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7. MLL-AF4 cooperates with PAF1 and FACT to drive high-density enhancer interactions in leukemia.

Author

Crump, Nicholas, Smith, Alastair, Godfrey, Laura, Dopico-Fernandez, Ana, Denny, Nicholas, Harman, Joe, Hamley, Joseph, Jackson, Nicole, Chahrour, Catherine, Riva, Simone, Rice, Siobhan, Kim, Jaehoon, Basrur, Venkatesha, Fermin, Damian, Elenitoba-Johnson, Kojo, Roeder, Robert, Allis, C, Roberts, Irene, Roy, Anindita, Geng, Huimin, Davies, James, and Milne, Thomas

Subjects
Humans, Nuclear Proteins, Transcription Factors, Regulatory Sequences, Nucleic Acid, Leukemia, Promoter Regions, Genetic, Cell Cycle Proteins, Oncogene Proteins, Fusion, Myeloid-Lymphoid Leukemia Protein
Abstract

Aberrant enhancer activation is a key mechanism driving oncogene expression in many cancers. While much is known about the regulation of larger chromosome domains in eukaryotes, the details of enhancer-promoter interactions remain poorly understood. Recent work suggests co-activators like BRD4 and Mediator have little impact on enhancer-promoter interactions. In leukemias controlled by the MLL-AF4 fusion protein, we use the ultra-high resolution technique Micro-Capture-C (MCC) to show that MLL-AF4 binding promotes broad, high-density regions of enhancer-promoter interactions at a subset of key targets. These enhancers are enriched for transcription elongation factors like PAF1C and FACT, and the loss of these factors abolishes enhancer-promoter contact. This work not only provides an additional model for how MLL-AF4 is able to drive high levels of transcription at key genes in leukemia but also suggests a more general model linking enhancer-promoter crosstalk and transcription elongation.

Published
2023

9. Tranexamic acid versus placebo to prevent bleeding in patients with haematological malignancies and severe thrombocytopenia (TREATT): a randomised, double-blind, parallel, phase 3 superiority trial

