Bacterial predation under changing viscosities.

Bdellovibrio and like organisms (BALOs) are largely distributed in soils and in water bodies obligate predators of gram-negative bacteria that can affect bacterial communities. Potential applications of BALOs include biomass reduction, their use against pathogenic bacteria in agriculture, and in medicine as an alternative against antibiotic-resistant pathogens. Such different environments and uses mean that BALOs should be active under a range of viscosities. In this study, the predatory behaviour of two strains of the periplasmic predator B. bacteriovorus and of the epibiotic predator Micavibrio aeruginosavorus was examined in viscous polyvinylpyrrolidone (PVP) solutions at 28 and at 37°C, using fluorescent markers and plate counts to track predator growth and prey decay. We found that at high viscosities, although swimming speed was largely decreased, the three predators reduced prey to levels similar to those of non-viscous suspensions, albeit with short delays. Prey motility and clumping did not affect the outcome. Strikingly, under low initial predator concentrations, predation dynamics were faster with increasing viscosity, an effect that dissipated with increasing predator concentrations. Changes in swimming patterns and in futile predator-predator encounters with viscosity, as revealed by path analysis under changing viscosities, along with possible PVP-mediated crowding effects, may explain the observed phenomena.

Transient and chronic seizure-induced inflammation in human focal epilepsy.

In animal models, inflammation is both a cause and consequence of seizures. Less is known about the role of inflammation in human epilepsy. We performed positron emission tomography (PET) using a radiotracer sensitive to brain inflammation in a patient with frontal epilepsy ~36 h after a seizure as well as during a seizure-free period. When statistically compared to a group of 12 matched controls, both of the patient's scans identified a frontal (supplementary motor area) region of increased inflammation corresponding to his clinically defined seizure focus, but the postseizure scan showed significantly greater inflammation intensity and spatial extent. These results provide new information about transient and chronic neuroinflammation in human epilepsy and may be relevant to understanding the process of epileptogenesis and guiding therapy.

Dependence of phase-2 reentry and repolarization dispersion on epicardial and transmural ionic heterogeneity: a simulation study.

AIMS: Phase-2 reentry (P2R) is a local arrhythmogenic phenomenon where electrotonic current propagates from a spike-and-dome action potential region to re-excite a loss-of-dome action potential region. While ionic heterogeneity has been shown to underlie P2R within the epicardium and has been hypothesized to occur transmurally, we are unaware of any study that has investigated the effects of combining these heterogeneities as they occur in the heart. Thus, we tested the hypothesis that P2R can result by either epicardial or transmural heterogeneity and that the realistic combination of the two would increase the likelihood of P2R. METHODS AND RESULTS: We used computational ionic models of cardiac myocyte dynamics to investigate initiation and development of P2R in simulated tissues with different ionic heterogeneities. In one-dimensional transmural cable simulations, P2R occurred when the conductance of the transient outward current in the epicardial region was near the range for which epicardial action potentials switched intermittently between spike-and-dome and loss-of-dome morphologies. Phase-2 reentry was more likely in two-dimensional tissue simulations by both epicardial and transmural heterogeneity and could expand beyond its local initiation site to create a macroscopic reentry. CONCLUSION: The characteristics and stability of action potential morphology in the epicardium are important determinants of the occurrence of both transmural and epicardial P2R and its associated arrhythmogenesis.

Adenovirus capsid-based anti-cocaine vaccine prevents cocaine from binding to the nonhuman primate CNS dopamine transporter.

Cocaine addiction is a major problem for which there is no approved pharmacotherapy. We have developed a vaccine to cocaine (dAd5GNE), based on the cocaine analog GNE linked to the capsid proteins of a serotype 5 adenovirus, designed to evoke anti-cocaine antibodies that sequester cocaine in the blood, preventing access to the CNS. To assess the efficacy of dAd5GNE in a large animal model, positron emission tomography (PET) and the radiotracer [(11)C]PE2I were used to measure cocaine occupancy of the dopamine transporter (DAT) in nonhuman primates. Repeat administration of dAd5GNE induced high anti-cocaine titers. Before vaccination, cocaine displaced PE2I from DAT in the caudate and putamen, resulting in 62±4% cocaine occupancy. In contrast, dAd5GNE-vaccinated animals showed reduced cocaine occupancy such that when anti-cocaine titers were >4 × 10(5), the cocaine occupancy was reduced to levels of <20%, significantly below the 47% threshold required to evoke the subjective 'high' reported in humans.

Instability in action potential morphology underlies phase 2 reentry: a mathematical modeling study.

BACKGROUND: Phase 2 reentry occurs when electrotonic current propagates from sites of normal notch-and-dome action potentials (APs) to loss-of-dome abbreviated AP sites, causing abnormal reexcitation. The existence of two neighboring regions exhibiting these two different AP morphologies is believed to be sufficient for local reexcitation and development of phase 2 reentry. OBJECTIVE: The purpose of this study was to investigate the mechanism of phase 2 reentry development in simulated tissues having no gradient or continuous gradients of ionic currents that affect phase 2. In particular, we investigated gradients of the transient outward current conductance G(to), representing hypothesized right ventricular G(to) gradients. METHODS: Single-cell simulations of Luo-Rudy dynamic model cells with a range of G(to) values were performed. In addition, one-dimensional fiber simulations were used to investigate the spatiotemporal phenomenon of phase 2 reentry. RESULTS: In single-cell simulations, low and normal values of G(to) produced the notch-and-dome morphology, whereas high values of G(to) produced abbreviated APs with loss-of-dome morphology. However, intermediate values of G(to) caused cells to switch intermittently between the two morphologies during constant pacing. Phase 2 reentry occurred in homogeneous and heterogeneous cable simulations, but only when a mass of cells had G(to) values close to the unstable "switching" behavior range. CONCLUSION: A main factor underlying phase 2 reentry apparently is not the presence of two different stable morphologies in adjacent regions but rather unstable switching AP morphology within a significant subset of cells.