A century of research: what have we learned about the interaction of Trypanosoma cruzi with host cells?

Since the discovery of Trypanosoma cruzi and the brilliant description of the then-referred to "new tripanosomiasis" by Carlos Chagas 100 years ago, a great deal of scientific effort and curiosity has been devoted to understanding how this parasite invades and colonises mammalian host cells. This is a key step in the survival of the parasite within the vertebrate host, and although much has been learned over this century, differences in strains or isolates used by different laboratories may have led to conclusions that are not as universal as originally interpreted. Molecular genotyping of the CL-Brener clone confirmed a genetic heterogeneity in the parasite that had been detected previously by other techniques, including zymodeme or schizodeme (kDNA) analysis. T. cruzi can be grouped into at least two major phylogenetic lineages: T. cruzi I, mostly associated with the sylvatic cycle and T. cruzi II, linked to human disease; however, a third lineage, T. cruziIII, has also been proposed. Hybrid isolates, such as the CL-Brener clone, which was chosen for sequencing the genome of the parasite (Elias et al. 2005, El Sayed et al. 2005a), have also been identified. The parasite must be able to invade cells in the mammalian host, and many studies have implicated the flagellated trypomastigotes as the main actor in this process. Several surface components of parasites and some of the host cell receptors with which they interact have been described. Herein, we have attempted to identify milestones in the history of understanding T. cruzi- host cell interactions. Different infective forms of T. cruzi have displayed unexpected requirements for the parasite to attach to the host cell, enter it, and translocate between the parasitophorous vacuole to its final cytoplasmic destination. It is noteworthy that some of the mechanisms originally proposed to be broad in function turned out not to be universal, and multiple interactions involving different repertoires of molecules seem to act in concert to give rise to a rather complex interplay of signalling cascades involving both parasite and cellular components.

Antibiosis and dark-pigments secretion by the phytopathogenic and environmental fungal species after interaction in vitro with a Bacillus subtilis isolate

In this work, different reactions in vitro between an environmental bacterial isolate and fungal species were related. The Gram-positive bacteria had terminal and subterminal endospores, presented metabolic characteristics of mesophilic and acidophilic growth, halotolerance, positive to nitrate reduction and enzyme production, as caseinase and catalase. The analysis of partial sequences containing 400 to 700 bases of the 16S ribosomal RNA gene showed identity with the genus Bacillus. However, its identity as B. subtilis was confirmed after analyses of the rpoB, gyrA, and 16S rRNA near-full-length sequences. Strong inhibitory activity of environmental microorganisms, such as Penicillium sp, Aspergillus flavus, A. niger, and phytopathogens, such as Colletotrichum sp, Alternaria alternata, Fusarium solani and F. oxysporum f.sp vasinfectum, was shown on co-cultures with B. subtilis strain, particularly on Sabouraud dextrose agar (SDA) and DNase media. Red and red-ochre color pigments, probably phaeomelanins, were secreted by A. alternata and A. niger respectively after seven days of co-culture.

Conducting polymer- hydrogel blends for electrochemically controlled drug release devices

Blends formed by electrochemical polymerization of polypyrrole (PPy) into polyacrylamide (PAAm) hydrogels were used as devices for controlled drug release. The influence of several parameters in the synthesis, such as type of hydrogel matrix and polymerization conditions was studied by using a fractional factorial design. The final goal was to obtain an adequate device for use in controlled release tests, based on electrochemical potential control. For controlled release tests, Safranin was used as model drug and release curves (amount of drug vs. time) have shown that these blends are promising materials for this use. The optimized blends obtained were characterized by cyclic voltammetry and Raman spectroscopy.

Pharmacist professionals in the prevention of drug abuse: updating roles, and opportunities

The objective of this paper was to prepare and provide resources to pharmacists and other healthcare professionals, enabling them to carry out a critical analysis on drug abuse, acquiring knowledge in several areas that effectively contribute to their personal development in this professional field. Professionals play a crucial role in the reduction and prevention of substances abuse, since they are able to advise patient about illicit drugs, psychotropic medicines and alcohol abuse. There is an urgent need to specialize pharmacists to act in the national public health service and contribute to actions aimed at the surrounding community.