Author

Estcourt, Lise J, McQuilten, Zoe K, Bardy, Peter, Cole-Sinclair, Merrole, Collins, Graham P., Crispin, Philip J., Curnow, Elinor, Curnow, Jennifer, Degelia, Amber, Dyer, Claire, Friebe, Adam, Floro, Lajos, Grand, Effie, Hudson, Cara, Jones, Gail, Joseph, Joanne, Kallmeyer, Charlotte, Karakantza, Marina, Kerr, Paul, Last, Sara, Lobo-Clarke, Maria, Lumley, Matthew, McMullin, Mary F, Medd, Patrick G., Morton, Suzy M., Mumford, Andrew D., Mushkbar, Maria, Parsons, Joseph, Powter, Gillian, Sekhar, Mallika, Smith, Laura, Soutar, Richard, Stevenson, William S., Subramoniapillai, Elango, Szer, Jeff, Thomas, Helen, Waters, Neil A., Wei, Andrew H., Westerman, David A., Wexler, Sarah A., Wood, Erica M., Stanworth, Simon J., Abioye, Adrienne, Afghan, Rabia, Ai, Sylvia Ai, Akanni, Magbor, Alajangi, Rajesh, Alam, Usmaan, Al-Bubseeree, Bahaa, Alderson, Sophie, Alderson, Craig, Ali, Sayed, Ali, Kabir, Alighan, Rookmeen, Allam, Rebecca Allam, Allen, Tania, Al-Sakkaf, Wesam, Ames, Kate, Anderson, Jacqueline, Andrews, Colin, Angel, Ann-Marie, Anlya, Manuela Anlya, Ansari, Farah, Appleby, Rowan, Arnold, Claire, Asbjornsdottir, Hulda, Asfaw, Biruk, Atkins, Elissa, Atkinson, Leela, Aubrey, Clare, Ayesha, Noor, Babbola, Lola, Badcock, David, Badcock, Samuel, Baggio, Diva, Bailiff, Ben, Baines, Kizzy, Baker, Holly, Baker, Victoria, Ball, Lindsay, Ball, Martin, Balquin, Irwin, Banks, Emma, Banos, George, Barnett, Jaytee, Barrie, Claire, Barron, Claire, Barton, Rebecca, Bason, Nina, Batta, Bindu, Bautista, Dianne, Bayley, Angela, Bayly, Emma, Baynes, Fionnuala, Bazargan, Ali, Bazeley, Rachel, Beadle, Yvonne, Beardsmore, Claire, Beattie, Kate, Bedford, Caroline, Behal, Rachna, Behan, Daniel, Bejan, Lilihna, Bell, Sarah, Bell, Karen, Bell, Louise, Bell, Kaitlyn, Benjamin, Reuben, Bennett, Sam, Benson, Gary, Benson, Warwick, Bent, Cameron, Bergin, Krystal, Berry, Alex, Besenyei, Stephanie, Besley, Caroline, Betteridge, Scott, Beveridge, Leigh, Bhattacharyya, Abir, Billen, Annelies, Bilmon, Ian, Binns, Emma, Birt, Mark, Bishop, David, Blanco, Andrea, Bleby, Lisa, Blemnerhet, Richard, Blombery, Piers, Blyth, Emily, Blythe, Nicola, Boal, Lauren, Boden, Ali, Bokhari, Syed W.I., Bongetti, Elisa, Booth, Stephen, Borley, Jayne, Bowen, David, Bowers, Dawn, Boyd, Stephen, Bradley, Sarah, Bradman, Helen, Bretag, Peta, Brillante, Maria, Brockbank, Rachel, Brough, Yasmin, Brown, Ellen, Brown, Jo, Brown, Eleanor, Brown, Claire, Brown, Jenny, Brown, Susan, Browning, Joe, Brownsdon, Alex, Bruce, David, Brydon-Hill, Ruth, Buckwell, Andrea, Burgess, Dannielle, Burke, Glenda, Burley, Kate, Burney, Claire, Burns, David, Burrows, Samuel, burton, Kieran, Butler, Jason, Cambalova, Lenka, Camozzi, Maria C., Campbell, Philip, Campfield, Karen, Campion, Victoria, Cargo, Catherine, Carmona, Julia, Carney, Dennis, Casan, Joshua, Cashman, Helen, Catt, Lorraine, Cattell, Michael, Cavill, Megan, Chadbone, Rachel, Chaganti, Sridhar, Chai, Yee, Chai, Khai Li, Chang, Joshua, Chapman, Judith, Chapman, Oliver G., Chapter, Tamika, Charlton, Andrew, Chau, Celina, Chauhan, Saleena, Chavda, Nikesh, Chen, Frederick, Chen, Melody, Chen, Meng Xi, Chen, Melanie, Chen, Melissa, Cheok, Kathleen, Cheung, Mai, Chidgey, Luke, Chmielokliec, Karolina, Choi, Philip, Choi, Jae, Chok, Anne, Chopra, Ruchika, Christopherson, Louise, Chu, Vicky, Chua, Chong Chyn, Chudakou, Pavel, Chugh, Vidushi, Chung, Chi, Clark, Erin, Clarke, Peter, Clarke, Kathleen, Clay, Jennifer, Clayton, Laura, Clements, Mitch, Clemmens, Jonathan, Clifford, Ruth, Collett, Dave, Collins, Maia, Collyer, Emily, Connolly, Maureen, Cook, Mark, Coombs, Sarah, Coppell, Jason, Cornwell, Sophie, Corrigan, Claire, Coughlin, Elizabeth, Couling, Jennifer, Cousins, Tony, Cowan, Catriona, Cox, Christine, Cox, Catherine, Coyle, Luke, Craig, Emily, Creasey, Thomas, Croan, Laura, Croft, Jane, Crosbie, Nicola, Crowe, Josephine, Crowther, Helen, Crozier, Jane, Culleton, Naomi, Cullis, Jonathan, Cumming, Anita, Cummins, Michelle, Cunningham, Adam, Curley, Cameron, Curtis, Samantha, Cuthbert, Robert, Cuthill, Kirsty, Dahahayake, Dinusha A, Dang, Amy, Davies, Marc, Davies, Ceri, Dawson, Emily, Day, Tom, De Abrew, Kanchana, De Lavallade, Hugues, De