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The Master Neural Transcription Factor BRN2 Is an Androgen Receptor–Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer
Published OnlineFirst October 26, 2016; DOI: 10.1158/2159-8290.CD-15-1263 RESEARCH ARTICLE The Master Neural Transcription Factor BRN2 Is an Androgen Receptor–Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer Jennifer L. Bishop1, Daksh Thaper1,2, Sepideh Vahid1,2, Alastair Davies1, Kirsi Ketola1, Hidetoshi Kuruma1, Randy Jama1, Ka Mun Nip1,2, Arkhjamil Angeles1, Fraser Johnson1, Alexander W. Wyatt1,2, Ladan Fazli1,2, Martin E. Gleave1,2, Dong Lin1, Mark A. Rubin3, Colin C. Collins1,2, Yuzhuo Wang1,2, Himisha Beltran3, and Amina Zoubeidi1,2 ABSTRACT Mechanisms controlling the emergence of lethal neuroendocrine prostate cancer (NEPC), especially those that are consequences of treatment-induced suppression of the androgen receptor (AR), remain elusive. Using a unique model of AR pathway inhibitor–resistant prostate cancer, we identified AR-dependent control of the neural transcription factor BRN2 (encoded by POU3F2) as a major driver of NEPC and aggressive tumor growth, both in vitro and in vivo. Mecha- nistic studies showed that AR directly suppresses BRN2 transcription, which is required for NEPC, and BRN2-dependent regulation of the NEPC marker SOX2. Underscoring its inverse correlation with clas- sic AR activity in clinical samples, BRN2 expression was highest in NEPC tumors and was significantly increased in castration-resistant prostate cancer compared with adenocarcinoma, especially in patients with low serum PSA. These data reveal a novel mechanism of AR-dependent control of NEPC and suggest that targeting BRN2 is a strategy to treat or prevent neuroendocrine differentiation in prostate tumors. SIGNIFICANCE: Understanding the contribution of the AR to the emergence of highly lethal, drug- resistant NEPC is critical for better implementation of current standard-of-care therapies and novel drug design. -
Clones Stick Together
TVhome The Daily Home April 12 - 18, 2015 Clones Stick Together Sarah (Tatiana Maslany) is on a mission to find the 000208858R1 truth about the clones on season three of “Orphan Black,” premiering Saturday at 8 p.m. on BBC America. The Future of Banking? We’ve Got A 167 Year Head Start. You can now deposit checks directly from your smartphone by using FNB’s Mobile App for iPhones and Android devices. No more hurrying to the bank; handle your deposits from virtually anywhere with the Mobile Remote Deposit option available in our Mobile App today. (256) 362-2334 | www.fnbtalladega.com Some products or services have a fee or require enrollment and approval. Some restrictions may apply. Please visit your nearest branch for details. 000209980r1 2 THE DAILY HOME / TV HOME Sun., April 12, 2015 — Sat., April 18, 2015 DISH AT&T DIRECTV CABLE CHARTER CHARTER PELL CITY PELL ANNISTON CABLE ONE CABLE TALLADEGA SYLACAUGA BIRMINGHAM BIRMINGHAM BIRMINGHAM CONVERSION CABLE COOSA SPORTS WBRC 6 6 7 7 6 6 6 6 AUTO RACING Friday WBIQ 10 4 10 10 10 10 6 p.m. FS1 St. John’s Red Storm at Drag Racing WCIQ 7 10 4 Creighton Blue Jays (Live) WVTM 13 13 5 5 13 13 13 13 Sunday Saturday WTTO 21 8 9 9 8 21 21 21 7 p.m. ESPN2 Summitracing.com 12 p.m. ESPN2 Vanderbilt Com- WUOA 23 14 6 6 23 23 23 NHRA Nationals from The Strip at modores at South Carolina WEAC 24 24 Las Vegas Motor Speedway in Las Gamecocks (Live) WJSU 40 4 4 40 Vegas (Taped) 2 p.m. -
