| 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. |
- Currie, Thayne, et al.
(författare)
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RECOVERY OF THE CANDIDATE PROTOPLANET HD 100546 b WITH GEMINI/NICI AND DETECTION OF ADDITIONAL (PLANET-INDUCED ?) DISK STRUCTURE AT SMALL SEPARATIONS
- 2014
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Ingår i: Astrophysical Journal Letters. - 2041-8205 .- 2041-8213. ; 796:2, s. L30-
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Tidskriftsartikel (refereegranskat)abstract
- We report the first independent, second epoch (re-) detection of a directly imaged protoplanet candidate. Using L' high-contrast imaging of HD 100546 taken with the Near-Infrared Coronagraph and Imager on Gemini South, we recover HD 100546 b with a position and brightness consistent with the original Very Large Telescope/NAos-COnica detection from Quanz et al., although data obtained after 2013 will be required to decisively demonstrate common proper motion. HD 100546 b may be spatially resolved, up to approximate to 12-13 AU in diameter, and is embedded in a finger of thermal IR-bright, polarized emission extending inward to at least 0 ''.3. Standard hot-start models imply a mass of approximate to 15 M-J. However, if HD 100546 b is newly formed or made visible by a circumplanetary disk, both of which are plausible, its mass is significantly lower (e.g., 1-7 M-J). Additionally, we discover a thermal IR-bright disk feature, possibly a spiral density wave, at roughly the same angular separation as HD 100546 b but 90 degrees. away. Our interpretation of this feature as a spiral arm is not decisive, but modeling analyses using spiral density wave theory implies a wave launching point exterior to approximate to 0 ''.45 embedded within the visible disk structure: plausibly evidence for a second, hitherto unseen, wide-separation planet. With one confirmed protoplanet candidate and evidence for one to two others, HD 100546 is an important evolutionary precursor to intermediate-mass stars with multiple super-Jovian planets at moderate/wide separations like HR 8799.
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| 3. |
- Ravasi, Timothy, et al.
(författare)
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An Atlas of Combinatorial Transcriptional Regulation in Mouse and Man
- 2010
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Ingår i: CELL. - : Elsevier BV. - 0092-8674 .- 1097-4172. ; 140:5, s. 744-752
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Tidskriftsartikel (refereegranskat)abstract
- Combinatorial interactions among transcription factors are critical to directing tissue-specific gene expression. To build a global atlas of these combinations, we have screened for physical interactions among the majority of human and mouse DNA-binding transcription factors (TFs). The complete networks contain 762 human and 877 mouse interactions. Analysis of the networks reveals that highly connected TFs are broadly expressed across tissues, and that roughly half of the measured interactions are conserved between mouse and human. The data highlight the importance of TF combinations for determining cell fate, and they lead to the identification of a SMAD3/FLI1 complex expressed during development of immunity. The availability of large TF combinatorial networks in both human and mouse will provide many opportunities to study gene regulation, tissue differentiation, and mammalian evolution.
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