Physiological susceptibility of the predator Macrolophus basicornis (Hemiptera: Miridae) to pesticides used to control of Tuta absoluta (Lepidoptera: Gelechiidae)

In order to aid the integration of biological and chemical controls for the tomato leaf miner, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae), this study evaluated the relative toxicity of five insecticides to the leaf miner predator Macrolophus basicornis (Stal) (Hemiptera: Miridae). The insecticides evaluated were teflubenzuron, abamectin, chlorantraniliprole, chlorfenapyr, and cartap hydrochloride, all of which are recommended for control of T. absoluta in Brazil. Nymphs and adults of M. basicornis were exposed to tomato leaves treated with the insecticides, under laboratory and greenhouse conditions. The overall mortality caused by the products in both situations was recorded, and the survival of congeneric groups was analysed using the Weibull model. The persistence of the insecticides was also evaluated and they were categorised into toxicity classes proposed by the International Organisation for Biological Control (IOBC) based on predator mortality and persistence. Abamectin and chlorfenapyr were toxic to M. basicornis nymphs and adults in all bioassays. Cartap hydrochloride was slightly harmful to adults in laboratory assays, but harmful to nymphs, and moderately harmful under greenhouse conditions. Chlorantraniliprole and teflubenzuron were harmless in most assays, except when nymphs were exposed in the laboratory, where they were moderately and slightly harmful, respectively. Chlorantraniliprole and teflubenzuron should be preferred insecticides for use in tomato leaf miner IPM programmes that aim to conserve M. basicornis populations.     

Enhancement of HERG K(+) currents by Cd(2+) destabilization of the inactivated state

We have studied the functional effects of extracellular Cd(2+) on human ether-a-go-go-related gene (HERG) encoded K(+) channels. Low concentrations (10-200 &mgr;M) of extracellular Cd(2+) increased outward currents through HERG channels; 200 &mgr;M Cd(2+) more than doubled HERG currents and altered current kinetics. Cd(2+) concentrations up to 200 &mgr;M did not change the voltage dependence of channel activation, but shifted the voltage dependence of inactivation to more depolarized membrane potentials. Cd(2+) concentrations >/=500 &mgr;M shifted the voltage dependence of channel activation to more positive potentials. These results are consistent with a somewhat specific ability of Cd(2+) to destabilize the inactivated state. We tested the hypothesis that channel inactivation is essential for Cd(2+)-induced increases in HERG K(+) currents, using a double point mutation (G628C/S631C) that diminishes HERG inactivation (Smith, P. L., T. Baukrowitz, and G. Yellen. 1996. Nature (Lond.). 379:833-836). This inactivation-removed mutant is insensitive to low concentrations of Cd(2+). Thus, Cd(2+) had two distinct effects on HERG K(+) channels. Low concentrations of Cd(2+) caused relatively selective effects on inactivation, resulting in a reduction of the apparent rectification of the channel and thereby increasing HERG K(+) currents. Higher Cd(2+) concentrations affected activation gating as well, possibly by a surface charge screening mechanism or by association with a lower affinity site.     

Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282

The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m² were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.     

Null Mutants of Individual RABA Genes Impact the Proportion of Different Cell Wall Components in Stem Tissue of Arabidopsis thaliana

In Arabidopsis, and other plants, the RABA GTPases (orthologous to the Rab11a of mammals) have expanded in number and diversity and have been shown to belong to eight sub clades, some of which have been implicated in controlling vesicles that traffic cell wall polymers and enzymes that synthesise or modify them to the cell wall. In order to investigate this, we have investigated whether T-DNA insertion knockouts of individual RABA genes belonging to different sub clades, impact on the composition of the plant cell wall. Single gene knockouts of the RABA1, RABA2 and RABA4 sub clades primarily affected the percentage composition of pectin, cellulose and hemicellulose within the cell wall, respectively, despite having no obvious phenotype in the whole plant. We hypothesise that vesicles carrying specific types of cargoes from the Golgi to the cell surface may be regulated by particular sub types of RABA proteins, a finding that could have wider implications for how trafficking systems work and could be a useful tool in cell wall research and other fields of plant biology.     

Pharmacological inhibition of GSK-3 in a guinea pig model of LPS-induced pulmonary inflammation: II. Effects on skeletal muscle atrophy

Background

Chronic obstructive pulmonary disease (COPD) is accompanied by pulmonary inflammation and associated with extra-pulmonary manifestations, including skeletal muscle atrophy. Glycogen synthase kinase-3 (GSK-3) has been implicated in the regulation of muscle protein- and myonuclear turnover; two crucial processes that determine muscle mass. In the present study we investigated the effect of the selective GSK-3 inhibitor SB216763 on muscle mass in a guinea pig model of lipopolysaccharide (LPS)-induced pulmonary inflammation-associated muscle atrophy.

Methods

Guinea pigs were pretreated with either intranasally instilled SB216763 or corresponding vehicle prior to each LPS/saline challenge twice weekly. Pulmonary inflammation was confirmed and indices of muscle mass were determined after 12 weeks. Additionally, cultured skeletal muscle cells were incubated with tumor necrosis factor α (TNF-α) or glucocorticoids (GCs) to model the systemic effects of pulmonary inflammation on myogenesis, in the presence or absence of GSK-3 inhibitors.

Results

Repeated LPS instillation induced muscle atrophy based on muscle weight and muscle fiber cross sectional area. Intriguingly, GSK-3 inhibition using SB216763 prevented the LPS-induced muscle mass decreases and myofiber atrophy. Indices of protein turnover signaling were unaltered in guinea pig muscle. Interestingly, inhibition of myogenesis of cultured muscle cells by TNF-α or synthetic GCs was prevented by GSK-3 inhibitors.

Conclusions

In a guinea pig model of LPS-induced pulmonary inflammation, GSK-3 inhibition prevents skeletal muscle atrophy without affecting pulmonary inflammation. Resistance to inflammation- or GC-induced impairment of myogenic differentiation, imposed by GSK-3 inhibition, suggests that sustained myogenesis may contribute to muscle mass maintenance despite persistent pulmonary inflammation. Collectively, these results warrant further exploration of GSK-3 as a potential novel drug target to prevent or reverse muscle wasting in COPD.     

Construction and evaluation of multisite recombinatorial (Gateway) cloning vectors for Gram-positive bacteria

Background  

The Gateway recombinatorial cloning system allows easy and rapid joining of DNA fragments. Here we report the construction and evaluation of three different Gram-positive vectors that can be used with the Multisite Gateway cloning system to rapidly produce new gene arrangements in plasmid constructs for use in a variety of Gram-positive bacteria.     

The robustness of two phylogenetic methods: four-taxon simulations reveal a slight superiority of maximum likelihood over neighbor joining

The robustness (sensitivity to violation of assumptions) of the maximum- likelihood and neighbor-joining methods was examined using simulation. Maximum likelihood and neighbor joining were implemented with Jukes- Cantor, Kimura, and gamma models of DNA substitution. Simulations were performed in which the assumptions of the methods were violated to varying degrees on three model four-taxon trees. The performance of the methods was evaluated with respect to ability to correctly estimate the unrooted four-taxon tree. Maximum likelihood outperformed neighbor joining in 29 of the 36 cases in which the assumptions of both methods were satisfied. In 133 of 180 of the simulations in which the assumptions of the maximum-likelihood and neighbor-joining methods were violated, maximum likelihood outperformed neighbor joining. These results are consistent with a general superiority of maximum likelihood over neighbor joining under comparable conditions. They extend and clarify an earlier study that found an advantage for neighbor joining over maximum likelihood for gamma-distributed mutation rates.