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https://www.readbyqxmd.com/read/28431249/macrophages-facilitate-electrical-conduction-in-the-heart
#1
Maarten Hulsmans, Sebastian Clauss, Ling Xiao, Aaron D Aguirre, Kevin R King, Alan Hanley, William J Hucker, Eike M Wülfers, Gunnar Seemann, Gabriel Courties, Yoshiko Iwamoto, Yuan Sun, Andrej J Savol, Hendrik B Sager, Kory J Lavine, Gregory A Fishbein, Diane E Capen, Nicolas Da Silva, Lucile Miquerol, Hiroko Wakimoto, Christine E Seidman, Jonathan G Seidman, Ruslan I Sadreyev, Kamila Naxerova, Richard N Mitchell, Dennis Brown, Peter Libby, Ralph Weissleder, Filip K Swirski, Peter Kohl, Claudio Vinegoni, David J Milan, Patrick T Ellinor, Matthias Nahrendorf
Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28409557/randomised-controlled-trial-of-silk-therapeutic-garments-for-the-management-of-atopic-eczema-in-children-the-clothes-trial
#2
Kim S Thomas, Lucy E Bradshaw, Tracey H Sach, Fiona Cowdell, Jonathan M Batchelor, Sandra Lawton, Eleanor F Harrison, Rachel H Haines, Amina Ahmed, Taraneh Dean, Nigel P Burrows, Ian Pollock, Hannah K Buckley, Hywel C Williams, Joanne Llewellyn, Clare Crang, Jane D Grundy, Juliet Guiness, Andrew Gribbin, Eileen V Wake, Eleanor J Mitchell, Sara J Brown, Alan A Montgomery
BACKGROUND: Atopic eczema (AE) is a chronic, itchy, inflammatory skin condition that affects the quality of life of children and their families. The role of specialist clothing in the management of AE is poorly understood. OBJECTIVES: To assess the effectiveness and cost-effectiveness of silk garments for the management of AE in children with moderate to severe disease. DESIGN: Parallel-group, observer-blind, randomised controlled trial of 6 months' duration, followed by a 2-month observational period...
April 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28399154/silk-garments-plus-standard-care-compared-with-standard-care-for-treating-eczema-in-children-a-randomised-controlled-observer-blind-pragmatic-trial-clothes-trial
#3
Kim S Thomas, Lucy E Bradshaw, Tracey H Sach, Jonathan M Batchelor, Sandra Lawton, Eleanor F Harrison, Rachel H Haines, Amina Ahmed, Hywel C Williams, Taraneh Dean, Nigel P Burrows, Ian Pollock, Joanne Llewellyn, Clare Crang, Jane D Grundy, Juliet Guiness, Andrew Gribbin, Eleanor J Mitchell, Fiona Cowdell, Sara J Brown, Alan A Montgomery
BACKGROUND: The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. METHODS AND FINDINGS: This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres...
April 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28380849/comparative-studies-of-long-wave-laser-induced-breakdown-spectroscopy-emissions-excited-at-1-064-%C3%A2%C2%B5m-and-eye-safe-1-574-%C3%A2%C2%B5m
#4
Ei E Brown, Clayton S-C Yang, Uwe Hommerich, Feng Jin, Sudhir B Trivedi, Alan C Samuels
In this work, comparative long-wave infrared (LWIR) laser-induced breakdown spectroscopy (LIBS) emission studies of two excitation sources: conventional 1.064 μm and eye-safe laser wavelength at 1.574 μm were performed to analyze several widely-used inorganic energetic materials such as ammonium and potassium compounds as well as the organic liquid chemical warfare agent simulant, dimethyl methylphosphate (DMMP). LWIR LIBS emissions generated by both excitation sources were examined using three different detection systems: a single element liquid nitrogen cooled Mercury Cadmium Telluride (MCT) detector, an MCT linear array detection system with multi-channel preamplifiers + integrators, and an MCT linear array detection system with readout integrated circuit...
