| 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. |
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| 3. |
- Mandenius, Carl-Fredrik, et al.
(författare)
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Toward Preclinical Predictive Drug Testing for Metabolism and Hepatotoxicity by Using In Vitro Models Derived from Human Embryonic Stem Cells and Human Cell Lines - A Report on the Vitrocellomics EU-project
- 2011
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Ingår i: ATLA-ALTERNATIVES TO LABORATORY ANIMALS. - : Fund for Replacement of Animals in Medical Experiments; 1999. - 0261-1929 .- 2632-3559. ; 39:2, s. 147-171
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Tidskriftsartikel (refereegranskat)abstract
- Drug-induced liver injury is a common reason for drug attrition in late clinical phases, and even for post-launch withdrawals. As a consequence, there is a broad consensus in the pharmaceutical industry, and within regulatory authorities, that a significant improvement of the current in vitro test methodologies for accurate assessment and prediction of such adverse effects is needed. For this purpose, appropriate in vivo-like hepatic in vitro models are necessary, in addition to novel sources of human hepatocytes. In this report, we describe recent and ongoing research toward the use of human embryonic stem cell (hESC)-derived hepatic cells, in conjunction with new and improved test methods, for evaluating drug metabolism and hepatotoxicity. Recent progress on the directed differentiation of human embryonic stem cells to the functional hepatic phenotype is reported, as well as the development and adaptation of bioreactors and toxicity assay technologies for the testing of hepatic cells. The aim of achieving a testing platform for metabolism and hepatotoxicity assessment, based on hESC-derived hepatic cells, has advanced markedly in the last 2-3 years. However, great challenges still remain, before such new test systems could be routinely used by the industry. In particular, we give an overview of results from the Vitrocellomics project (EU Framework 6) and discuss these in relation to the current state-of-the-art and the remaining difficulties, with suggestions on how to proceed before such in vitro systems can be implemented in industrial discovery and development settings and in regulatory acceptance.
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| 4. |
- Mueller-Wohlfahrt, H. W., et al.
(författare)
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Terminology and classification of muscle injuries in sport: The Munich consensus statement
- 2013
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To provide a clear terminology and classification of muscle injuries in order to facilitate Methods Thirty native English-speaking scientists and team doctors of national and first division Results The response rate of the survey was 63%. The responses confirmed the marked variability in Conclusions A consistent English terminology as well as a comprehensive classification system for What are the new things Consensus definitions of the terminology which is used in the field of muscle
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| 5. |
- Sakamoto, Kazuyuki, et al.
(författare)
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Valley spin polarization by using the extraordinary Rashba effect on silicon
- 2013
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Ingår i: Nature Communications. - : Nature Publishing Group: Nature Communications. - 2041-1723. ; 4:2073
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Tidskriftsartikel (refereegranskat)abstract
- The addition of the valley degree of freedom to a two-dimensional spin-polarized electronic system provides the opportunity to multiply the functionality of next-generation devices. So far, however, such devices have not been realized due to the difficulty to polarize the valleys, which is an indispensable step to activate this degree of freedom. Here we show the formation of 100% spin-polarized valleys by a simple and easy way using the Rashba effect on a system with C-3 symmetry. This polarization, which is much higher than those in ordinary Rashba systems, results in the valleys acting as filters that can suppress the backscattering of spin-charge. The present system is formed on a silicon substrate, and therefore opens a new avenue towards the realization of silicon spintronic devices with high efficiency.
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