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https://www.readbyqxmd.com/read/28733386/mir-99-regulates-normal-and-malignant-hematopoietic-stem-cell-self-renewal
#1
Mona Khalaj, Carolien M Woolthuis, Wenhuo Hu, Benjamin H Durham, S Haihua Chu, Sarah Qamar, Scott A Armstrong, Christopher Y Park
The microRNA-99 (miR-99) family comprises a group of broadly conserved microRNAs that are highly expressed in hematopoietic stem cells (HSCs) and acute myeloid leukemia stem cells (LSCs) compared with their differentiated progeny. Herein, we show that miR-99 regulates self-renewal in both HSCs and LSCs. miR-99 maintains HSC long-term reconstitution activity by inhibiting differentiation and cell cycle entry. Moreover, miR-99 inhibition induced LSC differentiation and depletion in an MLL-AF9-driven mouse model of AML, leading to reduction in leukemia-initiating activity and improved survival in secondary transplants...
July 21, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28732206/a-utx-mll4-p300-transcriptional-regulatory-network-coordinately-shapes-active-enhancer-landscapes-for-eliciting-transcription
#2
Shu-Ping Wang, Zhanyun Tang, Chun-Wei Chen, Miho Shimada, Richard P Koche, Lan-Hsin Wang, Tomoyoshi Nakadai, Alan Chramiec, Andrei V Krivtsov, Scott A Armstrong, Robert G Roeder
Enhancer activation is a critical step for gene activation. Here we report an epigenetic crosstalk at enhancers between the UTX (H3K27 demethylase)-MLL4 (H3K4 methyltransferase) complex and the histone acetyltransferase p300. We demonstrate that UTX, in a demethylase activity-independent manner, facilitates conversion of inactive enhancers in embryonic stem cells to an active (H3K4me1(+)/H3K27ac(+)) state by recruiting and coupling the enzymatic functions of MLL4 and p300. Loss of UTX leads to attenuated enhancer activity, characterized by reduced levels of H3K4me1 and H3K27ac as well as impaired transcription...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28724990/large-meta-analysis-of-genome-wide-association-studies-identifies-five-loci-for-lean-body-mass
#3
M Carola Zillikens, Serkalem Demissie, Yi-Hsiang Hsu, Laura M Yerges-Armstrong, Wen-Chi Chou, Lisette Stolk, Gregory Livshits, Linda Broer, Toby Johnson, Daniel L Koller, Zoltán Kutalik, Jian'an Luan, Ida Malkin, Janina S Ried, Albert V Smith, Gudmar Thorleifsson, Liesbeth Vandenput, Jing Hua Zhao, Weihua Zhang, Ali Aghdassi, Kristina Åkesson, Najaf Amin, Leslie J Baier, Inês Barroso, David A Bennett, Lars Bertram, Rainer Biffar, Murielle Bochud, Michael Boehnke, Ingrid B Borecki, Aron S Buchman, Liisa Byberg, Harry Campbell, Natalia Campos Obanda, Jane A Cauley, Peggy M Cawthon, Henna Cederberg, Zhao Chen, Nam H Cho, Hyung Jin Choi, Melina Claussnitzer, Francis Collins, Steven R Cummings, Philip L De Jager, Ilja Demuth, Rosalie A M Dhonukshe-Rutten, Luda Diatchenko, Gudny Eiriksdottir, Anke W Enneman, Mike Erdos, Johan G Eriksson, Joel Eriksson, Karol Estrada, Daniel S Evans, Mary F Feitosa, Mao Fu, Melissa Garcia, Christian Gieger, Thomas Girke, Nicole L Glazer, Harald Grallert, Jagvir Grewal, Bok-Ghee Han, Robert L Hanson, Caroline Hayward, Albert Hofman, Eric P Hoffman, Georg Homuth, Wen-Chi Hsueh, Monica J Hubal, Alan Hubbard, Kim M Huffman, Lise B Husted, Thomas Illig, Erik Ingelsson, Till Ittermann, John-Olov Jansson, Joanne M Jordan, Antti Jula, Magnus Karlsson, Kay-Tee Khaw, Tuomas O Kilpeläinen, Norman Klopp, Jacqueline S L Kloth, Heikki A Koistinen, William