sex drive in females.[54]

text: Homosexuality[edit]

text: Dr. Diana Fleischman, of the University of Portsmouth, and colleagues examined the relationship between progesterone and sexual attitudes. Their research was published in the Archives of Sexual Behavior.[55] They found that women who have higher levels of progesterone are more likely to be open to the idea of engaging in sexual behaviour with other women.[56] This pattern is particularly dramatic in men who have high levels of progesterone.[57]

text: Nervous system[edit]

text: Progesterone, like pregnenolone and dehydroepiandrosterone (DHEA), belongs to an important group of endogenous steroids called neurosteroids. It can be metabolized within all parts of the central nervous system.[58]

text: Neurosteroids are neuromodulators, and are neuroprotective, neurogenic, and regulate neurotransmission and myelination.[59] The effects of progesterone as a neurosteroid are mediated predominantly through its interactions with non-nuclear PRs, namely the mPRs and PGRMC1, as well as certain other receptors, such as the σ1 and nACh receptors.[citation needed]

text: Aging[edit]

text: Since most progesterone in males is created during testicular production of testosterone, and most in females by the ovaries, the shutting down (whether by natural or chemical means), or removal, of those inevitably causes a considerable reduction in progesterone levels. Previous concentration upon the role of progestogens in female reproduction, when progesterone was simply considered a "female hormone", obscured the significance of progesterone elsewhere in both sexes.

text: The tendency for progesterone to have a regulatory effect, the presence of progesterone receptors in many types of body tissue, and the pattern of deterioration (or tumor formation) in many of those increasing in later years when progesterone levels have dropped, is prompting widespread research into the potential value of maintaining progesterone levels in both males and females.[citation needed]

text: Brain damage[edit]

text: Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to traumatic brain injury and this protective effect has been hypothesized to be caused by increased circulating levels of estrogen and progesterone in females.[60]

text: Proposed mechanism[edit]

text: The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma and hemorrhage.[61][62]

text: Damage incurred by traumatic brain injury is believed to be caused in part by mass depolarization leading to excitotoxicity. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the voltage-dependent calcium channels that trigger neurotransmitter release.[63] It does so by manipulating the signaling pathways of transcription factors involved in this release. Another method for reducing the excitotoxicity is by up-regulating the GABAA, a widespread inhibitory neurotransmitter receptor.[64]

text: Progesterone has also been shown to prevent apoptosis in neurons, a common consequence of brain injury.[65] It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated caspase 3 and cytochrome c.

text: Not only does progesterone help prevent further damage, it has also been shown to aid in neuroregeneration. One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in edema levels by increasing the concentration of macrophages and microglia sent to the injured tissue.[63][66] This was observed in the form of reduced leakage from the blood brain barrier in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have antioxidant properties, reducing the concentration of oxygen free radicals faster than without.[64] There is also evidence that the addition of progesterone can also help remyelinate damaged axons due to trauma, restoring some lost neural signal conduction.[64] Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain.[67] This helps new vasculature to grow around scar tissue which helps repair the area of insult.

text: Addiction[edit]

text: Progesterone enhances the function of serotonin receptors in the brain, so an excess or deficit of progesterone has the potential to result in significant neurochemical issues. This provides an explanation for why some people resort to substances that enhance serotonin activity such as nicotine, alcohol, and cannabis when their progesterone levels fall below optimal levels.[68]

text:
Sex differences in hormone levels may induce women to respond differently than men to nicotine. When women undergo cyclic changes or different hormonal transition phases (menopause, pregnancy, adolescence), there are changes in their progesterone levels.[69] Therefore, females have an increased biological vulnerability to nicotine’s reinforcing effects compared to males and progesterone may be used to counter this enhanced vulnerability. This information supports the idea that progesterone can affect behavior.[68]
Similar to nicotine, cocaine also increases the release of dopamine in the brain. The neurotransmitter is involved in the reward center and is one of the main neurotransmitters involved with substance abuse and reliance. In a study of cocaine users, it was reported that progesterone reduced craving and the feeling of being stimulated by cocaine. Thus, progesterone was suggested as an agent that decreases cocaine craving by reducing the dopaminergic properties of the drug.[70]

text: Other effects[edit]

text:
Progesterone also has a role in skin elasticity and bone strength, in respiration, in nerve tissue and in female sexuality, and the presence of progesterone receptors in certain muscle and fat tissue may hint at a role in sexually dimorphic proportions of those.[71][copyright violation?]
During pregnancy, progesterone is said to decrease irritability.[72]
During pregnancy, progesterone helps to suppress immune responses of the mother to fetal antigens, which prevents rejection of the fetus.[72]
Progesterone raises epidermal growth factor-1 (EGF-1) levels, a factor often used to induce proliferation, and used to sustain cultures, of stem cells.[73]
Progesterone increases core temperature (thermogenic function) during ovulation.[74]
Progesterone reduces spasm and relaxes smooth muscle. Bronchi are widened and mucus regulated. (PRs are widely present in submucosal tissue.)
Progesterone acts as an antiinflammatory agent and regulates the immune response.
Progesterone reduces gall-bladder activity.[75]
Progesterone normalizes blood clotting and vascular tone, zinc and copper levels, cell oxygen levels, and use of fat stores for energy.
Progesterone may affect gum health, increasing risk of gingivitis (gum inflammation).[76]
Progesterone appears to prevent endometrial cancer (involving the uterine lining) by regulating the effects of estrogen.
Progesterone plays an important role in the signaling of insulin release and pancreatic function, and may affect the susceptibility to diabetes or gestational diabetes.[77][78]
Progesterone may play a role in male behavior, such as in male aggression towards infants.[79]

text: Biochemistry[edit]

text: Biosynthesis[edit]

text: In mammals, progesterone, like all other steroid hormones, is synthesized from pregnenolone, which itself is derived from cholesterol.

text: Cholesterol undergoes double oxidation to produce 22R-hydroxycholesterol and then 20α,22R-dihydroxycholesterol. This vicinal diol is then further oxidized with loss of the side chain starting at position C22 to produce pregnenolone. This reaction is catalyzed by cytochrome P450scc.

text: The conversion of pregnenolone to progesterone takes place in two steps. First, the 3β-hydroxyl group is oxidized to a keto group and second, the double bond is moved to C4, from C5 through a keto/enol tautomerization reaction.[81] This reaction is catalyzed by 3β-hydroxysteroid dehydrogenase/δ5-4-isomerase.

