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Bannister model

Ian J Hamling, Sigrun Hreinsdóttir, Kate Clark, John Elliott, Cunren Liang, Eric Fielding, Nicola Litchfield, Pilar Villamor, Laura Wallace, Tim J Wright, Elisabetta D'Anastasio, Stephen Bannister, David Burbidge, Paul Denys, Paula Gentle, Jamie Howarth, Christof Mueller, Neville Palmer, Chris Pearson, William Power, Philip Barnes, David J A Barrell, Russ Van Dissen, Robert Langridge, Tim Little, Andrew Nicol, Jarg Pettinga, Julie Rowland, Mark Stirling
On 14th November 2016, the northeastern South Island of New Zealand was struck by a major Mw 7.8 earthquake. Field observations, in conjunction with InSAR, GPS, and seismology reveal this to be one of the most complex earthquakes ever recorded. The rupture propagated northward for more than 170 km along both mapped and unmapped faults, before continuing offshore at its northeastern extent. Geodetic and field observations reveal surface ruptures along at least 12 major faults, including possible slip along the southern Hikurangi subduction interface, extensive uplift along much of the coastline and widespread anelastic deformation including the ~8 m uplift of a fault-bounded block...
March 23, 2017: Science
Dustin Siegel, Hon C Hui, Edward Doerffler, Michael O Clarke, Kwon Chun, Lijun Zhang, Sean Neville, Ernest Carra, Willard Lew, Bruce Ross, Queenie Wang, Lydia Wolfe, Robert Jordan, Veronica Soloveva, John Knox, Jason Perry, Michel Perron, Kirsten M Stray, Ona Barauskas, Joy Y Feng, Yili Xu, Gary Lee, Arnold L Rheingold, Adrian S Ray, Roy Bannister, Robert Strickley, Swami Swaminathan, William A Lee, Sina Bavari, Tomas Cihlar, Michael K Lo, Travis K Warren, Richard L Mackman
The recent Ebola virus (EBOV) outbreak in West Africa was the largest recorded in history with over 28,000 cases, resulting in >11,000 deaths including >500 healthcare workers. A focused screening and lead optimization effort identified 4b (GS-5734) with anti-EBOV EC50 = 86 nM in macrophages as the clinical candidate. Structure activity relationships established that the 1'-CN group and C-linked nucleobase were critical for optimal anti-EBOV potency and selectivity against host polymerases. A robust diastereoselective synthesis provided sufficient quantities of 4b to enable preclinical efficacy in a non-human-primate EBOV challenge model...
February 14, 2017: Journal of Medicinal Chemistry
Laura Bannister, Mandy Serran, Lindsey Bertrand, Dmitry Klokov, Heather Wyatt, Melinda Blimkie, Yann Gueguen, Nicholas Priest, Jean-René Jourdain, Pamela Sykes
The toxicity of tritium is a public health concern given its presence and mobility in the environment. For risk predictions using radiological protection models, it is essential to allocate an appropriate radiation weighting factor (WR). This in turn should be consistent with the observed relative biological effectiveness (RBE) of tritium beta radiation. Although the International Commission on Radiological Protection (ICRP) currently recommends a WR of 1 for the calculation of committed effective dose for X rays, gamma rays and electrons of all energies, including tritium energies, there are concerns that tritium health risks are underestimated and that current regulatory tritium drinking water standards need revision...
December 2016: Radiation Research
Franck Madoux, Daniela Dreymuller, Jean-Phillipe Pettiloud, Radleigh Santos, Christoph Becker-Pauly, Andreas Ludwig, Gregg B Fields, Thomas Bannister, Timothy P Spicer, Mare Cudic, Louis D Scampavia, Dmitriy Minond
ADAM10 and ADAM17 have been shown to contribute to the acquired drug resistance of HER2-positive breast cancer in response to trastuzumab. The majority of ADAM10 and ADAM17 inhibitor development has been focused on the discovery of compounds that bind the active site zinc, however, in recent years, there has been a shift from active site to secondary substrate binding site (exosite) inhibitor discovery in order to identify non-zinc-binding molecules. In the present work a glycosylated, exosite-binding substrate of ADAM10 and ADAM17 was utilized to screen 370,276 compounds from the MLPCN collection...
