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https://www.readbyqxmd.com/read/28934246/discovery-of-pf-06928215-as-a-high-affinity-inhibitor-of-cgas-enabled-by-a-novel-fluorescence-polarization-assay
#1
Justin Hall, Amy Brault, Fabien Vincent, Shawn Weng, Hong Wang, Darren Dumlao, Ann Aulabaugh, Dikran Aivazian, Dana Castro, Ming Chen, Jeffrey Culp, Ken Dower, Joseph Gardner, Steven Hawrylik, Douglas Golenbock, David Hepworth, Mark Horn, Lyn Jones, Peter Jones, Eicke Latz, Jing Li, Lih-Ling Lin, Wen Lin, David Lin, Frank Lovering, Nootaree Niljanskul, Ryan Nistler, Betsy Pierce, Olga Plotnikova, Daniel Schmitt, Suman Shanker, James Smith, William Snyder, Timothy Subashi, John Trujillo, Edyta Tyminski, Guoxing Wang, Jimson Wong, Bruce Lefker, Leslie Dakin, Karen Leach
Cyclic GMP-AMP synthase (cGAS) initiates the innate immune system in response to cytosolic dsDNA. After binding and activation from dsDNA, cGAS uses ATP and GTP to synthesize 2', 3' -cGAMP (cGAMP), a cyclic dinucleotide second messenger with mixed 2'-5' and 3'-5' phosphodiester bonds. Inappropriate stimulation of cGAS has been implicated in autoimmune disease such as systemic lupus erythematosus, thus inhibition of cGAS may be of therapeutic benefit in some diseases; however, the size and polarity of the cGAS active site makes it a challenging target for the development of conventional substrate-competitive inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28926300/an-updated-scheme-for-categorizing-foods-implicated-in-foodborne-disease-outbreaks-a-tri-agency-collaboration
#2
LaTonia C Richardson, Michael C Bazaco, Cary Chen Parker, Daniel Dewey-Mattia, Neal Golden, Karen Jones, Karl Klontz, Curtis Travis, Joanna Zablotsky Kufel, Dana Cole
BACKGROUND: Foodborne disease data collected during outbreak investigations are used to estimate the percentage of foodborne illnesses attributable to specific food categories. Current food categories do not reflect whether or how the food has been processed and exclude many multiple-ingredient foods. MATERIALS AND METHODS: Representatives from three federal agencies worked collaboratively in the Interagency Food Safety Analytics Collaboration (IFSAC) to develop a hierarchical scheme for categorizing foods implicated in outbreaks, which accounts for the type of processing and provides more specific food categories for regulatory purposes...
September 19, 2017: Foodborne Pathogens and Disease
https://www.readbyqxmd.com/read/28925533/stereospecific-reaction-of-donor-acceptor-cyclopropanes-with-thioketones-a-novel-access-to-highly-substituted-tetrahydrothiophenes
#3
Daniel B Werz, André Augustin, Peter G Jones, Maximilian Sensse
Lewis-acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with thioketones are described. Highly substituted tetrahydrothiophenes with two adjacent quaternary carbon atoms were obtained in a stereospecific manner under mild conditions and in high yield using AlCl3 as Lewis acid. Moreover, an intramolecular approach was successfully implemented to gain access to sulfur-bridged [n.2.1] bicyclic ring systems. Conversion of selenoketones, the heavier analogs, under similar conditions resulted in the formation of various tetrahydroselenophenes...
September 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28923824/snapin-promotes-hiv-1-transmission-from-dendritic-cells-by-dampening-tlr8-signaling
#4
Elham Khatamzas, Madeleine Maria Hipp, Daniel Gaughan, Tica Pichulik, Alasdair Leslie, Ricardo A Fernandes, Daniele Muraro, Sarah Booth, Kieran Zausmer, Mei-Yi Sun, Benedikt Kessler, Sarah Rowland-Jones, Vincenzo Cerundolo, Alison Simmons
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4(+) T cells in DCs, including the dynein motor protein Snapin...
September 18, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28920526/iatrogenic-injury-to-the-motor-branch-of-the-median-nerve-during-percutaneous-needle-fasciotomy
#5
Christopher Jones, Daniel Widdowson, Dominique M Davidson
No abstract text is available yet for this article.
