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Jeffrey Gordon

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https://www.readbyqxmd.com/read/28904197/differential-inhibitory-receptor-expression-on-t-cells-delineates-functional-capacities-in-chronic-viral-infection
#1
Jeffrey E Teigler, Gennadiy Zelinskyy, Michael A Eller, Diane L Bolton, Mary Marovich, Alexander D Gordon, Aljawharah Alrubayyi, Galit Alter, Merlin L Robb, Jeffrey N Martin, Steven G Deeks, Nelson L Michael, Ulf Dittmer, Hendrik Streeck
Inhibitory receptors have been extensively described for their importance in regulating immune responses in chronic infections and cancers. Blocking the function of inhibitory receptors such as PD-1, CTLA-4, 2B4, Tim-3, and LAG-3 have shown promise for augmenting CD8 T cell activity and boosting pathogen-specific immunity. However, the prevalence of inhibitory receptors on CD4 T cells and their relative influence on CD4 T cell functionality in chronic HIV infection remains poorly described. We therefore determined and compared inhibitory receptor expression patterns of 2B4, CTLA-4, LAG-3, PD-1, and Tim-3 on virus-specific CD4 and CD8 T cells in relation to their functional T cell profile...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28899863/a-unified-approach-to-targeting-the-lysosome-s-degradative-and-growth-signaling-roles
#2
Vito W Rebecca, Michael C Nicastri, Noel McLaughlin, Colin Fennelly, Quentin McAfee, Amruta Ronghe, Michel Nofal, Chun-Yan Lim, Eric Witze, Cynthia I Chude, Gao Zhang, Gretchen M Alicea, Shengfu Piao, Sengottuvelan Murugan, Rani Ojha, Samuel M Levi, Zhi Wei, Julie S Barber-Rotenberg, Maureen E Murphy, Gordon B Mills, Yiling Lu, Joshua Rabinowitz, Ronen Marmorstein, Qin Liu, Shujing Liu, Xiaowei Xu, Meenhard Herlyn, Roberto Zoncu, Donita C Brady, David W Speicher, Jeffrey D Winkler, Ravi K Amaravadi
Lysosomes serve dual roles in cancer metabolism, executing catabolic programs (i.e. autophagy and macropinocytosis), while promoting mTORC1-dependent anabolism. Antimalarial compounds such as chloroquine or quinacrine have been used as lysosomal inhibitors, but fail to inhibit mTOR signaling. Further, the molecular target of these agents has not been identified. We report a screen of novel dimeric antimalarials that identifies dimeric quinacrines (DQs) as potent anticancer compounds, which concurrently inhibit mTOR and autophagy...
September 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28899096/physical-and-rheological-properties-of-a-novel-emulsifier-frost-grape-polysaccharide-fgp-from-vitis-riparia-michx
#3
William T Hay, Steven F Vaughn, Jeffrey A Byars, Gordon W Selling, Derek M Holthaus, Neil P J Price
A novel emulsifier, Frost grape polysaccharide (FGP), isolated from natural exudate of the species Vitis riparia Michx, was physically and rheologically characterized. The determination of the physical, structural, thermodynamic, emulsification and rheological properties of FGP provide essential details for the commercial adoption of this novel plant polysaccharide. FGP is capable of producing exceptionally stable emulsions when compared with the industrially ubiquitous gum arabic (GA). The FGP isolate contained a negligible amount of nitrogen (0...
September 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28887323/atg5-mediates-a-positive-feedback-loop-between-wnt-signaling-and-autophagy-in-melanoma
#4
Abibatou Ndoye, Anna Budina-Kolomets, Curtis H Kugel, Marie R Webster, Amanpreet Kaur, Reeti Behera, Vito W Rebecca, Ling Li, Patricia A Brafford, Qin Liu, Y N Vashisht Gopal, Michael A Davies, Gordon B Mills, Xiaowei Xu, Hong Wu, Meenhard Herlyn, Michael C Nicastri, Jeffrey D Winkler, Maria S Soengas, Ravi K Amaravadi, Maureen E Murphy, Ashani T Weeraratna
Autophagy mediates resistance to various anticancer agents. In melanoma, resistance to targeted therapy has been linked to expression of Wnt5A, an intrinsic inhibitor of β-catenin, which also promotes invasion. In this study, we assessed the interplay between Wnt5A and autophagy by combining expression studies in human clinical biopsies with functional analyses in cell lines and mouse models. Melanoma cells with high Wnt5A and low β-catenin displayed increased basal autophagy. Genetic blockade of autophagy revealed an unexpected feedback loop whereby knocking down the autophagy factor ATG5 in Wnt5Ahigh cells decreased Wnt5A and increased β-catenin...
