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- 2019
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Tidskriftsartikel (refereegranskat)
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- Alexanderson, Helena, et al.
(författare)
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An Arctic perspective on dating Mid-Late Pleistocene environmental history
- 2014
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 92, s. 9-31
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Forskningsöversikt (refereegranskat)abstract
- To better understand Pleistocene climatic changes in the Arctic, integrated palaeoenvironmental andpalaeoclimatic signals from a variety of marine and terrestrial geological records as well as geochronologicage control are required, not least for correlation to extra-Arctic records. In this paper we discuss,from an Arctic perspective, methods and correlation tools that are commonly used to date ArcticPleistocene marine and terrestrial events. We review the state of the art of Arctic geochronology, withfocus on factors that affect the possibility and quality of dating, and support this overview by examples ofapplication of modern dating methods to Arctic terrestrial and marine sequences.Event stratigraphy and numerical ages are important tools used in the Arctic to correlate fragmentedterrestrial records and to establish regional stratigraphic schemes. Age control is commonly provided byradiocarbon, luminescence or cosmogenic exposure ages. Arctic Ocean deep-sea sediment successionscan be correlated over large distances based on geochemical and physical property proxies for sedimentcomposition, patterns in palaeomagnetic records and, increasingly, biostratigraphic data. Many of theseproxies reveal cyclical patterns that provide a basis for astronomical tuning.Recent advances in dating technology, calibration and age modelling allow for measuring smallerquantities of material and to more precisely date previously undatable material (i.e. foraminifera for 14C,and single-grain luminescence). However, for much of the Pleistocene there are still limits to the resolutionof most dating methods. Consequently improving the accuracy and precision (analytical andgeological uncertainty) of dating methods through technological advances and better understanding ofprocesses are important tasks for the future. Another challenge is to better integrate marine andterrestrial records, which could be aided by targeting continental shelf and lake records, exploringproxies that occur in both settings, and by creating joint research networks that promote collaborationbetween marine and terrestrial geologists and modellers.
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| 4. |
- Backman, Dan, 1972-
(författare)
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Interaction Studies of Secreted Aspartic Proteases (Saps) from Candida albicans : Application for Drug Discovery
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is focused on enzymatic studies of the secreted aspartic proteases (Saps) from Candida albicans as a tool for discovery of anti-candida drugs. C. albicans causes infections in a number of different locations, which differ widely in the protein substrates available and pH. Since C. albicans needs Saps during virulent growth, these enzymes are good targets for drug development.In order to investigate the catalytic characteristics of Saps and their inhibitor affinities, substrate-based kinetic assays were developed. Due to the low sensitivity of these assays, especially at the sub-optimal pH required to mimic the different locations of infections, these assays were not satisfactory. Therefore, a biosensor assay was developed whereby, it was possible to study interaction between Saps and inhibitors without the need to optimise catalytic efficacy. Furthermore, the biosensor assay allowed determination of affinity, as well as the individual association and dissociation rates for inhibitor interactions.Knowledge about substrate specificity, Sap subsite adaptivity, and the pH dependencies of catalytic efficacy has been accumulated. Also, screening of transition-state analogue inhibitors designed for HIV-1 protease has revealed inhibitors with affinity for Saps. Furthermore, the kinetics and pH dependencies of their interaction with Saps have been investigated. One of these inhibitors, BEA-440, displayed a complex interaction with Saps, indicating a conformational change upon binding and a very slow dissociation rate. A time dependent interaction was further supported by inhibition measurements. The structural information obtained affords possibilities for design of new more potent inhibitors that might ultimately become drugs against candidiasis. The strategy to combine substrate specificity studies with inhibitor screening has led to complementary results that generate a framework for further development of potent inhibitors.
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- Östling, Hanna, 1976-, et al.
(författare)
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Global microRNA and protein expression in human term placenta
- 2022
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Ingår i: Frontiers in Medicine. - : Frontiers Media S.A.. - 2296-858X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Description of the global expression of microRNAs (miRNAs) and proteins in healthy human term placentas may increase our knowledge of molecular biological pathways that are important for normal fetal growth and development in term pregnancy. The aim of this study was to explore the global expression of miRNAs and proteins, and to point out functions of importance in healthy term placentas.Materials and methods: Placental samples (n = 19) were identified in a local biobank. All samples were from uncomplicated term pregnancies with vaginal births and healthy, normal weight newborns. Next-generation sequencing and nano-scale liquid chromatographic tandem mass spectrometry were used to analyse miRNA and protein expression, respectively.Results: A total of 895 mature miRNAs and 6,523 proteins were detected in the placentas, of which 123 miRNAs and 346 proteins were highly abundant. The miRNAs were in high degree mapped to chromosomes 19, 14, and X. Analysis of the highly abundant miRNAs and proteins showed several significantly predicted functions in common, including immune and inflammatory response, lipid metabolism and development of the nervous system.Discussion: The predicted function inflammatory response may reflect normal vaginal delivery, while lipid metabolism and neurodevelopment may be important processes for the term fetus. The data presented in this study, with complete miRNA and protein findings, will enhance the knowledge base for future research in the field of placental function and pathology.
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