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- Irani, Ido, et al.
(författare)
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SN 2022oqm-A Ca-rich Explosion of a Compact Progenitor Embedded in C/O Circumstellar Material
- 2024
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Ingår i: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 962:2
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Tidskriftsartikel (refereegranskat)abstract
- We present the discovery and analysis of SN 2022oqm, a Type Ic supernova (SN) detected <1 day after the explosion. The SN rises to a blue and short-lived (2 days) initial peak. Early-time spectral observations of SN 2022oqm show a hot (40,000 K) continuum with high ionization C and O absorption features at velocities of 4000 km s−1, while its photospheric radius expands at 20,000 km s−1, indicating a pre-existing distribution of expanding C/O material. After ∼2.5 days, both the spectrum and light curves evolve into those of a typical SN Ic, with line velocities of ∼10,000 km s−1, in agreement with the evolution of the photospheric radius. The optical light curves reach a second peak at t ≈ 15 days. By t = 60 days, the spectrum of SN 2022oqm becomes nearly nebular, displaying strong Ca ii and [Ca ii] emission with no detectable [O i], marking this event as Ca-rich. The early behavior can be explained by 10−3M⊙ of optically thin circumstellar material (CSM) surrounding either (1) a massive compact progenitor such as a Wolf–Rayet star, (2) a massive stripped progenitor with an extended envelope, or (3) a binary system with a white dwarf. We propose that the early-time light curve is powered by both the interaction of the ejecta with the optically thin CSM and shock cooling (in the massive star scenario). The observations can be explained by CSM that is optically thick to X-ray photons, is optically thick in the lines as seen in the spectra, and is optically thin to visible-light continuum photons that come either from downscattered X-rays or from the shock-heated ejecta. Calculations show that this scenario is self-consistent.
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- Ivanics, Tommy, et al.
(författare)
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Impact of the acuity circle model for liver allocation on multivisceral transplant candidates
- 2022
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Ingår i: American Journal of Transplantation. - : John Wiley & Sons. - 1600-6135 .- 1600-6143. ; 22:2, s. 464-473
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Tidskriftsartikel (refereegranskat)abstract
- Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018–2020) and post-AC (2020–2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96–74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15–0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.
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- Rutten, Martijn G. S., et al.
(författare)
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Normalization of hepatic ChREBP activity does not protect against liver disease progression in a mouse model for Glycogen Storage Disease type Ia
- 2023
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Ingår i: Cancer & Metabolism. - : Springer Nature. - 2049-3002. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGlycogen storage disease type 1a (GSD Ia) is an inborn error of metabolism caused by a defect in glucose-6-phosphatase (G6PC1) activity, which induces severe hepatomegaly and increases the risk for liver cancer. Hepatic GSD Ia is characterized by constitutive activation of Carbohydrate Response Element Binding Protein (ChREBP), a glucose-sensitive transcription factor. Previously, we showed that ChREBP activation limits non-alcoholic fatty liver disease (NAFLD) in hepatic GSD Ia. As ChREBP has been proposed as a pro-oncogenic molecular switch that supports tumour progression, we hypothesized that ChREBP normalization protects against liver disease progression in hepatic GSD Ia.MethodsHepatocyte-specific G6pc knockout (L-G6pc−/−) mice were treated with AAV-shChREBP to normalize hepatic ChREBP activity.ResultsHepatic ChREBP normalization in GSD Ia mice induced dysplastic liver growth, massively increased hepatocyte size, and was associated with increased hepatic inflammation. Furthermore, nuclear levels of the oncoprotein Yes Associated Protein (YAP) were increased and its transcriptional targets were induced in ChREBP-normalized GSD Ia mice. Hepatic ChREBP normalization furthermore induced DNA damage and mitotic activity in GSD Ia mice, while gene signatures of chromosomal instability, the cytosolic DNA-sensing cGAS-STING pathway, senescence, and hepatocyte dedifferentiation emerged.ConclusionsIn conclusion, our findings indicate that ChREBP activity limits hepatomegaly while decelerating liver disease progression and protecting against chromosomal instability in hepatic GSD Ia. These results disqualify ChREBP as a therapeutic target for treatment of liver disease in GSD Ia. In addition, they underline the importance of establishing the context-specific roles of hepatic ChREBP to define its therapeutic potential to prevent or treat advanced liver disease.
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- van Loggerenberg, W, et al.
(författare)
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Systematically testing human HMBS missense variants to reveal mechanism and pathogenic variation
- 2023
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Defects in hydroxymethylbilane synthase (HMBS) can cause Acute Intermittent Porphyria (AIP), an acute neurological disease. Although sequencing-based diagnosis can be definitive, ~⅓ of clinical HMBS variants are missense variants, and most clinically-reported HMBS missense variants are designated as “variants of uncertain significance” (VUS). Using saturation mutagenesis,en masseselection, and sequencing, we applied a multiplexed validated assay to both the erythroid-specific and ubiquitous isoforms of HMBS, obtaining confident functional impact scores for >84% of all possible amino-acid substitutions. The resulting variant effect maps generally agreed with biochemical expectation. However, the maps showed variants at the dimerization interface to be unexpectedly well tolerated, and suggested residue roles in active site dynamics that were supported by molecular dynamics simulations. Most importantly, these HMBS variant effect maps can help discriminate pathogenic from benign variants, proactively providing evidence even for yet-to-be-observed clinical missense variants.
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