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Steve watson

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https://www.readbyqxmd.com/read/28839100/platelet-clec-2-protects-against-lung-injury-via-effects-of-its-ligand-podoplanin-on-inflammatory-alveolar-macrophages-in-the-mouse
#1
Sian Lax, Julie Rayes, Surasak Wichaiyo, Elizabeth J Haining, Kate Lowe, Beata Grygielska, Ryan Laloo, Per Flodby, Zea Borok, Edward D Crandall, David Thickett, Steve P Watson
There is no therapeutic intervention proven to prevent the acute respiratory syndrome (ARDS). Novel mechanistic insights into the pathophysiology of ARDS are therefore required. Platelets are implicated in regulating many of the pathogenic processes which occur during ARDS, however the mechanisms remain elusive. The platelet receptor C-type lectin-like 2 (CLEC-2) has been shown to regulate vascular integrity at sites of acute inflammation. Therefore, the purpose of this study was to establish the role of CLEC-2 and its ligand podoplanin in a mouse model of ARDS...
August 24, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28835437/clec-2-contributes-to-hemostasis-independently-of-classical-hemitam-signaling-in-mice
#2
Elizabeth J Haining, Deya Cherpokova, Karen Wolf, Isabelle C Becker, Sarah Beck, Johannes A Eble, David Stegner, Steve P Watson, Bernhard Nieswandt
C-type lectin-like receptor 2 (CLEC 2) is a platelet receptor that is critical during development in blood-lymph separation and implicated in thrombus stability in thrombosis and hemostasis. It is the only known platelet activatory receptor that participates in both these aspects of platelet function and is the only one to signal through a hemi-immunoreceptor tyrosine-based activation motif (hemITAM). Current investigations into the function of CLEC 2 in vivo have focused on knock-out studies in which both the receptor and its signaling are deleted, making it impossible to explore the possible signaling independent functions of the receptor which are indicated by its only known physiological ligand, podoplanin, being an integral membrane protein...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28834559/improving-the-pre-hospital-safety-of-steroid-dependent-patients-in-northern-england-a-hospital-initiated-ambulance-service-registration-pathway
#3
Anna L Mitchell, Kerri Devine, Vikram Lal, Paul Galloway, Matthew House, Katherine White, Julie Watson, Steve Parry, Margaret Miller, Margaret Morris, R Andy James, Petros Perros, Simon Hs Pearce, Richard Quinton
Acute adrenal crisis is a life-threatening medical emergency requiring immediate recognition and treatment. Among individuals with primary adrenal insufficiency it has a frequency of 6-8 per 100 patient-years(1) . Unfortunately, delays in diagnosis and management of acute adrenal crisis are commonplace - even in patients with documented steroid-dependency - constituting an avoidable source of patient harm. This article is protected by copyright. All rights reserved.
August 23, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28762304/identification-of-two-novel-mutations-in-rasgrp2-affecting-platelet-caldag-gefi-expression-and-function-in-patients-with-bleeding-diathesis
#4
Teresa Sevivas, José María Bastida, David S Paul, Eva Caparros, Verónica Palma-Barqueros, Margarida Coucelo, Dalila Marques, Francisca Ferrer-Marín, José Ramón González-Porras, Vicente Vicente, Jesús María Hernández-Rivas, Steve P Watson, María Luisa Lozano, Wolfgang Bergmeier, José Rivera
The RASGRP2 gene encodes the Ca(2+) and DAG-regulated guanine nucleotide exchange factor I (CalDAG-GEFI), which plays a key role in integrin activation in platelets and neutrophils. We here report two new RASGRP2 variants associated with platelet dysfunction and bleeding in patients. The homozygous patients had normal platelet and neutrophil counts and morphology. Platelet phenotyping showed: prolonged PFA-100 closure times; normal expression of major glycoprotein receptors; severely reduced platelet aggregation response to ADP and collagen (both patients); aggregation response to PAR1 and arachidonic acid markedly impaired in one patient; PMA-induced aggregation unaffected; platelet secretion, clot retraction, and spreading minimally affected...
