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Ian C. Zachary

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https://www.readbyqxmd.com/read/29898396/co-evolution-of-hiv-envelope-and-apex-targeting-neutralizing-antibody-lineage-provides-benchmarks-for-vaccine-design
#1
Kimmo Rantalainen, Zachary T Berndsen, Sasha Murrell, Liwei Cao, Oluwarotimi Omorodion, Jonathan L Torres, Mengyu Wu, Jeffrey Umotoy, Jeffrey Copps, Pascal Poignard, Elise Landais, James C Paulson, Ian A Wilson, Andrew B Ward
Broadly neutralizing antibodies (bnAbs) targeting the HIV envelope glycoprotein (Env) typically take years to develop. Longitudinal analyses of both neutralizing antibody lineages and viruses at serial time points during infection provide a basis for understanding the co-evolutionary contest between HIV and the humoral immune system. Here, we describe the structural characterization of an apex-targeting antibody lineage and autologous clade A viral Env from a donor in the Protocol C cohort. Comparison of Ab-Env complexes at early and late time points reveals that, within the antibody lineage, the CDRH3 loop rigidifies, the bnAb angle of approach steepens, and surface charges are mutated to accommodate glycan changes...
June 12, 2018: Cell Reports
https://www.readbyqxmd.com/read/29892015/multi-ethnic-genome-wide-association-study-for-atrial-fibrillation
#2
Carolina Roselli, Mark D Chaffin, Lu-Chen Weng, Stefanie Aeschbacher, Gustav Ahlberg, Christine M Albert, Peter Almgren, Alvaro Alonso, Christopher D Anderson, Krishna G Aragam, Dan E Arking, John Barnard, Traci M Bartz, Emelia J Benjamin, Nathan A Bihlmeyer, Joshua C Bis, Heather L Bloom, Eric Boerwinkle, Erwin B Bottinger, Jennifer A Brody, Hugh Calkins, Archie Campbell, Thomas P Cappola, John Carlquist, Daniel I Chasman, Lin Y Chen, Yii-Der Ida Chen, Eue-Keun Choi, Seung Hoan Choi, Ingrid E Christophersen, Mina K Chung, John W Cole, David Conen, James Cook, Harry J Crijns, Michael J Cutler, Scott M Damrauer, Brian R Daniels, Dawood Darbar, Graciela Delgado, Joshua C Denny, Martin Dichgans, Marcus Dörr, Elton A Dudink, Samuel C Dudley, Nada Esa, Tonu Esko, Markku Eskola, Diane Fatkin, Stephan B Felix, Ian Ford, Oscar H Franco, Bastiaan Geelhoed, Raji P Grewal, Vilmundur Gudnason, Xiuqing Guo, Namrata Gupta, Stefan Gustafsson, Rebecca Gutmann, Anders Hamsten, Tamara B Harris, Caroline Hayward, Susan R Heckbert, Jussi Hernesniemi, Lynne J Hocking, Albert Hofman, Andrea R V R Horimoto, Jie Huang, Paul L Huang, Jennifer Huffman, Erik Ingelsson, Esra Gucuk Ipek, Kaoru Ito, Jordi Jimenez-Conde, Renee Johnson, J Wouter Jukema, Stefan Kääb, Mika Kähönen, Yoichiro Kamatani, John P Kane, Adnan Kastrati, Sekar Kathiresan, Petra Katschnig-Winter, Maryam Kavousi, Thorsten Kessler, Bas L Kietselaer, Paulus Kirchhof, Marcus E Kleber, Stacey Knight, Jose E Krieger, Michiaki Kubo, Lenore J Launer, Jari Laurikka, Terho Lehtimäki, Kirsten Leineweber, Rozenn N Lemaitre, Man Li, Hong Euy Lim, Henry J Lin, Honghuang Lin, Lars Lind, Cecilia M Lindgren, Marja-Liisa Lokki, Barry London, Ruth J F Loos, Siew-Kee Low, Yingchang Lu, Leo-Pekka Lyytikäinen, Peter W Macfarlane, Patrik K Magnusson, Anubha Mahajan, Rainer Malik, Alfredo J Mansur, Gregory M Marcus, Lauren Margolin, Kenneth B Margulies, Winfried März, David D McManus, Olle Melander, Sanghamitra Mohanty, Jay A Montgomery, Michael P Morley, Andrew P Morris, Martina Müller-Nurasyid, Andrea Natale, Saman Nazarian, Benjamin Neumann, Christopher Newton-Cheh, Maartje N Niemeijer, Kjell Nikus, Peter Nilsson, Raymond Noordam, Heidi Oellers, Morten S Olesen, Marju Orho-Melander, Sandosh Padmanabhan, Hui-Nam Pak, Guillaume Paré, Nancy L Pedersen, Joanna Pera, Alexandre Pereira, David Porteous, Bruce M Psaty, Sara L Pulit, Clive R Pullinger, Daniel J Rader, Lena Refsgaard, Marta Ribasés, Paul M Ridker, Michiel Rienstra, Lorenz Risch, Dan M Roden, Jonathan Rosand, Michael A Rosenberg, Natalia Rost, Jerome I Rotter, Samir Saba, Roopinder K Sandhu, Renate B Schnabel, Katharina Schramm, Heribert Schunkert, Claudia Schurman, Stuart A Scott, Ilkka Seppälä, Christian Shaffer, Svati Shah, Alaa A Shalaby, Jaemin Shim, M Benjamin Shoemaker, Joylene E Siland, Juha Sinisalo, Moritz F Sinner, Agnieszka Slowik, Albert V Smith, Blair H Smith, J Gustav Smith, Jonathan D Smith, Nicholas L Smith, Elsayed Z Soliman, Nona Sotoodehnia, Bruno H Stricker, Albert Sun, Han Sun, Jesper H Svendsen, Toshihiro Tanaka, Kahraman Tanriverdi, Kent D Taylor, Maris Teder-Laving, Alexander Teumer, Sébastien Thériault, Stella Trompet, Nathan R Tucker, Arnljot Tveit, Andre G Uitterlinden, Pim Van Der Harst, Isabelle C Van Gelder, David R Van Wagoner, Niek Verweij, Efthymia Vlachopoulou, Uwe Völker, Biqi Wang, Peter E Weeke, Bob Weijs, Raul Weiss, Stefan Weiss, Quinn S Wells, Kerri L Wiggins, Jorge A Wong, Daniel Woo, Bradford B Worrall, Pil-Sung Yang, Jie Yao, Zachary T Yoneda, Tanja Zeller, Lingyao Zeng, Steven A Lubitz, Kathryn L Lunetta, Patrick T Ellinor
Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF...
