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Kenneth Wang

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https://www.readbyqxmd.com/read/29453451/prevalence-and-impact-of-baseline-resistance-associated-substitutions-on-the-efficacy-of-ledipasvir-sofosbuvir-or-simeprevir-sofosbuvir-against-gt1-hcv-infection
#1
Gary P Wang, Norah Terrault, Jacqueline D Reeves, Lin Liu, Eric Li, Lisa Zhao, Joseph K Lim, Giuseppe Morelli, Alexander Kuo, Josh Levitsky, Kenneth E Sherman, Lynn M Frazier, Ananthakrishnan Ramani, Joy Peter, Lucy Akuskevich, Michael W Fried, David R Nelson
Baseline resistance-associated substitutions (RASs) have variable impacts in clinical trials but their prevalence and impact in real-world patients remains unclear. We performed baseline resistance testing using a commercial assay (10% cutoff) for 486 patients treated with LDV/SOF or SMV/SOF, with or without ribavirin, in the multi-center, observational HCV-TARGET cohort. Linkage of RASs was evaluated in selected samples using a novel quantitative single variant sequencing assay. Our results showed that the prevalence of NS3, NS5A, NS5B RASs was 45%, 13%, and 8%, respectively, and 10% of patients harbored RASs in 2 or more drug classes...
February 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29449192/association-of-body-mass-index-and-outcomes-in-patients-with-metastatic-melanoma-treated-with-targeted-therapy-immunotherapy-or-chemotherapy-a-retrospective-multicohort-analysis
#2
Jennifer L McQuade, Carrie R Daniel, Kenneth R Hess, Carmen Mak, Daniel Y Wang, Rajat R Rai, John J Park, Lauren E Haydu, Christine Spencer, Matthew Wongchenko, Stephen Lane, Dung-Yang Lee, Mathilde Kaper, Meredith McKean, Kathryn E Beckermann, Samuel M Rubinstein, Isabelle Rooney, Luna Musib, Nageshwar Budha, Jessie Hsu, Theodore S Nowicki, Alexandre Avila, Tomas Haas, Maneka Puligandla, Sandra Lee, Shenying Fang, Jennifer A Wargo, Jeffrey E Gershenwald, Jeffrey E Lee, Patrick Hwu, Paul B Chapman, Jeffrey A Sosman, Dirk Schadendorf, Jean-Jacques Grob, Keith T Flaherty, Dana Walker, Yibing Yan, Edward McKenna, Jeffrey J Legos, Matteo S Carlino, Antoni Ribas, John M Kirkwood, Georgina V Long, Douglas B Johnson, Alexander M Menzies, Michael A Davies
BACKGROUND: Obesity has been linked to increased mortality in several cancer types; however, the relation between obesity and survival outcomes in metastatic melanoma is unknown. The aim of this study was to examine the association between body-mass index (BMI) and progression-free survival or overall survival in patients with metastatic melanoma who received targeted therapy, immunotherapy, or chemotherapy. METHODS: This retrospective study analysed independent cohorts of patients with metastatic melanoma assigned to treatment with targeted therapy, immunotherapy, or chemotherapy in randomised clinical trials and one retrospective study of patients treated with immunotherapy...