April 3, 2017: Optics Express
https://www.readbyqxmd.com/read/28374608/long-wave-infrared-lwir-molecular-laser-induced-breakdown-spectroscopy-libs-emissions-of-thin-solid-explosive-powder-films-deposited-on-aluminum-substrates
#5
Clayton S-C Yang, Feng Jin, Sudhir B Trivedi, Ei E Brown, Uwe Hommerich, Ashish Tripathi, Alan C Samuels
Thin solid films made of high nitro (NO2)/nitrate (NO3) content explosives were deposited on sand-blasted aluminum substrates and then studied using a mercury-cadmium-telluride (MCT) linear array detection system that is capable of rapidly capturing a broad spectrum of atomic and molecular laser-induced breakdown spectroscopy (LIBS) emissions in the long-wave infrared region (LWIR; ∼5.6-10 µm). Despite the similarities of their chemical compositions and structures, thin films of three commonly used explosives (RDX, HMX, and PETN) studied in this work can be rapidly identified in the ambient air by their molecular LIBS emission signatures in the LWIR region...
April 2017: Applied Spectroscopy
https://www.readbyqxmd.com/read/28374589/indazole-6-phenylcyclopropylcarboxylic-acids-as-selective-gpr120-agonists-with-in-vivo-efficacy
#6
William McCoull, Andrew Bailey, Peter Barton, Alan M Birch, Alastair J H Brown, Hayley S Butler, Scott Boyd, Roger J Butlin, Ben Chappell, Paul Clarkson, Shelley Collins, Robert M D Davies, Anne Ertan, Clare D Hammond, Jane L Holmes, Carol Lenaghan, Anita Midha, Pablo Morentin-Gutierrez, Jane E Moore, Piotr Raubo, Graeme Robb
GPR120 agonists have therapeutic potential for the treatment of diabetes, but few selective agonists have been reported. We identified an indazole-6-phenylcyclopropylcarboxylic acid series of GPR120 agonists and conducted SAR studies to optimize GPR120 potency. Furthermore, we identified a (S,S)-cyclopropylcarboxylic acid structural motif which gave selectivity against GPR40. Good oral exposure was obtained with some compounds displaying unexpected high CNS penetration. Increased MDCK efflux was utilized to identify compounds such as 33 with lower CNS penetration, and activity in oral glucose tolerance studies was demonstrated...
April 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28372073/fuselage-boundary-layer-refraction-of-fan-tones-radiated-from-an-installed-turbofan-aero-engine
#7
James Gaffney, Alan McAlpine, Michael J Kingan
A distributed source model to predict fan tone noise levels of an installed turbofan aero-engine is extended to include the refraction effects caused by the fuselage boundary layer. The model is a simple representation of an installed turbofan, where fan tones are represented in terms of spinning modes radiated from a semi-infinite circular duct, and the aircraft's fuselage is represented by an infinitely long, rigid cylinder. The distributed source is a disk, formed by integrating infinitesimal volume sources located on the intake duct termination...
March 2017: Journal of the Acoustical Society of America
https://www.readbyqxmd.com/read/28346229/clinical-efficacy-of-gene-modified-stem-cells-in-adenosine-deaminase-deficient-immunodeficiency
#8
Kit L Shaw, Elizabeth Garabedian, Suparna Mishra, Provaboti Barman, Alejandra Davila, Denise Carbonaro, Sally Shupien, Christopher Silvin, Sabine Geiger, Barbara Nowicki, E Monika Smogorzewska, Berkley Brown, Xiaoyan Wang, Satiro de Oliveira, Yeong Choi, Alan Ikeda, Dayna Terrazas, Pei-Yu Fu, Allen Yu, Beatriz Campo Fernandez, Aaron R Cooper, Barbara Engel, Greg Podsakoff, Arumugam Balamurugan, Stacie Anderson, Linda Muul, G Jayashree Jagadeesh, Neena Kapoor, John Tse, Theodore B Moore, Ken Purdy, Radha Rishi, Kathey Mohan, Suzanne Skoda-Smith, David Buchbinder, Roshini S Abraham, Andrew Scharenberg, Otto O Yang, Kenneth Cornetta, David Gjertson, Michael Hershfield, Rob Sokolic, Fabio Candotti, Donald B Kohn
BACKGROUND: Autologous hematopoietic stem cell transplantation (HSCT) of gene-modified cells is an alternative to enzyme replacement therapy (ERT) and allogeneic HSCT that has shown clinical benefit for adenosine deaminase-deficient (ADA-deficient) SCID when combined with reduced intensity conditioning (RIC) and ERT cessation. Clinical safety and therapeutic efficacy were evaluated in a phase II study. METHODS: Ten subjects with confirmed ADA-deficient SCID and no available matched sibling or family donor were enrolled between 2009 and 2012 and received transplantation with autologous hematopoietic CD34+ cells that were modified with the human ADA cDNA (MND-ADA) γ-retroviral vector after conditioning with busulfan (90 mg/m2) and ERT cessation...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28335873/parental-psychopathology-and-tourette-syndrome-chronic-tic-disorder-in-offspring-a-nationwide-case-control-study
#9
Susanna Leivonen, Jeremiah M Scharf, Carol A Mathews, Roshan Chudal, David Gyllenberg, Dan Sucksdorff, Auli Suominen, Arja Voutilainen, Alan S Brown, Andre Sourander
OBJECTIVE: To determine the associations between maternal and paternal psychiatric diagnoses and Tourette syndrome (TS)/chronic tic disorder (CT) in a nationwide study. METHOD: This nested case-control study linked data derived from three national registers. All singletons born and diagnosed with TS/CT in Finland between January 1991 and December 2010 were identified (n = 1,120) and matched to four controls (n = 4,299). Conditional logistic regression was used to examine the associations between parental psychopathology and TS/CT...
