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| 2. |
- Karwen, T., et al.
(författare)
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Platelet-derived lipids promote insulin secretion of pancreatic beta cells
- 2023
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Ingår i: Embo Molecular Medicine. - 1757-4676. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- Hyperreactive platelets are commonly observed in diabetic patients indicating a potential link between glucose homeostasis and platelet reactivity. This raises the possibility that platelets may play a role in the regulation of metabolism. Pancreatic beta cells are the central regulators of systemic glucose homeostasis. Here, we show that factor(s) derived from beta cells stimulate platelet activity and platelets selectively localize to the vascular endothelium of pancreatic islets. Both depletion of platelets and ablation of major platelet adhesion or activation pathways consistently resulted in impaired glucose tolerance and decreased circulating insulin levels. Furthermore, we found platelet-derived lipid classes to promote insulin secretion and identified 20-Hydroxyeicosatetraenoic acid (20-HETE) as the main factor promoting beta cells function. Finally, we demonstrate that the levels of platelet-derived 20-HETE decline with age and that this parallels with reduced impact of platelets on beta cell function. Our findings identify an unexpected function of platelets in the regulation of insulin secretion and glucose metabolism, which promotes metabolic fitness in young individuals.
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| 3. |
- Heinze, Karolin, et al.
(författare)
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Validated biomarker assays confirm ARID1A loss is confounded with MMR deficiency, CD8 TIL infiltration, and provides no independent prognostic value in endometriosis-associated ovarian carcinomas.
- 2021
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Ingår i: The Journal of pathology. - : Wiley. - 1096-9896 .- 0022-3417. ; 256:4, s. 388-401
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Tidskriftsartikel (refereegranskat)abstract
- ARID1A (BAF250a) is a component of the SWI/SNF chromatin modifying complex, plays an important tumour suppressor role, and is considered prognostic in several malignancies. However, in ovarian carcinomas there are contradictory reports on its relationship to outcome, immune response, and correlation with clinicopathological features. We assembled a series of 1,623 endometriosis-associated ovarian carcinomas, including 1,078 endometrioid (ENOC) and 545 clear cell (CCOC) ovarian carcinomas through combining resources of the Ovarian Tumor Tissue Analysis (OTTA) Consortium, the Canadian Ovarian Unified Experimental Resource (COEUR), local, and collaborative networks. Validated immunohistochemical surrogate assays for ARID1A mutations were applied to all samples. We investigated associations between ARID1A loss/mutation, clinical features, outcome, CD8+ tumour-infiltrating lymphocytes (CD8+ TIL), and DNA mismatch repair deficiency (MMRd). ARID1A loss was observed in 42% of CCOC and 25% of ENOC. We found no associations between ARID1A loss and outcomes, stage, age, or CD8+ TIL status in CCOC. Similarly, we found no association with outcome or stage in endometrioid cases. In ENOC, ARID1A loss was more prevalent in younger patients (p=0.012), and associated with MMRd (p<0.001), and presence of CD8+ TIL (p=0.008). Consistent with MMRd being causative of ARID1A mutations, in a subset of ENOC we also observed an association between ARID1A loss-of-function mutation as a result of small indels (p=0.035, versus single nucleotide variants). In ENOC, the association between ARID1A loss, CD8+ TIL, and age, appears confounded by MMRd status. Although this observation does not explicitly rule out a role for ARID1A influence on CD8+ TIL infiltration in ENOC, given current knowledge regarding MMRd, it seems more likely that effects are dominated by the hypermutation phenotype. This large dataset with consistently applied biomarker assessment now provides a benchmark for the prevalence of ARID1A loss-of-function mutations in endometriosis-associated ovarian cancers and brings clarity to the prognostic significance. This article is protected by copyright. All rights reserved.
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| 4. |
- Jenniskens, Peter, et al.
(författare)
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The impact and recovery of asteroid 2018 LA
- 2021
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Ingår i: Meteoritics and Planetary Science. - : John Wiley & Sons. - 1086-9379 .- 1945-5100. ; 56:4, s. 844-893
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Tidskriftsartikel (refereegranskat)abstract
- The June 2, 2018 impact of asteroid 2018 LA over Botswana is only the second asteroid detected in space prior to impacting over land. Here, we report on the successful recovery of meteorites. Additional astrometric data refine the approach orbit and define the spin period and shape of the asteroid. Video observations of the fireball constrain the asteroid's position in its orbit and were used to triangulate the location of the fireball's main flare over the Central Kalahari Game Reserve. Twenty‐three meteorites were recovered. A consortium study of eight of these classifies Motopi Pan as an HED polymict breccia derived from howardite, cumulate and basaltic eucrite, and diogenite lithologies. Before impact, 2018 LA was a solid rock of ~156 cm diameter with high bulk density ~2.85 g cm−3, a relatively low albedo pV ~ 0.25, no significant opposition effect on the asteroid brightness, and an impact kinetic energy of ~0.2 kt. The orbit of 2018 LA is consistent with an origin at Vesta (or its Vestoids) and delivery into an Earth‐impacting orbit via the ν6 resonance. The impact that ejected 2018 LA in an orbit toward Earth occurred 22.8 ± 3.8 Ma ago. Zircons record a concordant U‐Pb age of 4563 ± 11 Ma and a consistent 207Pb/206Pb age of 4563 ± 6 Ma. A much younger Pb‐Pb phosphate resetting age of 4234 ± 41 Ma was found. From this impact chronology, we discuss what is the possible source crater of Motopi Pan and the age of Vesta's Veneneia impact basin.
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| 5. |
- Smith, K. W., et al.
(författare)
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Design and Operation of the ATLAS Transient Science Server
- 2020
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Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 132:1014
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Tidskriftsartikel (refereegranskat)abstract
- The Asteroid Terrestrial impact Last Alert System (ATLAS) system consists of two 0.5 m Schmidt telescopes with cameras covering 29 square degrees at plate scale of 1.86 arcsec per pixel. Working in tandem, the telescopes routinely survey the whole sky visible from Hawaii (above delta > -50 degrees) every two nights, exposing four times per night, typically reaching o < 19 magnitude per exposure when the moon is illuminated and c < 19.5 magnitude per exposure in dark skies. Construction is underway of two further units to be sited in Chile and South Africa which will result in an all-sky daily cadence from 2021. Initially designed for detecting potentially hazardous near earth objects, the ATLAS data enable a range of astrophysical time domain science. To extract transients from the data stream requires a computing system to process the data, assimilate detections in time and space and associate them with known astrophysical sources. Here we describe the hardware and software infrastructure to produce a stream of clean, real, astrophysical transients in real time. This involves machine learning and boosted decision tree algorithms to identify extragalactic and Galactic transients. Typically we detect 10-15 supernova candidates per night which we immediately announce publicly. The ATLAS discoveries not only enable rapid follow-up of interesting sources but will provide complete statistical samples within the local volume of 100 Mpc. A simple comparison of the detected supernova rate within 100 Mpc, with no corrections for completeness, is already significantly higher (factor 1.5 to 2) than the current accepted rates.
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