September 8, 2017: Cancer Research
https://www.readbyqxmd.com/read/28867358/radiation-induced-large-vessel-cerebral-vasculopathy-in-pediatric-patients-with-brain-tumors-treated-with-proton-radiation-therapy
#5
Stephen F Kralik, Gordon A Watson, Chie-Schin Shih, Chang Y Ho, Whitney Finke, Jeffrey Buchsbaum
PURPOSE: The purpose of this research was to evaluate the incidence, time to development, imaging patterns, risk factors, and clinical significance of large vessel cerebral vasculopathy in pediatric patients with brain tumors treated with proton radiation therapy. METHODS AND MATERIALS: A retrospective study was performed on 75 consecutive pediatric patients with primary brain tumors treated with proton radiation therapy. Radiation-induced large vessel cerebral vasculopathy (RLVCV) was defined as intracranial large vessel arterial stenosis or occlusion confirmed on magnetic resonance angiography, computed tomographic angiography, catheter angiography, or a combination of these within an anatomic region with previous exposure to proton beam therapy and not present before radiation therapy...
July 12, 2017: International Journal of Radiation Oncology, Biology, Physics
https://www.readbyqxmd.com/read/28859014/comparisons-in-the-recovery-response-from-resistance-exercise-between-young-and-middle-aged-men
#6
Joseph A Gordon, Jay R Hoffman, Eliott Arroyo, Alyssa N Varanoske, Nicholas A Coker, Yftach Gepner, Adam J Wells, Jeffrey R Stout, David H Fukuda
The purpose of this study was to compare the effects of a bout of high-volume isokinetic resistance exercise (HVP) on lower-body strength and markers of inflammation and muscle damage during recovery between young and middle-aged men. Nineteen recreationally-trained men were classified as either a young adult (YA: 21.8 ± 2.0 y; 90.7 ± 11.6 kg) or middle-aged adult (MA: 47.0 ± 4.4 y; 96.0 ± 21.5 kg) group. The HVP consisted of 8 sets of 10 repetitions, with one minute of rest between each set, performed on an isokinetic dynamometer at 60°·sec...
August 29, 2017: Journal of Strength and Conditioning Research
https://www.readbyqxmd.com/read/28844421/adolescent-clavicle-nonunions-potential-risk-factors-and-surgical-management
#7
Andrew T Pennock, Eric W Edmonds, Donald S Bae, Mininder S Kocher, Ying Li, Frances A Farley, Henry B Ellis, Philip L Wilson, Jeffrey Nepple, J Eric Gordon, Samuel C Willimon, Michael T Busch, David D Spence, Derek M Kelly, Nirav K Pandya, Coleen S Sabatini, Kevin G Shea, Benton E Heyworth
BACKGROUND: Clavicle nonunions in adolescent patients are exceedingly rare. The purpose of this study was to evaluate a series of clavicle nonunions from a pediatric multicenter study group to assess potential risk factors and treatment outcomes. METHODS: A retrospective review of all clavicle nonunions in patients younger than 19 years was performed at 9 pediatric hospitals between 2006 and 2016. Demographic and surgical data were documented. Radiographs were evaluated for initial fracture classification, displacement, shortening, angulation, and nonunion type...
