| 1. |
- Pang, Siew Siew, et al.
(author)
-
The structural basis for complement inhibition by gigastasin, a protease inhibitor from the giant Amazon leech
- 2017
-
In: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 199:11, s. 3883-3891
-
Journal article (peer-reviewed)abstract
- Complement is crucial to the immune response, but dysregulation of the system causes inflammatory disease. Complement is activated by three pathways: classical, lectin, and alternative. The classical and lectin pathways are initiated by the C1r/C1s (classical) and MASP-1/MASP-2 (lectin) proteases. Given the role of complement in disease, there is a requirement for inhibitors to control the initiating proteases. In this article, we show that a novel inhibitor, gigastasin, from the giant Amazon leech, potently inhibits C1s and MASP-2, whereas it is also a good inhibitor of MASP-1. Gigastasin is a poor inhibitor of C1r. The inhibitor blocks the active sites of C1s and MASP-2, as well as the anion-binding exosites of the enzymes via sulfotyrosine residues. Complement deposition assays revealed that gigastasin is an effective inhibitor of complement activation in vivo, especially for activation via the lectin pathway. These data suggest that the cumulative effects of inhibiting both MASP-2 and MASP-1 have a greater effect on the lectin pathway than the more potent inhibition of only C1s of the classical pathway.
|
|
| 2. |
- Unsworth, Carolyn A., et al.
(author)
-
Development of a standardised Occupational Therapy - Driver Off-Road Assessment Battery to assess older and/or functionally impaired drivers
- 2012
-
In: Australian Occupational Therapy Journal. - : Wiley. - 0045-0766 .- 1440-1630. ; 59:1, s. 23-36
-
Journal article (peer-reviewed)abstract
- Introduction: Research has been conducted over several years to develop a new off-road assessment battery referred to as the Occupational Therapy - Driver Off-Road Assessment Battery. This article documents the development of the Battery, and provides preliminary research evidence to support its content and predictive validity. Methods: Literature reviews and a focus group with nine driver assessor occupational therapists were undertaken, as well as data collection using the Occupational Therapy Driver Off-Road Assessment Battery with 246 clients. A Classification and Regression Tree model was constructed to ascertain the predictive validity of the Battery, with fitness- to-drive as the outcome. Results: Twenty-one physical, 13 sensory and seven assessments of cognition / perception were identified as being reflective of the skills required for driving. Following rating of their psychometric properties, the best assessments were presented to focus group members. The driver assessors supported the inclusion of several assessments and encouraged the development of new assessments. A draft version of the Occupational Therapy -Driver Off-Road Assessment Battery was tested and found to have excellent predictive validity for client on-road performance of 82.6%. The Classification and Regression Tree model showed that client performance on tests included in the Battery should be used together, rather than in isolation, to support fitness-to-drive recommendations. Conclusion: This research identified the most suitable physical, sensory and cognitive assessments to include in the Occupational Therapy -Driver Off-Road Assessment Battery, and provided support for its validity. The development of this standardised battery assists driver assessors to accurately and consistently assess and report the offroad driving capacity of clients.
|
|