Silva, Neelaskshi, Dean, Georgina, Deane, Christopher, Demosthenous, Lisa, Desai, Amisha, Desborough, Michael, Devanny, Ian, Dhanapal, Jay, Dhani, Sundip, Di Martino, Vicky, Dickens, Emmy, DiCorleto, Carmen, Dinnett, Louise, Dirisan, Divya, Dixon, Karen, Dixon, Kiri, Doal, Inderjit, Dobivh, J, Docanto, Maria, Doecke, Helve, Donaldson, David, Donaldson, Kylee, Donohoe, Carrie, Douglas, Ashley, Doung, Stephen, Downer, Susan, D'Rozario, James, Drummond, Malcolm, Drummond, Mark, Drummond, Samantha, Drysdale, Elizabeth, D'Souza, Ross, D'Souza, Eugene, Dunn, Alex, Dutton, David, Dyson, Martin, Ediriwicurena, Kushani, Edleston, Sharon, Edwards, Dawn, Edwards, Morgan, Edwards, Anita, Eise, Nicole, Ellis, Steven, Ellis, Hayley, Elmonley, Shareef, Enstone, Rosemarie, Eordogh, Agnes, Erb, Sharon, Evans, Shannon, Evans, Megan, Ewing, Joanne, Eyre, Toby, Facey, Adam, Fammy, Mina, Farman, Jon, Farnell, Rachel, Favero, Laura, Fay, Keith, Ferguson, Karen, Fernon, Laura, Filshie, Robin, Finnegan, Damian, Fisher, Lisa, Flanagan, Asia, Fleck, Emma, Fletcher, Simon, Flora, Harpreet, Flower, Catherine, Fodor, Ioana, Foley, Heather, Folland, Emma, Folorunso, Comfort, Forbes, Molly, Fordwor, Katrina, Foster, Polly, Fox, Vanessa, Fox, Thomas, Francis, Olesya, Fryearson, Louise, Fuery, Madonna, Fung, Jiin, Furtado, Michelle, Galloway-Browne, Leanne, Gamble, Louise, Gamgee, Jeanette, Ganapathy, Arundathi, Gardner, Hayley, Gardner, Clare, Gasmelsheed, Noha, Gately, Amy, Gaynor, Lynda, Gebreid, Alex, Geffens, Ruth, George, Rachel, Gertner, Aniko, Ghebeh, Manar, Ghirardini, Emanuela, Giddings, Melainie, Gillett, Sandra, Gillett, Karen, Giri, Pratyush, Glass, Chris, Glewis, Sarah, Gooding, Sarah, Gordon, Olivia, Gordon, Joanne, Gottlieb, David, Gowda, Koushik, Gower, Elysie, Gray, Nicola, Grayer, Jo, Greaves, Elaine, Greenaway, Sally Anne, Greenfield, Graeme, Greenwood, Matthew, Gregory, Gareth, Griffin, James, Griffith, Julia, Griffith, James, Griffiths, Lindsey, Grzegrzolka, Paulina, Gu, Yisu, Guest, Jo, Guinai, Rosanna, Gullapalli, Veena, Gunolr, A., Guo, Lina, H, Wayne, Hagua, Sophia, Haile, Senait, Hall, Richard, Hamdollah-Zadeh, Maryam, Hanif, Zahra, Hanlon, Kathleen, Hann, Nicholas, Hanna, Ramez, Hannah, Guy, Hapuarachchi, Sameera, Hardman, Jacinta, Hardy, Alison, Harris, Anthony, Harris, Kylie, Harrison, Beth, Harrison, Simon, Harrison, Lea-Anne, Harrop, Sean, Harvey, Caroline, Hatcliffe, Faye, Hawking, Jo, Hawkins, Matthew, Hayden, Janet, Hayman, Michelle, Haynes, Elizabeth, Heaney, Nicholas, Hebbard, Andrew, Hempton, Jenny, Hendunneti, Sasanka, Henry, Maeve, Heywood, Jonathan, Hildyard, Catherine, Hill, Lydia, Hilldrith, Annette, Hitev, Petar, Hiwase, Smita, Hiwase, Devendra, Hoare, Chris, Hodge, Renate, Holloway, Amy, Holt, Chloe, Holton, Kelly, Homer, Lauren, Horne, Gillian, Horvath, Noemi, Hotong, Linda, Houdyk, Kristen, Houseman, Katy, Hoxhallari, Ilda, Hsu, Hannah, Hsu, Nina, Huang, Gillian, Hudson, Kerryn, Hufton, Melanie, Hughes, Timothy, Hughes, Siobhan, Hurley, Kate, Huxley, Rosie, Ibitoye, Temitope, Ibrouf, Abubaken, Inam, Farha, Indran, Tishya, Ingham, Karen, Innes, Calum, Irvine, David, Jaafar, Sarah, Jain, Manish, Jameson, Laura, Janjua, Pardeep, Jarvis, Rebecca, Jatheendran, Abirami, Javed, Abbie, Jen, Sheila, Jobanpura, Shailesh, Jobson, Irene, John, Deborah, Johns, Sophie, Johnston, Amanda, Jones, Hollie, Jones, Francesca, Joniak, Karolina, Jovanovic, Michael, Jovic, Anita, Joyce, Lauren, Judd, Andrew, Kakarlamudi, Sudhakar, Kakaroubas, Nick, Kalita, Maggie, Kam, Shirly, Kan, Julie, Kandle, P, Kanellopoulos, Alex, Kao, Chien, Kaparou, Maria, Kartsios, Charamlampos, Katsioulas, Vicki, Kaye, Russell, Keen, Katie, Kelly, Richard, Kelly, Pauline, Kelly, Donna, Kelly, Melanie, Kennedy, Glen, Kennedy, Nola, Kenny, Angela, Kenworthy, Zoe, Kerridge, Ian, Kesavan, Murali, Khafizi, Angelika, Khakwani, Muhammad, Khalid, Amna, Khamly, Kate, Khan, Anjum, Khan, Dalia, Khan, Mojid, Khan, Lubna, Khoo, Mona, Khwaja, Asim, Kim, Grace, King, Andrew, King, Vicky, King, Donna, Kinsella, Francesca, Kipp, David, Kirandeep, Pachoo, Kirui, Laura C., Kishore, Bhuvan, Knectlhi, Christopher, Knot, Amy, Knot, Armit, Ko, Cathy, Kolaric, Caitlin, Koo, Ray, Kotadia, Mary, Kothari, Jaimal, Kottaridis, Panagiotis