Core Transcriptional Regulatory Circuitries in Cancer
Oncogene (2020) 39:6633–6646 https://doi.org/10.1038/s41388-020-01459-w REVIEW ARTICLE Core transcriptional regulatory circuitries in cancer 1 1,2,3 1 2 1,4,5 Ye Chen ● Liang Xu ● Ruby Yu-Tong Lin ● Markus Müschen ● H. Phillip Koeffler Received: 14 June 2020 / Revised: 30 August 2020 / Accepted: 4 September 2020 / Published online: 17 September 2020 © The Author(s) 2020. This article is published with open access Abstract Transcription factors (TFs) coordinate the on-and-off states of gene expression typically in a combinatorial fashion. Studies from embryonic stem cells and other cell types have revealed that a clique of self-regulated core TFs control cell identity and cell state. These core TFs form interconnected feed-forward transcriptional loops to establish and reinforce the cell-type- specific gene-expression program; the ensemble of core TFs and their regulatory loops constitutes core transcriptional regulatory circuitry (CRC). Here, we summarize recent progress in computational reconstitution and biologic exploration of CRCs across various human malignancies, and consolidate the strategy and methodology for CRC discovery. We also discuss the genetic basis and therapeutic vulnerability of CRC, and highlight new frontiers and future efforts for the study of CRC in cancer. Knowledge of CRC in cancer is fundamental to understanding cancer-specific transcriptional addiction, and should provide important insight to both pathobiology and therapeutics. 1234567890();,: 1234567890();,: Introduction genes. Till now, one critical goal in biology remains to understand the composition and hierarchy of transcriptional Transcriptional regulation is one of the fundamental mole- regulatory network in each specified cell type/lineage. -
Booklist 3-4.Xlsx
2019 Years 3-4 Booklist Author Book Title ISBN Year Level Abela, Deborah The Stupendously Spectacular Spelling Bee 9781925324822 3-4, 5-6 Abramson, Ruth The Cresta Adventure 978-0-87306-493-4 3-4 Agard, John Hello New! 978-1-84121-621-8 3-4 Ahlberg, Allan Please Mrs Butler 9780140314946 3-4 Ahlberg, Allan The Bravest Ever Bear 9780744578645 3-4 Ahlberg, Allan; Ingham, Bruce The Pencil 9781406309621 3-4 Ahlberg, Allan; Ingman, Bruce Previously 9781844280629 3-4 Ahlberg, Allan; Ingman, Bruce (ill.) Everybody Was a Baby Once 9781406321562 EC-2, 3-4 Airey, Miriam No Hat Brigade 978-1-74051-773-7 3-4 Alderson, Maggie Evangeline 9780670075355 EC-2, 3-4 Alexander, Goldie The Youngest Cameleer 978-1-74130-495-4 3-4, 5-6 Alexander, Goldie; Gaudion, Michele (ill.) Lame Duck Protest 978-1-921479-13-7 3-4 Allaby, Michael DK Guide to Weather 978-0-7513-2856-1 3-4 Allen, Emma; Blackwood, Freya (ill.) The Terrible Suitcase 9781862919402 EC-2, 3-4 Allen, Judy Anthology for the Earth 978-0-7636-0301-4 3-4 Allen, Scott Jesse the Elephant 9781921638138 3-4 Almond, David; Pinfold, Levi (ill.) The Dam 9781406304879 EC-2, 3-4 Almond, David; Smith, Alex T. The Tale of Angelino Brown 9781406358070 3-4, 5-6 Amadio, Nadine; Blackman, Charles (ill.) The New Adventures of Alice in Rainforest Land 978-0-949284-07-5 3-4 Andreae, Giles; Sharrat, Nick (ill.) Billy Bonkers series 3-4 Anholt, Laurence Camille and the Sunflowers 978-0-7112-1050-9 3-4 Anholt, Laurence Frida Kahlo and the Bravest Girl in the World 9781847806666 3-4 Anna Ciddor A Roman Day to Remember 978-0816767960 -
PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain
Published OnlineFirst April 26, 2017; DOI: 10.1158/2159-8290.CD-16-1297 RESEARCH ARTICLE PAX3–FOXO1 Establishes Myogenic Super Enhancers and Confers BET Bromodomain Vulnerability Berkley E. Gryder 1 , Marielle E. Yohe 1 , 2 , Hsien-Chao Chou 1 , Xiaohu Zhang 3 , Joana Marques 4 , Marco Wachtel4 , Beat Schaefer 4 , Nirmalya Sen 1 , Young Song 1 , Alberto Gualtieri 5 , Silvia Pomella 5 , Rossella Rota5 , Abigail Cleveland 1 , Xinyu Wen 1 , Sivasish Sindiri 1 , Jun S. Wei 1 , Frederic G. Barr 6 , Sudipto Das7 , Thorkell Andresson 7 , Rajarshi Guha 3 , Madhu Lal-Nag 3 , Marc Ferrer 3 , Jack F. Shern 1 , 2 , Keji Zhao8 , Craig J. Thomas 3 , and Javed Khan 1 Downloaded from cancerdiscovery.aacrjournals.org on September 29, 2021. © 2017 American Association for Cancer Research. 16-CD-16-1297_p884-899.indd 884 7/20/17 2:21 PM Published OnlineFirst April 26, 2017; DOI: 10.1158/2159-8290.CD-16-1297 ABSTRACT Alveolar rhabdomyosarcoma is a life-threatening myogenic cancer of children and ado- lescent young adults, driven primarily by the chimeric transcription factor PAX3–FOXO1. The mechanisms by which PAX3–FOXO1 dysregulates chromatin are unknown. We fi nd PAX3–FOXO1 repro- grams the cis -regulatory landscape by inducing de novo super enhancers. PAX3–FOXO1 uses super enhancers to set up autoregulatory loops in collaboration with the master transcription factors MYOG, MYOD, and MYCN. This myogenic super enhancer circuitry is consistent across cell lines and primary tumors. Cells harboring the fusion gene are selectively sensitive to small-molecule inhibition of protein targets induced by, or bound to, PAX3–FOXO1-occupied super enhancers. -
2Friday 1Thursday 3Saturday 4Sunday 5Monday 6Tuesday 7Wednesday 8Thursday 9Friday 10Saturday
JULY 2021 1THURSDAY 2FRIDAY DAYTIME THEME: DAYTIME THEME: TCM BIRTHDAY TRIBUTE: WILLIAM WYLER KEEPING THE KIDS BUSY PRIMETIME THEME: PRIMETIME THEME: SELVIS FRIDAY NIGHT NEO-NOIR Seeing Double 8:00 PM Harper (‘66) 8:00 PM Kissin’ Cousins (‘64) 10:15 PM Point Blank (‘67) 10:00 PM Double Trouble (‘67) 12:00 AM Warning Shot (‘67) 12:00 AM Clambake (‘67) 2:00 AM Live A Little, Love a Little (‘68) 3SATURDAY 4SUNDAY DAYTIME THEME: DAYTIME THEME: SATURDAY MATINEE HAPPY INDEPENDENCE DAY PRIMETIME THEME: PRIMETIME THEME: GABLE GOES WEST HAPPY INDEPENDENCE DAY 8:00 PM The Misfits (‘61) 8:00 PM Yankee Doodle Dandy (‘42) 10:15 PM The Tall Men (‘55) 10:15 PM 1776 (‘72) JULY JailhouseThes Stranger’s Rock(‘57) Return (‘33) S STAR OF THE MONTH: Elvis 5MONDAY 6TUESDAY 7WEDNESDAY P TCM SPOTLIGHT: Star Signs DAYTIME THEME: DAYTIME AND PRIMETIME THEME(S): DAYTIME THEME: MEET CUTES DAYTIME THEME: TY HARDIN TCM PREMIERE PRIMETIME THEME: SOMETHING ON THE SIDE PRIMETIME THEME: DIRECTED BY BRIAN DE PALMA PRIMETIME THEME: THE GREAT AMERICAN MIDDLE TWITTER EVENTS 8:00 PM The Bonfire of the Vanities (‘90) PSTAR SIGNS Small Town Dramas NOT AVAILABLE IN CANADA 10:15 PM Obsession (‘76) Fire Signs 8:00 PM Peyton Place (‘57) 12:00 AM Sisters (‘72) 8:00 PM The Cincinnati Kid (‘65) 10:45 PM Picnic (‘55) 1:45 AM Blow Out (‘81) (Steeve McQueen – Aries) 12:45 AM East of Eden (‘55) 4:00 AM Body Double (‘84) 10:00 PM The Long Long Trailer (‘59) 3:00 AM Kings Row (‘42) (Lucille Ball – Leo) 5:15 AM Our Town (‘40) 12:00 AM The Bad and the Beautiful (‘52) (Kirk Douglas–Sagittarius) -
PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1 Alexandra Lacey1, Aline Rodrigues-Hoffman2, and Stephen Safe1