August 22, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28832619/correction-genome-wide-physical-activity-interactions-in-adiposity-a-meta-analysis-of-200-452-adults
#8
Mariaelisa Graff, Robert A Scott, Anne E Justice, Kristin L Young, Mary F Feitosa, Llilda Barata, Thomas W Winkler, Audrey Y Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L Heard-Costa, Marcel den Hoed, Tarunveer S Ahluwalia, Qibin Qi, Julius S Ngwa, Frida Renström, Lydia Quaye, John D Eicher, James E Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian'an Luan, Jennifer E Huffman, Weihua Zhang, Wei Zhao, Paula J Griffin, Toomas Haller, Shafqat Ahmad, Pedro M Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E Kleber, Mette Hollensted, Kurt Lohman, Natalia V Rivera, John B Whitfield, Jing Hua Zhao, Heather M Stringham, Leo-Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J van der Most, Anne U Jackson, Jennifer L Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Yu-Ching Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N Bergman, Sven Bergmann, Alain G Bertoni, John Blangero, Amélie Bonnefond, Lori L Bonnycastle, Judith B Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S Chines, Francis S Collins, Tanguy Corre, George Davey Smith, Graciela E Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D Hastie, Aki S Havulinna, Dena Hernandez, Lucia Hindorff, Lynne J Hocking, Oddgeir L Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L James, John-Olov Jansson, Min A Jhun, Markus Juonala, Leena Kinnunen, Heikki A Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A Lakka, Lenore J Launer, Benjamin Lehne, Cecilia M Lindgren, Mattias Lorentzon, Robert Luben, Michel Marre, Yuri Milaneschi, Keri L Monda, Grant W Montgomery, Marleen H M De Moor, Antonella Mulas, Martina Müller-Nurasyid, A W Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A Nettleton, Ilja M Nolte, Albertine J Oldehinkel, Matthias Olden, Ken K Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T Raitakari, Tuomo Rankinen, Laura J Rasmussen-Torvik, Rajesh Rawal, Paul M Ridker, Lynda M Rose, Igor Rudan, Cinzia Sarti, Mark A Sarzynski, Kai Savonen, William R Scott, Serena Sanna, Alan R Shuldiner, Steve Sidney, Günther Silbernagel, Blair H Smith, Jennifer A Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J Swift, Tuija Tammelin, Sian-Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V van Vliet-Ostaptchouk, Marie-Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah Wild, Andrew Wong, Alan F Wright, M Carola Zillikens, Niha Zubair, Christopher A Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G Uitterlinden, Louis Pérusse, James F Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C de Geus, Dorret I Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo-Riitta Järvelin, John C Chambers, Jaspal S Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, Göran Hallmans, Torben Hansen, Oluf Pedersen, Andres Metspalu, Nicholas J Wareham, Claudia Langenberg, David R Weir, David J Porteous, Eric Boerwinkle, Daniel I Chasman, Gonçalo R Abecasis, Inês Barroso, Mark I McCarthy, Timothy M Frayling, Jeffrey R O'Connell, Cornelia M van Duijn, Michael Boehnke, Iris M Heid, Karen L Mohlke, David P Strachan, Caroline S Fox, Ching-Ti Liu, Joel N Hirschhorn, Robert J Klein, Andrew D Johnson, Ingrid B Borecki, Paul W Franks, Kari E North, L Adrienne Cupples, Ruth J F Loos, Tuomas O Kilpeläinen
[This corrects the article DOI: 10.1371/journal.pgen.1006528.].