text: Progesterone in turn is the precursor of the mineralocorticoid aldosterone, and after conversion to 17α-hydroxyprogesterone, of cortisol and androstenedione. Androstenedione can be converted to testosterone, estrone, and estradiol.

text: Pregnenolone and progesterone can also be synthesized by yeast.[82]

text: Distribution[edit]

text: Progesterone binds extensively to plasma proteins, including albumin (50–54%) and transcortin (43–48%).[83] It has similar affinity for albumin relative to the PR.[13]

text: Metabolism[edit]

text: The metabolism of progesterone is rapid and extensive and occurs mainly in the liver,[84][85][86] though enzymes that metabolize progesterone are also expressed widely in the brain, skin, and various other extrahepatic tissues.[58][87] Progesterone has a terminal half-life of only approximately 5 minutes in circulation.[84] The metabolism of progesterone is complex, and it may form as many as 35 different unconjugated metabolites when it is ingested orally.[86][88] Progesterone is highly susceptible to enzymatic reduction via reductases and hydroxysteroid dehydrogenases due to its double bond (between the C4 and C5 positions) and its two ketones (at the C3 and C20 positions).[86]

text: The major metabolic pathway of progesterone is reduction by 5α-reductase[58] and 5β-reductase into the dihydrogenated 5α-dihydroprogesterone and 5β-dihydroprogesterone, respectively.[85][86][89][90] This is followed by the further reduction of these metabolites via 3α-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase into the tetrahydrogenated allopregnanolone, pregnanolone, isopregnanolone, and epipregnanolone.[91][85][86][89] Subsequently, 20α-hydroxysteroid dehydrogenase and 20β-hydroxysteroid dehydrogenase reduce these metabolites to form the corresponding hexahydrogenated pregnanediols (eight different isomers in total),[85][90] which are then conjugated via glucuronidation and/or sulfation, released from the liver into circulation, and excreted by the kidneys into the urine.[84][86] The major metabolite of progesterone in the urine is the 3α,5β,20α isomer of pregnanediol glucuronide, which has been found to constitute 15 to 30% of an injection of progesterone.[13][92] Other metabolites of progesterone formed by the enzymes in this pathway include 3α-dihydroprogesterone, 3β-dihydroprogesterone, 20α-dihydroprogesterone, and 20β-dihydroprogesterone, as well as various combination products of the enzymes aside from those already mentioned.[13][86][92][93] Progesterone can also first be hydroxylated (see below) and then reduced.[86]

text: Relatively small portions of progesterone are hydroxylated via 17α-hydroxylase (CYP17A1) and 21-hydroxylase (CYP21A2) into 17α-hydroxyprogesterone and 11-deoxycorticosterone (21-hydroxyprogesterone), respectively,[88] and pregnanetriols are formed secondarily to 17α-hydroxylation.[94][95] In addition, progesterone can be hydroxylated in the liver by other cytochrome P450 enzymes which are not steroid-specific.[96] 6β-Hydroxylation, which is catalyzed mainly by CYP3A4, is the major transformation, and is responsible for approximately 70% of cytochrome P450-mediated progesterone metabolism.[96] Other routes include 6α-, 16α-, and 16β-hydroxylation.[86] However, treatment of women with ketoconazole, a strong CYP3A4 inhibitor, had minimal effects on progesterone levels, producing only a slight and non-significant increase, and this suggests that cytochrome P450 enzymes play only a small role in progesterone metabolism.[97]

text: Levels[edit]

text:
Person type
Reference range for blood test

Lower limit
Upper limit
Unit

Female - menstrual cycle
(see diagram below)

Female - postmenopausal
<0.2[98]
1[98]
ng/mL

<0.6[99]
3[99]
nmol/L

Female on oral contraceptives
0.34[98]
0.92[98]
ng/mL

1.1[99]
2.9[99]
nmol/L

Males ≥16 years
0.27[98]
0.9[98]
ng/mL

0.86[99]
2.9[99]
nmol/L

Female or male 1–9 years
0.1[98]
4.1[98] or 4.5[98]
ng/mL

0.3[99]
13[99]
nmol/L

text: In women, progesterone levels are relatively low during the preovulatory phase of the menstrual cycle, rise after ovulation, and are elevated during the luteal phase, as shown in diagram below. Progesterone levels tend to be < 2 ng/ml prior to ovulation, and > 5 ng/ml after ovulation. If pregnancy occurs, human chorionic gonadotropin is released maintaining the corpus luteum allowing it to maintain levels of progesterone. Between 7–9 weeks the placenta begins to produce progesterone in place of the corpus luteum, this process is named the luteal-placental shift.[100]

text: After the luteal-placental shift progesterone levels start to rise further and may reach 100–200 ng/ml at term. Whether a decrease in progesterone levels is critical for the initiation of labor has been argued and may be species-specific. After delivery of the placenta and during lactation, progesterone levels are very low.

text: Progesterone levels are relatively low in children and postmenopausal women.[101] Adult males have levels similar to those in women during the follicular phase of the menstrual cycle.

text: Blood test results should always be interpreted using the reference ranges provided by the laboratory that performed the results. Example reference ranges are listed below.

text: Sources[edit]

text: Animal[edit]

text: Progesterone is produced in high amounts in the ovaries (by the corpus luteum) from the onset of puberty to menopause, and is also produced in smaller amounts by the adrenal glands after the onset of adrenarche in both males and females. To a lesser extent, progesterone is produced in nervous tissue, especially in the brain, and in adipose (fat) tissue, as well.

text: During human pregnancy, progesterone is produced in increasingly high amounts by the ovaries and placenta. At first, the source is the corpus luteum that has been "rescued" by the presence of human chorionic gonadotropin (hCG) from the conceptus. However, after the 8th week, production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and used as substrate for fetal corticosteroids. At term the placenta produces about 250 mg progesterone per day.

text: An additional animal source of progesterone is milk products. After consumption of milk products the level of bioavailable progesterone goes up.[103]

text: Plants[edit]

text: In at least one plant, Juglans regia, progesterone has been detected.[104] In addition, progesterone-like steroids are found in Dioscorea mexicana. Dioscorea mexicana is a plant that is part of the yam family native to Mexico.[105] It contains a steroid called diosgenin that is taken from the plant and is converted into progesterone.[106] Diosgenin and progesterone are also found in other Dioscorea species, as well as in other plants that are not closely related, such as fenugreek.

