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| 3. |
- 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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- Dalton, A. S., et al.
(författare)
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An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex
- 2020
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 234
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Tidskriftsartikel (refereegranskat)abstract
- The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; 'Quaternary Glaciations - Extent and Chronology, Part II' [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km(2), which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world's largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval. (C) 2020 Elsevier Ltd. All rights reserved.
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- Menounos, B., et al.
(författare)
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Cordilleran Ice Sheet mass loss preceded climate reversals near the Pleistocene Termination
- 2017
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 358:6364, s. 781-784
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Tidskriftsartikel (refereegranskat)abstract
- The Cordilleran Ice Sheet (CIS) once covered an area comparable to that of Greenland. Previous geologic evidence and numerical models indicate that the ice sheet covered much of westernmost Canada as late as 12.5 thousand years ago (ka). New data indicate that substantial areas throughout westernmost Canada were ice free prior to 12.5 ka and some as early as 14.0 ka, with implications for climate dynamics and the timing of meltwater discharge to the Pacific and Arctic oceans. Early Bolling-Allerod warmth halved the mass of the CIS in as little as 500 years, causing 2.5 to 3.0 meters of sea-level rise. Dozens of cirque and valley glaciers, along with the southern margin of the CIS, advanced into recently deglaciated regions during the Bolling-Allerod and Younger Dryas.
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- Timmins, Iain R., et al.
(författare)
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International pooled analysis of leisure-time physical activity and premenopausal breast cancer in women from 19 cohorts
- 2024
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Ingår i: Journal of Clinical Oncology. - : American Society of Clinical Oncology. - 0732-183X .- 1527-7755. ; 42:8, s. 927-939
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: There is strong evidence that leisure-time physical activity is protective against postmenopausal breast cancer risk but the association with premenopausal breast cancer is less clear. The purpose of this study was to examine the association of physical activity with the risk of developing premenopausal breast cancer.METHODS: We pooled individual-level data on self-reported leisure-time physical activity across 19 cohort studies comprising 547,601 premenopausal women, with 10,231 incident cases of breast cancer. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% CIs for associations of leisure-time physical activity with breast cancer incidence. HRs for high versus low levels of activity were based on a comparison of risk at the 90th versus 10th percentiles of activity. We assessed the linearity of the relationship and examined subtype-specific associations and effect modification across strata of breast cancer risk factors, including adiposity.RESULTS: Over a median 11.5 years of follow-up (IQR, 8.0-16.1 years), high versus low levels of leisure-time physical activity were associated with a 6% (HR, 0.94 [95% CI, 0.89 to 0.99]) and a 10% (HR, 0.90 [95% CI, 0.85 to 0.95]) reduction in breast cancer risk, before and after adjustment for BMI, respectively. Tests of nonlinearity suggested an approximately linear relationship (Pnonlinearity = .94). The inverse association was particularly strong for human epidermal growth factor receptor 2-enriched breast cancer (HR, 0.57 [95% CI, 0.39 to 0.84]; Phet = .07). Associations did not vary significantly across strata of breast cancer risk factors, including subgroups of adiposity.CONCLUSION: This large, pooled analysis of cohort studies adds to evidence that engagement in higher levels of leisure-time physical activity may lead to reduced premenopausal breast cancer risk.
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| 7. |
- Selck, H., et al.
