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(Ryan Shaw)

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https://www.readbyqxmd.com/read/28714976/rare-coding-variants-in-plcg2-abi3-and-trem2-implicate-microglial-mediated-innate-immunity-in-alzheimer-s-disease
#1
Rebecca Sims, Sven J van der Lee, Adam C Naj, Céline Bellenguez, Nandini Badarinarayan, Johanna Jakobsdottir, Brian W Kunkle, Anne Boland, Rachel Raybould, Joshua C Bis, Eden R Martin, Benjamin Grenier-Boley, Stefanie Heilmann-Heimbach, Vincent Chouraki, Amanda B Kuzma, Kristel Sleegers, Maria Vronskaya, Agustin Ruiz, Robert R Graham, Robert Olaso, Per Hoffmann, Megan L Grove, Badri N Vardarajan, Mikko Hiltunen, Markus M Nöthen, Charles C White, Kara L Hamilton-Nelson, Jacques Epelbaum, Wolfgang Maier, Seung-Hoan Choi, Gary W Beecham, Cécile Dulary, Stefan Herms, Albert V Smith, Cory C Funk, Céline Derbois, Andreas J Forstner, Shahzad Ahmad, Hongdong Li, Delphine Bacq, Denise Harold, Claudia L Satizabal, Otto Valladares, Alessio Squassina, Rhodri Thomas, Jennifer A Brody, Liming Qu, Pascual Sánchez-Juan, Taniesha Morgan, Frank J Wolters, Yi Zhao, Florentino Sanchez Garcia, Nicola Denning, Myriam Fornage, John Malamon, Maria Candida Deniz Naranjo, Elisa Majounie, Thomas H Mosley, Beth Dombroski, David Wallon, Michelle K Lupton, Josée Dupuis, Patrice Whitehead, Laura Fratiglioni, Christopher Medway, Xueqiu Jian, Shubhabrata Mukherjee, Lina Keller, Kristelle Brown, Honghuang Lin, Laura B Cantwell, Francesco Panza, Bernadette McGuinness, Sonia Moreno-Grau, Jeremy D Burgess, Vincenzo Solfrizzi, Petra Proitsi, Hieab H Adams, Mariet Allen, Davide Seripa, Pau Pastor, L Adrienne Cupples, Nathan D Price, Didier Hannequin, Ana Frank-García, Daniel Levy, Paramita Chakrabarty, Paolo Caffarra, Ina Giegling, Alexa S Beiser, Vilmantas Giedraitis, Harald Hampel, Melissa E Garcia, Xue Wang, Lars Lannfelt, Patrizia Mecocci, Gudny Eiriksdottir, Paul K Crane, Florence Pasquier, Virginia Boccardi, Isabel Henández, Robert C Barber, Martin Scherer, Lluis Tarraga, Perrie M Adams, Markus Leber, Yuning Chen, Marilyn S Albert, Steffi Riedel-Heller, Valur Emilsson, Duane Beekly, Anne Braae, Reinhold Schmidt, Deborah Blacker, Carlo Masullo, Helena Schmidt, Rachelle S Doody, Gianfranco Spalletta, W T Longstreth Jr, Thomas J Fairchild, Paola Bossù, Oscar L Lopez, Matthew P Frosch, Eleonora Sacchinelli, Bernardino Ghetti, Qiong Yang, Ryan M Huebinger, Frank Jessen, Shuo Li, M Ilyas Kamboh, John Morris, Oscar Sotolongo-Grau, Mindy J Katz, Chris Corcoran, Melanie Dunstan, Amy Braddel, Charlene Thomas, Alun Meggy, Rachel Marshall, Amy Gerrish, Jade Chapman, Miquel Aguilar, Sarah Taylor, Matt Hill, Mònica Díez Fairén, Angela Hodges, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Makrina Daniilidou, James Uphill, Yogen Patel, Joseph T Hughes, Jenny Lord, James Turton, Annette M Hartmann, Roberta Cecchetti, Chiara Fenoglio, Maria Serpente, Marina Arcaro, Carlo Caltagirone, Maria Donata Orfei, Antonio Ciaramella, Sabrina Pichler, Manuel Mayhaus, Wei Gu, Alberto Lleó, Juan Fortea, Rafael Blesa, Imelda S Barber, Keeley Brookes, Chiara Cupidi, Raffaele Giovanni Maletta, David Carrell, Sandro Sorbi, Susanne Moebus, Maria Urbano, Alberto