E Kraus, Stephen Kritchevsky, Teemu Kuulasmaa, Johanna Kuusisto, Markku Laakso, Jari Lahti, Thomas Lang, Bente L Langdahl, Lenore J Launer, Jong-Young Lee, Markus M Lerch, Joshua R Lewis, Lars Lind, Cecilia Lindgren, Yongmei Liu, Tian Liu, Youfang Liu, Östen Ljunggren, Mattias Lorentzon, Robert N Luben, William Maixner, Fiona E McGuigan, Carolina Medina-Gomez, Thomas Meitinger, Håkan Melhus, Dan Mellström, Simon Melov, Karl Michaëlsson, Braxton D Mitchell, Andrew P Morris, Leif Mosekilde, Anne Newman, Carrie M Nielson, Jeffrey R O'Connell, Ben A Oostra, Eric S Orwoll, Aarno Palotie, Stephan Parker, Munro Peacock, Markus Perola, Annette Peters, Ozren Polasek, Richard L Prince, Katri Räikkönen, Stuart H Ralston, Samuli Ripatti, John A Robbins, Jerome I Rotter, Igor Rudan, Veikko Salomaa, Suzanne Satterfield, Eric E Schadt, Sabine Schipf, Laura Scott, Joban Sehmi, Jian Shen, Chan Soo Shin, Gunnar Sigurdsson, Shad Smith, Nicole Soranzo, Alena Stančáková, Elisabeth Steinhagen-Thiessen, Elizabeth A Streeten, Unnur Styrkarsdottir, Karin M A Swart, Sian-Tsung Tan, Mark A Tarnopolsky, Patricia Thompson, Cynthia A Thomson, Unnur Thorsteinsdottir, Emmi Tikkanen, Gregory J Tranah, Jaakko Tuomilehto, Natasja M van Schoor, Arjun Verma, Peter Vollenweider, Henry Völzke, Jean Wactawski-Wende, Mark Walker, Michael N Weedon, Ryan Welch, H-Erich Wichman, Elisabeth Widen, Frances M K Williams, James F Wilson, Nicole C Wright, Weijia Xie, Lei Yu, Yanhua Zhou, John C Chambers, Angela Döring, Cornelia M van Duijn, Michael J Econs, Vilmundur Gudnason, Jaspal S Kooner, Bruce M Psaty, Timothy D Spector, Kari Stefansson, Fernando Rivadeneira, André G Uitterlinden, Nicholas J Wareham, Vicky Ossowski, Dawn Waterworth, Ruth J F Loos, David Karasik, Tamara B Harris, Claes Ohlsson, Douglas P Kiel
Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10(-8)) or suggestively genome wide (p < 2...
July 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28568650/robotic-proctectomy-for-rectal-cancer-analysis-of-71-patients-from-a-single-institution
#4
Philip M Spanheimer, John G Armstrong, Sunyang Fu, Junlin Liao, Scott E Regenbogen, John C Byrn
BACKGROUND: Despite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons. METHODS: A retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014. RESULTS: 46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184-275) and mean blood loss 164...
June 1, 2017: International Journal of Medical Robotics + Computer Assisted Surgery: MRCAS
https://www.readbyqxmd.com/read/28528542/performance-of-a-high-pressure-liquid-chromatography-ion-mobility-mass-spectrometry-system-for-metabolic-profiling
#5
Xing Zhang, Kimberly Kew, Richard Reisdorph, Mark Sartain, Roger Powell, Michael Armstrong, Kevin Quinn, Charmion Cruickshank-Quinn, Scott Walmsley, Samantha Bokatzian, Ed Darland, Matthew Rain, Ken Imatani, Nichole Reisdorph
A commercial liquid chromatography/drift tube ion mobility-mass spectrometer (LC/IM-MS) was evaluated for its utility in global metabolomics analysis. Performance was assessed using 12 targeted metabolite standards where the limit of detection (LOD), linear dynamic range, resolving power, and collision cross section (Ω) are reported for each standard. Data were collected in three different instrument operation modes: flow injection analysis with IM-MS (FIA/IM-MS), LC/MS, and LC/IM-MS. Metabolomics analyses of human plasma and HaCaT cells were used to compare the above three operation modes...