Cooperation, interaction and learning in local production systems: Evidence in Brazilian firms

In a local production system (LPS), besides external economies, the interaction, cooperation, and learning are indicated by the literature as complementary ways of enhancing the LPS's competitiveness and gains. In Brazil, the greater part of LPSs, mostly composed by small enterprises, displays incipient relationships and low levels of interaction and cooperation among their actors. The size of the participating enterprises itself for specificities that engender organizational constraints, which, in turn, can have a considerable impact on their relationships and learning dynamics. For that reason, it is the purpose of this article to present an analysis of interaction, cooperation, and learning relationships among several types of actors pertaining to an LPS in the farming equipment and machinery sector, bearing in mind the specificities of small enterprises. To this end, the fieldwork carried out in this study aimed at: (i) investigating external and internal knowledge sources conducive to learning and (ii) identifying and analyzing motivating and inhibiting factors related to specificities of small enterprises in order to bring the LPS members closer together and increase their cooperation and interaction. Empirical evidence shows that internal aspects of the enterprises, related to management and infrastructure, can have a strong bearing on their joint actions, interaction and learning processes.

AtPIN: Arabidopsis thaliana Protein Interaction Network

Background: Protein-protein interactions (PPIs) constitute one of the most crucial conditions to sustain life in living organisms. To study PPI in Arabidopsis thaliana we have developed AtPIN, a database and web interface for searching and building interaction networks based on publicly available protein-protein interaction datasets. Description: All interactions were divided into experimentally demonstrated or predicted. The PPIs in the AtPIN database present a cellular compartment classification (C(3)) which divides the PPI into 4 classes according to its interaction evidence and subcellular localization. It has been shown in the literature that a pair of genuine interacting proteins are generally expected to have a common cellular role and proteins that have common interaction partners have a high chance of sharing a common function. In AtPIN, due to its integrative profile, the reliability index for a reported PPI can be postulated in terms of the proportion of interaction partners that two proteins have in common. For this, we implement the Functional Similarity Weight (FSW) calculation for all first level interactions present in AtPIN database. In order to identify target proteins of cytosolic glutamyl-tRNA synthetase (Cyt-gluRS) (AT5G26710) we combined two approaches, AtPIN search and yeast two-hybrid screening. Interestingly, the proteins glutamine synthetase (AT5G35630), a disease resistance protein (AT3G50950) and a zinc finger protein (AT5G24930), which has been predicted as target proteins for Cyt-gluRS by AtPIN, were also detected in the experimental screening. Conclusions: AtPIN is a friendly and easy-to-use tool that aggregates information on Arabidopsis thaliana PPIs, ontology, and sub-cellular localization, and might be a useful and reliable strategy to map protein-protein interactions in Arabidopsis. AtPIN can be accessed at http://bioinfo.esalq.usp.br/atpin.

Increased Endothelial Cell-Leukocyte Interaction in Murine Schistosomiasis: Possible Priming of Endothelial Cells by the Disease

Background and Aims: Schistosomiasis is an intravascular parasitic disease associated with inflammation. Endothelial cells control leukocyte transmigration and vascular permeability being modulated by pro-inflammatory mediators. Recent data have shown that endothelial cells primed in vivo in the course of a disease keep the information in culture. Herein, we evaluated the impact of schistosomiasis on endothelial cell-regulated events in vivo and in vitro. Methodology and Principal Findings: The experimental groups consisted of Schistosoma mansoni-infected and age-matched control mice. In vivo infection caused a marked influx of leukocytes and an increased protein leakage in the peritoneal cavity, characterizing an inflamed vascular and cellular profile. In vitro leukocyte-mesenteric endothelial cell adhesion was higher in cultured cells from infected mice as compared to controls, either in the basal condition or after treatment with the pro-inflammatory cytokine tumor necrosis factor (TNF). Nitric oxide (NO) donation reduced leukocyte adhesion to endothelial cells from control and infected groups; however, in the later group the effect was more pronounced, probably due to a reduced NO production. Inhibition of control endothelial NO synthase (eNOS) increased leukocyte adhesion to a level similar to the one observed in the infected group. Besides, the adhesion of control leukocytes to endothelial cells from infected animals is similar to the result of infected animals, confirming that schistosomiasis alters endothelial cells function. Furthermore, NO production as well as the expression of eNOS were reduced in cultured endothelial cells from infected animals. On the other hand, the expression of its repressor protein, namely caveolin-1, was similar in both control and infected groups. Conclusion/Significance: Schistosomiasis increases vascular permeability and endothelial cell-leukocyte interaction in vivo and in vitro. These effects are partially explained by a reduced eNOS expression. In addition, our data show that the disease primes endothelial cells in vivo, which keep the acquired phenotype in culture.