Published OnlineFirst November 18, 2016; DOI: 10.1158/0008-5472.CAN-16-1546 Cancer Therapeutics, Targets, and Chemical Biology Research PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1 Alexandra Lacey1, Aline Rodrigues-Hoffman2, and Stephen Safe1 Abstract Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric PAX3-FOXO1A. Mechanistic investigations revealed a requirement disease driven by expression of the oncogenic fusion gene PAX3- for the NR4A1/Sp4 complex to bind GC-rich promoter regions FOXO1A. In this study, we report overexpression of the nuclear to elevate transcription of the PAX3-FOXO1A gene. In parallel, receptor NR4A1 in rhabdomyosarcomas that is sufficient to NR4A1 also regulated expression of b1-integrin, which with PAX3- drive high expression of PAX3-FOXO1A there. RNAi-mediated FOXO1A, contributed to tumor cell migration that was blocked by silencing of NR4A1 decreased expression of PAX3-FOXO1A and C-DIM/NR4A1 antagonists. Taken together, our results provide a its downstream effector genes. Similarly, cell treatment with the preclinical rationale for the use of NR4A1 small-molecule antago- NR4A1 small-molecule antagonists 1,1-bis(3-indolyl)-1-(p- nists to treat ARMS and other rhabdomyosarcomas driven by hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A. Cancer Res; 77(3); 1–10. Ó2016 AACR. Introduction activity for NR4A1. In contrast, NR4A1 exhibits tumor promoter activity (6, 7) in solid tumors. NR4A1 is also overexpressed in Rhabdomyosarcoma is the most common soft-tissue sarco- tumors from patients with breast, lung, pancreatic, colon, and ma that is primarily observed in children and adolescents and ovarian cancer and is a negative prognostic factor for patients with accounts for 50% of all pediatric cancers and 50% of soft-tissue breast, lung, and ovarian cancer (9–15). -
Hypersphere Anonymous
Hypersphere Anonymous This work is licensed under a Creative Commons Attribution 4.0 International License. ISBN 978-1-329-78152-8 First edition: December 2015 Fourth edition Part 1 Slice of Life Adventures in The Hypersphere 2 The Hypersphere is a big fucking place, kid. Imagine the biggest pile of dung you can take and then double-- no, triple that shit and you s t i l l h a v e n ’ t c o m e c l o s e t o o n e octingentillionth of a Hypersphere cornerstone. Hell, you probably don’t even know what the Hypersphere is, you goddamn fucking idiot kid. I bet you don’t know the first goddamn thing about the Hypersphere. If you were paying attention, you would have gathered that it’s a big fucking 3 place, but one thing I bet you didn’t know about the Hypersphere is that it is filled with fucked up freaks. There are normal people too, but they just aren’t as interesting as the freaks. Are you a freak, kid? Some sort of fucking Hypersphere psycho? What the fuck are you even doing here? Get the fuck out of my face you fucking deviant. So there I was, chilling out in the Hypersphere. I’d spent the vast majority of my life there, in fact. It did contain everything in my observable universe, so it was pretty hard to leave, honestly. At the time, I was stressing the fuck out about a fight I had gotten in earlier. I’d been shooting some hoops when some no-good shithouses had waltzed up to me and tried to make a scene. -
Helter Skelter” and Sixties Revisionism “Helter Skelter” Et L'héritage Polémique Des Années 1960