August 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28810145/integrative-analysis-identifies-four-molecular-and-clinical-subsets-in-uveal-melanoma
#9
A Gordon Robertson, Juliann Shih, Christina Yau, Ewan A Gibb, Junna Oba, Karen L Mungall, Julian M Hess, Vladislav Uzunangelov, Vonn Walter, Ludmila Danilova, Tara M Lichtenberg, Melanie Kucherlapati, Patrick K Kimes, Ming Tang, Alexander Penson, Ozgun Babur, Rehan Akbani, Christopher A Bristow, Katherine A Hoadley, Lisa Iype, Matthew T Chang, Andrew D Cherniack, Christopher Benz, Gordon B Mills, Roel G W Verhaak, Klaus G Griewank, Ina Felau, Jean C Zenklusen, Jeffrey E Gershenwald, Lynn Schoenfield, Alexander J Lazar, Mohamed H Abdel-Rahman, Sergio Roman-Roman, Marc-Henri Stern, Colleen M Cebulla, Michelle D Williams, Martine J Jager, Sarah E Coupland, Bita Esmaeli, Cyriac Kandoth, Scott E Woodman
Comprehensive multiplatform analysis of 80 uveal melanomas (UM) identifies four molecularly distinct, clinically relevant subtypes: two associated with poor-prognosis monosomy 3 (M3) and two with better-prognosis disomy 3 (D3). We show that BAP1 loss follows M3 occurrence and correlates with a global DNA methylation state that is distinct from D3-UM. Poor-prognosis M3-UM divide into subsets with divergent genomic aberrations, transcriptional features, and clinical outcomes. We report change-of-function SRSF2 mutations...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28801442/bangladesh-environmental-enteric-dysfunction-beed-study-protocol-for-a-community-based-intervention-study-to-validate-non-invasive-biomarkers-of-environmental-enteric-dysfunction
#10
Mustafa Mahfuz, Subhasish Das, Ramendra Nath Mazumder, M Masudur Rahman, Rashidul Haque, Md Muzibur Rahman Bhuiyan, Hasina Akhter, Md Shafiqul Alam Sarker, Dinesh Mondal, Syed Shafi Ahmed Muaz, A S M Bazlul Karim, Stephen M Borowitz, Christopher A Moskaluk, Michael J Barratt, William A Petri, Jeffrey I Gordon, Tahmeed Ahmed
INTRODUCTION: Environmental enteric dysfunction (EED) is a subacute inflammatory condition of the small intestinal mucosa with unclear aetiology that may account for more than 40% of all cases of stunting. Currently, there are no universally accepted protocols for the diagnosis, treatment and ultimately prevention of EED. The Bangladesh Environmental Enteric Dysfunction (BEED) study is designed to validate non-invasive biomarkers of EED with small intestinal biopsy, better understand disease pathogenesis and identify potential therapeutic targets for interventions designed to control EED and stunting...
August 11, 2017: BMJ Open
https://www.readbyqxmd.com/read/28799899/the-gut-microbiota-food-science-and-human-nutrition-a-timely-marriage
#11
REVIEW
Michael J Barratt, Carlito Lebrilla, Howard-Yana Shapiro, Jeffrey I Gordon
Analytic advances are enabling more precise definitions of the molecular composition of key food staples incorporated into contemporary diets and how the nutrient landscapes of these staples vary as a function of cultivar and food processing methods. This knowledge, combined with insights about the interrelationship between consumer microbiota configurations and biotransformation of food ingredients, should have a number of effects on agriculture, food production, and strategies for improving the nutritional value of foods and health status...
August 9, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28799444/the-msoac-approach-to-developing-performance-outcomes-to-measure-and-monitor-multiple-sclerosis-disability
#12
Nicholas G LaRocca, Lynn D Hudson, Richard Rudick, Dagmar Amtmann, Laura Balcer, Ralph Benedict, Robert Bermel, Ih Chang, Nancy D Chiaravalloti, Peter Chin, Jeffrey A Cohen, Gary R Cutter, Mat D Davis, John DeLuca, Peter Feys, Gordon Francis, Myla D Goldman, Emily Hartley, Raj Kapoor, Fred Lublin, Gary Lundstrom, Paul M Matthews, Nancy Mayo, Richard Meibach, Deborah M Miller, Robert W Motl, Ellen M Mowry, Rob Naismith, Jon Neville, Jennifer Panagoulias, Michael Panzara, Glenn Phillips, Ann Robbins, Matthew F Sidovar, Kathryn E Smith, Bjorn Sperling, Bernard Mj Uitdehaag, Jerry Weaver
BACKGROUND: The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability. OBJECTIVES: (1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials. METHODS: (1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials...
August 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28783708/preferential-induction-of-cross-group-influenza-a-hemagglutinin-stem-specific-memory-b-cells-after-h7n9-immunization-in-humans
#13
Sarah F Andrews, M Gordon Joyce, Michael J Chambers, Rebecca A Gillespie, Masaru Kanekiyo, Kwanyee Leung, Eun Sung Yang, Yaroslav Tsybovsky, Adam K Wheatley, Michelle C Crank, Jeffrey C Boyington, Madhu S Prabhakaran, Sandeep R Narpala, Xuejun Chen, Robert T Bailer, Grace Chen, Emily Coates, Peter D Kwong, Richard A Koup, John R Mascola, Barney S Graham, Julie E Ledgerwood, Adrian B McDermott
Antigenic drift and shift of influenza strains underscore the need for broadly protective influenza vaccines. One strategy is to design immunogens that elicit B cell responses against conserved epitopes on the hemagglutinin (HA) stem. To better understand the elicitation of HA stem-targeted B cells to group 1 and group 2 influenza subtypes, we compared the memory B cell response to group 2 H7N9 and group 1 H5N1 vaccines in humans. Upon H7N9 vaccination, almost half of the HA stem-specific response recognized the group 1 and group 2 subtypes, whereas the response to H5N1 was largely group 1-specific...
