Electroantennogram Responses of the Armyworm (Lepidoptera: Noctuidae) and Cereal Leaf Beetle (Coleoptera: Chrysomelidae) to Volatile Chemicals of Seedling Oats

Armyworm, Pseudaletia unipuncta, eIectroantennogram (EAG) responses to 10 volatile chemicals of seedling oats and three of injured green plants were significantly different from each other while cereal leaf beetle, Oulema melallopus, EAG responses were not significantly different. The EAG responses of both species did not vary significantly with respect to sex, age, or between the antennae of the same specimen. (E)-2-hexenol, a compound extracted from injured green plants, yielded the highest peak response for the armyworm while more cereal leaf beetle antennae responded to this chemical than any other chemical. Armyworm antennallife averaged 38 + 20 min while those of the cereal leaf beetle averaged 6 + 14 min

Integrin affinity modulation and lung cancer

Lung cancer accounts for the most deaths due to cancer in the United Kingdom and yet has historically been one of the most ignored of neoplastic diseases. The work presented in this thesis explores the fundamental processes that govern cell behaviour in the context of lung cancer and contributes to a deeper understanding of this behaviour at a molecular level. The work covers three main areas, centred upon the molecular regulation of integrins, proteins that are the key communicators between a cell and its local environment and which provide powerful signals governing cellular behaviour, including motility, cell survival and proliferation.Recent work has shown that the transmembrane protein CD98 is able to influence the affinity with which ß1 integrins bind to extracellular ligands. The first part of this thesis presents confocal microscopy and co-immunoprecipitation experiments that confirm the physical juxtaposition of the two proteins within the cell membrane, suggesting a direct link between the two, rather than an extensive signalling cascade. It also demonstrated that cross-linking CD98 stimulates both phosphoinositide 3- kinase intracellular signalling and increased ß1 integrin-dependent cellular adhesion. Because of the role of CD98 in integrin affinity modulation, the immunohistochemical expression of CD98 and its ligand, galectin-3, was studied in a variety of human lung diseases including lung cancers. The major finding of this work was a striking distinction between high expression of galectin-3 in non-small cell lung cancer and low expression in small cell lung cancer. This may have significant implications for the differing clinical behaviours of these two groups of cancers. The final section of this thesis returns to describe experiments aimed at defining the molecular regulators of integrin affinity more clearly. A genetic screen of a cDNA library was undertaken to identify candidate genes coding for proteins able to rescue integrins from the low affinity state induced by the small signalling protein H-Ras. This identified a candidate cDNA 480, recognised to be part of a novel gene Nessie, coding for a large protein with multiple transmembrane domains. Both 480 and Nessie appear to have the ability to rescue integrin affinity from H-Ras suppression.This thesis thus moves from the basic molecular science of integrin function to the cellular behaviour of lung cancer cells, both in vitro and in vivo, and back again. The understanding of cellular behaviour is central not just to lung cancer, but to all cancers and it is only through furthering this understanding that significant advances will be made in treating these diseases

Lysyl oxidase like 2 is increased in asthma and contributes to asthmatic airway remodelling

BACKGROUND: Airway smooth muscle (ASM) cells are fundamental to asthma pathogenesis, influencing bronchoconstriction, airway hyperresponsiveness and airway remodelling. The extracellular matrix (ECM) can influence tissue remodelling pathways; however, to date no study has investigated the effect of ASM ECM stiffness and cross-linking on the development of asthmatic airway remodelling. We hypothesised that transforming growth factor-β (TGF-β) activation by ASM cells is influenced by ECM in asthma and sought to investigate the mechanisms involved. METHODS: This study combines in vitro and in vivo approaches: human ASM cells were used in vitro to investigate basal TGF-β activation and expression of ECM cross-linking enzymes. Human bronchial biopsies from asthmatic and nonasthmatic donors were used to confirm lysyl oxidase like 2 (LOXL2) expression in ASM. A chronic ovalbumin (OVA) model of asthma was used to study the effect of LOXL2 inhibition on airway remodelling. RESULTS: We found that asthmatic ASM cells activated more TGF-β basally than nonasthmatic controls and that diseased cell-derived ECM influences levels of TGF-β activated. Our data demonstrate that the ECM cross-linking enzyme LOXL2 is increased in asthmatic ASM cells and in bronchial biopsies. Crucially, we show that LOXL2 inhibition reduces ECM stiffness and TGF-β activation in vitro, and can reduce subepithelial collagen deposition and ASM thickness, two features of airway remodelling, in an OVA mouse model of asthma. CONCLUSION: These data are the first to highlight a role for LOXL2 in the development of asthmatic airway remodelling and suggest that LOXL2 inhibition warrants further investigation as a potential therapy to reduce remodelling of the airways in severe asthma

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Managing educational experiences, student expectations and tuition fees. Is it possible to find the right balance?

In the aftermath of the COVID-19 pandemic, the traditional concept of a university has been turned upside down. This session will address the fundamental questions raised by this change, such as: How much should a university charge for online, blended and traditional courses? How can a university distinguish its student experience in the virtual space from online providers whilst ensuring that students and taxpayers are getting value for money

Switzerland's Imperative to face outwards

Robert Buttery explores the tumultuous history of the Swiss–EU relationship over the past 30 years and how it has impacted Swiss international higher education. As a non-EU country, Switzerland’s participation in European mobility and research programmes, such as Erasmus+ and Horizon 2020, have been shaped by the interplay between national and supranational politics. Since 1987, Swiss HEIs have lived in periods of uncertainty concerning their involvement in European programmes and networks. During these periods of precariousness, the Swiss higher education community lobbied the government and continued to draw strength from their international networks. Throughout the essay, Robert draws parallels between the Swiss case and the Brexit referendum and negotiations