August 1, 2017: Platelets
https://www.readbyqxmd.com/read/28751965/four-simple-recommendations-to-encourage-best-practices-in-research-software
#5
Rafael C Jiménez, Mateusz Kuzak, Monther Alhamdoosh, Michelle Barker, Bérénice Batut, Mikael Borg, Salvador Capella-Gutierrez, Neil Chue Hong, Martin Cook, Manuel Corpas, Madison Flannery, Leyla Garcia, Josep Ll Gelpí, Simon Gladman, Carole Goble, Montserrat González Ferreiro, Alejandra Gonzalez-Beltran, Philippa C Griffin, Björn Grüning, Jonas Hagberg, Petr Holub, Rob Hooft, Jon Ison, Daniel S Katz, Brane Leskošek, Federico López Gómez, Luis J Oliveira, David Mellor, Rowland Mosbergen, Nicola Mulder, Yasset Perez-Riverol, Robert Pergl, Horst Pichler, Bernard Pope, Ferran Sanz, Maria V Schneider, Victoria Stodden, Radosław Suchecki, Radka Svobodová Vařeková, Harry-Anton Talvik, Ilian Todorov, Andrew Treloar, Sonika Tyagi, Maarten van Gompel, Daniel Vaughan, Allegra Via, Xiaochuan Wang, Nathan S Watson-Haigh, Steve Crouch
Scientific research relies on computer software, yet software is not always developed following practices that ensure its quality and sustainability. This manuscript does not aim to propose new software development best practices, but rather to provide simple recommendations that encourage the adoption of existing best practices. Software development best practices promote better quality software, and better quality software improves the reproducibility and reusability of research. These recommendations are designed around Open Source values, and provide practical suggestions that contribute to making research software and its source code more discoverable, reusable and transparent...
2017: F1000Research
https://www.readbyqxmd.com/read/28740869/comparing-sequencing-assays-and-human-machine-analyses-in-actionable-genomics-for-glioblastoma
#6
Kazimierz O Wrzeszczynski, Mayu O Frank, Takahiko Koyama, Kahn Rhrissorrakrai, Nicolas Robine, Filippo Utro, Anne-Katrin Emde, Bo-Juen Chen, Kanika Arora, Minita Shah, Vladimir Vacic, Raquel Norel, Erhan Bilal, Ewa A Bergmann, Julia L Moore Vogel, Jeffrey N Bruce, Andrew B Lassman, Peter Canoll, Christian Grommes, Steve Harvey, Laxmi Parida, Vanessa V Michelini, Michael C Zody, Vaidehi Jobanputra, Ajay K Royyuru, Robert B Darnell
OBJECTIVE: To analyze a glioblastoma tumor specimen with 3 different platforms and compare potentially actionable calls from each. METHODS: Tumor DNA was analyzed by a commercial targeted panel. In addition, tumor-normal DNA was analyzed by whole-genome sequencing (WGS) and tumor RNA was analyzed by RNA sequencing (RNA-seq). The WGS and RNA-seq data were analyzed by a team of bioinformaticians and cancer oncologists, and separately by IBM Watson Genomic Analytics (WGA), an automated system for prioritizing somatic variants and identifying drugs...
