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- Aad, G., et al.
(författare)
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- 2011
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swepub:Mat__t (refereegranskat)
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| 2. |
- 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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| 5. |
- Abramowski, A., et al.
(författare)
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Constraints on the gamma-ray emission from the cluster-scale AGN outburst in the Hydra A galaxy cluster
- 2012
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 545, s. A103-
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Tidskriftsartikel (refereegranskat)abstract
- Context. In some galaxy clusters, powerful active galactic nuclei (AGN) have blown bubbles with cluster scale extent into the ambient medium. The main pressure support of these bubbles is not known to date, but cosmic rays are a viable possibility. For such a scenario copious gamma-ray emission is expected as a tracer of cosmic rays from these systems. Aims. Hydra A, the closest galaxy cluster hosting a cluster scale AGN outburst, located at a redshift of 0.0538, is investigated for being a gamma-ray emitter with the High Energy Stereoscopic System (H.E.S.S.) array and the Fermi Large Area Telescope (Fermi-LAT). Methods. Data obtained in 20.2 h of dedicated H. E. S. S. observations and 38 months of Fermi-LAT data, gathered by its usual all-sky scanning mode, have been analyzed to search for a gamma-ray signal. Results. No signal has been found in either data set. Upper limits on the gamma-ray flux are derived and are compared to models. These are the first limits on gamma-ray emission ever presented for galaxy clusters hosting cluster scale AGN outbursts. Conclusions. The non-detection of Hydra A in gamma-rays has important implications on the particle populations and physical conditions inside the bubbles in this system. For the case of bubbles mainly supported by hadronic cosmic rays, the most favorable scenario, which involves full mixing between cosmic rays and embedding medium, can be excluded. However, hadronic cosmic rays still remain a viable pressure support agent to sustain the bubbles against the thermal pressure of the ambient medium. The largest population of highly-energetic electrons, which are relevant for inverse-Compton gamma-ray production is found in the youngest inner lobes of Hydra A. The limit on the inverse-Compton gamma-ray flux excludes a magnetic field below half of the equipartition value of 16 mu G in the inner lobes.
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| 10. |
- Horikoshi, Momoko, et al.
(författare)
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:1
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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