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Blakemore S J

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https://www.readbyqxmd.com/read/29144972/building-bridges-through-science
#1
Thomas Lissek, Michelle Adams, John Adelman, Ehud Ahissar, Mohammed Akaaboune, Huda Akil, Mustafa al'Absi, Fazal Arain, Juan Carlos Arango-Lasprilla, Deniz Atasoy, Jesus Avila, Ashraf Badawi, Hilmar Bading, Abdul Mannan Baig, Jimena Baleriola, Carlos Belmonte, Ilaria Bertocchi, Heinrich Betz, Colin Blakemore, Olaf Blanke, Philipp Boehm-Sturm, Tobias Bonhoeffer, Paolo Bonifazi, Nils Brose, Patrizia Campolongo, Tansu Celikel, Cathy C Chang, Ta-Yuan Chang, Ami Citri, Hollis T Cline, Jesus M Cortes, Kathleen Cullen, Kellie Dean, José M Delgado-Garcia, Mathieu Desroches, John F Disterhoft, John E Dowling, Andreas Draguhn, Sherif F El-Khamisy, Abdeljabbar El Manira, S Ather Enam, Juan M Encinas, Asier Erramuzpe, José A Esteban, Isabel Fariñas, Edmond Fischer, Izumi Fukunaga, Iñigo Gabilondo, Detlev Ganten, Albert Gidon, Juan Carlos Gomez-Esteban, Paul Greengard, Valery Grinevich, Agnés Gruart, Roger Guillemin, Ahmad R Hariri, Bassem Hassan, Michael Häusser, Yasunori Hayashi, Natasha K Hussain, Adnan Abdul Jabbar, Mohamed Jaber, Reinhardt Jahn, Essam Mohammed Janahi, Mohamed Kabbaj, Helmut Kettenmann, Merel Kindt, Shira Knafo, Georg Köhr, Shoji Komai, Harm Krugers, Bernd Kuhn, Nouria Lakhdar Ghazal, Matthew E Larkum, Mickey London, Beat Lutz, Carlos Matute, Luis Martinez-Millan, Mouna Maroun, James McGaugh, Ahmed A Moustafa, Anwar Nasim, Klaus-Armin Nave, Erwin Neher, Karoly Nikolich, Tiago Outeiro, Lucy M Palmer, Olga Penagarikano, Isabel Perez-Otano, Donald W Pfaff, Bruno Poucet, Atta-Ur Rahman, Pedro Ramos-Cabrer, Ali Rashidy-Pour, Richard J Roberts, Serafim Rodrigues, Joshua R Sanes, Andreas T Schaefer, Menahem Segal, Idan Segev, Saad Shafqat, Nikhat Ahmed Siddiqui, Hermona Soreq, Eduardo Soriano-García, Rainer Spanagel, Rolf Sprengel, Greg Stuart, Thomas C Südhof, Jan Tønnesen, Mario Treviño, Basim M Uthman, J Craig Venter, Alexei Verkhratsky, Craig Weiss, Torsten N Wiesel, Emre Yaksi, Ofer Yizhar, Larry J Young, Paul Young, Nasser H Zawia, José L Zugaza, Mazahir T Hasan
Science is ideally suited to connect people from different cultures and thereby foster mutual understanding. To promote international life science collaboration, we have launched "The Science Bridge" initiative. Our current project focuses on partnership between Western and Middle Eastern neuroscience communities.
