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- Jansson, Anna M., 1979-
(författare)
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Targeting Infectious Disease : Structural and functional studies of proteins from two RNA viruses and Mycobacterium tuberculosis
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The recent emergence of a number of new viral diseases as well as the re-emergence of tuberculosis (TB), indicate an urgent need for new drugs against viral and bacterial infections.Coronavirus nsp1 has been shown to induce suppression of host gene expression and interfere with host immune response. However, the mechanism behind this is currently unknown. Here we present the first nsp1 structure from an alphacoronavirus, Transmissible gastroenteritis virus (TGEV) nsp1. Contrary to previous speculation, the TGEV nsp1 structure clearly shows that alpha- and betacoronavirus nsp1s have a common evolutionary origin. However, differences in conservation, shape and surface electrostatics indicate that the mechanism for nsp1-induced suppression of host mRNA translation is likely to be different in the alpha- and betacoronavirus genera.The Modoc virus is a neuroinvasive rodent virus with similar pathology as flavivirus encephalitis in humans. The flaviviral methyltransferase catalyses the two methylations required to complete 5´ mRNA capping, essential for mRNA stability and translation. The structure of the Modoc NS5 methyltransferase domain was determined in complex with its cofactor S-adenosyl-L-methionine. The observed methyltransferase conservation between Modoc and other flaviviral branches, indicates that it may be possible to identify drugs that target a range of flaviviruses and supports the use of Modoc virus as a model for general flaviviral studies.1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is part of the methylerythritol phosphate (MEP) pathway that produces essential precursors for isoprenoid biosynthesis. This pathway is used by a number of pathogens, including Mycobacterium tuberculosis and Plasmodium falciparum, but it is not present in humans. Using a structure-based approach, we designed a number of MtDXR inhibitors, including a novel fosmidomycin-analogue that exhibited improved activity against P.falciparum in an in vitro blood cell growth assay. The approach also allowed the first design of an inhibitor that bridge both DXR substrate and co-factor binding sites, providing a stepping-stone for further optimization.
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| 2. |
- Jones, Benjamin, 1991-
(författare)
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Of seagrass and society : Exploring contributions of tropical seagrass meadows to food security
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Conserving biodiversity while simultaneously feeding a growing population is one of the grand challenges of the Anthropocene. Recently, global assessments have shone a light on the importance of the marine environment for the supply of food (often termed blue food), as well as the diverse and many livelihood opportunities associated to it. Small-scale fisheries (SSF) are essential to this, in which the pursuit of fish and invertebrates are central. If we are to look to blue foods to tackle food insecurity, we need deeper understanding of how coastal habitats function at the nexus of biodiversity, people, and food. Simply put, we need to know how habitats contribute to the supply of food, both in terms of ecological functions and social-economic drivers. Seagrass meadows, diverse and abundant across the Indo-Pacific region, are one of numerous coastal ecosystems that provide food and livelihoods opportunities. Using these systems as a setting, this thesis aims to explore how seagrass meadows and their associated SSF contribute to food security. Comprised of five papers, this thesis relies on a mixed-methods approach to understand seagrass social-ecological systems. The papers range in their dependence on empirical data, their scale as well as the methods employed. Paper I used biodiversity ecosystem function theories to assess the influence of seagrass biota on the production of associated fish in the context of SSF in Tanzania. It highlighted that structural seagrass traits, rather than species richness, are key for driving the abundance and richness of species that are key for food. Paper II investigated the socio-economic drivers that influence seagrass use at the household level. It revealed that household use of seagrass meadows for food and income was higher than all other habitats, and that people use seagrass meadows because they are reliable. It also revealed that household income was key in shaping why people use seagrass meadows as fishing grounds, where both low- and high-income households were dependent on the habitat; low income as a safety-net and high income for high rewards. Paper III examined two key elements of food security, food quantity and quality, and revealed how seagrass meadows contribute to both in the context of micronutrients that are vital for human health. Data from across East Africa showed that seagrass meadows played a more important role than other habitats in providing micronutrient-rich fish species. Paper IV used local ecological knowledge to reveal perceived temporal change in fish and invertebrate abundance and size, but simultaneously identified potential contrasting cognitions that place human communities at risk. Finally, Paper V provided a synthesis of past studies that explored how certain sustainable development initiative result in unintended consequences that influence the supply of blue food. It revealed a number of unintended effects which place the people that use seagrass meadows at risk while at the same time lessening the positive effects of the sustainable development initiative itself. This thesis describes the dynamic interactions between biodiversity, people and food, and place seagrass meadows – habitats that exist globally – at the forefront of the blue food agenda. It highlights how seagrass meadows represent many of the qualities we hope for in a food system – a system that provides sufficient, safe, and nutritious food for multiple and diverse individuals across society.
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