| 1. |
- McCrae, Cristopher, et al.
(författare)
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Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells
- 2018
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Ingår i: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 59:6, s. 713-722
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Tidskriftsartikel (refereegranskat)abstract
- Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-beta. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.
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| 2. |
- Pérez-Consuegra, N., et al.
(författare)
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Provenance analysis of the Pliocene Ware Formation in the Guajira Peninsula, northern Colombia: Paleodrainage implications
- 2018
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Ingår i: Journal of South American Earth Sciences. - : Elsevier BV. - 0895-9811. ; 81, s. 66-77
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Tidskriftsartikel (refereegranskat)abstract
- The Cocinetas Basin in the Guajira Peninsula, the northernmost tip of South America, today has a dry climate with low rainfall (<500 mm/yr), a long dry season (>ten months) and no year-long rivers or permanent standing bodies of fresh water. In contrast, the fossil and geological record indicate that the Cocinetas Basin was much wetter during the Miocene-Pliocene (∼17–2.8 Ma). Water needed to sustain the paleofauna could either have originated from local sources or been brought by a larger river system (e.g. proto Magdalena/Orinoco river) with headwaters either in Andean ranges or the Guyana shield. We present a provenance study of the Pliocene Ware Formation, using petrographic analysis of conglomerate clasts and heavy minerals, and U-Pb dating of 140 detrital zircons. Clasts and heavy minerals are typical of ensialic metamorphic and igneous sources. The detrital zircon age distribution indicates the Guajira ranges as the most probable sediment source. The overall results indicate that the fluvial system of the Ware Formation drained the surrounding ranges. The water was probably derived by local precipitation onto the Guajira peninsula.
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| 4. |
- Vakis, A.I., et al.
(författare)
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Modeling and simulation in tribology across scales : An overview
- 2018
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Ingår i: Tribology International. - : Elsevier. - 0301-679X .- 1879-2464. ; 125, s. 169-199
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes recent advances in the area of tribology based on the outcome of a Lorentz Center workshop surveying various physical, chemical and mechanical phenomena across scales. Among the main themes discussed were those of rough surface representations, the breakdown of continuum theories at the nano- and micro-scales, as well as multiscale and multiphysics aspects for analytical and computational models relevant to applications spanning a variety of sectors, from automotive to biotribology and nanotechnology. Significant effort is still required to account for complementary nonlinear effects of plasticity, adhesion, friction, wear, lubrication and surface chemistry in tribological models. For each topic, we propose some research directions.
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| 7. |
- Cabrera, O, et al.
(författare)
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Automated, High-Throughput Assays for Evaluation of Human Pancreatic Islet Function
- 2007
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Ingår i: Cell transplantation. - : SAGE Publications. - 1555-3892 .- 0963-6897. ; 16:10, s. 1039-1048
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Tidskriftsartikel (refereegranskat)abstract
- An important challenge in pancreatic islet transplantation in association with type 1 diabetes is to define automatic high-throughput assays for evaluation of human islet function. The physiological techniques presently used are amenable to small-scale experimental samples and produce descriptive results. The postgenomic era provides an opportunity to analyze biological processes on a larger scale, but the transition to high-throughput technologies is still a challenge. As a first step to implement high-throughput assays for the study of human islet function, we have developed two methodologies: multiple automated perifusion to determine islet hormone secretion and high-throughput kinetic imaging to examine islet cellular responses. Both technologies use fully automated devices that allow performing simultaneous experiments on multiple islet preparations. Our results illustrate that these technologies can be applied to study the functional status and explore the pharmacological profiles of islet cells. These methodologies will enable functional characterization of human islet preparations before transplantation and thereby provide the basis for the establishment of predictive tests for β-cell potency.
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