The involvement of epithelial cells in arenavirus-induced pathogenesis.

Mammalian Arenaviruses are a geographically and genetically diverse family of viruses, which is separated into two sub-groups; the Old World (OW) and New World (NW) groups. Of the OW viruses, Lassa virus (LASV), found endemically in Western Africa, is an important human pathogen, causing hundreds of thousands of infections, and several thousand deaths annually. Interestingly, some villages in endemic regions, up to 45% of the population show seropositivity for the virus. It is hypothesized that seropositivity is a result of natural infection through inhalation or ingestion of infectious particles. However, the exact mechanism is still unknown. LASV’s natural reservoir is Mastomys natalensis, a common rat found in sub-Saharan Africa. Epidemiological studies have identified the inhalation, and/or ingestion of infectious rodent excreta as the primary route of transmission from rodent reservoir to human hosts. Additionally, controlled experiments investigating intragastric (i.g.) versus intravenous (i.v.) routes of inoculation of non-human primates (NHPs) have continued transmission through these routes. viii These studies utilized Lymphocytic Choriomeningitis Virus (LCMV)-WE, a strain of LCMV that results in Lassa Fever (LF)-like disease in NHPs, and LCMVArmstrong (ARM), a strain of LCMV that mimics subclinical infection. When administered i.v., LCMV-WE-infected NHPs became systemically infected, showing clinical signs much like that of LF, and died. However, when orally infected with this virus through i.g. inoculation, some of these animals recovered, and later, were protected from lethal doses of i.v. WE challenge. Due to the nature of natural transmission from rodent to humans, epithelial cells are amongst the first cells to come in contact with the virus. However, the role(s) of the epithelial barrier during these infections have yet to be investigated. In order to investigate the role of these cells during arenaviral infection, here, a cell culture model was developed to investigate the interaction of OW mammalian arenaviruses at the site of intragastric inoculation. An important finding of this works is that the patterns of entry and release are viral dependent, and attachment to epithelial surfaces may play a role in these phenomena. Furthermore, regardless of their pathogenic potential in NHPs, both strains of LCMV, as well as LASV’s close relative, MOPV, showed similar patterns of entry and release when exposed to the apical and basolateral surfaces of polarized intestinal epithelia. Additionally, the replication patters of vaccine candidate ML- 29; a reassortant virus that contains the L segment of MOPV, and S segment of LASV, providing the exact same GP1 of LASV, were characterized. Interestingly, ML-29 virus entered and released in a different pattern than was observed with LCMV and MOPV. ix To determine if patterns of viral entry and release were driven by attachment differences, LCMV, MOPV, and ML-29 viral attachment to the surface of polarized epithelia was analyzed. LCMV an MOPV attaches to the apical and basolateral surfaces of the cells with similar efficiency. However, ML-29 showed decreased attachment to the basolateral surface of these cells as compared to the apical surface. Due to differences in pathogenicity seen in NHPs infected i.v. with LCMVWE and ARM, we hypothesized that these viruses would show differences in entry and release patterns in the polarized Caco-2 cells. However, these viruses replicated in much the same way. From these observations, we sought to further investigate differences in viral replication that may explain pathogenic differences between these closely related viruses. To do so, we investigated intracellular trafficking under the hypothesis that it may be responsible for these differences. Through the use of chemical inhibitors and immunofluorescence with confocal microscopy, a number of differences through the intracellular trafficking of LCMV-ARM and WE. The data indicates that LCMV-WE bypasses the TLR-2 receptor interaction in early endosome, and does not produce an IL-6 response in infected macrophages, opposed to LCMV-ARM-infected cells. Additionally, co-staining with LCMV and late endosome marker RAB7, showed more colocalization with LCMV-ARM than that of LCMV-WE. Furthermore, when blocking acidification of late endosome/lysosome with bafilomycin treatments, LCMV-ARM was more sensitive to pH change in the late endosome, indicating x that fusion occurs at less acidic conditions. These less acidic conditions promote earlier release at viral RNA in the case of LCMV-ARM versus that of WE. Together, these results signify differences in viral replication are tissue and viral specific. Furthermore, this research provides a platform to continue investigating key differences in viral replication between viruses of close genetic relatedness

#IncludeTheirStories: Rethinking, Reimagining, and Reshaping Legal Education

This symposium gathered scholars and practitioners who have been deeply engaged in the work to examine historical roots of the legal profession and discuss best practices for exploring ethnic, gender, and related inequities alongside our law students. It is well established that the legal profession and legal education neither reflect the community they serve nor swiftly respond to the social shifts within the broader society.3 As 2020 grossly revealed, ethnic partiality and division are aches we have yet to really confront and bear. For example, the casebook method format of legal education continues to model Christopher Langdell’s Gilded Age curriculum, a proscriptive framework steeped in objectivity and intentionally withdrawn from both history and human experiences

Ecological criteria for evaluation candidate sites for marine reserves

Several schemes have been developed to help select the locations of marine reserves. All of them combine social, economic, and biological criteria, and few offer any guidance as to how to prioritize among the criteria identified. This can imply that the relative weights given to different criteria are unimportant. Where two sites are of equal value ecologically, then socioeconomic criteria should dominate the choice of which should be protected. However, in many cases, socioeconomic criteria are given equal or greater weight than ecological considerations in the choice of sites. This can lead to selection of reserves with little biological value that fail to meet many of the desired objectives. To avoid such a possibility, we develop a series of criteria that allow preliminary evaluation of candidate sites according to their relative biological values in advance of the application of socioeconomic criteria. We include criteria that, while not strictly biological, have a strong influence on the species present or ecological processes. Our scheme enables sites to be assessed according to their biodiversity, the processes which underpin that diversity, and the processes that support fisheries and provide a spectrum of other services important to people. Criteria that capture biodiversity values include biogeographic representation, habitat representation and heterogeneity, and presence of species or populations of special interest (e.g., threatened species). Criteria that capture sustainability of biodiversity and fishery values include the size of reserves necessary to protect viable habitats, presence of exploitable species, vulnerable life stages, connectivity among reserves, links among ecosystems, and provision of ecosystem services to people. Criteria measuring human and natural threats enable candidate sites to be eliminated from consideration if risks are too great, but also help prioritize among sites where threats can be mitigated by protection. While our criteria can be applied to the design of reserve networks, they also enable choice of single reserves to be made in the context of the attributes of existing protected areas. The overall goal of our scheme is to promote the development of reserve networks that will maintain biodiversity and ecosystem functioning at large scales. The values of ecosystem goods and services for people ultimately depend on meeting this objective