text: Another plant that contains substances readily convertible to progesterone is Dioscorea pseudojaponica native to Taiwan. Research has shown that the Taiwanese yam contains saponins — steroids that can be converted to diosgenin and thence to progesterone.[107]

text: Many other Dioscorea species of the yam family contain steroidal substances from which progesterone can be produced. Among the more notable of these are Dioscorea villosa and Dioscorea polygonoides. One study showed that the Dioscorea villosa contains 3.5% diosgenin.[108] Dioscorea polygonoides has been found to contain 2.64% diosgenin as shown by gas chromatography-mass spectrometry.[109] Many of the Dioscorea species that originate from the yam family grow in countries that have tropical and subtropical climates.[110]

text: Medical use[edit]

text: Progesterone is used as a medication, mainly in hormone replacement therapy.[88]

text: Chemistry[edit]

text: Progesterone is a pregnane (C21) steroid and is also known as pregn-4-ene-3,20-dione. It has a double bond (4-ene) between the C4 and C5 positions and two ketone groups (3,20-dione), one at the C3 position and the other at the C20 position.

text: Like all unconjugated steroid hormones, progesterone is lipophilic and hydrophobic.

text: Synthesis[edit]

text: Semisynthesis 1[edit]

text: An economical semisynthesis of progesterone from the plant steroid diosgenin isolated from yams was developed by Russell Marker in 1940 for the Parke-Davis pharmaceutical company.[111] This synthesis is known as the Marker degradation. Additional semisyntheses of progesterone have also been reported starting from a variety of steroids. For the example, cortisone can be simultaneously deoxygenated at the C-17 and C-21 position by treatment with iodotrimethylsilane in chloroform to produce 11-keto-progesterone (ketogestin), which in turn can be reduced at position-11 to yield progesterone.[112]

text: Semisynthesis 2[edit]

text: Progesterone can also be made from the stigmasterol found in soybean oil also. c.f. Percy Julian.

text: Total synthesis[edit]

text: A total synthesis of progesterone was reported in 1971 by W.S. Johnson.[118] The synthesis begins with reacting the phosphonium salt 7 with phenyl lithium to produce the phosphonium ylide 8. The ylide 8 is reacted with an aldehyde to produce the alkene 9. The ketal protecting groups of 9 are hydrolyzed to produce the diketone 10, which in turn is cyclized to form the cyclopentenone 11. The ketone of 11 is reacted with methyl lithium to yield the tertiary alcohol 12, which in turn is treated with acid to produce the tertiary cation 13. The key step of the synthesis is the π-cation cyclization of 13 in which the B-, C-, and D-rings of the steroid are simultaneously formed to produce 14. This step resembles the cationic cyclization reaction used in the biosynthesis of steroids and hence is referred to as biomimetic. In the next step the enol orthoester is hydrolyzed to produce the ketone 15. The cyclopentene A-ring is then opened by oxidizing with ozone to produce 16. Finally, the diketone 17 undergoes an intramolecular aldol condensation by treating with aqueous potassium hydroxide to produce progesterone.[118]

text: History[edit]

text: The hormonal action of progesterone was discovered in 1929, following that of estrogen in 1923.[13][119][120] By 1931–1932, nearly pure crystalline material of high progestational activity had been isolated from the corpus luteum of animals, and by 1934, pure crystalline progesterone had been refined and obtained and the chemical structure of progesterone was determined.[13][119] This was achieved by Adolf Butenandt at the Chemisches Institut of Technical University in Gdańsk, who extracted this new compound from several thousand liters of urine.[121]

text: Chemical synthesis of progesterone from stigmasterol and pregnanediol was accomplished later that year.[119][122] Up to this point, progesterone, known generically as corpus luteum hormone, had been being referred to by several groups by different names, including corporin, lutein, luteosterone, and progestin.[13][123] In 1935, at the time of the Second International Conference on the Standardization of Sex Hormones in London, England, a compromise was made between the groups and the name progesterone (progestational steroidal ketone) was created.[13][124]


document_title: Respiratory epithelium

question_text: where are ciliated cells found in the respiratory system

text: Respiratory epithelium

text:
Respiratory epithelium

Diagram of the trachea showing respiratory epithelium at the top

Illustration depicting Pseudostratified Ciliated Columnar Epithelium.

Details

System
[Respiratory system]]

Identifiers

MeSH
D020545

TH
H3.05.00.0.00003

Anatomical terms of microanatomy
[edit on Wikidata]

text:
This article is one of a series on

Epithelia

Squamous epithelial cell

Simple
Stratified

Columnar epithelial cell

Simple
Stratified
Pseudostratified

Cuboidal epithelial cell

Simple
Stratified

Specialised epithelia

Olfactory
Respiratory
Intestinal
Transitional
Vaginal
Germinal

female
male

Other

Table of epithelia of human organs

v
t
e

text: Respiratory epithelium is a type of ciliated epithelium found lining most of the respiratory tract, where it serves to moisten and protect the airways. It is not present in the larynx and pharynx. It also functions as a barrier to potential pathogens and foreign particles, preventing infection and tissue injury by the action of mucociliary clearance.

text: Structure[edit]

text: The respiratory epithelium lining the upper respiratory airways is classified as ciliated pseudostratified columnar epithelium.[1] This designation is due to the arrangement of the multiple cell types composing the respiratory epithelium. While all cells make contact with the basement membrane and are, therefore, a single layer of cells, the nuclei are not aligned in the same plane. Hence, it appears as though several layers of cells are present and the epithelium is called pseudostratified.

text: The majority of cells composing the ciliated pseudostratified columnar epithelium are of three types: a) ciliated cells, b) goblet cells, and c) basal cells. The ciliated cells are columnar epithelial cells with specialized ciliary modifications. Goblet cells, so named because they are shaped like a wine goblet, are columnar epithelial cells that contain membrane-bound mucous granules and secrete mucus, or epithelial lining fluid (ELF), the composition of which is tightly regulated; the mucus helps maintain epithelial moisture and traps particulate material and pathogens moving through the airway. and determines how well mucociliary clearance works.[2][3]:Section 4 pages 7-8 (Page 4-7ff) The basal cells are small, nearly cuboidal cells thought to have some ability to differentiate into other cells types found within the epithelium. For example, these basal cells respond to injury of the airway epithelium, migrating to cover a site denuded of differentiated epithelial cells, and subsequently differentiating to restore a healthy epithelial cell layer.