November 15, 2017: Neuron
https://www.readbyqxmd.com/read/29030403/new-blood-pressure-associated-loci-identified-in-meta-analyses-of-475%C3%A2-000-individuals
#2
Aldi T Kraja, James P Cook, Helen R Warren, Praveen Surendran, Chunyu Liu, Evangelos Evangelou, Alisa K Manning, Niels Grarup, Fotios Drenos, Xueling Sim, Albert Vernon Smith, Najaf Amin, Alexandra I F Blakemore, Jette Bork-Jensen, Ivan Brandslund, Aliki-Eleni Farmaki, Cristiano Fava, Teresa Ferreira, Karl-Heinz Herzig, Ayush Giri, Franco Giulianini, Megan L Grove, Xiuqing Guo, Sarah E Harris, Christian T Have, Aki S Havulinna, He Zhang, Marit E Jørgensen, AnneMari Käräjämäki, Charles Kooperberg, Allan Linneberg, Louis Little, Yongmei Liu, Lori L Bonnycastle, Yingchang Lu, Reedik Mägi, Anubha Mahajan, Giovanni Malerba, Riccardo E Marioni, Hao Mei, Cristina Menni, Alanna C Morrison, Sandosh Padmanabhan, Walter Palmas, Alaitz Poveda, Rainer Rauramaa, Nigel William Rayner, Muhammad Riaz, Ken Rice, Melissa A Richard, Jennifer A Smith, Lorraine Southam, Alena Stančáková, Kathleen E Stirrups, Vinicius Tragante, Tiinamaija Tuomi, Ioanna Tzoulaki, Tibor V Varga, Stefan Weiss, Andrianos M Yiorkas, Robin Young, Weihua Zhang, Michael R Barnes, Claudia P Cabrera, He Gao, Michael Boehnke, Eric Boerwinkle, John C Chambers, John M Connell, Cramer K Christensen, Rudolf A de Boer, Ian J Deary, George Dedoussis, Panos Deloukas, Anna F Dominiczak, Marcus Dörr, Roby Joehanes, Todd L Edwards, Tõnu Esko, Myriam Fornage, Nora Franceschini, Paul W Franks, Giovanni Gambaro, Leif Groop, Göran Hallmans, Torben Hansen, Caroline Hayward, Oksa Heikki, Erik Ingelsson, Jaakko Tuomilehto, Marjo-Riitta Jarvelin, Sharon L R Kardia, Fredrik Karpe, Jaspal S Kooner, Timo A Lakka, Claudia Langenberg, Lars Lind, Ruth J F Loos, Markku Laakso, Mark I McCarthy, Olle Melander, Karen L Mohlke, Andrew P Morris, Colin N A Palmer, Oluf Pedersen, Ozren Polasek, Neil R Poulter, Michael A Province, Bruce M Psaty, Paul M Ridker, Jerome I Rotter, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Peter J Sever, Tea Skaaby, Jeanette M Stafford, John M Starr, Pim van der Harst, Peter van der Meer, Cornelia M van Duijn, Anne-Claire Vergnaud, Vilmundur Gudnason, Nicholas J Wareham, James G Wilson, Cristen J Willer, Daniel R Witte, Eleftheria Zeggini, Danish Saleheen, Adam S Butterworth, John Danesh, Folkert W Asselbergs, Louise V Wain, Georg B Ehret, Daniel I Chasman, Mark J Caulfield, Paul Elliott, Cecilia M Lindgren, Daniel Levy, Christopher Newton-Cheh, Patricia B Munroe, Joanna M M Howson
BACKGROUND: Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association. METHODS AND RESULTS: Here, we augment the sample with 140 886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure...
October 2017: Circulation. Cardiovascular Genetics
https://www.readbyqxmd.com/read/29029933/highly-potent-and-selective-nav1-7-inhibitors-for-use-as-intravenous-agents-and-chemical-probes
#3
R Ian Storer, Andy Pike, Nigel A Swain, Aristos J Alexandrou, Bruce M Bechle, David C Blakemore, Alan D Brown, Neil A Castle, Matthew S Corbett, Neil J Flanagan, David Fengas, M Scott Johnson, Lyn H Jones, Brian E Marron, C Elizabeth Payne, David Printzenhoff, David J Rawson, Colin R Rose, Thomas Ryckmans, Jianmin Sun, Jonathan W Theile, Rubben Torella, Elaine Tseng, Joseph S Warmus
The discovery and selection of a highly potent and selective NaV1.7 inhibitor PF-06456384, designed specifically for intravenous infusion, is disclosed. Extensive in vitro pharmacology and ADME profiling followed by in vivo preclinical PK and efficacy model data are discussed. A proposed protein-ligand binding mode for this compound is also provided to rationalise the high levels of potency and selectivity over inhibition of related sodium channels. To further support the proposed binding mode, potent conjugates are described which illustrate the potential for development of chemical probes to enable further target evaluation...
