| 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. |
- Wang, Mo-Jin, et al.
(författare)
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Downregulation of microRNA-124 is an independent prognostic factor in patients with colorectal cancer
- 2013
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Ingår i: International Journal of Colorectal Disease. - : Springer Verlag (Germany). - 0179-1958 .- 1432-1262. ; 28:2, s. 183-189
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Tidskriftsartikel (refereegranskat)abstract
- PurposeRecently, microRNA-124 (miR-124) has been demonstrated as a potential tumor suppressor in several types of cancers. However, the role of miR-124 in colorectal cancer remains unclear. This study was aimed at investigating the clinicopathological significance of miR-124 expression in colorectal cancer.MethodsQuantitative real-time PCR was used to analyze miR-124 expression in 96 colorectal cancers and individual-matched normal mucosa samples. The expression of miR-124 was assessed for associations with clinicopathological characteristics using chi-square test. The survival curves were calculated by the Kaplan–Meier method. The influence of each variable on survival was examined by the Cox multivariate regression analysis.ResultsThe miR-124 expression was significantly downregulated in colorectal cancer compared to normal mucosa (P = 0.001). In colorectal cancer, miR-124 decreased expression correlated significantly with the grade of differentiation (P = 0.021). Univariate survival analysis showed that the downregulated miR-124 was significantly correlated with worse prognosis, both in terms of overall survival (P = 0.017) and disease-free survival (DFS) (P = 0.014). Further, the downregulated miR-124 was demonstrated as a prognostic factor for overall survival (hazard ratio, HR = 4.634; 95 % confidence interval, CI, 1.731–12.404; P = 0.002) and DFS (HR = 4.533, 95 % CI 1.733–11.856, P = 0.002), independently of gender, age, location, maximum tumor size, depth of invasion, differentiation, and TNM stage.ConclusionsMiR-124 may play a certain role in the development of colorectal cancer. The downregulation expression of miR-124 is an independent prognostic factor in patients with colorectal cancer.
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| 3. |
- Abeysinghe, Kasun S., et al.
(författare)
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Mercury flow through an Asian rice-based food web
- 2017
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Ingår i: Environmental Pollution. - : ELSEVIER SCI LTD. - 0269-7491 .- 1873-6424. ; 229, s. 219-228
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Tidskriftsartikel (refereegranskat)abstract
- Mercury (Hg) is a globally-distributed pollutant, toxic to humans and animals. Emissions are particularly high in Asia, and the source of exposure for humans there may also be different from other regions, including rice as well as fish consumption, particularly in contaminated areas. Yet the threats Asian wildlife face in rice-based ecosystems are as yet unclear. We sought to understand how Hg flows through rice-based food webs in historic mining and non-mining regions of Guizhou, China. We measured total Hg (THg) and methylmercury (MeHg) in soil, rice, 38 animal species (27 for MeHg) spanning multiple trophic levels, and examined the relationship between stable isotopes and Hg concentrations. Our results confirm biomagnification of THg/MeHg, with a high trophic magnification slope. Invertivorous songbirds had concentrations of THg in their feathers that were 15x and 3x the concentration reported to significantly impair reproduction, at mining and non-mining sites, respectively. High concentrations in specialist rice consumers and in granivorous birds, the later as high as in piscivorous birds,, suggest rice is a primary source of exposure. Spiders had the highest THg concentrations among invertebrates and may represent a vector through which Hg is passed to vertebrates, especially songbirds. Our findings suggest there could be significant population level health effects and consequent biodiversity loss in sensitive ecosystems, like agricultural wetlands, across Asia, and invertivorous songbirds would be good subjects for further studies investigating this possibility.
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