February 12, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29446198/mutational-spectrum-in-a-worldwide-study-of-29-700-families-with-brca1-or-brca2-mutations
#3
Timothy R Rebbeck, Tara M Friebel, Eitan Friedman, Ute Hamann, Dezheng Huo, Ava Kwong, Edith Olah, Olufunmilayo I Olopade, Angela R Solano, Soo-Hwang Teo, Mads Thomassen, Jeffrey N Weitzel, T L Chan, Fergus J Couch, David E Goldgar, Torben A Kruse, Edenir Inêz Palmero, Sue Kyung Park, Diana Torres, Elizabeth J van Rensburg, Lesley McGuffog, Michael T Parsons, Goska Leslie, Cora M Aalfs, Julio Abugattas, Julian Adlard, Simona Agata, Kristiina Aittomäki, Lesley Andrews, Irene L Andrulis, Adalgeir Arason, Norbert Arnold, Banu K Arun, Ella Asseryanis, Leo Auerbach, Jacopo Azzollini, Judith Balmaña, Monica Barile, Rosa B Barkardottir, Daniel Barrowdale, Javier Benitez, Andreas Berger, Raanan Berger, Amie M Blanco, Kathleen R Blazer, Marinus J Blok, Valérie Bonadona, Bernardo Bonanni, Angela R Bradbury, Carole Brewer, Bruno Buecher, Saundra S Buys, Trinidad Caldes, Almuth Caliebe, Maria A Caligo, Ian Campbell, Sandrine Caputo, Jocelyne Chiquette, Wendy K Chung, Kathleen B M Claes, J Margriet Collée, Jackie Cook, Rosemarie Davidson, Miguel de la Hoya, Kim De Leeneer, Antoine de Pauw, Capucine Delnatte, Orland Diez, Yuan Chun Ding, Nina Ditsch, Susan M Domchek, Cecilia M Dorfling, Carolina Velazquez, Bernd Dworniczak, Jacqueline Eason, Douglas F Easton, Ros Eeles, Hans Ehrencrona, Bent Ejlertsen, Christoph Engel, Stefanie Engert, D Gareth Evans, Laurence Faivre, Lidia Feliubadaló, Sandra Fert Ferrer, Lenka Foretova, Jeffrey Fowler, Debra Frost, Henrique C R Galvão, Patricia A Ganz, Judy Garber, Marion Gauthier-Villars, Andrea Gehrig, Anne-Marie Gerdes, Paul Gesta, Giuseppe Giannini, Sophie Giraud, Gord Glendon, Andrew K Godwin, Mark H Greene, Jacek Gronwald, Angelica Gutierrez-Barrera, Eric Hahnen, Jan Hauke, Alex Henderson, Julia Hentschel, Frans B L Hogervorst, Ellen Honisch, Evgeny N Imyanitov, Claudine Isaacs, Louise Izatt, Angel Izquierdo, Anna Jakubowska, Paul James, Ramunas Janavicius, Uffe Birk Jensen, Esther M John, Vijai Joseph, Katarzyna Kaczmarek, Beth Y Karlan, Karin Kast, KConFab Investigators, Sung-Won Kim, Irene Konstantopoulou, Jacob Korach, Yael Laitman, Adriana Lasa, Christine Lasset, Conxi Lázaro, Annette Lee, Min Hyuk Lee, Jenny Lester, Fabienne Lesueur, Annelie Liljegren, Noralane M Lindor, Michel Longy, Jennifer T Loud, Karen H Lu, Jan Lubinski, Eva Machackova, Siranoush Manoukian, Véronique Mari, Cristina Martínez-Bouzas, Zoltan Matrai, Noura Mebirouk, Hanne E J Meijers-Heijboer, Alfons Meindl, Arjen R Mensenkamp, Ugnius Mickys, Austin Miller, Marco Montagna, Kirsten B Moysich, Anna Marie Mulligan, Jacob Musinsky, Susan L Neuhausen, Heli Nevanlinna, Joanne Ngeow, Huu Phuc Nguyen, Dieter Niederacher, Henriette Roed Nielsen, Finn Cilius Nielsen, Robert L Nussbaum, Kenneth Offit, Anna Öfverholm, Kai-Ren Ong, Ana Osorio, Laura Papi, Janos Papp, Barbara Pasini, Inge Sokilde Pedersen, Ana Peixoto MSc, Nina Peruga MSc, Paolo Peterlongo, Esther Pohl, Nisha Pradhan Ba, Karolina Prajzendanc, Fabienne Prieur, Pascal Pujol, Paolo Radice, Susan J Ramus, Johanna Rantala, Muhammad