text: Certain parts of the respiratory tract, such as the oropharynx, are also subject to the abrasive swallowing of food. To prevent the destruction of the respiratory epithelium in these areas, it changes to stratified squamous epithelium, which is better suited to the constant sloughing and abrasion. The squamous layer of the oropharynx is continuous with the esophagus.[citation needed]


document_title: French and Indian War

question_text: who led the french army in the french and indian war

text: French and Indian War

text: The origin of the name

text: The conflict is known by multiple names. In British America, wars were often named after the sitting British monarch, such as King William's War or Queen Anne's War. There had already been a King George's War in the 1740s during the reign of King George II, so British colonists named this conflict after their opponents, and it became known as the French and Indian War.[9] This traditional name continues as the standard in the United States, but it obscures the fact that Indians fought on both sides of the conflict and that this was part of the Seven Years' War, a much larger conflict between France and Great Britain.[10] American historians generally use the traditional name or sometimes the Seven Years' War. Less frequently used names for the war include the Fourth Intercolonial War and the Great War for the Empire.[9]

text: In Europe, the North American theater of the Seven Years' War usually is not given a separate name. The entire international conflict is known as the Seven Years' War. "Seven Years" refers to events in Europe, from the official declaration of war in 1756 to the signing of the peace treaty in 1763. These dates do not correspond with the fighting on mainland North America, which was largely concluded in six years, from the Battle of Jumonville Glen in 1754 to the capture of Montreal in 1760.[9]

text: Canadians refer to both the European and North American conflicts as the Seven Years' War (Guerre de Sept Ans).[11][12] French Canadians also use the term "War of Conquest" (Guerre de la Conquête), since it is the war in which Canada was conquered by the British and became part of the British Empire.

text: North America in the 1750s

text: At this time, North America east of the Mississippi River was largely claimed by either Great Britain or France. Large areas had no colonial settlements. The French population numbered about 75,000 and was heavily concentrated along the St. Lawrence River valley, with some also in Acadia (present-day New Brunswick and parts of Nova Scotia), including Île Royale (present-day Cape Breton Island). Fewer lived in New Orleans, Biloxi, Mississippi, Mobile, Alabama, and small settlements in the Illinois Country, hugging the east side of the Mississippi River and its tributaries. French fur traders and trappers traveled throughout the St. Lawrence and Mississippi watersheds, did business with local Indian tribes, and often married Indian women.[13] Traders married daughters of chiefs, creating high-ranking unions.

text: British settlers outnumbered the French 20 to 1[14] with a population of about 1.5 million ranged along the eastern coast of the continent from Nova Scotia and Newfoundland in the north to Georgia in the south.[15] Many of the older colonies had land claims that extended arbitrarily far to the west, as the extent of the continent was unknown at the time when their provincial charters were granted. Their population centers were along the coast, yet the settlements were growing into the interior. Nova Scotia had been captured from France in 1713, and it still had a significant French-speaking population. Britain also claimed Rupert's Land where the Hudson's Bay Company traded for furs with local Indian tribes.

text: In between the French and British colonists, large areas were dominated by Indian tribes. To the north, the Mi'kmaqs and the Abenakis were engaged in Father Le Loutre's War and still held sway in parts of Nova Scotia, Acadia, and the eastern portions of the province of Canada, as well as much of Maine.[16] The Iroquois Confederation dominated much of Upstate New York and the Ohio Country, although Ohio also included Algonquian-speaking populations of Delaware and Shawnee, as well as Iroquoian-speaking Mingos. These tribes were formally under Iroquois rule and were limited by them in their authority to make agreements.[17]

text: The Southeast interior was dominated by Siouan-speaking Catawbas, Muskogee-speaking Creeks and Choctaw, and the Iroquoian-speaking Cherokee tribes.[18] When war broke out, the French colonists used their trading connections to recruit fighters from tribes in western portions of the Great Lakes region, which was not directly subject to the conflict between the French and British; these included the Hurons, Mississaugs, Ojibwas, Winnebagos, and Potawatomi. The British colonists were supported in the war by the Iroquois Six Nations and also by the Cherokees, until differences sparked the Anglo-Cherokee War in 1758. In 1758, the Pennsylvania government successfully negotiated the Treaty of Easton in which a number of tribes in the Ohio Country promised neutrality in exchange for land concessions and other considerations. Most of the other northern tribes sided with the French, their primary trading partner and supplier of arms. The Creeks and Cherokees were subject to diplomatic efforts by both the French and British to gain either their support or neutrality in the conflict.

text: By this time, Spain claimed only the province of Florida in eastern North America; it controlled Cuba and other territories in the West Indies that became military objectives in the Seven Years' War. Florida's European population was a few hundred, concentrated in St. Augustine and Pensacola.

text: At the start of the war, no French regular army troops were stationed in North America, and few British troops. New France was defended by about 3,000 troupes de la marine, companies of colonial regulars (some of whom had significant woodland combat experience). The colonial government recruited militia support when needed. Most British colonies mustered local militia companies to deal with Indian threats, generally ill trained and available only for short periods, but they did not have any standing forces. Virginia, by contrast, had a large frontier with several companies of British regulars.

text: The colonial governments were used to operating independently of one another and of the government in London, a situation that complicated negotiations with Indian tribes, whose territories often encompassed land claimed by multiple colonies. After the war began, the leaders of the British Army establishment tried to impose constraints and demands on the colonial administrations.

text: Events leading to war

text: Céloron's expedition

text: New France's Governor-General Roland-Michel Barrin de La Galissonière was concerned about the incursion and expanding influence in the Ohio Country of British colonial traders such as George Croghan. In June 1747, he ordered Pierre-Joseph Céloron to lead a military expedition through the area. Its objectives were:

text:
to reaffirm to New France's Indian allies that their trading arrangements with colonists were exclusive to those authorized by New France
to confirm Indian assistance in asserting and maintaining the French claim to the territories which French explorers had claimed
to discourage any alliances between Britain and local Indian tribes
to impress the Indians with a French show of force against British colonial settler incursion, unauthorized trading expeditions, and general trespass against French claims[19]

text: Céloron's expedition force consisted of about 200 Troupes de la marine and 30 Indians, and they covered about 3,000 miles (4,800 km) between June and November 1749. They went up the St. Lawrence, continued along the northern shore of Lake Ontario, crossed the portage at Niagara, and followed the southern shore of Lake Erie. At the Chautauqua Portage near Barcelona, New York, the expedition moved inland to the Allegheny River, which it followed to the site of Pittsburgh. There Céloron buried lead plates engraved with the French claim to the Ohio Country.[19] Whenever he encountered British colonial merchants or fur-traders, he informed them of the French claims on the territory and told them to leave.[19]

