406 research outputs found

    Identification and full genomic sequence of nerine yellow strip virus

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    This study reports the first complete genome sequence of nerine yellow stripe virus (NeYSV, GenBank MT396083). The genome consists of 10165 nucleotides, excluding the 3’ terminal poly(A) tail. A single open reading frame encodes a large polyprotein of 3294 amino acids with typical potyvirus features. The nuclear inclusion b and coat protein region shares 95% identity with previously reported NeYSV partial sequence (NC_043153.1). Phylogenetic analysis of polyprotein amino acid sequence showed that NeYSV clustered with hippeastrum mosaic virus (YP_006382256.1)

    What makes it so hard to look and to listen? Exploring the use of the Cognitive and Affective Supervisory Approach with children’s social work managers

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    This paper reports on the findings of an ESRC-funded Knowledge Exchange project designed to explore the contribution of an innovative approach to supervision to social work practitioners’ assessment and decision-making practices. The Cognitive and Affective Supervisory Approach (CASA) is informed by cognitive interviewing techniques originally designed to elicit best evidence from witnesses and victims of crime. Adapted here for use in childcare social work supervision contexts, this model is designed to enhance the quantity and quality of information available for decision-making. Facilitating the reporting of both ‘event information’ and ‘emotion information’, it allows a more detailed picture to emerge of events, as recalled by the individual involved, and the meaning they give to them. Practice supervisors from Children’s Services in two local authorities undertook to introduce the CASA into supervision sessions and were supported in this through the provision of regular reflective group discussions. The project findings highlight the challenges for practitioners of ‘detailed looking’ and for supervisors of ‘active listening’. The paper concludes by acknowledging that the CASA’s successful contribution to decision-making is contingent on both the motivation and confidence of supervisors to develop their skills and an organisational commitment to, and resourcing of, reflective supervisory practices and spaces

    Evaluation of immunogenicity and efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) fused to E. coli Heat-Labile Enterotoxin B Subunit LTB adjuvant following intranasal vaccination of cattle

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    Fasciolosis, caused by the liver flukes Fasciola hepatica and F. gigantica, is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the F. hepatica surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The Escherichia coli heat-labile enterotoxin’s B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of F. hepatica tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund’s adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy

    Evaluation of Immunogenicity and Efficacy of Fasciola hepatica Tetraspanin 2 (TSP2) Fused to E. coli Heat-Labile Enterotoxin B Subunit LTB Adjuvant Following Intranasal Vaccination of Cattle

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    Fasciolosis, caused by the liver flukes Fasciola hepatica and F. gigantica, is an economically important and globally distributed zoonotic disease. Liver fluke infections in livestock cause significant losses in production and are of particular concern to regions where drug resistance is emerging. Antigens of the F. hepatica surface tegument represent promising vaccine candidates for controlling this disease. Tetraspanins are integral tegumental antigens that have shown partial protection as vaccine candidates against other trematode species. The Escherichia coli heat-labile enterotoxin’s B subunit (LTB) is a potent mucosal adjuvant capable of inducing an immune response to fused antigens. This study investigates the potential of F. hepatica tetraspanin 2 extracellular loop 2 (rFhTSP2) as a protective vaccine antigen and determines if fusion of FhTSP2 to LTB can enhance protection in cattle. Cattle were immunised subcutaneously with rFhTSP2 mixed in the Freund’s adjuvant and intranasally with rLTB-FhTSP2 in saline, accounting for equal molar ratios of tetraspanin in both groups. Vaccination with rFhTSP2 stimulated a strong specific serum IgG response, whereas there was no significant serum IgG response following rLTB-FhTSP2 intranasal vaccination. There was no substantial antigen specific serum IgA generated in all groups across the trial. Contrastingly, after the fluke challenge, a rise in antigen specific saliva IgA was observed in both vaccination groups on Day 42, with the rLTB-FhTSP2 vaccination group showing significant mucosal IgA production at Day 84. However, neither vaccine group showed a significant reduction of fluke burden nor faecal egg output. These results suggest that intranasal vaccination with rLTB-FhTSP2 does elicit a humoral mucosal response but further work is needed to evaluate if mucosal delivery of liver fluke antigens fused to LTB is a viable vaccine strategy

    Best-Fit Ellipsoids of Atom-Probe Tomographic Data to Study Coalescence of Gamma Prime (L1_2) Precipitates in Ni-Al-Cr

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    An algorithm is presented to fit precipitates in atom probe tomographic data sets as equivalent ellipsoids. Unlike previous techniques, which measure only the radius of gyration, these ellipsoids retain the moments of inertia and principle axes of the original precipitate, preserving crystallographic orientational information. The algorithm is applied to study interconnected gamma prime precipitates (L1_2) in the Gamma-matrix (FCC) of a Ni-Al-Cr alloy. The precipitates are found to coagulate along -type directions.Comment: Accepted for publication in Scripta Materialia, added information about local magnification effect

    Sphingosine kinase 2 inhibition synergises with bortezomib to target myeloma by enhancing endoplasmic reticulum stress

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    Published: April 14, 2017The proteasome inhibitor bortezomib has proven to be invaluable in the treatment of myeloma. By exploiting the inherent high immunoglobulin protein production of malignant plasma cells, bortezomib induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in myeloma cell death. In most cases, however, the disease remains incurable highlighting the need for new therapeutic targets. Sphingosine kinase 2 (SK2) has been proposed as one such therapeutic target for myeloma. Our observations that bortezomib and SK2 inhibitors independently elicited induction of ER stress and the UPR prompted us to examine potential synergy between these agents in myeloma. Targeting SK2 synergistically contributed to ER stress and UPR activation induced by bortezomib, as evidenced by activation of the IRE1 pathway and stress kinases JNK and p38MAPK, thereby resulting in potent synergistic myeloma apoptosis in vitro. The combination of bortezomib and SK2 inhibition also exhibited strong in vivo synergy and favourable effects on bone disease. Therefore, our studies suggest that perturbations of sphingolipid signalling can synergistically enhance the effects seen with proteasome inhibition, highlighting the potential for the combination of these two modes of increasing ER stress to be formally evaluated in clinical trials for the treatment of myeloma patients.Craig T. Wallington-Beddoe, Melissa K. Bennett, Kate Vandyke, Lorena Davies, Julia R. Zebol, Paul A.B. Moretti, Melissa R. Pitman, Duncan R. Hewett, Andrew C.W. Zannettino and Stuart M. Pitso

    Assessing the energy implications of replacing car trips with bicycle trips in Sheffield, UK

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    A wide range of evidence supports policies which encourage people to cycle more and drive less, for health and environmental reasons. However, the likely energy implications of such a modal shift have remained relatively unexplored. In this paper we generate scenarios for increasing the cycling rate in Sheffield between 2010 and 2020. This is done through the novel application of a simple model, borrowed from population ecology. The analysis suggests that pro-cycling interventions result in energy savings through reduced consumption of fuel and cars, and energy costs through increased demand for food. The cumulative impact is a net reduction in primary energy consumption, the magnitude of which depends on a number of variables which are subject to uncertainty. Based on the evidence presented and analysed in this paper, we conclude that transport policy has a number of important energy implications, some of which remain unexplored. We therefore advocate the formation of closer links between energy policy and transport policy in academia and in practice; our approach provides a simple yet flexible framework for pursuing this aim in the context of modal shift
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