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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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2. |
- Wang, Mojin, et al.
(författare)
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A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer
- 2013
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Ingår i: Pathology and Oncology Research. - : Springer Verlag (Germany). - 1219-4956 .- 1532-2807. ; 19:3, s. 521-527
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Tidskriftsartikel (refereegranskat)abstract
- The cAMP/PKA signalling events regulated by A-kinase anchoring proteins 10 (AKAP10) is involved in tumorigenesis. Previous study showed that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. However, there was no literature reporting the role of AKAP10 in the pathogenesis of colorectal cancer. The aim of the study was to investigate the clinicopathologic significance of A-kinase anchoring proteins 10 (AKAP 10) expression and the relationship with its polymorphism in colorectal cancer. The expression of AKAP10 was determined by immunohistochemical staining (IHC) and western blot assay on colorectal cancer (n = 176), adenoma (n = 87) and distant normal mucosa (n = 72). 176 patients with colorectal cancer were genotyped for AKAP10 2073A/G polymorphism by TaqMan RT-PCR. We found that the positive expression rate of AKAP10 in colorectal cancer (59 %) was significantly higher than those in adenoma (39 %) and distant normal mucosa (42 %) (P = 0.004). There was no significant difference between adenoma and distant normal mucosa (P = 0.741). Positive AKAP10 staining was correlated with deeper tumor invasion (P < 0.001), lymph nodes metastasis (P = 0.022), advanced tumor stage (P < 0.001) and poorly differentiated degree (P = 0.003). Compared with AA genotype (52 %), positive expression of AKAP10 was significantly increased in colorectal cancer patients with the variant (AG+GG) genotypes (68 %, P = 0.033). It was concluded that AKAP10 may play an important role in the development and progression of colorectal cancer.
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- Tang, Ting-Ting, et al.
(författare)
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Impaired thymic export and apoptosis contribute to regulatory T-cell defects in patients with chronic heart failure.
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 6:9, s. e24272-
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Tidskriftsartikel (refereegranskat)abstract
- Animal studies suggest that regulatory T (T(reg)) cells play a beneficial role in ventricular remodeling and our previous data have demonstrated defects of T(reg) cells in patients with chronic heart failure (CHF). However, the mechanisms behind T(reg-)cell defects remained unknown. We here sought to elucidate the mechanism of T(reg-)cell defects in CHF patients.
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4. |
- 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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5. |
- Lin, Rui, et al.
(författare)
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An Ultra-dense Optical Comb Based DWDM-OFDM-PON System
- 2014
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Konferensbidrag (refereegranskat)abstract
- We proposed and demonstrated an ultra-dense optical comb based DWDM-OFDM-PON scheme. At the optical line terminal (OLT), a cost-effective optical frequency comb generator (OFCG) is proposed and achieved as the multi-wavelength optical source. The OFCG is capable to provide multiple channels with reconfigurable wavelength spacing for ultra-dense WDM-PON based access network. In our scheme, OFDMsignal with multi-level modulation will be encoded into the OFCG lines for the downstream transmission to enhance the spectral efficiency while the OFDM signal will be remodulated by OOK data for the upstream transmission due to its ease of implementation in optical network unit (ONU) side. In experiments, we demonstrated that 10 optical lines with 25 GHz channel spacing are generated and they were modulated by 2.5-GB/s QPSK-OFDM for the downlink signal transmission. We also demonstrated that the multiple wavelengths from the OFCG.
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