| 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. |
- Algaba, Juan-Carlos, et al.
(författare)
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Broadband Multi-wavelength Properties of M87 during the 2017 Event Horizon Telescope Campaign
- 2021
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Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 911:1
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Forskningsöversikt (refereegranskat)abstract
- In 2017, the Event Horizon Telescope (EHT) Collaboration succeeded in capturing the first direct image of the center of the M87 galaxy. The asymmetric ring morphology and size are consistent with theoretical expectations for a weakly accreting supermassive black hole of mass ∼6.5 × 109 M o˙. The EHTC also partnered with several international facilities in space and on the ground, to arrange an extensive, quasi-simultaneous multi-wavelength campaign. This Letter presents the results and analysis of this campaign, as well as the multi-wavelength data as a legacy data repository. We captured M87 in a historically low state, and the core flux dominates over HST-1 at high energies, making it possible to combine core flux constraints with the more spatially precise very long baseline interferometry data. We present the most complete simultaneous multi-wavelength spectrum of the active nucleus to date, and discuss the complexity and caveats of combining data from different spatial scales into one broadband spectrum. We apply two heuristic, isotropic leptonic single-zone models to provide insight into the basic source properties, but conclude that a structured jet is necessary to explain M87's spectrum. We can exclude that the simultaneous γ-ray emission is produced via inverse Compton emission in the same region producing the EHT mm-band emission, and further conclude that the γ-rays can only be produced in the inner jets (inward of HST-1) if there are strongly particle-dominated regions. Direct synchrotron emission from accelerated protons and secondaries cannot yet be excluded.
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| 3. |
- Joffrin, E., et al.
(författare)
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Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
- 2019
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Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11
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Forskningsöversikt (refereegranskat)abstract
- For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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| 4. |
- Aad, G., et al.
(författare)
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The ATLAS Experiment at the CERN Large Hadron Collider
- 2008
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 3:S08003
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Forskningsöversikt (refereegranskat)abstract
- The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.
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| 5. |
- Aharonian, F., et al.
(författare)
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Simultaneous multiwavelength observations of the second exceptional gamma-ray flare of PKS2155-304 in July 2006
- 2009
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 502:3, s. 749-770
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Forskningsöversikt (refereegranskat)abstract
- Aims. The X-ray-TeV connection and the evolution of the emitting particle population is studied in high-energy peaked BL Lac objects, by obtaining spectral information in both bands on sub-hour timescales. Methods. Simultaneous observations with HESS, Chandra and the Bronberg optical observatory were performed on the BL Lac object PKS 2155-304 in the night of July 29-30 2006, when the source underwent a major gamma-ray outburst during its high-activity state of Summer 2006. This event took place about 44 h after the other major outburst of the night of July 27-28, which is known for its ultrafast variability. An unprecedented 6 to 8 h of simultaneous, uninterrupted coverage was achieved, with spectra and light curves measured down to 7 and 2 min timescales, respectively. Results. The source exhibited one major flare along the night, at high energies. The gamma-ray flux reached a maximum of similar to 11 times the Crab flux (>400 GeV), with rise/decay timescales of similar to 1 h, plus a few smaller-amplitude flares superimposed on the decaying phase. The emission in the X-ray and VHE gamma-ray bands is strongly correlated, with no evidence of lags. The spectra also evolve with similar patterns, and are always soft ( photon index G > 2), indicating no strong shift of the peaks in the spectral energy distribution towards higher energies. Only at the flare maximum is there evidence that the gamma-ray peak is inside the observed passband, at similar to 400-600 GeV. The VHE spectrum shows a curvature that is variable with time and stronger at higher fluxes. The huge VHE variations (similar to 22x) are only accompanied by small-amplitude X-ray and optical variations (factor 2 and 15% respectively). The source has shown for the first time in a high-energy peaked BL Lac object a large Compton dominance (L(C)/L(S) similar to 10) - rapidly evolving - and a cubic relation between VHE and X-ray flux variations, during a decaying phase. These results challenge the common scenarios for the TeV-blazar emission.