D., Kuiluinathan, Gajan, Kulasekararaj, Austin, Kwan, John, Kwok, Marwan, Kwok, Phillip, Kwok, Fiona, Laane, Kristiina, Lad, Deena, Laird, Jennifer, Lam, Ada, Lane, Mary, Lanenco, Monica, Lang, Susan, Langridge, Alex, Langton, Catherine, Lannon, Michelle, Latif, Annie, Latimer, Maya, Latter, Ruth, Lau, I-Jun, Lawless, Sarah, Lawless, Theresa, Leach, Mike, Leaney, Sarah, Leary, Heather, Leavy, James, LeBlanc, Abbey, Lee, Vivienne, Lee, Edwin, Lee, Jenny, Lee, Tamara, Leischkie, Marian, Leitinger, Emma, Leon, Christopher, Leonard, Jayne, Lewis, David, Lewis, Ian, Lewis, Tania, Lim, Daniel, Littlewood, Kelly, Liu, Dara, Loh, Joanna, Lokare, Anand, Lomas, Oliver, Lovell, Richard, Lowe, Theresa, Lowry, Lisa, Lubowiecki, Marcin, Lumb, Rebecca, Lynch, Gail, Macaulay, Amanda, MacDonald, Lyndsey, MacDonald-Burn, Jill, Macmillan, Margaret, Maddock, Karen, Mahaliyana, Tomas, Mahon, Cassandra, Maidment, Alison, Maier, Susie, Mairos, Michelle, Majid, Mahseeman, Mak, Ka L, Mak, Anne, Malendrayogau, Arunthrthy, Malham, Hana, Malyon, Felicity, Mandadapu, Vineela, Mandel, Laura, Mant, Sarah, Manton, Ruth, Maouche, Nadjoua, Maqbool, Muhammad G., Marchant, Gregory, Marinho, Mariana, Marks, David, Marner, Mike, Marr, Helen, Marshall, Gillian, Martin, Siobhan, Martin, Abigail, Marzolini, Maria, Mason, Kiara, Massie, Jonathan, Masson, Rebecca, Mathavan, Vidya, Mathew, Siju, Mathie, Judith, Mattocks, Lehenta, Maybury, Bernard, Mayer, Georgina, McAlister, Chyrelle, McAllister, Jo, McConnell, Stewart, McCracken, James, McCullagh, Liz, McCulloch, Rory, Mcdermott, Christopher, Mcdonald, Kerian, McGinniss, Laura, McGurk, Fiona, McIlwain, Jessica, McIver, Kirsten, Mckay, Pam, McKenna, Lorraine, Mclornan, Donal, McMahon, Coalon, McNeice, Linda, McNeill, Susan, McNickle, Molly, McQueen, Fiona, McRae, Simon, McTaggart, Bobby, Mehew, Jenny, Mehra, Varnn, Melly, Michelle, Menichelli, Tara, Micklethwatte, Ken, Mihailescue, Loredana, Mijovic, Aleksander, Millband, Hannah, Miller, Lucy, Millien, Samuel T., Milnthorpe, James, Minson, Adrian, Molnar, Eva, Monsour, Marc, Moody, Mary, Moon, Rebecca, Moore, Sally, Moore, Katy, Morgan, Kelly, Morralley, Rebecca, Morris, Denise, Morris, Kirk, Morrison, Nicole, Moss, Merinda, Mughal, Muhammad, Muir, Paul, Mukkath, David, Mulla, Aasiyu, Mulligan, Stephen, Mullings, Joanne, Mulqueen, Angela, Muluey, Caitlin, Murdoch, Sarah, Murrani, Sura, Murthy, Vidhya, Musngi, Jimmy, Mustafa, Nadreen, Mynes, Tracey, Nalpantidis, Anastasios, Nandurkar, Harshal, Nardone, Linda, Nasari, Latifa, Nash, Monica, Naylor, Georgina, Ngu, Loretta, Nguethina, Melissa, Nguyen, John, Nguyen, Joseph, Nichol, Wendy, Nicholls, Emma, Nicole, Catherine S., Nicolson, Phillip, Nielson, David, Nikolousis, Emmanouil, Nix, Georgina, Njoku, Rita, Norman, Jane, Norman, Amy, Norris, Phoebe, North, Daniel, Norwood, Megan, Notcheva, Gaynor, Novitzky-Basso, Igor, Nyaboko, Joseph, Nygren, Maria, Obu, Ingrid, O'Connell, Siobhan, O'Connor, Jody, O'Kelly, Deanna, O'Niell, Aideen, Ony, Jeremy, Oo, Kathy, Oo, April, Oppermann, Anne, Orr, Ruth, O'Sullivan, Mary, Page, Jennifer, Palfreyman, Emma, Paneesha, Shankaranarayana, Panicker, Shyam, Parbutt, Catherine, Parigi, Elesha, Paris, Gemma, Parker, Tracey, Parnell, Caroline, Parrish, Christopher, Parsons, Alex, Pasat, Mioara, Patel, Natasha, Patel, Vijay, Patel, Pooja, Patel, Chaya, Pati, Nalini, Patterson, Andrea, Paul, Lauren, Payet, Danielle, Payne, Elspeth, Peachey, Victoria, Pearson, Amanda, Peniket, Andy, Percy, Laura, Pereyra, Millicent, Pervaiz, Omer, Phalod, Gunjan