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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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- Han, Y., et al.
(författare)
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X-Radiation Induces Non-Small-Cell Lung Cancer Apoptosis by Upregulation of Axin Expression
- 2009
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Ingår i: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 75:2, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Axis inhibition (Axin) is an important negative regulator of the Wnt pathway. This study investigated the relationship between Axin expression and sensitivity to X-rays in non-small-cell lung cancer (NSCLC) to find a useful indicator of radiosensitivity. Methods and Materials: Tissue from NSCLC patients, A549 cells, and BE1 cells expressing Axin were exposed to 1-Gy of X-radiation. Axin and p53 expression levels were detected by immunohistochemistry and reverse transcription-PCR. Apoptosis was determined by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay and FACS (fluorescence-activate cell sorter) analysis. Caspase-3 activity was determined by Western blotting. Phospho-JNK expression was determined by immunofluorescence. Results: The expression of Axin was significantly lower in NSCLC tissues than in normal lung tissues (p less than 0.05). Axin expression correlates with differentiation, TNM staging, and lymph node metastasis of NSCLC (p less than 0.05). Its expression negatively correlates with the expression of p53(mt) (p=0.000) and positively correlates with apoptosis (p=0.002). The prognosis of patients with high expression of Axin was better than those with low expression. X-radiation increases Axin expression in NSCLC tissue, and caspase-3 is significantly higher in samples in which Axin is increased (p less than 0.05). Both X-radiation and Axin induce apoptosis of A549 and BE1 cells; however, the combination of the two enhances the apoptotic effect (p less than 0.05). In A549 cells, inhibition of p53 blocks Axin-induced apoptosis, whereas in BE1 cells, the JNK pathway is required. Conclusions: Axin induces the p53 apoptotic pathway in cells where this pathway is intact; however, in cells expressing p53(mt), Axin induces apoptosis via the JNK pathway. Elevated Axin expression following X-ray exposure is a reliable indicator for determining the radiosensitivity of NSCLC.
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- Miao Jonasson, Junmei, 1972, et al.
(författare)
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Social Support, Social Network Size, Social Strain, Stressful Life Events, and Coronary Heart Disease in Women With Type 2 Diabetes: A Cohort Study Based on the Women's Health Initiative
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:8, s. 1759-1766
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE We studied associations between social support, social network size, social strain, or stressful life events and risk of coronary heart disease (CHD) in postmenopausal women with type 2 diabetes. RESEARCH DESIGN AND METHODS From the Women's Health Initiative, 5,262 postmenopausal women with type 2 diabetes at baseline were included. Cox proportional hazards regression models adjusted for demographics, depressive symptoms, anthropometric variables, and lifestyle factors were used to examine associations between social factors and CHD. RESULTS A total of 672 case subjects with CHD were observed during an average 12.79 (SD 6.29) years of follow-up. There was a significant linear trend toward higher risk of CHD as the number of stressful life events increased (Pfor trend = 0.01; hazard ratio [HR] [95% CI] for the third and fourth quartiles compared with first quartile: 1.27 [1.03-1.56] and 1.30 [1.04-1.64]). Being married or in an intimate relationship was related to decreased risk of CHD (HR 0.82 [95% CI 0.69-0.97]). CONCLUSIONS Among postmenopausal women with type 2 diabetes, higher levels of stressful life events were associated with higher risk of CHD. Experience of stressful life events might be considered as a risk factor for CHD among women with type 2 diabetes.
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- Link, Verena M, et al.
(författare)
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Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function.
- 2018
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Ingår i: Cell. - Cambridge, United States : Cell Press. - 0092-8674 .- 1097-4172. ; 173:7, s. 1796-1809.e17
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Tidskriftsartikel (refereegranskat)abstract
- Non-coding genetic variation is a major driver of phenotypic diversity and allows the investigation of mechanisms that control gene expression. Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites, and transcription factor binding in resting and activated macrophages. We observed substantial differences associated with distinct molecular pathways. Evaluating genetic variation provided evidence for roles of ∼100 TFs in shaping lineage-determining factor binding. Unexpectedly, a substantial fraction of strain-specific factor binding could not be explained by local mutations. Integration of genomic features with chromatin interaction data provided evidence for hundreds of connected cis-regulatory domains associated with differences in transcription factor binding and gene expression. This system and the >250 datasets establish a substantial new resource for investigation of how genetic variation affects cellular phenotypes.
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- Wang, Nana, et al.
(författare)
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Perovskite light-emitting diodes based on solution-processed self-organized multiple quantum wells
- 2016
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Ingår i: Nature Photonics. - : NATURE PUBLISHING GROUP. - 1749-4885 .- 1749-4893. ; 10:11, s. 699-
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Tidskriftsartikel (refereegranskat)abstract
- Organometal halide perovskites can be processed from solutions at low temperatures to form crystalline direct-bandgap semiconductors with promising optoelectronic properties(1-5). However, the efficiency of their electroluminescence is limited by non-radiative recombination, which is associated with defects and leakage current due to incomplete surface coverage(6-9). Here we demonstrate a solution-processed perovskite light-emitting diode (LED) based on self-organized multiple quantum wells (MQWs) with excellent film morphologies. The MQW-based LED exhibits a very high external quantum efficiency of up to 11.7%, good stability and exceptional highpower performance with an energy conversion efficiency of 5.5% at a current density of 100 mA cm(-2). This outstanding performance arises because the lower bandgap regions that generate electroluminescence are effectively confined by perovskite MQWs with higher energy gaps, resulting in very efficient radiative decay. Surprisingly, there is no evidence that the large interfacial areas between different bandgap regions cause luminescence quenching.
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- Zou, Wei, et al.
(författare)
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Minimising efficiency roll-off in high-brightness perovskite light-emitting diodes
- 2018
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Efficiency roll-off is a major issue for most types of light-emitting diodes (LEDs), and its origins remain controversial. Here we present investigations of the efficiency roll-off in perovskite LEDs based on two-dimensional layered perovskites. By simultaneously measuring electroluminescence and photoluminescence on a working device, supported by transient photoluminescence decay measurements, we conclude that the efficiency roll-off in perovskite LEDs is mainly due to luminescence quenching which is likely caused by non-radiative Auger recombination. This detrimental effect can be suppressed by increasing the width of quantum wells, which can be easily realized in the layered perovskites by tuning the ratio of large and small organic cations in the precursor solution. This approach leads to the realization of a perovskite LED with a record external quantum efficiency of 12.7%, and the efficiency remains to be high, at approximately 10%, under a high current density of 500 mA cm(-2).
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