Literatura académica sobre el tema "James Carson Breckinridge Library"

Abstract The androgen receptor (AR) is a ligand-responsive transcription factor (TF) that binds as a homodimer at FOXA1-pioneered enhancer elements containing a palindromic DNA motif. Prostate cancer (PCa) is highly dependent on the AR enhanceosome complex, and in castration-resistant disease, this dependency is reinforced through alterations in the AR pathway. This centrally involves extensive rewiring of the AR cistrome to gain de novo binding at enhancer sites (aka neo-enhancers) that activate hyperproliferative and metastatic gene programs. However, requisite subunits of the AR neo-enhanceosome and the genes it uniquely activates remain uncharacterized. Here, we CRISPR-engineered an endogenous AR reporter system by fusing the mCherry coding sequence in-frame with the KLK3/PSA gene and conducted a CRISPR knock-out screen to identify druggable chromatin/epigenetic cofactors of AR. Using a sgRNA library covering >200 druggable transcriptional coregulators, ranked alongside BRD4 and TRIM24/28, we identified NSD2 as a novel AR coactivator. NSD2 is an H3K36 di-methyltransferase that activates gene expression through antagonism of the PRC2/EZH2 complex. In PCa cells, genetic inhibition of NSD2 function significantly attenuated the expression of AR targets without affecting the AR protein level, suggesting that NSD2 regulates either AR’s chromatin assembly or trans-activational competence. Cistromic profiling of AR (ChIPseq) in NSD2-null PCa cells showed complete loss of binding at >40,000 genomic sites (~65% of the cistrome), with HOMER motif analyses of NSD2-dependent AR sites showing a higher recurrence of hexameric 5′-AGAACA-3′ AR half-site juxtaposed to the FOXA1, ETS, or HOXB13 motifs. In contrast, NSD2-independent AR sites, a large fraction of which show increased binding in NSD2-null cells, housed the canonical 15-bp palindromic AR motif with two invertedly-oriented half-sites separately recognized by each half of the AR homodimer. Notably, analyses of primary AR cistromes from human tissues revealed AR loading at half-motifs to be 20-30-fold enriched in the tumor-specific AR enhancer circuitry. In phenotypic assays, we found NSD2-deficient PCa cells to lose cancer hallmarks such as colony formation, invasion, and hyper-proliferation. We further developed a potent NSD2 PROTAC, LLC0150, which showed preferential cytotoxicity in AR/FOXA1+ PCa relative to the AR-negative disease, and other cancer and normal cell lines from 22 distinct lineages. In a pan-cancer screen comprising over 100 cell lines, treatment with LLC0150 triggered apoptotic death in AR/FOXA1+ malignancies and NSD2-mutant acute lymphocytic leukemia, and multiple myeloma. Altogether, we identify NSD2 as a novel AR neo-cofactor that assists oncogenic TFs in loading the AR enhanceosome at degenerate, low-affinity AR elements, thereby wiring its cancer-specific gene programs. We develop a novel NSD2 PROTAC that selectively kills AR/FOXA1-driven prostate and NSD2-altered tumors in preclinical models, positioning NSD2 therapeutics for safety and efficacy evaluation in human clinical trials. Citation Format: Abhijit Parolia, Brijesh K. Verma, Sanjana Eyunni, Sweta Aras, Sandra E. Carson, Eleanor Young, Chandan K. Das, James M. George, Reyaz ur Rasool, Prathibha Gajjala, Mohammed Alhusayan, Erick Mitchell-Velasquez, Lanbo Xiao, Jie Luo, Mustapha Jaber, Xuhong Cao, Fengyun Su, Rui Wang, Lianchao Liu, Zhen Wang, Ke Ding, Arul M. Chinnaiyan, Irfan Asangani. NSD2 is a requisite and targetable subunit of the AR/FOXA1 neo-enhanceosome complex in prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A055.