D, Pham, Anh, Pho, Jason, Pickard, Keir, Pidcock, Michael, Piggin, Anna, Pishyar, Yalda, Pocock, Abigail, Pol, Ranjendres, Polzella, Paolo, Poolan, Sonia, Portingale, Vicki, Posnett, Claire, Potluri, Sandeep, Potter, Victoria, Pratt, Guy, Prodger, Catherine, Pueblo, Andres, Puliyayil, Anish, Puvanakumar, Pratheepan, Qadri, Abdul, Quach, Hang, Quinn, Michael, Rafferty, Mark, Rahman, Marzia, Raj, Kavita, Raj, Sonia, Rajendran, Ramina, Ramanan, Radha, Ramasamy, Karthik, Rampotas, Alexandros, Ranchhod, Natasha, Rashid, Sabia, Ratanjee, Sunita, Rathore, Gurpreet, Ratnasingam, Sumita, Rayat, Manjit, Rayner, Michael, Reddell-Denton, Rebecca, Redding, Nicola, Reddy, Udaya, Rehman, Atique, Rice, Carol, Riches, Iwona, Rider, Thomas, Riley, John, Rinaldi, Ciro, Roberts, Kayleigh, Roberts, Andrew, Robertson, Bryony, Robertson, Peter, Robinson, Dan, Robinson, Rebecca, Robjohns, Emma, Robledo, Laura, Rodrigues, Ana, Rofe, Chris, Roff, Bridie, Rogers, Rachel, Rolt, Jill, Rooney, Carmela, Rose, Kathy, Rose, Hannah, Ross, David, Rouf, Shahara, Rourke, Claire, Routledge, David, Ruggiero, Janet, Rule, Simon, Rumsey, Richard, Sagge, Cherry, Saldhana, Helen, Salisbury, Richard, Salisbury, Sarah, Salvaris, Ross, Sanders, Kay, Sangombe, Mirriam, Sanigorska, Anna, Santos, Kristine, Sarkis, Taylah, Sarma, Anita, Saunders, Natalie, Schmidt, Kara, Schmidtmann, Anja, Schumacher, Ann, Scorer, Tom Scorer, Scott, Asleigh, Seath, Ingrid, Sejman, Frances, Selim, Adrian, Shamim, Nadia, Shan, Jocelyn, Shanmuganathan, Naranie, Shanmugaranjan, Shaminie, Sharpe, Michelle, Sharpley, Faye, Shaw, Emma, Sheath, Cara, Sheehy, Oonagh, Shen, Vivian, Sherbide, Solomon, Sheridan, Mathew, Sheridan, Jane, Sheridon, Matthew, Shields, Tracy, Sim, Hau V, Sim, Shirlene, Sims, Matt, Singaraveloo, Lydia, Singh, Gurcharan, Singh, Jasmine, Sladesal, Shree, Sloan, Andrew, Slobodian, Peter, Smith, Sophie, Smith, Sarit, Smith, Claire, Smith, Alastair, Smith, Neil, Snowden, Katherine, Solis, Joel, Somios, Denise, Soo, Jade, Spanevello, Michelle, Spaulding, Madeleie, Spence, Laura, Spillane, Liz, Spiteri, Alisha, Sprigg, Naomi, Springett, Sally, Stafford, Lynn, Stainthorp, Katherine, Stark, Kate, Steeden, Louise, Stephen, Ella, Stephenson, Aisling, Stewart, Andrew, Stewart, Orla, Stobie, Emma, Stokes, Chelsea, Streater, Jacqui, Suddens, Charlie-Marie, Suntharalingam, Surenthini, Surana, Narinder, Sutherland, Robyn, Sutherland, Antony, Sutton, David, Sweeney, Connor, Sweet, Reilly, Szucs, Aniko P, Taheri, Leila E., Tailor, Hinesh, Tam, Constantine, Tambakis, George, Tamplin, Mary, Tan, Chee, Tan, Sui, Tan, Joanne, Tan, Zhi, Taran, Tatiana, Tarpey, Fiona, Taseka, Angela, Tasker, Suzy, Tatarczuch, Maciej, Tayabali, Sarrah, Taylor, Hannah, Taylor, Robert, Taylor, Melaine, Taylor-Moore, Ella, Teasdale, Lesley, Tebbet, Elizabeth, Tedjasepstra, Aditya, Tedjaseputra, Aditya, Tepkumkun, Oummy, Terpstra, Andrew, Thomas, Wayne, Thomas, Shanice, Thompson, Rachel, Thornton, Thomas, Thorp, Bronwyn, Thrift, Moi Yap, Thwaites, Phillipa, Timbres, Jasmine, Tindall, Lauren, Tiong, Ing Soo, Tippler, Nicole, Todd, Tony, Todd, Shirley, Toghill, Neil, Tomlinson, Eve, Tooth, Jacinta, Topp, M., Trail, Nicola, Tran, Nguyen, Tran, Elizabeth, Tran, Vi, Treder, Bona, Tribbeck, Michelle, Trochowski, Siobhan, Truslove, Maria, Tse, Tsun, Tseu, Bing, Tucker, David, Turner, Kelly, Turner, Dianne, Turner, Herleen, Turner, Gillian, Twohig, Julie, Tylee, Thomas, Uhe, Micheleine, Underhill, Lauren, V, Joanne, Van der Vliet, Georgina, Van Tonder, Tina, VanderWeyden, Carrie, Varghese, Jerry, Vaughan, Lachlan, Veale, David, Vickaryyous, Nicky, Vince, Kathryn, Von Welligh, Jacoba, Vora, Sona, Wadehra, Karan, Walker, Rebecca, Walker, Stephen, Wallace, Roslyn, Wallniosve, Stephanie, Wallwork, S., Walmsley, Zoe, Walters, Fiona, Wang, Joyce, Wang, Angela, Wang, Chen, Wanyika, Mercy, Warcel, Dana, Wardrobe, Katrina, Warnes, Kristian, Waterhouse, Christopher, Waterworth, Adam, Watson, Caroline, Watson, Edmund, Watts, Emily, Weaver, Emma, Weber, Nicholas, Webley, Kaytie, Welford, Anna, Wells, Matt, Westbury, Sarah, Westcott, Jackie, Western, Robyn, Weston, Julia, White, Jessica, White, Phillipa, Whitehead, Anna, Whitehouse, James, Wieringa, Samantha, Willan, John, Williams, Sandra, Williams, Bethany, Williamson, Stephanie, Willoughby, Brett, Wilmot, Gail, Wilmott, Rosalind, Wilson, Joanna, Wilson, Emma, Wilson, Suzy, Wilson, Heather, Wilson, Caroline, Wilson, Tanya, Wilton, Margaret, Wiltshire, Paula, Wincup, Joanne, Wolf, Julia, Wong, Henna, Wong, Cyndi, Wong, Daniel, Wong, Jonathan, Wong, Shi Qin, Wood, Sarah, Wood, Henry, Wooding, Jackie, Woolley, Kelly, Wright, Myles, Wynn-Williams, Roland, Yannakou, Costas, Yeoh, Zhi Han, Yeung, David, Young, Agnes, Yuen, Flora, Yuen, Agnes, Zaja, Oliver, Zhang, Xiao-Yin, and Zhang, Mei