August 2017: Neurology. Genetics
https://www.readbyqxmd.com/read/28727496/modulation-of-vegf-induced-migration-and-network-formation-by-lymphatic-endothelial-cells-roles-of-platelets-and-podoplanin
#7
Stacey A Langan, Leyre Navarro-Núñez, Steve P Watson, Gerard B Nash
Lymphatic endothelial cells (LEC) express the transmembrane receptor podoplanin whose only known endogenous ligand CLEC-2 is found on platelets. Both podoplanin and CLEC-2 are required for normal lymphangiogenesis as mice lacking either protein develop a blood-lymphatic mixing phenotype. We investigated the roles of podoplanin and its interaction with platelets in migration and tube formation by LEC. Addition of platelets or antibody-mediated crosslinking of podoplanin inhibited LEC migration induced by vascular endothelial growth factors (VEGF-A or VEGF-C), but did not modify basal migration or the response to basic fibroblast growth factor or epidermal growth factor...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28576877/presenting-adamts13-antibody-and-antigen-levels-predict-prognosis-in-immune-mediated-thrombotic-thrombocytopenic-purpura
#8
MULTICENTER STUDY
Ferras Alwan, Chiara Vendramin, Karen Vanhoorelbeke, Katy Langley, Vickie McDonald, Steve Austin, Amanda Clark, William Lester, Richard Gooding, Tina Biss, Tina Dutt, Nichola Cooper, Oliver Chapman, Tanya Cranfield, Kenny Douglas, H G Watson, J J van Veen, Keith Sibson, William Thomas, Lynn Manson, Quentin A Hill, Sylvia Benjamin, Debra Ellis, John-Paul Westwood, Mari Thomas, Marie Scully
Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder caused by antibodies against ADAMTS13. From the United Kingdom TTP registry, we undertook a prospective study investigating the impact of the presenting anti-ADAMTS13 IgG antibody and ADAMTS13 antigen on mortality. A total of 312 episodes involving 292 patients over 87 months were included; 68% were female, median age 46 (range, 11-88 years), and median presenting ADAMTS13 of <5% (range, <5%-18%). The mortality rate was 10...
July 27, 2017: Blood
https://www.readbyqxmd.com/read/28399988/youth-social-behaviour-and-network-therapy-y-sbnt-adaptation-of-a-family-and-social-network-intervention-for-young-people-who-misuse-alcohol-and-drugs-a-randomised-controlled-feasibility-trial
#9
Judith Watson, Paul Toner, Ed Day, Donna Back, Louca-Mai Brady, Caroline Fairhurst, Charlotte Renwick, Lorna Templeton, Shabana Akhtar, Charlie Lloyd, Jinshuo Li, Kim Cocks, Sangeeta Ambegaokar, Steve Parrott, Paul McArdle, Eilish Gilvarry, Alex Copello
BACKGROUND: Family interventions appear to be effective at treating young people's substance misuse. However, implementation of family approaches in UK services is low. This study aimed to demonstrate the feasibility of recruiting young people to an intervention based on an adaptation of adult social behaviour and network therapy. It also sought to involve young people with experience of using substance misuse services in the research process. OBJECTIVES: To demonstrate the feasibility of recruiting young people to family and social network therapy and to explore ways in which young people with experience of using substance misuse services could be involved in a study of this nature...
March 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28394669/emotion-recognition-training-in-autism-spectrum-disorder-a-systematic-review-of-challenges-related-to-generalizability
#10
Steve Berggren, Sue Fletcher-Watson, Nina Milenkovic, Peter B Marschik, Sven Bölte, Ulf Jonsson
PURPOSE: To assess the generalizability of findings from randomized controlled trials (RCTs) evaluating emotion recognition (ER) training for children and adolescents with autism spectrum disorder (ASD). METHODS: We present a systematic review and narrative synthesis of the determinants of external validity in RCTs on ER training. Generalizability of the findings across situations, populations, settings, treatment delivery, and intervention formats was considered...
April 10, 2017: Developmental Neurorehabilitation
https://www.readbyqxmd.com/read/28387827/cost-effectiveness-of-cascade-testing-for-familial-hypercholesterolaemia-based-on-data-from-familial-hypercholesterolaemia-services-in-the-uk
#11
Marion Kerr, Robert Pears, Zofia Miedzybrodzka, Kate Haralambos, Moyra Cather, Melanie Watson, Steve E Humphries
Aims: Familial hypercholesterolaemia (FH) is a vastly under-diagnosed genetic disorder, associated with early development of coronary heart disease and premature mortality which can be substantially reduced by effective treatment. Patents have recently expired on high-intensity statins, reducing FH treatment costs. We build a model using UK data to estimate the cost effectiveness of DNA testing of relatives of those with monogenic FH. Methods and Results: A Markov model was used to estimate the cost effectiveness of cascade testing, using data from UK cascade services...
