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Alan Brown

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https://www.readbyqxmd.com/read/28199108/application-of-off-rate-screening-in-the-identification-of-novel-pan-isoform-inhibitors-of-pyruvate-dehydrogenase-kinase
#1
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, 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
#2
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...
February 15, 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
#3
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
#4
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
https://www.readbyqxmd.com/read/28163926/rapid-analgesia-for-prehospital-hip-disruption-rapid-protocol-for-feasibility-study-of-randomised-controlled-trial
#5
Jenna K Bulger, Alan Brown, Bridie A Evans, Greg Fegan, Simon Ford, Katy Guy, Sian Jones, Leigh Keen, Ashrafunnesa Khanom, Ian Pallister, Nigel Rees, Ian T Russell, Anne C Seagrove, Helen A Snooks
BACKGROUND: Adequate pain relief at the point of injury and during transport to hospital is a major challenge in all acute traumas, especially for those with hip fractures, whose injuries are difficult to immobilise and whose long-term outcomes may be adversely affected by administration of opiate analgesics. Fascia iliaca compartment block (FICB) is a procedure routinely undertaken by doctors and nurses in the emergency department for patients with hip fracture but not yet evaluated for use by paramedics at the scene of emergency calls...
2017: Pilot and Feasibility Studies
https://www.readbyqxmd.com/read/28162249/impacts-of-turbidity-on-corals-the-relative-importance-of-light-limitation-and-suspended-sediments
#6
Pia Bessell-Browne, Andrew P Negri, Rebecca Fisher, Peta L Clode, Alan Duckworth, Ross Jones
As part of an investigation of the effects of water quality from dredging/natural resuspension on reefs, the effects of suspended sediment concentrations (SSCs) (0, 30, 100mgL(-1)) and light (~0, 1.1, 8.6molphotonsm(-2)d(-1)) were examined alone and in combination, on the corals Acropora millepora, Montipora capricornis and Porites spp. over an extended (28d) period. No effects were observed at any sediment concentrations when applied alone. All corals in the lowest light treatments lost chlorophyll a and discoloured (bleached) after a week...
February 2, 2017: Marine Pollution Bulletin
https://www.readbyqxmd.com/read/28154081/the-structure-of-the-yeast-mitochondrial-ribosome
#7
Nirupa Desai, Alan Brown, Alexey Amunts, V Ramakrishnan
Mitochondria have specialized ribosomes (mitoribosomes) dedicated to the expression of the genetic information encoded by their genomes. Here, using electron cryomicroscopy, we have determined the structure of the 75-component yeast mitoribosome to an overall resolution of 3.3 angstroms. The mitoribosomal small subunit has been built de novo and includes 15S ribosomal RNA (rRNA) and 34 proteins, including 14 without homologs in the evolutionarily related bacterial ribosome. Yeast-specific rRNA and protein elements, including the acquisition of a putatively active enzyme, give the mitoribosome a distinct architecture compared to the mammalian mitoribosome...
February 3, 2017: Science
https://www.readbyqxmd.com/read/28142274/data-selection-importance-in-the-study-of-the-association-between-maternal-smoking-during-pregnancy-and-schizophrenia-response-to-meier-et-al
#8
Solja Niemelä, Andre Sourander, Heljä-Marja Surcel, Susanna Hinkka-Yli-Salomäki, Ian W McKeague, Keely Cheslack-Postava, Alan S Brown
No abstract text is available yet for this article.
February 1, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/28138034/azd6738-a-novel-oral-inhibitor-of-atr-induces-synthetic-lethality-with-atm-deficiency-in-gastric-cancer-cells
#9
Ahrum Min, Seock-Ah Im, Hyemin Jang, Seongyeong Kim, Miso Lee, Debora Keunyoung Kim, Yaewon Yang, Hee-Jun Kim, Kyung-Hun Lee, Jin Won Kim, Tae-Yong Kim, Do-Youn Oh, Jeff Brown, Alan Lau, Mark J O Connor, Yung-Jue Bang
Ataxia telangiectasia and Rad3-related (ATR) can be considered an attractive target for cancer treatment due to its deleterious effect on cancer cells harboring a homologous recombination defect (HRD). The aim of this study was to investigate the potential use of the ATR inhibitor, AZD6738, to treat gastric cancer. In SNU-601 cells with dysfunctional ATM, AZD6738 treatment led to an accumulation of DNA damage due to dysfunctional RAD51 foci formation, S phase arrest, and caspase 3-dependent apoptosis. In contrast, SNU-484 cells with functional ATM were not sensitive to AZD6738...