Usman Rashid, Kerstin Rhiem, Mark Robson, Gustavo C Rodriguez, Mark T Rogers, Vilius Rudaitis, Ane Y Schmidt, Rita Katharina Schmutzler, Leigha Senter, Payal D Shah, Priyanka Sharma, Lucy E Side, Jacques Simard, Christian F Singer, Anne-Bine Skytte, Thomas P Slavin, Katie Snape, Hagay Sobol, Melissa Southey, Linda Steele, Doris Steinemann, Grzegorz Sukiennicki, Christian Sutter, Csilla I Szabo, Yen Y Tan, Manuel R Teixeira, Mary Beth Terry, Alex Teulé, Abigail Thomas, Darcy L Thull, Marc Tischkowitz, Silvia Tognazzo, Amanda Ewart Toland, Sabine Topka, Alison H Trainer, Nadine Tung, Christi J van Asperen, Annemieke H van der Hout, Lizet E van der Kolk, Rob B van der Luijt, Mattias Van Heetvelde, Liliana Varesco, Raymonda Varon-Mateeva, Ana Vega, Cynthia Villarreal-Garza, Anna von Wachenfeldt, Lisa Walker, Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H F Weber, Drakoulis Yannoukakos, Sook-Yee Yoon, Cristina Zanzottera, Jamal Zidan, Kristin K Zorn, Christina G Hutten Selkirk, Peter J Hulick, Georgia Chenevix-Trench, Amanda B Spurdle, Antonis C Antoniou, Katherine L Nathanson
The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on Caucasians in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on 6 continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database...
February 15, 2018: Human Mutation
https://www.readbyqxmd.com/read/29440233/comprehensive-characterisation-of-compartment-specific-long-non-coding-rnas-associated-with-pancreatic-ductal-adenocarcinoma
#4
Luis Arnes, Zhaoqi Liu, Jiguang Wang, Hans Carlo Maurer, Irina Sagalovskiy, Marta Sanchez-Martin, Nikhil Bommakanti, Diana C Garofalo, Dina A Balderes, Lori Sussel, Kenneth P Olive, Raul Rabadan
OBJECTIVE: Pancreatic ductal adenocarcinoma (PDA) is a highly metastatic disease with limited therapeutic options. Genome and transcriptome analyses have identified signalling pathways and cancer driver genes with implications in patient stratification and targeted therapy. However, these analyses were performed in bulk samples and focused on coding genes, which represent a small fraction of the genome. DESIGN: We developed a computational framework to reconstruct the non-coding transcriptome from cross-sectional RNA-Seq, integrating somatic copy number alterations (SCNA), common germline variants associated to PDA risk and clinical outcome...
February 10, 2018: Gut
https://www.readbyqxmd.com/read/29436821/ph-sensitive-compounds-for-selective-inhibition-of-acid-producing-bacteria
#5
Yin Yang, Vytas Reipa, Guo Liu, Yuan Meng, Xiaohong Wang, Kenneth P Mineart, Vivek M Prabhu, Wenyuan Shi, Nancy J Lin, Xuesong He, Jirun Sun
Stimuli-responsive compounds that provide on-site, controlled antimicrobial activity promise an effective approach to prevent infections, reducing the need for systemic antibiotics. We present one novel pH-sensitive quaternary pyridinium salt (QPS) whose antibacterial activity is boosted by low pH and controlled by adjusting the pH between 4 and 8. Particularly, this compound selectively inhibits growth of acid-producing bacteria within a multispecies community. The successful antibacterial action of this QPS maintains the environmental pH above 5...
