Sensitivity of Pseudomonas aeruginosa to Normal Serum and to Polymyxin

Strains of Pseudomonas aeruginosa isolated from clinical material were very variable in their sensitivity to the bactericidal action of normal serum mediated by the complement system. Fifty per cent killing end points ranged from 0.015 ml to greater than 0.4 ml. Most of the strains with relatively greater sensitivity to serum were isolated from patients with cystic fibrosis. Immunization of rabbits resulted in antisera with enhanced levels of bactericidal antibody, except with one strain which was resistant to the bactericidal action of normal serum and antiserum. When P. aeruginosa was cultivated at 41 C instead of at 37 C, it was significantly more sensitive to serum and to several antibiotics, thereby implicating fever as a host defense mechanism in Pseudomonas infections. In contrast to their heterogeneity to serum bactericidal activity, the strains were relatively homogeneous in their sensitivity to polymyxin, with no apparent association between their sensitivity to the two antimicrobial agents.     

The Barnes Maze Task Reveals Specific Impairment of Spatial Learning Strategy in the Intrahippocampal Kainic Acid Model for Temporal Lobe Epilepsy

Neurochemical Research - Temporal lobe epilepsy (TLE) is an acquired form of focal epilepsy, in which patients not only suffer from unprovoked, devastating seizures, but also from severe...     

Aryl tetrahydropyridine inhibitors of farnesyltransferase: bioavailable analogues with improved cellular potency

Inhibitors of farnesyltransferase are effective against a variety of tumors in mouse models of cancer. Clinical trials to evaluate these agents in humans are ongoing. In our effort to develop new farnesyltransferase inhibitors, we have discovered bioavailable aryl tetrahydropyridines that are potent in cell culture. The design, synthesis, SAR and biological properties of these compounds will be discussed.     

Discovery of piperidine-aryl urea-based stearoyl-CoA desaturase 1 inhibitors

A series of structurally novel stearoyl-CoA desaturase1 (SCD1) inhibitors has been identified via molecular scaffold manipulation. Preliminary structure–activity relationship (SAR) studies led to the discovery of potent, and orally bioavailable piperidine-aryl urea-based SCD1 inhibitors. 4-(2-Chlorophenoxy)-N-[3-(methyl carbamoyl)phenyl]piperidine-1-carboxamide 4c exhibited robust in vivo activity with dose-dependent desaturation index lowering effects.     

Recovery of Foredune and Blowout Habitats in a Freshwater Dune Following Removal of Invasive Austrian Pine (Pinus nigra)

Invasive species removal is an important first step toward restoring invaded ecosystems; however, restoration following removal may be hindered by (1) unintended consequences of management, such as habitat destabilization, and/or (2) legacy effects of the invader, such as persistent alterations of soil structure or plant community composition. During 1956–1972, approximately 26,000 individuals of the non‐native pine, Pinus nigra, were planted into multiple freshwater sand dune habitats as a stabilization measure on the eastern shore of Lake Michigan in Allegan County, MI, U.S.A. From 2004 to 2010, we evaluated the recovery of foredune and blowout habitats following P. nigra removal in 2003–2005. We compared sand movement and plant community structure, composition, and richness between removal and control sites over the 6 years following pine removal. In addition, we evaluated the impact of litter removal on recolonization of native graminoids in foredunes. Sand movement patterns never differed between removal and control sites in foredunes; however, accumulation was more common in removal sites in blowouts 1 and 6 years following pine removal. Vegetation cover in removal sites became indistinguishable from control sites in both foredunes and blowouts, but species richness for both forb and woody species was higher in removal sites in blowouts. Removal sites in both foredunes and blowouts had higher cover by forbs and lower cover by graminoids. Pine litter did not inhibit recolonization of foredunes by native graminoids. These results suggest that high disturbance habitats, such as sand dunes, have the potential to recover from invasion if the mechanism of disturbance is restored and pioneer species are present to recolonize the system.     

Effect of Lysogeny on Serum Sensitivity

When Escherichia coli K-12 was infected with lambda phage and mutants of lambda characterized by the production of temperature-sensitive repressors, the lysogenic bacteria were significantly more resistant to normal serum than the uninfected organisms. Infection of E. coli K-12 with a lambdoid phage, phi80, whose prophage attachment site is different from that of lambda, did not result in a detectable change in serum resistance. Similarly, infection with certain Pseudomonas and Shigella phages caused no detectable differences in serum resistance. Finally, the well-known conversion of the Salmonella anatum serotype to S. newington by E(15) phage indicated that, despite the relatively greater roughness of S. anatum, S. newington was more sensitive to normal serum than S. anatum. Thus, the effects of lysogeny on the sensitivity of bacteria to the bactericidal action of serum mediated by the complement system may be quite variable.