January 30, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28137642/deriving-a-provisional-tolerable-intake-for-intravenous-exposure-to-silver-nanoparticles-released-from-medical-devices
#10
Laura C Savery, René Viñas, Amber Nagy, Prachi Pradeep, Stephen J Merrill, Alan M Hood, Subhas G Malghan, Peter L Goering, Ronald P Brown
Silver nanoparticles (AgNP) are incorporated into medical devices for their anti-microbial characteristics. The potential exposure and toxicity of AgNPs is unknown due to varying physicochemical particle properties and lack of toxicological data. The aim of this safety assessment is to derive a provisional tolerable intake (pTI) value for AgNPs released from blood-contacting medical devices. A literature review of in vivo studies investigating critical health effects induced from intravenous (i.v.) exposure to AgNPs was evaluated by the Annapolis Accords principles and Toxicological Data Reliability Assessment Tool (ToxRTool)...
January 27, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28121232/minimum-wear-duration-for-the-activpal%C3%A2-professional-activity-monitor-in-adolescent-females
#11
Kieran P Dowd, Helen Purtill, Deirdre M Harrington, Jane F Hislop, John J Reilly, Alan E Donnelly
OBJECTIVES: This study aims to determine the minimum number of days of monitoring required to reliably predict sitting/lying time, standing time, light intensity physical activity (LIPA), moderate-to-vigorous intensity physical activity (MVPA) and steps in adolescent females. METHODS: 195 adolescent females (mean age=15.7 years; SD=0.9) participated in the study. Participants wore the activPAL activity monitor for a seven day protocol. The amount of time spent sitting/lying, standing, in LIPA and in MVPA and the number of steps per day were quantified...
25, 2017: Pediatric Exercise Science
https://www.readbyqxmd.com/read/28080979/the-peatland-vegetation-burning-debate-keep-scientific-critique-in-perspective-a-response-to-brown-et-al-and-douglas-et-al
#12
G Matt Davies, Nicholas Kettridge, Cathelijne R Stoof, Alan Gray, Rob Marrs, Davide Ascoli, Paulo M Fernandes, Katherine A Allen, Stefan H Doerr, Gareth D Clay, Julia McMorrow, Vigdis Vandvik
No abstract text is available yet for this article.
November 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28077392/bidirectional-crosstalk-between-the-sensory-and-sympathetic-motor-systems-innervating-brown-and-white-adipose-tissue-in-male-siberian-hamsters
#13
Vitaly Ryu, Alan G Watts, Bingzhong Xue, Timothy J Bartness
The brain networks connected to the sympathetic motor and sensory innervations of brown (BAT) and white (WAT) adipose tissues were originally described using two transneuronally transported viruses: the retrogradely transported pseudorabies virus (PRV), and the anterogradely transported H129 strain of herpes simplex virus-1 (HSV-1 H129). Further complexity was added to this network organization when combined injections of PRV and HSV-1 H129 into either BAT or WAT of the same animal generated sets of co-infected neurons in the brain, spinal cord, sympathetic and dorsal root ganglia...
January 11, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28073530/variation-in-the-abundance-of-pseudo-nitzschia-and-domoic-acid-with-surf-zone-type
#14
Alan L Shanks, Steven G Morgan, Jamie MacMahan, Ad J H M Reniers, Raphael Kudela, Marley Jarvis, Jenna Brown, Atsushi Fujimura, Lisa Ziccarelli, Chris Griesemer
Most harmful algal blooms (HAB) originate away from the shore and, for them to endanger human health, they must be first transported to shore after which they must enter the surf zone where they can be feed upon by filter feeders. The last step in this sequence, entrance into the surf zone, depends on surf zone hydrodynamics. During two 30-day periods, we sampled Pseudo-nitzschia and particulate domoic acid (pDA) in and offshore of a more dissipative surf zone at Sand City, California (2010) and sampled Pseudo-nitzschia in and out of reflective surf zones at a beach and rocky shores at Carmel River State Beach, California (2011)...
May 2016: Harmful Algae
https://www.readbyqxmd.com/read/28065850/deep-grey-matter-iron-accumulation-in-alcohol-use-disorder
#15
Michal Juhás, Hongfu Sun, Matthew R G Brown, Marnie B MacKay, Karl F Mann, Wolfgang H Sommer, Alan H Wilman, Serdar M Dursun, Andrew J Greenshaw
PURPOSE: Evaluate brain iron accumulation in alcohol use disorder (AUD) patients compared to controls using quantitative susceptibility mapping (QSM). METHODS: QSM was performed retrospectively by using phase images from resting state functional magnetic resonance imaging (fMRI). 20 male AUD patients and 15 matched healthy controls were examined. Susceptibility values were manually traced in deep grey matter regions including caudate nucleus, combined putamen and globus pallidus, combined substantia nigra and red nucleus, dentate nucleus, and a reference white matter region in the internal capsule...
