Interference with Hemozoin Formation Represents an Important Mechanism of Schistosomicidal Action of Antimalarial Quinoline Methanols

Background: The parasitic trematode Schistosoma mansoni is one of the major causative agents of human schistosomiasis, which afflicts 200 million people worldwide. Praziquantel remains the main drug used for schistosomiasis treatment, and reliance on the single therapy has been prompting the search for new therapeutic compounds against this disease. Our group has demonstrated that heme crystallization into hemozoin (Hz) within the S. mansoni gut is a major heme detoxification route with lipid droplets involved in this process and acting as a potential chemotherapeutical target. In the present work, we investigated the effects of three antimalarial compounds, quinine (QN), quinidine (QND) and quinacrine (QCR) in a murine schistosomiasis model by using a combination of biochemical, cell biology and molecular biology approaches. Methodology/Principal Findings: Treatment of S. mansoni-infected female Swiss mice with daily intraperitoneal injections of QN, and QND (75 mg/kg/day) from the 11(th) to 17(th) day after infection caused significant decreases in worm burden (39%-61%) and egg production (42%-98%). Hz formation was significantly inhibited (40%-65%) in female worms recovered from QN- and QND-treated mice and correlated with reduction in the female worm burden. We also observed that QN treatment promoted remarkable ultrastructural changes in male and female worms, particularly in the gut epithelium and reduced the granulomatous reaction to parasite eggs trapped in the liver. Microarray gene expression analysis indicated that QN treatment increased the expression of transcripts related to musculature, protein synthesis and repair mechanisms. Conclusions: The overall significant reduction in several disease burden parameters by the antimalarial quinoline methanols indicates that interference with Hz formation in S. mansoni represents an important mechanism of schistosomicidal action of these compounds and points out the heme crystallization process as a valid chemotherapeutic target to treat schistosomiasis.

Dual-task interference: Attentional and neurophysiological influences

Performing two tasks simultaneously often degrades performance of one or both tasks. While this dual-task interference is classically interpreted in terms of shared attentional resources, where two motor tasks are performed simultaneously interactions within primary motor cortex (i.e., activity-dependent coupling) may also be a contributing factor. In the present study TMS (transcranial magnetic stimulation) was used to examine the contribution of activity-dependent coupling to dual-task interference during concurrent performance of a bimanual coordination task and a discrete probe reaction time (RT) task involving the foot. Experiments 1 and 2 revealed that activity-dependent coupling within the leg corticomotor pathway was greater during dual-task performance than single-task performance, and this was associated with interference on the probe RT task (i.e., increased RT). Experiment 3 revealed that dual-task interference occurred regardless of whether the dual-task involved two motor tasks or a motor and cognitive task, however activity-dependent coupling was present only when a dual motor task was performed. This suggests that activity-dependent coupling is less detrimental to performance than attentional processes operating upstream of the corticomotor system. Finally, while prioritising the RT task reduced, but did not eliminate, dual-task interference the contribution of activity-dependent coupling to dual-task interference was not affected by task prioritisation. This suggests that although activity-dependent coupling may contribute to dual motor-task interference, attentional processes appear to be more important. It also suggests that activity-dependent coupling may not be subject to modulation by attentional processes. (C) 2009 Elsevier B.V. All rights reserved.

Interference of raw milk autochthonous microbiota on the performance of conventional methodologies for Listeria monocytogenes and Salmonella spp. detection

Pathogen detection in foods by reliable methodologies is very important to guarantee microbilogical safety. However, peculiar characteristics of certain foods, such as autochthonous microbiota, can directly influence pathogen development and detection. With the objective of verifying the performance of the official analytical methodologies for the isolation of Listeria monocytogenes and Salmonella in milk, different concentrations of these pathogens were inoculated in raw milk treatments with different levels of mesophilic aerobes, and then submitted to the traditional isolation procedures for the inoculated pathogens. Listeria monocytogenes was inoculated at the range of 0.2-5.2 log CFU/mL in treatments with 1.8-8.2 log CFU/mL. Salmonella Enteritidis was inoculated at 0.9-3.9 log CFU/mL in treatments with 3.0-8.2 log CFU/mL. The results indicated that recovery was not possible or was more difficult in the treatments with high counts of mesophilic aerobes and low levels of the pathogens, indicating interference of raw milk autochthonous microbiota. This interference was more evident for L. monocytogenes, once the pathogen recovery was not possible in treatments with mesophilic aerobes up to 4.0 log CFU/mL and inoculum under 2.0 log CFU/mL. For S. Enteritidis the interference appeared to be more non-specific. (C) 2007 Elsevier GmbH. All rights reserved.

Listeria monocytogenes and Salmonella spp. in raw milk produced in Brazil: Occurrence and interference of indigenous microbiota in their isolation and development

This study aimed to verify the occurrence of Listeria monocytogenes and Salmonella spp. in raw milk produced in Brazil. On account of the poor microbiological quality of this product, possible interference from the indigenous microbiota in these pathogens was also evaluated. Two-hundred and ten raw milk samples were collected in four important milk-producing areas in Brazil, tested for L. monocytogenes and Salmonella spp. presence, and for enumeration of indicator microorganisms: mesophilic aerobes, total coliforms and Escherichia coli. The interference of the indigenous microbiota in the isolation procedures was also tested, as well the frequency of naturally occurring raw milk strains with antagonistic activity against both pathogens. The pathogens were not isolated in any raw milk sample, but poor microbiological quality was confirmed by the high levels of indicator microorganisms. When present at high levels, the indigenous microbiota generated an evident interference in the methodologies of L. monocytogenes and Salmonella spp. isolation, mainly when the pathogens appeared at low levels. Three-hundred and sixty raw milk strains were tested for antagonistic activity against both pathogens, and 91 (25.3%) showed inhibitory activity against L. monocytogenes and 33 (9.2%) against Salmonella spp. The majority of the antagonistic strains were identified as Lactic Acid Bacteria species, mainly Lactococcus lactis subsp. lactis and Enterococcus faecium, known by antimicrobial substance production.

