Research Roundtable (SCRC Behind the Scenes)

This entry briefly describes Maarten van Gageldonk\u27s resarch as it relates to the SCRC holdings, as well as the research roundtable on the same topic

Doing It Yourself: Special Collections as a Springboard for Personal, Critical Approaches to Information

This chapter documents the collaboration between a curator of special collections, a subject specialist librarian, and a writing instructor to develop a different kind of instructional approach for undergraduate research and writing. We sought to use special collections as a springboard to create an environment in which students could investigate research questions that connect to their personal lives and interests; engage in various of modes of writing; conceive of the potential networks of production and circulation for their work; and identify the library as a locus for sustained, organic, social, and productive inquiry

Senior scientists: Engaging the elderly in National Science Week activities

Science and technology outreach events often focus on children and teenagers, intending to incentivise their interest in STEM to the detriment of other age groups. Other populations, including our seniors are afforded few opportunities to interact with technological developments in a positive way, making their encounters with this technology on hospital visits even more distressful. Through a series of outreach activities for National Science Week, we aimed to highlight an approach for interaction with the elderly in a safe and adaptive environment. These events are taken directly to elderly facilities and community spaces in the Perth metropolitan area, using an LED screen truck to display the activities and make the sensory experience accessible to the elderly community. We demonstrate how glass can allow us to capture more than meets the eye with health-integrated examples (e.g. lenses, microscopy and cameras). The event series aimed to stimulate an enhanced sense of agency and comfortability around new technology. Here, we will share the event’s logistical considerations, interest and outcomes of delivering this event to encourage future activities with our elderly population

N 1 -methylpseudouridylation of mRNA causes +1 ribosomal frameshifting

In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1, 2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization

Age-associated B cells predict impaired humoral immunity after COVID-19 vaccination in patients receiving immune checkpoint blockade

Age-associated B cells (ABC) accumulate with age and in individuals with different immunological disorders, including cancer patients treated with immune checkpoint blockade and those with inborn errors of immunity. Here, we investigate whether ABCs from different conditions are similar and how they impact the longitudinal level of the COVID-19 vaccine response. Single-cell RNA sequencing indicates that ABCs with distinct aetiologies have common transcriptional profiles and can be categorised according to their expression of immune genes, such as the autoimmune regulator (AIRE). Furthermore, higher baseline ABC frequency correlates with decreased levels of antigen-specific memory B cells and reduced neutralising capacity against SARS-CoV-2. ABCs express high levels of the inhibitory FcγRIIB receptor and are distinctive in their ability to bind immune complexes, which could contribute to diminish vaccine responses either directly, or indirectly via enhanced clearance of immune complexed-antigen. Expansion of ABCs may, therefore, serve as a biomarker identifying individuals at risk of suboptimal responses to vaccination

Accelerated waning of the humoral response to COVID-19 vaccines in obesity

Funding: EAVE II is funded by the Medical Research Council (MRC) (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant MC_PC_20058) and National Core Studies–Immunity. Additional support was provided through Public Health Scotland, the Scottish Government Director-General Health and Social Care and the University of Edinburgh. The SCORPIO study was supported by the MRC (MR/W020564/1, a core award to J.E.T.; MC_UU_0025/12 and MR/T032413/1, awards to N.J.M.) and the Medical Research Foundation (MRF-057-0002-RG-THAV-C0798). Additional support was provided by NHS Blood and Transplant (WPA15-02 to N.J.M.), the Wellcome Trust (Institutional Strategic Support Fund 204845/Z/16/Z to N.J.M.), Addenbrooke’s Charitable Trust (900239 to N.J.M.) and the NIHR Cambridge Biomedical Research Centre and NIHR BioResource. M.A.L is supported by the Biotechnology and Biological Sciences Research Council (BBSRC) (BBS/E/B/000C0427 and BBS/E/B/000C0428) and is a Lister Institute Fellow and an EMBO Young Investigator. I.M.H. is supported by a Cambridge Institute for Medical Research PhD studentship. H.J.S. is supported by a Sir Henry Dale Fellowship, jointly funded by the Wellcome Trust and the Royal Society (109407), and a BBSRC institutional program grant (BBS/E/B/000C0433). I.S.F. is supported by the Wellcome Trust (207462/Z/17/Z), the Botnar Fondation, the Bernard Wolfe Health Neuroscience Endowment and an NIHR Senior Investigator Award.Obesity is associated with an increased risk of severe Coronavirus Disease 2019 (COVID-19) infection and mortality. COVID-19 vaccines reduce the risk of serious COVID-19 outcomes; however, their effectiveness in people with obesity is incompletely understood. We studied the relationship among body mass index (BMI), hospitalization and mortality due to COVID-19 among 3.6 million people in Scotland using the Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) surveillance platform. We found that vaccinated individuals with severe obesity (BMI > 40 kg/m2) were 76% more likely to experience hospitalization or death from COVID-19 (adjusted rate ratio of 1.76 (95% confidence interval (CI), 1.60–1.94). We also conducted a prospective longitudinal study of a cohort of 28 individuals with severe obesity compared to 41 control individuals with normal BMI (BMI 18.5–24.9 kg/m2). We found that 55% of individuals with severe obesity had unquantifiable titers of neutralizing antibody against authentic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus compared to 12% of individuals with normal BMI (P = 0.0003) 6 months after their second vaccine dose. Furthermore, we observed that, for individuals with severe obesity, at any given anti-spike and anti-receptor-binding domain (RBD) antibody level, neutralizing capacity was lower than that of individuals with a normal BMI. Neutralizing capacity was restored by a third dose of vaccine but again declined more rapidly in people with severe obesity. We demonstrate that waning of COVID-19 vaccine-induced humoral immunity is accelerated in individuals with severe obesity. As obesity is associated with increased hospitalization and mortality from breakthrough infections, our findings have implications for vaccine prioritization policies.Publisher PDFPeer reviewe

