| 1. |
- Aguilar-Calvo, Patricia, et al.
(author)
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Post-translational modifications in PrP expand the conformational diversity of prions in vivo
- 2017
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In: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Journal article (peer-reviewed)abstract
- Misfolded prion protein aggregates (PrPSc) show remarkable structural diversity and are associated with highly variable disease phenotypes. Similarly, other proteins, including amyloid-beta, tau, alpha-synuclein, and serum amyloid A, misfold into distinct conformers linked to different clinical diseases through poorly understood mechanisms. Here we use mice expressing glycophosphatidylinositol (GPI)anchorless prion protein, PrPC, together with hydrogen-deuterium exchange coupled with mass spectrometry (HXMS) and a battery of biochemical and biophysical tools to investigate how posttranslational modifications impact the aggregated prion protein properties and disease phenotype. Four GPI-anchorless prion strains caused a nearly identical clinical and pathological disease phenotype, yet maintained their structural diversity in the anchorless state. HXMS studies revealed that GPIanchorless PrPSc is characterized by substantially higher protection against hydrogen/deuterium exchange in the C-terminal region near the N-glycan sites, suggesting this region had become more ordered in the anchorless state. For one strain, passage of GPI-anchorless prions into wild type mice led to the emergence of a novel strain with a unique biochemical and phenotypic signature. For the new strain, histidine hydrogen-deuterium mass spectrometry revealed altered packing arrangements of beta-sheets that encompass residues 139 and 186 of PrPSc. These findings show how variation in posttranslational modifications may explain the emergence of new protein conformations in vivo and also provide a basis for understanding how the misfolded protein structure impacts the disease.
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| 2. |
- Bett, Cyrus, et al.
(author)
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Structure of the beta 2-alpha 2 loop and interspecies prion transmission
- 2012
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In: The FASEB Journal. - : Federation of American Society of Experimental Biology (FASEB). - 0892-6638 .- 1530-6860. ; 26:7, s. 2868-2876
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Journal article (peer-reviewed)abstract
- Prions are misfolded, aggregated conformers of the prion protein that can be transmitted between species. The precise determinants of interspecies transmission remain unclear, although structural similarity between the infectious prion and host prion protein is required for efficient conversion to the misfolded conformer. The beta 2-alpha 2 loop region of endogenous prion protein, PrPC, has been implicated in barriers to prion transmission. We recently discovered that conversion was efficient when incoming and host prion proteins had similar beta 2-alpha 2 loop structures; however, the roles of primary vs. secondary structural homology could not be distinguished. Here we uncouple the effect of primary and secondary structural homology of the beta 2-alpha 2 loop on prion conversion. We inoculated prions from animals having a disordered or an ordered beta 2-alpha 2 loop into mice having a disordered loop or an ordered loop due to a single residue substitution (D167S). We found that prion conversion was driven by a homologous primary structure and occurred independently of a homologous secondary structure. Similarly, cell-free conversion using PrPC from mice with disordered or ordered loops and prions from 5 species correlated with primary but not secondary structural homology of the loop. Thus, our findings support a model in which efficient interspecies prion conversion is determined by small stretches of the primary sequence rather than the secondary structure of PrP.
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| 3. |
- Cestino-Castilla, Joaquín, et al.
(author)
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Aiming for validity : The experience of conflicts in legitimacy judgments in esports actors and new grassroots activism
- 2021
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In: Proceedings of the 5th International GamiFIN Conference. - : CEUR-WS. ; , s. 190-199
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Conference paper (peer-reviewed)abstract
- Esports is a phenomenon which continues to grow in socio-cultural and economic importance, yet it remains at the edges of mainstream society. To date, there have been few works which address the topic in terms of legitimacy, particularly the micro-processes of legitimization. Given that the esports system is one which currently operates outside wider societal practices, the lived experiences of actors in the ecosystem can offer valuable insights into the world of esports. This research employs IPA in order to understand how actors in organized grassroots esports movements make sense of their individual experiences and actions. A series of novel contributions are provided by this work. First, micro-level theories of legitimacy are applied to a phenomenon which has recently come to mainstream attention, one which is at the same time a business and a culture. Second, it is the first, in our knowledge, to apply a qualitative methodology to the explicit issue of legitimacy in esports. Third, it adds to theories of legitimacy and institutional change by providing empirical insights into the circumstances in which the experience of conflicts in legitimacy judgments independently mobilizes actors, shaping collective action into grassroots activism efforts. Finally, it highlights tensions between international success and the foundations of grassroots esports.
