Éditeur(s) : HAL CCSD Landes Bioscience
Résumé : International audience
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.
Autophagy

hal-00735751
https://hal.archives-ouvertes.fr/hal-00735751
PUBMED : 22966490

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The ∼55 km-long Firouzkuh fault is located in the Central Alborz Mountains of Iran. It is a left-lateral fault, which dips to the south, and possesses a small dip-slip component of motion that we interpret to result from extension. The ratio of horizontal to vertical displacement across the fault, calculated from the cumulative displacement of landscape features, is 7.6. We provide constraints on the timing of the last earthquake on the Firouzkuh fault from two trenches (T1 and T2) across the fault zone, excavated in 2004, and located east of Firouzkuh city. The trenches expose faulted sedimentary deposits. Two optically-stimulated luminescence (OSL) ages from sediments in the lower part of trench T1 date from the late Pleistocene (15.9 ± 0.9 ka and 27.1 ± 1.7 ka). The younger of the two dated units in T1 is displaced vertically across the fault by 2.2–4.4 m, from which we estimate a strike-slip displacement of 18.2–33.4 m, and hence a average horizontal slip-rate of 1.1–2.2 mm/yr. The sediments exposed in T1 do not yield constraints on the most recent earthquake history. In trench T2, however, human skeletal remains of a middle aged male, which yield a radiocarbon age of 1159 ± 28 BP (corresponding to a mean calendar age of 791 AD), were found within a faulted alluvial layer at a depth of 60–70 cm from the surface. The existence of these medieval human places shows that a surface-rupturing earthquake occurred at some time after 1159 ± 28 BP. The amount of slip in each earthquake on the Firouzkuh fault is difficult to estimate, but assuming the entire ∼55 km fault length ruptures in each event, they will have had a maximum magnitude of 7.1. At our estimated late Quaternary slip-rate of ∼1.1–2.2 mm/yr magnitude 7.1 earthquakes, involving ∼1.2 m average displacement, would be expected to occur every ∼1100–540 years. As the last earthquake on the Firouzkuh fault may be up to ∼700 years in age we suggest that the Firouzkuh fault is a major hazard for earthquakes in the near future.
ISSN: 0743-9547

hal-01122835
https://hal.archives-ouvertes.fr/hal-01122835
DOI : 10.1016/j.jseaes.2013.12.018