December 2016: Scientific Reports
Donald Beqollari, Christin F Romberg, Gabriella Dobrowolny, Martina Martini, Andrew A Voss, Antonio Musarò, Roger A Bannister
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3-5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events that underlie its pathology are not restricted to the nervous system. In this regard, ALS muscle atrophies and weakens significantly before presentation of neurological symptoms. Since the skeletal muscle L-type Ca(2+) channel (CaV1.1) is a key regulator of both mass and force, we investigated whether CaV1...
June 23, 2016: Skeletal Muscle
K R Rusimova, N Bannister, P Harrison, D Lock, S Crampin, R E Palmer, P A Sloan
The tip of a scanning tunnelling microscope is an atomic-scale source of electrons and holes. As the injected charge spreads out, it can induce adsorbed molecules to react. By comparing large-scale 'before' and 'after' images of an adsorbate covered surface, the spatial extent of the nonlocal manipulation is revealed. Here, we measure the nonlocal manipulation of toluene molecules on the Si(111)-7 × 7 surface at room temperature. Both the range and probability of nonlocal manipulation have a voltage dependence...
2016: Nature Communications
Helen Swaisland, Ruth Plummer, Karen So, Sally Garnett, Wendy Bannister, Marc-Antoine Fabre, Corina Dota, Anitra Fielding
BACKGROUND: Some therapeutic agents in oncology can be causally associated with specific cardiovascular events including QT/QTc interval prolongation. We investigated the effect of multiple dosing of the oral poly (ADP-ribose)-polymerase (PARP) inhibitor, olaparib (tablet formulation) on QT/QTc interval. METHODS: Two phase I, open-label, three-part studies (NCT01921140 [study 4] and NCT01900028 [study 7]) were conducted in adults with refractory/resistant advanced solid tumours...
October 2016: Cancer Chemotherapy and Pharmacology
Donald Beqollari, Christin F Romberg, Gabriella Dobrowolny, Martina Martini, Andrew A Voss, Antonio Musarò, Roger A Bannister
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder that is typically fatal within 3-5 years of diagnosis. While motoneuron death is the defining characteristic of ALS, the events that underlie its pathology are not restricted to the nervous system. In this regard, ALS muscle atrophies and weakens significantly before presentation of neurological symptoms. Since the skeletal muscle L-type Ca(2+) channel (CaV1.1) is a key regulator of both mass and force, we investigated whether CaV1...
2016: Skeletal Muscle
Omer Gilan, Enid Y N Lam, Isabelle Becher, Dave Lugo, Ester Cannizzaro, Gerard Joberty, Aoife Ward, Meike Wiese, Chun Yew Fong, Sarah Ftouni, Dean Tyler, Kym Stanley, Laura MacPherson, Chen-Fang Weng, Yih-Chih Chan, Margherita Ghisi, David Smil, Christopher Carpenter, Peter Brown, Neil Garton, Marnie E Blewitt, Andrew J Bannister, Tony Kouzarides, Brian J P Huntly, Ricky W Johnstone, Gerard Drewes, Sarah-Jane Dawson, Cheryl H Arrowsmith, Paola Grandi, Rab K Prinjha, Mark A Dawson
Targeted therapies against disruptor of telomeric silencing 1-like (DOT1L) and bromodomain-containing protein 4 (BRD4) are currently being evaluated in clinical trials. However, the mechanisms by which BRD4 and DOT1L regulate leukemogenic transcription programs remain unclear. Using quantitative proteomics, chemoproteomics and biochemical fractionation, we found that native BRD4 and DOT1L exist in separate protein complexes. Genetic disruption or small-molecule inhibition of BRD4 and DOT1L showed marked synergistic activity against MLL leukemia cell lines, primary human leukemia cells and mouse leukemia models...
July 2016: Nature Structural & Molecular Biology
Travis K Warren, Robert Jordan, Michael K Lo, Adrian S Ray, Richard L Mackman, Veronica Soloveva, Dustin Siegel, Michel Perron, Roy Bannister, Hon C Hui, Nate Larson, Robert Strickley, Jay Wells, Kelly S Stuthman, Sean A Van Tongeren, Nicole L Garza, Ginger Donnelly, Amy C Shurtleff, Cary J Retterer, Dima Gharaibeh, Rouzbeh Zamani, Tara Kenny, Brett P Eaton, Elizabeth Grimes, Lisa S Welch, Laura Gomba, Catherine L Wilhelmsen, Donald K Nichols, Jonathan E Nuss, Elyse R Nagle, Jeffrey R Kugelman, Gustavo Palacios, Edward Doerffler, Sean Neville, Ernest Carra, Michael O Clarke, Lijun Zhang, Willard Lew, Bruce Ross, Queenie Wang, Kwon Chun, Lydia Wolfe, Darius Babusis, Yeojin Park, Kirsten M Stray, Iva Trancheva, Joy Y Feng, Ona Barauskas, Yili Xu, Pamela Wong, Molly R Braun, Mike Flint, Laura K McMullan, Shan-Shan Chen, Rachel Fearns, Swami Swaminathan, Douglas L Mayers, Christina F Spiropoulou, William A Lee, Stuart T Nichol, Tomas Cihlar, Sina Bavari
The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV...
