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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. |
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| 3. |
- Arsava, E. M., et al.
(författare)
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The Causative Classification of Stroke system An international reliability and optimization study
- 2010
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Ingår i: Neurology. - 1526-632X. ; 75:14, s. 1277-1284
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Tidskriftsartikel (refereegranskat)abstract
- Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results: The kappa value for causative classification was 0.80 (95% confidence interval [ CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: kappa = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The kappa value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. Conclusions: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras. Neurology (R) 2010;75:1277-1284
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| 5. |
- Ognissanto, F, et al.
(författare)
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The elastic He-3+d cross section of relevance for knock-on effects in radio frequency heated (He-3)D plasmas
- 2011
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Ingår i: Nuclear Instruments and Methods in Physics Research Section B. - : Elsevier BV. - 0168-583X .- 1872-9584. ; 269:8, s. 786-792
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Tidskriftsartikel (refereegranskat)abstract
- The cross section for d+He-3 elastic scattering has been determined for the angular range 20-180 degrees (CM) for beam energies E-d = 0.05 to 11 MeV through combined use of experimental data, Coulomb scattering and extrapolations. The results are used to study, for instance, how the cross section is affected by nuclear interaction contributions. Implications of these results on the calculation of knock on effects in (He-3)D plasmas subjected to RF heating and their manifestations in the spectrum of the d + d fusion neutron emission are discussed.
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| 6. |
- Chavan, Swapnil, et al.
(författare)
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Towards Global QSAR Model Building for Acute Toxicity : Munro Database Case Study
- 2014
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 15:10, s. 18162-18174
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Tidskriftsartikel (refereegranskat)abstract
- A series of 436 Munro database chemicals were studied with respect to their corresponding experimental LD50 values to investigate the possibility of establishing a global QSAR model for acute toxicity. Dragon molecular descriptors were used for the QSAR model development and genetic algorithms were used to select descriptors better correlated with toxicity data. Toxic values were discretized in a qualitative class on the basis of the Globally Harmonized Scheme: the 436 chemicals were divided into 3 classes based on their experimental LD50 values: highly toxic, intermediate toxic and low to non-toxic. The k-nearest neighbor (k-NN) classification method was calibrated on 25 molecular descriptors and gave a non-error rate (NER) equal to 0.66 and 0.57 for internal and external prediction sets, respectively. Even if the classification performances are not optimal, the subsequent analysis of the selected descriptors and their relationship with toxicity levels constitute a step towards the development of a global QSAR model for acute toxicity.
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| 7. |
- Hellesen, Carl, 1980-, et al.
(författare)
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Neutron spectroscopy measurements and modeling of neutral beam heating fast ion dynamics
- 2010
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Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 52:8, s. 085013-
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Tidskriftsartikel (refereegranskat)abstract
- The energy spectrum of the neutron emission from beam-target reactions in fusion plasmas at the Joint European Torus (JET) has been investigated. Different beam energies as well as injection angles were used. Both measurements and simulations of the energy spectrum were done. The measurements were made with the time-of-flight spectrometer TOFOR. Simulations of the neutron spectrum were based on first-principle calculations of neutral beam deposition profiles and the fast ion slowing down in the plasma using the code NUBEAM, which is a module of the TRANSP package. The shape of the neutron energy spectrum was seen to vary significantly depending on the energy of the beams as well as the injection angle and the deposition profile in the plasma. Cross validations of the measured and modeled neutron energy spectra were made, showing a good agreement for all investigated scenarios.
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