June 11, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29880492/vegf-vascular-endothelial-growth-factor-induces-nrp1-neuropilin-1-cleavage-via-adams-a-disintegrin-and-metalloproteinase-9-and-10-to-generate-novel-carboxy-terminal-nrp1-fragments-that-regulate-angiogenic-signaling
#3
Vedanta Mehta, Laura Fields, Ian M Evans, Maiko Yamaji, Caroline Pellet-Many, Timothy Jones, Marwa Mahmoud, Ian Zachary
OBJECTIVE: NRP1(neuropilin-1) acts as a coreceptor for VEGF (vascular endothelial growth factor) with an essential role in angiogenesis. Recent findings suggest that posttranslational proteolytic cleavage of VEGF receptors may be an important mechanism for regulating angiogenesis, but the role of NRP1 proteolysis and the NRP1 species generated by cleavage in endothelial cells is not known. To characterize NRP1 proteolytic cleavage in endothelial cells, determine the mechanism, and investigate the role of NRP1 cleavage in regulation of endothelial cell function...
June 7, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29847165/perinatal-and-long-term-effects-of-maternal-uterine-artery-adenoviral-vegf-a-165-gene-therapy-in-the-growth-restricted-guinea-pig-fetus
#4
Owen Rhys Vaughan, Carlo A Rossi, Yuval Ginsberg, Anthony White, Mariya Hristova, Neil J Sebire, John Martin, Ian C Zachary, Donald M Peebles, Anna L David
Uterine artery application of adenoviral vascular endothelial growth factor gene therapy (Ad.VEGF-A165 ) increases uterine blood flow and fetal growth in experimental animals with fetal growth restriction (FGR). Whether Ad.VEGF-A165 reduces lifelong cardiovascular disease risk imposed by FGR remains unknown. Here, pregnant guinea pigs fed 70% normal food intake to induce FGR received Ad.VEGF-A165 (1x1010 viral particles, n=15) or vehicle (n=10), delivered to the external surface of the uterine arteries, in mid-pregnancy...
May 30, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29648813/small-molecule-neuropilin-1-antagonists-combine-antiangiogenic-and-antitumor-activity-with-immune-modulation-through-reduction-of-transforming-growth-factor-beta-tgf%C3%AE-production-in-regulatory-t-cells
#5
Jonathan Powell, Filipa Mota, David Steadman, Christelle Soudy, Jeremy T Miyauchi, Stuart Crosby, Ashley Jarvis, Tifelle Reisinger, Natalie Winfield, Graham Evans, Aled Finniear, Tamas Yelland, Yi-Tai Chou, A W Edith Chan, Andrew O'Leary, Lili Cheng, Dan Liu, Constantina Fotinou, Carla Milagre, John F Martin, Haiyan Jia, Paul Frankel, Snezana Djordjevic, Stella E Tsirka, Ian C Zachary, David L Selwood
We report the design, synthesis, and biological evaluation of some potent small-molecule neuropilin-1 (NRP1) antagonists. NRP1 is implicated in the immune response to tumors, particularly in Treg cell fragility, required for PD1 checkpoint blockade. The design of these compounds was based on a previously identified compound EG00229. The design of these molecules was informed and supported by X-ray crystal structures. Compound 1 (EG01377) was identified as having properties suitable for further investigation...