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| 4. |
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| 5. |
- Cestino-Castilla, Joaquín, et al.
(author)
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External enablers in existing organizations : Emergence, novelty, and persistence of entrepreneurial initiatives
- 2023
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In: Strategic Entrepreneurship Journal. - : John Wiley & Sons. - 1932-4391 .- 1932-443X. ; 17:2, s. 335-371
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Journal article (peer-reviewed)abstract
- Research Summary: There is growing consensus that exogenous environmental changes can affect entrepreneurship. The external enabler framework, which provides the structures and terminology to analyze these enabling effects, has typically focused on new venture creation. In an attempt to extend the external enabler framework to corporate entrepreneurship and innovation, our longitudinal multiple-case study explores how environmental changes enable entrepreneurial initiatives in existing organizations. Our findings contribute to the external enabler framework, corporate entrepreneurship, and innovation literature by identifying new conceptual tools to understand the enabling effect of environmental change for the emergence, novelty, and persistence of entrepreneurial initiatives in existing organizations.Managerial Summary: We studied how the Covid-19 pandemic enabled the initiation and continuation of entrepreneurial activities. Our study of eight small US-based news companies shows that some entrepreneurial initiatives emerged as these organizations redirected their course of action toward new initiatives enabled by the changes in the external environment. Notably, the entrepreneurial initiatives that were new-to-the-industry originated from ideas that were already available in some form within the organization but were not in use until the pandemic gave them a second life. Furthermore, the continuation of these initiatives depended on the persistence of the changes in the environment and on the low maintenance requirements of these initiatives in terms of time, effort, and resources.
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| 6. |
- Cestino-Castilla, Joaquín, et al.
(author)
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Legitimizing the game : how gamers' personal experiences shape the emergence of grassroots collective action in esports
- 2023
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In: Internet Research. - : Emerald Group Publishing Limited. - 1066-2243. ; 33:7, s. 111-132
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Journal article (peer-reviewed)abstract
- Purpose: This paper studies early stages of actor mobilization for institutional change within Swedish esports. Design/methodology/approach: The authors employ interpretative phenomenological analysis. Findings: The authors’ findings explain how actors become motivated to act in critical reflections linked to conflicting legitimacy judgments and emotionally charged personal struggles. Moreover, the findings show how, as actors get activated in collective action, they identify efficacy lines around valid domains and experience emotionally charged collective endeavors. Furthermore, the findings explain how particularities in early experiences project legitimacy aspirations that orient collective action toward validity ends and particular values and ideals shaping actors' grassroots movements. Originality/value: This study adds to legitimacy and institutional change theory through individual actors' perspectives, providing key insights into how they are motivated, activated, and oriented. This study is the first to investigate grassroots activists' personal stories in esports.
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| 7. |
- Cestino-Castilla, Joaquín
(author)
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SHAPING THE NEW LOCAL : THE FUTURE OF LOCAL JOURNALISM IN THE PUBLIC DISCOURSE OF COLLECTIVE ACTORS IN THE USA
- 2023
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In: Local Journalism: Critical Perspectives on the Provincial Newspaper. - : Taylor and Francis. - 9780429430343 ; , s. 127-147
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Book chapter (other academic/artistic)abstract
- It is impossible to think about the role of local journalism out of its context. In the United States of America, as in many other Western societies, this context is of increasing precarity. This chapter analyses observations made at key industrial and academic events, which are complemented by interviews with local players and articles, reports and studies produced by prominent actors in the field of news. Despite the significant changes brought by the digital, the core ideas that organise the business of providing local journalistic content in the regional press remain virtually unchanged from the analogic age. By the beginning of the COVID-19 crisis, the technological disruption brought by the internet had already syphoned advertising revenue from local newspapers to a reduced number of big technological players. Print advertising is collapsing and collective actors, increasingly aware of the inability of newspapers to compete with SMP for digital advertising, take issue with the sustainability of advertising as a revenue stream.
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| 8. |
- Nyström, Anna-Greta, et al.