text: Céloron's expedition arrived at Logstown where the Indians in the area informed him that they owned the Ohio Country and that they would trade with the British colonists regardless of the French.[20] He continued south until his expedition reached the confluence of the Ohio and the Miami rivers, which lay just south of the village of Pickawillany, the home of the Miami chief known as "Old Briton". Céloron threatened Old Briton with severe consequences if he continued to trade with British colonists, but Old Briton ignored the warning. Céloron returned disappointedly to Montreal in November 1749.[21]

text: Céloron wrote an extensively detailed report. "All I can say is that the Natives of these localities are very badly disposed towards the French," he wrote, "and are entirely devoted to the English. I don't know in what way they could be brought back."[20] Even before his return to Montreal, reports on the situation in the Ohio Country were making their way to London and Paris, each side proposing that action be taken. Massachusetts governor William Shirley was particularly forceful, stating that British colonists would not be safe as long as the French were present.[22]

text: Negotiations

text: In 1749, the British government gave land to the Ohio Company of Virginia for the purpose of developing trade and settlements in the Ohio Country.[23] The grant required that it settle 100 families in the territory and construct a fort for their protection. But the territory was also claimed by Pennsylvania, and both colonies began pushing for action to improve their respective claims.[24] In 1750, Christopher Gist explored the Ohio territory, acting on behalf of both Virginia and the company, and he opened negotiations with the Indian tribes at Logstown.[25] He completed the 1752 Treaty of Logstown in which the local Indians agreed to terms through their "Half-King" Tanacharison and an Iroquois representative. These terms included permission to build a strong house at the mouth of the Monongahela River on the modern site of Pittsburgh, Pennsylvania.[26] By the late 17th century, the Iroquois had pushed many tribes out of the Ohio Valley, and they laid claim to it as their hunting ground by right of conquest.

text: The War of the Austrian Succession (better known as King George's War) formally ended in 1748 with the signing of the Treaty of Aix-la-Chapelle, which was primarily focused on resolving issues in Europe. The issues of conflicting territorial claims between British and French colonies were turned over to a commission, but it reached no decision. Frontier areas were claimed by both sides, from Nova Scotia and Acadia in the north to the Ohio Country in the south. The disputes also extended into the Atlantic Ocean, where both powers wanted access to the rich fisheries of the Grand Banks off Newfoundland.

text: Attack on Pickawillany

text: Governor-General of New France Marquis de la Jonquière died on March 17, 1752, and he was temporarily replaced by Charles le Moyne de Longueuil. His permanent replacement was to be the Marquis Duquesne, but he did not arrive in New France until 1752 to take over the post.[27] The continuing British activity in the Ohio territories prompted Longueuil to dispatch another expedition to the area under the command of Charles Michel de Langlade, an officer in the Troupes de la Marine. Langlade was given 300 men, including French-Canadians and warriors of the Ottawa tribe. His objective was to punish the Miami people of Pickawillany for not following Céloron's orders to cease trading with the British. On June 21, the French war party attacked the trading centre at Pickawillany, capturing three traders[21] and killing 14 Miami Indians, including Old Briton. He was reportedly ritually cannibalized by some Indians in the expedition party.

text: French fort construction

text: This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (April 2017) (Learn how and when to remove this template message)

text: In the spring of 1753, Paul Marin de la Malgue was given command of a 2,000-man force of Troupes de la Marine and Indians. His orders were to protect the King's land in the Ohio Valley from the British. Marin followed the route that Céloron had mapped out four years earlier. Céloron, however, had limited the record of French claims to the burial of lead plates, whereas Marin constructed and garrisoned forts. He first constructed Fort Presque Isle on Lake Erie's south shore near Erie, Pennsylvania, and he had a road built to the headwaters of LeBoeuf Creek. He then constructed a second fort at Fort Le Boeuf in Waterford, Pennsylvania, designed to guard the headwaters of LeBoeuf Creek. As he moved south, he drove off or captured British traders, alarming both the British and the Iroquois. Tanaghrisson was a chief of the Mingo Indians, who were remnants of Iroquois and other tribes who had been driven west by colonial expansion. He intensely disliked the French whom he accused of killing and eating his father. He traveled to Fort Le Boeuf and threatened the French with military action, which Marin contemptuously dismissed.[28]

text: The Iroquois sent runners to the manor of William Johnson in upstate New York, who was the British Superintendent for Indian Affairs in the New York region and beyond. Johnson was known to the Iroquois as Warraghiggey, meaning "he who does great things." He spoke their languages and had become a respected honorary member of the Iroquois Confederacy in the area, and he was made a colonel of the Iroquois in 1746; he was later commissioned as a colonel of the Western New York Militia.

text: The Indian representatives and Johnson met with Governor Clinton and officials from some of the other American colonies at Albany, New York. Mohawk Chief Hendrick was the speaker of their tribal council, and he insisted that the British abide by their obligations[which?] and block French expansion. Clinton did not respond to his satisfaction, and Hendrick said that the "Covenant Chain" was broken, a long-standing friendly relationship between the Iroquois Confederacy and the British Crown.

text: Virginia's response

text: Governor Robert Dinwiddie of Virginia was an investor in the Ohio Company, which stood to lose money if the French held their claim.[29] He ordered 21 year-old Major George Washington (whose brother was another Ohio Company investor) of the Virginia Regiment to warn the French to leave Virginia territory in October 1753.[30] Washington left with a small party, picking up Jacob Van Braam as an interpreter, Christopher Gist (a company surveyor working in the area), and a few Mingos led by Tanaghrisson. On December 12, Washington and his men reached Fort Le Boeuf.[31][32]

text: Jacques Legardeur de Saint-Pierre succeeded Marin as commander of the French forces after Marin died on October 29, and he invited Washington to dine with him. Over dinner, Washington presented Saint-Pierre with the letter from Dinwiddie demanding an immediate French withdrawal from the Ohio Country. Saint-Pierre said, "As to the Summons you send me to retire, I do not think myself obliged to obey it."[33] He told Washington that France's claim to the region was superior to that of the British, since René-Robert Cavelier, Sieur de La Salle had explored the Ohio Country nearly a century earlier.[34]

text: Washington's party left Fort Le Boeuf early on December 16 and arrived in Williamsburg on January 16, 1754. He stated in his report, "The French had swept south",[35] detailing the steps which they had taken to fortify the area, and their intention to fortify the confluence of the Allegheny and Monongahela rivers.[36]

