Phosphine Resistance in the Rust Red Flour Beetle, Tribolium castaneum (Coleoptera: Tenebrionidae): Inheritance, Gene Interactions and Fitness Costs

The recent emergence of heritable high level resistance to phosphine in stored grain pests is a serious concern among major grain growing countries around the world. Here we describe the genetics of phosphine resistance in the rust red flour beetle Tribolium castaneum (Herbst), a pest of stored grain as well as a genetic model organism. We investigated three field collected strains of T. castaneum viz., susceptible (QTC4), weakly resistant (QTC1012) and strongly resistant (QTC931) to phosphine. The dose-mortality responses of their test- and inter-cross progeny revealed that most resistance was conferred by a single major resistance gene in the weakly (3.2×) resistant strain. This gene was also found in the strongly resistant (431×) strain, together with a second major resistance gene and additional minor factors. The second major gene by itself confers only 12–20× resistance, suggesting that a strong synergistic epistatic interaction between the genes is responsible for the high level of resistance (431×) observed in the strongly resistant strain. Phosphine resistance is not sex linked and is inherited as an incompletely recessive, autosomal trait. The analysis of the phenotypic fitness response of a population derived from a single pair inter-strain cross between the susceptible and strongly resistant strains indicated the changes in the level of response in the strong resistance phenotype; however this effect was not consistent and apparently masked by the genetic background of the weakly resistant strain. The results from this work will inform phosphine resistance management strategies and provide a basis for the identification of the resistance genes

The rph1 Gene Is a Common Contributor to the Evolution of Phosphine Resistance in Independent Field Isolates of Rhyzopertha Dominica

Phosphine is the only economically viable fumigant for routine control of insect pests of stored food products, but its continued use is now threatened by the world-wide emergence of high-level resistance in key pest species. Phosphine has a unique mode of action relative to well-characterised contact pesticides. Similarly, the selective pressures that lead to resistance against field sprays differ dramatically from those encountered during fumigation. The consequences of these differences have not been investigated adequately. We determine the genetic basis of phosphine resistance in Rhyzopertha dominica strains collected from New South Wales and South Australia and compare this with resistance in a previously characterised strain from Queensland. The resistance levels range from 225 and 100 times the baseline response of a sensitive reference strain. Moreover, molecular and phenotypic data indicate that high-level resistance was derived independently in each of the three widely separated geographical regions. Despite the independent origins, resistance was due to two interacting genes in each instance. Furthermore, complementation analysis reveals that all three strains contain an incompletely recessive resistance allele of the autosomal rph1 resistance gene. This is particularly noteworthy as a resistance allele at rph1 was previously proposed to be a necessary first step in the evolution of high-level resistance. Despite the capacity of phosphine to disrupt a wide range of enzymes and biological processes, it is remarkable that the initial step in the selection of resistance is so similar in isolated outbreaks

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Differential vulnerability to relapse into heroin versus cocaine-seeking as a function of setting

RATIONALE Previous studies have shown that the effect of setting on drug-taking is substance specific in both humans and rats. In particular, we have shown that when the setting of drug self-administration (SA) coincides with the home environment of the rats (resident rats), the rats tend to prefer heroin to cocaine. The opposite was found in nonresident rats, for which the SA chambers represented a distinct environment. OBJECTIVES The aim of the present study was to investigate the influence of setting on the ability of different doses of cocaine and heroin to prime cocaine- versus heroin-seeking in rats that had been trained to self-administer both drugs and had then undergone an extinction procedure. METHODS Resident (N = 62) and nonresident (N = 63) rats with double-lumen intra-jugular catheters were trained to self-administer cocaine (400 μg/kg/infusion) and heroin (25 μg/kg/infusion) on alternate days for 10 consecutive daily sessions (3 h each). After the extinction phase, independent groups of rats were given a noncontingent intravenous infusion of heroin (25, 50, or 100 μg/kg) or cocaine (400, 800, or 1600 μg/kg), and drug-seeking was quantified by counting nonreinforced lever presses. RESULTS All resident and nonresident rats acquired heroin and cocaine SA. However, cocaine primings reinstated cocaine-seeking only in nonresident rats, whereas heroin primings reinstated heroin-seeking only in resident rats. CONCLUSIONS We report here that the susceptibility to relapse into drug-seeking behavior is drug-specific and setting-specific, confirming the crucial role played by drug, set, and setting interactions in drug addiction

Reduction in Cerebral Perfusion after Heroin Administration: A Resting State Arterial Spin Labeling Study

Heroin dependence is a chronic relapsing brain disorder, characterized by the compulsion to seek and use heroin. Heroin itself has a strong potential to produce subjective experiences characterized by intense euphoria, relaxation and release from craving. The neurofunctional foundations of these perceived effects are not well known. In this study, we have used pharmacological magnetic resonance imaging (phMRI) in 15 heroin-dependent patients from a stable heroin-assisted treatment program to observe the steady state effects of heroin (60 min after administration). Patients were scanned in a cross-over and placebo controlled design. They received an injection of their regular dose of heroin or saline (placebo) before or after the scan. As phMRI method, we used a pulsed arterial spin labeling (ASL) sequence based on a flow-sensitive alternating inversion recovery (FAIR) spin labeling scheme combined with a single-shot 3D GRASE (gradient-spin echo) readout on a 3 Tesla scanner. Analysis was performed with Statistical Parametric Mapping (SPM 8), using a general linear model for whole brain comparison between the heroin and placebo conditions. We found that compared to placebo, heroin was associated with reduced perfusion in the left anterior cingulate cortex (ACC), the left medial prefrontal cortex (mPFC) and in the insula (both hemispheres). Analysis of extracted perfusion values indicate strong effect sizes and no gender related differences. Reduced perfusion in these brain areas may indicate self- and emotional regulation effects of heroin in maintenance treatment