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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. |
- Chen, Jiajia, et al.
(författare)
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Passive wide area network solutions : Filterless and semi-filterless optical networks
- 2011
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Ingår i: 13th International Conference on Transparent Optical Networks (ICTON). - 9781457708800
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Konferensbidrag (refereegranskat)abstract
- Advances in optical coherent transmission and electrical compensation technologies (such as coherent receiver and forward error correction FEC) have stimulated ideas for novel optical network architectures. Recently proposed passive wide area network solution, referred to as filterless optical network [1 #x2013;2] eliminates or minimizes the usage of active photonic reconfigurable network elements. In this approach, only the passive splitters and combiners for interconnecting the fiber links are utilized, which makes this network architecture more cost- and energy-effective as well as more reliable compared with networks based on active optical switching. However, the filterless optical network architecture implies some constraints on fiber interconnection design, maximum fiber-tree length and wavelength reuse due to its broadcast nature. Consequently, filterless solution always requires more resources (i.e. number of wavelengths) compared with the active switched optical networks which are allowed to utilize reconfigurable and coloured components. In order to improve the wavelength utilization while maintaining flexibility of resource allocation, this work extends the idea of filterless optical network by introducing some passive coloured components (e.g., fiber Bragg grating FBG, red/blue filters, etc) to drop local signals at some determined nodes. This approach is referred to as semi-filterless optical network. Furthermore, the semi-filterless solution maintains the passive feature, enabling high reliability and efficiency of cost and energy. Meanwhile, its non-broadcast property at some determined nodes has potential to decrease the transmission impairments and hence relax the constraints on fiber interconnection design and the maximal transparent length, which are strict in the filterless optical network. Our preliminary results confirm the advantages of semi-filterless solution.
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| 3. |
- Ji, Zhenyu, et al.
(författare)
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Vemurafenib Synergizes with Nutlin-3 to Deplete Survivin and Suppresses Melanoma Viability and Tumor Growth
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 19:16, s. 4383-4391
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: For patients with advanced melanoma, primary and secondary resistance to selective BRAF inhibition remains one of the most critically compelling challenges. One rationale argues that novel biologically informed strategies are needed to maximally cripple melanoma cells up front before compensatory mechanisms emerge. As p53 is uncommonly mutated in melanoma, restoration of its function represents an attractive adjunct to selective BRAF inhibition. Experimental Design: Thirty-seven BRAF(V600E)-mutated melanoma lines were subjected to synergy studies in vitro using a combination of vemurafenib and nutlin-3 (Nt-3). In addition, cellular responses and in vivo efficacy were also determined. We also analyzed changes in the levels of canonical apoptotic/survival factors in response to vemurafenib. Results: Dual targeting of BRAF(V600E) and Hdm2 with vemurafenib and Nt-3, respectively, synergistically induced apoptosis and suppressed melanoma viability in vitro and tumor growth in vivo. Suppression of p53 in melanoma cells abrogated Nt-3's effects fully and vemurafenib's effects partially. A survey of canonical survival factors revealed that both vemurafenib and Nt-3 independently attenuated levels of the antiapoptotic protein, survivin. Genetic depletion of survivin reproduces the cytotoxic effects of the combination strategy. Conclusion: These results show preclinical feasibility for overcoming primary vemurafenib resistance by restoring p53 function. Moreover, it identifies survivin as one downstream mediator of the observed synergism and a potential secondary target. (C)2013 AACR.
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| 4. |
- Tremblay, Christine, et al.
(författare)
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Proposed filterless architecture and control plane for emerging flexible coherent networks
- 2013
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Ingår i: ICTON 2013. - 9781479906833 ; , s. 1-1
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Konferensbidrag (refereegranskat)abstract
- Recent developments in coherent modem performance and digital signal processing (DSP) technologies have opened the opportunity for new agile network architectures [1, 2]. The filterless network concept has been proposed in [3] and it is shown that they are more cost-effective and reliable compared to active optical switching networks. Filterless optical networks use broadcast-and-select techniques in which passive non-filtered optical splitters and combiners are used for channel add-drop and fiber link interconnection. Furthermore, DSP-based coherent modems are complementary foundational technologies for flexible optical networking owing to their properties of dynamic impairment compensation, performance monitoring and tuneability. The resulting network architecture makes an attractive candidate solution for flexible optical networking [4]. In this talk, we review the recent progress in filterless optical network design and control [5]ￜ[7]. In the first part, filterless architectural solutions are proposed for different network topologies and compared to active photonic switching solutions. A cost and performance analysis of filterless network solutions with 1 + 1 optical layer protection is also presented. In the second part, we present a control plane for filterless optical networks and describe its main characteristics through a performance study. Our results show that passive filterless networks can be considered as a cost effective and simpler alternative to active optical switching networks whenever traffic loading is not approaching full network capacity.
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