| 1. |
- 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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| 2. |
- Middeldorp, Christel M., et al.
(författare)
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The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
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Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
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| 3. |
- Mathieu, François, et al.
(författare)
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Relationship Between Measures of Cerebrovascular Reactivity and Intracranial Lesion Progression in Acute TBI Patients : an Exploratory Analysis.
- 2020
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Ingår i: Neurocritical Care. - : Springer. - 1541-6933 .- 1556-0961. ; 32:2, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Failure of cerebral autoregulation and progression of intracranial lesion have both been shown to contribute to poor outcome in patients with acute traumatic brain injury (TBI), but the interplay between the two phenomena has not been investigated. Preliminary evidence leads us to hypothesize that brain tissue adjacent to primary injury foci may be more vulnerable to large fluctuations in blood flow in the absence of intact autoregulatory mechanisms. The goal of this study was therefore to assess the influence of cerebrovascular reactivity measures on radiological lesion expansion in a cohort of patients with acute TBI.METHODS: We conducted a retrospective cohort analysis on 50 TBI patients who had undergone high-frequency multimodal intracranial monitoring and for which at least two brain computed tomography (CT) scans had been performed in the acute phase of injury. We first performed univariate analyses on the full cohort to identify non-neurophysiological factors (i.e., initial lesion volume, timing of scan, coagulopathy) associated with traumatic lesion growth in this population. In a subset analysis of 23 patients who had intracranial recording data covering the period between the initial and repeat CT scan, we then correlated changes in serial volumetric lesion measurements with cerebrovascular reactivity metrics derived from the pressure reactivity index (PRx), pulse amplitude index (PAx), and RAC (correlation coefficient between the pulse amplitude of intracranial pressure and cerebral perfusion pressure). Using multivariate methods, these results were subsequently adjusted for the non-neurophysiological confounders identified in the univariate analyses.RESULTS: We observed significant positive linear associations between the degree of cerebrovascular reactivity impairment and progression of pericontusional edema. The strongest correlations were observed between edema progression and the following indices of cerebrovascular reactivity between sequential scans: % time PRx > 0.25 (r = 0.69, p = 0.002) and % time PAx > 0.25 (r = 0.64, p = 0.006). These associations remained significant after adjusting for initial lesion volume and mean cerebral perfusion pressure. In contrast, progression of the hemorrhagic core and extra-axial hemorrhage volume did not appear to be strongly influenced by autoregulatory status.CONCLUSIONS: Our preliminary findings suggest a possible link between autoregulatory failure and traumatic edema progression, which warrants re-evaluation in larger-scale prospective studies.
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| 4. |
- Mathieu, François, et al.
(författare)
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Relationship between Measures of CerebrovascularReactivity and Intracranial Lesion Progressionin Acute Traumatic Brain Injury Patients:A CENTER-TBI Study
- 2020
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 37:13, s. 1556-1565
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Tidskriftsartikel (refereegranskat)abstract
- Failure of cerebral autoregulation has been linked to unfavorable outcome after traumatic brain injury (TBI). Preliminary evidence from a small, retrospective, single-center analysis suggests that autoregulatory dysfunction may be associated with traumatic lesion expansion, particularly for pericontusional edema. The goal of this study was to further explore these associations using prospective, multi-center data from the Collaborative European Neurotrauma Effectiveness Research in TBI (CENTER-TBI) and to further explore the relationship between autoregulatory failure, lesion progression, and patient outcome. A total of 88 subjects from the CENTER-TBI High Resolution ICU Sub-Study cohort were included. All patients had an admission computed tomography (CT) scan and early repeat scan available, as well as high-frequency neurophysiological recordings covering the between-scan interval. Using a novel, semiautomated approach at lesion segmentation, we calculated absolute changes in volume of contusion core, pericontusional edema, and extra-axial hemorrhage between the imaging studies. We then evaluated associations between cerebrovascular reactivity metrics and radiological lesion progression using mixed-model regression. Analyses were adjusted for baseline covariates and non-neurophysiological factors associated with lesion growth using multi-variate methods. Impairment in cerebrovascular reactivity was significantly associated with progression of pericontusional edema and, to a lesser degree, intraparenchymal hemorrhage. In contrast, there were no significant associations with extra-axial hemorrhage. The strongest relationships were observed between RAC-based metrics and edema formation. Pulse amplitude index showed weaker, but consistent, associations with contusion growth. Cerebrovascular reactivity metrics remained strongly associated with lesion progression after taking into account contributions from non-neurophysiological factors and mean cerebral perfusion pressure. Total hemorrhagic core and edema volumes on repeat CT were significantly larger in patients who were deceased at 6 months, and the amount of edema was greater in patients with an unfavourable outcome (Glasgow Outcome Scale-Extended 1–4). Our study suggests associations between autoregulatory failure, traumatic edema progression, and poor outcome. This is in keeping with findings from a single-center retrospective analysis, providing multi-center prospective data to support those results.