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| 6. |
- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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| 7. |
- De Backer, Daniel, et al.
(författare)
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A plea for personalization of the hemodynamic management of septic shock
- 2022
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Ingår i: Critical Care. - : BMC. - 1364-8535 .- 1466-609X. ; 26:1
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Forskningsöversikt (refereegranskat)abstract
- Although guidelines provide excellent expert guidance for managing patients with septic shock, they leave room for personalization according to patients condition. Hemodynamic monitoring depends on the evolution phase: salvage, optimization, stabilization, and de-escalation. Initially during the salvage phase, monitoring to identify shock etiology and severity should include arterial pressure and lactate measurements together with clinical examination, particularly skin mottling and capillary refill time. Low diastolic blood pressure may trigger vasopressor initiation. At this stage, echocardiography may be useful to identify significant cardiac dysfunction. During the optimization phase, echocardiographic monitoring should be pursued and completed by the assessment of tissue perfusion through central or mixed-venous oxygen saturation, lactate, and carbon dioxide veno-arterial gradient. Transpulmonary thermodilution and the pulmonary artery catheter should be considered in the most severe patients. Fluid therapy also depends on shock phases. While administered liberally during the resuscitation phase, fluid responsiveness should be assessed during the optimization phase. During stabilization, fluid infusion should be minimized. In the de-escalation phase, safe fluid withdrawal could be achieved by ensuring tissue perfusion is preserved. Norepinephrine is recommended as first-line vasopressor therapy, while vasopressin may be preferred in some patients. Essential questions remain regarding optimal vasopressor selection, combination therapy, and the most effective and safest escalation. Serum renin and the angiotensin I/II ratio may identify patients who benefit most from angiotensin II. The optimal therapeutic strategy for shock requiring high-dose vasopressors is scant. In all cases, vasopressor therapy should be individualized, based on clinical evaluation and blood flow measurements to avoid excessive vasoconstriction. Inotropes should be considered in patients with decreased cardiac contractility associated with impaired tissue perfusion. Based on pharmacologic properties, we suggest as the first test a limited dose of dobutamine, to add enoximone or milrinone in the second line and substitute or add levosimendan if inefficient. Regarding adjunctive therapies, while hydrocortisone is nowadays advised in patients receiving high doses of vasopressors, patients responding to corticosteroids may be identified in the future by the analysis of selected cytokines or specific transcriptomic endotypes. To conclude, although some general rules apply for shock management, a personalized approach should be considered for hemodynamic monitoring and support.
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| 8. |
- De Backer, Daniel, et al.
(författare)
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How can assessing hemodynamics help to assess volume status?
- 2022
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Ingår i: Intensive Care Medicine. - : SPRINGER. - 0342-4642 .- 1432-1238. ; 48, s. 11482-1494
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Forskningsöversikt (refereegranskat)abstract
- In critically ill patients, fluid infusion is aimed at increasing cardiac output and tissue perfusion. However, it may contribute to fluid overload which may be harmful. Thus, volume status, risks and potential efficacy of fluid administration and/or removal should be carefully evaluated, and monitoring techniques help for this purpose. Central venous pressure is a marker of right ventricular preload. Very low values indicate hypovolemia, while extremely high values suggest fluid harmfulness. The pulmonary artery catheter enables a comprehensive assessment of the hemodynamic profile and is particularly useful for indicating the risk of pulmonary oedema through the pulmonary artery occlusion pressure. Besides cardiac output and preload, transpulmonary thermodilution measures extravascular lung water, which reflects the extent of lung flooding and assesses the risk of fluid infusion. Echocardiography estimates the volume status through intravascular volumes and pressures. Finally, lung ultrasound estimates lung edema. Guided by these variables, the decision to infuse fluid should first consider specific triggers, such as signs of tissue hypoperfusion. Second, benefits and risks of fluid infusion should be weighted. Thereafter, fluid responsiveness should be assessed. Monitoring techniques help for this purpose, especially by providing real time and precise measurements of cardiac output. When decided, fluid resuscitation should be performed through fluid challenges, the effects of which should be assessed through critical endpoints including cardiac output. This comprehensive evaluation of the risk, benefits and efficacy of fluid infusion helps to individualize fluid management, which should be preferred over a fixed restrictive or liberal strategy.
