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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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- Riedel, M., et al.
(author)
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Improving e-Science with Interoperability of the e-Infrastructures EGEE and DEISA
- 2008
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In: MIPRO 2008 - 31st International Convention Proceedings. - 9789532330366 ; , s. 225-231
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Conference paper (peer-reviewed)abstract
- In the last couple of years, many e-Science infrastructures have begun to offer production services to e- Scientists with an increasing number of applications that require access to different kinds of computational resources. Within Europe two rather different multi-national e-Science infrastructures evolved over time namely Distributed European Infrastructure for Supercomputing Applications (DEISA) and Enabling Grids for E-SciencE (EGEE). DEISA provides access to massively parallel systems such as supercomputers that are well suited for scientific applications that require many interactions between their typically high numbers of CPUs. EGEE on the other hand provides access to a world-wide Grid of university clusters and PC pools that are well suited for farming applications that require less or even no interactions between the distributed CPUs. While DEISA uses the HPC-driven Grid technology UNICORE, EGEE is based on the gLite Grid middleware optimized for farming jobs. Both have less adoption of open standards and therefore both systems are technically non-interoperable, which means that no e-Scientist can easily leverage the DEISA and EGEE infrastructure with one suitable client environment for scientific applications. This paper argues that future interoperability of such large e-Science infrastructures is required to improve e-Science in general and to increase the real scientific impact of world-wide Grids in particular. We discuss the interoperability achieved by the OMII-Europe project that fundamentally improved the interoperability between UNICORE and gLite by using open standards. We also outline one specific scientific scenario of the WISDOM initiative that actually benefits from the recently established interoperability.
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- Roels, Juliette, et al.
(author)
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Aging of preleukemic thymocytes drives CpG island hypermethylation in T-cell acute lymphoblastic leukemia
- 2020
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In: Blood cancer discovery. - : American Association for Cancer Research. - 2643-3249. ; 1:3, s. 274-289
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Journal article (peer-reviewed)abstract
- Cancer cells display DNA hypermethylation at specific CpG islands in comparison to their normal healthy counterparts, but the mechanism that drives this so-called CpG island methylator phenotype (CIMP) remains poorly understood. Here, we show that CpG island methylation in human T-cell acute lymphoblastic leukemia (T-ALL) mainly occurs at promoters of Polycomb Repressor Complex 2 (PRC2) target genes that are not expressed in normal or malignant T-cells and which display a reciprocal association with H3K27me3 binding. In addition, we revealed that this aberrant methylation profile reflects the epigenetic history of T-ALL and is established already in pre-leukemic, self-renewing thymocytes that precede T-ALL development. Finally, we unexpectedly uncover that this age-related CpG island hypermethylation signature in T-ALL is completely resistant to the FDA-approved hypomethylating agent Decitabine. Altogether, we here provide conceptual evidence for the involvement of a pre-leukemic phase characterized by self-renewing thymocytes in the pathogenesis of human T-ALL.
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- Marzolla, M., et al.
(author)
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Open standards-based interoperability of job submission and management interfaces across the grid middleware platforms gLite and UNICORE
- 2007
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In: Proceedings - e-Science 2007, 3rd IEEE International Conference on e-Science and Grid Computing. - : IEEE Computer Society. - 0769530648 - 9780769530642 ; , s. 592-599
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Conference paper (peer-reviewed)abstract
- In a distributed Grid environment with ambitious service demands the job submission and management interfaces provide functionality of major importance. Emerging e-Science and Grid infrastructures such as EGEE and DEISA rely on highly available services that are capable of managing scientific jobs. It is the adoption of emerging open standard interfaces which allows the distribution of Grid resources in such a way that their actual service implementation or Grid technologies are not isolated from each other, especially when these resources are deployed in different e-Science infrastructures that consist of different types of computational resources. This paper motivates the interoperability of these infrastructures and discusses solutions. We describe the adoption of various open standards that recently emerged from the Open Grid Forum (OGF) in the field of job submission and management by well-known Grid technologies, respectively gLite and UNICORE. This has a fundamental impact on the interoperability between these technologies and thus within the next generation e-Science infrastructures that rely on these technologies.
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