November 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28894287/prognostic-significance-of-high-gfi1-expression-in-aml-of-normal-karyotype-and-its-association-with-a-flt3-itd-signature
#4
Giacomo Volpe, David S Walton, David E Grainger, Carl Ward, Pierre Cauchy, Daniel Blakemore, Daniel J L Coleman, Peter N Cockerill, Paloma Garcia, Jon Frampton
Growth Factor Independence 1 (GFI1) is a transcriptional repressor that plays a critical role during both myeloid and lymphoid haematopoietic lineage commitment. Several studies have demonstrated the involvement of GFI1 in haematological malignancies and have suggested that low expression of GFI1 is a negative indicator of disease progression for both myelodysplastic syndromes (MDS) and acute myeloid leukaemia (AML). In this study, we have stratified AML patients into those defined as having a normal karyotype (CN-AML)...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28663304/determinants-of-postprandial-plasma-bile-acid-kinetics-in-human-volunteers
#5
RANDOMIZED CONTROLLED TRIAL
Jarlei Fiamoncini, Andrianos M Yiorkas, Kurt Gedrich, Milena Rundle, Sanne I Alsters, Guus Roeselers, Tim J van den Broek, Thomas Clavel, Ilias Lagkouvardos, Suzan Wopereis, Gary Frost, Ben van Ommen, Alexandra I Blakemore, Hannelore Daniel
Bile acids (BA) are signaling molecules with a wide range of biological effects, also identified among the most responsive plasma metabolites in the postprandial state. We here describe this response to different dietary challenges and report on key determinants linked to its interindividual variability. Healthy men and women (n = 72, 62 ± 8 yr, mean ± SE) were enrolled into a 12-wk weight loss intervention. All subjects underwent an oral glucose tolerance test and a mixed-meal tolerance test before and after the intervention...
October 1, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28420965/dopamine-a-modulator-of-circadian-rhythms-in-the-central-nervous-system
#6
REVIEW
Kirill S Korshunov, Laura J Blakemore, Paul Q Trombley
Circadian rhythms are daily rhythms that regulate many biological processes - from gene transcription to behavior - and a disruption of these rhythms can lead to a myriad of health risks. Circadian rhythms are entrained by light, and their 24-h oscillation is maintained by a core molecular feedback loop composed of canonical circadian ("clock") genes and proteins. Different modulators help to maintain the proper rhythmicity of these genes and proteins, and one emerging modulator is dopamine. Dopamine has been shown to have circadian-like activities in the retina, olfactory bulb, striatum, midbrain, and hypothalamus, where it regulates, and is regulated by, clock genes in some of these areas...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27890934/egr2-mutations-define-a-new-clinically-aggressive-subgroup-of-chronic-lymphocytic-leukemia
#7
E Young, D Noerenberg, L Mansouri, V Ljungström, M Frick, L-A Sutton, S J Blakemore, J Galan-Sousa, K Plevova, P Baliakas, D Rossi, R Clifford, D Roos-Weil, V Navrkalova, B Dörken, C A Schmitt, K E Smedby, G Juliusson, B Giacopelli, J S Blachly, C Belessi, P Panagiotidis, N Chiorazzi, F Davi, A W Langerak, D Oscier, A Schuh, G Gaidano, P Ghia, W Xu, L Fan, O A Bernard, F Nguyen-Khac, L Rassenti, J Li, T J Kipps, K Stamatopoulos, S Pospisilova, T Zenz, C C Oakes, J C Strefford, R Rosenquist, F Damm
Recurrent mutations within EGR2 were recently reported in advanced-stage chronic lymphocytic leukemia (CLL) patients and associated with a worse outcome. To study their prognostic impact, 2403 CLL patients were examined for mutations in the EGR2 hotspot region including a screening (n=1283) and two validation cohorts (UK CLL4 trial patients, n=366; CLL Research Consortium (CRC) patients, n=490). Targeted deep-sequencing of 27 known/postulated CLL driver genes was also performed in 38 EGR2-mutated patients to assess concurrent mutations...
