Analysis of the mitochondrial and nuclear genomes of two basidiomycetes, Coprinus cinereus and Coprinus stercorarius

The mitochondrial and nuclear genomes of Coprinus stercorarius and C. cinereus were compared to assess their evolutionary relatedness and to characterize at the molecular level changes that have occurred since they diverged from a common ancestor. The mitochondrial genome of C. stercorarius (91.1 kb) is approximately twice as large as that of C. cinereus (43.3 kb). The pattern of restriction enzyme recognition sites shows both genomes to be circular, but reveals no clear homologies; furthermore, the order of structural genes is different in each species. The C. stercorarius mitochondrial genome contains a region homologous to a probe derived from the yeast mitochondrial var1 gene, whereas its nuclear genome does not. By contrast, the C. cinereus nuclear, but not mitochondrial, genome contains a region homologous to the var1 probe. Only a small fraction of either the nuclear or mitochondrial genomes, perhaps corresponding to the coding sequences, is capable of forming duplexes in interspecies solution reassociations, as measured by binding to hydroxylapatite. Those sequences capable of reassociating were found to have approximately 15% divergence for the mitochondrial genomes and 7%–15% divergence for the nuclear genomes, depending on the conditions of reassociation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46959/1/294_2004_Article_BF00447385.pd

A Geometric Approach to Local Indeterminacy & Local Bifurcations in Three-Dimensional Dynamical Systems.

In discrete three-dimensional dynamical systems frequently encountered in dynamic general equilibrium models, local indeterminacy -sunspot equilibria - and local bifurcations -endogenous deterministic fluctuations - issues are quite difficult to handle. Pitfalls derive from the fact that in generic models a standard analysis of the spectrum of the 3 x 3 Jacobian matrix, though achievable, usually turns out to be of no use. It is the purpose of this contribution to develop geometrical tools which avoid cumbersome computations or numerical investigations. Rather tractable necessary and sufficient conditions are provided, that ensure the occurence of generic local bifurcations and also a useful "toolkit" for assessing the local determinacy / indeterminacy of intertemporal equilibria. The usefulness of this method is finally illustrated in a productive model of overlapping generations with elastic labour supply.BUSINESS CYCLES ; MATHEMATICAL ANALYSIS ; ECONOMIC GROWTH

Treatment of experimental endocarditis due to erythromycin-susceptible or -resistant methicillin-resistant Staphylococcus aureus with RP 59500.

RP 59500 is a new injectable streptogramin composed of two synergistic components (quinupristin and dalfopristin) which are active against erythromycin-susceptible and -resistant gram-positive pathogens. The present experiments compared the therapeutic efficacy of RP 59500 with that of vancomycin against experimental endocarditis due to either of two erythromycin-susceptible or two constitutively erythromycin-resistant isolates of methicillin-resistant Staphylococcus aureus. RP 59500 had low MICs for the four test organisms as well as for 24 additional isolates (the MIC at which 90% of the isolates were inhibited was < 1 mg/liter) which were mostly inducibly (47%) or constitutively (39%) erythromycin resistant. Aortic endocarditis in rats was produced with catheter-induced vegetations. Three-day therapy was initiated 12 h after infection, and the drugs were delivered via a computerized pump, which permitted the mimicking of the drug kinetics produced in human serum by twice-daily intravenous injections of 7 mg of RP 59500 per kg of body weight or 1 g of vancomycin. Both antibiotics reduced vegetation bacterial titers to below detection levels in ca. 70% of animals infected with the erythromycin-susceptible isolates (P < 0.05 compared with titers in controls). Vancomycin was also effective against the constitutively resistant strains, but RP 59500 failed against these isolates. Further experiments proved that RP 59500 failures were related to the very short life span of dalfopristin in serum (< or = 2 h, compared with > or = 6 h for quinupristin), since successful treatment was restored by artificially prolonging the dalfopristin levels for 6 h. Thus, RP 59500 is a promising alternative to vancomycin against methicillin-resistant S. aureus infections, provided that pharmacokinetic parameters are adjusted to afford prolonged levels of both of its constituents in serum. This observation is also relevant to humans, in whom the life span of dalfopristin in serum is also shorter than that of quinupristin