January 1, 2017: Journal of Hand Surgery, European Volume
https://www.readbyqxmd.com/read/28915331/dual-specificity-phosphatase-5-substrate-interaction-a-mechanistic-perspective
#6
Raman G Kutty, Marat R Talipov, Robert D Bongard, Rachel A Jones Lipinski, Noreena L Sweeney, Daniel S Sem, Rajendra Rathore, Ramani Ramchandran
The mammalian genome contains approximately 200 phosphatases that are responsible for catalytically removing phosphate groups from proteins. In this review, we discuss dual specificity phosphatase 5 (DUSP5). DUSP5 belongs to the dual specificity phosphatase (DUSP) family, so named after the family members' abilities to remove phosphate groups from serine/threonine and tyrosine residues. We provide a comparison of DUSP5's structure to other DUSPs and, using molecular modeling studies, provide an explanation for DUSP5's mechanistic interaction and specificity toward phospho-extracellular regulated kinase, its only known substrate...
September 12, 2017: Comprehensive Physiology
https://www.readbyqxmd.com/read/28914269/looking-beyond-the-exome-a-phenotype-first-approach-to-molecular-diagnostic-resolution-in-rare-and-undiagnosed-diseases
#7
Loren D M Pena, Yong-Hui Jiang, Kelly Schoch, Rebecca C Spillmann, Nicole Walley, Nicholas Stong, Sarah Rapisardo Horn, Jennifer A Sullivan, Allyn McConkie-Rosell, Sujay Kansagra, Edward C Smith, Mays El-Dairi, Jane Bellet, Martha Ann Keels, Joan Jasien, Peter G Kranz, Richard Noel, Shashi K Nagaraj, Robert K Lark, Daniel S G Wechsler, Daniela Del Gaudio, Marco L Leung, Laura G Hendon, Collette C Parker, Kelly L Jones, David B Goldstein, Vandana Shashi
PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software...
September 14, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/28912319/complete-genome-sequence-of-mycobacterium-chimaera-sj42-a-nonoutbreak-strain-from-an-immunocompromised-patient-with-pulmonary-disease
#8
Nabeeh A Hasan, René L Warren, L Elaine Epperson, Allyson Malecha, David C Alexander, Christine Y Turenne, Daniel MacMillan, Inanc Birol, Stephen Pleasance, Robin Coope, Steven J M Jones, Marc G Romney, Monica Ng, Tracy Chan, Mabel Rodrigues, Patrick Tang, Jennifer L Gardy, Michael Strong
Mycobacterium chimaera, a nontuberculous mycobacterium (NTM) belonging to the Mycobacterium avium complex (MAC), is an opportunistic pathogen that can cause respiratory and disseminated disease. We report the complete genome sequence of a strain, SJ42, isolated from an immunocompromised male presenting with MAC pneumonia, assembled from Illumina and Oxford Nanopore data.
September 14, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28903073/reconciling-disparate-information-in-continuity-of-care-documents-piloting-a-system-to-consolidate-structured-clinical-documents
#9
Masoud Hosseini, Josette Jones, Anthony Faiola, Daniel J Vreeman, Huanmei Wu, Brian E Dixon
BACKGROUND: Due to the nature of information generation in health care, clinical documents contain duplicate and sometimes conflicting information. Recent implementation of health information exchange (HIE) mechanisms in which clinical summary documents are exchanged among disparate health care organizations can proliferate duplicate and conflicting information. MATERIALS AND METHODS: To reduce information overload, a system to automatically consolidate information across multiple clinical summary documents was developed for an HIE network...
September 10, 2017: Journal of Biomedical Informatics
https://www.readbyqxmd.com/read/28901583/improved-protein-contact-predictions-with-the-metapsicov2-server-in-casp12
#10
Daniel W A Buchan, David T Jones
In this paper we present the results for the MetaPSICOV2 contact prediction server in the CASP12 community experiment (http://predictioncenter.org). Over the 35 assessed Free Modelling target domains the MetaPSICOV2 server achieved a mean precision of 43.27%, a substantial increase relative to the server's performance in the CASP11 experiment (Kinch, Li et al. 2016). In the following paper, we discuss improvements to the MetaPSICOV2 server, covering both changes to the neural network and attempts to integrate contact predictions on a domain basis into the prediction pipeline...
September 13, 2017: Proteins
https://www.readbyqxmd.com/read/28900119/analysis-of-potential-protein-modifying-variants-in-9000-endometriosis-patients-and-150000-controls-of-european-ancestry
#11
Yadav Sapkota, Immaculata De Vivo, Valgerdur Steinthorsdottir, Amelie Fassbender, Lisa Bowdler, Julie E Buring, Todd L Edwards, Sarah Jones, Dorien O, Daniëlle Peterse, Kathryn M Rexrode, Paul M Ridker, Andrew J Schork, Gudmar Thorleifsson, Leanne M Wallace, Peter Kraft, Andrew P Morris, Dale R Nyholt, Digna R Velez Edwards, Mette Nyegaard, Thomas D'Hooghe, Daniel I Chasman, Kari Stefansson, Stacey A Missmer, Grant W Montgomery
Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication...