July 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27843137/pi3k%C3%AE-inhibition-elicits-anti-leukemic-effects-through-bim-dependent-apoptosis
#8
M J Carter, K L Cox, S J Blakemore, A H Turaj, R J Oldham, L N Dahal, S Tannheimer, F Forconi, G Packham, M S Cragg
PI3Kδ plays pivotal roles in the maintenance, proliferation and survival of malignant B-lymphocytes. Although not curative, PI3Kδ inhibitors (PI3Kδi) demonstrate impressive clinical efficacy and, alongside other signaling inhibitors, are revolutionizing the treatment of hematological malignancies. However, only limited in vivo data are available regarding their mechanism of action. With the rising number of novel treatments, the challenge is to identify combinations that deliver curative regimes. A deeper understanding of the molecular mechanism is required to guide these selections...
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27783255/targeting-the-protein-ubiquitination-machinery-in-melanoma-by-the-nedd8-activating-enzyme-inhibitor-pevonedistat-mln4924
#9
Kit Man Wong, Lindsey N Micel, Heather M Selby, Aik Choon Tan, Todd M Pitts, Stacey M Bagby, Anna Spreafico, Peter J Klauck, Stephen J Blakemore, Peter F Smith, Alice McDonald, Allison Berger, John J Tentler, S Gail Eckhardt
Background The neddylation pathway conjugates NEDD8 to cullin-RING ligases and controls the proteasomal degradation of specific proteins involved in essential cell processes. Pevonedistat (MLN4924) is a selective small molecule targeting the NEDD8-activating enzyme (NAE) and inhibits an early step in neddylation, resulting in DNA re-replication, cell cycle arrest and death. We investigated the anti-tumor potential of pevonedistat in preclinical models of melanoma. Methods Melanoma cell lines and patient-derived tumor xenografts (PDTX) treated with pevonedistat were assessed for viability/apoptosis and tumor growth, respectively, to identify sensitive/resistant models...
February 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/27773930/non-coding-notch1-mutations-in-chronic-lymphocytic-leukemia-their-clinical-impact-in-the-uk-cll4-trial
#10
LETTER
M Larrayoz, M J J Rose-Zerilli, L Kadalayil, H Parker, S Blakemore, J Forster, Z Davis, A J Steele, A Collins, M Else, D Catovsky, D G Oscier, J C Strefford
No abstract text is available yet for this article.