February 13, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29435069/serum-microrna-193b-as-a-promising-biomarker-for-prediction-of-chemoradiation-sensitivity-in-esophageal-squamous-cell-carcinoma-patients
#6
Chung Man Chan, Kenneth K Y Lai, Enders K O Ng, Mei Na Kiang, Tiffany W H Kwok, Hector K Wang, Kwok Wah Chan, Tsz Ting Law, Daniel K Tong, Kin Tak Chan, Nikki P Lee, Simon Law
Esophageal squamous cell carcinoma (ESCC) is the most predominantly occurring type of esophageal cancer worldwide. Locally advanced ESCC patients are treated by neoadjuvant chemoradiation for tumor downstaging prior to tumor resection. Patients receiving this treatment have an increased expectation of cure via the following tumor resection and have better survival outcomes. However, not all patients respond well to chemoradiation and poor responders suffer from treatment-associated toxicity and complications without benefits...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29431639/cxcl12%C3%AE-%C3%A2-promotes-development-of-metastatic-castration-resistant-prostate-cancer-by-induction-of-cancer-stem-cell-and-neuroendocrine-phenotypes
#7
Younghun Jung, Frank C Cackowski, Kenji Yumoto, Ann Decker, Jingcheng Wang, Jinkoo Kim, Eunsohl Lee, Yugang Wang, Jae-Seung Chung, Amy M Gursky, Paul H Krebsbach, Kenneth J Pienta, Todd M Morgan, Russell S Taichman
There is evidence that cancer stem-like cells (CSC) and neuroendocrine (NE) behavior play critical roles in the pathogenesis and clinical course of metastatic castration-resistant prostate cancer (m-CRPC). However, there is limiting mechanistic understanding of how CSC and NE phenotypes impact the development of m-CRPC, which could improve opportunities to identify useful biomarkers and therapeutics. In this study, we explored the role of the intracellular chemokine CXCL12γ in CSC induction and NE differentiation and its impact on m-CRPC...
February 5, 2018: Cancer Research
https://www.readbyqxmd.com/read/29420226/serial-circulating-tumour-dna-analysis-during-multimodality-treatment-of-locally-advanced-rectal-cancer-a-prospective-biomarker-study
#8
Jeanne Tie, Joshua D Cohen, Yuxuan Wang, Lu Li, Michael Christie, Koen Simons, Hany Elsaleh, Suzanne Kosmider, Rachel Wong, Desmond Yip, Margaret Lee, Ben Tran, David Rangiah, Matthew Burge, David Goldstein, Madhu Singh, Iain Skinner, Ian Faragher, Matthew Croxford, Carolyn Bampton, Andrew Haydon, Ian T Jones, Christos S Karapetis, Timothy Price, Mary J Schaefer, Jeanne Ptak, Lisa Dobbyn, Natallie Silliman, Isaac Kinde, Cristian Tomasetti, Nickolas Papadopoulos, Kenneth Kinzler, Bert Volgestein, Peter Gibbs
OBJECTIVE: For patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC. DESIGN: We enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4-10 weeks after surgery...
February 2, 2018: Gut
https://www.readbyqxmd.com/read/29401398/aircraft-measurements-of-total-mercury-and-monomethyl-mercury-in-summertime-marine-stratus-cloud-water-from-coastal-california-usa
#9
Peter Weiss-Penzias, Armin Sorooshian, Kenneth Coale, Wesley Heim, Ewan Crosbie, Hossein Dadashazar, Alexander B MacDonald, Zhen Wang, Haflidi Jonsson
Water samples from marine stratus clouds were collected during 16 aircraft flights above the Pacific Ocean near the Central California coast during the summer of 2016. These samples were analyzed for total mercury (THg), monomethyl mercury (MMHg) and 32 other chemical species in addition to aerosol physical parameters. The mean concentrations of THg and MMHg in the cloud water samples were 9.2 ± 6.0 ng L-1 (2.3-33.8 ng L-1) (N = 97) and 0.87 ± 0.66 ng L-1 (0.17-2.9 ng L-1) (N = 22), respectively. This corresponds to 9...