Volume ! La revue des musiques populaires 9 : 2 | 2012 Contre-cultures n°2 “Helter Skelter” and Sixties Revisionism “Helter Skelter” et l'héritage polémique des années 1960 Gerald Carlin and Mark Jones Electronic version URL: http://journals.openedition.org/volume/3407 DOI: 10.4000/volume.3407 ISSN: 1950-568X Printed version Date of publication: 15 December 2012 Number of pages: 34-49 ISBN: 978-2-913169-33-3 ISSN: 1634-5495 Electronic reference Gerald Carlin and Mark Jones, « “Helter Skelter” and Sixties Revisionism », Volume ! [Online], 9 : 2 | 2012, Online since 15 June 2014, connection on 10 December 2020. URL : http:// journals.openedition.org/volume/3407 ; DOI : https://doi.org/10.4000/volume.3407 This text was automatically generated on 10 December 2020. L'auteur & les Éd. Mélanie Seteun “Helter Skelter” and Sixties Revisionism 1 “Helter Skelter” and Sixties Revisionism “Helter Skelter” et l'héritage polémique des années 1960 Gerald Carlin and Mark Jones EDITOR'S NOTE This text was published in Countercultures & Popular Music (Farnham, Ashgate, 2014), while its French translation appeared in this issue of Volume! in 2012. “Helter Skelter” and the End of the Sixties Volume !, 9 : 2 | 2012 “Helter Skelter” and Sixties Revisionism 2 1 In late August 1968, within a few days of each other, new singles were released by the Beatles and the Rolling Stones. The unusual proximity of release dates by the world’s two most significant rock bands was echoed by the congruity of the songs’ themes: the Stones’ “Street Fighting Man” and the Beatles’ “Revolution” were both responses to the political unrest and protest which characterised the spring and summer of 1968. -
PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1 Alexandra Lacey1, Aline Rodrigues-Hoffman2, and Stephen Safe1
Published OnlineFirst November 18, 2016; DOI: 10.1158/0008-5472.CAN-16-1546 Cancer Therapeutics, Targets, and Chemical Biology Research PAX3-FOXO1A Expression in Rhabdomyosarcoma Is Driven by the Targetable Nuclear Receptor NR4A1 Alexandra Lacey1, Aline Rodrigues-Hoffman2, and Stephen Safe1 Abstract Alveolar rhabdomyosarcoma (ARMS) is a devastating pediatric PAX3-FOXO1A. Mechanistic investigations revealed a requirement disease driven by expression of the oncogenic fusion gene PAX3- for the NR4A1/Sp4 complex to bind GC-rich promoter regions FOXO1A. In this study, we report overexpression of the nuclear to elevate transcription of the PAX3-FOXO1A gene. In parallel, receptor NR4A1 in rhabdomyosarcomas that is sufficient to NR4A1 also regulated expression of b1-integrin, which with PAX3- drive high expression of PAX3-FOXO1A there. RNAi-mediated FOXO1A, contributed to tumor cell migration that was blocked by silencing of NR4A1 decreased expression of PAX3-FOXO1A and C-DIM/NR4A1 antagonists. Taken together, our results provide a its downstream effector genes. Similarly, cell treatment with the preclinical rationale for the use of NR4A1 small-molecule antago- NR4A1 small-molecule antagonists 1,1-bis(3-indolyl)-1-(p- nists to treat ARMS and other rhabdomyosarcomas driven by hydroxy or p-carbomethoxyphenyl)methane (C-DIM) decreased PAX3-FOXO1A. Cancer Res; 77(3); 1–10. Ó2016 AACR. Introduction activity for NR4A1. In contrast, NR4A1 exhibits tumor promoter activity (6, 7) in solid tumors. NR4A1 is also overexpressed in Rhabdomyosarcoma is the most common soft-tissue sarco- tumors from patients with breast, lung, pancreatic, colon, and ma that is primarily observed in children and adolescents and ovarian cancer and is a negative prognostic factor for patients with accounts for 50% of all pediatric cancers and 50% of soft-tissue breast, lung, and ovarian cancer (9–15). -
Ebook Download Elvis Presley: a Life in Pictures