June 14, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28336561/mice-lacking-the-inhibitory-collagen-receptor-lair-1-exhibit-a-mild-thrombocytosis-and-hyperactive-platelets
#12
Christopher W Smith, Steven G Thomas, Zaher Raslan, Pushpa Patel, Maxwell Byrne, Marie Lordkipanidzé, Danai Bem, Linde Meyaard, Yotis A Senis, Steve P Watson, Alexandra Mazharian
OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor that belongs to the inhibitory immunoreceptor tyrosine-based inhibition motif-containing receptor family. It is an inhibitor of signaling via the immunoreceptor tyrosine-based activation motif-containing collagen receptor complex, glycoprotein VI-FcRγ-chain. It is expressed on hematopoietic cells, including immature megakaryocytes, but is not detectable on platelets. Although the inhibitory function of LAIR-1 has been described in leukocytes, its physiological role in megakaryocytes and in particular in platelet formation has not been explored...
May 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28320406/the-acceptability-and-feasibility-of-a-brief-psychosocial-intervention-to-reduce-blood-borne-virus-risk-behaviours-among-people-who-inject-drugs-a-randomised-control-feasibility-trial-of-a-psychosocial-intervention-the-protect-study-versus-treatment-as-usual
#13
Gail Gilchrist, Davina Swan, April Shaw, Ada Keding, Sarah Towers, Noel Craine, Alison Munro, Elizabeth Hughes, Steve Parrott, John Strang, Avril Taylor, Judith Watson
BACKGROUND: While opiate substitution therapy and injecting equipment provision (IEP) have reduced blood-borne viruses (BBV) among people who inject drugs (PWID), some PWID continue to share injecting equipment and acquire BBV. Psychosocial interventions that address risk behaviours could reduce BBV transmission among PWID. METHODS: A pragmatic, two-armed randomised controlled, open feasibility study of PWID attending drug treatment or IEP in four UK regions. Ninety-nine PWID were randomly allocated to receive a three-session manualised psychosocial group intervention and BBV transmission information booklet plus treatment as usual (TAU) (n = 52) or information booklet plus TAU (n = 47)...
March 21, 2017: Harm Reduction Journal
https://www.readbyqxmd.com/read/28267383/whole-exome-sequencing-identifies-a-mutation-in-thrombomodulin-as-the-genetic-cause-of-a-suspected-platelet-disorder-in-a-family-with-normal-platelet-function
#14
Annabel Maclachlan, Gerry Dolan, Charlotte Grimley, Steve P Watson, Neil V Morgan, On Behalf Of The Uk Gapp Study Group
Here, we describe a mother and son with a lifelong bleeding tendency and posttraumatic bleeding who were recruited to the UK Genotyping and Phenotyping of Platelets (GAPP) study with a suspected platelet function disorder. However, despite a clinically significant bleeding score, both had normal platelet counts and normal platelet function. The patients' blood was analyzed by light transmission aggregometry and genotyping by whole exome sequencing, as outlined by the GAPP study. Approximately 25 000 genetic variants were found for each patient as a result of sequencing and were filtered using a specialized bioinformatics pipeline...
