Biomedical subjects

Derek Wilson

Publications and source records attributed to Derek Wilson.

6 recordsLinked to original sources

PubMed2025

High-Affinity, Structure-Validated and Selective Macrocyclic Peptide Tools for Chemical Biology Studies of Huntingtin.

Huntington's disease (HD) is a fatal neurodegenerative disorder caused by a CAG repeat expansion in the Huntingtin (HTT) gene, with no disease-modifying therapies currently available. The precise molecular function of the HTT protein is unclear, and the lack of selective chemical tools has limited functional studies. We have identified and characterized macrocyclic peptide binders targeting HTT. These binders exhibit low-nanomolar affinity in vitro and engage distinct HTT and HTT-HAP40 interfaces, as revealed by hydrogen-deuterium exchange mass spectrometry and cryo-electron microscopy. Chemoproteomics confirmed selective binding in cell extracts from wildtype but not HTT-null cell lines. HAP40 consistently and stoichiometrically co-purified with HTT across cell lines, including with HTT variants containing different CAG repeat lengths, highlighting the broad presence of the HTT-HAP40 complex.

HAP40↗

PubMed2007

New developments in the InterPro database.

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

Databases, Protein↗

PubMed2006

The SUPERFAMILY database in 2007: families and functions.

The SUPERFAMILY database provides protein domain assignments, at the SCOP 'superfamily' level, for the predicted protein sequences in over 400 completed genomes. A superfamily groups together domains of different families which have a common evolutionary ancestor based on structural, functional and sequence data. SUPERFAMILY domain assignments are generated using an expert curated set of profile hidden Markov models. All models and structural assignments are available for browsing and download from http://supfam.org. The web interface includes services such as domain architectures and alignment details for all protein assignments, searchable domain combinations, domain occurrence network visualization, detection of over- or under-represented superfamilies for a given genome by comparison with other genomes, assignment of manually submitted sequences and keyword searches. In this update we describe the SUPERFAMILY database and outline two major developments: (i) incorporation of family level assignments and (ii) a superfamily-level functional annotation. The SUPERFAMILY database can be used for general protein evolution and superfamily-specific studies, genomic annotation, and structural genomics target suggestion and assessment.

Databases, Protein↗

PubMed2004

A model for predicting dissolved organic carbon distribution in a reservoir water using fluorescence spectroscopy.

A number of water treatment works (WTW) in the north of England (UK) have experienced problems in reducing the dissolved organic carbon (DOC) present in the water to a sufficiently low level. The problems are experienced in autumn/winter when the colour increases and the coagulant dose at the WTW needs to be increased in order to achieve sufficient colour removal. However, the DOC content of the water varies little throughout the year. To investigate this further, the water was fractionated using resin adsorption techniques into its hydrophobic (fulvic and humic acid fractions) and hydrophilic (acid and non-acid fractions) components. The fractionation process yields useful information on the changing concentration of each fraction but is time consuming and labour intensive. Here, a method of rapidly determining fraction concentration was developed using fluorescence spectroscopy. The model created used synchronous spectra of fractionated material compared against bulk water spectra and predicted the fraction concentrations to within 10% for a specific water. The model was unable to predict fraction concentrations for waters from a different watershed.

Carbon↗

PubMed2004

Combination of ferric and MIEX for the treatment of a humic rich water.

Seasonal periods of high rainfall have been shown to cause elevated natural organic matter (NOM) loadings at treatment works. These high levels lead to difficulties in removing sufficient NOM to meet trihalomethane (THM) standards, and hence better alternative treatments are required. Here the removal of NOM was investigated by a new ion exchange process (MIEX) using both bulk and fractionated NOM. Initial results showed that in excess of 80% of the raw water dissolved organic carbon (DOC) and greater than 85% of the UV absorbance from the bulk raw water could be removed by the use of MIEX alone. It was also seen that the removal of the more recalcitrant isolated fractions was increased. When MIEX was combined with a significantly reduced dose of coagulant a slight improvement on the overall DOC and UV removals was observed, however a significant decrease in the amount of THM formation potential (THMFP) in the final water was seen. This combined with the reduction in coagulant would imply a more efficient process during the times when the water becomes increasingly difficult to treat.

Carbon↗

PubMed2003

A follow-up study of persons found not criminally responsible on account of mental disorder in British Columbia.

OBJECTIVE: To describe the characteristics of individuals found not criminally responsible on account of mental disorder (NCRMD) after the 1992 Criminal Code amendments and to track their movement through the forensic system, as well as to unveil the changes to British Columbia's forensic psychiatric system that resulted from Bill C-30. METHOD: Profile information relating to persons found NCRMD between February 4, 1992, and February 4, 1998, in British Columbia was collected and analyzed. Community follow-up data was collected and analyzed for a 24-month period following a subject's discharge from hospital. RESULTS: A substantially greater number of individuals entered the forensic psychiatric system in British Columbia after Bill C-30 was implemented. The post-1992 forensic psychiatric population contained fewer persons charged with serious index offences and a greater number of persons charged with relatively minor offences. The length of hospitalization for the NCRMD cohort decreased substantially after the 1992 Criminal Code amendments. CONCLUSION: The Bill C-30 provisions have made the NCRMD defence an attractive option for defendants and legal counsel.

Adolescent↗