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Steve watson

Okuma Emile Kasende, Vincent de Paul N Nziko, Steve Scheiner
Temozolomide (TMZ) was paired with each of the five nucleic acid bases, and the potential energy surface searched for all minima, in the context of dispersion-corrected density functional theory and MP2 methods. Three types of arrangements were observed, with competitive stabilities. Coplanar H-bonding structures, reminiscent of Watson-Crick base pairs were typically the lowest in energy, albeit by a small amount. Also very stable were perpendicular arrangements that included one or more H-bonds. The two monomers were stacked approximately parallel to one another in the third category, some of which contained weak and distorted H-bonds...
September 8, 2016: Journal of Physical Chemistry. B
Ben Johnson, Gillian C Lowe, Jane Futterer, Marie Lordkipanidzé, David MacDonald, Michael A Simpson, Isabel Sanchez-Guiú, Sian Drake, Danai Bem, Vincenzo Leo, Sarah J Fletcher, Ban Dawood, José Rivera, David Allsup, Tina Biss, Paula Hb Bolton-Maggs, Peter Collins, Nicola Curry, Charlotte Grimley, Beki James, Mike Makris, Jayashree Motwani, Sue Pavord, Katherine Talks, Jecko Thachil, Jonathan Wilde, Mike Williams, Paul Harrison, Paul Gissen, Stuart Mundell, Andrew Mumford, Martina E Daly, Steve P Watson, Neil V Morgan
Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study...
October 2016: Haematologica
Saba Nayar, Joana Campos, Ming May Chung, Leyre Navarro-Núñez, Menka Chachlani, Nathalie Steinthal, David H Gardner, Philip Rankin, Thomas Cloake, Jorge H Caamaño, Helen M McGettrick, Steve P Watson, Sanjiv Luther, Christopher D Buckley, Francesca Barone
Lymphangiogenesis associated with tertiary lymphoid structure (TLS) has been reported in numerous studies. However, the kinetics and dynamic changes occurring to the lymphatic vascular network during TLS development have not been studied. Using a viral-induced, resolving model of TLS formation in the salivary glands of adult mice we demonstrate that the expansion of the lymphatic vascular network is tightly regulated. Lymphatic vessel expansion occurs in two distinct phases. The first wave of expansion is dependent on IL-7...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Debi Bhattacharya, Clare F Aldus, Garry Barton, Christine M Bond, Sathon Boonyaprapa, Ian S Charles, Robert Fleetcroft, Richard Holland, Christina Jerosch-Herold, Charlotte Salter, Lee Shepstone, Christine Walton, Steve Watson, David J Wright
BACKGROUND: Medication organisation devices (MODs) provide compartments for a patient's medication to be organised into the days of the week and the recommended times the medication should be taken. AIM: To define the optimal trial design for testing the clinical effectiveness and cost-effectiveness of MODs. DESIGN: The feasibility study comprised a systematic review and focus groups to inform a randomised controlled trial (RCT) design. The resulting features were tested on a small scale, using a 2 × 2 factorial design to compare MODs with usual packaging and to compare weekly with monthly supply...
July 2016: Health Technology Assessment: HTA
Annabel Maclachlan, Steve P Watson, Neil V Morgan
Inherited platelet disorders (IPDs) are a heterogeneous group of disorders associated with normal or reduced platelet counts and bleeding diatheses of varying severities. The identification of the underlying cause of IPDs is clinically challenging due to the absence of a gold-standard platelet test, and is often based on a clinical presentation and normal values in other hematology assays. As a consequence, a DNA-based approach has a potentially important role in the investigation of these patients. Next-generation sequencing (NGS) technologies are allowing the rapid analysis of genes that have been previously implicated in IPDs or that are known to have a key role in platelet regulation, as well as novel genes that have not been previously implicated in platelet dysfunction...