May 10, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29566793/genome-wide-analyses-identify-kif5a-as-a-novel-als-gene
#6
Aude Nicolas, Kevin P Kenna, Alan E Renton, Nicola Ticozzi, Faraz Faghri, Ruth Chia, Janice A Dominov, Brendan J Kenna, Mike A Nalls, Pamela Keagle, Alberto M Rivera, Wouter van Rheenen, Natalie A Murphy, Joke J F A van Vugt, Joshua T Geiger, Rick A Van der Spek, Hannah A Pliner, Shankaracharya, Bradley N Smith, Giuseppe Marangi, Simon D Topp, Yevgeniya Abramzon, Athina Soragia Gkazi, John D Eicher, Aoife Kenna, Gabriele Mora, Andrea Calvo, Letizia Mazzini, Nilo Riva, Jessica Mandrioli, Claudia Caponnetto, Stefania Battistini, Paolo Volanti, Vincenzo La Bella, Francesca L Conforti, Giuseppe Borghero, Sonia Messina, Isabella L Simone, Francesca Trojsi, Fabrizio Salvi, Francesco O Logullo, Sandra D'Alfonso, Lucia Corrado, Margherita Capasso, Luigi Ferrucci, Cristiane de Araujo Martins Moreno, Sitharthan Kamalakaran, David B Goldstein, Aaron D Gitler, Tim Harris, Richard M Myers, Hemali Phatnani, Rajeeva Lochan Musunuri, Uday Shankar Evani, Avinash Abhyankar, Michael C Zody, Julia Kaye, Steven Finkbeiner, Stacia K Wyman, Alex LeNail, Leandro Lima, Ernest Fraenkel, Clive N Svendsen, Leslie M Thompson, Jennifer E Van Eyk, James D Berry, Timothy M Miller, Stephen J Kolb, Merit Cudkowicz, Emily Baxi, Michael Benatar, J Paul Taylor, Evadnie Rampersaud, Gang Wu, Joanne Wuu, Giuseppe Lauria, Federico Verde, Isabella Fogh, Cinzia Tiloca, Giacomo P Comi, Gianni Sorarù, Cristina Cereda, Philippe Corcia, Hannu Laaksovirta, Liisa Myllykangas, Lilja Jansson, Miko Valori, John Ealing, Hisham Hamdalla, Sara Rollinson, Stuart Pickering-Brown, Richard W Orrell, Katie C Sidle, Andrea Malaspina, John Hardy, Andrew B Singleton, Janel O Johnson, Sampath Arepalli, Peter C Sapp, Diane McKenna-Yasek, Meraida Polak, Seneshaw Asress, Safa Al-Sarraj, Andrew King, Claire Troakes, Caroline Vance, Jacqueline de Belleroche, Frank Baas, Anneloor L M A Ten Asbroek, José Luis Muñoz-Blanco, Dena G Hernandez, Jinhui Ding, J Raphael Gibbs, Sonja W Scholz, Mary Kay Floeter, Roy H Campbell, Francesco Landi, Robert Bowser, Stefan M Pulst, John M Ravits, Daniel J L MacGowan, Janine Kirby, Erik P Pioro, Roger Pamphlett, James Broach, Glenn Gerhard, Travis L Dunckley, Christopher B Brady, Neil W Kowall, Juan C Troncoso, Isabelle Le Ber, Kevin Mouzat, Serge Lumbroso, Terry D Heiman-Patterson, Freya Kamel, Ludo Van Den Bosch, Robert H Baloh, Tim M Strom, Thomas Meitinger, Aleksey Shatunov, Kristel R Van Eijk, Mamede de Carvalho, Maarten Kooyman, Bas Middelkoop, Matthieu Moisse, Russell L McLaughlin, Michael A Van Es, Markus Weber, Kevin B Boylan, Marka Van Blitterswijk, Rosa Rademakers, Karen E Morrison, A Nazli Basak, Jesús S Mora, Vivian E Drory, Pamela J Shaw, Martin R Turner, Kevin Talbot, Orla Hardiman, Kelly L Williams, Jennifer A Fifita, Garth A Nicholson, Ian P Blair, Guy A Rouleau, Jesús Esteban-Pérez, Alberto García-Redondo, Ammar Al-Chalabi, Ekaterina Rogaeva, Lorne Zinman, Lyle W Ostrow, Nicholas J Maragakis, Jeffrey D Rothstein, Zachary Simmons, Johnathan Cooper-Knock, Alexis Brice, Stephen A Goutman, Eva L Feldman, Summer B Gibson, Franco Taroni, Antonia Ratti, Cinzia Gellera, Philip Van Damme, Wim Robberecht, Pietro Fratta, Mario Sabatelli, Christian Lunetta, Albert C Ludolph, Peter M Andersen, Jochen H Weishaupt, William Camu, John Q Trojanowski, Vivianna M Van Deerlin, Robert H Brown, Leonard H van den Berg, Jan H Veldink, Matthew B Harms, Jonathan D Glass, David J Stone, Pentti Tienari, Vincenzo Silani, Adriano Chiò, Christopher E Shaw, Bryan J Traynor, John E Landers
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2)...
March 21, 2018: Neuron
https://www.readbyqxmd.com/read/29543760/receptor-tyrosine-kinase-ubiquitination-and-de-ubiquitination-in-signal-transduction-and-receptor-trafficking
#7
REVIEW
William R Critchley, Caroline Pellet-Many, Benjamin Ringham-Terry, Michael A Harrison, Ian C Zachary, Sreenivasan Ponnambalam
Receptor tyrosine kinases (RTKs) are membrane-based sensors that enable rapid communication between cells and their environment. Evidence is now emerging that interdependent regulatory mechanisms, such as membrane trafficking, ubiquitination, proteolysis and gene expression, have substantial effects on RTK signal transduction and cellular responses. Different RTKs exhibit both basal and ligand-stimulated ubiquitination, linked to trafficking through different intracellular compartments including the secretory pathway, plasma membrane, endosomes and lysosomes...