Published
2025
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19. Reviews

Author

Smith, Alastair G

Published
2001

30. Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT‐V Study.

Author

Shiffman, Mitchell, Reddy, K. Rajender, Leise, Michael D., Qureshi, Kamran, Smith, Alastair D., Helmke, Steve, Kittelson, John, McRae, Michael P., Imperial, Joanne C., and Everson, Gregory T.

Subjects
ESOPHAGEAL varices, CHRONIC hepatitis C, PORTAL hypertension, ORAL drug administration, LIVER function tests
Abstract

Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH. Aims: In the US multicentre SHUNT‐V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy. Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut‐off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%. Results: SHUNT‐V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child–Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%–100% for LEV and 97.3%–100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%–35% of EGDs could have been avoided with 0%–3.7% of LEV and 0%–2.7% of all significant PH lesions missed. Conclusions: HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal‐systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child–Pugh A cirrhosis. Trial Registration: The SHUNT‐V study was registered at ClinicalTrials.gov (NCT03583996) [ABSTRACT FROM AUTHOR]

Published
2025
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32. Modality Effects in Vocabulary Acquisition

Author

Wolf, Merel C., Smith, Alastair C., Meyer, Antje S., and Rowland, Caroline F.

Subjects
modality effects, word learning, vocabularyacquisition, reading
Abstract

It is unknown whether modality affects the efficiency withwhich humans learn novel word forms and their meanings,with previous studies reporting both written and auditoryadvantages. The current study implements controls whoseabsence in previous work likely offers explanation for suchcontradictory findings. In two novel word learningexperiments, participants were trained and tested onpseudoword - novel object pairs, with controls on: modality oftest, modality of meaning, duration of exposure andtransparency of word form. In both experiments word formswere presented in either their written or spoken form, eachpaired with a pictorial meaning (novel object). Following a 20-minute filler task, participants were tested on their ability toidentify the picture-word form pairs on which they weretrained. A between subjects design generated four participantgroups per experiment 1) written training, written test; 2)written training, spoken test; 3) spoken training, written test; 4)spoken training, spoken test. In Experiment 1 the writtenstimulus was presented for a time period equal to the durationof the spoken form. Results showed that when the duration ofexposure was equal, participants displayed a written trainingbenefit. Given words can be read faster than the time taken forthe spoken form to unfold, in Experiment 2 the written formwas presented for 300 ms, sufficient time to read the word yet65% shorter than the duration of the spoken form. No modalityeffect was observed under these conditions, when exposure tothe word form was equivalent. These results demonstrate, atleast for proficient readers, that when exposure to the wordform is controlled across modalities the efficiency with whichword form-meaning associations are learnt does not differ. Ourresults therefore suggest that, although we typically begin asaural-only word learners, we ultimately converge ondeveloping learning mechanisms that learn equally efficientlyfrom both written and spoken materials.

Published
2019

38. Clinical and Neurologic Outcomes in Acetaminophen-Induced Acute Liver Failure: A 21-Year Multicenter Cohort Study

Author

Lee, William M., Larson, Anne M., Liou, Iris, Fix, Oren, Schilsky, Michael, McCashland, Timothy, Eileen Hay, J., Murray, Natalie, Shaikh, A. Obaid S., Blei, Andres, Ganger, Daniel, Zaman, Atif, Han, Steven H.B., Robert Fontana, McGuire, Brendan, Chung, Raymond T., Smith, Alastair, Brown, Robert, Crippin, Jeffrey, Harrison, Edwin, Reuben, Adrian, Munoz, Santiago, Reddy, Rajender, Todd Stravitz, R., Rossaro, Lorenzo, Satyanarayana, Raj, Hassanein, Tarek, Karvellas, Constantine J., Olson, Jodi, Subramanian, Ram, Hanje, James, Hameed, Bilal, MacDonald, Andrew J., Speiser, Jaime L., Ganger, Daniel R., Nilles, Kathleen M., and Orandi, Babak J.