Pilotto, Johannes Kornhuber, Paolo Bosco, Stephen Todd, David Craig, Janet Johnston, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Nick C Fox, John Hardy, Roger L Albin, Liana G Apostolova, Steven E Arnold, Sanjay Asthana, Craig S Atwood, Clinton T Baldwin, Lisa L Barnes, Sandra Barral, Thomas G Beach, James T Becker, Eileen H Bigio, Thomas D Bird, Bradley F Boeve, James D Bowen, Adam Boxer, James R Burke, Jeffrey M Burns, Joseph D Buxbaum, Nigel J Cairns, Chuanhai Cao, Chris S Carlson, Cynthia M Carlsson, Regina M Carney, Minerva M Carrasquillo, Steven L Carroll, Carolina Ceballos Diaz, Helena C Chui, David G Clark, David H Cribbs, Elizabeth A Crocco, Charles DeCarli, Malcolm Dick, Ranjan Duara, Denis A Evans, Kelley M Faber, Kenneth B Fallon, David W Fardo, Martin R Farlow, Steven Ferris, Tatiana M Foroud, Douglas R Galasko, Marla Gearing, Daniel H Geschwind, John R Gilbert, Neill R Graff-Radford, Robert C Green, John H Growdon, Ronald L Hamilton, Lindy E Harrell, Lawrence S Honig, Matthew J Huentelman, Christine M Hulette, Bradley T Hyman, Gail P Jarvik, Erin Abner, Lee-Way Jin, Gyungah Jun, Anna Karydas, Jeffrey A Kaye, Ronald Kim, Neil W Kowall, Joel H Kramer, Frank M LaFerla, James J Lah, James B Leverenz, Allan I Levey, Ge Li, Andrew P Lieberman, Kathryn L Lunetta, Constantine G Lyketsos, Daniel C Marson, Frank Martiniuk, Deborah C Mash, Eliezer Masliah, Wayne C McCormick, Susan M McCurry, Andrew N McDavid, Ann C McKee, Marsel Mesulam, Bruce L Miller, Carol A Miller, Joshua W Miller, John C Morris, Jill R Murrell, Amanda J Myers, Sid O'Bryant, John M Olichney, Vernon S Pankratz, Joseph E Parisi, Henry L Paulson, William Perry, Elaine Peskind, Aimee Pierce, Wayne W Poon, Huntington Potter, Joseph F Quinn, Ashok Raj, Murray Raskind, Barry Reisberg, Christiane Reitz, John M Ringman, Erik D Roberson, Ekaterina Rogaeva, Howard J Rosen, Roger N Rosenberg, Mark A Sager, Andrew J Saykin, Julie A Schneider, Lon S Schneider, William W Seeley, Amanda G Smith, Joshua A Sonnen, Salvatore Spina, Robert A Stern, Russell H Swerdlow, Rudolph E Tanzi, Tricia A Thornton-Wells, John Q Trojanowski, Juan C Troncoso, Vivianna M Van Deerlin, Linda J Van Eldik, Harry V Vinters, Jean Paul Vonsattel, Sandra Weintraub, Kathleen A Welsh-Bohmer, Kirk C Wilhelmsen, Jennifer Williamson, Thomas S Wingo, Randall L Woltjer, Clinton B Wright, Chang-En Yu, Lei Yu, Fabienne Garzia, Feroze Golamaully, Gislain Septier, Sebastien Engelborghs, Rik Vandenberghe, Peter P De Deyn, Carmen Muñoz Fernadez, Yoland Aladro Benito, Hakan Thonberg, Charlotte Forsell, Lena Lilius, Anne Kinhult-Stählbom, Lena Kilander, RoseMarie Brundin, Letizia Concari, Seppo Helisalmi, Anne Maria Koivisto, Annakaisa Haapasalo, Vincent Dermecourt, Nathalie Fievet, Olivier Hanon, Carole Dufouil, Alexis Brice, Karen Ritchie, Bruno Dubois, Jayanadra J Himali, C Dirk Keene, JoAnn Tschanz, Annette L Fitzpatrick, Walter A Kukull, Maria Norton, Thor Aspelund, Eric B Larson, Ron Munger, Jerome I Rotter, Richard B Lipton, María J Bullido, Albert Hofman, Thomas J Montine, Eliecer Coto, Eric Boerwinkle, Ronald C Petersen, Victoria Alvarez, Fernando Rivadeneira, Eric M Reiman, Maura Gallo, Christopher J O'Donnell, Joan S Reisch, Amalia