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| 5. |
- Bailey, Lydia R., et al.
(författare)
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Characteristics and Consequences of Red Bed Bleaching by Hydrocarbon Migration : A Natural Example From the Entrada Sandstone, Southern Utah
- 2022
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Ingår i: Geochemistry Geophysics Geosystems. - : John Wiley & Sons. - 1525-2027. ; 23:8
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Tidskriftsartikel (refereegranskat)abstract
- Extensive regions of yellow and white ("bleached") sandstones within the terrestrial Jurassic red bed deposits of the Colorado Plateau reflect widespread interaction with subsurface reduced fluids which resulted in the dissolution of iron-oxide grain coatings. Reduced fluids such as hydrocarbons, CO2, and organic acids have been proposed as bleaching agents. In this study, we characterize an altered section of the Slick Rock member of the Jurassic Entrada Sandstone that exposes bleached sandstone with bitumen-saturated pore spaces. We observe differences in texture, porosity, mineralogy, and geochemistry between red, pink, yellow, and gray facies. In the bleached yellow facies we observe quartz overgrowths, partially dissolved K-feldspar, calcite cement, fine-grained illite, TiO2-minerals, and pyrite concretions. Clay mineral content is highest at the margins of the bleached section. Fe2O3 concentrations are reduced up to 3x from the red to gray facies but enriched up to 50x in iron-oxide concretions. Metals such as Zn, Pb, and rare-earth elements are significantly enriched in the concretions. Supported by a batch geochemical model, we conclude the interaction of red sandstones with reduced hydrocarbon-bearing fluids caused iron-oxide and K-feldspar dissolution, and precipitation of quartz, calcite, clay, and pyrite. Localized redistribution of iron into concretions can account for most of the iron removed during bleaching. Pyrite and carbonate stable isotopic data suggest the hydrocarbons were sourced from the Pennsylvanian Paradox Formation. Bitumen in pore spaces and pyrite precipitation formed a reductant trap required to produce Cu, U, and V enrichment in all altered facies by younger, oxidized saline brines.
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| 6. |
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| 7. |
- Bergemann, Christian A., et al.
(författare)
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Constraining long-term fault activity in the brittle domain through in situ dating of hydrothermal monazite
- 2018
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Ingår i: Terra Nova. - : Wiley. - 0954-4879. ; 30:6, s. 440-446
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Tidskriftsartikel (refereegranskat)abstract
- Abstract SIMS Th–Pb dating of hydrothermal fissure-vein monazite-(Ce) has the unique potential to date multiple tectonic events under low-grade metamorphic brittle/ductile conditions over large time frames. Monazites-(Ce) from brittle fault systems in the Eastern Alps allow us to constrain their Cretaceous activity over 20 Ma within single crystals, recording all major tectonic events. Eo-Alpine formation of the fluid-filled fissure-veins occurred 90 Ma ago at 352 ± 19°C and 342 ± 42 MPa. This corresponds to peak conditions during regional metamorphism of the Cretaceous collisional nappe stacking. Several stages of dissolution–reprecipitation/recrystallization record fault activity between 84 and 70 Ma. Corresponding fluid inclusions indicate conditions of 229 ± 10°C and 143 ± 20 MPa. This correlates with the formation of sedimentary basins during post-orogenic extension associated with strike-slip movements. The results strengthen the hypothesis that many large fault systems in the Eastern Alps developed during the Cretaceous orogeny and became reactivated during Neogene Alpine tectonics.