July 14, 2017: Science Immunology
https://www.readbyqxmd.com/read/28775213/lactobacillus-reuteri-induces-gut-intraepithelial-cd4-cd8%C3%AE-%C3%AE-t-cells
#14
Luisa Cervantes-Barragan, Jiani N Chai, Ma Diarey Tianero, Blanda DiLuccia, Philip P Ahern, Joseph Merriman, Victor S Cortez, Michael G Caparon, Mohamed S Donia, Susan Gilfillan, Marina Cella, Jeffrey I Gordon, Chyi-Song Hsieh, Marco Colonna
The small intestine contains CD4(+)CD8αα(+) double-positive intraepithelial T lymphocytes (DP IELs), which originate from intestinal CD4(+) T cells through downregulation of the transcription factor ThPOK and have regulatory functions. DP IELs are absent in germ-free mice, suggesting that their differentiation depends on microbial factors. We found that DP IEL numbers in mice varied in different vivaria, correlating with the presence of Lactobacillus reuteri This species induced DP IELs in germ-free mice and conventionally raised mice lacking these cells...
August 3, 2017: Science
https://www.readbyqxmd.com/read/28765138/attitudes-on-cost-effectiveness-and-equity-a-cross-sectional-study-examining-the-viewpoints-of-medical-professionals
#15
David G Li, Gordon X Wong, David T Martin, David J Tybor, Jennifer Kim, Jeffrey Lasker, Roger Mitty, Deeb Salem
OBJECTIVE: To determine the attitudes of physicians and trainees in regard to the roles of both cost-effectiveness and equity in clinical decision making. DESIGN: In this cross-sectional study, electronic surveys containing a hypothetical decision-making scenario were sent to medical professionals to select between two colon cancer screening tests for a population. SETTING: Three Greater Boston academic medical institutions: Tufts University School of Medicine, Tufts Medical Centre and Lahey Hospital and Medical Centre...
August 1, 2017: BMJ Open
https://www.readbyqxmd.com/read/28757305/precision-functional-mapping-of-individual-human-brains
#16
Evan M Gordon, Timothy O Laumann, Adrian W Gilmore, Dillan J Newbold, Deanna J Greene, Jeffrey J Berg, Mario Ortega, Catherine Hoyt-Drazen, Caterina Gratton, Haoxin Sun, Jacqueline M Hampton, Rebecca S Coalson, Annie L Nguyen, Kathleen B McDermott, Joshua S Shimony, Abraham Z Snyder, Bradley L Schlaggar, Steven E Petersen, Steven M Nelson, Nico U F Dosenbach
Human functional MRI (fMRI) research primarily focuses on analyzing data averaged across groups, which limits the detail, specificity, and clinical utility of fMRI resting-state functional connectivity (RSFC) and task-activation maps. To push our understanding of functional brain organization to the level of individual humans, we assembled a novel MRI dataset containing 5 hr of RSFC data, 6 hr of task fMRI, multiple structural MRIs, and neuropsychological tests from each of ten adults. Using these data, we generated ten high-fidelity, individual-specific functional connectomes...