Cecilia Bruni, Donald R Royall, Martin Dichgans, Mary Sano, Daniela Galimberti, Peter St George-Hyslop, Elio Scarpini, Debby W Tsuang, Michelangelo Mancuso, Ubaldo Bonuccelli, Ashley R Winslow, Antonio Daniele, Chuang-Kuo Wu, Oliver Peters, Benedetta Nacmias, Matthias Riemenschneider, Reinhard Heun, Carol Brayne, David C Rubinsztein, Jose Bras, Rita Guerreiro, Ammar Al-Chalabi, Christopher E Shaw, John Collinge, David Mann, Magda Tsolaki, Jordi Clarimón, Rebecca Sussams, Simon Lovestone, Michael C O'Donovan, Michael J Owen, Timothy W Behrens, Simon Mead, Alison M Goate, Andre G Uitterlinden, Clive Holmes, Carlos Cruchaga, Martin Ingelsson, David A Bennett, John Powell, Todd E Golde, Caroline Graff, Philip L De Jager, Kevin Morgan, Nilufer Ertekin-Taner, Onofre Combarros, Bruce M Psaty, Peter Passmore, Steven G Younkin, Claudine Berr, Vilmundur Gudnason, Dan Rujescu, Dennis W Dickson, Jean-François Dartigues, Anita L DeStefano, Sara Ortega-Cubero, Hakon Hakonarson, Dominique Campion, Merce Boada, John Keoni Kauwe, Lindsay A Farrer, Christine Van Broeckhoven, M Arfan Ikram, Lesley Jones, Jonathan L Haines, Christophe Tzourio, Lenore J Launer, Valentina Escott-Price, Richard Mayeux, Jean-François Deleuze, Najaf Amin, Peter A Holmans, Margaret A Pericak-Vance, Philippe Amouyel, Cornelia M van Duijn, Alfredo Ramirez, Li-San Wang, Jean-Charles Lambert, Sudha Seshadri, Julie Williams, Gerard D Schellenberg
We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p...
July 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28622927/evolution-of-the-hominin-knee-and-ankle
#2
Mélanie A Frelat, Colin N Shaw, Simone Sukhdeo, Jean-Jacques Hublin, Stefano Benazzi, Timothy M Ryan
The dispersal of the genus Homo out of Africa approximately 1.8 million years ago (Ma) has been understood within the context of changes in diet, behavior, and bipedal locomotor efficiency. While various morphological characteristics of the knee and ankle joints are considered part of a suite of traits indicative of, and functionally related to, habitual bipedal walking, the timing and phylogenetic details of these morphological changes remain unclear. To evaluate the timing of knee and ankle joint evolution, we apply geometric morphometric methods to three-dimensional digital models of the proximal and distal tibiae of fossil hominins, Holocene Homo sapiens, and extant great apes...
July 2017: Journal of Human Evolution
https://www.readbyqxmd.com/read/28616546/late-gadolinium-enhancement-does-occur-in-tako-tsubo-cardiomyopathy-a-quantitative-cardiac-magnetic-resonance-and-speckle-tracking-strain-study
#3
Niranjan Gaikwad, Thomas Butler, Ryan Maxwell, Elizabeth Shaw, Wendy E Strugnell, Jonathan Chan, Gemma A Figtree, Richard E Slaughter, Christian Hamilton-Craig
BACKGROUND: Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) has been recommended to distinguish Tako-tsubo cardiomyopathy (TTC) from either acute myocardial infarction or myocarditis. METHOD: 44 consecutive patients with confirmed Mayo Clinic criteria for TTC underwent CMR imaging at 1.5 Tesla during the acute phase. 10 patients who had CMRI to exclude scar related ventricular tachycardia, and had negative studies, were used as negative controls...