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| 9. |
- Gundale, Michael, et al.
(författare)
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The biological controls of soil carbon accumulation following wildfire and harvest in boreal forests : a review
- 2024
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Ingår i: Global Change Biology. - : John Wiley & Sons. - 1354-1013 .- 1365-2486. ; 30:5
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Forskningsöversikt (refereegranskat)abstract
- Boreal forests are frequently subjected to disturbances, including wildfire and clear-cutting. While these disturbances can cause soil carbon (C) losses, the long-term accumulation dynamics of soil C stocks during subsequent stand development is controlled by biological processes related to the balance of net primary production (NPP) and outputs via heterotrophic respiration and leaching, many of which remain poorly understood. We review the biological processes suggested to influence soil C accumulation in boreal forests. Our review indicates that median C accumulation rates following wildfire and clear-cutting are similar (0.15 and 0.20 Mg ha−1 year−1, respectively), however, variation between studies is extremely high. Further, while many individual studies show linear increases in soil C stocks through time after disturbance, there are indications that C stock recovery is fastest early to mid-succession (e.g. 15–80 years) and then slows as forests mature (e.g. >100 years). We indicate that the rapid build-up of soil C in younger stands appears not only driven by higher plant production, but also by a high rate of mycorrhizal hyphal production, and mycorrhizal suppression of saprotrophs. As stands mature, the balance between reductions in plant and mycorrhizal production, increasing plant litter recalcitrance, and ectomycorrhizal decomposers and saprotrophs have been highlighted as key controls on soil C accumulation rates. While some of these controls appear well understood (e.g. temporal patterns in NPP, changes in aboveground litter quality), many others remain research frontiers. Notably, very little data exists describing and comparing successional patterns of root production, mycorrhizal functional traits, mycorrhizal-saprotroph interactions, or C outputs via heterotrophic respiration and dissolved organic C following different disturbances. We argue that these less frequently described controls require attention, as they will be key not only for understanding ecosystem C balances, but also for representing these dynamics more accurately in soil organic C and Earth system models.
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| 10. |
- Halabowski, Dariusz, et al.
(författare)
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Off the conservation radar : the hidden story of Europe’s tiny pea clams (Bivalvia: Sphaeriidae)
- 2024
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Ingår i: Biodiversity and Conservation. - : Springer. - 0960-3115 .- 1572-9710.
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Forskningsöversikt (refereegranskat)abstract
- This study highlights the conservation problems faced by the tiny freshwater bivalves of the family Sphaeriidae, also known as pea, pill, or fingernail clams (or mussels) in Europe. Despite their global distribution, assumed ecological importance, and potential uses, basic knowledge about their taxonomy, biology, and ecology is very limited and much lower than for the larger freshwater bivalve taxa. Immediate scientific priorities are required to fill knowledge gaps regarding their taxonomy, genetic diversity, distribution, reproductive cycle, ecosystem functions, and population trends. Such fundamental knowledge is necessary to identify specific threats and develop appropriate conservation actions. Deploying environmental DNA analysis at a large scale could be a valuable way to fill gaps in distribution and strengthen monitoring in areas where local taxonomic knowledge is lacking. Until taxon-specific management plans can be developed, we recommend that efforts concentrate on the general protection and restoration of wetland habitats, implementing pollution control measures, and managing invasive species. These actions should be complemented by community engagement through citizen science initiatives. Additionally, prioritising data collection to fill existing knowledge gaps and updating conservation statuses (Red Lists) based on comprehensive assessments will be crucial. Implementing these actions will provide a starting point for the broader protection of freshwater ecosystems, thus benefiting pea clams and other interconnected species within these habitats.
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