| 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. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Armandi, Angelo, et al.
(författare)
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Serum ferritin levels can predict long-term outcomes in patients with metabolic dysfunction-associated steatotic liver disease
- 2024
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Ingår i: Gut. - : BMJ PUBLISHING GROUP. - 0017-5749 .- 1468-3288.
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Tidskriftsartikel (refereegranskat)abstract
- Objective Hyperferritinaemia is associated with liver fibrosis severity in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), but the longitudinal implications have not been thoroughly investigated. We assessed the role of serum ferritin in predicting long-term outcomes or death. Design We evaluated the relationship between baseline serum ferritin and longitudinal events in a multicentre cohort of 1342 patients. Four survival models considering ferritin with confounders or non-invasive scoring systems were applied with repeated five-fold cross-validation schema. Prediction performance was evaluated in terms of Harrell's C-index and its improvement by including ferritin as a covariate. Results Median follow-up time was 96 months. Liver-related events occurred in 7.7%, hepatocellular carcinoma in 1.9%, cardiovascular events in 10.9%, extrahepatic cancers in 8.3% and all-cause mortality in 5.8%. Hyperferritinaemia was associated with a 50% increased risk of liver-related events and 27% of all-cause mortality. A stepwise increase in baseline ferritin thresholds was associated with a statistical increase in C-index, ranging between 0.02 (lasso-penalised Cox regression) and 0.03 (ridge-penalised Cox regression); the risk of developing liver-related events mainly increased from threshold 215.5 mu g/L (median HR=1.71 and C-index=0.71) and the risk of overall mortality from threshold 272 mu g/L (median HR=1.49 and C-index=0.70). The inclusion of serum ferritin thresholds (215.5 mu g/L and 272 mu g/L) in predictive models increased the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score in the longitudinal risk assessment of liver-related events (C-indices>0.71) and overall mortality (C-indices>0.65). Conclusions This study supports the potential use of serum ferritin values for predicting the long-term prognosis of patients with MASLD.
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| 4. |
- Bhat, P. Narayana, et al.
(författare)
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THE THIRD FERMI GBM GAMMA-RAY BURST CATALOG : THE FIRST SIX YEARS
- 2016
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 223:2
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Tidskriftsartikel (refereegranskat)abstract
- Since its launch in 2008, the Fermi Gamma-ray Burst Monitor (GBM) has triggered and located on average approximately two.-ray bursts (GRBs) every three days. Here, we present the third of a series of catalogs of GRBs detected by GBM, extending the second catalog by two more years through the middle of 2014 July. The resulting list includes 1405 triggers identified as GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM-detected GRBs. For each GRB, the location and main characteristics of the prompt emission, the duration, peak flux, and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band where the maximum energy release of GRBs in the instrument reference system is observed, and also for a broader energy band from 10 to 1000 keV, exploiting the full energy range of GBM's low-energy [NaI[Tl)] detectors. Using statistical methods to assess clustering, we find that the hardness and duration of GRBs are better fit by a two-component model with short-hard and long-soft bursts than by a model with three components. Furthermore, information is provided on the settings and modifications of the triggering criteria and exceptional operational conditions during years five and six in the mission. This third catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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| 5. |
- Hardy, Timothy, et al.