September 2016: IJC Heart & Vasculature
https://www.readbyqxmd.com/read/28613340/energy-transfer-from-colloidal-nanocrystals-to-strongly-absorbing-perovskites
#4
Yasiel Cabrera, Sara M Rupich, Ryan Shaw, Benoy Anand, Manuel de Anda Villa, Rezwanur Rahman, Aaron Dangerfield, Yuri N Gartstein, Anton V Malko, Yves J Chabal
Integration of colloidal nanocrystal quantum dots (NQDs) with strongly absorbing semiconductors offers the possibility of developing optoelectronic and photonic devices with new functionalities. We examine the process of energy transfer (ET) from photoactive CdSe/ZnS core/shell NQDs into lead-halide perovskite polycrystalline films as a function of distance from the perovskite surface using time-resolved photoluminescence (TRPL) spectroscopy. We demonstrate near-field electromagnetic coupling between vastly dissimilar excitation in two materials that can reach an efficiency of 99% at room temperature...
June 29, 2017: Nanoscale
https://www.readbyqxmd.com/read/28607831/primary-care-integration-of-psychiatric-and-behavioral-health-services-a-primer-for-providers-and-case-report-of-local-implementation
#5
Anthony Ps Guerrero, Cori L Takesue, Jared Hn Medeiros, Aileen A Duran, Joseph W Humphry, Ryan M Lunsford, Diana V Shaw, Michael H Fukuda, Earl S Hishinuma
Mental health conditions are common, disabling, potentially life-threatening, and costly; however, they are mostly treatable with early detection and intervention. Unfortunately, mental healthcare is in significantly short supply both nationally and locally, and particularly in small, rural, and relatively isolated communities. This article provides physicians and other health practitioners with a primer on the basic rationale and principles of integrating behavioral healthcare - particularly psychiatric specialty care - in primary care settings, including effective use of teleconferencing...
June 2017: Hawai'i Journal of Medicine & Public Health: a Journal of Asia Pacific Medicine & Public Health
https://www.readbyqxmd.com/read/28592496/male-infertility-is-responsible-for-nearly-half-of-the-extinction-observed-in-the-mouse-collaborative-cross
#6
John R Shorter, Fanny Odet, David L Aylor, Wenqi Pan, Chia-Yu Kao, Chen-Ping Fu, Andrew P Morgan, Seth Greenstein, Timothy A Bell, Alicia M Stevans, Ryan W Feathers, Sunny Patel, Sarah E Cates, Ginger D Shaw, Darla R Miller, Elissa J Chesler, Leonard McMillian, Deborah A O'Brien, Fernando Pardo-Manuel de Villena
The goal of the Collaborative Cross (CC) project was to generate and distribute over 1000 independent mouse recombinant inbred strains derived from eight inbred founders. With inbreeding nearly complete, we estimated the extinction rate among CC lines at a remarkable 95%, which is substantially higher than in the derivation of other mouse recombinant inbred populations. Here, we report genome-wide allele frequencies in 347 extinct CC lines. Contrary to expectations, autosomes had equal allelic contributions from the eight founders, but chromosome X had significantly lower allelic contributions from the two inbred founders with underrepresented subspecific origins (PWK/PhJ and CAST/EiJ)...
June 2017: Genetics
https://www.readbyqxmd.com/read/28546579/corrigendum-smchd1-mutations-associated-with-a-rare-muscular-dystrophy-can-also-cause-isolated-arhinia-and-bosma-arhinia-microphthalmia-syndrome
#7
Natalie D Shaw, Harrison Brand, Zachary A Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I Jones, Serkan Erdin, Kathleen A Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B Currall, Donncha S Dunican, Ryan L Collins, Jason R Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F Lippincott, Sylvia S Singh, Nirav Patel, Jenny W Jing, Jennifer R Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E García-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D Hoffman, Wolfgang Mühlbauer, Klaus W Ruprecht, Bart L Loeys, Masato Shino, Angela M Kaindl, Chie-Hee Cho, Cynthia C Morton, Richard R Meehan, Veronica van Heyningen, Eric C Liao, Ravikumar Balasubramanian, Janet E Hall, Stephanie B Seminara, Daniel Macarthur, Steven A Moore, Koh-Ichiro Yoshiura, James F Gusella, Joseph A Marsh, John M Graham, Angela E Lin, Nicholas Katsanis, Peter L Jones, William F Crowley, Erica E Davis, David R FitzPatrick, Michael E Talkowski
No abstract text is available yet for this article.