Andy Warhol, publisher

Thesis (Ph. D.)--University of Rochester. Program in Visual and Cultural Studies, 2013.This dissertation looks at a specific selection of Warhol’s books and magazines. These publications span his first years in New York City in the 1950s to the height of his career in the 1960s to the last book he published before his death in 1987. While unabashedly a monographic study, my project sets out to de-center the act of publication to a cast of co-producers, technologies, institutional frameworks, and readers. Along those lines, the title of my dissertation is meant to signal a necessary shift in how we grapple with the medium of the artist’s book. Warhol was a publisher in the sense that he self-published his first books and he was listed on the masthead of inter/VIEW magazine as its publisher, yet many of his books were published by established publishing houses-Harcourt, Random House, Harper and Row-therefore, my title also refers to Warhol as a publisher in a less literal sense. His books and magazines incorporate the conditions of their production and reception into their content and meaning. Whether the capacities of the typesetter, the graphic display of the magazine’s front page, the input of an editor, the publisher’s publicity program, or the reader’s response, Warhol shows us that these elements of publication are available for him to take up as his art. A recurrent theme in this dissertation is to unpack how Warhol’s art challenges our understanding of the construction of “reading” publics and the social performance of identity and affiliation that is facilitated through and in print media. I attend to the specific technological and social processes that define each of Warhol’s publications and I historicize these publications in relationship to Warhol’s other work, the work of his contemporaries, and the broader spheres of the literary marketplace and American popular culture. Unpacking what publishing meant to Warhol, then, becomes a means of understanding how a major postwar artist appropriated the mechanisms of print culture-of publishing, publication, and publicity-as a way of exploring and exploiting the value of being visible, or even partially visible, in a public

N 1 -methylpseudouridylation of mRNA causes +1 ribosomal frameshifting

Acknowledgements: A.E.W. and T.P. are supported by the Medical Research Council, grant number MC_UU_00025/7(A.E.W.). J.C.Y.-P., E.H., A.P.F. and J.E.D.T. are supported by the Medical Research Council (RG95376 and MC_UU_00025/12). T.E.M. was financially supported by the Integrative Toxicology Training Partnership. T.E.M., M.R., T.V.d.H., C.M.S., J.E.D.T., K.S.L. and A.E.W. acknowledge funding from Wellcome Leap as part of the R3 Program. PITCH was funded by the UK Department of Health and Social Care and UKRI (MR/W02067X/1 and MR/X009297/1), with contributions from UKRI/NIHR through the UK Coronavirus Immunology Consortium (UK-CIC), the Huo Family Foundation and The National Institute for Health Research (COV19-RECPLAS). In Liverpool PITCH is a sub-study of UKHSA’s SIREN study. P.K. is an NIHR Senior Investigators and is funded by WT109965MA. S.J.D. is funded by an NIHR Global Research Professorship (NIHR300791). L.T. is supported by the Wellcome Trust (grant number 205228/Z/16/Z), the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections (EZI) (NIHR200907) and the Centre of Excellence in Infectious Diseases Research (CEIDR) and the Alder Hey Charity. This research was supported by the NIHR Cambridge Biomedical Research Centre (NIHR203312). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The authors thank the MRC Toxicology Unit Proteomics Facility for assistance with mass spectrometry analysis and A. Chong and D. Launer for assistance with DNA extraction and HLA typing.In vitro-transcribed (IVT) mRNAs are modalities that can combat human disease, exemplified by their use as vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IVT mRNAs are transfected into target cells, where they are translated into recombinant protein, and the biological activity or immunogenicity of the encoded protein exerts an intended therapeutic effect1, 2. Modified ribonucleotides are commonly incorporated into therapeutic IVT mRNAs to decrease their innate immunogenicity3–5, but their effects on mRNA translation fidelity have not been fully explored. Here we demonstrate that incorporation of N1-methylpseudouridine into mRNA results in +1 ribosomal frameshifting in vitro and that cellular immunity in mice and humans to +1 frameshifted products from BNT162b2 vaccine mRNA translation occurs after vaccination. The +1 ribosome frameshifting observed is probably a consequence of N1-methylpseudouridine-induced ribosome stalling during IVT mRNA translation, with frameshifting occurring at ribosome slippery sequences. However, we demonstrate that synonymous targeting of such slippery sequences provides an effective strategy to reduce the production of frameshifted products. Overall, these data increase our understanding of how modified ribonucleotides affect the fidelity of mRNA translation, and although there are no adverse outcomes reported from mistranslation of mRNA-based SARS-CoV-2 vaccines in humans, these data highlight potential off-target effects for future mRNA-based therapeutics and demonstrate the requirement for sequence optimization