| 1. |
- Bianco, Federica B., et al.
(författare)
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Optimization of the Observing Cadence for the Rubin Observatory Legacy Survey of Space and Time : A Pioneering Process of Community-focused Experimental Design
- 2022
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Ingår i: Astrophysical Journal Supplement Series. - : American Astronomical Society. - 0067-0049 .- 1538-4365. ; 258:1
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Tidskriftsartikel (refereegranskat)abstract
- Vera C. Rubin Observatory is a ground-based astronomical facility under construction, a joint project of the National Science Foundation and the U.S. Department of Energy, designed to conduct a multipurpose 10 yr optical survey of the Southern Hemisphere sky: the Legacy Survey of Space and Time. Significant flexibility in survey strategy remains within the constraints imposed by the core science goals of probing dark energy and dark matter, cataloging the solar system, exploring the transient optical sky, and mapping the Milky Way. The survey's massive data throughput will be transformational for many other astrophysics domains and Rubin's data access policy sets the stage for a huge community of potential users. To ensure that the survey science potential is maximized while serving as broad a community as possible, Rubin Observatory has involved the scientific community at large in the process of setting and refining the details of the observing strategy. The motivation, history, and decision-making process of this strategy optimization are detailed in this paper, giving context to the science-driven proposals and recommendations for the survey strategy included in this Focus Issue.
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| 2. |
- Dewhurst, Matthew R, et al.
(författare)
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Loss of hepatocyte cell division leads to liver inflammation and fibrosis
- 2020
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:11, s. 1009084-1009084
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Tidskriftsartikel (refereegranskat)abstract
- The liver possesses a remarkable regenerative capacity based partly on the ability of hepatocytes to re-enter the cell cycle and divide to replace damaged cells. This capability is substantially reduced upon chronic damage, but it is not clear if this is a cause or consequence of liver disease. Here, we investigate whether blocking hepatocyte division using two different mouse models affects physiology as well as clinical liver manifestations like fibrosis and inflammation. We find that in P14 Cdk1Liv-/- mice, where the division of hepatocytes is abolished, polyploidy, DNA damage, and increased p53 signaling are prevalent. Cdk1Liv-/- mice display classical markers of liver damage two weeks after birth, including elevated ALT, ALP, and bilirubin levels, despite the lack of exogenous liver injury. Inflammation was further studied using cytokine arrays, unveiling elevated levels of CCL2, TIMP1, CXCL10, and IL1-Rn in Cdk1Liv-/- liver, which resulted in increased numbers of monocytes. Ablation of CDK2-dependent DNA re-replication and polyploidy in Cdk1Liv-/- mice reversed most of these phenotypes. Overall, our data indicate that blocking hepatocyte division induces biological processes driving the onset of the disease phenotype. It suggests that the decrease in hepatocyte division observed in liver disease may not only be a consequence of fibrosis and inflammation, but also a pathological cue.
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| 3. |
- Major, Triin, et al.
(författare)
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Pro-IL-1β Is an Early Prognostic Indicator of Severe Donor Lung Injury During Ex Vivo Lung Perfusion
- 2021
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Ingår i: Transplantation. - 1534-6080. ; 105:4, s. 768-774
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ex vivo lung perfusion (EVLP) is used to evaluate and recondition extended criteria donor lungs for transplantation. Interleukin-1β (IL-1β) has been identified as a prognostic indicator of nonrecovery during EVLP. This may be an effect of inflammasome activation or cellular necrosis following donation and graft preservation. Delineating the mechanism of IL-1β release is required. METHODS: The inactive intracellular precursor molecule, pro-IL-1β, was characterized along with the pro-IL-1β processing enzyme, caspase-1, in the perfusate of n = 20 human lungs that had undergone EVLP (n = 10 lungs that failed to recover and were discarded versus n = 10 lungs that reconditioned and were transplanted). In an experimental porcine model, n = 8 lungs underwent EVLP and were randomized to receive either a specific NLRP3 inflammasome inhibitor or control. RESULTS: Significant increases in pro-IL-1β and caspase-1 were observed in the perfusate from human lungs that did not recondition during EVLP compared with those that successfully reconditioned and were used for transplantation. Within the porcine EVLP, NLRP3 inflammasome inhibition reduced IL-1β within the perfusate compared with controls, but this had no impact on lung function, hemodynamics, or inflammation. CONCLUSIONS: Our data suggest that pro-IL-1β is passively released following cellular necrosis of the donor lung.
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