In vitro antibacterial activity of moxifloxacin against hospital isolates: a multicentre study

ObjectiveTo evaluate the in vitro antibacterial activity of moxifloxacinin in comparison to that of other fluoroquinolones (ciprofloxacin, ofloxacin and trovafloxacin).MethodsA total of 2196 strains was collected in 11 French hospitals in 1998. Minimum inhibitory concentrations (MICs) (mg/L) were determined by agar dilution and agar diffusion was performed with 5-μg discs. Internal quality control was carried out with genetically defined strains.ResultsMIC50s and MIC90s of moxifloxacin against nalidixic acid (NAL)-susceptible Enterobacteriaceae (n = 663) were 0.12 and 0.5. As for other quinolones, the activity of moxifloxacin (4–32) was reduced against NAL-intermediate and NAL-resistant strains (n = 222). MIC50s and MIC90s of moxifloxacin were 2 and 4 for ciprofloxacin-susceptible P. aeruginosa (n = 128); moxifloxacin had no activity against ciprofloxacin-resistant strains (n = 56). The activity of moxifloxacin was maintained against NAL-susceptible A. baumannii (n = 11; 0.032–0.125), but reduced against NAL-resistant strains (n = 30; 16–32). H. influenzae (n = 97) and M. catarrhalis (n = 40) were inhibited by low concentrations (0.03–0.06 and 0.06–0.25, respectively). Moxifloxacin had better activity (0.06–0.12) than other tested quinolones against methicillin-susceptible S. aureus strains (n = 110); ciprofloxacin-resistant strains (n = 85) (2–8) were usually methicillin-resistant. Moxifloxacin was moderately active against enterococci (n = 149) (E. faecalis: 0.5–16; E. faecium: 2–4). Streptococci (n = 194) and pneumococci (n = 136), including 70 penicillin G-intermediate or G-resistant strains, were inhibited by low concentrations (0.25–0.5 for each species). Based on the regression curve, tentative zone diameter breakpoints could be ≥21 and <18 mm for MIC breakpoints of ≤1 and >2 mg/L, respectively.ConclusionsWhile retaining activity against Enterobacteriaceae, moxifloxacin was moderately active against P. aeruginosa. Its activity was inferior to that of ciprofloxacin for these species. This study confirmed the comparatively high in vitro activity of moxifloxacin against Gram-positive cocci and other pathogens isolated from community-acquired respiratory tract infections

Identification of factors affecting in vivo aminoglycoside activity in an experimental model of gram-negative endocarditis.

Aminoglycoside bactericidal activity during the first 24 h of treatment probably is a determining parameter in the prognosis of severe gram-negative infections in immunocompromised patients. To identify the predictive factors involved in the definition of the best therapeutic regimen for Enterobacter cloacae and Serratia marcescens infections, we studied different gentamicin, tobramycin, and amikacin regimens by using an experimental model of rabbit endocarditis. Two factors appear to play an important role in predicting in vivo efficacy: (i) the level of in vivo bactericidal activity, which can differ widely from one aminoglycoside to another for the same bacterial strain and from one strain to another of the same species, and (ii) the critical serum drug concentration (CSC, in milligrams per liter), defined as the lowest serum antibiotic concentration capable of producing a significant CFU reduction (P less than 0.05) in endocarditis vegetations 24 h after the beginning of a continuous infusion. Stepwise regression analysis showed that for gentamicin and S. marcescens, the area under the concentration-time curve above the CSC and then the time above the CSC are the determining parameters for efficacy (R = 0.69; F = 13.5; P = 0.001), whereas for amikacin and S. marcescens, the time above the CSC and then the area under the concentration-time curve above the CSC predict efficacy (R = 0.74; F = 24.0; P = 0.0001). The lowest CSC is that of amikacin (about 8 mg/liter); those of gentamicin and tobramycin are about 15 mg/liter. In severe S. marcescens infections, intermittent amikacin dosing offers excellent bactericidal activity within the first 24 h