February 5, 2018: Environmental Science & Technology
https://www.readbyqxmd.com/read/29400789/photodiode-array-for-characterizing-optical-fibers
#10
F Kenneth Hopkins, Nicholas G Usechak, Hyunjun Kim, Xiaojin Wang, Hiren Trada, Kevin M Walsh
An innovative approach is proposed and demonstrated for measuring the attenuation of light in optical fibers. The technique utilizes a silicon device containing a v-groove that positions the fiber and detector array along the v-groove. The detectors within the v-groove are designed to partially surround the fiber in order to maximize the coupling of scattered light from the fiber into each detector.
January 20, 2018: Applied Optics
https://www.readbyqxmd.com/read/29395064/senataxin-mutation-reveals-how-r-loops-promote-transcription-by-blocking-dna-methylation-at-gene-promoters
#11
Christopher Grunseich, Isabel X Wang, Jason A Watts, Joshua T Burdick, Robert D Guber, Zhengwei Zhu, Alan Bruzel, Tyler Lanman, Kelian Chen, Alice B Schindler, Nancy Edwards, Abhik Ray-Chaudhury, Jianhua Yao, Tanya Lehky, Grzegorz Piszczek, Barbara Crain, Kenneth H Fischbeck, Vivian G Cheung
R-loops are three-stranded nucleic acid structures found abundantly and yet often viewed as by-products of transcription. Studying cells from patients with a motor neuron disease (amyotrophic lateral sclerosis 4 [ALS4]) caused by a mutation in senataxin, we uncovered how R-loops promote transcription. In ALS4 patients, the senataxin mutation depletes R-loops with a consequent effect on gene expression. With fewer R-loops in ALS4 cells, the expression of BAMBI, a negative regulator of transforming growth factor β (TGF-β), is reduced; that then leads to the activation of the TGF-β pathway...
February 1, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29388129/linking-science-and-policy-to-support-the-implementation-of-the-minamata-convention-on-mercury
#12
Henrik Selin, Susan Egan Keane, Shuxiao Wang, Noelle E Selin, Kenneth Davis, Dominique Bally
The Minamata Convention on Mercury, with its objective to protect human health and the environment from the dangers of mercury (Hg), entered into force in 2017. The Convention outlines a life-cycle approach to the production, use, emissions, releases, handling, and disposal of Hg. As it moves into the implementation phase, scientific work and information are critically needed to support decision-making and management. This paper synthesizes existing knowledge and examines three areas in which researchers across the natural sciences, engineering, and social sciences can mobilize and disseminate knowledge in support of Hg abatement and the realization of the Convention's objective: (1) uses, emissions, and releases; (2) support, awareness raising, and education; and (3) impacts and effectiveness...
January 31, 2018: Ambio
https://www.readbyqxmd.com/read/29373717/integrated-transcriptomic-and-regulatory-network-analyses-identify-microrna-200c-as-a-novel-repressor-of-human-pluripotent-stem-cell-derived-cardiomyocyte-differentiation-and-maturation
#13
Ellen Ngar Yun Poon, Baixia Hao, Daogang Guan, Mulin Jun Li, Jun Lu, Yong Yang, Binbin Wu, Stanley Chun Ming Wu, Sarah E Webb, Yan Liang, Andrew L Miller, Xiaoqiang Yao, Junwen Wang, Bin Yan, Kenneth R Boheler
Aims: MicroRNAs (miRNAs) are crucial for the post-transcriptional control of protein-encoding genes, and together with transcription factors (TFs) regulate gene expression; however, the regulatory activities of miRNAs during cardiac development are only partially understood. In this study, we tested the hypothesis that integrative computational approaches could identify miRNAs that experimentally could be shown to regulate cardiomyogenesis. Methods and results: We integrated expression profiles with bioinformatics analyses of miRNA and TF regulatory programs to identify candidate miRNAs involved with cardiac development...