Greetings Everyone,The news for this new year’s issue consists mainly of a list of a major children’s literature awards that have been announced, as well as a few upcoming conferences.AWARDS2017 ALSC (Association for Library Service to Children) Book and Media Award WinnersJohn Newberry MedalThe Girl Who Drank the Moon Written by Kelly Barnhill and published by Algonquin Young Readers, an imprint of Algonquin Books of Chapel Hill, a division of Workman PublishingNewberry Honour BooksFreedom Over Me: Eleven Slaves, Their Lives and Dreams Brought to Life by Ashley Bryan written and illustrated by Ashley Bryan and published by Atheneum Books for Young Readers, an imprint of Simon & Schuster Children's Publishing DivisionThe Inquisitor’s Tale: Or, The Three Magical Children and Their Holy Dog written by Adam Gidwitz, illustrated by Hatem Aly and published by Dutton Children's Books, Penguin Young Readers Group, an imprint of Penguin Random House LLCWolf Hollow written by Lauren Wolk and published by Dutton Children's Books, Penguin Young Readers Group, an imprint of Penguin Random House LLCRandolph Caldecott MedalRadiant Child: The Story of Young Artist Jean-Michel Basquiat illustrated by Javaka Steptoe, written by Javaka Steptoe and published by Little, Brown and Company, a division of Hachette Book Group, Inc.Caldecot Honour BooksDu Iz Tak? illustrated and written by Carson Ellis, and published by Candlewick PressFreedom in Congo Square illustrated by R. Gregory Christie, written by Carole Boston Weatherford and published by Little Bee Books, an imprint of Bonnier Publishing GroupLeave Me Alone! illustrated and written by Vera Brosgol and published by Roaring Brook Press, a division of Holtzbrinck Publishing Holdings Limited PartnershipThey All Saw a Cat illustrated and written by Brendan Wenzel and published by Chronicle Books LLCLaura Ingalls Wilder AwardNikki Grimes -- Her award-winning works include “Bronx Masquerade,” recipient of the Coretta Scott King Author Award in 2003, and “Words with Wings,” the recipient of a Coretta Scott King Author Honor in 2014. Grimes is also the recipient of the Virginia Hamilton Literary Award in 2016 and the NCTE (National Council of Teachers of English) Award for Excellence in Poetry for Children in 2006.2018 May Hill Arbuthnot Honor AwardNaomi Shihab Nye will deliver the 2018 May Hill Arbuthnot Honor Lecture.Mildred L. Batchelder AwardCry, Heart, But Never Break - Originally published in Danish in 2001 as “Græd blot hjerte,” the book was written by Glenn Ringtved, illustrated by Charolotte Pardi, translated by Robert Moulthrop and published by Enchanted Lion Books.Batchelder Honour BooksAs Time Went By published by NorthSouth Books, Inc., written and illustrated by José Sanabria and translated from the German by Audrey HallOver the Ocean published by Chronicle Books LLC, written and illustrated by Taro Gomi and translated from the Japanese by Taylor NormanPura Belpre (Author) AwardJuana & Lucas written by Juana Medina, is the Pura Belpré Author Award winner. The book is illustrated by Juana Medina and published by Candlewick PressPura Belpre (Illustrator) AwardLowriders to the Center of the Earth illustrated by Raúl Gonzalez, written by Cathy Camper and published by Chronicle Books LLCAndrew Carnegie MedalRyan Swenar Dreamscape Media, LLC, producer of “Drum Dream Girl: How One Girl’s Courage Changed Music”Theodor Seuss Geisel AwardWe Are Growing: A Mo Willems’ Elephant & Piggie Like Reading! Book written by Laurie Keller. The book is published by Hyperion Books for Children, an imprint of Disney Book GroupRobert F. Sibert Informational Book MedalMarch: Book Three written by John Lewis and Andrew Aydin and illustrated by Nate Powell, published by Top Shelf Productions, an imprint of IDW Publishing, a division of Idea and Design Works LLC Stonewall Book Awards - ALA Gay, Lesbian, Bisexual, and Transgender Round Table (GLBTRT)Mike Morgan & Larry Romans Children’s & Young Adult Literature AwardIf I Was Your Girl written by Meredith Russo and published by Flatiron BooksMagnus Chase and the Gods of Asgard: The Hammer of Thor written by Rick Riordan and published by Disney Hyperion, an imprint of Disney Book GroupHonor BooksPride: Celebrating Diversity & Community written by Robin Stevenson and published by Orca Book PublishersUnbecoming written by Jenny Downham and published by Scholastic Inc. by arrangement with David Fickling BooksWhen the Moon Was Ours written by Anna-Marie McLemore and published by Thomas Dunne Books, an imprint of St. Martin’s Press2017 Children’s Literature Association Phoenix AwardsPhoenix Award 2017Wish Me Luck by James Heneghan Farrar Straus Giroux, 1997Phoenix Honor Books 2017Seedfolks by Paul Fleischman HarperCollins, 1997Habibi by Naomi Shihab Nye Simon & Schuster, 19972017 Phoenix Picture Book AwardTell Me a Season by Mary McKenna Siddals & Petra Mathers Clarion Books, 1997One Grain of Rice: A Mathematical Tale by Demi Scholastic, 1997 CONFERENCESMarchSerendipity 2017: From Beginning to End (Life, Death, and Everything In Between) The Vancouver Children’s Literature Roundtable Mar. 4, 2017 | 8am to 3:30 pm | UBC Ike Barber LibraryJuneChildren’s Literature Association ConferenceHosted by the University of South Florida June 22-24, 2017 Tampa, FL Hilton Tampa Downtown Hotel Conference Theme: Imagined FuturesJulyInternational Research Society for Children’s Literature (IRSCL) Congress 2017 – Toronto July 29 - August 2, 2017 Keele Campus, York University The Congress theme is “Possible & Impossible Children: Intersections of Children’s Literature & Childhood Studies." That is all for this issue. Best wishes!Hanne Pearce, Communication Editor

Master of Arts
Department of History
Michael A. Ramsay
Immediately after World War I, the Commandant of the United States Marine Corps implemented an officer education program. Called the Marine Corps Schools (MCS), the Commandant, Major General John A. Lejeune, gave the schools the mission of educating officers throughout their career. MCS struggled during its first decade of existence due to operational tempo and a poor curriculum. The direction of MCS changed greatly with the assignment of James Carson Breckinridge as the commanding officer in 1928. The purpose of this thesis is to examine the role Breckinridge, an unconventional and intellectual officer, played in reviving the MCS and turning it into the authority on Small Wars and Amphibious Operations. It will show that Breckinridge, drawing on observations made of college education systems, focused the Marine Corps Schools on the task of teaching officers to analyze problems and find solutions and not rely on memorized book answers.