(author)
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Current issues of sustainability in esports
- 2022
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In: International Journal of Esports. - : International Journal of Esports. - 2634-1069. ; 1:1
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Journal article (peer-reviewed)abstract
- Aims: The aim of the paper is to explore emerging themes, which support the development of a sustainable esports industry.Methods and results: This study is based on a workshop methodology, which aims to identify and explore topics perceived as most pertinent by individuals with an intimate understanding of the dynamics of the esports context. Two workshops were held with a total of 64 participants, representing both academia and industry stakeholders. Interpretations of the sustainability of esports were thus recorded, developed, critiqued, and refined through social interaction with experts. The results indicate three critical themes to address regarding the development of sustainability of esports, namely a) health and inclusiveness, b) the incomplete industry structure, and c) the immature business logic.Conclusions: Sustainability refers to the ability of esports to survive or persist. We argue that sustainability is dependent on how well industry stakeholders can address the identified themes. Currently, social sustainability is the primary concern of both practitioners and researchers of esports. Economic sustainability mostly deals with securing business growth, while environmental sustainability is not yet perceived as a relevant topic (e.g., using sustainable technologies and energy-saving related to gaming and competitive events). Structures and processes within esports presently constitute the focus of sustainability in esports.
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| 9. |
- Rose, Angela M.C., et al.
(author)
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Vaccine effectiveness against COVID-19 hospitalisation in adults (≥ 20 years) during Omicron-dominant circulation : I-MOVECOVID-19 and VEBIS SARI VE networks, Europe, 2021 to 2022
- 2023
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In: Eurosurveillance. - 1025-496X. ; 28:47
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Journal article (peer-reviewed)abstract
- Introduction: The I-MOVE-COVID-19 and VEBIS hospital networks have been measuring COVID-19 vaccine effectiveness (VE) in participating European countries since early 2021. Aim: We aimed to measure VE against PCR-confirmed SARS-CoV-2 in patients ≥20 years hospitalised with severe acute respiratory infection (SARI) from December 2021 to July 2022 (Omicron-dominant period). Methods: In both networks, 46 hospitals (13 countries) follow a similar test-negative case–control protocol. We defined complete primary series vaccination (PSV) and first booster dose vaccination as last dose of either vaccine received≥14 days before symptom onset (stratifying first booster into received<150 and≥150 days after last PSV dose). We measured VE overall, by vaccine category/product, age group and time since first mRNA booster dose, adjusting by site as a fixed effect, and by swab date, age, sex, and presence/absence of at least one commonly collected chronic condition. Results: We included 2,779 cases and 2,362 controls. The VE of all vaccine products combined against hospitalisation for laboratory-confirmed SARS-CoV-2 was 43% (95% CI: 29–54) for complete PSV (with last dose received≥150 days before onset), while it was 59% (95% CI: 51–66) after addition of one booster dose. The VE was 85% (95% CI: 78–89), 70% (95% CI: 61–77) and 36% (95% CI: 17–51) for those with onset 14–59 days, 60–119 days and 120–179 days after booster vaccination, respectively. Conclusions: Our results suggest that, during the Omicron period, observed VE against SARI hospitalisation improved with first mRNA booster dose, particularly for those having symptom onset<120 days after first booster dose.
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| 10. |
- Sigurdson, Christina J., et al.
(author)
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A molecular switch controls interspeciesprion disease transmission in mice
- 2010
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In: Journal of Clinical Investigation. - : American Society for Clinical Investigation. - 0021-9738 .- 1558-8238. ; 120, s. 2590-2599
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Journal article (peer-reviewed)abstract
- Transmissible spongiform encephalopathies are lethal neurodegenerative disorders that present with aggregated forms of the cellular prion protein (PrPC), which are known as PrPSc. Prions from different species vary considerably in their transmissibility to xenogeneic hosts. The variable transmission barriers depend on sequence differences between incoming PrPSc and host PrPC and additionally, on strain-dependent conformational properties of PrPSc. The β2-α2 loop region within PrPC varies substantially between species, with its structure being influenced by the residue types in the 2 amino acid sequence positions 170 (most commonly S or N) and 174 (N or T). In this study, we inoculated prions from 5 different species into transgenic mice expressing either disordered-loop or rigid-loop PrPC variants. Similar β2-α2 loop structures correlated with efficient transmission, whereas dissimilar loops correlated with strong transmission barriers. We then classified literature data on cross-species transmission according to the 170S/N polymorphism. Transmission barriers were generally low between species with the same amino acid residue in position 170 and high between those with different residues. These findings point to a triggering role of the local β2-α2 loop structure for prion transmissibility between different species.
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