text: Course of the war

text: Even before Washington returned, Dinwiddie had sent a company of 40 men under William Trent to that point where they began construction of a small stockaded fort in the early months of 1754.[37] Governor Duquesne sent additional French forces under Claude-Pierre Pecaudy de Contrecœur to relieve Saint-Pierre during the same period, and Contrecœur led 500 men south from Fort Venango on April 5, 1754.[38] These forces arrived at the fort on April 16, but Contrecœur generously allowed Trent's small company to withdraw. He purchased their construction tools to continue building what became Fort Duquesne.[39]

text: Battle of Jumonville Glen

text: Dinwiddie had ordered Washington to lead a larger force to assist Trent in his work, and Washington learned of Trent's retreat while he was en route.[40] Mingo sachem Tanaghrisson had promised support to the British, so Washington continued toward Fort Duquesne and met with him. He then learned of a French scouting party in the area, so he combined Tanaghrisson's force with his own and surprised the Canadians on May 28 in what became known as the Battle of Jumonville Glen. They killed many of the Canadians, including their commanding officer Joseph Coulon de Jumonville, whose head was reportedly split open by Tanaghrisson with a tomahawk. Historian Fred Anderson suggests that Tanaghrisson was acting to gain the support of the British and to regain authority over his own people. They had been inclined to support the French, with whom they had long trading relationships. One of Tanaghrisson's men told Contrecoeur that Jumonville had been killed by British musket fire.[41]

text: Historians generally consider the Battle of Jumonville Glen as the opening battle of the French and Indian War in North America, and the start of hostilities in the Ohio valley.

text: Following the battle, Washington pulled back several miles and established Fort Necessity, which the Canadians attacked under the command of Jummonville's brother at the Battle of Fort Necessity on July 3. Washington surrendered and negotiated a withdrawal under arms. One of his men reported that the Canadian force was accompanied by Shawnee, Delaware, and Mingo warriors—just those whom Tanaghrisson was seeking to influence.[42]

text: News of the two battles reached England in August. After several months of negotiations, the government of the Duke of Newcastle decided to send an army expedition the following year to dislodge the French.[43] They chose Major General Edward Braddock to lead the expedition.[44] Word of the British military plans leaked to France well before Braddock's departure for North America. In response, King Louis XV dispatched six regiments to New France under the command of Baron Dieskau in 1755.[45] The British sent out their fleet in February 1755, intending to blockade French ports, but the French fleet had already sailed. Admiral Edward Hawke detached a fast squadron to North America in an attempt to intercept them.

text: In a second British action, Admiral Edward Boscawen fired on the French ship Alcide on June 8, 1755, capturing her and two troop ships.[46] The British harassed French shipping throughout 1755, seizing ships and capturing seamen. These actions contributed to the eventual formal declarations of war in spring 1756.[47]

text: Albany Congress

text: An early important political response to the opening of hostilities was the convening of the Albany Congress in June and July, 1754. The goal of the congress was to formalize a unified front in trade and negotiations with various Indians, since allegiance of the various tribes and nations was seen to be pivotal in the war that was unfolding. The plan that the delegates agreed to was neither ratified by the colonial legislatures nor approved of by the crown. Nevertheless, the format of the congress and many specifics of the plan became the prototype for confederation during the War of Independence.

text: British campaigns, 1755

text: The British formed an aggressive plan of operations for 1755. General Braddock was to lead the expedition to Fort Duquesne,[48] while Massachusetts governor William Shirley was given the task of fortifying Fort Oswego and attacking Fort Niagara. Sir William Johnson was to capture Fort St. Frédéric at present-day Crown Point, New York,[49] and Lieutenant Colonel Robert Monckton was to capture Fort Beauséjour to the east, on the frontier between Nova Scotia and Acadia.[50]

text: Braddock led about 1,500 army troops and provincial militia on an expedition in June 1755 to take Fort Duquesne, with George Washington as one of his aides. The expedition was a disaster. It was attacked by French soldiers and Indian warriors ambushing them from up in trees and behind logs, and Braddock called for a retreat. He was killed and approximately 1,000 British soldiers were killed or injured.[48] The remaining 500 British troops retreated to Virginia, led by Washington. Two future opponents in the American Revolutionary War played key roles in organizing the retreat: Washington and Thomas Gage.

text: The French acquired a copy of the British war plans, including the activities of Shirley and Johnson. Shirley's efforts to fortify Oswego were bogged down in logistical difficulties, exacerbated by his inexperience in managing large expeditions. In conjunction, Shirley was made aware that the French were massing for an attack on Fort Oswego in his absence when he planned to attack Fort Niagara. As a response, he left garrisons at Oswego, Fort Bull, and Fort Williams, the last two located on the Oneida Carry between the Mohawk River and Wood Creek at present-day Rome, New York. Supplies were cached at Fort Bull for use in the projected attack on Niagara.

text: Johnson's expedition was better organized than Shirley's, which was noticed by New France's governor the Marquis de Vaudreuil. He had primarily been concerned about the extended supply line to the forts on the Ohio, and he had sent Baron Dieskau to lead the defenses at Frontenac against Shirley's expected attack. Vaudreuil saw Johnson as the larger threat and sent Dieskau to Fort St. Frédéric to meet that threat. Dieskau planned to attack the British encampment at Fort Edward at the upper end of navigation on the Hudson River, but Johnson had strongly fortified it, and Dieskau's Indian support was reluctant to attack. The two forces finally met in the bloody Battle of Lake George between Fort Edward and Fort William Henry. The battle ended inconclusively, with both sides withdrawing from the field. Johnson's advance stopped at Fort William Henry, and the French withdrew to Ticonderoga Point, where they began the construction of Fort Carillon (later renamed Fort Ticonderoga after British capture in 1759).

text: Colonel Monckton captured Fort Beauséjour in June 1755 in the sole British success that year, cutting off the French fortress at Louisbourg from land-based reinforcements. To cut vital supplies to Louisbourg, Nova Scotia's Governor Charles Lawrence ordered the deportation of the French-speaking Acadian population from the area. Monckton's forces, including companies of Rogers' Rangers, forcibly removed thousands of Acadians, chasing down many who resisted and sometimes committing atrocities. More than any other factor, cutting off supplies to Louisbourg led to its demise.[51] The Acadian resistance was sometimes quite stiff, in concert with Indian allies including the Mi'kmaq, with ongoing frontier raids against Dartmouth and Lunenburg, among others. The only clashes of any size were at Petitcodiac in 1755 and at Bloody Creek near Annapolis Royal in 1757, other than the campaigns to expel the Acadians ranging around the Bay of Fundy, on the Petitcodiac and St. John rivers, and Île Saint-Jean.