Published
2021
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40. A novel microRNA-based prognostic model outperforms standard prognostic models in patients with acetaminophen-induced acute liver failure

Author

Lee, W.M., Larson, Anne M., Liou, Iris, Fix, Oren, Schilsky, Michael, McCashland, Timothy, Hay, J. Eileen, Murray, Natalie, Shaikh, A. Obaid S., Blei, Andres, Ganger, Daniel, Zaman, Atif, Han, Steven H.B., Fontana, Robert, McGuire, Brendan, Chung, Raymond T., Smith, Alastair, Brown, Robert, Crippin, Jeffrey, Harrison, Edwin, Reuben, Adrian, Munoz, Santiago, Reddy, Rajender, Stravitz, R. Todd, Rossaro, Lorenzo, Satyanarayana, Raj, Hassanein, Tarek, Karvellas, Constantine J., Olson, Jodi, Subramanian, Ram, Hanje, James, Hameed, Bilal, Lalani, Ezmina, Pezzia, Carla, Sanders, Corron, Attar, Nahid, Hynan, Linda S., Durkalski, Valerie, Zhao, Wenle, Speiser, Jaime, Dillon, Catherine, Battenhouse, Holly, Gottfried, Michelle, Tavabie, Oliver D., Salehi, Siamak, Speiser, Jaime L., Rose, Christopher F., Menon, Krishna, Prachalias, Andreas, Heneghan, Michael A., Agarwal, Kosh, Lee, William M., McPhail, Mark J.W., and Aluvihare, Varuna R.

Published
2021
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43. How do marine bacteria respond to nutrient limitation? : a lipidomics approach

Author

Smith, Alastair F.

Subjects
570, QR Microbiology
Abstract

Microbes inhabiting surface waters of the Earth’s oceans are exquisitely adapted to their nutrient-poor environment. Marine phytoplankton, for example, are able to reduce their requirements for phosphorus by replacing membrane phospholipids with alternative non-phosphorus lipids. Heterotrophic bacteria, which can also thrive when phosphorus is scarce, had not, however, been shown to carry out this process – seemingly placing these organisms at a competitive disadvantage. In this thesis, I show that substitution of membrane phospholipids for a variety of non-phosphorus lipids is a conserved response to phosphorus deficiency amongst phylogenetically diverse marine heterotrophic bacteria. By deletion mutagenesis and complementation in the model marine bacterium Phaeobacter sp. MED193 and heterologous expression in recombinant Escherichia coli, I confirmed the roles of a phospholipase C (PlcP) and a glycosyltransferase in lipid remodelling. Analyses of two large collections of marine metagenomes, the Global Ocean Sampling (GOS) and Tara datasets, demonstrate that PlcP is particularly abundant in areas characterised by low phosphate concentrations. To better understand the lipids that potentially replace phospholipids during this remodeling process, I investigated a number of poorly-characterised aminolipids that are prevalent in the globally important marine Roseobacter group. I was able to identify two genes involved in the synthesis of one of these lipids, a glutamine lipid. Subsequent phylogenetic analysis of one of these genes revealed that the capacity to synthesise glutamine lipid appears to be virtually ubiquitous within the Roseobacter group. A further class of aminolipids was present in many Roseobacter strains, which I identified as a novel class of homotaurine-containing lipids using high-resolution, accurate mass spectrometry. These homotaurine lipids were detected in a battery of Roseobacter strains, enabling me to employ a comparative genomics approach to identify genes potentially involved in their biosynthesis. Surprisingly, neither of these aminolipids appeared to play an important role in the response to phosphorus limitation in the Roseobacter strains tested. Together, these results point to a key role for lipid substitution as an adaptive strategy enabling heterotrophic bacteria to thrive in vast, phosphorus-depleted areas of the ocean. Although phosphorus-free lipids play a crucial role in this process of adaptation, my work emphasises that many of these lipids are not simply substitutes for phospholipids but rather appear to have important roles in the cell in their own right.

Published
2017

45. Characterising the anxiogenic network from functional connectivity analysis of the CO2 challenge model.

Author

Graham, Daniel, Mathew, Santra, Marsden, Jonathan, Smith, Alastair D., Smerdon, Gary, and Hall, Stephen D.

Abstract

The CO2 challenge model (CCM) is a gas inhalation paradigm that provides precisely controlled anxiety induction in experimental settings. Despite its potential as an experimental model of anxiety, our understanding of the neural effects of the CCM is incomplete. This study employs resting-state functional magnetic resonance imaging (rs-fMRI) to explore functional connectivity (FC) changes underlying the CCM. Following a preliminary CO2 tolerance assessment, participants completed an MRI session that included three rs-fMRI scans: during inhalation of control air (pre and post), and during a 6% CCM exposure. Here, we confirm that 6% CCM is a tolerable anxiogenic model in the MRI setting. We demonstrate that a transient CCM-induced increase in subjective anxiety is associated with an increase in FC within limbic and anxiety-related regions, with the insula emerging as a central node in this altered connectivity pattern. Further analysis revealed a significant correlation between the levels of subjective anxiety and enhanced FC between the brainstem and medial frontal cortex, highlighting the dynamic role of the brainstem in response to CO2-induced anxiety. These findings underscore the value of combining CCM and rs-fMRI to characterise the neural mechanisms of anxiety, with important implications for evaluating potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Published
2024
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50. Measurement of the prompt fission y -rays from slow neutron-induced fission of 235 U with STEFF