ELVIS PRESLEY: A LIFE IN PICTURES PDF, EPUB, EBOOK none | 48 pages | 01 Jul 2012 | Atlantic Publishing,Croxley Green | 9781908533975 | English | Croxley Green, United Kingdom Elvis Presley: A Life in Pictures PDF Book Sunset Boulevard Getty Images. TIME Apps. He was stationed in Germany for two years. Today's Top Stories. Office of Presidential Libraries. Space He received deferment so that he could complete production on King Creole and entered the army as a private in A young Elvis, age 10, is pictured with his parents outside his family home in Tupelo, Mississippi in While living on the German army base, Presley met year-old Priscilla Beaulieu , who was living there with her parents. Your email address will not be published. Presley brought his iconic gold Cadillac on tour with him to promote his film Tickle Me. TIME Shop. Published in the Memphis Commercial Appeal. He released his first two albums and a string of singles including the US number one, Heartbreak Hotel. Sign In. After his film success started to decline and it became clear Presley was losing some of his box office charm, he returned to TV with a special in Available via Getty. Or subscribe to articles in the subject area by email or RSS. Originally published in the Memphis Press-Scimitar. His new single "Heartbreak Hotel" climbed the charts and quickly took over the top spot. A year later, Elvis would be given his first guitar. Paramount Pictures Getty Images. The Comeback Special, which saw the King in raucous form, was a massive success. TIME Magazine's first-ever consideration of Elvis Presley, a snippet review of the single Heartbreak Hotel in , did not contain many clues about what was to come. -
In Mediating Transcriptional Activity of Androgen Receptor Splice Variants
ROLE OF TRANSCRIPTIONAL ACTIVATION UNIT 5 (TAU5) IN MEDIATING TRANSCRIPTIONAL ACTIVITY OF ANDROGEN RECEPTOR SPLICE VARIANTS A THESIS SUBMITTED TO THE FACULTY OF THE GRADUATE SCHOOL OF THE UNIVERSITY OF MINNESOTA BY SARITA KUMARI MUTHA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE SCOTT DEHM & JIM McCARTHY DECEMBER 2012 © Sarita Kumari Mutha 2012 ACKNOWLEDGEMENTS I would like to thank the Dehm Lab: Scott Dehm, Yingming Li, Siu Chiu Chan, and Luke Brand for the support, discussions, journal clubs, and training. I would like to thank MCBD&G faculty Kathleen Conklin and Meg Titus for their support. Finally, I would also to acknowledge my committee Scott Dehm, Jim McCarthy, and Kaylee Schwertfeger for their time and support. i DEDICATION This thesis is dedicated to my mentor and advisor Scott Dehm. This work would not have been possible without his support. I am very grateful for my time under his mentorship and the opportunity to learn from him. ii ABSTRACT The standard treatment for advanced prostate cancer is chemical castration, which inhibits the activity of the androgen receptor (AR). Eventually, prostate cancer reemerges with a castration-resistant phenotype (CRPC) but still depends on AR signaling. One mechanism of AR activity in CRPC is the synthesis of AR splice variants, which lack the ligand binding domain. These splice variants function as constitutively active transcription factors that promote expression of endogenous AR target genes and support androgen independent prostate cancer cell growth. Previous work has shown transcriptional activation unit 5 (TAU5) is necessary for ligand independent activity of the full length AR in low or no androgen conditions and that this activation is mediated by the WHTLF motif.