April 2017: Journal of the American Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/28334996/amelogenesis-imperfecta-caused-by-n-terminal-enamelin-point-mutations-in-mice-and-men-is-driven-by-endoplasmic-reticulum-stress
#10
Steven J Brookes, Martin J Barron, Claire E L Smith, James A Poulter, Alan J Mighell, Chris F Inglehearn, Catriona J Brown, Helen Rodd, Jennifer Kirkham, Michael J Dixon
"Amelogenesis imperfecta" (AI) describes a group of inherited diseases of dental enamel that have major clinical impact. Here, we identify the aetiology driving AI in mice carrying a p.S55I mutation in enamelin; one of the most commonly mutated proteins underlying AI in humans. Our data indicate that the mutation inhibits the ameloblast secretory pathway leading to ER stress and an activated unfolded protein response (UPR). Initially, with the support of the UPR acting in pro-survival mode, Enamp.S55I heterozygous mice secreted structurally normal enamel...
March 11, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28334978/therapeutic-window-of-dopamine-d2-3-receptor-occupancy-to-treat-psychosis-in-alzheimer-s-disease
#11
Suzanne Reeves, Emma McLachlan, Julie Bertrand, Fabrizia D Antonio, Stuart Brownings, Akshay Nair, Suki Greaves, Alan Smith, David Taylor, Joel Dunn, Paul Marsden, Robert Kessler, Robert Howard
See Caravaggio and Graff-Guerrero (doi:10.1093/awx023) for a scientific commentary on this article.Antipsychotic drugs, originally developed to treat schizophrenia, are used to treat psychosis, agitation and aggression in Alzheimer's disease. In the absence of dopamine D2/3 receptor occupancy data to inform antipsychotic prescribing for psychosis in Alzheimer's disease, the mechanisms underpinning antipsychotic efficacy and side effects are poorly understood. This study used a population approach to investigate the relationship between amisulpride blood concentration and central D2/3 occupancy in older people with Alzheimer's disease by combining: (i) pharmacokinetic data (280 venous samples) from a phase I single (50 mg) dose study in healthy older people (n = 20, 65-79 years); (ii) pharmacokinetic, 18F-fallypride D2/3 receptor imaging and clinical outcome data on patients with Alzheimer's disease who were prescribed amisulpride (25-75 mg daily) to treat psychosis as part of an open study (n = 28; 69-92 years; 41 blood samples, five pretreatment scans, 19 post-treatment scans); and (iii) 18F-fallypride imaging of an antipsychotic free Alzheimer's disease control group (n = 10, 78-92 years), to provide additional pretreatment data...
April 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28296990/serotonin-reuptake-inhibitor-use-during-pregnancy-reply
#12
Alan S Brown, Heli Malm, Andre Sourander
No abstract text is available yet for this article.
March 15, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28288098/mefloquine-targets-the-plasmodium-falciparum-80s-ribosome-to-inhibit-protein-synthesis
#13
Wilson Wong, Xiao-Chen Bai, Brad E Sleebs, Tony Triglia, Alan Brown, Jennifer K Thompson, Katherine E Jackson, Eric Hanssen, Danushka S Marapana, Israel S Fernandez, Stuart A Ralph, Alan F Cowman, Sjors H W Scheres, Jake Baum
Malaria control is heavily dependent on chemotherapeutic agents for disease prevention and drug treatment. Defining the mechanism of action for licensed drugs, for which no target is characterized, is critical to the development of their second-generation derivatives to improve drug potency towards inhibition of their molecular targets. Mefloquine is a widely used antimalarial without a known mode of action. Here, we demonstrate that mefloquine is a protein synthesis inhibitor. We solved a 3.2 Å cryo-electron microscopy structure of the Plasmodium falciparum 80S ribosome with the (+)-mefloquine enantiomer bound to the ribosome GTPase-associated centre...