September 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892515/strong-interferon-gamma-mediated-cellular-immunity-to-scrub-typhus-demonstrated-using-a-novel-whole-cell-antigen-elispot-assay-in-rhesus-macaques-and-humans
#12
Manutsanun Sumonwiriya, Daniel H Paris, Piyanate Sunyakumthorn, Tippawan Anantatat, Kemajittra Jenjaroen, Suchintana Chumseng, Rawiwan Im-Erbsin, Ampai Tanganuchitcharnchai, Suthatip Jintaworn, Stuart D Blacksell, Fazle R Chowdhury, Barbara Kronsteiner, Prapit Teparrukkul, Robin L Burke, Eric D Lombardini, Allen L Richards, Carl J Mason, James W Jones, Nicholas P J Day, Susanna J Dunachie
Scrub typhus is a febrile infection caused by the obligate intracellular bacterium Orientia tsutsugamushi, which causes significant morbidity and mortality across the Asia-Pacific region. The control of this vector-borne disease is challenging due to humans being dead-end hosts, vertical maintenance of the pathogen in the vector itself, and a potentially large rodent reservoir of unclear significance, coupled with a lack of accurate diagnostic tests. Development of an effective vaccine is highly desirable. This however requires better characterization of the natural immune response of this neglected but important disease...
September 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28889292/congo-red-stain-identifies-matrix-overproduction-and-is-an-indirect-measurement-for-c-di-gmp-in-many-species-of-bacteria
#13
Christopher J Jones, Daniel J Wozniak
Congo red is a diazo textile dye that has been used to visualize the production of amyloid fibers for nearly a century. Microbiological applications were later developed, especially in identifying strains that produce amyloid appendages called curli and overexpressing polysaccharides in the biofilm matrix. The second messenger cyclic diguanylate (c-di-GMP) regulates the production of biofilm matrix polysaccharides, and therefore Congo red staining of samples can be utilized as an indirect measurement of elevated c-di-GMP production in bacteria...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28888927/the-effects-of-improving-sleep-on-mental-health-oasis-a-randomised-controlled-trial-with-mediation-analysis
#14
Daniel Freeman, Bryony Sheaves, Guy M Goodwin, Ly-Mee Yu, Alecia Nickless, Paul J Harrison, Richard Emsley, Annemarie I Luik, Russell G Foster, Vanashree Wadekar, Christopher Hinds, Andrew Gumley, Ray Jones, Stafford Lightman, Steve Jones, Richard Bentall, Peter Kinderman, Georgina Rowse, Traolach Brugha, Mark Blagrove, Alice M Gregory, Leanne Fleming, Elaine Walklet, Cris Glazebrook, E Bethan Davies, Chris Hollis, Gillian Haddock, Bev John, Mark Coulson, David Fowler, Katherine Pugh, John Cape, Peter Moseley, Gary Brown, Claire Hughes, Marc Obonsawin, Sian Coker, Edward Watkins, Matthias Schwannauer, Kenneth MacMahon, A Niroshan Siriwardena, Colin A Espie
BACKGROUND: Sleep difficulties might be a contributory causal factor in the occurrence of mental health problems. If this is true, improving sleep should benefit psychological health. We aimed to determine whether treating insomnia leads to a reduction in paranoia and hallucinations. METHODS: We did this single-blind, randomised controlled trial (OASIS) at 26 UK universities. University students with insomnia were randomly assigned (1:1) with simple randomisation to receive digital cognitive behavioural therapy (CBT) for insomnia or usual care, and the research team were masked to the treatment...
September 6, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28885238/improving-the-implementation-of-lung-cancer-screening-guidelines-at-an-academic-primary-care-practice
#15
Alison T Brenner, Laura Cubillos, Katherine Birchard, Caleb Doyle-Burr, John Eick, Louise Henderson, Laura Jones, Michael Massaro, Bailey Minish, Paul Molina, Michael Pignone, Shana Ratner, Maria Patricia Rivera, Daniel S Reuland
Expert groups recommend annual chest computed tomography for lung cancer screening (LCS) in high-risk patients. Lung cancer screening in primary care is a complex process that includes identification of the at-risk population, comorbidity assessment, and shared decision making. We identified three key processes required for high-quality screening implementation in our academic primary care practice: (1) systematic collection of lifetime cumulative smoking history to identify potentially eligible patients; (2) visit-based clinical reminders and order sets embedded in the electronic health record (EHR); and (3) tools to facilitate shared decision making and appropriate test ordering...
