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The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Integrating protein annotations for the in silico prioritization of putative drug target proteins in malariaMpangase, Phelelani Thokozani 15 May 2013 (has links)
Current anti-malarial methods have been effective in reducing the number of malarial cases. However, these methods do not completely block the transmission of the parasite. Research has shown that repeated use of the current anti-malarial drugs, which include artemisinin-based drug combinations, might be toxic to humans. There have also been reports of an emergence of artemisinin-resistant parasites. Finding anti-malarial drugs through the drug discovery process takes a long time and failure results in a great financial loss. The failure of drug discovery projects can be partly attributed to the improper selection of drug targets. There is thus a need for an eff ective way of identifying and validating new potential malaria drug targets for entry into the drug discovery process. The availability of the genome sequences for the Plasmodium parasite, human host and the Anopheles mosquito vector has facilitated post-genomic studies on malaria. Proper utilizationof this data, in combination with computational biology and bioinformatics techniques, could aid in the in silico prioritization of drug targets. This study was aimed at extensively annotating the protein sequences from the Plasmodium parasites, H. sapiens and A. gambiae with data from di fferent online databases in order to create a resource for the prioritization of drug targets in malaria. Essentiality, assay feasibility, resistance, toxicity, structural information and druggability were the main target selection criteria which were used to collect data for protein annotations. The data was used to populate the Discovery resource (http://malport. bi.up.ac.za/) for the in silico prioritization of potential drug targets. A new version of the Discovery system, Discovery 2.0 (http://discovery.bi.up.ac.za/), has been developed using Java. The system contains new and automatically updated data as well as improved functionalities. The new data in Discovery 2.0 includes UniProt accessions, gene ontology annotations from the UniProt-GOA project, pathways from Reactome and Malaria Parasite Metabolic Pathways databases, protein-protein interactions data from. IntAct as well as druggability data from the DrugEBIlity resource hosted by ChEMBL. Users can access the data by searching with a protein identi er, UniProt accession, protein name or through the advanced search which lets users filter protein sequences based on different protein properties. The results are organized in a tabbed environment, with each tab displaying different protein annotation data. A sample investigation using a previously proposed malarial target, S-adenosyl-Lhomocysteine hydrolase, was carried out to demonstrate the diff erent categories of data available in Discovery 2.0 as well as to test if the available data is su fficient for assessment and prioritization of drug targets. The study showed that using the annotation data in Discovery 2.0, a protein can be assessed, in a species comparative manner, on the potential of being a drug target based on the selection criteria mentioned here. However, supporting data from literature is also needed to further validate the findings. / Dissertation (MSc)--University of Pretoria, 2012. / Biochemistry / unrestricted
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Gemensamma Symboliska Beteenden Och Interaktioner Mellan Neanderthalare Och H. SapiensKarlsson, Julia January 2022 (has links)
The behaviours that the Neanderthals and Homo sapiens sapiens had in common could have made their interaction more advanced and deeper. Ever since Richard E. Green et al’s discovery in 2010 that a lot of the modern day population have inherited about 1-4 % of the genome from Neanderthals, the assumption that Neanderthals are primitive beings lacking advanced cognition has changed. For H. Sapiens to interbreed with Neanderthals one could argue that they could not have been that dissimilar. Since the modern day population inherited parts of the Neanderthals it could be very interesting to bring more insight into how their relationship and interaction would have looked in relation to H. Sapiens. In this thesis some behaviours will be analysed and compared that existed among them both. In this remark it will be about behaviors of a symbolic nature, indicating a more advanced thinking. These are the usage of personal ornaments, the burial practice, and lastly language and speech. The personal ornaments they used are in some instances very similar, but there is also variation in what they put value in as personal ornaments, later H. Sapiens put a lot of energy into making beads of different types, and Neanderthals having a focus on birds of prey. The burial practice is in general nothing that is too common among either of them during the middle palaeolithic or African Middle stone age. Before the upper palaeolithic there is not too much evidence indicating that they had a tradition of burying their dead. In cases they did bury their dead there is evidence of places with multiple burials, maybe working as grave centers. The anatomical capacities for speech existed among them both. When it comes to language it is harder to discern, since it does not fossilise, but since language is symbolic it could be argued that evidence of symbolism among them could indicate that they had language as well. In the discussion and conclusions it is argued that these common behaviours could have made it possible for a more advanced interaction and relationship between the two.
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