Towards detection of structurally-diverse glycated epitopes in native proteins : single-chain antibody directed to non-A1c epitope in human haemoglobin

Over 500 million people worldwide are affected by diabetes mellitus, a chronic disease that leads to high blood glucose levels and causes severe side effects. The predominant biological marker for diagnosis of diabetes is glycated haemoglobin (GHb). In human blood the predominant reducing sugar, glucose, irreversibly conjugates onto accessible amine groups within Hb. Most methods for diagnosis and monitoring of diabetes selectively detect N-terminal glycation at Val-1 on the β-globin chain, but not glycation at other sites. Detection of other glycated epitopes of GHb has the potential to provide new information on the extent, duration and timing of elevated glucose, facilitating personalised diagnosis and intelligent diabetic control. In this work, a new anti-GHb Fab antibody (Fab-1) specific for haemoglobin A1c (HbA1c) with nanomolar affinity was discovered via epitope-directed immunisation and phage display. A single chain variable fragment (scFv) antibody derived from Fab-1 retained affinity and specificity for HbA1c, and affinity was enhanced tenfold upon addition of an enhanced green fluorescent protein tag. Both the scFv and Fab-1 recognised an epitope within HbA1c that was distinct from β-Val-1, and our data suggest that this epitope may include glycation at Lys-66 in the β-globin chain. To our knowledge, this is the first report of an scFv/Fab anti-glycated epitope antibody that recognises a non-A1c epitope in GHb, and confirms that fructosamine attached to different, discrete glycation sites within the same protein can be resolved from one another by immunoassay. [Abstract copyright: Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.

Social Value at Universities: Policy and Practice Guidance

Universities globally can be major hubs of social and economic activity which drive change in society. We know that they can create multiple and diverse routes into employment, can have significant purchasing power which can inform standards across supply chains, can create learning opportunities which directly nourish and enrich local communities, and can deliver research and innovation which impact health for the better. However, the measurable difference these make to lives – and how universities and the funding bodies account for this impact - is still unknown. We created the Global Symposia for Social Value at Universities in 2022, as a way to accelerate the movement. Over 130 joined from 12 countries to contribute to the analysis, from different disciplines such as health, arts, environmental sciences, alongside private, public and third sector stakeholders. There were two symposiums. The first was related to understanding policy and practice across disciplines at universities; the second was focused on one of the biggest sectors, business and management studies. This report presents the findings from both symposiums from the perspective of different stakeholders: 1. what is currently being done that is valued 2. recommendations for improvement The Global Symposia at Universities 2022 was co-hosted between Social Value UK and Liverpool John Moores University, the British Academy of Management (Sustainable and Responsible Business SIG), Principles for Responsible Management Education (Working Group on Poverty), University Vocational Awards Council, Social Value International, The Academy of Business in Society, American International Accreditation Association for Schools and Colleges, and the National Society for Experiential Education. Maddy England and Clare Bentley at Social Value UK were also central to delivering this guidance. Supported by Liverpool John Moores University’s Quality Research Funds

Phospholipase A2 as a point of care alternative to serum amylase and pancreatic lipase

Acute pancreatitis is a relatively common and potentially fatal condition, but the presenting symptoms are non-specific and diagnosis relies largely on the measurement of amylase activity by the hospital clinical laboratory. In this work we develop a point of care test for pancreatitis measuring concentration of secretory phospholipase A2 group IB (sPLA2-IB). Novel antibodies for sPLA2-IB were raised and used to design an ELISA and a lateral flow device (LFD) for the point of care measurement of sPLA2-IB concentration, which was compared to pancreatic amylase activity, lipase activity, and sPLA2-IB activity in 153 serum samples. 98 of these samples were obtained from the pathology unit of a major hospital and classified retrospectively according to presence or absence of pancreatitis, and the remaining 55 were obtained from commercial sources to serve as high lipase (n = 20), CA19-9 positive (n = 15), and healthy (n = 20) controls. sPLA2-IB concentration correlated well with the serum activity of both amylase and lipase, and performed at least as well as either markers in the differentiation of pancreatitis from controls