(författare)
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Assessing and managing multiple risks in a changing worldThe Roskilde recommendations
- 2017
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Ingår i: Environmental Toxicology and Chemistry. - Hoboken, NJ : Wiley. - 0730-7268 .- 1552-8618. ; 36:1, s. 7-16
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Tidskriftsartikel (refereegranskat)abstract
- Roskilde University (Denmark) hosted a November 2015 workshop, Environmental RiskAssessing and Managing Multiple Risks in a Changing World. This Focus article presents the consensus recommendations of 30 attendees from 9 countries regarding implementation of a common currency (ecosystem services) for holistic environmental risk assessment and management; improvements to risk assessment and management in a complex, human-modified, and changing world; appropriate development of protection goals in a 2-stage process; dealing with societal issues; risk-management information needs; conducting risk assessment of risk management; and development of adaptive and flexible regulatory systems. The authors encourage both cross-disciplinary and interdisciplinary approaches to address their 10 recommendations: 1) adopt ecosystem services as a common currency for risk assessment and management; 2) consider cumulative stressors (chemical and nonchemical) and determine which dominate to best manage and restore ecosystem services; 3) fully integrate risk managers and communities of interest into the risk-assessment process; 4) fully integrate risk assessors and communities of interest into the risk-management process; 5) consider socioeconomics and increased transparency in both risk assessment and risk management; 6) recognize the ethical rights of humans and ecosystems to an adequate level of protection; 7) determine relevant reference conditions and the proper ecological context for assessments in human-modified systems; 8) assess risks and benefits to humans and the ecosystem and consider unintended consequences of management actions; 9) avoid excessive conservatism or possible underprotection resulting from sole reliance on binary, numerical benchmarks; and 10) develop adaptive risk-management and regulatory goals based on ranges of uncertainty. Environ Toxicol Chem 2017;36:7-16. (c) 2016 SETAC
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| 8. |
- Von Holle, Ann, et al.
(författare)
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BMI and breast cancer risk around age at menopause
- 2024
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Ingår i: Cancer Epidemiology. - : Elsevier. - 1877-7821 .- 1877-783X. ; 89
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Tidskriftsartikel (refereegranskat)abstract
- Background: A high body mass index (BMI, kg/m2) is associated with decreased risk of breast cancer before menopause, but increased risk after menopause. Exactly when this reversal occurs in relation to menopause is unclear. Locating that change point could provide insight into the role of adiposity in breast cancer etiology.Methods: We examined the association between BMI and breast cancer risk in the Premenopausal Breast Cancer Collaborative Group, from age 45 up to breast cancer diagnosis, loss to follow-up, death, or age 55, whichever came first. Analyses included 609,880 women in 16 prospective studies, including 9956 who developed breast cancer before age 55. We fitted three BMI hazard ratio (HR) models over age-time: constant, linear, or nonlinear (via splines), applying piecewise exponential additive mixed models, with age as the primary time scale. We divided person-time into four strata: premenopause; postmenopause due to natural menopause; postmenopause because of interventional loss of ovarian function (bilateral oophorectomy (BO) or chemotherapy); postmenopause due to hysterectomy without BO. Sensitivity analyses included stratifying by BMI in young adulthood, or excluding women using menopausal hormone therapy.Results: The constant BMI HR model provided the best fit for all four menopausal status groups. Under this model, the estimated association between a five-unit increment in BMI and breast cancer risk was HR=0.87 (95% CI: 0.85, 0.89) before menopause, HR=1.00 (95% CI: 0.96, 1.04) after natural menopause, HR=0.99 (95% CI: 0.93, 1.05) after interventional loss of ovarian function, and HR=0.88 (95% CI: 0.76, 1.02) after hysterectomy without BO.Conclusion: The BMI breast cancer HRs remained less than or near one during the 45–55 year age range indicating that the transition to a positive association between BMI and risk occurs after age 55.
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| 9. |
- Dalton, April S., et al.