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| 8. |
- Cnudde, Peter, 1970, et al.
(författare)
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Risk of further surgery on the same or opposite side and mortality after primary total hip arthroplasty: A multi-state analysis of 133,654 patients from the Swedish Hip Arthroplasty Register
- 2018
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 89:4, s. 386-393
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - The hip-related timeline of patients following a total hip arthroplasty (THA) can vary. Ideally patients will live their life without need for further surgery; however, some will undergo replacement on the contralateral hip and/or reoperations. We analyzed the probability of mortality and further hip-related surgery on the same or contralateral hip. Patients and methods - We performed a multi-state survival analysis on a prospectively followed cohort of 133,654 Swedish patients undergoing an elective THA between 1999 and 2012. The study used longitudinally collected information from the Swedish Hip Arthroplasty Register and administrative databases. The analysis considered the patients' sex, age, prosthesis type, surgical approach, diagnosis, comorbidities, education, and civil status. Results - During the study period patients were twice as likely to have their contralateral hip replaced than to die. However, with passing time, probabilities converged and for a patient who only had 1 non-revised THA at 10 years, there was an equal chance of receiving a second THA and dying (24%). It was 8 times more likely that the second hip would become operated with a primary THA than that the first hip would be revised. Multivariable regression analysis reinforced the influence of age at operation, sex, diagnosis, comorbidity, and socioeconomic status influencing state transition. Interpretation - Multi-state analysis can provide a comprehensive model of further states and transition probabilities after an elective THA. Information regarding the lifetime risk for bilateral surgery, revision, and death can be of value when discussing the future possible outcomes with patients, in healthcare planning, and for the healthcare, economy.
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| 9. |
- Drake, Henrik, et al.
(författare)
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Extreme C-13 depletion of carbonates formed during oxidation of biogenic methane in fractured granite
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Precipitation of exceptionally C-13-depleted authigenic carbonate is a result of, and thus a tracer for, sulphate-dependent anaerobic methane oxidation, particularly in marine sediments. Although these carbonates typically are less depleted in C-13 than in the source methane, because of incorporation of C also from other sources, they are far more depleted in C-13 (delta C-13 as light as - 69% V-PDB) than in carbonates formed where no methane is involved. Here we show that oxidation of biogenic methane in carbon-poor deep groundwater in fractured granitoid rocks has resulted in fracture-wall precipitation of the most extremely C-13-depleted carbonates ever reported, delta C-13 down to - 125% V-PDB. A microbial consortium of sulphate reducers and methane oxidizers has been involved, as revealed by biomarker signatures in the carbonates and S-isotope compositions of co-genetic sulphide. Methane formed at shallow depths has been oxidized at several hundred metres depth at the transition to a deep-seated sulphate-rich saline water. This process is so far an unrecognized terrestrial sink of methane.
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| 10. |
- Dunca, Elena, et al.
(författare)
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Using ocean quahog (Arctica islandica) shells to reconstruct palaeoenvironment in A-resund, Kattegat and Skagerrak, Sweden
- 2009
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Ingår i: International Journal of Earth Sciences. - : Springer Science and Business Media LLC. - 1437-3254 .- 1437-3262. ; 98:1, s. 3-17
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Shells of Arctica islandica collected between 1884 and 2004 from A-resund, Kattegat and Skagerrak (Swedish West Coast) were used to monitor local climate variations and the influence of human activities on the local environment. For this purpose, we analysed the growth, structure and chemical composition of these shells and compared them with shells collected from Kiel Bay, Norway and Iceland. The growth rate of the studied shells registers an NAO periodicity of ca 8 years. However, the observed signal is weak because of other environmental interferences that are either of natural or anthropogenic origin. For example, the oxygen isotope ratios show temperature fluctuation, but also the influx of low salinity water. Higher contents of S, N, Cu, Zn, As, Cd and P in shell portions formed during the last century are related to human activities such as mining and industrial development. Our study indicates that in order to use Arctica shells as archives of climate change it is necessary to study the full range of environmental data that is recorded in the shells by using a multi element and isotope approach in combination with different analytical techniques including investigation of growth rates and shell structure.
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