Comparison between the minimal inhibitory concentration of tilmicosin and oxytetracycline for bovine pneumonic pasteurella haemolytica isolates

Summary

The minimal inhititory concentration (MIC) of tilmicosin and oxytetracycline was dertermined for Pasteurella haemolytica isolated from Dutch cattle in 1991. The agar dilution method was used. Of the Pasteurella haemolytica strains examined, 96% (24) had a MIC for tilmicosin of 2 μg/ml or lower; in one strain the MIC was 8 μg/ml. The MIC for oxytetracycline was equal to or higher than 64 μg/ml in 19 strains (76%), whereas for 5 strains the MIC was 1 μg/ml and for 1 strain 2 μg/ml.     

HTRA1 promoter polymorphism in wet age-related macular degeneration

Age-related macular degeneration (AMD), the most common cause of irreversible vision loss in individuals aged older than 50 years, is classified as either wet (neovascular) or dry (nonneovascular). Inherited variation in the complement factor H gene is a major risk factor for drusen in dry AMD. Here we report that a single-nucleotide polymorphism in the promoter region of HTRA1, a serine protease gene on chromosome 10q26, is a major genetic risk factor for wet AMD. A whole-genome association mapping strategy was applied to a Chinese population, yielding a P value of <10(-11). Individuals with the risk-associated genotype were estimated to have a likelihood of developing wet AMD 10 times that of individuals with the wild-type genotype.     

Cardiac myosin activation: a potential therapeutic approach for systolic heart failure

Decreased cardiac contractility is a central feature of systolic heart failure. Existing drugs increase cardiac contractility indirectly through signaling cascades but are limited by their mechanism-related adverse effects. To avoid these limitations, we previously developed omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin. Here, we show that it binds to the myosin catalytic domain and operates by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. Paradoxically, it inhibits adenosine 5'-triphosphate turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of contraction. Cardiac myosin activation may provide a new therapeutic approach for systolic heart failure.     

Genetic reconstitution of functional acetylcholine receptor channels in mouse fibroblasts

Foreign genes can be stably integrated into the genome of a cell by means of DNA-mediated gene transfer techniques, and large quantities of homogenous cells that continuously express these gene products can then be isolated. Such an expression system can be used to study the functional consequences of introducing specific mutations into genes and to study the expressed protein in the absence of cellular components with which it is normally in contact. All four Torpedo acetylcholine receptor (AChR) subunit complementary DNA's were introduced into the genome of a mouse fibroblast cell by DNA-mediated gene transfer. A clonal cell line that stably produced high concentrations of correctly assembled cell surface AChR's and formed proper ligand-gated ion channels was isolated. With this new expression system, recombinant DNA, biochemical, pharmacological, and electrophysiological techniques were combined to study Torpedo AChR's in a single intact system. The physiological and pharmacological profiles of Torpedo AChR's expressed in mouse fibroblast cells differ in some details from those described earlier, and may provide a more accurate reflection of the properties of this receptor in its natural environment.     

Organochlorine pesticides and polychlorinated biphenyls in sediment and fish from Wetlands in the north central United States

Sediment samples collected in 1980-1982 from riverine and pothole wetlands at 17 locations in the north central United States were analyzed for organochlorine pesticides, certain of their metabolites, and polychlorinated biphenyls (PCBs). Concentrations were above minimum detection levels (5 ng/g of organochlorines and 20 ng/g of PCBs) in less than 4% of the samples taken. Fish samples taken at 9 of these 17 locations, and analyzed for the same compounds, showed a higher frequency of detectable contaminants. The most common compound found in fish was DDE, which was found in 51% of the samples at levels up to 512 ng/g. alpha-BHC was present at concentrations of 5 to 27 ng/g in 36% of the fish samples, and DDD was found at levels of 5 to 60 ng/g in 14%. Four other compounds, DDT, dieldrin, PCB, and trans-nonachlor, were detected in fish at relatively low concentrations in less than 10% of the samples. This survey, thus, indicated little contamination by organochlorine pesticides or PCBs in the wetland habitats of this region.     

The detection and characterization of a nontransiting planet by transit timing variations

The Kepler mission is monitoring the brightness of ~150,000 stars, searching for evidence of planetary transits. As part of the Hunt for Exomoons with Kepler (HEK) project, we report a planetary system with two confirmed planets and one candidate planet discovered with the publicly available data for KOI-872. Planet b transits the host star with a period P(b) = 33.6 days and exhibits large transit timing variations indicative of a perturber. Dynamical modeling uniquely detects an outer nontransiting planet c near the 5:3 resonance (P(c) = 57.0 days) with a mass 0.37 times that of Jupiter. Transits of a third planetary candidate are also found: a 1.7-Earth radius super-Earth with a 6.8-day period. Our analysis indicates a system with nearly coplanar and circular orbits, reminiscent of the orderly arrangement within the solar system.     

Hycanthone: a frameshift mutagen

Rapid spot-test screening of antischistosomal agents reveals that hycanthone is a potent frameshift mutagen while the closely related compound, miracil D, is nonmutagenic in Salmonella. Both hycanthone and miracil D are frameshift mutagens for T4 bacteriophage during growth in Escherichia coli.