March 17, 2016: Nature
Keith W Bannister, Jamie Stevens, Artem V Tuntsov, Mark A Walker, Simon Johnston, Cormac Reynolds, Hayley Bignall
Extreme scattering events (ESEs) are distinctive fluctuations in the brightness of astronomical radio sources caused by occulting plasma lenses in the interstellar medium. The inferred plasma pressures of the lenses are ~10(3) times the ambient pressure, challenging our understanding of gas conditions in the Milky Way. Using a new survey technique, we discovered an ESE while it was in progress. Here we report radio and optical follow-up observations. Modeling of the radio data demonstrates that the lensing structure is a density enhancement and the lens is diverging, ruling out one of two competing physical models...
January 22, 2016: Science
Ainara Ruiz de Sabando, Chao Wang, Yuanjun He, Mónica García-Barros, Julie Kim, Kenneth R Shroyer, Thomas D Bannister, Vincent W Yang, Agnieszka B Bialkowska
Colorectal cancer is one of the leading causes of cancer mortality in Western civilization. Studies have shown that colorectal cancer arises as a consequence of the modification of genes that regulate important cellular functions. Deregulation of the WNT and RAS/MAPK/PI3K signaling pathways has been shown to be important in the early stages of colorectal cancer development and progression. Krüppel-like factor 5 (KLF5) is a transcription factor that is highly expressed in the proliferating intestinal crypt epithelial cells...
January 2016: Molecular Cancer Therapeutics
Michel Rickhaus, Oliver T Unke, Rajesh Mannancherry, Linda M Bannwart, Markus Neuburger, Daniel Häussinger, Marcel Mayor
Conceptually and experimentally, a new set of helical model compounds is presented herein that allow correlations between structural features and their expression in the secondary structure to be investigated. A cross-linked oligomer with two strands of mismatching lengths connected in a ladder-type fashion serves as a model system. Compensation for the dimensional mismatch leads to the adoption of a helical arrangement. A strategically placed relay ensures the continuity and uniformity of the helix. Upon exchanging the heteroatomic linkage, the helix responds by increasing or decreasing the torsion of the backbone...
December 7, 2015: Chemistry: a European Journal
Sarah Falk, Kirsty Bannister, Anthony H Dickenson
Mechanisms of inflammatory and neuropathic pains have been elucidated and translated to patient care by the use of animal models of these pain states. Cancer pain has lagged behind since early animal models of cancer-induced bone pain were based on the systemic injection of carcinoma cells. This precluded systematic investigation of specific neuronal and pharmacological alterations that occur in cancer-induced bone pain. In 1999, Schwei et al. described a murine model of cancer-induced bone pain that paralleled the clinical condition in terms of pain development and bone destruction, confined to the mouse femur...
November 2014: British Journal of Pain
Valentina Escott-Price, Rebecca Sims, Christian Bannister, Denise Harold, Maria Vronskaya, Elisa Majounie, Nandini Badarinarayan, Kevin Morgan, Peter Passmore, Clive Holmes, John Powell, Carol Brayne, Michael Gill, Simon Mead, Alison Goate, Carlos Cruchaga, Jean-Charles Lambert, Cornelia van Duijn, Wolfgang Maier, Alfredo Ramirez, Peter Holmans, Lesley Jones, John Hardy, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams
The identification of subjects at high risk for Alzheimer's disease is important for prognosis and early intervention. We investigated the polygenic architecture of Alzheimer's disease and the accuracy of Alzheimer's disease prediction models, including and excluding the polygenic component in the model. This study used genotype data from the powerful dataset comprising 17 008 cases and 37 154 controls obtained from the International Genomics of Alzheimer's Project (IGAP). Polygenic score analysis tested whether the alleles identified to associate with disease in one sample set were significantly enriched in the cases relative to the controls in an independent sample...