text: French victories, 1756–1757

text: Following the death of Braddock, William Shirley assumed command of British forces in North America, and he laid out his plans for 1756 at a meeting in Albany in December 1755. He proposed renewing the efforts to capture Niagara, Crown Point, and Duquesne, with attacks on Fort Frontenac on the north shore of Lake Ontario and an expedition through the wilderness of the Maine district and down the Chaudière River to attack the city of Quebec. His plan, however, got bogged down by disagreements and disputes with others, including William Johnson and New York's Governor Sir Charles Hardy, and consequently gained little support.

text: Newcastle replaced him in January 1756 with Lord Loudoun, with Major General James Abercrombie as his second in command. Neither of these men had as much campaign experience as the trio of officers whom France sent to North America.[47] French regular army reinforcements arrived in New France in May 1756, led by Major General Louis-Joseph de Montcalm and seconded by the Chevalier de Lévis and Colonel François-Charles de Bourlamaque, all experienced veterans from the War of the Austrian Succession. On May 18, 1756, England formally declared war on France, which expanded the war into Europe and came to be known as the Seven Years' War.

text: Governor Vaudreuil had ambitions to become the French commander in chief, in addition to his role as governor, and he acted during the winter of 1756 before those reinforcements arrived. Scouts had reported the weakness of the British supply chain, so he ordered an attack against the forts which Shirley had erected at the Oneida Carry. In the Battle of Fort Bull, French forces destroyed the fort and large quantities of supplies, including 45,000 pounds of gunpowder. They set back any British hopes for campaigns on Lake Ontario and endangered the Oswego garrison, already short on supplies. French forces in the Ohio valley also continued to intrigue with Indians throughout the area, encouraging them to raid frontier settlements. This led to ongoing alarms along the western frontiers, with streams of refugees returning east to get away from the action.

text: The new British command was not in place until July. Abercrombie arrived in Albany but refused to take any significant actions until Loudoun approved them, and Montcalm took bold action against his inertia. He built on Vaudreuil's work harassing the Oswego garrison and executed a strategic feint by moving his headquarters to Ticonderoga, as if to presage another attack along Lake George. With Abercrombie pinned down at Albany, Montcalm slipped away and led the successful attack on Oswego in August. In the aftermath, Montcalm and the Indians under his command disagreed about the disposition of prisoners' personal effects. The Europeans did not consider them prizes and prevented the Indians from stripping the prisoners of their valuables, which angered the Indians.

text: Loudoun was a capable administrator but a cautious field commander, and he planned one major operation for 1757: an attack on New France's capital of Quebec. He left a sizable force at Fort William Henry to distract Montcalm and began organizing for the expedition to Quebec. He was then ordered to attack Louisbourg first by William Pitt, the Secretary of State responsible for the colonies. The expedition was beset by delays of all kinds but was finally ready to sail from Halifax, Nova Scotia in early August. In the meantime, French ships had escaped the British blockade of the French coast, and a fleet awaited Loudoun at Louisbourg which outnumbered the British fleet. Faced with this strength, Loudoun returned to New York amid news that a massacre had occurred at Fort William Henry.

text: French irregular forces (Canadian scouts and Indians) harassed Fort William Henry throughout the first half of 1757. In January, they ambushed British rangers near Ticonderoga. In February, they launched a raid against the position across the frozen Lake George, destroying storehouses and buildings outside the main fortification. In early August, Montcalm and 7,000 troops besieged the fort, which capitulated with an agreement to withdraw under parole. When the withdrawal began, some of Montcalm's Indian allies attacked the British column because they were angry about the lost opportunity for loot, killing and capturing several hundred men, women, children, and slaves. The aftermath of the siege may have contributed to the transmission of smallpox into remote Indian populations, as some Indians were reported to have traveled from beyond the Mississippi to participate in the campaign and returned afterward. Modern writer William Nester believes that the Indians might have been exposed to European carriers, although no proof exists.[52]

text: British conquest, 1758–1760

text: Vaudreuil and Montcalm were minimally resupplied in 1758, as the British blockade of the French coastline limited French shipping. The situation in New France was further exacerbated by a poor harvest in 1757, a difficult winter, and the allegedly corrupt machinations of François Bigot, the intendant of the territory. His schemes to supply the colony inflated prices and were believed by Montcalm to line his pockets and those of his associates. A massive outbreak of smallpox among western Indian tribes led many of them to stay away from trading in 1758. The disease probably spread through the crowded conditions at William Henry after the battle;[53] yet the Indians blamed the French for bringing "bad medicine" as well as denying them prizes at Fort William Henry.

text: Montcalm focused his meager resources on the defense of the St. Lawrence, with primary defenses at Carillon, Quebec, and Louisbourg, while Vaudreuil argued unsuccessfully for a continuation of the raiding tactics that had worked quite effectively in previous years.[54] The British failures in North America combined with other failures in the European theater and led to Newcastle's fall from power along with the Duke of Cumberland, his principal military advisor.

text: Newcastle and Pitt joined in an uneasy coalition in which Pitt dominated the military planning. He embarked on a plan for the 1758 campaign that was largely developed by Loudoun. He had been replaced by Abercrombie as commander in chief after the failures of 1757. Pitt's plan called for three major offensive actions involving large numbers of regular troops supported by the provincial militias, aimed at capturing the heartlands of New France. Two of the expeditions were successful, with Fort Duquesne and Louisbourg falling to sizable British forces.

text: The Forbes Expedition was a British campaign in September–October 1758, with 6,000 troops led by General John Forbes sent to drive out the French from the contested Ohio Country. The French withdrew from Fort Duquesne and left the British in control of the Ohio River Valley.[55] The great French fortress at Louisbourg in Nova Scotia was captured after a siege.[56]

text: The third invasion was stopped with the improbable French victory in the Battle of Carillon, in which 3,600 Frenchmen defeated Abercrombie's force of 18,000 regulars, militia, and Indian allies outside the fort which the French called Carillon and the British called Ticonderoga. Abercrombie saved something from the disaster when he sent John Bradstreet on an expedition that successfully destroyed Fort Frontenac, including caches of supplies destined for New France's western forts and furs destined for Europe. Abercrombie was recalled and replaced by Jeffery Amherst, victor at Louisbourg.