March 15, 2018: Cells
https://www.readbyqxmd.com/read/29432117/closed-loop-continuous-hand-control-via-chronic-recording-of-regenerative-peripheral-nerve-interfaces
#8
Philip P Vu, Zachary T Irwin, Autumn J Bullard, Shoshana W Ambani, Ian C Sando, Melanie G Urbanchek, Paul S Cederna, Cynthia A Chestek
Loss of the upper limb imposes a devastating interruption to everyday life. Full restoration of natural arm control requires the ability to simultaneously control multiple degrees of freedom of the prosthetic arm and maintain that control over an extended period of time. Current clinically available myoelectric prostheses do not provide simultaneous control or consistency for transradial amputees. To address this issue, we have implemented a standard Kalman filter for continuous hand control using intramuscular electromyography (EMG) from both regenerative peripheral nerve interfaces (RPNI) and an intact muscle within non-human primates...
February 2018: IEEE Transactions on Neural Systems and Rehabilitation Engineering
https://www.readbyqxmd.com/read/29431741/sugar-release-and-growth-of-biofuel-crops-are-improved-by-downregulation-of-pectin-biosynthesis
#9
Ajaya K Biswal, Melani A Atmodjo, Mi Li, Holly L Baxter, Chang Geun Yoo, Yunqiao Pu, Yi-Ching Lee, Mitra Mazarei, Ian M Black, Ji-Yi Zhang, Hema Ramanna, Adam L Bray, Zachary R King, Peter R LaFayette, Sivakumar Pattathil, Bryon S Donohoe, Sushree S Mohanty, David Ryno, Kelsey Yee, Olivia A Thompson, Miguel Rodriguez, Alexandru Dumitrache, Jace Natzke, Kim Winkeler, Cassandra Collins, Xiaohan Yang, Li Tan, Robert W Sykes, Erica L Gjersing, Angela Ziebell, Geoffrey B Turner, Stephen R Decker, Michael G Hahn, Brian H Davison, Michael K Udvardi, Jonathan R Mielenz, Mark F Davis, Richard S Nelson, Wayne A Parrott, Arthur J Ragauskas, C Neal Stewart, Debra Mohnen
Cell walls in crops and trees have been engineered for production of biofuels and commodity chemicals, but engineered varieties often fail multi-year field trials and are not commercialized. We engineered reduced expression of a pectin biosynthesis gene (Galacturonosyltransferase 4, GAUT4) in switchgrass and poplar, and find that this improves biomass yields and sugar release from biomass processing. Both traits were maintained in a 3-year field trial of GAUT4-knockdown switchgrass, with up to sevenfold increased saccharification and ethanol production and sixfold increased biomass yield compared with control plants...
March 2018: Nature Biotechnology
https://www.readbyqxmd.com/read/29430837/architecture-and-hydration-of-the-arginine-binding-site-of-neuropilin-1
#10
Filipa Mota, Constantina Fotinou, Rohini R Rana, A W Edith Chan, Tamas Yelland, Mohamed T Arooz, Andrew P O'Leary, Jennie Hutton, Paul Frankel, Ian Zachary, David Selwood, Snezana Djordjevic
Neuropilin-1 (NRP1) is a transmembrane co-receptor involved in binding interactions with variety of ligands and receptors, including receptor tyrosine kinases. Expression of NRP1 in several cancers correlates with cancer stages and poor prognosis. Thus, NRP1 has been considered a therapeutic target and is the focus of multiple drug discovery initiatives. Vascular endothelial growth factor (VEGF) binds to the b1 domain of NRP1 through interactions between the C-terminal arginine of VEGF and residues in the NRP1-binding site including Tyr297, Tyr353, Asp320, Ser346 and Thr349...
April 2018: FEBS Journal
https://www.readbyqxmd.com/read/29366785/1%C3%AE-25-dihydroxyvitamin-d-3-mitigates-cancer-cell-mediated-mitochondrial-dysfunction-in-human-skeletal-muscle-cells
#11
Zachary C Ryan, Theodore A Craig, Xuewei Wang, Philippe Delmotte, Jeffrey L Salisbury, Ian R Lanza, Gary C Sieck, Rajiv Kumar
Cancer cachexia is associated with muscle weakness and atrophy. We investigated whether 1α,25-dihydroxyvitamin D3 (1α,25(OH)2 D3 ), which has previously been shown to increase skeletal myoblast oxygen consumption rate, could reverse the deleterious effects of tumor cell conditioned medium on myoblast function. Conditioned medium from Lewis lung carcinoma (LLC1) cells inhibits oxygen consumption, increases mitochondrial fragmentation, inhibits pyruvate dehydrogenase activity, and enhances proteasomal activity in human skeletal muscle myoblasts...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29351429/removal-of-interscapular-brown-adipose-tissue-increases-aortic-stiffness-despite-normal-systemic-glucose-metabolism-in-mice
#12
Zachary I Grunewald, Nathan C Winn, Michelle L Gastecki, Makenzie L Woodford, James R Ball, Sarah A Hansen, Harold S Sacks, Victoria J Vieira-Potter, Jaume Padilla
Brown adipose tissue (BAT) is considered protective against obesity and related cardiometabolic dysfunction. Indeed, activation of BAT improves glucose homeostasis and attenuates cardiovascular disease development. However, whether a reduction in BAT mass perturbs metabolic function and increases risk for cardiovascular disease remains largely unknown. To address this question, C57BL/6J male mice underwent a sham procedure or surgical bilateral excision of interscapular BAT (iBATx) and were fed a normal chow or a Western diet for 18 wk, creating four groups ( n = 10/group)...