Interference of dexamethasone in the pulmonary cycle of Strongyloides venezuelensis in rats

The aim of this study was to investigate the interference of a daily treatment of dexamethasone in the pulmonary cycle of Strongyloides venezuelensis infection in rats. Three principal effects were found: 1) increased alveolar hemorrhagic inflammation provoked by the passage of larvae into alveolar spaces; 2) significant decrease of eosinophil and mast cell migration to the axial septum of the lungs; and 3) impaired formation of the reticular fiber network, interfering with granuloma organization. This study showed that the use of drugs with immunomodulatory actions, such as dexamethasone, in addition to interfering with the morbidity from the pulmonary cycle of S. venezuelensis infection, may contribute to showing the mechanisms involved in its pathogenesis.

Interference in hyperbolic space

The interference in a phase space algorithm of Schleich and Wheeler [Nature 326, 574 (1987)] is extended to the hyperbolic space underlying the group SU(1,1). The extension involves introducing the notion of weighted areas. Analytic expressions for the asymptotic forms for overlaps between the eigenstates of the generators of su(1,1) thus obtained are found to be in excellent agreement with the numerical results.[S1050-2947(98)08602-8].

Creating proactive interference in immediate recall: Building a DOG from a DART, a MOP, and a FIG

Phonemic codes are accorded a privileged role in most current models of immediate serial recall, although their effects are apparent in short-term proactive interference (PI) effects as well. The present research looks at how assumptions concerning distributed representation and distributed storage involving both semantic and phonemic codes might be operationalized to produce PI in a short-term cued recall task. The four experiments reported here attempted to generate the phonemic characteristics of a nonrhyming, interfering foil from unrelated filler items in the same list. PI was observed when a rhyme of the foil was studied or when the three phonemes of the foil were distributed across three studied filler items. The results suggest that items in short-term memory are stored in terms of feature bundles and that all items are simultaneously available at retrieval.

Interference pattern with a dark center from two atoms driven by a coherent laser field

In a recent paper Meyer and Yeoman [Phys. Rev. Lett. 79, 2650 (1997)] have shown that the resonance fluorescence from two atoms placed in a cavity and driven by an incoherent field can produce an interference pattern with a dark center. We study the fluorescence from two coherently driven atoms in free space and show that this system can also produce an interference pattern with a dark center. This happens when the atoms are in nonequivalent positions in the driving: field, i.e., the atoms experience different intensities and phases of the driving field. We discuss the role of the interatomic interactions in this process and find that the interference pattern with a dark center results from the participation of the antisymmetric state in the dynamics of the driven two-atom system.

Interference pattern with a dark center in resonance fluorescence from two atoms driven by a squeezed vacuum field

We study the resonance fluorescence from two interacting atoms driven by a squeezed vacuum field and show that this system produces an interference pattern with a dark center. We discuss the role of the interatomic interactions in this process and find that the interference pattern results from an unequal population of the symmetric and antisymmetric states of the two-atom system. We also identify intrinsically nonclassical effects versus classical squeezed field effects, (C) 1998 Elsevier Science B.V. All rights reserved.

Associative priming in color naming: Interference and facilitation

In Experiment 1, color-naming interference for target stimuli following associated primes was greater in a group making a lexical decision to the prime than in a group reading the prime silently. High-frequency targets were responded to more quickly than low-frequency targets. In Experiment 2, with subjects naming the prime, there was evidence of associative interference when the prime and the target were grouped temporally but not when the intertrial interval was comparable with the prime-target interval. Associative primes presented at a short (120-msec) prime-target stimulus onset asynchrony facilitated color naming in Experiment 3. Taken together, the results suggest that the effect of faster processing of the base word in a color-naming task is facilitatory and that color-naming priming interference arises when associative prime processing increases conflict between word and color responses by enhancing phonological or articulatory activation of the base word.

Decoherence and coherent population transfer between two coupled systems

We show that an arbitrary system described by two dipole moments exhibits coherent superpositions of internal states that can be completely decoupled fi om the dissipative interactions (responsible for decoherence) and an external driving laser field. These superpositions, known as dark or trapping states, can he completely stable or can coherently interact with the remaining states. We examine the master equation describing the dissipative evolution of the system and identify conditions for population trapping and also classify processes that can transfer the population to these undriven and nondecaying states. It is shown that coherent transfers are possible only if the two systems are nonidentical, that is the transitions have different frequencies and/or decay rates. in particular, we find that the trapping conditions can involve both coherent and dissipative interactions, and depending on the energy level structure of the system, the population can be trapped in a linear superposition of two or more bare states, a dressed state corresponding to an eigenstate of the system plus external fields or, in some cases. in one of the excited states of the system. A comprehensive analysis is presented of the different processes that are responsible for population trapping, and we illustrate these ideas with three examples of two coupled systems: single V- and Lambda-type three-level atoms and two nonidentical tao-level atoms, which are known to exhibit dark states. We show that the effect of population trapping does not necessarily require decoupling of the antisymmetric superposition from the dissipative interactions. We also find that the vacuum-induced coherent coupling between the systems could be easily observed in Lambda-type atoms. Our analysis of the population trapping in two nonidentical atoms shows that the atoms can be driven into a maximally entangled state which is completely decoupled from the dissipative interaction.