September 1, 2017: Journal for Healthcare Quality: Official Publication of the National Association for Healthcare Quality
https://www.readbyqxmd.com/read/28880972/effect-of-modified-vaccinia-ankara-5t4-and-low-dose-cyclophosphamide-on-antitumor-immunity-in-metastatic-colorectal-cancer-a-randomized-clinical-trial
#16
Martin Scurr, Tom Pembroke, Anja Bloom, David Roberts, Amanda Thomson, Kathryn Smart, Hayley Bridgeman, Richard Adams, Alison Brewster, Robert Jones, Sarah Gwynne, Daniel Blount, Richard Harrop, Melissa Wright, Robert Hills, Awen Gallimore, Andrew Godkin
Importance: The success of immunotherapy with checkpoint inhibitors is not replicated in most cases of colorectal cancer; therefore, different strategies are urgently required. The oncofetal antigen 5T4 is expressed in more than 90% of cases of metastatic colorectal cancer (mCRC). Preliminary data using modified vaccinia Ankara-5T4 (MVA-5T4) in mCRC demonstrated that it safely induced serologic and T-cell responses. Objective: To determine whether antitumor immunity in mCRC could be increased using MVA-5T4, metronomic low-dose cyclophosphamide, or a combination of both treatments...
September 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28880856/update-increase-in-human-infections-with-novel-asian-lineage-avian-influenza-a-h7n9-viruses-during-the-fifth-epidemic-china-october-1-2016-august-7-2017
#17
James C Kile, Ruiqi Ren, Liqi Liu, Carolyn M Greene, Katherine Roguski, A Danielle Iuliano, Yunho Jang, Joyce Jones, Sharmi Thor, Ying Song, Suizan Zhou, Susan C Trock, Vivien Dugan, David E Wentworth, Min Z Levine, Timothy M Uyeki, Jacqueline M Katz, Daniel B Jernigan, Sonja J Olsen, Alicia M Fry, Eduardo Azziz-Baumgartner, C Todd Davis
Among all influenza viruses assessed using CDC's Influenza Risk Assessment Tool (IRAT), the Asian lineage avian influenza A(H7N9) virus (Asian H7N9), first reported in China in March 2013,* is ranked as the influenza virus with the highest potential pandemic risk (1). During October 1, 2016-August 7, 2017, the National Health and Family Planning Commission of China; CDC, Taiwan; the Hong Kong Centre for Health Protection; and the Macao CDC reported 759 human infections with Asian H7N9 viruses, including 281 deaths, to the World Health Organization (WHO), making this the largest of the five epidemics of Asian H7N9 infections that have occurred since 2013 (Figure 1)...
September 8, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28877533/comprehensive-assessment-of-cytochromes-p450-and-transporter-genetics-with-endoxifen-concentration-during-tamoxifen-treatment
#18
Lauren A Marcath, Allison M Deal, Emily Van Wieren, William Danko, Christine M Walko, Joseph G Ibrahim, Karen E Weck, David R Jones, Zeruesenay Desta, Howard L McLeod, Lisa A Carey, William J Irvin, Daniel L Hertz
OBJECTIVES: Tamoxifen bioactivation to endoxifen is mediated primarily by CYP2D6; however, considerable variability remains unexplained. Our aim was to perform a comprehensive assessment of the effect of genetic variation in tamoxifen-relevant enzymes and transporters on steady-state endoxifen concentrations. PATIENTS AND METHODS: Comprehensive genotyping of CYP enzymes and transporters was performed using the iPLEX ADME PGx Pro Panel in 302 tamoxifen-treated breast cancer patients...
September 4, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28876074/synthetic-study-toward-total-synthesis-of-%C3%A2-germine-synthesis-of-%C3%A2-4-methylenegermine
#19
Gilbert Stork, Ayako Yamashita, Robert M Hanson, Ly Phan, Eifion Phillips, Daniel Dubé, Pieter H Bos, Andrew J Clark, Maxwell Gough, Mark L Greenlee, Yimin Jiang, Keith Jones, Masato Kitamura, John Leonard, Tongzhu Liu, Philip J Parsons, Aranapakam M Venkatesan
The total synthesis of 4-methylenegermine is described.
September 6, 2017: Organic Letters
https://www.readbyqxmd.com/read/28872001/pulmonary-toxicity-following-proton-therapy-for-thoracic-lymphoma
#20
Ronica Nanda, Stella Flampouri, Nancy P Mendenhall, Daniel J Indelicato, Lisa M Jones, Vandana K Seeram, Bradford S Hoppe
No abstract text is available yet for this article.
October 1, 2017: International Journal of Radiation Oncology, Biology, Physics
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