A coiled coil trigger site is essential for rapid binding of synaptobrevin to the SNARE acceptor complex.

Exocytosis from synaptic vesicles is driven by stepwise formation of a tight alpha-helical complex between the fusing membranes. The complex is composed of the three SNAREs: synaptobrevin 2, SNAP-25, and syntaxin 1a. An important step in complex formation is fast binding of vesicular synaptobrevin to the preformed syntaxin 1.SNAP-25 dimer. Exactly how this step relates to neurotransmitter release is not well understood. Here, we combined different approaches to gain insights into this reaction. Using computational methods, we identified a stretch in synaptobrevin 2 that may function as a coiled coil "trigger site." This site is also present in many synaptobrevin homologs functioning in other trafficking steps. Point mutations in this stretch inhibited binding to the syntaxin 1.SNAP-25 dimer and slowed fusion of liposomes. Moreover, the point mutations severely inhibited secretion from chromaffin cells. Altogether, this demonstrates that the trigger site in synaptobrevin is crucial for productive SNARE zippering.

Report of Recommendations to the Iowa Commission of Veterans Affairs, June 30, 2005

State Audit Reports

Report of Recommendations to the Iowa Department of Transportation on Review of Selected General and Application Controls over the Accounts Payable System, July 11, 2005 to August 3, 2005

State Audit Reports

The Paediatric Rheumatology International Trials Organisation provisional criteria for the evaluation of response to therapy in juvenile dermatomyositis.

OBJECTIVE: To develop a provisional definition for the evaluation of response to therapy in juvenile dermatomyositis (DM) based on the Paediatric Rheumatology International Trials Organisation juvenile DM core set of variables. METHODS: Thirty-seven experienced pediatric rheumatologists from 27 countries achieved consensus on 128 difficult patient profiles as clinically improved or not improved using a stepwise approach (patient's rating, statistical analysis, definition selection). Using the physicians' consensus ratings as the "gold standard measure," chi-square, sensitivity, specificity, false-positive and-negative rates, area under the receiver operating characteristic curve, and kappa agreement for candidate definitions of improvement were calculated. Definitions with kappa values >0.8 were multiplied by the face validity score to select the top definitions. RESULTS: The top definition of improvement was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 1 of the remaining worsening by more than 30%, which cannot be muscle strength. The second-highest scoring definition was at least 20% improvement from baseline in 3 of 6 core set variables with no more than 2 of the remaining worsening by more than 25%, which cannot be muscle strength (definition P1 selected by the International Myositis Assessment and Clinical Studies group). The third is similar to the second with the maximum amount of worsening set to 30%. This indicates convergent validity of the process. CONCLUSION: We propose a provisional data-driven definition of improvement that reflects well the consensus rating of experienced clinicians, which incorporates clinically meaningful change in core set variables in a composite end point for the evaluation of global response to therapy in juvenile DM.

Report of Recommendations to the Iowa Law Enforcement Academy, June 30, 2005

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Report of Recommendations to the Iowa Department of Revenue, June 30, 2005

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Report of Recommendations to the Iowa Braille and Sight Saving School, June 30, 2005

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Report of Recommendations to the Iowa Department of Agriculture and Land Stewardship, June 30, 2005

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Report of Recommendations to the Office of the Governor, June 30, 2005

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Report of Recommendations to the Office of Secretary of State, June 30, 2005

State Audit Reports

Report of Recommendations to the Iowa Department of Elder Affairs, June 30, 2005

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Report of Recommendations to the Iowa Department of Public Health, June 30, 2005

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Report of Recommendations to the Iowa Department of Human Rights, June 30, 2005

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Report of Recommendations to the Iowa Department of Justice, June 30, 2005

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Report of Recommendations to the Iowa Department of Human Services - Central Distribution Center, June 30, 2005

Other Audit Reports - DHS Institutions