Biocuration is manual scientific collection, annotation and validation of literary information of biological and model organisms into a single database. Successful biocuration processes involve those with an extensive collection of literature, a user-friendly database interfaces for entering and analyzing data from published papers, and highly regulated training and quality assurance protocols. Due to the rapid expansion of biomedical literature, an efficient and accurate biocuration process has become more valuable due to the magnitude of data available in published literature. As the biocuration process incorporates undergraduates, it is critical that the medium for data collection is simple, ergonomic, and infallible. A reconstructed FileMaker Pro database was introduced to previously trained undergraduate students for process evaluation. Streamlining the biocuration process and grouping data structure to be more intuitive were two goals the new database interface hoped to achieve. The creation of a rigorous training program and strict quality management protocol is needed to prepare the lab for the introduction of efficient biocuration processes. Through the database designing process, training protocols were drafted to effectively call the biocurator’s attention to important changes in the interface design. Upon prototyping the database, entry errors were reviewed, training protocols were adjusted, and the quality protocols were drafted. When the combination of undergraduate biocurators and the reconstructed database under these new protocols was compared to statistics in the biocuration field, results proved to show increase in both productivity rates as well as accuracy rates. By having such efficiency at the undergraduate level, subject matter experts will no longer be required to perform this type of research and can focus on analysis. This will increase research productivity and reduce costs in the overall biocuration process. With over 12,000 published papers regarding Amyotrophic Lateral Sclerosis on Pubmed in 2014 alone, this revolutionary combination could lead to quickly finding a suitable cure for these patients.

published_or_final_version / Zoology / Master / Master of Philosophy

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease of unclear aetiology, although the general consensus is of a multifactorial disease. The kynurenine pathway (KP), activated during neuroinflammation, is emerging as a possible contributory factor in ALS. The KP is the major route for tryptophan (TRP) catabolism. The intermediates generated can be either neurotoxic, such as quinolinic acid (QUIN), or neuroprotective, such as picolinic acid (PIC), an important endogenous metal chelator. The first and inducible enzyme is indoleamine 2,3-dioxygenase (IDO). As the extent of the involvement of the KP in ALS is unknown, the main aim of this thesis was to attempt to answer that question. The techniques used in this work include HPLC, GC/MS, RT-PCR, immunohistochemistry and immunocyctochemsitry. The main findings of this project are: (1) the complete KP is present in the mouse motor neuron cell line, NSC-34; (2) QUIN toxicity on NSC-34 cells may be ameliorated through the administration of NMDA antagonists, neuroprotective kynurenines, kynurenine inhibitor and QUIN monoclonal antibody; (3) in ALS patients, QUIN CSF and serum levels are significantly elevated, while PIC serum levels are significantly reduced; (4) ALS brain and spinal cord tissue show extensive microglia activation and positive immunoreactivity IDO and QUIN in spinal motor neurons and Betz cells in the motor cortex; and (5) kynurenine pathway inhibitor and analogue, R061-8048 and tranilast, are able to prolong the survival in the G93A SOD1 ALS transgenic mouse model. In conclusion, this study provide the first strong evidence for the involvement of the KP in ALS, and these data point to an inflammation-driven excitotoxic-chelation defective mechanism in ALS, which is amenable to KP analogue and inhibitor in ALS transgenic mice.

Diss. (sammanfattning) Umeå : Univ., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2008. / Title from title screen (site viewed Mar. 10, 2009). PDF text: xvi, 170 p. : ill. (some col.) ; 2 Mb. UMI publication number: AAT 3331437. Includes bibliographical references. Also available in microfilm and microfiche formats.

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 166-193).

Thesis (M. Phil.)--University of Hong Kong, 1998. / Cover title. Includes bibliographical references (leaves 169-192).

Thesis (Ph. D.)--University of Washington, 1996. / Vita. Includes bibliographical references (leaves [117]-142).

Thesis (M.Sc.)--York University, 2008. Graduate Programme in Kinesiology and Health Science. / Typescript. Includes bibliographical references (leaves 84-103). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&res_dat=xri:pqdiss&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR51577