| 1. |
- Hill, Rosemary, et al.
(författare)
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Knowledge co-production for Indigenous adaptation pathways : Transform post-colonial articulation complexes to empower local decision-making
- 2020
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Ingår i: Global Environmental Change. - : Elsevier BV. - 0959-3780 .- 1872-9495. ; 65
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Tidskriftsartikel (refereegranskat)abstract
- Co-production between scientific and Indigenous knowledge has been identified as useful to generating adaptation pathways with Indigenous peoples, who are attached to their traditional lands and thus highly exposed to the impacts of climate change. However, ignoring the complex and contested histories of nation-state colonisation can result in naïve adaptation plans that increase vulnerability. Here, through a case study in central Australia, we investigate the conditions under which co-production between scientific and Indigenous knowledge can support climate change adaptation pathways among place-attached Indigenous communities. A research team including scientists, Ltyentye Apurte Rangers and other staff from the Central Land Council first undertook activities to co-produce climate change presentations in the local Arrernte language; enable community members to identify potential adaptation actions; and implement one action, erosion control. Second, we reflected on the outcomes of these activities in order to unpack deeper influences. Applying the theory of articulation complexes, we show how ideologies, institutions and economies have linked Indigenous societies and the establishing Australian nation-state since colonisation. The sequence of complexes characterised as frontier, mission, pastoral, land-rights, community-development and re-centralisation, which is current, have both enabled and constrained adaptation options. We found knowledge co-production generates adaptation pathways when: (1) effective methods for knowledge co-production are used, based on deeply respectful partnerships, cultural governance and working together through five co-production tasks—prepare, communicate, discuss, bring together and apply; (2) Indigenous people have ongoing connection to their traditional territories to maintain their Indigenous knowledge; (3) the relationship between the Indigenous people and the nation-state empowers local decision-making and learning, which requires and creates consent, trust, accountability, reciprocity, and resurgence of Indigenous culture, knowledge and practices. These conditions foster the emergence of articulation complexes that enable the necessary transformative change from the colonial legacies. Both these conditions and our approach are likely to be relevant for place-attached Indigenous peoples across the globe in generating climate adaptation pathways.
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| 2. |
- 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. |
- Mattis, Katia K, et al.
(författare)
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Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression
- 2023
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 66:4, s. 674-694
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Genome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk.METHODS: A zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo. Using transcriptomic and cellular phenotyping of a human beta cell model (EndoC-βH1) and human induced pluripotent stem cell (hiPSC)-derived beta-like cells, we investigated how loss of RREB1 expression and activity affects pancreatic endocrine cell development and function. Ex vivo measurements of human islet function were performed in donor islets from carriers of RREB1 type 2 diabetes risk alleles.RESULTS: CRISPR/Cas9-mediated loss of rreb1a and rreb1b function in zebrafish supports an in vivo role for the transcription factor in beta cell mass, beta cell insulin expression and glucose levels. Loss of RREB1 also reduced insulin gene expression and cellular insulin content in EndoC-βH1 cells and impaired insulin secretion under prolonged stimulation. Transcriptomic analysis of RREB1 knockdown and knockout EndoC-βH1 cells supports RREB1 as a novel regulator of genes involved in insulin secretion. In vitro differentiation of RREB1KO/KO hiPSCs revealed dysregulation of pro-endocrine cell genes, including RFX family members, suggesting that RREB1 also regulates genes involved in endocrine cell development. Human donor islets from carriers of type 2 diabetes risk alleles in RREB1 have altered glucose-stimulated insulin secretion ex vivo, consistent with a role for RREB1 in regulating islet cell function.CONCLUSIONS/INTERPRETATION: Together, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function.
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