PLBD: protein–ligand binding database of thermodynamic and kinetic intrinsic parameters

We introduce a protein–ligand binding database (PLBD) that presents thermodynamic and kinetic data of reversible protein interactions with small molecule compounds. The manually curated binding data are linked to protein–ligand crystal structures, enabling structure–thermodynamics correlations to be determined. The database contains over 5500 binding datasets of 556 sulfonamide compound interactions with the 12 catalytically active human carbonic anhydrase isozymes defined by fluorescent thermal shift assay, isothermal titration calorimetry, inhibition of enzymatic activity and surface plasmon resonance. In the PLBD, the intrinsic thermodynamic parameters of interactions are provided, which account for the binding-linked protonation reactions. In addition to the protein–ligand binding affinities, the database provides calorimetrically measured binding enthalpies, providing additional mechanistic understanding. The PLBD can be applied to investigations of protein–ligand recognition and could be integrated into small molecule drug design

The rationale and design of the perindopril genetic association study (PERGENE): A pharmacogenetic analysis of angiotensin-converting enzyme inhibitor therapy in patients with stable coronary artery disease

Background: Angiotensin-converting enzyme (ACE) inhibitors reduce clinical symptoms and improve outcome in patients with hypertension, heart failure, and stable coronary artery disease (CAD) and are among the most frequently used drugs in these patient groups. For hypertension, treatment is guided by the level of blood pressure. In the secondary prevention setting, there are no means of guiding therapy. Prior attempts to target ACE-inhibitors to those patients that are most likely to benefit have not been successful, mainly due to the consistency in the treatment effect in clinical subgroups. Still, for prolonged prophylactic treatment with ACE-inhibitors it would be best to target treatment to only those patients most likely to benefit, which would considerably lower the number needed to treat and increase cost-effectiveness. A new approach for such "tailored-therapy" may be to integrate information on the genetic variation between patients. Until now, pharmacogenetic research of the efficacy of ACE-inhibitor therapy in CAD patients is still in a preliminary stage. Methods: The PERindopril GENEtic association study (PERGENE) is a substudy of the EUROPA trial, a randomized double-blind placebo-controlled multicentre clinical trial which demonstrated a beneficial effect of the ACE-inhibitor perindopril in reducing cardiovascular morbidity and mortality in 12.218 patients with stable coronary artery disease (mean follow-up 4.2 years). Blood tubes were received from patients at the beginning of the EUROPA trial and buffy coats were stored at -40°C at the central core laboratory. Candidate genes were selected in the renin-angiotensin-system and bradykinin pathways. Polymorphisms were selected based on haplotype tagging principles using the HapMap genome project, Seattle and other up-to-date genetic database platforms to comprehensively cover all common genetic variation within the genes. Selection also took into consideration the functionality of SNP's, location within the gene (promoter) and existing relevant literature. The main outcome measure of PERGENE is the effect of genetic factors on the treatment benefit with ACE-inhibitors. The size of this pharmacogenetic substudy allows detection with a statistical power of 98% to detect a difference in hazard ratios (treatment effect) of 20% between genotypes with minor allele frequency of 0.20 (two-sided alpha 0.05). Conclusion: The PERGENE study is a large cardiovascular pharmacogenetic study aimed to assess the feasibility of pharmacogenetic profiling of the treatment effect of ACE-inhibitor use with the perspective to individualize treatment in patients with stable coronary artery disease

A Coordinated Effort to Manage Soybean Rust in North America: A Success Story in Soybean Disease Monitoring

Existing crop monitoring programs determine the incidence and distribution of plant diseases and pathogens and assess the damage caused within a crop production region. These programs have traditionally used observed or predicted disease and pathogen data and environmental information to prescribe management practices that minimize crop loss (3,69). Monitoring programs are especially important for crops with broad geographic distribution or for diseases that can cause rapid and great economic losses. Successful monitoring programs have been developed for several plant diseases, including downy mildew of cucurbits, Fusarium head blight of wheat, potato late blight, and rusts of cereal crops (13,36,51,80)

Registration of ‘Choptank’ Wheat

‘Choptank’ (Reg. no. CV-976, PI 639724) is a soft red winter wheat (Triticum aestivum L.) that was jointly developed and released by the Maryland Agricultural Experiment Station, Department of Natural Resource Sciences and Landscape Architecture, and the Virginia Agricultural Experiment Station in 2004. Choptank is named after Maryland’s longest scenic river, which flows 70 miles from the western part of Delaware through Maryland and into the Chesapeake Bay, on Maryland’s Eastern Shore. Choptank has performed well in Maryland, Virginia, and Delaware and provides growers with a high-yielding cultivar with short stature, excellent powdery mildew [caused by Blumeria graminis (DC.) E.O. Speer f. sp. tritici Em. Marchal] resistance and early heading date. Choptank was derived from the cross ‘Coker 9803’ (PI 548845)/‘Freedom’ (PI 562382) that was made in 1990 at Virginia Polytechnic Institute and State University. The population was advanced from the F2 to F5 generation using a modified bulk breeding method. Wheat spikes were selected in Virginia from the population in each generation (F2–F5) based on the absence of obvious disease, early maturity, short straw, and desirable head shape and size. Selected spikes were threshed in bulk and the seed was planted the following fall of each selection year. Spikes selected from the F5:6 bulk block were threshed individually and planted in separate headrows in the fall of 1996 at Beltsville, MD. Choptank was derived as a bulk of one of these F6:7 headrows selected in 1997 and assigned the breeding line designation MD11–52. In addition to high grain yield, Choptank was selected on the basis of earliness of head emergence, short plant height, and resistance to powdery mildew. Choptank was evaluated in the Maryland Wheat Variety Test for 5 yr (from 2000–2004), in the Virginia and Delaware State Wheat Variety Tests for 3 yr, and in the USDA-ARS Uniform Eastern and Uniform Southern Soft Red Winter Wheat Nurseries in 2004. Coleoptiles of Choptank are white. Juvenile plants exhibit a semierect growth habit. Plant color at boot stage (Feekes growth stage 9–10) is blue green and a waxy bloom is present on the stem and flag leaf sheath. Anther color is yellow. Spikes are tapering, middense, and awnletted. Glumes are long and wide, with oblique shoulders and obtuse beaks. Kernels of Choptank are red, soft, and ovate with a crease of medium width and depth, rounded cheeks, and a long noncollared brush. Choptank carries the 1BL.1RS wheat–rye chromosomal translocation. Head emergence of Choptank in Maryland is similar to that of ‘Sisson’ and 2 d earlier than Pioneer brand ‘25R37’. In Maryland, average plant height of Choptank (77.5 cm) is 5 cm shorter than that of Sisson and 2 cm shorter than that of USG ‘3209’. Average straw strength (0.0 lodging score) of Choptank in Maryland is similar to that of Sisson (0.3)