Supernatants from lymphocytes stimulated with Bacillus Calmette-Guerin can modify the antigenicity of tumours and stimulate allogeneic T-cell responses

BACKGROUND: Reduced expression of class 1 human leucocyte antigens (HLA1) is often a mechanism by which tumours evade surveillance by the host immune system. This is often associated with an immune function that is unable to mount appropriate responses against disease, which can result in a state that favours carcinogenesis. METHODS: In the current study, we have explored the effects of Bacillus Calmette-Guerin (BCG) on the cytokine output of leucocytes, which is a key determinant in generating antitumour action, and have also assessed the effect of these cytokine cocktails on HLA1 expression in solid tumour cell lines. RESULTS: BCG potently activated a broad range of leucocytes, and also enhanced the production of cytokines that were Th(1)-predominant. Supernatants from BCG-treated leucocytes significantly increased the expression of HLA1 on the surface of cancer cell lines, which correlated with increased cytolytic T-cell activity. We also showed that the increased HLA1 expression was associated with activation of intracellular signalling pathways, which was triggered by the increases in the Th(1)-cytokines interferon-γ and tumour necrosis factor-α, as counteracting their effects negated the enhancement. CONCLUSION: These studies reaffirm the role of BCG as a putative immunotherapy through their cytokine-modifying effects on leucocytes and their capacity to enhance tumour visibility

A model describing photosynthesis in terms of gas diffusion and enzyme kinetics

A model predicting net photosynthesis of individual plant leaves for a variety of environmental conditions has been developed. It is based on an electrical analogue describing gas diffusion from the free atmosphere to the sites of CO 2 fixation and a Michaelis-Menten equation describing CO 2 fixation. The model is presented in two versions, a simplified form without respiration and a more complex form including respiration. Both versions include terms for light and temperature dependence of CO 2 fixation and light control of stomatal resistance. The second version also includes terms for temperature, light, and oxygen dependence of respiration and O 2 dependence of CO 2 fixation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47495/1/425_2004_Article_BF00387066.pd

Transition in Career Counselling Practice: What can Solution-Orientated Counselling Offer?

The counselling profession has been challenged to respond to the demands of an increasingly complex and rapidly changing world. In personal counselling, the response has seen the increased adoption of principles, processes and approaches informed by the constructivist worldview, such as solution-oriented counselling and narrative counselling. Such a response is less evident in career counselling, which continues to be dominated by the approaches of the traditional positivist worldvlew. However, the early stages of a transition in career counselling are becoming more evident. This article overviews the antecedents of transition in career counselling and explores the influence of the constructivist and traditional positivist worldviews on elements of career counselling. Further, It examines the possible contribution of solution-oriented counselling and illustrates its application to career counselling

Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection

Abstract TANK-binding kinase 1 (TBK1) is a key signalling component in the production of type-I interferons, which have essential antiviral activities, including against SARS-CoV-2. TBK1, and its homologue IκB kinase-ε (IKKε), can also induce pro-inflammatory responses that contribute to pathogen clearance. While initially protective, sustained engagement of type-I interferons is associated with damaging hyper-inflammation found in severe COVID-19 patients. The contribution of TBK1/IKKε signalling to these responses is unknown. Here we find that the small molecule idronoxil inhibits TBK1/IKKε signalling through destabilisation of TBK1/IKKε protein complexes. Treatment with idronoxil, or the small molecule inhibitor MRT67307, suppresses TBK1/IKKε signalling and attenuates cellular and molecular lung inflammation in SARS-CoV-2-challenged mice. Our findings additionally demonstrate that engagement of STING is not the major driver of these inflammatory responses and establish a critical role for TBK1/IKKε signalling in SARS-CoV-2 hyper-inflammation