May 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28544228/synthesis-of-benzodihydrofurans-by-asymmetric-c-h-insertion-reactions-of-donor-donor-carbenoids
#8
Jared Thomas Shaw, Kellan N Lamb, Richard A Squitieri, Srinivasa R Chintala, Ada J Kwong, Edward I Balmond, Cristian Soldi, Olga Dmytrenko, Marta Castiñeira Reis, Ryan Chung, J Bennett Addison, James C Fettinger, Jason C Hein, Dean J Tantillo, Joseph M Fox
Metal carbenoids appended with two electron-donating groups, known as "donor/donor" carbenoids, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of carbenoids with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2)...
May 22, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28523115/discovery-of-fevipiprant-nvp-qaw039-a-potent-and-selective-dp2-receptor-antagonist-for-treatment-of-asthma
#9
David A Sandham, Lucy Barker, Lyndon Brown, Zarin Brown, David Budd, Steven J Charlton, Devnandan Chatterjee, Brian Cox, Gerald Dubois, Nicholas Duggan, Edward Hall, Julia Hatto, Janet Maas, Jodie Manini, Rachael Profit, Darren Riddy, Catherine Ritchie, Bindi Sohal, Duncan Shaw, Rowan Stringer, David A Sykes, Matthew Thomas, Katharine L Turner, Simon J Watson, Ryan West, Elisabeth Willard, Gareth Williams, Jennifer Willis
Further optimization of an initial DP2 receptor antagonist clinical candidate NVP-QAV680 led to the discovery of a follow-up molecule 2-(2-methyl-1-(4-(methylsulfonyl)-2-(trifluoromethyl)benzyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)acetic acid (compound 11, NVP-QAW039, fevipiprant), which exhibits improved potency on human eosinophils and Th2 cells, together with a longer receptor residence time, and is currently in clinical trials for severe asthma.
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28411174/evaluation-of-hematopoietic-stem-cell-mobilization-rates-with-early-plerixafor-administration-for-adult-stem-cell-transplantation
#10
Jessica T Stover, J Ryan Shaw, Maragatha Kuchibhatla, Mitchell E Horwitz, Ashley M Engemann
The addition of plerixafor to high-dose colony-stimulating growth factor has been shown to improve stem cell mobilization rates in autologous transplant patients with multiple myeloma and non-Hodgkin lymphoma. This study evaluates the change in administration time of plerixafor to determine if cell mobilization rates are similar between the US Food and Drug Administration-approved administration time of 11 hours before apheresis and an earlier administration time of 16 hours before apheresis. Medical records of patients age ≥ 18 years undergoing autologous stem cell transplantation requiring the use of plerixafor after at least 4 days of granulocyte colony-stimulating factor therapy to complete stem cell mobilization from January 1, 2010 through September 30, 2014 were retrospectively reviewed...
August 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28347480/electrocardiographic-interference-by-a-sacral-neuromodulation-device
#11
Laiden Suarez-Fuster, Bryce Alexander, Ryan Renaud, Catherine Shaw, Adrian Baranchuk
No abstract text is available yet for this article.
July 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28323896/biological-phosphorylation-of-an-unnatural-base-pair-ubp-using-a-drosophila-melanogaster-deoxynucleoside-kinase-dmdnk-mutant
#12
Fei Chen, Yuan Zhang, Ashley B Daugherty, Zunyi Yang, Ryan Shaw, Mengxing Dong, Stefan Lutz, Steven A Benner
One research goal for unnatural base pair (UBP) is to replicate, transcribe and translate them in vivo. Accordingly, the corresponding unnatural nucleoside triphosphates must be available at sufficient concentrations within the cell. To achieve this goal, the unnatural nucleoside analogues must be phosphorylated to the corresponding nucleoside triphosphates by a cascade of three kinases. The first step is the monophosphorylation of unnatural deoxynucleoside catalyzed by deoxynucleoside kinases (dNK), which is generally considered the rate limiting step because of the high specificity of dNKs...