April 1, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29166592/hiv-envelope-glycoform-heterogeneity-and-localized-diversity-govern-the-initiation-and-maturation-of-a-v2-apex-broadly-neutralizing-antibody-lineage
#13
Elise Landais, Ben Murrell, Bryan Briney, Sasha Murrell, Kimmo Rantalainen, Zachary T Berndsen, Alejandra Ramos, Lalinda Wickramasinghe, Melissa Laird Smith, Kemal Eren, Natalia de Val, Mengyu Wu, Audrey Cappelletti, Jeffrey Umotoy, Yolanda Lie, Terri Wrin, Paul Algate, Po-Ying Chan-Hui, Etienne Karita, Andrew B Ward, Ian A Wilson, Dennis R Burton, Davey Smith, Sergei L Kosakovsky Pond, Pascal Poignard
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25 amino acids, among the shortest known for this class of Abs, and achieved breadth with only 10% nucleotide somatic hypermutation and no insertions or deletions...
November 21, 2017: Immunity
https://www.readbyqxmd.com/read/29141949/microvascular-insulin-resistance-in-skeletal-muscle-and-brain-occurs-early-in-the-development-of-juvenile-obesity-in-pigs
#14
T Dylan Olver, Zachary I Grunewald, Thomas J Jurrissen, Rebecca E K MacPherson, Paul J LeBlanc, Teagan R Schnurbusch, Alana M Czajkowski, M Harold Laughlin, R Scott Rector, Shawn B Bender, Eric M Walters, Craig A Emter, Jaume Padilla
Impaired microvascular insulin signaling may develop before overt indices of microvascular endothelial dysfunction and represent an early pathological feature of adolescent obesity. Using a translational porcine model of juvenile obesity, we tested the hypotheses that in the early stages of obesity development, impaired insulin signaling manifests in skeletal muscle (triceps), brain (prefrontal cortex), and corresponding vasculatures, and that depressed insulin-induced vasodilation is reversible with acute inhibition of protein kinase Cβ (PKCβ)...
February 1, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/29049607/dose-response-association-of-cd8-tumor-infiltrating-lymphocytes-and-survival-time-in-high-grade-serous-ovarian-cancer
#15
Ellen L Goode, Matthew S Block, Kimberly R Kalli, Robert A Vierkant, Wenqian Chen, Zachary C Fogarty, Aleksandra Gentry-Maharaj, Aleksandra Tołoczko, Alexander Hein, Aliecia L Bouligny, Allan Jensen, Ana Osorio, Andreas Hartkopf, Andy Ryan, Anita Chudecka-Głaz, Anthony M Magliocco, Arndt Hartmann, Audrey Y Jung, Bo Gao, Brenda Y Hernandez, Brooke L Fridley, Bryan M McCauley, Catherine J Kennedy, Chen Wang, Chloe Karpinskyj, Christiani B de Sousa, Daniel G Tiezzi, David L Wachter, Esther Herpel, Florin Andrei Taran, Francesmary Modugno, Gregg Nelson, Jan Lubiński, Janusz Menkiszak, Jennifer Alsop, Jenny Lester, Jesús García-Donas, Jill Nation, Jillian Hung, José Palacios, Joseph H Rothstein, Joseph L Kelley, Jurandyr M de Andrade, Luis Robles-Díaz, Maria P Intermaggio, Martin Widschwendter, Matthias W Beckmann, Matthias Ruebner, Mercedes Jimenez-Linan, Naveena Singh, Oleg Oszurek, Paul R Harnett, Peter F Rambau, Peter Sinn, Philipp Wagner, Prafull Ghatage, Raghwa Sharma, Robert P Edwards, Roberta B Ness, Sandra Orsulic, Sara Y Brucker, Sharon E Johnatty, Teri A Longacre, Eilber Ursula, Valerie McGuire, Weiva Sieh, Yanina Natanzon, Zheng Li, Alice S Whittemore, deFazio Anna, Annette Staebler, Beth Y Karlan, Blake Gilks, David D Bowtell, Estrid Høgdall, Francisco J Candido dos Reis, Helen Steed, Ian G Campbell, Jacek Gronwald, Javier Benítez, Jennifer M Koziak, Jenny Chang-Claude, Kirsten B Moysich, Linda E Kelemen, Linda S Cook, Marc T Goodman, María José García, Peter A Fasching, Stefan Kommoss, Suha Deen, Susanne K Kjaer, Usha Menon, James D Brenton, Paul DP Pharoah, Georgia Chenevix-Trench, David G Huntsman, Stacey J Winham, Martin Köbel, Susan J Ramus
Importance: Cytotoxic CD8+ tumor-infiltrating lymphocytes (TILs) participate in immune control of epithelial ovarian cancer; however, little is known about prognostic patterns of CD8+ TILs by histotype and in relation to other clinical factors. Objective: To define the prognostic role of CD8+ TILs in epithelial ovarian cancer. Design, Setting, and Participants: This was a multicenter observational, prospective survival cohort study of the Ovarian Tumor Tissue Analysis Consortium...
