“Polaroids from Heaven”: Collaboration Between the Marian Library and the Course, Alternative Photography

This presentation covers a collaborative project between the Marian Library and the Department of Art and Design at the University of Dayton

Nitrates in cattle feeding

Published July 1966. Facts and recommendations in this publication may no longer be valid. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalo

Multicenter Phase 2 Trial of Sirolimus for Tuberous Sclerosis: Kidney Angiomyolipomas and Other Tumors Regress and VEGF- D Levels Decrease

Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.We completed a phase 2 multicenter trial to evaluate the efficacy and tolerability of the mTOR inhibitor, sirolimus, for the treatment of kidney angiomyolipomas.36 adults with TSC or TSC/LAM were enrolled and started on daily sirolimus. The overall response rate was 44.4% (95% confidence intervals [CI] 28 to 61); 16/36 had a partial response. The remainder had stable disease (47.2%, 17/36), or were unevaluable (8.3%, 3/36). The mean decrease in kidney tumor size (sum of the longest diameters [sum LD]) was 29.9% (95% CI, 22 to 37; n = 28 at week 52). Drug related grade 1-2 toxicities that occurred with a frequency of >20% included: stomatitis, hypertriglyceridemia, hypercholesterolemia, bone marrow suppression (anemia, mild neutropenia, leucopenia), proteinuria, and joint pain. There were three drug related grade 3 events: lymphopenia, headache, weight gain. Kidney angiomyolipomas regrew when sirolimus was discontinued but responses tended to persist if treatment was continued after week 52. We observed regression of brain tumors (SEGAs) in 7/11 cases (26% mean decrease in diameter), regression of liver angiomyolipomas in 4/5 cases (32.1% mean decrease in longest diameter), subjective improvement in facial angiofibromas in 57%, and stable lung function in women with TSC/LAM (n = 15). A correlative biomarker study showed that serum VEGF-D levels are elevated at baseline, decrease with sirolimus treatment, and correlate with kidney angiomyolipoma size (Spearman correlation coefficient 0.54, p = 0.001, at baseline).Sirolimus treatment for 52 weeks induced regression of kidney angiomyolipomas, SEGAs, and liver angiomyolipomas. Serum VEGF-D may be a useful biomarker for monitoring kidney angiomyolipoma size. Future studies are needed to determine benefits and risks of longer duration treatment in adults and children with TSC.Clinicaltrials.gov NCT00126672

Functional bacteriorhodopsin is efficiently solubilized and delivered to membranes by the chaperonin GroEL

Soluble complexes between the tetradecameric chaperonin GroEL and integral membrane proteins can be efficiently formed by detergent dialysis. For example, GroEL(14) was found to bind a limit of two molecules of bacteriorhodopsin (BR). The GroEL-solubilized BR molecules were rapidly ejected from the chaperonin complexes on the addition of ATP or adenosine 5′-[β,γ-imido]triphosphate but not AMP, indicating that conformational changes induced by nucleotide binding eliminate a binding site for the hydrophobic transmembrane domains. BR retains its native conformation in the GroEL complexes, as judged by the spectral characteristics of the bound retinal. Moreover, the chaperonin-solubilized BR could be transferred efficiently to liposomes and used to effect a light-driven proton gradient, indicating that both native conformation and vectorial insertion were accomplished. These results suggest new approaches to the study of purified integral membrane proteins in their natural membrane environment and raise the prospect that GroEL may have a role in the integration of proteins into the cytoplasmic membrane in vivo