February 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27647477/perception-and-recognition-of-faces-in-adolescence
#11
D Fuhrmann, L J Knoll, A L Sakhardande, M Speekenbrink, K C Kadosh, S-J Blakemore
Most studies on the development of face cognition abilities have focussed on childhood, with early maturation accounts contending that face cognition abilities are mature by 3-5 years. Late maturation accounts, in contrast, propose that some aspects of face cognition are not mature until at least 10 years. Here, we measured face memory and face perception, two core face cognition abilities, in 661 participants (397 females) in four age groups (younger adolescents (11.27-13.38 years); mid-adolescents (13.39-15...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27618447/trans-ancestry-meta-analyses-identify-rare-and-common-variants-associated-with-blood-pressure-and-hypertension
#12
Praveen Surendran, Fotios Drenos, Robin Young, Helen Warren, James P Cook, Alisa K Manning, Niels Grarup, Xueling Sim, Daniel R Barnes, Kate Witkowska, James R Staley, Vinicius Tragante, Taru Tukiainen, Hanieh Yaghootkar, Nicholas Masca, Daniel F Freitag, Teresa Ferreira, Olga Giannakopoulou, Andrew Tinker, Magdalena Harakalova, Evelin Mihailov, Chunyu Liu, Aldi T Kraja, Sune Fallgaard Nielsen, Asif Rasheed, Maria Samuel, Wei Zhao, Lori L Bonnycastle, Anne U Jackson, Narisu Narisu, Amy J Swift, Lorraine Southam, Jonathan Marten, Jeroen R Huyghe, Alena Stančáková, Cristiano Fava, Therese Ohlsson, Angela Matchan, Kathleen E Stirrups, Jette Bork-Jensen, Anette P Gjesing, Jukka Kontto, Markus Perola, Susan Shaw-Hawkins, Aki S Havulinna, He Zhang, Louise A Donnelly, Christopher J Groves, N William Rayner, Matt J Neville, Neil R Robertson, Andrianos M Yiorkas, Karl-Heinz Herzig, Eero Kajantie, Weihua Zhang, Sara M Willems, Lars Lannfelt, Giovanni Malerba, Nicole Soranzo, Elisabetta Trabetti, Niek Verweij, Evangelos Evangelou, Alireza Moayyeri, Anne-Claire Vergnaud, Christopher P Nelson, Alaitz Poveda, Tibor V Varga, Muriel Caslake, Anton Jm de Craen, Stella Trompet, Jian'an Luan, Robert A Scott, Sarah E Harris, David Cm Liewald, Riccardo Marioni, Cristina Menni, Aliki-Eleni Farmaki, Göran Hallmans, Frida Renström, Jennifer E Huffman, Maija Hassinen, Stephen Burgess, Ramachandran S Vasan, Janine F Felix, Maria Uria-Nickelsen, Anders Malarstig, Dermot F Reily, Maarten Hoek, Thomas Vogt, Honghuang Lin, Wolfgang Lieb, Matthew Traylor, Hugh F Markus, Heather M Highland, Anne E Justice, Eirini Marouli, Jaana Lindström, Matti Uusitupa, Pirjo Komulainen, Timo A Lakka, Rainer Rauramaa, Ozren Polasek, Igor Rudan, Olov Rolandsson, Paul W Franks, George Dedoussis, Timothy D Spector, Pekka Jousilahti, Satu Männistö, Ian J Deary, John M Starr, Claudia Langenberg, Nick J Wareham, Morris J Brown, Anna F Dominiczak, John M Connell, J Wouter Jukema, Naveed Sattar, Ian Ford, Chris J Packard, Tõnu Esko, Reedik Mägi, Andres Metspalu, Rudolf A de Boer, Peter van der Meer, Pim van der Harst, Giovanni Gambaro, Erik Ingelsson, Lars Lind, Paul Iw de Bakker, Mattijs E Numans, Ivan Brandslund, Cramer Christensen, Eva Rb Petersen, Eeva Korpi-Hyövälti, Heikki Oksa, John C Chambers, Jaspal S Kooner, Alexandra If Blakemore, Steve Franks, Marjo-Riitta Jarvelin, Lise L Husemoen, Allan Linneberg, Tea Skaaby, Betina Thuesen, Fredrik Karpe, Jaakko Tuomilehto, Alex Sf Doney, Andrew D Morris, Colin Na Palmer, Oddgeir Lingaas Holmen, Kristian Hveem, Cristen J Willer, Tiinamaija Tuomi, Leif Groop, AnneMari Käräjämäki, Aarno Palotie, Samuli Ripatti, Veikko Salomaa, Dewan S Alam, Abdulla Al Shafi Majumder, Emanuele Di Angelantonio, Rajiv Chowdhury, Mark I McCarthy, Neil Poulter, Alice V Stanton, Peter Sever, Philippe Amouyel, Dominique Arveiler, Stefan Blankenberg, Jean Ferrières, Frank Kee, Kari Kuulasmaa, Martina Müller-Nurasyid, Giovanni Veronesi, Jarmo Virtamo, Panos Deloukas, Paul Elliott, Eleftheria Zeggini, Sekar Kathiresan, Olle Melander, Johanna Kuusisto, Markku Laakso, Sandosh Padmanabhan, David Porteous, Caroline Hayward, Generation Scotland, Francis S Collins, Karen L Mohlke, Torben Hansen, Oluf Pedersen, Michael Boehnke, Heather M Stringham, Philippe Frossard, Christopher Newton-Cheh, Martin D Tobin, Børge Grønne Nordestgaard, Mark J Caulfield, Anubha Mahajan, Andrew P Morris, Maciej Tomaszewski, Nilesh J Samani, Danish Saleheen, Folkert W Asselbergs, Cecilia M Lindgren, John Danesh, Louise V Wain, Adam S Butterworth, Joanna Mm Howson, Patricia B Munroe
High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1...