June 27, 2016: Platelets
Sarah C Walpole, Clare Shortall, May Ci van Schalkwyk, Abi Merriel, Jayne Ellis, Lucy Obolensky, Marisa Casanova Dias, Jessica Watson, Colin S Brown, Jennifer Hall, Luisa M Pettigrew, Steve Allen
BACKGROUND: Globalisation is having profound impacts on health and healthcare. We solicited the views of a wide range of stakeholders in order to develop core global health competencies for postgraduate doctors. METHODS: Published literature and existing curricula informed writing of seven global health competencies for consultation. A modified policy Delphi involved an online survey and face-to-face and telephone interviews over three rounds. RESULTS: Over 250 stakeholders participated, including doctors, other health professionals, policymakers and members of the public from all continents of the world...
September 2016: International Health
María Luisa Lozano, Aaron Cook, José María Bastida, David S Paul, Gemma Iruin, Ana Rosa Cid, Rosa Adan-Pedroso, José Ramón González-Porras, Jesús María Hernández-Rivas, Sarah J Fletcher, Ben Johnson, Neil Morgan, Francisca Ferrer-Marin, Vicente Vicente, John Sondek, Steve P Watson, Wolfgang Bergmeier, José Rivera
In addition to mutations in ITG2B or ITGB3 genes that cause defective αIIbβ3 expression and/or function in Glanzmann's thrombasthenia patients, platelet dysfunction can be a result of genetic variability in proteins that mediate inside-out activation of αIIbβ3 The RASGRP2 gene is strongly expressed in platelets and neutrophils, where its encoded protein CalDAG-GEFI facilitates the activation of Rap1 and subsequent activation of integrins. We used next-generation sequencing (NGS) and whole-exome sequencing (WES) to identify 2 novel function-disrupting mutations in RASGRP2 that account for bleeding diathesis and platelet dysfunction in 2 unrelated families...
September 1, 2016: Blood
Jerico Revote, Nathan S Watson-Haigh, Steve Quenette, Blair Bethwaite, Annette McGrath, Catherine A Shang
The Bioinformatics Training Platform (BTP) has been developed to provide access to the computational infrastructure required to deliver sophisticated hands-on bioinformatics training courses. The BTP is a cloud-based solution that is in active use for delivering next-generation sequencing training to Australian researchers at geographically dispersed locations. The BTP was built to provide an easy, accessible, consistent and cost-effective approach to delivering workshops at host universities and organizations with a high demand for bioinformatics training but lacking the dedicated bioinformatics training suites required...
April 15, 2016: Briefings in Bioinformatics
John C Beaulieu, Rebecca E Stein-Chisholm, Steve W Lloyd, Karen L Bett-Garber, Casey C Grimm, Michael A Watson, Jeanne M Lea
BACKGROUND: High antioxidant content and keen marketing have increased blueberry demand and increased local production which in turn mandates new uses for abundant harvests. Pilot scale processes were employed to investigate the anthocyanidin profiles, qualitative volatile compositions, and sensorial attributes in not-from-concentrate (NFC) 'Tifblue' rabbiteye blueberry juices. RESULTS: Processing prior to pasteurization generally resulted in increased L* and hue angle color, while a*, b*, and C* decreased...
April 6, 2016: Journal of the Science of Food and Agriculture
Srimoyee Ghosh, Alexander Taylor, Melissa Chin, Hon-Ren Huang, Andrew R Conery, Jennifer A Mertz, Andres Salmeron, Pranal J Dakle, Deanna Mele, Alexandre Cote, Hari Jayaram, Jeremy W Setser, Florence Poy, Georgia Hatzivassiliou, Denise DeAlmeida-Nagata, Peter Sandy, Charlie Hatton, F Anthony Romero, Eugene Chiang, Thornik Reimer, Terry Crawford, Eneida Pardo, Venita G Watson, Vickie Tsui, Andrea G Cochran, Laura Zawadzke, Jean-Christophe Harmange, James E Audia, Barbara M Bryant, Richard T Cummings, Steven R Magnuson, Jane L Grogan, Steve F Bellon, Brian K Albrecht, Robert J Sims, Jose M Lora
Covalent modification of histones is a fundamental mechanism of regulated gene expression in eukaryotes, and interpretation of histone modifications is an essential feature of epigenetic control. Bromodomains are specialized binding modules that interact with acetylated histones, linking chromatin recognition to gene transcription. Because of their ability to function in a domain-specific fashion, selective disruption of bromodomain:acetylated histone interactions with chemical probes serves as a powerful means for understanding biological processes regulated by these chromatin adaptors...