March 13, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28245284/metabolically-distinct-weight-loss-by-10-12-cla-and-caloric-restriction-highlight-the-importance-of-subcutaneous-white-adipose-tissue-for-glucose-homeostasis-in-mice
#14
Laura J den Hartigh, Shari Wang, Leela Goodspeed, Tomasz Wietecha, Barbara Houston, Mohamed Omer, Kayoko Ogimoto, Savitha Subramanian, G A Nagana Gowda, Kevin D O'Brien, Karl J Kaiyala, Gregory J Morton, Alan Chait
BACKGROUND: Widely used as a weight loss supplement, trans-10,cis-12 conjugated linoleic acid (10,12 CLA) promotes fat loss in obese mice and humans, but has also been associated with insulin resistance. OBJECTIVE: We therefore sought to directly compare weight loss by 10,12 CLA versus caloric restriction (CR, 15-25%), an acceptable healthy method of weight loss, to determine how 10,12 CLA-mediated weight loss fails to improve glucose metabolism. METHODS: Obese mice with characteristics of human metabolic syndrome were either supplemented with 10,12 CLA or subjected to CR to promote weight loss...
2017: PloS One
https://www.readbyqxmd.com/read/28240264/overexpressing-the-novel-autocrine-endocrine-adipokine-wisp2-induces-hyperplasia-of-the-heart-white-and-brown-adipose-tissues-and-prevents-insulin-resistance
#15
John R Grünberg, Jenny M Hoffmann, Shahram Hedjazifar, Annika Nerstedt, Lachmi Jenndahl, Johannes Elvin, John Castellot, Lan Wei, Sofia Movérare-Skrtic, Claes Ohlsson, Louise Mannerås Holm, Fredrik Bäckhed, Ismail Syed, Fatima Bosch, Alan Saghatelian, Barbara B Kahn, Ann Hammarstedt, Ulf Smith
WISP2 is a novel adipokine, most highly expressed in the adipose tissue and primarily in undifferentiated mesenchymal cells. As a secreted protein, it is an autocrine/paracrine activator of canonical WNT signaling and, as an intracellular protein, it helps to maintain precursor cells undifferentiated. To examine effects of increased WISP2 in vivo, we generated an aP2-WISP2 transgenic (Tg) mouse. These mice had increased serum levels of WISP2, increased lean body mass and whole body energy expenditure, hyperplastic brown/white adipose tissues and larger hyperplastic hearts...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223508/c-terminal-phosphorylation-regulates-the-kinetics-of-a-subset-of-melanopsin-mediated-behaviors-in-mice
#16
Preethi Somasundaram, Glenn R Wyrick, Diego Carlos Fernandez, Alireza Ghahari, Cindy M Pinhal, Melissa Simmonds Richardson, Alan C Rupp, Lihong Cui, Zhijian Wu, R Lane Brown, Tudor Constantin Badea, Samer Hattar, Phyllis R Robinson
Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and mediate several non-image-forming visual functions, including circadian photoentrainment and the pupillary light reflex (PLR). ipRGCs act as autonomous photoreceptors via the intrinsic melanopsin-based phototransduction pathway and as a relay for rod/cone input via synaptically driven responses. Under low light intensities, where only synaptically driven rod/cone input activates ipRGCs, the duration of the ipRGC response will be determined by the termination kinetics of the rod/cone circuits...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28199108/application-of-off-rate-screening-in-the-identification-of-novel-pan-isoform-inhibitors-of-pyruvate-dehydrogenase-kinase
#17
Paul A Brough, Lisa Baker, Simon Bedford, Kirsten Brown, Seema Chavda, Victoria Chell, Jalanie D'Alessandro, Nicholas G M Davies, Ben Davis, Loic Le Strat, Alba T Macias, Daniel Maddox, Patrick C Mahon, Andrew J Massey, Natalia Matassova, Sean McKenna, Johannes W G Meissner, Jonathan D Moore, James B Murray, Christopher J Northfield, Charles Parry, Rachel Parsons, Stephen D Roughley, Terry Shaw, Heather Simmonite, Stephen Stokes, Allan Surgenor, Emma Stefaniak, Alan Robertson, Yikang Wang, Paul Webb, Neil Whitehead, Mike Wood
Libraries of nonpurified resorcinol amide derivatives were screened by surface plasmon resonance (SPR) to determine the binding dissociation constant (off-rate, kd) for compounds binding to the pyruvate dehydrogenase kinase (PDHK) enzyme. Parallel off-rate measurements against HSP90 and application of structure-based drug design enabled rapid hit to lead progression in a program to identify pan-isoform ATP-competitive inhibitors of PDHK. Lead optimization identified selective sub-100-nM inhibitors of the enzyme which significantly reduced phosphorylation of the E1α subunit in the PC3 cancer cell line in vitro...