October 2016: Nature Genetics
https://www.readbyqxmd.com/read/27466198/analysis-with-the-exome-array-identifies-multiple-new-independent-variants-in-lipid-loci
#13
Stavroula Kanoni, Nicholas G D Masca, Kathleen E Stirrups, Tibor V Varga, Helen R Warren, Robert A Scott, Lorraine Southam, Weihua Zhang, Hanieh Yaghootkar, Martina Müller-Nurasyid, Alexessander Couto Alves, Rona J Strawbridge, Lazaros Lataniotis, Nikman An Hashim, Céline Besse, Anne Boland, Peter S Braund, John M Connell, Anna Dominiczak, Aliki-Eleni Farmaki, Stephen Franks, Harald Grallert, Jan-Håkan Jansson, Maria Karaleftheri, Sirkka Keinänen-Kiukaanniemi, Angela Matchan, Dorota Pasko, Annette Peters, Neil Poulter, Nigel W Rayner, Frida Renström, Olov Rolandsson, Maria Sabater-Lleal, Bengt Sennblad, Peter Sever, Denis Shields, Angela Silveira, Alice V Stanton, Konstantin Strauch, Maciej Tomaszewski, Emmanouil Tsafantakis, Melanie Waldenberger, Alexandra I F Blakemore, George Dedoussis, Stefan A Escher, Jaspal S Kooner, Mark I McCarthy, Colin N A Palmer, Anders Hamsten, Mark J Caulfield, Timothy M Frayling, Martin D Tobin, Marjo-Riitta Jarvelin, Eleftheria Zeggini, Christian Gieger, John C Chambers, Nick J Wareham, Patricia B Munroe, Paul W Franks, Nilesh J Samani, Panos Deloukas
It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance...
September 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27282254/genomic-disruption-of-the-histone-methyltransferase-setd2-in-chronic-lymphocytic-leukaemia
#14
MULTICENTER STUDY
H Parker, M J J Rose-Zerilli, M Larrayoz, R Clifford, J Edelmann, S Blakemore, J Gibson, J Wang, V Ljungström, T K Wojdacz, T Chaplin, A Roghanian, Z Davis, A Parker, E Tausch, S Ntoufa, S Ramos, P Robbe, R Alsolami, A J Steele, G Packham, A E Rodríguez-Vicente, L Brown, F McNicholl, F Forconi, A Pettitt, P Hillmen, M Dyer, M S Cragg, C Chelala, C C Oakes, R Rosenquist, K Stamatopoulos, S Stilgenbauer, S Knight, A Schuh, D G Oscier, J C Strefford
Histone methyltransferases (HMTs) are important epigenetic regulators of gene transcription and are disrupted at the genomic level in a spectrum of human tumours including haematological malignancies. Using high-resolution single nucleotide polymorphism (SNP) arrays, we identified recurrent deletions of the SETD2 locus in 3% (8/261) of chronic lymphocytic leukaemia (CLL) patients. Further validation in two independent cohorts showed that SETD2 deletions were associated with loss of TP53, genomic complexity and chromothripsis...