December 2015: Brain: a Journal of Neurology
Melanie Bannister-Tyrrell, Jillian A Patterson, Jane B Ford, Jonathan M Morris, Michael C Nicholl, Christine L Roberts
BACKGROUND: Evidence about optimal mode of delivery for preterm birth is lacking, and there is thought to be considerable variation in practice. OBJECTIVE: To assess whether variation in hospital preterm caesarean section rates (Robson Classification Group 10) and outcomes are explained by casemix, labour or hospital characteristics. MATERIALS AND METHODS: Population-based cohort study in NSW, 2007-2011. Births were categorised according to degree of prematurity and hospital service capability: 26-31, 32-33 and 34-36 weeks' gestation...
August 2015: Australian & New Zealand Journal of Obstetrics & Gynaecology
Kirsty Bannister, Ryan Patel, Leonor Goncalves, Louisa Townson, Anthony H Dickenson
Diffuse noxious inhibitory controls (DNICs) utilize descending inhibitory controls through poorly understood brain stem pathways. The human counterpart, conditioned pain modulation, is reduced in patients with neuropathy aligned with animal data showing a loss of descending inhibitory noradrenaline controls together with a gain of 5-HT3 receptor-mediated facilitations after neuropathy. We investigated the pharmacological basis of DNIC and whether it can be restored after neuropathy. Deep dorsal horn neurons were activated by von Frey filaments applied to the hind paw, and DNIC was induced by a pinch applied to the ear in isoflurane-anaesthetized animals...
September 2015: Pain
Ross Stewart, Michelle Morrow, Scott A Hammond, Kathy Mulgrew, Danielle Marcus, Edmund Poon, Amanda Watkins, Stefanie Mullins, Matthieu Chodorge, John Andrews, David Bannister, Emily Dick, Nicola Crawford, Julie Parmentier, Marat Alimzhanov, John S Babcook, Ian N Foltz, Andrew Buchanan, Vahe Bedian, Robert W Wilkinson, Matthew McCourt
Programmed cell-death 1 ligand 1 (PD-L1) is a member of the B7/CD28 family of proteins that control T-cell activation. Many tumors can upregulate expression of PD-L1, inhibiting antitumor T-cell responses and avoiding immune surveillance and elimination. We have identified and characterized MEDI4736, a human IgG1 monoclonal antibody that binds with high affinity and specificity to PD-L1 and is uniquely engineered to prevent antibody-dependent cell-mediated cytotoxicity. In vitro assays demonstrate that MEDI4736 is a potent antagonist of PD-L1 function, blocking interaction with PD-1 and CD80 to overcome inhibition of primary human T-cell activation...
September 2015: Cancer Immunology Research
Manuela Bozzi, Alberto Cassetta, Sonia Covaceuszach, Maria Giulia Bigotti, Saskia Bannister, Wolfgang Hübner, Francesca Sciandra, Doriano Lamba, Andrea Brancaccio
The severe dystroglycanopathy known as a form of limb-girdle muscular dystrophy (LGMD2P) is an autosomal recessive disease caused by the point mutation T192M in α-dystroglycan. Functional expression analysis in vitro and in vivo indicated that the mutation was responsible for a decrease in posttranslational glycosylation of dystroglycan, eventually interfering with its extracellular-matrix receptor function and laminin binding in skeletal muscle and brain. The X-ray crystal structure of the missense variant T190M of the murine N-terminal domain of α-dystroglycan (50-313) has been determined, and showed an overall topology (Ig-like domain followed by a basket-shaped domain reminiscent of the small subunit ribosomal protein S6) very similar to that of the wild-type structure...
2015: PloS One
Mark L Bannister, N Lowri Thomas, Markus B Sikkel, Saptarshi Mukherjee, Chloe Maxwell, Kenneth T MacLeod, Christopher H George, Alan J Williams
RATIONALE: Flecainide, a class 1c antiarrhythmic, has emerged as an effective therapy in preventing arrhythmias in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) refractory to β-adrenergic receptor blockade. It has been proposed that the clinical efficacy of flecainide in CPVT is because of the combined actions of direct blockade of ryanodine receptors (RyR2) and Na(+) channel inhibition. However, there is presently no direct evidence to support the notion that flecainide blocks RyR2 Ca(2+) flux in the physiologically relevant (luminal-to-cytoplasmic) direction...
April 10, 2015: Circulation Research
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