Electrochemical Reduction Using Glassy Carbon Electrode in Aqueous Medium of a Potential Anti-Chagas Drug: NFOH

Nitrofurazone (NF) presents activity against Chagas' disease, yet it has a high toxicity. Its analog, hydroxymethylnitrofurazone (NFOH), is more potent against Trypanosoma cruzi and much less toxic than the parent drug, NF. The electrochemical reduction of NFOH in an aqueous medium using a glassy carbon electrode (GCE) is presented. By cyclic voltammetry in anacidic medium, one irreversible reduction peak related to hydroxylamine derivative formation was registered, being linearly pH dependent. However, from pH > 7, a reversible reduction peak at a more positive potential appears and corresponds to the formation of a nitro radical anion. The radical-anion kinetic stability was evaluated by Ip(a)/Ip(c) the current ratio of the R-NO(2)/R-NO(2)-redox couple. The nitro radical anion decays with a second-order rate constant (k(2)) of 6.07, 2.06, and 1.44(X 10(3)) L mol(-1) s(-1) corresponding to pH 8.29, 9.29, and 10.2, respectively, with a corresponding half-time life (t(1/2)) of 0.33, 0.97, and 1.4 s for each pH value. By polishing the GCE surface with diamond powder and comparing with the GCE surface polished with alumina, it is shown that the presence of alumina affects the lifetime of the nitro radical anion. (C) 2009 The Electrochemical Society. [DOI: 10.1149/1.3130082] All rights reserved.

Interaction and behavior of virgin and physogastric queens in three Meliponini species (Hymenoptera, Apidae)

We studied the behavior of virgin queens of the stingless bee species Schwarziana quadripunctata, Paratrigona lineata and Tetragona clavipes, investigating internal nest activities, including the cell provisioning and oviposition process. We made direct observation of queen behavior, with the aid of video filming. Forty-four virgin queens of S. quadripunctata were observed; one was larger and more attractive than the others. Miniature queens were more abundant than normal-size queens; both were found in prison chambers. Agonistic behavior between virgin and physogastric queens of P. lineata was observed during attempts at queen supersedure. After the disappearance of the physogastric queen and the appearance of a virgin queen in T. clavipes nests, the brood cells were sealed with pollen alone, but no egg. In all three species, the presence of one or more virgin queens appeared to make the colonies nervous, even though constant production of virgin queens is vital to the survival of the colony and is part of the colony cycle in these bees.

Electrochemical Evidence of Strong Electronic Interaction of PtRu on Carbon Nanotubes with High Density of Defects

We show that carbon nanotubes (CNTs) with high density of defects can present a strong electronic interaction with nanoparticles of Pt-Ru with average particle size of 3.5 +/- 0.8 nm. Depending on the Pt-Ru loading on the CNTs, CO and methanol oxidation reactions suggest there is a charge transfer between Pt-Ru that in turn provokes a decrease in the electronic interaction taking place between Ru and Pt in the PtRu alloy. The CO stripping potentials were observed at about 0.65 and 0.5 V for Pt-Ru/CNT electrodes with Pt-Ru loadings of 10 and 20, and 30 wt %, respectively. (C) 2008 The Electrochemical Society. [DOI: 10.1149/1.2990222] All rights reserved.

Preliminary biocompatibility investigation of magnetic albumin nanosphere designed as a potential versatile drug delivery system

Background: The magnetic albumin nanosphere (MAN), encapsulating maghemite nanoparticles, was designed as a magnetic drug delivery system (MDDS) able to perform a variety of biomedical applications. It is noteworthy that MAN was efficient in treating Ehrlich's tumors by the magnetohyperthermia procedure. Methods and materials: In this study, several nanotoxicity tests were systematically carried out in mice from 30 minutes until 30 days after MAN injection to investigate their biocompatibility status. Cytometry analysis, viability tests, micronucleus assay, and histological analysis were performed. Results: Cytometry analysis and viability tests revealed MAN promotes only slight and temporary alterations in the frequency of both leukocyte populations and viable peritoneal cells, respectively. Micronucleus assay showed absolutely no genotoxicity or cytotoxicity effects and histological analysis showed no alterations or even nanoparticle clusters in several investigated organs but, interestingly, revealed the presence of MAN clusters in the central nervous system (CNS). Conclusion: The results showed that MAN has desirable in vivo biocompatibility, presenting potential for use as a MDDS, especially in CNS disease therapy.