December 1, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28874413/a-phase-ii-trial-of-neoadjuvant-mk-2206-an-akt-inhibitor-with-anastrozole-in-clinical-stage-ii-or-iii-pik3ca-mutant-er-positive-and-her2-negative-breast-cancer
#16
Cynthia X Ma, Vera Suman, Matthew P Goetz, Donald Northfelt, Mark E Burkard, Foluso Ademuyiwa, Michael Naughton, Julie Margenthaler, Rebecca Aft, Richard Gray, Amye Tevaarwerk, Lee Wilke, Tufia Haddad, Timothy Moynihan, Charles Loprinzi, Tina Hieken, Erica K Barnell, Zachary L Skidmore, Yan-Yang Feng, Kilannin Krysiak, Jeremy Hoog, Zhanfang Guo, Leslie Nehring, Kari B Wisinski, Elaine Mardis, Ian S Hagemann, Kiran Vij, Souzan Sanati, Hussam Al-Kateb, Obi L Griffith, Malachi Griffith, Laurence Doyle, Charles Erlichman, Matthew J Ellis
Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER+ ) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA -mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer. Experimental Design: Potential eligible patients with clinical stage II/III ER+ /HER2- breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing...
November 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28794122/organizational-structure-staffing-resources-and-educational-initiatives-in-cardiac-intensive-care-units-in-the-united-states-an-american-heart-association-acute-cardiac-care-committee-and-american-college-of-cardiology-critical-care-cardiology-working-group
#17
Sean van Diepen, Christopher B Fordyce, Zachary K Wegermann, Christopher B Granger, Amanda Stebbins, David A Morrow, Michael A Solomon, Jeffrey Soble, Timothy D Henry, Ian C Gilchrist, Jason N Katz, Mauricio G Cohen, L Kristin Newby
No abstract text is available yet for this article.
August 2017: Circulation. Cardiovascular Quality and Outcomes
https://www.readbyqxmd.com/read/28476427/clinical-phenotypes-of-perinatal-depression-and-time-of-symptom-onset-analysis-of-data-from-an-international-consortium
#18
Karen T Putnam, Marsha Wilcox, Emma Robertson-Blackmore, Katherine Sharkey, Veerle Bergink, Trine Munk-Olsen, Kristina M Deligiannidis, Jennifer Payne, Margaret Altemus, Jeffrey Newport, Gisele Apter, Emmanuel Devouche, Alexander Viktorin, Patrik Magnusson, Brenda Penninx, Anne Buist, Justin Bilszta, Michael O'Hara, Scott Stuart, Rebecca Brock, Sabine Roza, Henning Tiemeier, Constance Guille, C Neill Epperson, Deborah Kim, Peter Schmidt, Pedro Martinez, Arianna Di Florio, Katherine L Wisner, Zachary Stowe, Ian Jones, Patrick F Sullivan, David Rubinow, Kevin Wildenhaus, Samantha Meltzer-Brody
BACKGROUND: The perinatal period is a time of high risk for onset of depressive disorders and is associated with substantial morbidity and mortality, including maternal suicide. Perinatal depression comprises a heterogeneous group of clinical subtypes, and further refinement is needed to improve treatment outcomes. We sought to empirically identify and describe clinically relevant phenotypic subtypes of perinatal depression, and further characterise subtypes by time of symptom onset within pregnancy and three post-partum periods...
June 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28356307/visualizing-localized-reentry-with-ultra-high-density-mapping-in-iatrogenic-atrial-tachycardia-beware-pseudo-reentry
#19
Vishal Luther, Markus Sikkel, Nathan Bennett, Fernando Guerrero, Kevin Leong, Norman Qureshi, Fu Siong Ng, Sajad A Hayat, S M Afzal Sohaib, Louisa Malcolme-Lawes, Elaine Lim, Ian Wright, Michael Koa-Wing, David C Lefroy, Nick W F Linton, Zachary Whinnett, Prapa Kanagaratnam, D Wyn Davies, Nicholas S Peters, Phang Boon Lim
BACKGROUND: The activation pattern of localized reentry (LR) in atrial tachycardia remains incompletely understood. We used the ultra-high density Rhythmia mapping system to study activation patterns in LR. METHODS AND RESULTS: LR was suggested by small rotatory activations (carousels) containing the full spectrum of the color-coded map. Twenty-three left-sided atrial tachycardias were mapped in 15 patients (age: 64±11 years). 16 253±9192 points were displayed per map, collected over 26±14 minutes...
