| 1. |
- 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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| 2. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 3. |
- Olalde, I., et al.
(författare)
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The Beaker phenomenon and the genomic transformation of northwest Europe
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 555:7695, s. 190-196
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Tidskriftsartikel (refereegranskat)abstract
- From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.
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| 4. |
- Cronin, M. F., et al.
(författare)
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Developing an Observing Air-Sea Interactions Strategy (OASIS) for the global ocean
- 2022
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Ingår i: Ices Journal of Marine Science. - : Oxford University Press (OUP). - 1054-3139 .- 1095-9289. ; 80:2, s. 367-73
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Tidskriftsartikel (refereegranskat)abstract
- The Observing Air-Sea Interactions Strategy (OASIS) is a new United Nations Decade of Ocean Science for Sustainable Development programme working to develop a practical, integrated approach for observing air-sea interactions globally for improved Earth system (including ecosystem) forecasts, CO2 uptake assessments called for by the Paris Agreement, and invaluable surface ocean information for decision makers. Our "Theory of Change" relies upon leveraged multi-disciplinary activities, partnerships, and capacity strengthening. Recommendations from >40 OceanObs'19 community papers and a series of workshops have been consolidated into three interlinked Grand Ideas for creating #1: a globally distributed network of mobile air-sea observing platforms built around an expanded array of long-term time-series stations; #2: a satellite network, with high spatial and temporal resolution, optimized for measuring air-sea fluxes; and #3: improved representation of air-sea coupling in a hierarchy of Earth system models. OASIS activities are organized across five Theme Teams: (1) Observing Network Design & Model Improvement; (2) Partnership & Capacity Strengthening; (3) UN Decade OASIS Actions; (4) Best Practices & Interoperability Experiments; and (5) Findable-Accessible-Interoperable-Reusable (FAIR) models, data, and OASIS products. Stakeholders, including researchers, are actively recruited to participate in Theme Teams to help promote a predicted, safe, clean, healthy, resilient, and productive ocean.
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| 5. |
- Libby, J. B., et al.
(författare)
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Whole blood transcript and protein abundance of the vascular endothelial growth factor family relate to cognitive performance
- 2023
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 124, s. 11-17
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Tidskriftsartikel (refereegranskat)abstract
- The vascular endothelial growth factor (VEGF) family of genes has been implicated in the clinical devel-opment of Alzheimer's Disease (AD). A previous study identified associations between gene expression of VEGF family members in the prefrontal cortex and cognitive performance and AD pathology. This study explored if those associations were also observed in the blood. Consistent with previous observations in brain tissue, higher blood gene expression of placental growth factor (PGF) was associated with a faster rate of memory decline (p= 0.04). Higher protein abundance of FMS-related receptor tyrosine kinase 4 (FLT4) in blood was associated with biomarker levels indicative of lower amyloid and tau pathology, op-posite the direction observed in brain. Also, higher gene expression of VEGFB in blood was associated with better baseline memory (p= 0.008). Notably, we observed that higher gene expression of VEGFB in blood was associated with lower expression of VEGFB in the brain (r =-0.19, p= 0.02). Together, these re-sults suggest that the VEGFB, FLT4, and PGF alterations in the AD brain may be detectable in the blood compartment.Published by Elsevier Inc.This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )
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| 6. |
- Paterson, R. W., et al.
(författare)
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SILK studies — capturing the turnover of proteins linked to neurodegenerative diseases
- 2019
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Ingår i: Nature Reviews Neurology. - : Springer Science and Business Media LLC. - 1759-4758 .- 1759-4766. ; 15:7, s. 419-427
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer disease (AD) is one of several neurodegenerative diseases characterized by dysregulation, misfolding and accumulation of specific proteins in the CNS. The stable isotope labelling kinetics (SILK) technique is based on generating amino acids labelled with naturally occurring stable (that is, nonradioactive) isotopes of carbon and/or nitrogen. These labelled amino acids can then be incorporated into proteins, enabling rates of protein production and clearance to be determined in vivo and in vitro without the use of radioactive or chemical labels. Over the past decade, SILK studies have been used to determine the turnover of key pathogenic proteins amyloid-β (Aβ), tau and superoxide dismutase 1 (SOD1) in the cerebrospinal fluid of healthy individuals, patients with AD and those with other neurodegenerative diseases. These studies led to the identification of several factors that alter the production and/or clearance of these proteins, including age, sleep and disease-causing genetic mutations. SILK studies have also been used to measure Aβ turnover in blood and within brain tissue. SILK studies offer the potential to elucidate the mechanisms underlying various neurodegenerative disease mechanisms, including neuroinflammation and synaptic dysfunction, and to demonstrate target engagement of novel disease-modifying therapies. © 2019, Springer Nature Limited.
