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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Vervoort, Joost M., et al.
(författare)
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9 Dimensions for evaluating how art and creative practice stimulate societal transformations
- 2024
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Ingår i: Ecology and Society. - : Resilience Alliance. - 1708-3087. ; 29:1
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Tidskriftsartikel (refereegranskat)abstract
- There is an urgent need to engage with deep leverage points in sustainability transformations-fundamental myths, paradigms, and systems of meaning making-to open new collective horizons for action. Art and creative practice are uniquely suited to help facilitate change in these deeper transformational leverage points. However, understandings of how creative practices contribute to sustainability transformations are lacking in practice and fragmented across theory and research. This lack of understanding shapes how creative practices are evaluated and therefore funded and supported, limiting their potential for transformative impact. This paper presents the 9 Dimensions tool, created to support reflective and evaluative dialogues about links between creative practice and sustainability transformations. It was developed in a transdisciplinary process between the potential users of this tool: researchers, creative practitioners, policy makers, and funders. It also brings disciplinary perspectives on societal change from evaluation theory, sociology, anthropology, psychology, and more in connection with each other and with sustainability transformations, opening new possibilities for research. The framework consists of three categories of change, and nine dimensions: changing meanings (embodying, learning, and imagining); changing connections (caring, organizing, and inspiring); and changing power (co-creating, empowering, and subverting). We describe how the 9 Dimensions tool was developed, and describe each dimension and the structure of the tool. We report on an application of the 9 Dimensions tool to 20 creative practice projects across the European project Creative Practices for Transformational Futures (CreaTures). We discuss user reflections on the potential and challenges of the tool, and discuss insights gained from the analysis of the 20 projects. Finally, we discuss how the 9 Dimensions can effectively act as a transdisciplinary research agenda bringing creative practice further in contact with transformation research.
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| 4. |
- Adams, Charleen, et al.
(författare)
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Circulating Metabolic Biomarkers of Screen-Detected Prostate Cancer in the ProtecT Study
- 2019
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research (AACR). - 1055-9965 .- 1538-7755. ; 28:1, s. 208-216
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).MATERIALS AND METHODS: The case-control portion of the study was conducted in nine UK centres with men aged 50-69 years who underwent prostate-specific antigen (PSA) screening for prostate cancer within the Prostate testing for cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (p <0.0014, multiple-testing threshold). These fell into four classes: i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); ii) fatty acids and ratios; iii) amino acids; iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.
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| 5. |
- Lane, Ruth, et al.
(författare)
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Responsibility and innovation for low waste and circular economy transitions: what roles for households?
- 2023
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Ingår i: Critical Policy Studies RCPS.
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Tidskriftsartikel (refereegranskat)abstract
- The need for waste policy to embrace CE principles through measures to avoid waste generation and improve recycling rates can be understood within the broader context of sustainability transitions. We analyze three Australian waste policies to understand how households are framed as framing policy actors. Using a governance rationalities framework inspired by Hajer (2005) and Dryzek’s (2013) work on environmental governance, we identified four discursive structures, i.e. four different problem frames with suggested solutions, measures and responsibilities. These problem frames reveal an expanding role for government and industry in waste management, alongside a more passive role for households. While anticipating that households will undertake more sorting and will reduce the amount of waste they generate, the policies lack a coherent conceptualization of the role of households as actors in circular economy transitions in Australia. Our analysis highlights and helps to understand the discrepancy between high-level CE and zero-waste policy ambitions and their implementation in practice. We conclude with suggestions on how waste policy could benefit from deliberative approaches that engage with agency for social innovation and transformation in norms and practices at the household scale.
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| 6. |
- Machacek, Erika, et al.
(författare)
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Governance and Risk–Value Constructions in Closing Loops of Rare Earth Elements in Global Value Chains
- 2017
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Ingår i: Resources. - : MDPI AG. - 2079-9276. ; 6:4
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Tidskriftsartikel (refereegranskat)abstract
- This article addresses a research gap on the challenges—specifically risk and value—connected to realizing the potential for closing loops for rare earth elements (REE). We develop an analytical framework from conceptual elements of the global value chain (GVC) framework and the relational theory of risk to examine several empirical REE industry cases for loop closure. The aim of the paper is to identify how risk–value relationships are constructed by different actors as governance structures form in transactions prior to price setting and how these have impacts on the closure of REE loops. Often, REE loops are not closed, and we find that constructions of the risk–value relationship by industrial actors and by government agencies are unstable as they pursue different motivations, consequently hindering REE loop closure in GVCs. In light of this, we propose that governments mediate against the construction of risk–value relationships by facilitating information on the characteristics of end-of-life materials that qualify these for re-entry into loops.
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| 7. |
- Watts, Eleanor L., et al.
(författare)
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The associations of anthropometric, behavioural and sociodemographic factors with circulating concentrations of IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 in a pooled analysis of 16,024 men from 22 studies
- 2019
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 145:12, s. 3244-3256
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Tidskriftsartikel (refereegranskat)abstract
- Insulin‐like growth factors (IGFs) and insulin‐like growth factor binding proteins (IGFBPs) have been implicated in the aetiology of several cancers. To better understand whether anthropometric, behavioural and sociodemographic factors may play a role in cancer risk via IGF signalling, we examined the cross‐sectional associations of these exposures with circulating concentrations of IGFs (IGF‐I and IGF‐II) and IGFBPs (IGFBP‐1, IGFBP‐2 and IGFBP‐3). The Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset includes individual participant data from 16,024 male controls (i.e. without prostate cancer) aged 22–89 years from 22 prospective studies. Geometric means of protein concentrations were estimated using analysis of variance, adjusted for relevant covariates. Older age was associated with higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGF‐I, IGF‐II and IGFBP‐3. Higher body mass index was associated with lower concentrations of IGFBP‐1 and IGFBP‐2. Taller height was associated with higher concentrations of IGF‐I and IGFBP‐3 and lower concentrations of IGFBP‐1. Smokers had higher concentrations of IGFBP‐1 and IGFBP‐2 and lower concentrations of IGFBP‐3 than nonsmokers. Higher alcohol consumption was associated with higher concentrations of IGF‐II and lower concentrations of IGF‐I and IGFBP‐2. African Americans had lower concentrations of IGF‐II, IGFBP‐1, IGFBP‐2 and IGFBP‐3 and Hispanics had lower IGF‐I, IGF‐II and IGFBP‐3 than non‐Hispanic whites. These findings indicate that a range of anthropometric, behavioural and sociodemographic factors are associated with circulating concentrations of IGFs and IGFBPs in men, which will lead to a greater understanding of the mechanisms through which these factors influence cancer risk.
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