2017: PloS One
https://www.readbyqxmd.com/read/28298420/staged-induction-of-hiv-1-glycan-dependent-broadly-neutralizing-antibodies
#13
Mattia Bonsignori, Edward F Kreider, Daniela Fera, R Ryan Meyerhoff, Todd Bradley, Kevin Wiehe, S Munir Alam, Baptiste Aussedat, William E Walkowicz, Kwan-Ki Hwang, Kevin O Saunders, Ruijun Zhang, Morgan A Gladden, Anthony Monroe, Amit Kumar, Shi-Mao Xia, Melissa Cooper, Mark K Louder, Krisha McKee, Robert T Bailer, Brendan W Pier, Claudia A Jette, Garnett Kelsoe, Wilton B Williams, Lynn Morris, John Kappes, Kshitij Wagh, Gift Kamanga, Myron S Cohen, Peter T Hraber, David C Montefiori, Ashley Trama, Hua-Xin Liao, Thomas B Kepler, M Anthony Moody, Feng Gao, Samuel J Danishefsky, John R Mascola, George M Shaw, Beatrice H Hahn, Stephen C Harrison, Bette T Korber, Barton F Haynes
A preventive HIV-1 vaccine should induce HIV-1-specific broadly neutralizing antibodies (bnAbs). However, bnAbs generally require high levels of somatic hypermutation (SHM) to acquire breadth, and current vaccine strategies have not been successful in inducing bnAbs. Because bnAbs directed against a glycosylated site adjacent to the third variable loop (V3) of the HIV-1 envelope protein require limited SHM, the V3-glycan epitope is an attractive vaccine target. By studying the cooperation among multiple V3-glycan B cell lineages and their coevolution with autologous virus throughout 5 years of infection, we identify key events in the ontogeny of a V3-glycan bnAb...
March 15, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28280493/t-cells-specific-for-a-self-peptide-of-apob-100-exacerbate-aortic-atheroma-in-murine-atherosclerosis
#14
Michael K Shaw, Kevin Y Tse, Xiaoqing Zhao, Kathryn Welch, Daniel T Eitzman, Raghavendar R Thipparthi, Paul C Montgomery, Ryan Thummel, Harley Y Tse
On the basis of mouse I-A(b)-binding motifs, two sequences of the murine apolipoprotein B-100 (mApoB-100), mApoB-1003501-3515 (designated P3) and mApoB-100978-992 (designated P6), were found to be immunogenic. In this report, we show that P6 is also atherogenic. Immunization of Apoe(-/-) mice fed a high-fat diet (HFD) with P6 resulted in enhanced development of aortic atheroma as compared to control mice immunized with an irrelevant peptide MOG35-55 or with complete Freund's adjuvant alone. Adoptive transfer of lymph node cells from P6-immunized donor mice to recipients fed an HFD caused exacerbated aortic atheromas, correlating P6-primed cells with disease development...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28249154/%C3%AE-hydroxybutyrate-deactivates-neutrophil-nlrp3-inflammasome-to-relieve-gout-flares
#15
Emily L Goldberg, Jennifer L Asher, Ryan D Molony, Albert C Shaw, Caroline J Zeiss, Chao Wang, Ludmilla A Morozova-Roche, Raimund I Herzog, Akiko Iwasaki, Vishwa Deep Dixit
Aging and lipotoxicity are two major risk factors for gout that are linked by the activation of the NLRP3 inflammasome. Neutrophil-mediated production of interleukin-1β (IL-1β) drives gouty flares that cause joint destruction, intense pain, and fever. However, metabolites that impact neutrophil inflammasome remain unknown. Here, we identified that ketogenic diet (KD) increases β-hydroxybutyrate (BHB) and alleviates urate crystal-induced gout without impairing immune defense against bacterial infection. BHB inhibited NLRP3 inflammasome in S100A9 fibril-primed and urate crystal-activated macrophages, which serve to recruit inflammatory neutrophils in joints...