Qualitative Analysis of the Interdisciplinary Interaction between Data Analysis Specialists and Novice Clinical Researchers

Background: The inherent complexity of statistical methods and clinical phenomena compel researchers with diverse domains of expertise to work in interdisciplinary teams, where none of them have a complete knowledge in their counterpart's field. As a result, knowledge exchange may often be characterized by miscommunication leading to misinterpretation, ultimately resulting in errors in research and even clinical practice. Though communication has a central role in interdisciplinary collaboration and since miscommunication can have a negative impact on research processes, to the best of our knowledge, no study has yet explored how data analysis specialists and clinical researchers communicate over time. Methods/Principal Findings: We conducted qualitative analysis of encounters between clinical researchers and data analysis specialists (epidemiologist, clinical epidemiologist, and data mining specialist). These encounters were recorded and systematically analyzed using a grounded theory methodology for extraction of emerging themes, followed by data triangulation and analysis of negative cases for validation. A policy analysis was then performed using a system dynamics methodology looking for potential interventions to improve this process. Four major emerging themes were found. Definitions using lay language were frequently employed as a way to bridge the language gap between the specialties. Thought experiments presented a series of ""what if'' situations that helped clarify how the method or information from the other field would behave, if exposed to alternative situations, ultimately aiding in explaining their main objective. Metaphors and analogies were used to translate concepts across fields, from the unfamiliar to the familiar. Prolepsis was used to anticipate study outcomes, thus helping specialists understand the current context based on an understanding of their final goal. Conclusion/Significance: The communication between clinical researchers and data analysis specialists presents multiple challenges that can lead to errors.

Merging Resource Availability with Isotope Mixing Models: The Role of Neutral Interaction Assumptions

Background: Bayesian mixing models have allowed for the inclusion of uncertainty and prior information in the analysis of trophic interactions using stable isotopes. Formulating prior distributions is relatively straightforward when incorporating dietary data. However, the use of data that are related, but not directly proportional, to diet (such as prey availability data) is often problematic because such information is not necessarily predictive of diet, and the information required to build a reliable prior distribution for all prey species is often unavailable. Omitting prey availability data impacts the estimation of a predator's diet and introduces the strong assumption of consumer ultrageneralism (where all prey are consumed in equal proportions), particularly when multiple prey have similar isotope values. Methodology: We develop a procedure to incorporate prey availability data into Bayesian mixing models conditional on the similarity of isotope values between two prey. If a pair of prey have similar isotope values (resulting in highly uncertain mixing model results), our model increases the weight of availability data in estimating the contribution of prey to a predator's diet. We test the utility of this method in an intertidal community against independently measured feeding rates. Conclusions: Our results indicate that our weighting procedure increases the accuracy by which consumer diets can be inferred in situations where multiple prey have similar isotope values. This suggests that the exchange of formalism for predictive power is merited, particularly when the relationship between prey availability and a predator's diet cannot be assumed for all species in a system.

Signature of the interaction between dark energy and dark matter in observations

We investigate the effect of an interaction between dark energy and dark matter upon the dynamics of galaxy clusters. This effect is computed through the Layser-Irvine equation, which describes how an astrophysical system reaches virial equilibrium and was modified to include the dark interactions. Using observational data from almost 100 purportedly relaxed galaxy clusters we put constraints on the strength of the couplings in the dark sector. We compare our results with those from other observations and find that a positive (in the sense of energy flow from dark energy to dark matter) nonvanishing interaction is consistent with the data within several standard deviations.

Field theory model for dark matter and dark energy in interaction

We propose a field theory model for dark energy and dark matter in interaction. Comparing the classical solutions of the field equations with the observations of the CMB shift parameter, baryonic acoustic oscillations, lookback time, and the Gold supernovae sample, we observe a possible interaction between dark sectors with energy decay from dark energy into dark matter. The observed interaction provides an alleviation to the coincidence problem.