| 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. |
- Eriksson, Olivia, PhD, 1971-, et al.
(författare)
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Combining hypothesis- and data-driven neuroscience modeling in FAIR workflows
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications, Ltd. - 2050-084X. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Modeling in neuroscience occurs at the intersection of different points of view and approaches. Typically, hypothesis-driven modeling brings a question into focus so that a model is constructed to investigate a specific hypothesis about how the system works or why certain phenomena are observed. Data-driven modeling, on the other hand, follows a more unbiased approach, with model construction informed by the computationally intensive use of data. At the same time, researchers employ models at different biological scales and at different levels of abstraction. Combining these models while validating them against experimental data increases understanding of the multiscale brain. However, a lack of interoperability, transparency, and reusability of both models and the workflows used to construct them creates barriers for the integration of models representing different biological scales and built using different modeling philosophies. We argue that the same imperatives that drive resources and policy for data - such as the FAIR (Findable, Accessible, Interoperable, Reusable) principles - also support the integration of different modeling approaches. The FAIR principles require that data be shared in formats that are Findable, Accessible, Interoperable, and Reusable. Applying these principles to models and modeling workflows, as well as the data used to constrain and validate them, would allow researchers to find, reuse, question, validate, and extend published models, regardless of whether they are implemented phenomenologically or mechanistically, as a few equations or as a multiscale, hierarchical system. To illustrate these ideas, we use a classical synaptic plasticity model, the Bienenstock-Cooper-Munro rule, as an example due to its long history, different levels of abstraction, and implementation at many scales.
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| 3. |
- Fossati, L., et al.
(författare)
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The chemical abundance analysis of normal early A- and late B-type stars
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 503:3, s. 945-962
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Forskningsöversikt (refereegranskat)abstract
- Context. Modern spectroscopy of early-type stars often aims at studying complex physical phenomena such as stellar pulsation, the peculiarity of the composition of the photosphere, chemical stratification, the presence of a magnetic field, and its interplay with the stellar atmosphere and the circumstellar environment. Comparatively less attention is paid to identifying and studying the "normal" A- and B-type stars and testing how the basic atomic parameters and standard spectral analysis allow one to fit the observations. By contrast, this kind of study is paramount for eventually allowing one to correctly quantify the impact of the various physical processes that occur inside the atmospheres of A- and B-type stars. Aims. We wish to establish whether the chemical composition of the solar photosphere can be regarded as a reference for early A- and B-late B-type stars. Methods. We have obtained optical high-resolution, high signal-to-noise ratio spectra of three slowly rotating early-type stars (HD 145788, 21 Peg and pi Cet) that show no obvious sign of chemical peculiarity, and performed a very accurate LTE abundance analysis of up to 38 ions of 26 elements (for 21 Peg), using a vast amount of spectral lines visible in the spectral region covered by our spectra. Results. We provide an exhaustive description of the abundance characteristics of the three analysed stars with a critical review of the line parameters used to derive the abundances. We compiled a table of atomic data for more than 1100 measured lines that may be used in the future as a reference. The abundances we obtained for He, C, Al, S, V, Cr, Mn, Fe, Ni, Sr, Y, and Zr are compatible with the solar ones derived with recent 3D radiative-hydrodynamical simulations of the solar photosphere. The abundances of the remaining studied elements show some degree of discrepancy compared to the solar photosphere. Those of N, Na, Mg, Si, Ca, Ti, and Nd may well be ascribed to non-LTE effects; for P, Cl, Sc and Co, non-LTE effects are totally unknown; O, Ne, Ar, and Ba show discrepancies that cannot be ascribed to non-LTE effects. The discrepancies obtained for O (in two stars) and Ne agree with very recent non-LTE abundance analysis of early B-type stars in the solar neighbourhood.
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