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| 23. |
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| 24. |
- Steele, A., et al.
(författare)
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Organic synthesis on Mars by electrochemical reduction of CO2
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:10
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Tidskriftsartikel (refereegranskat)abstract
- The sources and nature of organic carbon on Mars have been a subject of intense research. Steele et al. (2012) showed that 10 martian meteorites contain macromolecular carbon phases contained within pyroxene- and olivine-hosted melt inclusions. Here, we show that martian meteorites Tissint, Nakhla, and NWA 1950 have an inventory of organic carbon species associated with fluid-mineral reactions that are remarkably consistent with those detected by the Mars Science Laboratory (MSL) mission. We advance the hypothesis that interactions among spinel-group minerals, sulfides, and a brine enable the electrochemical reduction of aqueous CO2 to organic molecules. Although documented here in martian samples, a similar process likely occurs wherever igneous rocks containing spinel-group minerals and/or sulfides encounter brines.
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| 25. |
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| 26. |
- Biederstädt, A., et al.
(författare)
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SUMO pathway inhibition targets an aggressive pancreatic cancer subtype
- 2020
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 69, s. 1472-1482
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies. Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC. Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition. Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype. © 2020 American Medical Association. All rights reserved.
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| 27. |
- Bloecker, K., et al.
(författare)
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Tibial coverage, meniscus position, size and damage in knees discordant for joint space narrowing - data from the Osteoarthritis Initiative
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:3, s. 419-427
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Meniscal extrusion is thought to be associated with less meniscus coverage of the tibial surface, but the association of radiographic disease stage with quantitative measures of tibial plateau coverage is unknown. We therefore compared quantitative and semi-quantitative measures of meniscus position and morphology in individuals with bilateral painful knees discordant on medial joint space narrowing (mJSN). Methods: A sample of 60 participants from the first half (2,678 cases) of the Osteoarthritis Initiative cohort fulfilled the inclusion criteria: bilateral frequent pain, Osteoarthritis Research Society International (OARSI) mJSN grades 1-3 in one, no-JSN in the contra-lateral (CL), and no lateral JSN in either knee (43 unilateral mJSN1; 17 mJSN2/3; 22 men, 38 women, body mass index (BMI) 31.3 +/- 3.9 kg/m(2)). Segmentation and three-dimensional quantitative analysis of the tibial plateau and meniscus, and semiquantitative evaluation of meniscus damage (magnetic resonance imaging (MRI) osteoarthritis knee score = MOAKS) was performed using coronal 3T MR images (MPR DESSwe and intermediate-weighted turbo spin echo (IW-TSE) images). CL knees were compared using paired t-tests (between-knee, within-person design). Results: Medial tibial plateau coverage was 36 +/- 9% in mJSN1 vs 45 +/- 8% in CL no-JSN knees, and was 31 +/- 9% in mJSN2/3 vs 46 +/- 6% in no-JSN knees (both P < 0.001). mJSN knees showed greater meniscus extrusion and damage (MOAKS), but no significant difference in meniscus volume. No significant differences in lateral tibial coverage, lateral meniscus morphology or position were observed. Conclusions: Knees with medial JSN showed substantially less medial tibial plateau coverage by the meniscus. We suggest that the less meniscal coverage, i.e., less mechanical protection may be a reason for greater rates of cartilage loss observed in JSN knees. (C) 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 28. |
- Carrasco, Marta, et al.
(författare)
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Probing the Azaaurone Scaffold against the Hepatic and Erythrocytic Stages of Malaria Parasites
- 2016
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Ingår i: Chemmedchem. - : Wiley. - 1860-7179. ; 11:19, s. 2194-2204
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Tidskriftsartikel (refereegranskat)abstract
- The potential of azaaurones as dual-stage antimalarial agents was investigated by assessing the effect of a small library of azaaurones on the inhibition of liver and intraerythrocytic lifecycle stages of the malaria parasite. The whole series was screened against the blood stage of a chloroquine-resistant Plasmodium falciparum strain and the liver stage of P.berghei, yielding compounds with dual-stage activity and sub-micromolar potency against erythrocytic parasites. Studies with genetically modified parasites, using a phenotypic assay based on the P.falciparum Dd2-ScDHODH line, which expresses yeast dihydroorotate dehydrogenase (DHODH), showed that one of the azaaurone derivatives has the potential to inhibit the parasite mitochondrial electron-transport chain. The global urgency in finding new therapies for malaria, especially against the underexplored liver stage, associated with chemical tractability of azaaurones, warrants further development of this chemotype. Overall, these results emphasize the azaaurone chemotype as a promising scaffold for dual-stage antimalarials.
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| 29. |
- Cotofana, S., et al.
(författare)
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Relationship between knee pain and the presence, location, size and phenotype of femorotibial denuded areas of subchondral bone as visualized by MRI
- 2013
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 21:9, s. 1214-1222
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Conflicting associations between imaging biomarkers and pain in knee osteoarthritis (OA) have been reported. A relation between pain and denuded areas of subchondral bone (dABs) has been suggested and this study explores this relationship further by relating the presence, phenotype, location and size of dABs to different measures of knee pain. Methods: 633 right knees from the Osteoarthritis Initiative (OAI) (250 men, age 61.7 +/- 9.6 yrs, BMI 29.4 +/- 4.7 kg/m(2)) were included. Manual segmentation of the femorotibial cartilage plates was performed on 3 T coronal fast low angle shot with water excitation (FLASHwe) images. dABs were defined as areas where the subchondral bone was uncovered by cartilage. The following measures of pain were used: weightbearing-, non-weightbearing-, moderate-to-severe-, infrequent- and frequent knee pain. Results: Using pain measures from subjects without dABs as a reference, those with at least one dAB had a 1.64-fold higher prevalence ratio [PR, 95% confidence interval (CI) 1.24-2.18] to have frequent and 1.45-fold higher for moderate-to-severe knee pain (95% CI 1.13-1.85). Subjects with dABs in central subregions had a 1.53-fold increased prevalence of having weightbearing pain (95% Cl 1.20-1.97), especially when the central subregion was moderately (>10%) denuded (PR 1.81, 95% CI 135-2.42). Individuals with cartilage-loss-type dABs had a slightly higher prevalence (PR 1.13, 95% CI 1.00-1.27) of having frequent knee pain compared to individuals with intra-chondral-osteophyte-type dABs. Conclusion: This study supports a positive relation between femorotibial dABs and knee pain, especially when the dABs are located centrally (i.e., in weightbearing regions) or when the respective central subregion is moderately denuded. (C) 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
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| 30. |
- Evangelista, C, et al.
(författare)
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Measurement of the (p)over-barp->KsKs reaction for 0.6 to 1.9 GeV/c
- 1997
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Ingår i: PHYSICAL REVIEW D. - : AMER INST PHYSICS. - 0556-2821. ; 56:7, s. 3803-3810
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Tidskriftsartikel (refereegranskat)abstract
- The <(p)over bar p> --> KSKS --> 4 pi(+/-) cross section was measured at incident antiproton momenta between 0.6 and 1.9 GeV/c using the CERN Low Energy Antiproton Ring. This investigation was part of a systematic study of in-flight antiproton-proton anni
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