Author

Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. ANT - Advanced Nuclear Technologies Research Group, Wright, Tobias, Smith, Alastair, Sosnin, Nikolay Viktorovich, Bennett, Sam, Davies, Paul John, Popescu, Alexandra, Ryan, Joanne, Sekhar, Adhitya, Warren, Saskia, Aberle, Oliver, Amaducci, Simone, Andrzejewski, Józef, Calviño Tavares, Francisco, Casanovas Hoste, Adrià, Cortés Rossell, Guillem Pere, Tarifeño Saldivia, Ariel Esteban, Universitat Politècnica de Catalunya. Departament de Física, Universitat Politècnica de Catalunya. ANT - Advanced Nuclear Technologies Research Group, Wright, Tobias, Smith, Alastair, Sosnin, Nikolay Viktorovich, Bennett, Sam, Davies, Paul John, Popescu, Alexandra, Ryan, Joanne, Sekhar, Adhitya, Warren, Saskia, Aberle, Oliver, Amaducci, Simone, Andrzejewski, Józef, Calviño Tavares, Francisco, Casanovas Hoste, Adrià, Cortés Rossell, Guillem Pere, and Tarifeño Saldivia, Ariel Esteban

Abstract

The average energy and multiplicity of prompt y -rays from slow neutron-induced fission of 235 U have been measured using the STEFF spectrometer at the neutron time-of-flight facility n_TOF. The individual responses from 11 NaI scintillators were corrected for multiple y -ray interactions, prompt fission neutrons and background counts before being deconvolved to estimate the emitted spectrum of prompt fission y -rays. The results give an average y -ray energy ¯Ey of 1.71(5) MeV and multiplicity ¯vy of 2.66(18) considering y -rays emitted within the energy range 0.8–6.8 MeV. The n_TOF data has a slightly larger ¯Ey and smaller ¯vy than other recent measurements, however the product of the two is in agreement within quoted uncertainties., This work was supported by the UK Nuclear Data Network, the BEIS Advanced Fuel Cycle programme, the SANDA Nuclear Data Euratom Project, and the funding agencies of the participating institutes., Article signat per 124 autors/es: T. Wright, A.G.Smith, N. V. Sosnin, S. A. Bennett, P.J.Davies, A. V. Popescu, J. A. Ryan, A. Sekhar, S. Warren, O. Aberle, S. Amaducci, J. Andrzejewski, L. Audouin, M. Bacak, J. Balibrea, M. Barbagallo, F.Becvár, E. Berthoumieux, J. Billowes, D. Bosnar, A.Brown, M. Caamaño, F. Calviño, M. Calviani, D. Cano-Ott, R. Cardella, A. Casanovas, F. Cerutti, Y. H. Chen, E. Chiaveri, N. Colonna, G. Cortés, M. A. Cortés-Giraldo, L. Cosentino, L. A. Damone, M. Diakaki, C. Domingo-Pardo, R. Dressler, E. Dupont, I. Durán, B. Fernández-Domínguez, A. Ferrari, P. Ferreira, P. Finocchiaro, V. Furman, K. Göbel, A. R. García, A. Gawlik-Ramie ̨ga, S. Gilardoni, T. Glodariu, I. F. Gonçalves, E. González-Romero, E. Griesmayer, C. Guerrero, F. Gunsing, H. Harada, S. Heinitz, J. Heyse, D. G. Jenkins, E. Jericha, F. Käppeler, Y. Kadi, A. Kalamara, P. Kavrigin, A. Kimura, N.Kivel, M. Kokkoris, M.Krtiˇcka, D. Kurtulgil, E. Leal-Cidoncha, C. Lederer-Woods, H. Leeb, J. Lerendegui-Marco, S.LoMeo, S. J. Lonsdale, D. Macina, A. Manna, J. Marganiec, T. Martínez, A.Masi, C. Massimi, P. Mastinu, M. Mastromarco, E. A. Maugeri, A. Mazzone, E. Mendoza, A. Mengoni, P. M. Milazzo, F. Mingrone, A. Musumarra, A. Negret, R.Nolte, A. Oprea, N. Patronis, A. Pavlik, J. Perkowski, I. Porras, J. Praena, J. M. Quesada, D. Radeck, T. Rauscher, R. Reifarth, C. Rubbia, M. Sabaté-Gilarte, A. Saxena, P. Schillebeeckx, D. Schumann, P. Sedyshev, A. Stamatopoulos, G. Tagliente, J.L.Tain, A. Tarifeño-Saldivia, L. Tassan-Got, S. Valenta, G. Vannini, V. Variale, P.Vaz, A. Ventura, V. Vlachoudis, R.Vlastou, A. Wallner, C. Weiss, P. J. Woods, P. Žugec., Postprint (published version)

Published
2024

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