June 17, 2016: Journal of Biological Chemistry
Callum N Watson, Steven W Kerrigan, Dermot Cox, Ian R Henderson, Steve P Watson, Mònica Arman
Gram-negative Escherichia coli cause diseases such as sepsis and hemolytic uremic syndrome in which thrombotic disorders can be found. Direct platelet-bacterium interactions might contribute to some of these conditions; however, mechanisms of human platelet activation by E. coli leading to thrombus formation are poorly understood. While the IgG receptor FcγRIIA has a key role in platelet response to various Gram-positive species, its role in activation to Gram-negative bacteria is poorly defined. This study aimed to investigate the molecular mechanisms of human platelet activation by E...
September 2016: Platelets
Kathleen M MacQueen, Sarah Dlamini, Brian Perry, Eunice Okumu, Steve Sortijas, Chitra Singh, Diantha Pillay, Alesha Majors, Sonja Jerome, Sharon Watson, Salim Abdool Karim, Quarraisha Abdool Karim, Leila E Mansoor
CAPRISA 008, an open-label extension study of tenofovir gel with coitally-related dosing, provided an opportunity to explore the relationship between product adherence and gender dynamics in a context where women knew they were receiving an active product with evidence of HIV prevention effectiveness. Interviews with 63 CAPRISA 008 participants and 13 male partners in KwaZulu-Natal, South Africa, highlighted that the process of negotiating gel use was determined in part by relationship dynamics including the duration of the relationship, the living situation, an evaluation of the relationship (e...
March 5, 2016: AIDS and Behavior
Abhishek Chauhan, David H Adams, Steve P Watson, Patricia F Lalor
: Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes...
November 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Briana Danielson, Matthew Barnhart, Adam Watson, Shawn Kennedy, Steve Naber
The objective of this study is to report on the short-term radiographic complications and bone healing associated with single-session bilateral tibial tuberosity advancements (TTAs). This retrospective study consists of 74 client-owned dogs with bilateral cranial cruciate ligament rupture that underwent consecutive single-session bilateral TTAs. Radiographs from 74 dogs (148 stifles) were evaluated for evidence of postoperative complications. One hundred forty-three of 148 stifles were scored for radiographic healing using a previously described scoring system...
March 2016: Journal of the American Animal Hospital Association
Brittany M Salter, John Paul Oliveria, Graeme Nusca, Steve G Smith, Damian Tworek, Patrick D Mitchell, Rick M Watson, Roma Sehmi, Gail M Gauvreau
BACKGROUND: The alarmin cytokines IL-25 and IL-33 are key promoters of type 2 inflammation. Basophils respond to alarmin cytokines, however the relationship of these cytokines with basophil activation and recruitment in human studies of allergic asthma has not been well characterized. This study investigated the effect of IL-25 and IL-33 on basophils in a model of allergic asthma. METHODS: 10 mild allergic asthmatics underwent allergen and diluent inhalation challenges...