February 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/28221189/a-retrospective-analysis-of-the-efficacy-of-pembrolizumab-in-melanoma-patients-with-brain-metastasis
#16
Ibiayi Dagogo-Jack, Michael Lanfranchi, Justin F Gainor, Anita Giobbie-Hurder, Donald P Lawrence, Alice T Shaw, Ryan J Sullivan
A total of 50% of patients with melanoma will develop brain metastasis (BM). Pembrolizumab was approved for treatment of metastatic melanoma on the basis of significant systemic antitumor activity. Because of low enrollment of patients with BM in pembrolizumab trials, efficacy against melanoma BM remains unknown. We reviewed records of 89 consecutive patients with melanoma treated with pembrolizumab at our institution between May 1, 2014 and October 31, 2015 to determine the time to progression. Thirty-six (40%) patients had BM before pembrolizumab...
February 17, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28114542/wearable-technology-and-long-term-weight-loss
#17
LETTER
Corrine I Voils, Ryan J Shaw
No abstract text is available yet for this article.
January 17, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28104455/a-novel-role-for-endothelial-tetrahydrobiopterin-in-mitochondrial-redox-balance
#18
Jade Bailey, Andrew Shaw, Roman Fischer, Brent J Ryan, Benedikt M Kessler, James McCullagh, Richard Wade-Martins, Keith M Channon, Mark J Crabtree
The redox co-factor tetrahydrobiopterin (BH4) regulates nitric oxide (NO) and reactive oxygen species (ROS) production by endothelial NOS (eNOS) and is an important redox-dependent signalling molecule in the endothelium. Loss of endothelial BH4 is observed in cardiovascular disease (CVD) states and results in decreased NO and increased superoxide (O2(-)) generation via eNOS uncoupling. Genetic mouse models of augmented endothelial BH4 synthesis have shown proof of concept that endothelial BH4 can alter CVD pathogenesis...
March 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28093637/exploring-differences-in-adverse-symptom-event-grading-thresholds-between-clinicians-and-patients-in-the-clinical-trial-setting
#19
Thomas M Atkinson, Lauren J Rogak, Narre Heon, Sean J Ryan, Mary Shaw, Liora P Stark, Antonia V Bennett, Ethan Basch, Yuelin Li
PURPOSE: Symptomatic adverse event (AE) monitoring is essential in cancer clinical trials to assess patient safety, as well as inform decisions related to treatment and continued trial participation. As prior research has demonstrated that conventional concordance metrics (e.g., intraclass correlation) may not capture nuanced aspects of the association between clinician and patient-graded AEs, we aimed to characterize differences in AE grading thresholds between doctors (MDs), registered nurses (RNs), and patients using the Bayesian Graded Item Response Model (GRM)...
April 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28067909/smchd1-mutations-associated-with-a-rare-muscular-dystrophy-can-also-cause-isolated-arhinia-and-bosma-arhinia-microphthalmia-syndrome
#20
Natalie D Shaw, Harrison Brand, Zachary A Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I Jones, Serkan Erdin, Kathleen A Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B Currall, Donncha S Dunican, Ryan L Collins, Jason R Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F Lippincott, Sylvia S Singh, Nirav Patel, Jenny W Jing, Jennifer R Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E García-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D Hoffman, Wolfgang Mühlbauer, Klaus W Ruprecht, Bart L Loeys, Masato Shino, Angela M Kaindl, Chie-Hee Cho, Cynthia C Morton, Richard R Meehan, Veronica van Heyningen, Eric C Liao, Ravikumar Balasubramanian, Janet E Hall, Stephanie B Seminara, Daniel Macarthur, Steven A Moore, Koh-Ichiro Yoshiura, James F Gusella, Joseph A Marsh, John M Graham, Angela E Lin, Nicholas Katsanis, Peter L Jones, William F Crowley, Erica E Davis, David R FitzPatrick, Michael E Talkowski
Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders...
February 2017: Nature Genetics
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