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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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| 3. |
- Estes, James A., et al.
(författare)
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Trophic Downgrading of Planet Earth
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 333:6040, s. 301-306
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Forskningsöversikt (refereegranskat)abstract
- Until recently, large apex consumers were ubiquitous across the globe and had been for millions of years. The loss of these animals may be humankind's most pervasive influence on nature. Although such losses are widely viewed as an ethical and aesthetic problem, recent research reveals extensive cascading effects of their disappearance in marine, terrestrial, and freshwater ecosystems worldwide. This empirical work supports long-standing theory about the role of top-down forcing in ecosystems but also highlights the unanticipated impacts of trophic cascades on processes as diverse as the dynamics of disease, wildfire, carbon sequestration, invasive species, and biogeochemical cycles. These findings emphasize the urgent need for interdisciplinary research to forecast the effects of trophic downgrading on process, function, and resilience in global ecosystems.
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| 8. |
- Rae, Dale E, et al.
(författare)
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Skeletal muscle telomere length in healthy, experienced, endurance runners.
- 2010
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Ingår i: European journal of applied physiology. - : Springer Science and Business Media LLC. - 1439-6327 .- 1439-6319. ; 109:2, s. 323-330
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Tidskriftsartikel (refereegranskat)abstract
- Measuring the DNA telomere length of skeletal muscle in experienced endurance runners may contribute to our understanding of the effects of chronic exposure to endurance exercise on skeletal muscle. This study compared the minimum terminal restriction fragment (TRF) length in the vastus lateralis muscle of 18 experienced endurance runners (mean age: 42 +/- 7 years) to those of 19 sedentary individuals (mean age: 39 +/- 10 years). The runners had covered almost 50,000 km in training and racing over 15 years. Minimum TRF lengths measured in the muscle of both groups were similar (P = 0.805) and within the normal range. Minimum TRF length in the runners, however, was inversely related to their years spent running (r = -0.63, P = 0.007) and hours spent training (r = -0.52, P = 0.035). Therefore, since exposure to endurance running may influence minimum TRF length, and by implication, the proliferative potential of the satellite cells, chronic endurance running may be seen as a stressor to skeletal muscle.
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| 11. |
- Suh, J., et al.
(författare)
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Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection
- 2014
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Methods: Antiretroviral-naive subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD) 4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. Results: A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P < 0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P < 0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Conclusions: Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.
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| 12. |
- Cederbom, Charlotte E., et al.
(författare)
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Rapid extensive erosion of the North Alpine foreland basin at 5-4 Ma
- 2011
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Ingår i: Basin Research. - : Blackwell Publishing. - 0950-091X .- 1365-2117. ; 23:5, s. 528-550
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Tidskriftsartikel (refereegranskat)abstract
- An extensive low-temperature thermochronology study of the Swiss part of the North Alpine Foreland Basin has been conducted with the aim of deciphering the late Neogene basin development. Apatite fission-track (AFT) ages from wells located in the distal and weakly deformed Plateau Molasse reveal rapid, km-scale erosion with an onset in early Pliocene times. The distribution of erosion implies that there was a strong gradient in late Miocene deposition rates along the strike of the basin, with an increase towards the northeast. Additionally, renewed tectonic activity and km-scale out-of-sequence thrusting during Plio-Pleistocene times is indicated by AFT data from wells within the thrusted, proximal Subalpine Molasse. Several different mechanisms driving late Neogene basin erosion and accelerated erosional discharge from the European Alps have been considered in the literature. Based on our AFT results, we reevaluate previously published hypotheses, and suggest that a change in climate and/or drainage reorganisation coincided and possibly interacted with preexisting tectonic and geodynamic forces in the Alpine region.
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