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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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- Meyer, H., et al.
(författare)
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Overview of physics results from MAST
- 2009
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 49:10, s. 104017-
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Tidskriftsartikel (refereegranskat)abstract
- Several improvements to the MAST plant and diagnostics have facilitated new studies advancing the physics basis for ITER and DEMO, as well as for future spherical tokamaks (STs). Using the increased heating capabilities P-NBI <= 3.8 MW H-mode at I-P = 1.2 MA was accessed showing that the energy confinement on MAST scales more weakly with I-P and more strongly with B-t than in the ITER IPB98(y, 2) scaling. Measurements of the fuel retention of shallow pellets extrapolate to an ITER particle throughput of 70% of its original designed total throughput capacity. The anomalous momentum diffusion, chi(phi), is linked to the ion diffusion, chi(i), with a Prandtl number close to P-phi approximate to chi(phi)/chi(i) approximate to 1, although chi(i) approaches neoclassical values. New high spatial resolution measurements of the edge radial electric field, E-r, show that the position of steepest gradients in electron pressure and E-r (i.e. shearing rate) are coincident, but their magnitudes are not linked. The T-e pedestal width on MAST scales with root beta(ped)(pol) rather than rho(pol). The edge localized mode (ELM) frequency for type-IV ELMs, new in MAST, was almost doubled using n = 2 resonant magnetic perturbations from a set of four external coils (n = 1, 2). A new internal 12 coil set (n <= 3) has been commissioned. The filaments in the inter-ELM and L-mode phase are different from ELM filaments, and the characteristics in L-mode agree well with turbulence calculations. A variety of fast particle driven instabilities were studied from 10 kHz saturated fishbone like activity up to 3.8 MHz compressional Alfven eigenmodes. Fast particle instabilities also affect the off-axis NBI current drive, leading to fast ion diffusion of the order of 0.5 m(2) s(-1) and a reduction in the driven current fraction from 40% to 30%. EBW current drive start-up is demonstrated for the first time in a ST generating plasma currents up to 55 kA. Many of these studies contributed to the physics basis of a planned upgrade to MAST.
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- Lissek, T, et al.
(författare)
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Building Bridges through Science
- 2017
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Ingår i: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 96:4, s. 730-735
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Lloyd, B., et al.
(författare)
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Overview of physics results from MAST
- 2007
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Ingår i: Nuclear Fusion. - 0029-5515 .- 1741-4326. ; 47:10, s. S658-S667
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Tidskriftsartikel (refereegranskat)abstract
- Substantial advances have been made on the Mega AmpÚre Spherical Tokamak (MAST). The parameter range of the MAST confinement database has been extended and it now also includes pellet-fuelled discharges. Good pellet retention has been observed in H-mode discharges without triggering an ELM or an H/L transition during peripheral ablation of low speed pellets. Co-ordinated studies on MAST and DIII-D demonstrate a strong link between the aspect ratio and the beta scaling of H-mode energy confinement, consistent with that obtained when MAST data were merged with a subset of the ITPA database. Electron and ion ITBs are readily formed and their evolution has been investigated. Electron and ion thermal diffusivities have been reduced to values close to the ion neoclassical level. Error field correction coils have been used to determine the locked mode threshold scaling which is comparable to that in conventional aspect ratio tokamaks. The impact of plasma rotation on sawteeth has been investigated and the results have been well-modelled using the MISHKA-F code. Alfvén cascades have been observed in discharges with reversed magnetic shear. Measurements during off-axis NBCD and heating are consistent with classical fast ion modelling and indicate efficient heating and significant driven current. Central electron Bernstein wave heating has been observed via the O-X-B mode conversion process in special magnetically compressed plasmas. Plasmas with low pedestal collisionality have been established and further insight has been gained into the characteristics of filamentary structures at the plasma edge. Complex behaviour of the divertor power loading during plasma disruptions has been revealed by high resolution infra-red measurements.
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| 7. |
- Almeida, R. P., et al.
(författare)
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Effect of Cognitive Reserve on Age-Related Changes in Cerebrospinal Fluid Biomarkers of Alzheimer Disease
- 2015
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149. ; 72:6, s. 699-706
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Although advancing age is the strongest risk factor for the development of symptomatic Alzheimer disease (AD), recent studies have shown that there are individual differences in susceptibility to age-related alterations in the biomarkers of AD pathophysiology. OBJECTIVE To investigate whether cognitive reserve (CR) modifies the adverse influence of age on key cerebrospinal fluid (CSF) biomarkers of AD. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional cohort of 268 individuals (211 in a cognitively normal group and 57 in a cognitively impaired group) from the Wisconsin Registry for Alzheimer's Prevention and the Wisconsin Alzheimer's Disease Research Center participated in this study. They underwent lumbar puncture for collection of CSF samples, from which A beta 42, total tau (t-tau), and phosphorylated tau (p-tau) were immunoassayed. In addition, we computed t-tau/A beta 42 and p-tau/A beta 42 ratios. Cognitive reserve was indexed by years of education, with 16 or more years taken to confer high reserve. Covariate-adjusted regression analyses were used to test whether the effect of age on CSF biomarkers was modified by CR. The study dates were March 5, 2010, to February 13, 2013. MAIN OUTCOMES AND MEASURES Cerebrospinal fluid levels of A beta 42, t-tau, p-tau, t-tau/A beta 42, and p-tau/A beta 42. RESULTS There were significant age x CR interactions for CSF t-tau (beta [SE] = -6.72 [2.84], P = .02), p-tau (beta [SE] = -0.71 [0.27], P = .01), t-tau/A beta 42 (beta [SE] = -0.02 [0.01], P = .02), and p-tau/A beta 42 (beta [SE] = -0.002 [0.001], P = .004). With advancing age, individuals with high CR exhibited attenuated adverse alterations in these CSF biomarkers compared with individuals with low CR. This attenuation of age effects by CR tended to be more pronounced in the cognitively impaired group compared with the cognitively normal group. There was evidence of a dose-response relationship such that the effect of age on the biomarkers was progressively attenuated given additional years of schooling. CONCLUSIONS AND RELEVANCE In a sample composed of a cognitively normal group and a cognitively impaired group, higher CR was associated with a diminution of age-related alterations in CSF biomarkers of AD. This suggests one pathway through which CR might favorably alter lifetime risk for symptomatic AD.
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