June 2, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28504702/pgbd5-promotes-site-specific-oncogenic-mutations-in-human-tumors
#6
Anton G Henssen, Richard Koche, Jiali Zhuang, Eileen Jiang, Casie Reed, Amy Eisenberg, Eric Still, Ian C MacArthur, Elias Rodríguez-Fos, Santiago Gonzalez, Montserrat Puiggròs, Andrew N Blackford, Christopher E Mason, Elisa de Stanchina, Mithat Gönen, Anne-Katrin Emde, Minita Shah, Kanika Arora, Catherine Reeves, Nicholas D Socci, Elizabeth Perlman, Cristina R Antonescu, Charles W M Roberts, Hanno Steen, Elizabeth Mullen, Stephen P Jackson, David Torrents, Zhiping Weng, Scott A Armstrong, Alex Kentsis
Genomic rearrangements are a hallmark of human cancers. Here, we identify the piggyBac transposable element derived 5 (PGBD5) gene as encoding an active DNA transposase expressed in the majority of childhood solid tumors, including lethal rhabdoid tumors. Using assembly-based whole-genome DNA sequencing, we found previously undefined genomic rearrangements in human rhabdoid tumors. These rearrangements involved PGBD5-specific signal (PSS) sequences at their breakpoints and recurrently inactivated tumor-suppressor genes...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28440674/late-talkers-and-later-language-outcomes-predicting-the-different-language-trajectories
#7
Rebecca Armstrong, James G Scott, Andrew J O Whitehouse, David A Copland, Katie L Mcmahon, Wendy Arnott
PURPOSE: The aim of the current study was to investigate the risk factors present at 2 years for children who showed language difficulties that persisted from 2 to 10 years and difficulties that emerged later, at 10 years. METHOD: Participants (n = 783) were drawn from the Raine Study in Western Australia. Patterns of change from 2 to 10 years were identified based on child performance on the Language Development Survey and the Clinical Evaluation of Language Fundamentals, respectively...
April 25, 2017: International Journal of Speech-language Pathology
https://www.readbyqxmd.com/read/28436985/functional-screen-of-msi2-interactors-identifies-an-essential-role-for-syncrip-in-myeloid-leukemia-stem-cells
#8
Ly P Vu, Camila Prieto, Elianna M Amin, Sagar Chhangawala, Andrei Krivtsov, M Nieves Calvo-Vidal, Timothy Chou, Arthur Chow, Gerard Minuesa, Sun Mi Park, Trevor S Barlowe, James Taggart, Patrick Tivnan, Raquel P Deering, Lisa P Chu, Jeong-Ah Kwon, Cem Meydan, Javier Perales-Paton, Arora Arshi, Mithat Gönen, Christopher Famulare, Minal Patel, Elisabeth Paietta, Martin S Tallman, Yuheng Lu, Jacob Glass, Francine E Garret-Bakelman, Ari Melnick, Ross Levine, Fatima Al-Shahrour, Marcus Järås, Nir Hacohen, Alexia Hwang, Ralph Garippa, Christopher J Lengner, Scott A Armstrong, Leandro Cerchietti, Glenn S Cowley, David Root, John Doench, Christina Leslie, Benjamin L Ebert, Michael G Kharas
The identity of the RNA-binding proteins (RBPs) that govern cancer stem cells remains poorly characterized. The MSI2 RBP is a central regulator of translation of cancer stem cell programs. Through proteomic analysis of the MSI2-interacting RBP network and functional shRNA screening, we identified 24 genes required for in vivo leukemia. Syncrip was the most differentially required gene between normal and myeloid leukemia cells. SYNCRIP depletion increased apoptosis and differentiation while delaying leukemogenesis...
June 2017: Nature Genetics
https://www.readbyqxmd.com/read/28418626/degradation-of-the-baf-complex-factor-brd9-by-heterobifunctional-ligands
#9
David Remillard, Dennis L Buckley, Joshiawa Paulk, Gerard L Brien, Matthew Sonnett, Hyuk-Soo Seo, Shiva Dastjerdi, Martin Wühr, Sirano Dhe-Paganon, Scott A Armstrong, James E Bradner
The bromodomain-containing protein BRD9, a subunit of the human BAF (SWI/SNF) nucleosome remodeling complex, has emerged as an attractive therapeutic target in cancer. Despite the development of chemical probes targeting the BRD9 bromodomain, there is a limited understanding of BRD9 function beyond acetyl-lysine recognition. We have therefore created the first BRD9-directed chemical degraders, through iterative design and testing of heterobifunctional ligands that bridge the BRD9 bromodomain and the cereblon E3 ubiquitin ligase complex...
