Analysis of Chlamydia Pneumoniae and AD-like Pathology in the Brains of BALB/c Mice Following Direct Intracranial Infection with Chlamydia Pneumoniae

Alzheimer’s disease (AD) is an age-related progressive neurodegenerative disorder and the most common form of dementia. The pathology in the central nervous system (CNS) impairs memory and cognition, hindering the capabilities and the quality of life of the individual. This project continues studying the role of infection and Alzheimer’s disease and contributes to the overall understanding of the possible causes of this disease. In this study, BALB/c mice were infected, via direct intracranial injection, with a respiratory isolate (AR-39) of Chlamydia pneumoniae. Their brains were analyzed at 7 and 14 days post-infection, using immunohistochemistry, for the presence of C. pneumoniae, amyloid deposits and activated glial cells. The goal of this project was to measure the location and degree of C. pneumoniae burden, amyloid deposition and glial cell activation in the CNS following direct intracranial injection and to compare this data with results obtained from previous studies in this laboratory. We hypothesized that C. pneumoniae antigen and activated inflammatory cells will be observed in the infected mouse brains following direct intracranial injection and Aβ deposition will be observed in areas where inflammation occurs. C. pneumoniae, amyloid deposits and activated glial cells were detected in the brains following direct intracranial infection with C. pneumoniae. At 7 days post-infection the average number of C. pneumoniae-specific immunoreactive sites was 68 ± 51.06 for the infected mice and, at 14 days post-infection, the average was 60 ± 43.79 for the infected mice. Within 0.84 mm of Bregma, the location of the injection, 166 of 203 total C. pneumoniae-specific immunoreactive sites (82%) and 26 of 27 (96%) total amyloid deposits were detected at 7 days post-infection. At 14 days post-infection, 126 of 179 total C. pneumoniae-specific immunoreactive sites (70%) and 13 of 32 (41%) total amyloid deposits were detected (within 0.84 mm of Bregma). From 7 to 14 days post-infection the C. pneumoniae and amyloid deposits located near the injection site spread distally from this location to other regions of the brain. These data confirm that C. pneumoniae is capable of establishing an infection in the CNS. Although deposits were observed, the lack of a substantial amount of amyloid deposits suggested that the generation of deposits may require longer than 14 days following C. pneumoniae infection. As early as 7 days post-infection, inflammation is observed in response to the presence of C. pneumoniae and/or soluble amyloid in the CNS and the contribution of both infection with C. pneumoniae and the presence of soluble amyloid elicit the inflammatory response that presumably precedes and contributes to amyloid deposition

Self-amplifying RNA vaccine development: transcriptomic profiling of a Venezuelan equine encephalitis virus self-amplifying RNA vector in human muscle

Next-generation RNA constructs are emerging as exciting new platforms for both vaccination and therapeutic applications. The last few years have seen the first mRNA vaccines licensed for use in humans and the first-in-human clinical trial of a self-amplifying RNA vaccine. With their short time-to-market, rapid manufacture, low cost, and ultra-low dosage, saRNA vaccines are potentially a game-changer when it comes to dealing with novel disease outbreaks. Whilst the pre-clinical testing of a VEEV-derived saRNA vaccine yielded robust neutralisation and 100% seroconversion, the results from the first-in-human trial were notably more muted, with poor neutralisation and failure to induce 100% seroconversion. Our aim, therefore, was to investigate why humans and mice respond so differently to the VEEV saRNA construct; we hypothesised that there is a difference in the innate immune responses to saRNA in the cells that are responsible for taking up saRNA and synthesising antigen at the site of injection, i.e. muscle tissue. To investigate this, we used a transcriptomics approach to characterise the response of human muscle cells to VEEV saRNA and compared it with the transcriptomic changes seen in murine muscle cells. We observed that both human and mouse muscle cells produce a robust innate immune response to VEEV saRNA; however, there were several notable differences. Murine cells elevated the expression of cytokines and chemokines to a far greater extent than human muscle cells, while the expression of IRF7, a key transcription factor for orchestrating the antiviral response, was markedly higher in humans. Overall, these results indicate that there are distinct differences in the way that human cells react to saRNA compared to murine cells and that this should be taken into account when designing and testing saRNA vaccines in the future.Open Acces

The socio‐spatial nature of organisational creativity: experiences along the road toward transdisciplinarity

This paper sets out to explore characteristics of transdisciplinary organisational research in practice and in particular how the process of research may be shared and co-produced by both university and business. The case studies presented here outline recent work conducted through ‘Innovation Futures’, a Sheffield Hallam University project which aims to contribute to the development of a region-wide culture of innovation and to create strong links between businesses and the University. The multidisciplinary team, based across Sheffield Business School and the Cultural, Communication and Computing Research Institute, has worked with numerous companies from the manufacturing and service sectors in the last three years. Through a strong process of collaboration throughout the stages of problem structuring,problem investigation, and realisation of findings in practice, the work has sought to help businesses improve processes and, ultimately, performance via a range of analytical measures. By employing a holistic approach to understanding the social-cultural nature of the workspace through the integrated use of Social Network Analysis, Space Syntax and participatory design methods, managers have been able to develop a much greater level of reflexive management practice through their experiences of collaborative research. There is increasing recognition that organisational creativity is not formed through the innate attributes of the individual but is instead a wholly social process involving complex phases of interaction thus making the socio-spatial environment of the organisation, within which such phases are carried out, a key determinant of success. This environment is both shaped, and also shapes, those within it through the requirements of organisation and it is through the experience of transdisciplinary boundary spanning that both academic institution and business can help form research driven management practices

Evolving innovation through office knowledge networks : mapping the ephemeral architecture of organizational creativity

This paper explores positive conditions for the evolution of creative innovation through informal social networks in the office. By drawing on both Social Network Analysis (SNA) and the abstracted evolutionary mechanisms of variation, selection and retention, a multilevel conceptualization of the evolutionary processes underpinning the emergence and development of ideas within an organization is put forward. In this way SNA is used to visualize not just the connectivity of individuals within the company who offer 'expert advice' and 'new ideas' in the development of these products, but also the role of mediators in this process at a digital media company, Dataco

Relocating, Downsizing, and Merging: Inventory Projects to Manage Change in a Digital Environment

With a new library location and newly created librarian position, the Health Sciences Library (HSL) of the University Libraries at the University of Memphis needed a comprehensive inventory. Having previously completed a small-scale inventory, technical services librarians led the project to assess the HSL collection before the newly hired librarian arrived. Beyond ensuring that all materials were in the collection and reflected properly in the integrated library system (ILS), an up-to- date inventory asserts the value of the physical collections to a variety of campus stakeholders. This chapter offers ideas for working collaboratively with personnel across library departments to conduct and complete a major technical services project

Using Photographs and Human Body Diagrams as Visual Aids to Help Children Talk About Bodily Touch

The present study aimed to examine whether using two separate visual aids (Human Body Diagram vs. photograph of subject) for different purposes (to clarify/elaborate reported touches vs. elicit unreported touches) effected the accuracy and amount of touch-related information reported by children aged between 5 and 6 years. It was found that children reported more correct touches from the scripted event when they were interviewed using a photograph of their bodies. Contrary to expectations though, the amount and accuracy of touch-related information did not significantly differ between interviewing conditions. Additionally, all children reported the most accurate information prior to touch-inquiry before visual aids were introduced. In light of these findings, it is suggested that visual aids may not provide any more substantial benefits compared to verbal prompting alone. Given the risks associated with their use (i.e., leading to increases in reported errors) the present study endorses future research that seeks to develop more effective verbal interviewing techniques, which assist in the retrieval of more complete and accurate statements from children