621 research outputs found

    The Expression and Roles of Nde1 and Ndel1 in the Adult Mammalian Central Nervous System

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    Open Access funded by Wellcome Trust Under a Creative Commons license Acknowledgments We thank Prof Angelo Sementilli, Department of Pathology, Universidade Metropolitana de Santos, SP, Brazil, for the human sample collection. This study is funded by Scottish Universities Life Sciences Alliance (HR07019 to S. Shen and C.D. McCaig), Medical Research Scotland (384 FRG to B. Lang, United Kingdom), Tenovus Scotland (G12/25 to B. Lang), Sino-UK Higher Education Research Partnership for PhD Studies (C.D. McCaig and Y.Q. Ding) and Wellcome Trust (WT081633MA-NCE to P.J.A. McCaffery, United Kingdom).Peer reviewedPublisher PD

    Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12

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    Chemokines and their ligands play a critical role in enabling chronic lymphocytic leukaemia (CLL) cells access to protective microenvironmental niches within tissues, ultimately resulting in chemoresistance and relapse: disruption of these signaling pathways has become a novel therapeutic approach in CLL. The tyrosine kinase inhibitor dasatinib inhibits migration of several cell lines from solid-organ tumours, but effects on CLL cells have not been reported. We studied the effect of clinically achievable concentrations of dasatinib on signaling induced by the chemokine CXCL12 through its' receptor CXCR4, which is highly expressed on CLL cells. Dasatinib pre-treatment inhibited Akt and ERK phosphorylation in CLL cells upon stimulation with CXCL12. Dasatinib also significantly diminished the rapid increase in actin polymerisation observed in CLL cells following CXCL12 stimulation. Moreover, the drug significantly inhibited chemotaxis in a transwell assay, and reduced the percentage of cells able to migrate beneath a CXCL12-expressing murine stromal cell line. Dasatinib also abrogated the anti-apoptotic effect of prolonged CXCL12 stimulation on cultured CLL cells. These data suggest that dasatinib, akin to other small molecule kinase inhibitors targeting the B-cell receptor signaling pathway, may redistribute CLL cells from protective tissue niches to the peripheral blood, and support the investigation of dasatinib in combination strategies

    AAC W1876 hard red spring wheat

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    AAC W1876 hard red spring wheat (Triticum aestivum L.) has grain yield and time to maturity within the range of the check cultivars: Katepwa, Laura, Lillian, Carberry, and CDC Kernen. AAC W1876 has an awned spike, a low lodging score indicative of strong straw, and a short plant stature typical of a semidwarf wheat. AAC W1876 expressed resistance to prevalent races of leaf rust, moderate resistance to stem rust, intermediate resistance to fusarium head blight, yellow rust, common bunt, and loose smut. Compared to the Canada Western Red Spring check cultivars, AAC W1876 had improved flour yield and lower flour ash. AAC W1876 is eligible for grades of Canada Western Red Spring

    Large scale three-dimensional modelling for wave and tidal energy resource and environmental impact : methodologies for quantifying acceptable thresholds for sustainable exploitation

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    We describe a modelling project to estimate the potential effects of wave & tidal stream renewables on the marine environment. • Realistic generic devices to be used by those without access to the technical details available to developers are described. • Results show largely local sea bed effects at the level of the currently proposed renewables developments in our study area. • Large scale 3D modelling is critical to quantify the direct, indirect and cumulative effects of renewable energy extraction. • This is critical to comply with planning & environmental impact assessment regulations and achieve Good Environmental Status

    Modelling corneal epithelial wound closure in the presence of physiological electric fields via a moving boundary formalism

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    A new framework for the modelling of corneal epithelial wound healing is presented, which can include the presence of a physiological electric field. The difficulty inherent in the inclusion of this biological phenomenon motivates our use of a moving boundary formalism. A key conclusion is that the model predicts a linear relation between the wound healing speed and the physiological electric field strengths over a physiologically large range of electric field strength. Another key point is that this linear relationship between electric field strength and wound healing speed is robust to variations in critical parameters that are difficult to estimate. The linearity is also robust to different realizations of the modelling framework presented

    Clinician Knowledge and Beliefs after Statewide Program to Promote Appropriate Antimicrobial Drug Use

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    In 1999, Wisconsin initiated an educational campaign for primary care clinicians and the public to promote judicious antimicrobial drug use. We evaluated its impact on clinician knowledge and beliefs; Minnesota served as a control state. Results of pre- (1999) and post- (2002) campaign questionnaires indicated that Wisconsin clinicians perceived a significant decline in the proportion of patients requesting antimicrobial drugs (50% in 1999 to 30% in 2002; p<0.001) and in antimicrobial drug requests from parents for children (25% in 1999 to 20% in 2002; p = 0.004). Wisconsin clinicians were less influenced by nonpredictive clinical findings (purulent nasal discharge [p = 0.044], productive cough [p = 0.010]) in terms of antimicrobial drug prescribing. In 2002, clinicians from both states were less likely to recommend antimicrobial agent treatment for the adult case scenarios of viral respiratory illness. For the comparable pediatric case scenarios, only Wisconsin clinicians improved significantly from 1999 to 2002. Although clinicians in both states improved on several survey responses, greater overall improvement occurred in Wisconsin
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