May 15, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28355185/myeloid-progenitor-cluster-formation-drives-emergency-and-leukaemic-myelopoiesis
#10
Aurélie Hérault, Mikhail Binnewies, Stephanie Leong, Fernando J Calero-Nieto, Si Yi Zhang, Yoon-A Kang, Xiaonan Wang, Eric M Pietras, S Haihua Chu, Keegan Barry-Holson, Scott Armstrong, Berthold Göttgens, Emmanuelle Passegué
Although many aspects of blood production are well understood, the spatial organization of myeloid differentiation in the bone marrow remains unknown. Here we use imaging to track granulocyte/macrophage progenitor (GMP) behaviour in mice during emergency and leukaemic myelopoiesis. In the steady state, we find individual GMPs scattered throughout the bone marrow. During regeneration, we observe expanding GMP patches forming defined GMP clusters, which, in turn, locally differentiate into granulocytes. The timed release of important bone marrow niche signals (SCF, IL-1β, G-CSF, TGFβ and CXCL4) and activation of an inducible Irf8 and β-catenin progenitor self-renewal network control the transient formation of regenerating GMP clusters...
April 6, 2017: Nature
https://www.readbyqxmd.com/read/28351866/shh-promotes-direct-interactions-between-epidermal-cells-and-osteoblast-progenitors-to-shape-regenerated-zebrafish-bone
#11
Benjamin E Armstrong, Astra Henner, Scott Stewart, Kryn Stankunas
Zebrafish innately regenerate amputated fins by mechanisms that expand and precisely position injury-induced progenitor cells to re-form tissue of the original size and pattern. For example, cell signaling networks direct osteoblast progenitors (pObs) to rebuild thin cylindrical bony rays with a stereotypical branched morphology. Hedgehog/Smoothened (Hh/Smo) signaling has been variably proposed to stimulate overall fin regenerative outgrowth or promote ray branching. Using a photoconvertible patched2 reporter, we resolve active Hh/Smo output to a narrow distal regenerate zone comprising pObs and adjacent motile basal epidermal cells...
April 1, 2017: Development
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#12
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28302555/development-of-bioinformatics-infrastructure-for-genomics-research-in-h3africa
#13
Nicola J Mulder, Ezekiel Adebiyi, Marion Adebiyi, Seun Adeyemi, Azza Ahmed, Rehab Ahmed, Bola Akanle, Mohamed Alibi, Don L Armstrong, Shaun Aron, Efejiro Ashano, Shakuntala Baichoo, Alia Benkahla, David K Brown, Emile R Chimusa, Faisal M Fadlelmola, Dare Falola, Segun Fatumo, Kais Ghedira, Amel Ghouila, Scott Hazelhurst, Itunuoluwa Isewon, Segun Jung, Samar Kamal Kassim, Jonathan K Kayondo, Mamana Mbiyavanga, Ayton Meintjes, Somia Mohammed, Abayomi Mosaku, Ahmed Moussa, Mustafa Muhammd, Zahra Mungloo-Dilmohamud, Oyekanmi Nashiru, Trust Odia, Adaobi Okafor, Olaleye Oladipo, Victor Osamor, Jellili Oyelade, Khalid Sadki, Samson Pandam Salifu, Jumoke Soyemi, Sumir Panji, Fouzia Radouani, Oussama Souiai, Özlem Tastan Bishop
BACKGROUND: Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community...
March 13, 2017: Global Heart
https://www.readbyqxmd.com/read/28300853/the-international-dermatology-outcome-measures-ideom-initiative-a-review-and-update
#14
Scott A Elman, Joseph F Merola, April W Armstrong, Kristina Callis Duffin, John Latella, Amit Garg, Alice B Gottlieb
<p>The International Dermatology Outcome Measures (IDEOM) group, comprising patients, physicians, health economists, industry partners, payers, and regulatory agencies, was established to develop unified and validated patient-centered outcome measures in dermatology in response to increasing demand to quantify effectiveness of treatments and performance outcomes among providers. IDEOM has chosen to start with psoriasis outcome measures, and then apply its methodology to other dermatologic diseases. In this paper, we review the background and progress to date of IDEOM, including an update of IDEOM activities as of our 2016 meeting in Washington DC, USA...
February 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28292935/selective-killing-of-smarca2-and-smarca4-deficient-small-cell-carcinoma-of-the-ovary-hypercalcemic-type-cells-by-inhibition-of-ezh2-in-vitro-and-in-vivo-preclinical-models
#15
Elayne Chan-Penebre, Kelli Armstrong, Allison Drew, Alexandra R Grassian, Igor Feldman, Sarah K Knutson, Kristy Kuplast-Barr, Maria Roche, John Campbell, Peter Ho, Robert A Copeland, Richard Chesworth, Jesse J Smith, Heike Keilhack, Scott A Ribich
The SWI/SNF complex is a major regulator of gene expression and is increasingly thought to play an important role in human cancer, as evidenced by the high frequency of subunit mutations across virtually all cancer types. We previously reported that in preclinical models, malignant rhabdoid tumors, which are deficient in the SWI/SNF core component INI1 (SMARCB1), are selectively killed by inhibitors of the H3K27 histone methyltransferase EZH2. Given the demonstrated antagonistic activities of the SWI/SNF complex and the EZH2-containing PRC2 complex, we investigated whether additional cancers with SWI/SNF mutations are sensitive to selective EZH2 inhibition...