August 16, 2017: Neuron
https://www.readbyqxmd.com/read/28741850/no-evidence-for-ecological-segregation-protecting-native-trout-from-invasive-hybridization
#17
Ryan P Kovach, Clint C Muhlfeld, Robert Al-Chokhachy, Stephen J Amish, Jeffrey L Kershner, Robb F Leary, Winsor H Lowe, Gordon Luikart, Phil Matson, David A Schmetterling, Bradley B Shepard, Peter A H Westley, Diane Whited, Andrew Whiteley, Fred W Allendorf
We appreciate the comments of Young et al. (2017) on our recent paper (Muhlfeld et al., 2017) concerning spatiotemporal dynamics of hybridization between native westslope cutthroat trout (Oncoryhnchus clarkii lewisi; WCT) and introduced coastal rainbow trout (O. mykiss irideus; RBT). Nevertheless, we believe there is no evidence for "ecological segregation" protecting WCT from invasive RBT. Here we consider their three major arguments for ecological segregation and find their conclusions invalid. This article is protected by copyright...
July 25, 2017: Global Change Biology
https://www.readbyqxmd.com/read/28737409/low-buffer-capacity-and-alternating-motility-along-the-human-gastrointestinal-tract-implications-for-in-vivo-dissolution-and-absorption-of-ionizable-drugs
#18
Bart Hens, Yasuhiro Tsume, Marival Bermejo, Paulo Paixao, Mark J Koenigsknecht, Jason R Baker, William L Hasler, Robert Lionberger, Jianghong Fan, Joseph Dickens, Kerby Shedden, Bo Wen, Jeffrey Wysocki, Raimar Loebenberg, Allen Lee, Ann Frances, Greg Amidon, Alex Yu, Gail Benninghoff, Niloufar Salehi, Arjang Talattof, Duxin Sun, Gordon L Amidon
In this study, we determined the pH and buffer capacity of human gastrointestinal (GI) fluids (aspirated from the stomach, duodenum, proximal jejunum, and mid/distal jejunum) as a function of time, from 37 healthy subjects after oral administration of an 800 mg immediate-release tablet of ibuprofen (reference listed drug; RLD) under typical prescribed bioequivalence (BE) study protocol conditions in both fasted and fed states (simulated by ingestion of a liquid meal). Simultaneously, motility was continuously monitored using water-perfused manometry...
August 4, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28714866/ibrutinib-treatment-improves-t-cell-number-and-function-in-cll-patients
#19
Meixiao Long, Kyle Beckwith, Priscilla Do, Bethany L Mundy, Amber Gordon, Amy M Lehman, Kami J Maddocks, Carolyn Cheney, Jeffrey A Jones, Joseph M Flynn, Leslie A Andritsos, Farrukh Awan, Joseph A Fraietta, Carl H June, Marcela V Maus, Jennifer A Woyach, Michael A Caligiuri, Amy J Johnson, Natarajan Muthusamy, John C Byrd
BACKGROUND: Ibrutinib has been shown to have immunomodulatory effects by inhibiting Bruton's tyrosine kinase (BTK) and IL-2-inducible T cell kinase (ITK). The relative importance of inhibiting these 2 kinases has not been examined despite its relevance to immune-based therapies. METHODS: Peripheral blood mononuclear cells from chronic lymphocytic leukemia (CLL) patients on clinical trials of ibrutinib (BTK/ITK inhibitor; n = 19) or acalabrutinib (selective BTK inhibitor; n = 13) were collected serially...
August 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28693366/idarucizumab-for-dabigatran-reversal-full-cohort-analysis
#20
MULTICENTER STUDY
Charles V Pollack, Paul A Reilly, Joanne van Ryn, John W Eikelboom, Stephan Glund, Richard A Bernstein, Robert Dubiel, Menno V Huisman, Elaine M Hylek, Chak-Wah Kam, Pieter W Kamphuisen, Jörg Kreuzer, Jerrold H Levy, Gordon Royle, Frank W Sellke, Joachim Stangier, Thorsten Steiner, Peter Verhamme, Bushi Wang, Laura Young, Jeffrey I Weitz
BACKGROUND: Idarucizumab, a monoclonal antibody fragment, was developed to reverse the anticoagulant effect of dabigatran. METHODS: We performed a multicenter, prospective, open-label study to determine whether 5 g of intravenous idarucizumab would be able to reverse the anticoagulant effect of dabigatran in patients who had uncontrolled bleeding (group A) or were about to undergo an urgent procedure (group B). The primary end point was the maximum percentage reversal of the anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, on the basis of the diluted thrombin time or ecarin clotting time...
August 3, 2017: New England Journal of Medicine
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