University of Massachusetts Amherst Libraries Master Plan

Amherst Libraries, which is on the edge of significant change moving into a new era serving scholars, researchers and learners in the 21st Century. Over the last decade the Library has been a leader in many initiatives: increasing development of digital resources; collaborating with the Five Colleges Consortium, which was one of the first in the country to develop a shared book depository; developing a highly successful Learning Commons that engages partners in providing a broad range, of services and settings for learners; providing services through partners welcomed into library facilities, such the peer learning activities of the Learning Resources Center; and converting space to nontraditional library uses that are compatible with the mission of the library with facilities like the Teaching Commons. The visioning and conceptual development that was done for this study sought to build on the success of these initiatives, improve library space, and seek new types of blended facilities with partners that could enhance what the library offers the campus community. The Libraries master plan is aligned with the University’s strategic plan to become a major research institution through growth of new areas for research and academic development, and to grow its student body. Whereas the previous decade focused a great deal on supporting undergraduate learning and research, for the next decade the Library plans to improve support for scholars, researchers and graduate students, combined with expanded services for undergraduates. The Du Bois tower is in need of major renovation, upgrading to enable new types of activities, as well as to support traditional study and scholarship more effectively. Many options were studied for conversion of spaces to new activities or functions compatible with the library’s mission, and these are outlined in the sections that follow. Du Bois tower was the primary challenge: how to find ways to exploit the building’s potential yet mitigate its challenges

Clergy work-related satisfactions in parochial ministry: the influence of personality and churchmanship

The aim of this study was to test several hypotheses that clergy work-related satisfaction could be better explained by a multidimensional rather than a unidimensional model. A sample of 1071 male stipendiary parochial clergy in the Church of England completed the Clergy Role Inventory, together with the short-form Revised Eysenck Personality Questionnaire. Factor analysis of the Clergy Role Inventory identified five separate clergy roles: Religious Instruction, Administration, Statutory Duties (conducting marriages and funerals), Pastoral Care, and Role Extension (including extra-parochial activities). Respondents also provided an indication of their predispositions on the catholic-evangelical and liberal-conservative dimensions. The significant associations of the satisfactions derived from each of the roles with the demographic, personality, and churchmanship variables were numerous, varied, and, with few exceptions, small in magnitude. Separate hierarchical regressions for each of the five roles indicated that the proportion of total variance explained by churchmanship was, in general, at least as great as that explained by personality, and was greater for three roles: Religious Instruction, Statutory Duties, and Role Extension. It was concluded that clergy satisfactions derived from different roles are not uniform and that churchmanship is at least as important as personality in accounting for clergy work satisfaction

Work-related psychological health and psychological type among lead elders within the Newfrontiers network of churches in the United Kingdom

Building on a series of recent studies concerned with assessing work-related psychological health and psychological type among various groups of church leaders, this study reports new data provided by 134 Lead Elders within the Newfrontiers network of churches in the United Kingdom who completed the Francis Psychological Type Scales (FPTS) together with the two scales of the Francis Burnout Inventory (FBI) concerned with emotional exhaustion and satisfaction in ministry. Compared with other groups of church leaders, Lead Elders within the Newfrontiers network of churches reported lower levels of emotional exhaustion and higher levels of satisfaction in ministry. Compared with other groups of church leaders, there was a higher proportion of extraverts among Lead Elders within the Newfrontiers network of churches. There was only a weak association between psychological type and burnout

Learning how to learn: The role of music and other expressive arts in responding to Early Leaving from Education and Training (ELET) in the STALWARTS project

This project report describes policy, practice and theory related to a cross-sectoral international project funded by the European Union’s Erasmus+ programme. STALWARTS – Sustaining Teachers and Learners with the Arts: Relational Health in European Schools – aimed to promote relational health in schools through engagement with the arts. The project was developed in five European countries: Estonia, Italy, Norway, Portugal, and the UK. The local partnerships between five universities and community-based schools are diverse in terms of their locations in the European region and the populations they serve, in terms of age, social status and learning conditions.In this article we focus on the link between ELET policies in each country and local contexts. We ask: How can identified ELET policy drives in the five partner countries relate to the achievements of the STALWARTS partner schools when working with the expressive arts? Some related theoretical background underpinning the practical aspects of the project brings this report to a conclusion

A micromechanical-based model of stimulus responsive liquid crystal elastomers

Stimulus responsive elastomers are advanced engineered materials that perform desired functionalities when triggered by external stimuli. Liquid crystal elastomers (LCEs) are one important example that exhibit reversible actuation when cycled above and below their nematic-to-isotropic transition temperature. Here, we propose a micromechanical-based model that is centered on the evolution of the chain distribution tensor of the LCE network. Our model, framed within the statistical model of the chain network, enables a mesoscale description of their mechanical response under an external thermal stimulus. We compare the model to prior experimental observations of the bending response of 3D printed LCE elements with controlled director alignment