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28292175/determining-band-edge-energies-and-morphology-dependent-stability-of-formamidinium-lead-perovskite-films-using-spectroelectrochemistry-and-photoelectron-spectroscopy
#16
R Clayton Shallcross, Yilong Zheng, S Scott Saavedra, Neal R Armstrong
We show for the first time that the frontier orbital energetics (conduction band minimum (CBM) and valence band maximum (VBM)) of device-relevant, methylammonium bromide (MABr)-doped, formamidinium lead trihalide perovskite (FA-PVSK) thin films can be characterized using UV-vis spectroelectrochemistry, which provides an additional and straightforward experimental technique for determining energy band values relative to more traditional methods based on photoelectron spectroscopy. FA-PVSK films are processed via a two-step deposition process, known to provide high efficiency solar cells, on semitransparent indium tin oxide (ITO) and titanium dioxide (TiO2) electrodes...
March 24, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28264936/deletion-of-ribosomal-protein-genes-is-a-common-vulnerability-in-human-cancer-especially-in-concert-with-tp53-mutations
#17
Ram Ajore, David Raiser, Marie McConkey, Magnus Jöud, Bernd Boidol, Brenton Mar, Gordon Saksena, David M Weinstock, Scott Armstrong, Steven R Ellis, Benjamin L Ebert, Björn Nilsson
Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10(-10)), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells...
April 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28242784/mixed-lineage-leukemia-fusions-and-chromatin-in-leukemia
#18
Andrei V Krivtsov, Takayuki Hoshii, Scott A Armstrong
Recent studies have shown the importance of chromatin-modifying complexes in the maintenance of developmental gene expression and human disease. The mixed lineage leukemia gene (MLL1) encodes a chromatin-modifying protein and was discovered as a result of the cloning of translocations involved in human leukemias. MLL1 is a histone lysine 4 (H3K4) methyltransferase that supports transcription of genes that are important for normal development including homeotic (Hox) genes. MLL1 rearrangements result in expression of fusion proteins without H3K4 methylation activity but may gain the ability to recruit other chromatin-associated complexes such as the H3K79 methyltransferase DOT1L and the super elongation complex...
February 27, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28241208/association-between-telomere-length-and-risk-of-cancer-and-non-neoplastic-diseases-a-mendelian-randomization-study
#19
Philip C Haycock, Stephen Burgess, Aayah Nounu, Jie Zheng, George N Okoli, Jack Bowden, Kaitlin Hazel Wade, Nicholas J Timpson, David M Evans, Peter Willeit, Abraham Aviv, Tom R Gaunt, Gibran Hemani, Massimo Mangino, Hayley Patricia Ellis, Kathreena M Kurian, Karen A Pooley, Rosalind A Eeles, Jeffrey E Lee, Shenying Fang, Wei V Chen, Matthew H Law, Lisa M Bowdler, Mark M Iles, Qiong Yang, Bradford B Worrall, Hugh Stephen Markus, Rayjean J Hung, Chris I Amos, Amanda B Spurdle, Deborah J Thompson, Tracy A O'Mara, Brian Wolpin, Laufey Amundadottir, Rachael Stolzenberg-Solomon, Antonia Trichopoulou, N Charlotte Onland-Moret, Eiliv Lund, Eric J Duell, Federico Canzian, Gianluca Severi, Kim Overvad, Marc J Gunter, Rosario Tumino, Ulrika Svenson, Andre van Rij, Annette F Baas, Matthew J Bown, Nilesh J Samani, Femke N G van t'Hof, Gerard Tromp, Gregory T Jones, Helena Kuivaniemi, James R Elmore, Mattias Johansson, James Mckay, Ghislaine Scelo, Robert Carreras-Torres, Valerie Gaborieau, Paul Brennan, Paige M Bracci, Rachel E Neale, Sara H Olson, Steven Gallinger, Donghui Li, Gloria