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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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- Smith, Jennifer A, et al.
(författare)
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Genome-wide association study identifies 74 loci associated with educational attainment
- 2016
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Ingår i: Nature (London). - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 533:7604, s. 539-542
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.
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- Wyckelsma, VL, et al.
(författare)
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Vitamin C and E Treatment Blunts Sprint Interval Training-Induced Changes in Inflammatory Mediator-, Calcium-, and Mitochondria-Related Signaling in Recreationally Active Elderly Humans
- 2020
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Ingår i: Antioxidants (Basel, Switzerland). - : MDPI AG. - 2076-3921. ; 9:9
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Tidskriftsartikel (refereegranskat)abstract
- Sprint interval training (SIT) has emerged as a time-efficient training regimen for young individuals. Here, we studied whether SIT is effective also in elderly individuals and whether the training response was affected by treatment with the antioxidants vitamin C and E. Recreationally active elderly (mean age 65) men received either vitamin C (1 g/day) and vitamin E (235 mg/day) or placebo. Training consisted of nine SIT sessions (three sessions/week for three weeks of 4-6 repetitions of 30-s all-out cycling sprints) interposed by 4 min rest. Vastus lateralis muscle biopsies were taken before, 1 h after, and 24 h after the first and last SIT sessions. At the end of the three weeks of training, SIT-induced changes in relative mRNA expression of reactive oxygen/nitrogen species (ROS)- and mitochondria-related proteins, inflammatory mediators, and the sarcoplasmic reticulum Ca2+ channel, the ryanodine receptor 1 (RyR1), were blunted in the vitamin treated group. Western blots frequently showed a major (>50%) decrease in the full-length expression of RyR1 24 h after SIT sessions; in the trained state, vitamin treatment seemed to provide protection against this severe RyR1 modification. Power at exhaustion during an incremental cycling test was increased by ~5% at the end of the training period, whereas maximal oxygen uptake remained unchanged; vitamin treatment did not affect these measures. In conclusion, treatment with the antioxidants vitamin C and E blunts SIT-induced cellular signaling in skeletal muscle of elderly individuals, while the present training regimen was too short or too intense for the changes in signaling to be translated into a clear-cut change in physical performance.
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- Carlsen, Hanne Krage, et al.
(författare)
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Indicators of residential traffic exposure: Modelled NOX, traffic proximity, and self-reported exposure in RHINE III
- 2017
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 167, s. 416-425
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Tidskriftsartikel (refereegranskat)abstract
- Few studies have investigated associations between self-reported and modelled exposure to traffic pollution. The objective of this study was to examine correlations between self-reported traffic exposure and modelled (a) NOX and (b) traffic proximity in seven different northern European cities; Aarhus (Denmark), Bergen (Norway), Gothenburg, Umeå, and Uppsala (Sweden), Reykjavik (Iceland), and Tartu (Estonia). We analysed data from the RHINE III (Respiratory Health in Northern Europe, www.rhine.nu) cohorts of the seven study cities. Traffic proximity (distance to the nearest road with >10,000 vehicles per day) was calculated and vehicle exhaust (NOX) was modelled using dispersion models and land-use regression (LUR) data from 2011. Participants were asked a question about self-reported traffic intensity near bedroom window and another about traffic noise exposure at the residence. The data were analysed using rank correlation (Kendall's tau) and inter-rater agreement (Cohen's Kappa) between tertiles of modelled NOX and traffic proximity tertile and traffic proximity categories (0–150 metres (m), 150–200 m, >300 m) in each centre. Data on variables of interest were available for 50–99% of study participants per each cohort. Mean modelled NOX levels were between 6.5 and 16.0 μg/m3; median traffic intensity was between 303 and 10,750 m in each centre. In each centre, 7.7–18.7% of respondents reported exposure to high traffic intensity and 3.6–16.3% of respondents reported high exposure to traffic noise. Self-reported residential traffic exposure had low or no correlation with modelled exposure and traffic proximity in all centres, although results were statistically significant (tau = 0.057–0.305). Self-reported residential traffic noise correlated weakly (tau = 0.090–0.255), with modelled exposure in all centres except Reykjavik. Modelled NOX had the highest correlations between self-reported and modelled traffic exposure in five of seven centres, traffic noise exposure had the highest correlation with traffic proximity in tertiles in three centres. Self-reported exposure to high traffic intensity and traffic noise at each participant's residence had low or weak although statistically significant correlations with modelled vehicle exhaust pollution levels and traffic proximity. © 2017
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