Neuregulin 1-Erbb4 in the rodent prefrontal cortex: Investigations of schizophrenia-related behaviours and signalling pathways

Schizophrenia is a severe, chronic and debilitating psychiatric disorder. Current therapies have no efficacy in treating the cognitive impairments which are largely responsible for the poor quality of life of schizophrenia patients and contribute to the massive economic burden that is associated with the disorder. Although it is known that schizophrenia is highly heritable, the underlying genetic basis is still poorly understood due to the complex polygenetic nature of the disorder. Several candidate genes which are thought to increase risk for the incidence of schizophrenia have been identified. Two such schizophrenia candidate genes are neuregulin 1 (NRG1) and v-erb-a erythroblastic leukaemia viral oncogene homolog 4 (ERBB4). As well as the genetic evidence from genetic association studies, studies of animal models and the endogenous biological functions of NRG1 and ERBB4 in the CNS suggest that these genes may play an important role in the pathophysiology of schizophrenia. However, very little is known about the functions of these genes in specific brain regions in adulthood with respect to cognition. To address this, I have utilised recombinant adeno-associated viral particles (rAAVs) as a vehicle to mediate knockdown of the expression of Erbb4 specifically within the medial prefrontal (mPFC) cortex of adult rats. This allows for a spatially and temporally controlled investigation of the role that Erbb4 signalling may play in prefrontal cortex-dependent behaviours in adulthood. Following initial in vitro and in vivo validation of the functionality of the rAAVs, further in vivo studies confirmed that, five weeks after stereotaxic injection of rAAVs encoding a short hairpin sequence corresponding to Erbb4 (shErbb4.rAAV), into the mPFC of rats, there was significant Erbb4 protein knockdown, as analysed by ELISA. Subsequent western blot analysis revealed that Erbb4 knockdown consequently increased the level of Nrg1 expression and decreased the activity of Akt signalling, but had no effect on Erk signalling. Erbb4 knockdown specifically within the mPFC increased performance accuracy in the 5-choice serial reaction time task at 5 weeks post-surgery. Furthermore, viral mediated Erbb4 knockdown specifically within the mPFC heightened the II sensitivity to the locomotor inducing effects of amphetamine. There were, however, no effects of Erbb4 knockdown on pre-pulse inhibition at any time points assessed. These results indicate that Nrg1-Erbb4 signalling in the PFC modulates cognitive performance but not sensorimotor gating, and that dopaminergic transmission may be regulated by Nrg1-Erbb4 signalling. In conclusion, this study highlights the ability of viral mediated gene manipulation to investigate regionally specific roles of schizophrenia candidate genes in adulthood in terms of cognition and downstream signalling pathways. This may translate to a better understanding of how these genes may exert potentially pathophysiological effects in patients and ultimately lead to improved treatments

Immunological Responses Elicited by Different Infection Regimes with Strongyloides ratti

Nematode infections are a ubiquitous feature of vertebrate life. In nature, such nematode infections are acquired by continued exposure to infective stages over a prolonged period of time. By contrast, experimental laboratory infections are typically induced by the administration of a single (and often large) dose of infective stages. Previous work has shown that the size of an infection dose can have significant effects on anti-nematode immune responses. Here we investigated the effect of different infection regimes of Strongyloides ratti, comparing single and repeated dose infections, on the host immune response that was elicited. We considered and compared infections of the same size, but administered in different ways. We considered infection size in two ways: the maximum dose of worms administered and the cumulative worm exposure time. We found that both infection regimes resulted in Th2-type immune response, characterised by IL4 and IL13 produced by S. ratti stimulated mesenteric lymph node cells, anti-S. ratti IgG1 and intestinal rat mast cell protease II (RMCPII) production. We observed some small quantitative immunological differences between different infection regimes, in which the concentration of IL4, IL13, anti-S. ratti IgG1 and IgG2a and RMCPII were affected. However, these differences were quantitatively relatively modest compared with the temporal dynamics of the anti-S. ratti immune response as a whole

University of Glasgow: Our Digital Transformation

Poster created for IDCC20, charting the journey of the University of Glasgow's recordkeeping since 1451, from parchment to digital, and our plans for the future

Evaluating Digital Preservation Capability with Large At-Risk Collections: Lessons learnt from preserving the NVA Archive

This paper presents the efforts of the Archives & Special Collections (ASC) unit at the University of Glasgow to preserve the large, at-risk collection of the NVA Archive. We discuss the nature of the collection, and the way it was used to evaluate our digital preservation capability

Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus

A nonneutropenic patient with treated low-grade non-Hodgkin's (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure

A disciplinary commons for database teaching

This paper discusses the experience of taking part in a disciplinary commons devoted to the teaching of database systems. It will discuss the structure of a disciplinary commons and our experience of the database version

A systematic review:Unfinished nursing care and the impact on the nurse outcomes of job satisfaction, burnout, intention-to-leave and turnover

Aim: To investigate the association of unfinished nursing care on nurse outcomes. Design: Systematic review in line with National Institute for Health and Care Excellence guideline. Data sources: CINAHL, the Cochrane Library, Embase, Medline, ProQuest and Scopus databases were searched up until April 2020. Review methods: Two independent reviewers conducted each stage of the review process: screening eligibility, quality appraisal using Mixed Methods Appraisal Tool; and data extraction. Narrative synthesis compared measurements and outcomes. Results: Nine hospital studies were included, and all but one were cross-sectional multicentre studies with a variety of sampling sizes (136-4169 nurses). Studies had low internal validity implying a high risk of bias. There was also a high potential for bias due to non-response. Only one study explicitly sought to examine nurse outcomes as a primary dependent variable, as most included nurse outcomes as mediating variables. Of the available data, unfinished nursing care was associated with: reduced job satisfaction (5/7 studies); burnout (1/3); and intention-to-leave (2/2). No association was found with turnover (2/2). Conclusion: Unfinished nursing care remains a plausible mediator of negative nurse outcomes, but research is limited to single-country studies and self-reported outcome measures. Given challenges in the sector for nurse satisfaction, recruitment and retention, future research needs to focus on nurse outcomes as a specific aim of inquiry in relation to unfinished nursing care. Impact: Unfinished nursing care has previously been demonstrated to be associated with staffing, education and work environments, with negative associations with patient outcomes (patient satisfaction, medication errors, infections, incidents and readmissions). This study offers new evidence that the impact of unfinished nursing care on nurses is under investigated. Policymakers can prioritize the funding of robust observational studies and quasi-experimental studies with a primary aim to understand the impact of unfinished nursing care on nurse outcomes to better inform health workforce sustainability

Little House in the Mountains? A small Mesolithic structure from the Cairngorm Mountains, Scotland

This paper describes a small Mesolithic structure from the Cairngorm Mountains, Scotland. Excavations at Caochanan Ruadha identified a small oval structure (c. 3 m×2.2 m) with a central fire setting, in an upland valley (c.540 m asl). The site was occupied at c. 8200 cal BP and demonstrates hunter-gatherer use of the uplands during a period of significant climatic deterioration. The interpretation of the structure is primarily based on the distribution of the lithic assemblage, as the heavily podsolised soils have left no trace of light structural features. The lithic assemblage is specialised, dominated by microlith fragments, and functional analysis has identified different uses of different areas inside the structure. The identification of small, specialised Mesolithic sites is unusual and this paper will discuss the evidence for the presence of the structure and its use, compare it to other Mesolithic structures in Britain and highlight some methodological implications

Case Report Treated Follicular Lymphoma, Recurrent Invasive Pneumococcal Disease, Nonresponsiveness to Vaccination, and a Unique Pneumococcus

A nonneutropenic patient with treated low-grade non-Hodgkin's (Follicular) lymphoma and secondary hypogammaglobulinemia recovered from pneumococcal pneumonia and septicemia (serotype 7F; ST191) subsequent to influenza A H1N1 (2009). Both infections were potentially vaccine preventable. The patient then developed pneumococcal meningitis due to a serotype 35F pneumococcus with a unique Multilocus Sequence Type (ST7004) which was not vaccine preventable. Patient management was influenced by host predisposition to pneumococcal infection, antibiotic intolerance, and poor response to polysaccharide pneumococcal vaccine. Indirect immunofluorescence with anti-human immunoglobulin confirmed a poor or intermediate response to Pneumovax II. Prophylactic erythromycin was initiated, and immunoglobulin transfusions were also commenced as a preventive strategy. ST7004 is a single locus variant of ST1635 which has been associated with the serotype 35F capsule in England. The spi gene in ST7004, which differentiates it from ST1635, is the same as the spi gene present in ST191 which could have arisen from the first disease episode suggesting that horizontal gene transfer may have occurred between different populations of pneumococci present within the patient in an attempt to evade vaccination selection pressure