2016: Respiratory Research
Graeme T Swindles, Paul J Morris, Donal Mullan, Elizabeth J Watson, T Edward Turner, Thomas P Roland, Matthew J Amesbury, Ulla Kokfelt, Kristian Schoning, Steve Pratte, Angela Gallego-Sala, Dan J Charman, Nicole Sanderson, Michelle Garneau, Jonathan L Carrivick, Clare Woulds, Joseph Holden, Lauren Parry, Jennifer M Galloway
Permafrost peatlands contain globally important amounts of soil organic carbon, owing to cold conditions which suppress anaerobic decomposition. However, climate warming and permafrost thaw threaten the stability of this carbon store. The ultimate fate of permafrost peatlands and their carbon stores is unclear because of complex feedbacks between peat accumulation, hydrology and vegetation. Field monitoring campaigns only span the last few decades and therefore provide an incomplete picture of permafrost peatland response to recent rapid warming...
2015: Scientific Reports
Jacqueline Stockley, Shaista P Nisar, Vincenzo C Leo, Essa Sabi, Margaret R Cunningham, Jeroen C Eikenboom, Stefan Lethagen, Reinhard Schneppenheim, Anne C Goodeve, Steve P Watson, Stuart J Mundell, Martina E Daly
The clinical expression of type 1 von Willebrand disease may be modified by co-inheritance of other mild bleeding diatheses. We previously showed that mutations in the platelet P2Y12 ADP receptor gene (P2RY12) could contribute to the bleeding phenotype in patients with type 1 von Willebrand disease. Here we investigated whether variations in platelet G protein-coupled receptor genes other than P2RY12 also contributed to the bleeding phenotype. Platelet G protein-coupled receptor genes P2RY1, F2R, F2RL3, TBXA2R and PTGIR were sequenced in 146 index cases with type 1 von Willebrand disease and the potential effects of identified single nucleotide variations were assessed using in silico methods and heterologous expression analysis...
2015: PloS One
Jessica R Hitchcock, Charlotte N Cook, Saeeda Bobat, Ewan A Ross, Adriana Flores-Langarica, Kate L Lowe, Mahmood Khan, C Coral Dominguez-Medina, Sian Lax, Manuela Carvalho-Gaspar, Stefan Hubscher, G Ed Rainger, Mark Cobbold, Christopher D Buckley, Tim J Mitchell, Andrea Mitchell, Nick D Jones, N Van Rooijen, Daniel Kirchhofer, Ian R Henderson, David H Adams, Steve P Watson, Adam F Cunningham
Thrombosis is a common, life-threatening consequence of systemic infection; however, the underlying mechanisms that drive the formation of infection-associated thrombi are poorly understood. Here, using a mouse model of systemic Salmonella Typhimurium infection, we determined that inflammation in tissues triggers thrombosis within vessels via ligation of C-type lectin-like receptor-2 (CLEC-2) on platelets by podoplanin exposed to the vasculature following breaching of the vessel wall. During infection, mice developed thrombi that persisted for weeks within the liver...
December 2015: Journal of Clinical Investigation
David C Watson, Warren W Wakarchuk, Christian Gervais, Yves Durocher, Anna Robotham, Steve M Fernandes, Ronald L Schnaar, N Martin Young, Michel Gilbert
Legionaminic acids are analogs of sialic acid that occur in several bacteria. The most commonly occurring form is Leg5Ac7Ac, which differs from Neu5Ac only at the C7 (acetamido) and C9 (deoxy) positions. While these differences greatly reduce the susceptibility of Leg compounds to sialidases, several sialyltransferases have been identified that can use CMP-Leg5Ac7Ac as a donor (Watson et al. 2011). We report the successful modification with Leg5Ac7Ac of a glycolipid, GM1a, and two glycoproteins, interferon-α2b and α1-antitrypsin, by means of two mammalian sialyltransferases, namely porcine ST3Gal1 and human ST6Gal1...
December 2015: Glycoconjugate Journal
Brittany M Salter, Graeme Nusca, Damian Tworek, John-Paul Oliveria, Steve G Smith, Rick M Watson, Tara Scime, Catie Obminski, Roma Sehmi, Gail M Gauvreau
No abstract text is available yet for this article.
March 2016: Journal of Allergy and Clinical Immunology
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