April 2017: Circulation. Arrhythmia and Electrophysiology
https://www.readbyqxmd.com/read/28346442/identification-of-12-new-susceptibility-loci-for-different-histotypes-of-epithelial-ovarian-cancer
#20
Catherine M Phelan, Karoline B Kuchenbaecker, Jonathan P Tyrer, Siddhartha P Kar, Kate Lawrenson, Stacey J Winham, Joe Dennis, Ailith Pirie, Marjorie J Riggan, Ganna Chornokur, Madalene A Earp, Paulo C Lyra, Janet M Lee, Simon Coetzee, Jonathan Beesley, Lesley McGuffog, Penny Soucy, Ed Dicks, Andrew Lee, Daniel Barrowdale, Julie Lecarpentier, Goska Leslie, Cora M Aalfs, Katja K H Aben, Marcia Adams, Julian Adlard, Irene L Andrulis, Hoda Anton-Culver, Natalia Antonenkova, Gerasimos Aravantinos, Norbert Arnold, Banu K Arun, Brita Arver, Jacopo Azzollini, Judith Balmaña, Susana N Banerjee, Laure Barjhoux, Rosa B Barkardottir, Yukie Bean, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marina Bermisheva, Marcus Q Bernardini, Michael J Birrer, Line Bjorge, Amanda Black, Kenneth Blankstein, Marinus J Blok, Clara Bodelon, Natalia Bogdanova, Anders Bojesen, Bernardo Bonanni, Åke Borg, Angela R Bradbury, James D Brenton, Carole Brewer, Louise Brinton, Per Broberg, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Bruno Buecher, Ralf Butzow, Saundra S Buys, Trinidad Caldes, Maria A Caligo, Ian Campbell, Rikki Cannioto, Michael E Carney, Terence Cescon, Salina B Chan, Jenny Chang-Claude, Stephen Chanock, Xiao Qing Chen, Yoke-Eng Chiew, Jocelyne Chiquette, Wendy K Chung, Kathleen B M Claes, Thomas Conner, Linda S Cook, Jackie Cook, Daniel W Cramer, Julie M Cunningham, Aimee A D'Aloisio, Mary B Daly, Francesca Damiola, Sakaeva Dina Damirovna, Agnieszka Dansonka-Mieszkowska, Fanny Dao, Rosemarie Davidson, Anna DeFazio, Capucine Delnatte, Kimberly F Doheny, Orland Diez, Yuan Chun Ding, Jennifer Anne Doherty, Susan M Domchek, Cecilia M Dorfling, Thilo Dörk, Laure Dossus, Mercedes Duran, Matthias Dürst, Bernd Dworniczak, Diana Eccles, Todd Edwards, Ros Eeles, Ursula Eilber, Bent Ejlertsen, Arif B Ekici, Steve Ellis, Mingajeva Elvira, Kevin H Eng, Christoph Engel, D Gareth Evans, Peter A Fasching, Sarah Ferguson, Sandra Fert Ferrer, James M Flanagan, Zachary C Fogarty, Renée T Fortner, Florentia Fostira, William D Foulkes, George Fountzilas, Brooke L Fridley, Tara M Friebel, Eitan Friedman, Debra Frost, Patricia A Ganz, Judy Garber, María J García, Vanesa Garcia-Barberan, Andrea Gehrig, Aleksandra Gentry-Maharaj, Anne-Marie Gerdes, Graham G Giles, Rosalind Glasspool, Gord Glendon, Andrew K Godwin, David E Goldgar, Teodora Goranova, Martin Gore, Mark H Greene, Jacek Gronwald, Stephen Gruber, Eric Hahnen, Christopher A Haiman, Niclas Håkansson, Ute Hamann, Thomas V O Hansen, Patricia A Harrington, Holly R Harris, Jan Hauke, Alexander Hein, Alex Henderson, Michelle A T Hildebrandt, Peter Hillemanns, Shirley Hodgson, Claus K Høgdall, Estrid Høgdall, Frans B L Hogervorst, Helene Holland, Maartje J Hooning, Karen Hosking, Ruea-Yea Huang, Peter J Hulick, Jillian Hung, David J Hunter, David G Huntsman, Tomasz Huzarski, Evgeny N Imyanitov, Claudine Isaacs, Edwin S Iversen, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul James, Ramunas Janavicius, Mats Jernetz, Allan Jensen, Uffe Birk Jensen, Esther M John, Sharon Johnatty, Michael E Jones, Päivi Kannisto, Beth Y Karlan, Anthony Karnezis, Karin Kast, Catherine J Kennedy, Elza Khusnutdinova, Lambertus A Kiemeney, Johanna I Kiiski, Sung-Won Kim, Susanne K Kjaer, Martin Köbel, Reidun K Kopperud, Torben A Kruse, Jolanta Kupryjanczyk, Ava Kwong, Yael Laitman, Diether Lambrechts, Nerea Larrañaga, Melissa C Larson, Conxi Lazaro, Nhu D Le, Loic Le Marchand, Jong Won Lee, Shashikant B Lele, Arto Leminen, Dominique Leroux, Jenny