| 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. |
- Lin, Keshuo, et al.
(författare)
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Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: The COSMIC consortium
- 2024
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Ingår i: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - 2352-8729. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTIONWhite matter hyperintensities (WMHs) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well documented in populations of different ethnicities and/or from different geographical regions.METHODSWe investigated how WMHs were associated with vascular risk factors and cognition in both Whites and Asians, using data from five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1946). WMH volumes (whole brain, periventricular, and deep) were quantified with UBO Detector and harmonized using the ComBat model. We also harmonized various vascular risk factors and scores for global cognition and individual cognitive domains.RESULTSFactors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake, and insufficient physical activity. Hypertension and stroke had stronger associations with WMH volumes in Whites than in Asians. No associations between WMH volumes and cognitive performance were found after correction for multiple testing.CONCLUSIONThe current study highlights ethnic differences in the contributions of vascular risk factors to WMHs.
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| 3. |
- Li, Shan Shan, et al.
(författare)
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Coupled U-Pb and Rb-Sr laser ablation geochronology trace Archean to Proterozoic crustal evolution in the Dharwar Craton, India
- 2020
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Ingår i: Precambrian Research. - : Elsevier BV. - 0301-9268. ; 343
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 Elsevier B.V. The Western Dharwar Craton (WDC) and the Karwar Block (KB) in southern Peninsular India provide important windows to Earth's early crustal evolution and continental growth as these domains likely represent fragments of the first landmass or supercontinent on our planet. Here we employ, for the first time, a coupled laser ablation zircon U-Pb dating and in-situ Rb-Sr dating of micas (biotite, muscovite) and feldspars to evaluate the Meso- to Neoarchean crustal evolution and Proterozoic magmatism/metamorphism in the Karwar Block. This novel approach based on integrated geochronological results show that the WDC and KB experienced (i) a major Mesoarchean continental growth event (c. 3.2 to 2.9 Ga), (ii) younger Neoarchean and Paleoproterozoic magmatism/migmatization (syn- and post-tectonic granite formation events at c. 2.8–2.6 Ga and 2.2 Ga, respectively), and (iii) Mesoproterozoic metamorphism/thermal imprint (as young as 1.2 Ga). The zircon εHf(t) values exhibit a range from +0.4 to +9.8 in amphibolite, hornblende gneiss and trondhjemite (3.28–3.08 Ga), as well as the +6.1 to +9.7 range for 2.96 Ga old zircons in porphyritic granite, which suggests juvenile source for the magmatism that constructed this crustal block. Overall, this study illustrates the benefits of using coupled zircon U-Pb and in-situ Rb-Sr mica and feldspar dating approaches, as the former (U/Pb) provides robust constraints or a ‘baseline age’ for initial crystallization of crustal sequences whereas the latter (Rb/Sr) is sensitive to younger magmatic and metamorphic events. Thus, the integration of these two laser ablation ICP-MS based geochronometers applied to crustal evolution studies, has the potential to provide more comprehensive insights into continental growth in the early Earth, and later magmatic and metamorphic history of the region.
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