September 2017: Platelets
https://www.readbyqxmd.com/read/28107764/endoscopic-ultrasound-guided-biliary-access-versus-precut-papillotomy-in-patients-with-failed-biliary-cannulation-a-retrospective-study
#15
Alexander Lee, Anupam Aditi, Yasser M Bhat, Kenneth F Binmoeller, Chris Hamerski, Oriol Sendino, Steve Kane, John P Cello, Lukejohn W Day, Medi Mohamadnejad, V Raman Muthusamy, Rabindra Watson, Jason B Klapman, Sri Komanduri, Sachin Wani, Janak N Shah
Background and aims Precut papillotomy is widely used after failed biliary cannulation. Endoscopic ultrasound (EUS)-guided biliary access techniques are newer methods to facilitate access and therapy in failed cannulation. We evaluated the impact of EUS-guided biliary access on endoscopic retrograde cholangiopancreatography (ERCP) success and compared these techniques to precut papillotomy. Patients and methods We retrospectively compared two ERCP cohorts. One cohort consisted of biliary ERCPs (n = 1053) attempted in patients with native papillae and surgically unaltered anatomy in whom precut papillotomy and/or EUS-guided biliary access were routinely performed immediately after failed cannulation...
February 2017: Endoscopy
https://www.readbyqxmd.com/read/28104688/mice-with-a-deficiency-in-clec-2-are-protected-against-deep-vein-thrombosis
#16
Holly Payne, Tatyana Ponomaryov, Steve P Watson, Alexander Brill
Deep vein thrombosis (DVT) with its major complication, pulmonary embolism, is a global health problem. Mechanisms of DVT remain incompletely understood. Platelets play a role in DVT, but the impact of specific platelet receptors remains unclear. Platelet C-type lectin-like receptor 2 (CLEC-2) is known to maintain the physiological state of blood vasculature under inflammatory conditions. DVT is a thromboinflammatory disorder developing largely as sterile inflammation in the vessel wall. We hypothesized therefore that CLEC-2 might play a role in DVT...
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28095212/platelets-a-fine-balance
#17
EDITORIAL
Paul Harrison, Steve Watson
No abstract text is available yet for this article.
January 2017: Platelets
https://www.readbyqxmd.com/read/28032533/tetraspanin-tspan9-regulates-platelet-collagen-receptor-gpvi-lateral-diffusion-and-activation
#18
Elizabeth J Haining, Alexandra L Matthews, Peter J Noy, Hanna M Romanska, Helen J Harris, Jeremy Pike, Martina Morowski, Rebecca L Gavin, Jing Yang, Pierre-Emmanuel Milhiet, Fedor Berditchevski, Bernhard Nieswandt, Natalie S Poulter, Steve P Watson, Michael G Tomlinson
The tetraspanins are a superfamily of four-transmembrane proteins, which regulate the trafficking, lateral diffusion and clustering of the transmembrane proteins with which they interact. We have previously shown that tetraspanin Tspan9 is expressed on platelets. Here we have characterised gene-trap mice lacking Tspan9. The mice were viable with normal platelet numbers and size. Tspan9-deficient platelets were specifically defective in aggregation and secretion induced by the platelet collagen receptor GPVI, despite normal surface GPVI expression levels...
December 29, 2016: Platelets
https://www.readbyqxmd.com/read/27810998/postnatal-deletion-of-podoplanin-in-lymphatic-endothelium-results-in-blood-filling-of-the-lymphatic-system-and-impairs-dendritic-cell-migration-to-lymph-nodes
#19
Roberta Bianchi, Erica Russo, Samia B Bachmann, Steven T Proulx, Marko Sesartic, Nora Smaadahl, Steve P Watson, Christopher D Buckley, Cornelia Halin, Michael Detmar
OBJECTIVE: The lymphatic vascular system exerts major physiological functions in the transport of interstitial fluid from peripheral tissues back to the blood circulation and in the trafficking of immune cells to lymph nodes. Previous studies in global constitutive knockout mice for the lymphatic transmembrane molecule podoplanin reported perinatal lethality and a complex phenotype with lung abnormalities, cardiac defects, lymphedema, blood-filled lymphatic vessels, and lack of lymph node organization, reflecting the importance of podoplanin expression not only by the lymphatic endothelium but also by a variety of nonendothelial cell types...
January 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27513011/interactions-of-nucleic-acid-bases-with-temozolomide-stacked-perpendicular-and-coplanar-heterodimers
#20
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
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