M Petersen, Harvey A Risch, Alison P Klein, Jiali Han, Christian C Abnet, Neal D Freedman, Philip R Taylor, John M Maris, Katja K Aben, Lambertus A Kiemeney, Sita H Vermeulen, John K Wiencke, Kyle M Walsh, Margaret Wrensch, Terri Rice, Clare Turnbull, Kevin Litchfield, Lavinia Paternoster, Marie Standl, Gonçalo R Abecasis, John Paul SanGiovanni, Yong Li, Vladan Mijatovic, Yadav Sapkota, Siew-Kee Low, Krina T Zondervan, Grant W Montgomery, Dale R Nyholt, David A van Heel, Karen Hunt, Dan E Arking, Foram N Ashar, Nona Sotoodehnia, Daniel Woo, Jonathan Rosand, Mary E Comeau, W Mark Brown, Edwin K Silverman, John E Hokanson, Michael H Cho, Jennie Hui, Manuel A Ferreira, Philip J Thompson, Alanna C Morrison, Janine F Felix, Nicholas L Smith, Angela M Christiano, Lynn Petukhova, Regina C Betz, Xing Fan, Xuejun Zhang, Caihong Zhu, Carl D Langefeld, Susan D Thompson, Feijie Wang, Xu Lin, David A Schwartz, Tasha Fingerlin, Jerome I Rotter, Mary Frances Cotch, Richard A Jensen, Matthias Munz, Henrik Dommisch, Arne S Schaefer, Fang Han, Hanna M Ollila, Ryan P Hillary, Omar Albagha, Stuart H Ralston, Chenjie Zeng, Wei Zheng, Xiao-Ou Shu, Andre Reis, Steffen Uebe, Ulrike Hüffmeier, Yoshiya Kawamura, Takeshi Otowa, Tsukasa Sasaki, Martin Lloyd Hibberd, Sonia Davila, Gang Xie, Katherine Siminovitch, Jin-Xin Bei, Yi-Xin Zeng, Asta Försti, Bowang Chen, Stefano Landi, Andre Franke, Annegret Fischer, David Ellinghaus, Carlos Flores, Imre Noth, Shwu-Fan Ma, Jia Nee Foo, Jianjun Liu, Jong-Won Kim, David G Cox, Olivier Delattre, Olivier Mirabeau, Christine F Skibola, Clara S Tang, Merce Garcia-Barcelo, Kai-Ping Chang, Wen-Hui Su, Yu-Sun Chang, Nicholas G Martin, Scott Gordon, Tracey D Wade, Chaeyoung Lee, Michiaki Kubo, Pei-Chieng Cha, Yusuke Nakamura, Daniel Levy, Masayuki Kimura, Shih-Jen Hwang, Steven Hunt, Tim Spector, Nicole Soranzo, Ani W Manichaikul, R Graham Barr, Bratati Kahali, Elizabeth Speliotes, Laura M Yerges-Armstrong, Ching-Yu Cheng, Jost B Jonas, Tien Yin Wong, Isabella Fogh, Kuang Lin, John F Powell, Kenneth Rice, Caroline L Relton, Richard M Martin, George Davey Smith
Importance: The causal direction and magnitude of the association between telomere length and incidence of cancer and non-neoplastic diseases is uncertain owing to the susceptibility of observational studies to confounding and reverse causation. Objective: To conduct a Mendelian randomization study, using germline genetic variants as instrumental variables, to appraise the causal relevance of telomere length for risk of cancer and non-neoplastic diseases. Data Sources: Genomewide association studies (GWAS) published up to January 15, 2015...
May 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28241141/enl-links-histone-acetylation-to-oncogenic-gene-expression-in-acute-myeloid-leukaemia
#20
Liling Wan, Hong Wen, Yuanyuan Li, Jie Lyu, Yuanxin Xi, Takayuki Hoshii, Julia K Joseph, Xiaolu Wang, Yong-Hwee E Loh, Michael A Erb, Amanda L Souza, James E Bradner, Li Shen, Wei Li, Haitao Li, C David Allis, Scott A Armstrong, Xiaobing Shi
Cancer cells are characterized by aberrant epigenetic landscapes and often exploit chromatin machinery to activate oncogenic gene expression programs. Recognition of modified histones by 'reader' proteins constitutes a key mechanism underlying these processes; therefore, targeting such pathways holds clinical promise, as exemplified by the development of bromodomain and extra-terminal (BET) inhibitors. We recently identified the YEATS domain as an acetyl-lysine-binding module, but its functional importance in human cancer remains unknown...
March 9, 2017: Nature
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