February 15, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28198109/progenitors-in-peripheral-nerves-launch-heterotopic-ossification
#18
Elizabeth A Olmsted-Davis, Elizabeth A Salisbury, Diana Hoang, Eleanor L Davis, ZaWaunyka Lazard, Corinne Sonnet, Thomas A Davis, Jonathan A Forsberg, Alan R Davis
Studies presented here, using a murine model of bone morphogenetic protein type 2 (BMP2)-induced heterotopic ossification (HO) show that the protein initiates HO by signaling through progenitors in the endoneurium of peripheral nerves. In the mouse, these cells were identified in the endoneurium one day after BMP2 induction using antibody against phosphoSMAD (PS) 1, 5, and 8. Studies conducted in a tracking mouse that contains a tamoxifen-regulated Wnt1-Cre recombinase crossed with a td Tomato red (TR) reporter (Wnt1(CreErt) :Ai9Tm) confirmed their neural origin...
April 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28188239/treatment-outcome-in-early-diffuse-cutaneous-systemic-sclerosis-the-european-scleroderma-observational-study-esos
#19
Ariane L Herrick, Xiaoyan Pan, Sébastien Peytrignet, Mark Lunt, Roger Hesselstrand, Luc Mouthon, Alan Silman, Edith Brown, László Czirják, Jörg H W Distler, Oliver Distler, Kim Fligelstone, William J Gregory, Rachel Ochiel, Madelon Vonk, Codrina Ancuţa, Voon H Ong, Dominique Farge, Marie Hudson, Marco Matucci-Cerinic, Alexandra Balbir-Gurman, Øyvind Midtvedt, Alison C Jordan, Paresh Jobanputra, Wendy Stevens, Pia Moinzadeh, Frances C Hall, Christian Agard, Marina E Anderson, Elisabeth Diot, Rajan Madhok, Mohammed Akil, Maya H Buch, Lorinda Chung, Nemanja Damjanov, Harsha Gunawardena, Peter Lanyon, Yasmeen Ahmad, Kuntal Chakravarty, Søren Jacobsen, Alexander J MacGregor, Neil McHugh, Ulf Müller-Ladner, Gabriela Riemekasten, Michael Becker, Janet Roddy, Patricia E Carreira, Anne Laure Fauchais, Eric Hachulla, Jennifer Hamilton, Murat İnanç, John S McLaren, Jacob M van Laar, Sanjay Pathare, Susannah Proudman, Anna Rudin, Joanne Sahhar, Brigitte Coppere, Christine Serratrice, Tom Sheeran, Douglas J Veale, Claire Grange, Georges-Selim Trad, Christopher P Denton
OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'...
February 10, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28173840/morphological-and-molecular-description-of-ixodes-woyliei-n-sp-ixodidae-with-consideration-for-co-extinction-with-its-critically-endangered-marsupial-host
#20
Amanda Ash, Aileen Elliot, Stephanie Godfrey, Halina Burmej, Mohammad Yazid Abdad, Amy Northover, Adrian Wayne, Keith Morris, Peta Clode, Alan Lymbery, R C Andrew Thompson
BACKGROUND: Taxonomic identification of ticks obtained during a longitudinal survey of the critically endangered marsupial, Bettongia penicillata Gray, 1837 (woylie, brush-tailed bettong) revealed a new species of Ixodes Latrielle, 1795. Here we provide morphological data for the female and nymphal life stages of this novel species (Ixodes woyliei n. sp.), in combination with molecular characterisation using the mitochondrial cytochrome c oxidase subunit 1 gene (cox1). In addition, molecular characterisation was conducted on several described Ixodes species and used to provide phylogenetic context...
February 7, 2017: Parasites & Vectors
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