November 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26957556/transposon-mutagenesis-reveals-fludarabine-resistance-mechanisms-in-chronic-lymphocytic-leukemia
#15
Tatjana Pandzic, Jimmy Larsson, Liqun He, Snehangshu Kundu, Kenneth Ban, Muhammad Akhtar-Ali, Anders R Hellström, Anna Schuh, Ruth Clifford, Stuart J Blakemore, Jonathan C Strefford, Tycho Baumann, Armando Lopez-Guillermo, Elias Campo, Viktor Ljungström, Larry Mansouri, Richard Rosenquist, Tobias Sjöblom, Mats Hellström
PURPOSE: To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. EXPERIMENTAL DESIGN: We used piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. RESULTS: In total, this screen identified 782 genes with transposon integrations in fludarabine-resistant pools of cells...
December 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26604143/genome-wide-association-analysis-identifies-three-new-susceptibility-loci-for-childhood-body-mass-index
#16
MULTICENTER STUDY
Janine F Felix, Jonathan P Bradfield, Claire Monnereau, Ralf J P van der Valk, Evie Stergiakouli, Alessandra Chesi, Romy Gaillard, Bjarke Feenstra, Elisabeth Thiering, Eskil Kreiner-Møller, Anubha Mahajan, Niina Pitkänen, Raimo Joro, Alana Cavadino, Ville Huikari, Steve Franks, Maria M Groen-Blokhuis, Diana L Cousminer, Julie A Marsh, Terho Lehtimäki, John A Curtin, Jesus Vioque, Tarunveer S Ahluwalia, Ronny Myhre, Thomas S Price, Natalia Vilor-Tejedor, Loïc Yengo, Niels Grarup, Ioanna Ntalla, Wei Ang, Mustafa Atalay, Hans Bisgaard, Alexandra I Blakemore, Amelie Bonnefond, Lisbeth Carstensen, Johan Eriksson, Claudia Flexeder, Lude Franke, Frank Geller, Mandy Geserick, Anna-Liisa Hartikainen, Claire M A Haworth, Joel N Hirschhorn, Albert Hofman, Jens-Christian Holm, Momoko Horikoshi, Jouke Jan Hottenga, Jinyan Huang, Haja N Kadarmideen, Mika Kähönen, Wieland Kiess, Hanna-Maaria Lakka, Timo A Lakka, Alexandra M Lewin, Liming Liang, Leo-Pekka Lyytikäinen, Baoshan Ma, Per Magnus, Shana E McCormack, George McMahon, Frank D Mentch, Christel M Middeldorp, Clare S Murray, Katja Pahkala, Tune H Pers, Roland Pfäffle, Dirkje S Postma, Christine Power, Angela Simpson, Verena Sengpiel, Carla M T Tiesler, Maties Torrent, André G Uitterlinden, Joyce B van Meurs, Rebecca Vinding, Johannes Waage, Jane Wardle, Eleftheria Zeggini, Babette S Zemel, George V Dedoussis, Oluf Pedersen, Philippe Froguel, Jordi Sunyer, Robert Plomin, Bo Jacobsson, Torben Hansen, Juan R Gonzalez, Adnan Custovic, Olli T Raitakari, Craig E Pennell, Elisabeth Widén, Dorret I Boomsma, Gerard H Koppelman, Sylvain Sebert, Marjo-Riitta Järvelin, Elina Hyppönen, Mark I McCarthy, Virpi Lindi, Niinikoski Harri, Antje Körner, Klaus Bønnelykke, Joachim Heinrich, Mads Melbye, Fernando Rivadeneira, Hakon Hakonarson, Susan M Ring, George Davey Smith, Thorkild I A Sørensen, Nicholas J Timpson, Struan F A Grant, Vincent W V Jaddoe
A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity...
