Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding

Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. These diseases can be hereditary in humans and four of the many disease-associated missense mutants of PrP are in the hydrophobic core: V180I, F198S, V203I and V210I. The T183A mutation is related to the hydrophobic core mutants as it is close to the hydrophobic core and known to cause instability. We have performed extensive molecular dynamics simulations of these five PrP mutants and compared their dynamics and conformations to wild-type PrP. The simulations highlight the changes that occur upon introduction of mutations and help to rationalize experimental findings. Changes can occur around the mutation site, but they can also be propagated over long distances. In particular, the F198S and T183A mutations lead to increased flexibility in parts of the structure that are normally stable, and the short β-sheet moves away from the rest of the protein. Mutations V180I, V210I and, to a lesser extent, V203I cause changes similar to those observed upon lowering the pH, which has been linked to misfolding. Early misfolding is observed in one V180I simulation. Overall, mutations in the hydrophobic core have a significant effect on the dynamics and stability of PrP, including the propensity to misfold, which helps to explain their role in the development of familial prion diseases

EVALUATING MEASURES TO IMPROVE AGRICULTURAL INPUT USE

This paper provides guidelines to assist policymakers and analysts in (1) identifying promising public and private actions for promoting agricultural intensification by improving the availability and profitability of agricultural inputs; and (2) evaluating the relative costs and benefits of alternative actions. The guidelines are illustrated by reference to a study of phosphate fertilizer promotion in Mali originally conducted by IFDC researchers.Farm Management,

Antimicrobial Activity and Effect of Selected Essential Oil Components on Cell Membrane Lipids

The objectives of this study were to evaluate the antimicrobial activity of essential oil components (EOC) against Salmonella Typhimurium and Listeria monocytogenes and evaluate changes in bacterial membrane composition by observing changes in the fatty acids of Salmonella associated with exposure and adaptation to (or growth in the presence of) cinnamaldehyde (CIN) and carvacrol (CRV) EOC. Ten EOC were tested for efficacy using the broth microdilution and macrodilution methods. Beta-caryophyllene, limonene, alpha-pinene, and thymol were not lethal to Salmonella and Listeria at 2800mg/L. Dose-response models showed that the most effective EOC against Salmonella were CIN and CRV (50% probability of lethality with avg. of 280mg/L and 1080mg/L, respectively) regardless of method. CIN (790mg/L) and RHO (1810mg/L) were the most lethal against Listeria. CIN- or CRV-adapted or non-adapted Salmonella were inoculated into broth containing 250mg/L CIN, 871mg/L CRV, or no EOC. At 2 and 24h, the saturated fatty acid (SFA) to unsaturated fatty acid (UFA) ratio in the membrane of CIN- or CRV-adapted cells treated with CIN or CRV was numerically higher than in the non-adapted cells treated with CIN or CRV. Significant (p\u3c0.05) changes were observed with CIN or CRV exposure. After 2h of exposure to CIN, the non-adapted CIN-treated cells had lower total phospholipid fatty acid (PLFA), lower C16:1w7c, and higher C18:0 and SFA than the non-adapted control. After 24h of exposure to CIN, the non-adapted CIN-treated Salmonella had lower Cy17:0 and Cy19:0 than the non-adapted control and higher C16:0 and SFA. Compared to the non-adapted control at 2h, the non-adapted CRV-treated Salmonella had lower PLFA, and lower C16:1w7c, Cy17:0, C18:1w9c, C18:1w7c, and UFA and higher C14:0, C18:0, SFA, and SFA/UFA ratio. At 24h, the non-adapted CRV-treated cells had lower PLFA, Cy17:0, C18:1w7c, and UFA and higher C16:1w7c and SFA than the non-adapted control. Antimicrobial treatment appeared to decrease the fluidity of the Salmonella membrane by increasing SFA. This decreased fluidity may prevent additional CIN and CRV from permeating. Growth in the presence of the antimicrobial had a much smaller effect on the fatty acid composition. Additional measurement of the membrane transition temperature from gel-to-liquid-crystalline phase would indicate fluidity

FINANCIAL AND RISK ANALYSIS OF MAIZE TECHNOLOGY IN ETHIOPIA, BASED ON CERES-MAIZE MODEL RESULTS

This paper presents a financial and risk analysis of improved versus traditional maize production technology in Ethiopia, based on yields simulated with the CERES-Maize crop growth model (Schulthess and Ward, 2000). The purpose is to analyze the potential performance of the SG2000/Ministry of Agriculture program technology under less favorable meteorological conditions (rainfall level and distribution), and in areas with lower agroecological potential than those covered by the SG2000/MOA program through 1998. At the time of this study, expansion of the MOA program into lower potential zones seemed likely. Results show that use of fertilizer and improved seed is highly profitable under a variety of assumptions about crop growth conditions, maize prices, and fertilizer costs. Risk is examined using simple sensitivity and breakeven analysis, and stochastic dominance analysis.Crop Production/Industries, Research and Development/Tech Change/Emerging Technologies,

Fertilizer Consumption Trends in Sub-Saharan Africa

Crop Production/Industries, Downloads December 2008 - July 2009: 12,

Advanced Transport Operating System (ATOPS) color displays software description microprocessor system

This document describes the software created for the Sperry Microprocessor Color Display System used for the Advanced Transport Operating Systems (ATOPS) project on the Transport Systems Research Vehicle (TSRV). The software delivery known as the 'baseline display system', is the one described in this document. Throughout this publication, module descriptions are presented in a standardized format which contains module purpose, calling sequence, detailed description, and global references. The global reference section includes procedures and common variables referenced by a particular module. The system described supports the Research Flight Deck (RFD) of the TSRV. The RFD contains eight cathode ray tubes (CRTs) which depict a Primary Flight Display, Navigation Display, System Warning Display, Takeoff Performance Monitoring System Display, and Engine Display

Advanced Transport Operating System (ATOPS) color displays software description: MicroVAX system

This document describes the software created for the Display MicroVAX computer used for the Advanced Transport Operating Systems (ATOPS) project on the Transport Systems Research Vehicle (TSRV). The software delivery of February 27, 1991, known as the 'baseline display system', is the one described in this document. Throughout this publication, module descriptions are presented in a standardized format which contains module purpose, calling sequence, detailed description, and global references. The global references section includes subroutines, functions, and common variables referenced by a particular module. The system described supports the Research Flight Deck (RFD) of the TSRV. The RFD contains eight Cathode Ray Tubes (CRTs) which depict a Primary Flight Display, Navigation Display, System Warning Display, Takeoff Performance Monitoring System Display, and Engine Display