Publications by authors named "Gary Britton"

The severity of sterile inflammation, as seen in acute pancreatitis, is determined by damage-sensing receptors, signalling cascades and cytokine production. Stat2 is a type I interferon signalling mediator that also has interferon-independent roles in murine lipopolysaccharide-induced NF-κB-mediated sepsis. However, its role in sterile inflammation is unknown.

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Background And Objectives: The effect of a worry manipulation on the clinical constructs intolerance of uncertainty (IU), negative beliefs about the consequences of worry (NCOW), positive beliefs about the consequences of worry (PCOW), in addition to the emotions anxiety and sadness, was examined.

Methods: A non-clinical sample was split into two groups, a worry group (n = 29), who were asked to generate 20 potential worries about a hypothetical scenario, and a control group (n = 28), who were asked to generate 2 potential worries about the same scenario. Subsequently, participants were asked to complete measures of IU, NCOW, PCOW, sadness and anxiety.

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Emerging evidence suggests that many of the clinical constructs used to help understand and explain obsessive-compulsive (OC) symptoms, and negative mood, may be causally interrelated. One approach to understanding this interrelatedness is a motivational systems approach. This approach suggests that rather than considering clinical constructs and negative affect as separable entities, they are all features of an integrated threat management system, and as such are highly coordinated and interdependent.

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HIV infection affects 37 million people and about 1.7 million are infected annually. Among the phase III clinical trials only the RV144 vaccine trial elicited significant protection against HIV-1 acquisition, but the efficacy and immune memory were inadequate.

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p130Cas is a polyvalent adapter protein essential for cardiovascular development, and with a key role in cell movement. In order to identify the pathways by which p130Cas exerts its biological functions in endothelial cells we mapped the p130Cas interactome and its dynamic changes in response to VEGF using high-resolution mass spectrometry and reconstruction of protein interaction (PPI) networks with the aid of multiple PPI databases. VEGF enriched the p130Cas interactome in proteins involved in actin cytoskeletal dynamics and cell movement, including actin-binding proteins, small GTPases and regulators or binders of GTPases.

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Although bacillus Calmette-Guérin (BCG) is an established vaccine with excellent efficacy against disseminated Mycobacterium tuberculosis infection in young children, efficacy in adults suffering from respiratory tuberculosis (TB) is suboptimal. Prime-boost viral vectored vaccines have been shown to induce effective immune responses and lentivectors (LV) have been shown to improve mucosal immunity in the lung. A mucosal boost to induce local immunogenicity is also referred to as a 'pull' in a prime and pull approach, which has been found to be a promising vaccine strategy.

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Article Synopsis
  • Expression of the costimulatory receptor 4-1BB is triggered by TCR recognition of an antigen, which is important for the survival of activated and memory CD8(+) T cells, particularly when paired with the 4-1BB ligand (4-1BBL) found on activated antigen-presenting cells (APCs).
  • Researchers tested a vaccine strategy using lentiviral vectors to coexpress 4-1BBL and the influenza nucleoprotein (NP) in dendritic cells (DC), discovering enhanced CD8(+) T cell responses and protection against influenza when 4-1BBL was expressed.
  • Their findings indicated that using separate vectors for 4-1BBL and NP resulted in
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A series of three experiments was designed to test predictions from a motivational systems approach to understanding the role of clinical constructs in anxiety-based problems. Negative mood, inflated responsibility, and intolerance of uncertainty (IU) were separately manipulated within analog samples to examine their effect on the other two factors. In the first experiment (n = 59) the negative mood group scored significantly higher in terms of inflated responsibility than the positive mood group.

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DOK1 regulates platelet-derived growth factor (PDGF)-BB-stimulated glioma cell motility. Mechanisms regulating tumour cell motility are essential for invasion and metastasis. We report here that PDGF-BB-mediated glioma cell invasion and migration are dependent on the adaptor protein downstream of kinase 1 (DOK1).

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In endothelial cells, neuropilin-1 (NRP1) binds vascular endothelial growth factor (VEGF)-A and is thought to act as a coreceptor for kinase insert domain-containing receptor (KDR) by associating with KDR and enhancing VEGF signaling. Here we report mutations in the NRP1 b1 domain (Y297A and D320A), which result in complete loss of VEGF binding. Overexpression of Y297A and D320A NRP1 in human umbilical vein endothelial cells reduced high-affinity VEGF binding and migration toward a VEGF gradient, and markedly inhibited VEGF-induced angiogenesis in a coculture cell model.

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Neuropilin-1 (NRP1) is a receptor for vascular endothelial growth factor (VEGF) and plays an important role in mediating cell motility. However, the NRP1 signaling pathways important for cell motility are poorly understood. Here we report that p130(Cas) tyrosine phosphorylation is stimulated by hepatocyte growth factor and platelet-derived growth factor in U87MG glioma cells and VEGF in endothelial cells and is dependent on NRP1 via its intracellular domain.

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Proteomic analysis identified HSP27 phosphorylation as a major change in protein phosphorylation stimulated by Vascular Endothelial Growth Factor (VEGF) in Human Umbilical Vein Endothelial Cells (HUVEC). VEGF-induced HSP27 phosphorylation at serines 15, 78 and 82, but whereas HSP27 phosphorylation induced by H2O2 and TNFalpha was completely blocked by the p38 kinase inhibitor, SB203580, VEGF-stimulated serine 82 phosphorylation was resistant to SB203580 and small interfering(si)RNA-mediated knockdown of p38 kinase and MAPKAPK2. The PKC inhibitor, GF109203X, partially reduced VEGF-induced HSP27 serine 82 phosphorylation, and SB203580 plus GF109203X abolished phosphorylation.

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