January 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/26488112/the-sf3b1-inhibitor-spliceostatin-a-ssa-elicits-apoptosis-in-chronic-lymphocytic-leukaemia-cells-through-downregulation-of-mcl-1
#17
M Larrayoz, S J Blakemore, R C Dobson, M D Blunt, M J J Rose-Zerilli, R Walewska, A Duncombe, D Oscier, K Koide, F Forconi, G Packham, M Yoshida, M S Cragg, J C Strefford, A J Steele
The pro-survival Bcl-2 family member Mcl-1 is expressed in chronic lymphocytic leukaemia (CLL), with high expression correlated with progressive disease. The spliceosome inhibitor spliceostatin A (SSA) is known to regulate Mcl-1 and so here we assessed the ability of SSA to elicit apoptosis in CLL. SSA induced apoptosis of CLL cells at low nanomolar concentrations in a dose- and time-dependent manner, but independently of SF3B1 mutational status, IGHV status and CD38 or ZAP70 expression. However, normal B and T cells were less sensitive than CLL cells (P=0...
February 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/26184912/bcr-signaling-induced-cell-death-demonstrates-dependency-on-multiple-bh3-only-proteins-in-a-murine-model-of-b-cell-lymphoma
#18
M J Carter, K L Cox, S J Blakemore, Y D Bogdanov, L Happo, C L Scott, A Strasser, G K Packham, M S Cragg
Genetic recombination during B-cell development regularly results in the generation of autoreactive, potentially pathogenic B-cell receptors (BCRs). Consequently, multiple mechanisms link inappropriate BCR specificity to clonal deletion. Similar pathways remain in malignant B cells, offering the potential for targeting BCR signaling. Recently, small molecule inhibitors have realized this potential and, therefore, a deeper understanding of BCR-induced signaling networks in malignant cells is vital. The BH3-only protein Bim has a key role in BCR-induced apoptosis, but it has long been proposed that additional BH3-only proteins also contribute, although conclusive proof has been lacking...
February 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/26075510/unusual-cause-of-a-facial-pressure-ulcer-the-helmet-securing-the-sengstaken-blakemore-tube
#19
S M Kim, R K Ju, J H Lee, Y J Jun, Y J Kim
Many medical devices, such as pulse oximetry, ventilation masks and other splints are put on critically ill patients. Although these devices are designed to deliver relatively low physical pressure to the skin of the patient, they can still cause pressure ulcers (PUs) in critically ill patients. There are reports of medical device-related PUs on the face. Here we describe forehead skin necrosis caused by the securing helmet for the Sengstaken-Blakemore tube. It is difficult to detect this kind of PU early, because most of the patients have decreased mental status or delirium due to varix bleeding...
June 2015: Journal of Wound Care
https://www.readbyqxmd.com/read/25980517/pdgfr%C3%AE-demarcates-the-cardiogenic-clonogenic-sca1-stem-progenitor-cell-in-adult-murine-myocardium
#20
Michela Noseda, Mutsuo Harada, Sara McSweeney, Thomas Leja, Elisa Belian, Daniel J Stuckey, Marta S Abreu Paiva, Josef Habib, Iain Macaulay, Adam J de Smith, Farah al-Beidh, Robert Sampson, R Thomas Lumbers, Pulivarthi Rao, Sian E Harding, Alexandra I F Blakemore, Sten Eirik Jacobsen, Mauricio Barahona, Michael D Schneider
Cardiac progenitor/stem cells in adult hearts represent an attractive therapeutic target for heart regeneration, though (inter)-relationships among reported cells remain obscure. Using single-cell qRT-PCR and clonal analyses, here we define four subpopulations of cardiac progenitor/stem cells in adult mouse myocardium all sharing stem cell antigen-1 (Sca1), based on side population (SP) phenotype, PECAM-1 (CD31) and platelet-derived growth factor receptor-α (PDGFRα) expression. SP status predicts clonogenicity and cardiogenic gene expression (Gata4/6, Hand2 and Tbx5/20), properties segregating more specifically to PDGFRα(+) cells...
May 18, 2015: Nature Communications
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