January 24, 2018: Cardiovascular Research
https://www.readbyqxmd.com/read/29360641/cop1-det1-ets-axis-regulates-erk-transcriptome-and-sensitivity-to-mapk-inhibitors
#14
Yuanyuan Xie, Zhen Cao, Elissa Wp Wong, Youxin Guan, Wenfu Ma, Jenny Q Zhang, Edward G Walczak, Devan Murphy, Leili Ran, Inna Sirota, Shangqian Wang, Shipra Shukla, Dong Gao, Simon Rv Knott, Kenneth Chang, Justin Leu, John Wongvipat, Cristina R Antonescu, Gregory Hannon, Ping Chi, Yu Chen
Aberrant activation of MAPK signaling leads to activation of oncogenic transcriptomes. How MAPK signaling is coupled with transcriptional response in cancer is not fully understood. In gastrointestinal stromal tumor and melanoma, both with oncogenic MAPK activation, we find that ETV1 and other Pea3-ETS transcription factors are critical nuclear effectors of MAPK signaling that are regulated through protein stability. Expression of stabilized Pea3-ETS factors can partially rescue the MAPK transcriptome and cell viability after MAPK inhibition...
January 23, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29358651/genomes-of-13-domesticated-and-wild-rice-relatives-highlight-genetic-conservation-turnover-and-innovation-across-the-genus-oryza
#15
Joshua C Stein, Yeisoo Yu, Dario Copetti, Derrick J Zwickl, Li Zhang, Chengjun Zhang, Kapeel Chougule, Dongying Gao, Aiko Iwata, Jose Luis Goicoechea, Sharon Wei, Jun Wang, Yi Liao, Muhua Wang, Julie Jacquemin, Claude Becker, Dave Kudrna, Jianwei Zhang, Carlos E M Londono, Xiang Song, Seunghee Lee, Paul Sanchez, Andrea Zuccolo, Jetty S S Ammiraju, Jayson Talag, Ann Danowitz, Luis F Rivera, Andrea R Gschwend, Christos Noutsos, Cheng-Chieh Wu, Shu-Min Kao, Jhih-Wun Zeng, Fu-Jin Wei, Qiang Zhao, Qi Feng, Moaine El Baidouri, Marie-Christine Carpentier, Eric Lasserre, Richard Cooke, Daniel da Rosa Farias, Luciano Carlos da Maia, Railson S Dos Santos, Kevin G Nyberg, Kenneth L McNally, Ramil Mauleon, Nickolai Alexandrov, Jeremy Schmutz, Dave Flowers, Chuanzhu Fan, Detlef Weigel, Kshirod K Jena, Thomas Wicker, Mingsheng Chen, Bin Han, Robert Henry, Yue-Ie C Hsing, Nori Kurata, Antonio Costa de Oliveira, Olivier Panaud, Scott A Jackson, Carlos A Machado, Michael J Sanderson, Manyuan Long, Doreen Ware, Rod A Wing
The genus Oryza is a model system for the study of molecular evolution over time scales ranging from a few thousand to 15 million years. Using 13 reference genomes spanning the Oryza species tree, we show that despite few large-scale chromosomal rearrangements rapid species diversification is mirrored by lineage-specific emergence and turnover of many novel elements, including transposons, and potential new coding and noncoding genes. Our study resolves controversial areas of the Oryza phylogeny, showing a complex history of introgression among different chromosomes in the young 'AA' subclade containing the two domesticated species...
January 22, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29354018/joint-nonparametric-correction-estimator-for-excess-relative-risk-regression-in-survival-analysis-with-exposure-measurement-error
#16
Ching-Yun Wang, Harry Cullings, Xiao Song, Kenneth J Kopecky
Observational epidemiological studies often confront the problem of estimating exposure-disease relationships when the exposure is not measured exactly. In the paper, we investigate exposure measurement error in excess relative risk regression, which is a widely used model in radiation exposure effect research. In the study cohort, a surrogate variable is available for the true unobserved exposure variable. The surrogate variable satisfies a generalized version of the classical additive measurement error model, but it may or may not have repeated measurements...