(författare)
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Deglaciation of the north American ice sheet complex in calendar years based on a comprehensive database of chronological data: NADI-1
- 2023
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Ingår i: QUATERNARY SCIENCE REVIEWS. - 0277-3791 .- 1873-457X. ; 321
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Tidskriftsartikel (refereegranskat)abstract
- The most recent deglaciation of the North American Ice Sheet Complex (NAISC: comprising the Innuitian, Cordilleran, and Laurentide ice sheets) offers a broad perspective from which to analyze the timing and rate of ice retreat, deglacial sea-level rise, and abrupt climate change events. Previous efforts to portray the retreat of the NAISC have been focused largely on minimum-limiting radiocarbon ages and ice margin location(s) tied to deglacial landforms that were not, for the most part, chronologically constrained. Here, we present the first version of North American Deglaciation Isochrones (NADI-1) spanning 25 to 1 ka in calendar years before present. Key new features of this work are (i) the incorporation of cosmogenic nuclide data, which offer a direct constraint on the timing of ice recession; (ii) presentation of all data and time-steps in calendar years; (iii) optimal, minimum, and maximum ice extents for each time-step that are designed to capture uncertainties in the ice margin position, and; (iv) extensive documentation and justification for the placement of each ice margin. Our data compilation includes 2229 measurements of Be-10, 459 measurements of Al-26 and 35 measurements of Cl-36 from a variety of settings, including boulders, bedrock surfaces, cobbles, pebbles, and sediments. We also updated a previous radiocarbon dataset (n = 4947), assembled luminescence ages (n = 397) and gathered uranium-series data (n = 2). After scrutiny of the geochronological dataset, we consider >90% of data to be reliable or likely reliable. Key findings include (i) a highly asynchronous maximum glacial extent in North America, occurring as early as 27 ka to as late as 17 ka, within and between ice sheets. In most marine realms, extension of the ice margin to the continental shelf break at 25 ka is somewhat speculative because it is based on undated and spatially scattered ice stream and geomorphic evidence; (ii) detachment of the Laurentide and Cordilleran ice sheets took place gradually via southerly and northerly 'unzipping' of the ice masses, starting at 17.5 ka and ending around 14 ka; (iii) the final deglaciation of Hudson Bay began at 8.5 ka, with the collapse completed by 8 ka. The maximum extent of ice during the last glaciation occurred at 22 ka and covered 15,470,000 km(2). All North American ice sheets merged at 22 ka for the first time in the Quaternary. The highly asynchronous Last Glacial Maximum in North America means that our isochrones (starting at 25 ka) capture ice advance across some areas, which is based on limited evidence and is therefore somewhat speculative. In the Supplementary Data, the complete NADI-1 chronology is available in PDF, GIF and shapefile format, together with additional visualizations and spreadsheets of geochronological data. The NADI-1 shapefiles are also available at https://doi.org/10.5281/zenodo.8161764.
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| 10. |
- Dalton, April S., et al.
(författare)
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The marine δ18O record overestimates continental ice volume during Marine Isotope Stage 3
- 2022
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Ingår i: Global and Planetary Change. - Amsterdam : Elsevier. - 0921-8181 .- 1872-6364. ; 212, s. 103814-103814
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Tidskriftsartikel (refereegranskat)abstract
- There is disagreement in the Quaternary research community in how much of the marine δ18O signal is driven by change in ice volume. Here, we examine this topic by bringing together empirical and modelling work for Marine Isotope Stage 3 (MIS 3; 57 ka to 29 ka), a time when the marine δ18O record indicates moderate continental glaciation and a global mean sea level between −60 m and −90 m. We compile and interpret geological data dating to MIS 3 to constrain the extent of major Northern Hemisphere ice sheets (Eurasian, Laurentide, Cordilleran). Many key data, especially published in the past ~15 years, argue for an ice-free core of the formerly glaciated regions that is inconsistent with inferences from the marine δ18O record. We compile results from prior studies of glacial isostatic adjustment to show the volume of ice inferred from the marine δ18O record is unable to fit within the plausible footprint of Northern Hemisphere ice sheets during MIS 3. Instead, a global mean sea level between −30 m and − 50 m is inferred from geological constraints and glacial isostatic modelling. Furthermore, limited North American ice volumes during MIS 3 are consistent with most sea-level bounds through that interval. We can find no concrete evidence of large-scale glaciation during MIS 3 that could account for the missing ~30 m of sea-level equivalent during that time, which suggests that changes in the marine δ18O record are driven by other variables, including water temperature. This work urges caution regarding the reliance of the marine δ18O record as a de facto indicator of continental ice when few geological constraints are available, which underpins many Quaternary studies.
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