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| 7. |
- Tomlinson, B., et al.
(författare)
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Analyzing the sustainability of 28 'Blockchain for Good' projects via affordances and constraints
- 2021
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Ingår i: Information Technology for Development. - : Informa UK Limited. - 0268-1102 .- 1554-0170. ; 27:3, s. 439-469
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Tidskriftsartikel (refereegranskat)abstract
- Proponents of 'Blockchain for Good' - blockchain efforts seeking to enable benefits to humans and the environment - have suggested that the technology can support sustainability. However, while previous research has addressed aspects of the sustainabilityaffordancesof Blockchain for Good projects, theconstraintsthat these projects impose have not faced equal consideration. Furthermore, the theoretical concepts of sustainability 'problems' and 'solutions' implicit in these projects have not been made clear. In this exploratory study, we evaluate the sustainability of 28 Blockchain for Good projects that use cryptocurrencies or tradable tokens with regard to the UN sustainability goals. These projects span a range of goals, such as supply chain tracking, transparent charity, and fairer voting. Despite their admirable goals, we find that current Blockchain for Good projects are unlikely to contribute to a sustainable future due to technical limitations and a conceptual framing that favors the status quo rather than transformative change.
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| 8. |
- Van Wert, J. C., et al.
(författare)
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Population variability in thermal performance of pre-spawning adult Chinook salmon
- 2023
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Ingår i: Conservation Physiology. - 2051-1434. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Climate change is causing large declines in many Pacific salmon populations. In particular, warm rivers are associated with high levels of premature mortality in migrating adults. The Fraser River watershed in British Columbia, Canada, supports some of the largest Chinook salmon (Oncorhynchus tshawytscha) runs in the world. However, the Fraser River is warming at a rate that threatens these populations at critical freshwater life stages. A growing body of literature suggests salmonids are locally adapted to their thermal migratory experience, and thus, population-specific thermal performance information can aid in management decisions. We compared the thermal performance of pre-spawning adult Chinook salmon from two populations, a coastal fall-run from the Chilliwack River (125 km cooler migration) and an interior summer-run from the Shuswap River (565 km warmer migration). We acutely exposed fish to temperatures reflecting current (12 degrees C, 18 degrees C) and future projected temperatures (21 degrees C, 24 degrees C) in the Fraser River and assessed survival, aerobic capacity (resting and maximum metabolic rates, absolute aerobic scope (AAS), muscle and ventricle citrate synthase), anaerobic capacity (muscle and ventricle lactate dehydrogenase) and recovery capacity (post-exercise metabolism, blood physiology, tissue lactate). Chilliwack Chinook salmon performed worse at high temperatures, indicated by elevated mortality, reduced breadth in AAS, enhanced plasma lactate and potassium levels and elevated tissue lactate concentrations compared with Shuswap Chinook salmon. At water temperatures exceeding the upper pejus temperatures (T-pejus, defined here as 80% of maximum AAS) of Chilliwack (18.7 degrees C) and Shuswap (20.2 degrees C) Chinook salmon populations, physiological performance will decline and affect migration and survival to spawn. Our results reveal population differences in pre-spawning Chinook salmon performance across scales of biological organization at ecologically relevant temperatures. Given the rapid warming of rivers, we show that it is critical to consider the intra-specific variation in thermal physiology to assist in the conservation and management of Pacific salmon. Warming water temperatures threaten aquatic species and impact economies and cultures. Yet, vulnerability can vary within a species. We assessed the thermal performance of two populations of pre-spawning adult Chinook salmon and found that an interior summer-run population of Chinook salmon performed better at warmer temperatures than a coastal fall-run population. Current river temperatures already exceed the functional warming tolerances of both populations and highlight the value of physiological studies in supporting management decisions.
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