January 5, 2017: NeuroImage
https://www.readbyqxmd.com/read/28045551/use-of-a-low-literacy-written-action-plan-to-improve-parent-understanding-of-pediatric-asthma-management-a-randomized-controlled-study
#16
Hsiang Shonna Yin, Ruchi Gupta, Alan L Mendelsohn, Benard P Dreyer, Linda van Schaick, Christina R Brown, Karen Encalada, Dayana Sanchez, Christopher Warren, Suzy Tomopoulos
OBJECTIVES: To determine whether parents who use a low literacy, pictogram- and photograph-based written asthma action plan have a better understanding of child asthma management compared to parents using a standard plan. METHODS: Randomized controlled study in 2 urban pediatric outpatient clinics. INCLUSION CRITERIA: English/Spanish-speaking parents of 2-12 year old asthmatic children. Parents were randomized to receive a low literacy or standard asthma action plan (American Academy of Allergy, Asthma and Immunology) for a hypothetical patient on controller and rescue medications...
January 3, 2017: Journal of Asthma: Official Journal of the Association for the Care of Asthma
https://www.readbyqxmd.com/read/28024301/issues-surrounding-age-adjusted-d-dimer-cutoffs-that-practicing-physicians-need-to-know-when-evaluating-patients-with-suspected-pulmonary-embolism
#17
Andrew J Goodwin, Russell A Higgins, Karen A Moser, Kristi J Smock, Wayne L Chandler, Kandice Kottke-Marchant, Sarah K Hartman, Oksana Volod, Alan F Brown, Vandita P Johari, Sharon Burr, Nataliya Polyakov, Dong Chen
No abstract text is available yet for this article.
December 27, 2016: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28011028/statistical-analysis-of-seoul-air-quality-to-assess-the-efficacy-of-emission-abatement-strategies-since-1987
#18
Scott D Chambers, Ki-Hyun Kim, Eilhann E Kwon, Richard J C Brown, Alan D Griffiths, Jagoda Crawford
The combined influences of recent mitigation measures on urban air quality have been assessed using hourly observations of the criteria air pollutants (NO, NO2, O3, CO, and SO2) made from the Yongsan district of Seoul, Korea, over 26years (1987 to 2013). A number of data selection criteria are proposed in order to minimize variability associated with temporal changes (at diurnal, weekly, and seasonal timescales) in source strengths, their spatial distribution, and the atmospheric volume into which they mix...
December 20, 2016: Science of the Total Environment
https://www.readbyqxmd.com/read/27984435/tissue-fluorescence-imaging-velscope-for-quick-non-invasive-diagnosis-in-oral-pathology
#19
Marco Cicciù, Alan Scott Herford, Gabriele Cervino, Giuseppe Troiano, Floriana Lauritano, Luigi Laino
Oral squamous cell carcinoma is the most common form of malignancy of the oral cavity; its incidence is increasing and late-stage presentation is common. It is usually predated by oral premalignant disorders. For this reason, early diagnosis is fundamental to reduce the malignant transformation of oral premalignant disorders and for increase the survival rate for oral cancer. Scraping the surface of the lesion is useful for having cytological features of the investigated tissue. The features of smears of oral premalignant lesions are the keratinization growth (red, orange, brown), the increased nuclear area and so the nuclear hyperchromatism, the nuclear pleomorphism, and the chromatin clumping...
December 14, 2016: Journal of Craniofacial Surgery
https://www.readbyqxmd.com/read/27956846/repository-corticotropin-injection-in-patients-with-refractory-psoriatic-arthritis-a-case-series
#20
Alan N Brown
PURPOSE: Although numerous treatment options are available for patients with psoriatic arthritis (PsA), a need for effective and tolerable treatments remains for patients with refractory disease who have failed previous therapies and continue to experience tender and/or swollen joints, pain, and disease activity. Repository corticotropin injection (RCI) is believed to produce steroidogenic, steroid-independent, anti-inflammatory, and immunomodulatory effects in patients with rheumatic disorders, such as PsA...
2016: Open Access Rheumatology: Research and Reviews
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