Courage for the Era to Come

Commencement address given by Dr. Raymond Walters, President of the University of Cincinnati, to the Autumn 1947 graduating class of The Ohio State University, Men's Gymnasium, Columbus, Ohio, December 19, 1947

Components of the ubiquitin-proteasome pathway compete for surfaces on Rad23 family proteins

Background: The delivery of ubiquitinated proteins to the proteasome for degradation is a key step in the regulation of the ubiquitin-proteasome pathway, yet the mechanisms underlying this step are not understood in detail. The Rad23 family of proteins is known to bind ubiquitinated proteins through its two ubiquitin-associated (UBA) domains, and may participate in the delivery of ubiquitinated proteins to the proteasome through docking via the Rad23 ubiquitin-like (UBL) domain. Results: In this study, we investigate how the interaction between the UBL and UBA domains may modulate ubiquitin recognition and the delivery of ubiquitinated proteins to the proteasome by autoinhibition. We have explored a competitive binding model using specific mutations in the UBL domain. Disrupting the intramolecular UBL-UBA domain interactions in HHR23A indeed potentiates ubiquitin-binding. Additionally, the analogous surface on the Rad23 UBL domain overlaps with that required for interaction with both proteasomes and the ubiquitin ligase Ufd2. We have found that mutation of residues on this surface affects the ability of Rad23 to deliver ubiquitinated proteins to the proteasome. Conclusions: We conclude that the competition of ubiquitin-proteasome pathway components for surfaces on Rad23 is important for the role of the Rad23 family proteins in proteasomal targeting

Inclusion of Experimental Information in First Principles Modeling of Materials

We propose a novel approach to model amorphous materials using a first principles density functional method while simultaneously enforcing agreement with selected experimental data. We illustrate our method with applications to amorphous silicon and glassy GeSe$_2$. The structural, vibrational and electronic properties of the models are found to be in agreement with experimental results. The method is general and can be extended to other complex materials.Comment: 11 pages, 8 PostScript figures, submitted to J. Phys.: Condens. Matter in honor of Mike Thorpe's 60th birthda

Recreational boating activity and its impact on the recruitment and survival of the oyster Crassostrea virginica on intertidal reefs in Mosquito Lagoon, Florida

Along the east coast of central Florida in the Indian River Lagoon system, intense recreational boating activity occurs year-round, and intertidal reefs of the eastern oyster Crassostrea virginica (Gmelin) with dead margins (mounds of disarticulated shells) on their seaward edges are commonly found adjacent to major boating channels. These dead margins are caused, at least in part, by boat wakes and extend significantly higher above the high water line than reefs lacking dead margins (pristine reefs). To determine if these impacted oyster reefs alter recruitment and subsequent survival of C. virginica, three 8-wk field trials were run between May 2001 and April 2002 in Mosquito Lagoon. During each trial, data were also collected on total sediment loads, silt/clay fractions and relative water motion. Although recruitment did not differ between impacted and pristine reef\u27s, juvenile survival was significantly reduced on impacted reefs. Additionally, larval recruitment and subsequent mortality were greatest during our summer trial. Total sediment loads, percent silt/clay, and relative water motion were significantly higher on impacted reefs. For these three variables, the largest values were consistently found at the bases of exposed (seaward) regions of impacted reefs. By documenting a positive relationship between reduced success of C. virginica and dead margins, and knowing that boat wakes contribute to the development of dead margins. we have provided the first cause and effect mechanism between intense recreational boating activity and increased oyster morality

Reverse Monte Carlo modeling of amorphous silicon

An implementation of the Reverse Monte Carlo algorithm is presented for the study of amorphous tetrahedral semiconductors. By taking into account a number of constraints that describe the tetrahedral bonding geometry along with the radial distribution function, we construct a model of amorphous silicon using the reverse monte carlo technique. Starting from a completely random configuration, we generate a model of amorphous silicon containing 500 atoms closely reproducing the experimental static structure factor and bond angle distribution and in improved agreement with electronic properties. Comparison is made to existing Reverse Monte Carlo models, and the importance of suitable constraints beside experimental data is stressed.Comment: 6 pages, 4 PostScript figure

Challenges facing gap-based silviculture and possible solutions for mesic northern forests in North America

Gap-based silvicultural systems were developed under the assumption that richness, and diversity of tree species and other biota positively respond to variation in size of harvest-created canopy gaps. However, varying gap size alone often does not meet diversity objectives and broader goals to address contemporary forest conditions. Recent research highlights the need to consider site factors and history, natural disturbance models, within-gap structure and recruitment requirements in addition to light resources for desired tree diversity. This synthesis brings together silvicultural developments and ecological literature on gap-based management, highlighting interactions with other factors such as microsite conditions, non-tree vegetation and more. We pose a revised concept for managers and researchers to use in prescriptions and studies focused on integrated overstory and understory manipulations that increase structural complexity within and around canopy openings

Specific Inhibition of p97/VCP ATPase and Kinetic Analysis Demonstrate Interaction between D1 and D2 ATPase domains

The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings, and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP, and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (k_(cat)/K_m) of D1 ATP hydrolysis 280-fold, by increasing k_(cat) 7-fold and decreasing K_m about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N-domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97