(författare)
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The European NAFLD Registry : A real-world longitudinal cohort study of nonalcoholic fatty liver disease
- 2020
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Ingår i: Contemporary Clinical Trials. - : Elsevier. - 1551-7144 .- 1559-2030. ; 98
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Tidskriftsartikel (refereegranskat)abstract
- Non-Alcoholic Fatty Liver Disease (NAFLD), a progressive liver disease that is closely associated with obesity, type 2 diabetes, hypertension and dyslipidaemia, represents an increasing global public health challenge. There is significant variability in the disease course: the majority exhibit only fat accumulation in the liver but a significant minority develop a necroinflammatory form of the disease (non-alcoholic steatohepatitis, NASH) that may progress to cirrhosis and hepatocellular carcinoma. At present our understanding of pathogenesis, disease natural history and long-term outcomes remain incomplete. There is a need for large, well characterised patient cohorts that may be used to address these knowledge gaps and to support the development of better biomarkers and novel therapies. The European NAFLD Registry is an international, prospectively recruited observational cohort study that aims to establish a large, highly-phenotyped patient cohort and linked bioresource. Here we describe the infrastructure, data management and monitoring plans, and the standard operating procedures implemented to ensure the timely and systematic collection of high-quality data and samples. Already recruiting subjects at secondary/tertiary care centres across Europe, the Registry is supporting the European Union IMI2-funded LITMUS Liver Investigation: Testing Marker Utility in Steatohepatitis consortium, which is a major international effort to robustly validate biomarkers that diagnose, risk stratify and/or monitor NAFLD progression and liver fibrosis stage. The European NAFLD Registry has the demonstrable capacity to support research and biomarker development at scale and pace.
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| 6. |
- von Kienlin, Andreas, et al.
(författare)
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The Second Fermi GBM Gamma-Ray Burst Catalog : The First Four Years
- 2014
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Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 211:1
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Tidskriftsartikel (refereegranskat)abstract
- This is the second of a series of catalogs of gamma-ray bursts (GRBs) observed with the Fermi Gamma-ray Burst Monitor (GBM). It extends the first two-year catalog by two more years, resulting in an overall list of 953 GBM triggered GRBs. The intention of the GBM GRB catalog is to provide information to the community on the most important observables of the GBM detected GRBs. For each GRB the location and main characteristics of the prompt emission, the duration, peak flux and fluence are derived. The latter two quantities are calculated for the 50-300 keV energy band, where the maximum energy release of GRBs in the instrument reference system is observed and also for a broader energy band from 10-1000 keV, exploiting the full energy range of GBMs low-energy detectors. Furthermore, information is given on the settings and modifications of the triggering criteria and exceptional operational conditions during years three and four in the mission. This second catalog is an official product of the Fermi GBM science team, and the data files containing the complete results are available from the High-Energy Astrophysics Science Archive Research Center.
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| 7. |
- Younes, George, et al.
(författare)
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X-Ray Burst and Persistent Emission Properties of the Magnetar SGR 1830-0645 in Outburst
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 924:2
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Tidskriftsartikel (refereegranskat)abstract
- We report on NICER X-ray monitoring of the magnetar SGR 1830-0645 covering 223 days following its 2020 October outburst, as well as Chandra and radio observations. We present the most accurate spin ephemerides of the source so far: nu = 0.096008680(2) Hz, = -6.2(1) x 10(-14) Hz s(-1), and significant second and third frequency derivative terms indicative of nonnegligible timing noise. The phase-averaged 0.8-7 keV spectrum is well fit with a double-blackbody (BB) model throughout the campaign. The BB temperatures remain constant at 0.46 and 1.2 keV. The areas and flux of each component decreased by a factor of 6, initially through a steep decay trend lasting about 46 days, followed by a shallow long-term one. The pulse shape in the same energy range is initially complex, exhibiting three distinct peaks, yet with clear continuous evolution throughout the outburst toward a simpler, single-pulse shape. The rms pulsed fraction is high and increases from about 40% to 50%. We find no dependence of pulse shape or fraction on energy. These results suggest that multiple hot spots, possibly possessing temperature gradients, emerged at outburst onset and shrank as the outburst decayed. We detect 84 faint bursts with NICER, having a strong preference for occurring close to the surface emission pulse maximum-the first time this phenomenon is detected in such a large burst sample. This likely implies a very low altitude for the burst emission region and a triggering mechanism connected to the surface active zone. Finally, our radio observations at several epochs and multiple frequencies reveal no evidence of pulsed or burst-like radio emission.
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