November 2017: Journal of the Royal Statistical Society. Series B, Statistical Methodology
https://www.readbyqxmd.com/read/29353102/aging-african-green-monkeys-manifest-transcriptional-pathological-and-cognitive-hallmarks-of-human-alzheimer-s-disease
#17
Paige E Cramer, Renee C Gentzel, Keith Q Tanis, Joshua Vardigan, Yi Wang, Brett Connolly, Philip Manfre, Kenneth Lodge, John J Renger, Celina Zerbinatti, Jason M Uslaner
While many preclinical models of Alzheimer's disease (AD) have been reported, none fully recapitulate the disease. In an effort to identify an appropriate preclinical disease model, we characterized age-related changes in 2 higher order species, the African green monkey (AGM) and the rhesus macaque. Gene expression profiles in the dorsolateral prefrontal cortex and the visual cortex showed age-related changes in AGMs that are strikingly reminiscent of AD, whereas aged rhesus were most similar to healthy elderly humans...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29348807/discovery-of-spiro-oxazolidinediones-as-selective-orally-bioavailable-inhibitors-of-p300-cbp-histone-acetyltransferases
#18
Michael R Michaelides, Arthur Kluge, Michael Patane, John H Van Drie, Ce Wang, T Matthew Hansen, Roberto M Risi, Robert Mantei, Carmen Hertel, Kannan Karukurichi, Alexandre Nesterov, David McElligott, Peter de Vries, J William Langston, Philip A Cole, Ronen Marmorstein, Hong Liu, Loren Lasko, Kenneth D Bromberg, Albert Lai, Edward A Kesicki
p300 and its paralog CBP can acetylate histones and other proteins and have been implicated in a number of diseases characterized by aberrant gene activation, such as cancer. A novel, highly selective, orally bioavailable histone acetyltransferase (HAT) domain inhibitor has been identified through virtual ligand screening and subsequent optimization of a unique hydantoin screening hit. Conformational restraint in the form of a spirocyclization followed by substitution with a urea led to a significant improvement in potency...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348365/detection-and-localization-of-surgically-resectable-cancers-with-a-multi-analyte-blood-test
#19
Joshua D Cohen, Lu Li, Yuxuan Wang, Christopher Thoburn, Bahman Afsari, Ludmila Danilova, Christopher Douville, Ammar A Javed, Fay Wong, Austin Mattox, Ralph H Hruban, Christopher L Wolfgang, Michael G Goggins, Marco Dal Molin, Tian-Li Wang, Richard Roden, Alison P Klein, Janine Ptak, Lisa Dobbyn, Joy Schaefer, Natalie Silliman, Maria Popoli, Joshua T Vogelstein, James D Browne, Robert E Schoen, Randall E Brand, Jeanne Tie, Peter Gibbs, Hui-Li Wong, Aaron S Mansfield, Jin Jen, Samir M Hanash, Massimo Falconi, Peter J Allen, Shibin Zhou, Chetan Bettegowda, Luis A Diaz, Cristian Tomasetti, Kenneth W Kinzler, Bert Vogelstein, Anne Marie Lennon, Nickolas Papadopoulos
Earlier detection is key to reducing cancer deaths. Here we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1,005 patients with non-metastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69% to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29345061/monocyte-subsets-exhibit-transcriptional-plasticity-and-a-shared-response-to-interferon-in-siv-infected-rhesus-macaques
#20
Brian T Nowlin, John Wang, Jamie L Schafer, Patrick Autissier, Tricia H Burdo, Kenneth C Williams
The progression to AIDS is influenced by changes in the biology of heterogeneous monocyte subsets. Classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes may represent progressive stages of monocyte maturation or disparate myeloid lineages with different turnover rates and function. To investigate the relationship between monocyte subsets and the response to SIV infection, we performed microarray analysis of monocyte subsets in rhesus macaques at three time points: prior to SIV infection, 26 days postinfection, and necropsy with AIDS...
January 2018: Journal of Leukocyte Biology
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