Lester, Fabienne Lesueur, Douglas A Levine, Dong Liang, Clemens Liebrich, Jenna Lilyquist, Loren Lipworth, Jolanta Lissowska, Karen H Lu, Jan Lubinński, Craig Luccarini, Lene Lundvall, Phuong L Mai, Gustavo Mendoza-Fandiño, Siranoush Manoukian, Leon F A G Massuger, Taymaa May, Sylvie Mazoyer, Jessica N McAlpine, Valerie McGuire, John R McLaughlin, Iain McNeish, Hanne Meijers-Heijboer, Alfons Meindl, Usha Menon, Arjen R Mensenkamp, Melissa A Merritt, Roger L Milne, Gillian Mitchell, Francesmary Modugno, Joanna Moes-Sosnowska, Melissa Moffitt, Marco Montagna, Kirsten B Moysich, Anna Marie Mulligan, Jacob Musinsky, Katherine L Nathanson, Lotte Nedergaard, Roberta B Ness, Susan L Neuhausen, Heli Nevanlinna, Dieter Niederacher, Robert L Nussbaum, Kunle Odunsi, Edith Olah, Olufunmilayo I Olopade, Håkan Olsson, Curtis Olswold, David M O'Malley, Kai-Ren Ong, N Charlotte Onland-Moret, Nicholas Orr, Sandra Orsulic, Ana Osorio, Domenico Palli, Laura Papi, Tjoung-Won Park-Simon, James Paul, Celeste L Pearce, Inge Søkilde Pedersen, Petra H M Peeters, Bernard Peissel, Ana Peixoto, Tanja Pejovic, Liisa M Pelttari, Jennifer B Permuth, Paolo Peterlongo, Lidia Pezzani, Georg Pfeiler, Kelly-Anne Phillips, Marion Piedmonte, Malcolm C Pike, Anna M Piskorz, Samantha R Poblete, Timea Pocza, Elizabeth M Poole, Bruce Poppe, Mary E Porteous, Fabienne Prieur, Darya Prokofyeva, Elizabeth Pugh, Miquel Angel Pujana, Pascal Pujol, Paolo Radice, Johanna Rantala, Christine Rappaport-Fuerhauser, Gad Rennert, Kerstin Rhiem, Patricia Rice, Andrea Richardson, Mark Robson, Gustavo C Rodriguez, Cristina Rodríguez-Antona, Jane Romm, Matti A Rookus, Mary Anne Rossing, Joseph H Rothstein, Anja Rudolph, Ingo B Runnebaum, Helga B Salvesen, Dale P Sandler, Minouk J Schoemaker, Leigha Senter, V Wendy Setiawan, Gianluca Severi, Priyanka Sharma, Tameka Shelford, Nadeem Siddiqui, Lucy E Side, Weiva Sieh, Christian F Singer, Hagay Sobol, Honglin Song, Melissa C Southey, Amanda B Spurdle, Zsofia Stadler, Doris Steinemann, Dominique Stoppa-Lyonnet, Lara E Sucheston-Campbell, Grzegorz Sukiennicki, Rebecca Sutphen, Christian Sutter, Anthony J Swerdlow, Csilla I Szabo, Lukasz Szafron, Yen Y Tan, Jack A Taylor, Muy-Kheng Tea, Manuel R Teixeira, Soo-Hwang Teo, Kathryn L Terry, Pamela J Thompson, Liv Cecilie Vestrheim Thomsen, Darcy L Thull, Laima Tihomirova, Anna V Tinker, Marc Tischkowitz, Silvia Tognazzo, Amanda Ewart Toland, Alicia Tone, Britton Trabert, Ruth C Travis, Antonia Trichopoulou, Nadine Tung, Shelley S Tworoger, Anne M van Altena, David Van Den Berg, Annemarie H van der Hout, Rob B van der Luijt, Mattias Van Heetvelde, Els Van Nieuwenhuysen, Elizabeth J van Rensburg, Adriaan Vanderstichele, Raymonda Varon-Mateeva, Ana Vega, Digna Velez Edwards, Ignace Vergote, Robert A Vierkant, Joseph Vijai, Athanassios Vratimos, Lisa Walker, Christine Walsh, Dorothea Wand, Shan Wang-Gohrke, Barbara Wappenschmidt, Penelope M Webb, Clarice R Weinberg, Jeffrey N Weitzel, Nicolas Wentzensen, Alice S Whittemore, Juul T Wijnen, Lynne R Wilkens, Alicja Wolk, Michelle Woo, Xifeng Wu, Anna H Wu, Hannah Yang, Drakoulis Yannoukakos, Argyrios Ziogas, Kristin K Zorn, Steven A Narod, Douglas F Easton, Christopher I Amos, Joellen M Schildkraut, Susan J Ramus, Laura Ottini, Marc T Goodman, Sue K Park, Linda E Kelemen, Harvey A Risch, Mads Thomassen, Kenneth Offit, Jacques Simard, Rita Katharina Schmutzler, Dennis Hazelett, Alvaro N Monteiro, Fergus J Couch, Andrew Berchuck, Georgia Chenevix-Trench, Ellen L Goode, Thomas A Sellers, Simon A Gayther, Antonis C Antoniou, Paul D P Pharoah
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC...
May 2017: Nature Genetics
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