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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Research review (peer-reviewed)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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- Kim, Ji-Hoon, et al.
(author)
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A Pulse of Meteoric Subsurface Fluid Discharging Into the Chukchi Sea During the Early Holocene Thermal Maximum (EHTM)
- 2021
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In: Geochemistry Geophysics Geosystems. - 1525-2027. ; 22:8
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Journal article (peer-reviewed)abstract
- The response of Arctic Ocean biogeochemistry to subsurface flow driven by permafrost thaw is poorly understood. We present dissolved chloride and water isotopic data from the Chukchi Sea Shelf sediments that reveal the presence of a meteoric subsurface flow enriched in cations with a radiogenic Sr fingerprint. This subsurface fluid is also enriched in dissolved inorganic carbon and methane that bear isotopic compositions indicative of a carbon reservoir modified by reactions in a closed system. Such fluid characteristics are in stark contrast with those from other sites in the Chukchi Sea where the pore water composition shows no sign of meteoric input, but reflect typical biogeochemical reactions associated with early diagenetic sequences in marine sediment. The most likely source of the observed subsurface flow at the Chukchi Sea Shelf is from the degradation of permafrost that had extended to the shelf region during the Last Glacial Maximum. Our data suggest that the permafrost-driven subsurface flow most likely took place during the 2-3 degrees C warming in the Early Holocene Thermal Maximum. This time scale is supported by numerical simulation of pore water profiles, which indicate that a minimum of several thousand years must have passed since the cessation of the subsurface methane-bearing fluid flow.
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- Kariippanon, Katharina E., et al.
(author)
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Levels and Correlates of Objectively Measured Sedentary Behavior in Young Children : SUNRISE Study Results from 19 Countries
- 2022
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In: Medicine & Science in Sports & Exercise. - : Lippincott, Williams & Wilkins. - 0195-9131 .- 1530-0315. ; 54:7, s. 1123-1130
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Journal article (peer-reviewed)abstract
- Purpose There is a paucity of global data on sedentary behavior during early childhood. The purpose of this study was to examine how device-measured sedentary behavior in young children differed across geographically, economically, and sociodemographically diverse populations, in an international sample. Methods This multinational, cross-sectional study included data from 1071 children 3-5 yr old from 19 countries, collected between 2018 and 2020 (pre-COVID). Sedentary behavior was measured for three consecutive days using activPAL accelerometers. Sedentary time, sedentary fragmentation, and seated transport duration were calculated. Linear mixed models were used to examine the differences in sedentary behavior variables between sex, country-level income groups, urban/rural settings, and population density. Results Children spent 56% (7.4 h) of their waking time sedentary. The longest average bout duration was 81.1 +/- 45.4 min, and an average of 61.1 +/- 50.1 min center dot d(-1) was spent in seated transport. Children from upper-middle-income and high-income countries spent a greater proportion of the day sedentary, accrued more sedentary bouts, had shorter breaks between sedentary bouts, and spent significantly more time in seated transport, compared with children from low-income and lower-middle-income countries. Sex and urban/rural residential setting were not associated with any outcomes. Higher population density was associated with several higher sedentary behavior measures. Conclusions These data advance our understanding of young childrens sedentary behavior patterns globally. Country income levels and population density appear to be stronger drivers of the observed differences, than sex or rural/urban residential setting.
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- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)abstract
- We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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- Okely, Anthony D., et al.
(author)
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Cross-sectional examination of 24-hour movement behaviours among 3-and 4-year-old children in urban and rural settings in low-income, middle-income and high-income countries : the SUNRISE study protocol
- 2021
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In: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:10
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Journal article (peer-reviewed)abstract
- Introduction 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap. Methods and analysis SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study. Ethics and dissemination The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.
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