text: The French had generally poor results in 1758 in most theaters of the war. The new foreign minister was the duc de Choiseul, and he decided to focus on an invasion of Britain to draw British resources away from North America and the European mainland. The invasion failed both militarily and politically, as Pitt again planned significant campaigns against New France and sent funds to Britain's mainland ally of Prussia, while the French Navy failed in the 1759 naval battles at Lagos and Quiberon Bay. In one piece of good fortune, some French supply ships did manage to depart France and elude the British blockade of the French coast.

text: British victories continued in all theaters in the Annus Mirabilis of 1759: the British captured Ticonderoga, James Wolfe defeated Montcalm at Quebec in a battle that claimed the lives of both commanders, and a British victory at Fort Niagara cut off the French frontier forts to the west and south. The victory was made complete in 1760; the British did suffer a defeat outside Quebec City in the Battle of Sainte-Foy, but they prevented the arrival of French relief ships in the naval Battle of the Restigouche while armies marched on Montreal from three sides.

text: Governor Vaudreuil in Montreal negotiated a capitulation with General Amherst in September 1760. Amherst granted his requests that any French residents who chose to remain in the colony would be given freedom to continue worshiping in their Roman Catholic tradition, to own property, and to remain undisturbed in their homes. The British provided medical treatment for the sick and wounded French soldiers, and French regular troops were returned to France aboard British ships with an agreement that they were not to serve again in the present war.[57]

text: End of the war

text: Most of the fighting ended in continental North America in 1760, although it continued in Europe between France and Britain. The notable exception was the French seizure of St. John's, Newfoundland. General Amherst heard of this surprise action and immediately dispatched troops under his nephew William Amherst, who regained control of Newfoundland after the Battle of Signal Hill in September 1762.[58] Many troops from North America were reassigned to participate in further British actions in the West Indies, including the capture of Spanish Havana when Spain belatedly entered the conflict on the side of France, and a British expedition against French Martinique in 1762 led by Major General Robert Monckton.[59]

text: General Amherst also oversaw the transition of French forts to British control in the western lands. The policies which he introduced in those lands disturbed large numbers of Indians and contributed to Pontiac's Rebellion in 1763.[60] This series of attacks on frontier forts and settlements required the continued deployment of British troops, and it was not resolved until 1766.[61]

text: The war in North America officially ended with the signing of the Treaty of Paris on 10 February 1763, and war in the European theater was settled by the Treaty of Hubertusburg on 15 February 1763. The British offered France the choice of surrendering either its continental North American possessions east of the Mississippi or the Caribbean islands of Guadeloupe and Martinique, which had been occupied by the British. France chose to cede the former but was able to negotiate the retention of Saint Pierre and Miquelon, two small islands in the Gulf of St. Lawrence, along with fishing rights in the area. They viewed the economic value of the Caribbean islands' sugar cane to be greater and easier to defend than the furs from the continent. French philosopher Voltaire referred to Canada disparagingly as nothing more than a few acres of snow. The British, however, were happy to take New France, as defence of their North American colonies would no longer be an issue; they also had ample places from which to obtain sugar. Spain traded Florida to Britain in order to regain Cuba, but they also gained Louisiana from France, including New Orleans, in compensation for their losses. Great Britain and Spain also agreed that navigation on the Mississippi River was to be open to vessels of all nations.[62]

text: Consequences

text: The war changed economic, political, governmental, and social relations among the three European powers, their colonies, and the people who inhabited those territories. France and Britain both suffered financially because of the war, with significant long-term consequences.

text: Britain gained control of French Canada and Acadia, colonies containing approximately 80,000 primarily French-speaking Roman Catholic residents. The deportation of Acadians beginning in 1755 made land available to immigrants from Europe and migrants from the colonies to the south. The British resettled many Acadians throughout its North American provinces, but many went to France, and some went to New Orleans, which they had expected to remain French. Some were sent to colonize places as diverse as French Guiana and the Falkland Islands, but these efforts were unsuccessful. Others migrated to places such as Saint-Domingue or fled to New Orleans after the Haitian Revolution. The Louisiana population contributed to the founding of the modern Cajun population. (The French word "Acadien" changed to "Cadien" then to "Cajun".)[63]

text: Following the treaty, King George III issued the Royal Proclamation of 1763 on October 7, 1763 which outlined the division and administration of the newly conquered territory, and it continues to govern relations to some extent between the government of modern Canada and the First Nations. Included in its provisions was the reservation of lands west of the Appalachian Mountains to its Indian population,[64] a demarcation that was only a temporary impediment to a rising tide of westward-bound settlers.[65] The proclamation also contained provisions that prevented civic participation by the Roman Catholic Canadians.[66] The Quebec Act addressed this and other issues in 1774, raising concerns in the largely Protestant Thirteen Colonies over the advance of "popery." The Act maintained French Civil law, including the seigneurial system, a medieval code removed from France within a generation by the French Revolution.

text: The Seven Years' War nearly doubled Great Britain's national debt. The Crown sought sources of revenue to pay it off and attempted to impose new taxes on its colonies. These attempts were met with increasingly stiff resistance, until troops were called in to enforce the Crown's authority. These acts ultimately led to the start of the American Revolutionary War.[67]

text: France attached comparatively little value to its North American possessions, apart from the highly profitable sugar-producing Antilles islands which it retained. Minister Choiseul considered that he had made a good deal at the Treaty of Paris, and Voltaire wrote that Louis XV had lost "a few acres of snow".[68] For France, however, the military defeat and the financial burden of the war weakened the monarchy and contributed to the advent of the French Revolution in 1789.[69]

text: For some of the Indian tribes, the elimination of French power in North America meant the disappearance of a strong ally, although other tribes were not so affected.[69] The Ohio Country was now more available to colonial settlement, due to the construction of military roads by Braddock and Forbes.[70] The Spanish takeover of the Louisiana territory was not completed until 1769, and it had modest repercussions. The British takeover of Spanish Florida resulted in the westward migration of Indian tribes who did not want to do business with them. This migration also caused a rise in tensions between the Choctaw and the Creek, historic enemies who were now competing for land.[71] The change of control in Florida also prompted most of its Spanish Catholic population to leave. Most went to Cuba, including the entire governmental records from St. Augustine, although some Christianized Yamasee were resettled to the coast of Mexico.[72]

text: France returned to North America in 1778 with the establishment of a Franco-American alliance against Great Britain in the American War of Independence. This time, France succeeded in prevailing over Great Britain in what historian Alfred A. Cave describes as "French… revenge for Montcalm's death".[73]