Imatinib Restores Vasp Activity And Its Interaction With Zyxin In Bcr-abl Leukemic Cells.

Vasodilator-stimulated phosphoprotein (VASP) and Zyxin are interacting proteins involved in cellular adhesion and motility. PKA phosphorylates VASP at serine 157, regulating VASP cellular functions. VASP interacts with ABL and is a substrate of the BCR-ABL oncoprotein. The presence of BCR-ABL protein drives oncogenesis in patients with chronic myeloid leukemia (CML) due to a constitutive activation of tyrosine kinase activity. However, the function of VASP and Zyxin in BCR-ABL pathway and the role of VASP in CML cells remain unknown. In vitro experiments using K562 cells showed the involvement of VASP in BCR-ABL signaling. VASP and Zyxin inhibition decreased the expression of anti-apoptotic proteins, BCL2 and BCL-XL. Imatinib induced an increase in phosphorylation at Ser157 of VASP and decreased VASP and BCR-ABL interaction. VASP did not interact with Zyxin in K562 cells; however, after Imatinib treatment, this interaction was restored. Corroborating our data, we demonstrated the absence of phosphorylation at Ser157 in VASP in the bone marrow of CML patients, in contrast to healthy donors. Phosphorylation of VASP on Ser157 was restored in Imatinib responsive patients though not in the resistant patients. Therefore, we herein identified a possible role of VASP in CML pathogenesis, through the regulation of BCR-ABL effector proteins or the absence of phosphorylation at Ser157 in VASP.

Interaction between staining and degradation of a composite resin in contact with colored foods

Composite resins might be susceptible to degradation and staining when in contact with some foods and drinks. This study evaluated color alteration and changes in microhardness of a microhybrid composite after immersion in different colored foods and determined whether there was a correlation between these two variables. Eighty composite disks were randomly divided into 8 experimental groups (n = 10): kept dry; deionized water; orange juice; passion fruit juice; grape juice; ketchup; mustard and soy sauce. The disks were individually immersed in their respective test substance at 37 ºC, for a period of 28 days. Superficial analysis of the disk specimens was performed by taking microhardness measurements (Vickers, 50 g load for 45 seconds) and color alterations were determined with a spectrophotometer (CINTRA 10- using a CIEL*a*b* system, 400-700 nm wavelength, illuminant d65 and standard observer of 2º) at the following times: baseline (before immersion), 1, 7, 14, 21 and 28 days. Results were analyzed by ANOVA and Tukey's test (p < 0.05). Both variables were also submitted to Pearson's correlation test (p < 0.05). The passion fruit group underwent the greatest microhardness change, while the mustard group suffered the greatest color alteration. Significant positive correlation was found between the two variables for the groups deionized water, grape juice, soy sauce and ketchup. Not all color alteration could be associated with surface degradation.

Alluvial-eolian interaction in a Cambrian rift margin: the Pedra das Torrinhas and Pedra Pintada formations (Guaritas Group, RS)

This work presents a study of selected outcrops from the Pedra das Torrinhas Formation of the Guaritas Group (Cambrian, Camaquã Basin), near the basin bordering Encantadas Fault Zone. The studied succession includes alluvial fan deposits that pass laterally into eolian deposits. Sedimentary facies and architectural element analysis were performed, followed by sedimentary petrography and microscopic porosity analysis, aiming to characterize the porosity of the deposits and its spatial distribution. The main objective was to contribute to a better understanding of the porosity spatial distribution in depositional systems characterized by the interaction between alluvial and eolian processes, with special reference to deposits formed prior to the development of terrestrial plants. Porosity values are related to depositional processes, with higher porosities associated to eolian dune deposits (mean of 8.4%), and lower porosity related to interdunes (mean of 3.4%) and alluvial fans (mean of 4.3%). Architectural elements analysis revealed the spatial relationships of these deposits, a response to the interplay of the eolian and alluvial processes. The integration of porosity data reveals that the interaction of alluvial and eolian processes results in heterogeneous distribution of porosity at the facies association scale. Eolian reworking of alluvial facies increases porosity whereas sheet-flood and other alluvial processes in the interdune areas reduce porosity.

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.

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.

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.

Effect of zinc insertion and hydrophobicity on the membrane interactions and PDT activity of porphyrin photosensitizers

A series of photosensitizers (PS), which are meso-substituted tetra-cationic porphyrins, was synthesized in order to study the role of amphiphilicity and zinc insertion in photodynamic therapy (PDT) efficacy. Several properties of the PS were evaluated and compared within the series including photophysical properties (absorption spectra, fluorescence quantum yield Phi(f), and singlet oxygen quantum yield Phi(Delta)), uptake by vesicles, mitochondria and HeLa cells, dark and phototoxicity in HeLa cells. The photophysical properties of all compounds are quite similar (Phi(f) <= 0.02; Phi(Delta) similar to 0.8). An increase in lipophilicity and the presence of zinc in the porphyrin ring result in higher vesicle and cell uptake. Binding in mitochondria is dependent on the PS lipophilicity and on the electrochemical membrane potential, i.e., in uncoupled mitochondria PS binding decreases by up to 53%. The porphyrin substituted with octyl groups (TC8PyP) is the compound that is most enriched in mitochondria, and its zinc derivative (ZnTC8PyP) has the highest global uptake. The stronger membrane interaction of the zinc-substituted porphyrins is attributed to a complexing effect with phosphate groups of the phospholipids. Zinc insertion was also shown to decrease the interaction with isolated mitochondria and with the mitochondria of HeLa cells, an effect that has been explained by the particular characteristics of the mitochondrial internal membrane. Phototoxicity was shown to increase proportionally with membrane binding efficiency, which is attributed to favorable membrane interactions which allow more efficient membrane photooxidation. For this series of compounds, photodynamic efficiency is directly proportional to the membrane binding and cell uptake, but it is not totally related to mitochondrial targeting.

Hepatitis B (HBV), Hepatitis C (HCV) and Hepatitis Delta (HDV) Viruses in the Colombian Population-How Is the Epidemiological Situation?

Background: Viral hepatitis B, C and delta still remain a serious problem worldwide. In Colombia, data from 1980s described that HBV and HDV infection are important causes of hepatitis, but little is known about HCV infection. The aim of this study was to determine the currently frequency of HBV, HCV and HDV in four different Colombian regions. Methodology/Principal Findings: This study was conducted in 697 habitants from 4 Colombian departments: Amazonas, Choco, Magdalena and San Andres Islands. Epidemiological data were obtained from an interview applied to each individual aiming to evaluate risk factors related to HBV, HCV or HDV infections. All samples were tested for HBsAg, anti-HBc, anti-HBs and anti-HCV markers. Samples that were positive to HBsAg and/or anti-HBc were tested to anti-HDV. Concerning the geographical origin of the samples, the three HBV markers showed a statistically significant difference: HBsAg (p = 0.033) and anti-HBc (p < 0.001) were more frequent in Amazonas and Magdalena departments. Isolated anti-HBs (a marker of previous vaccination) frequencies were: Choco (53.26%), Amazonas (32.88%), Magdalena (17.0%) and San Andres (15.33%) p < 0.001. Prevalence of anti-HBc increased with age; HBsAg varied from 1.97 to 8.39% (p = 0.033). Amazonas department showed the highest frequency for anti-HCV marker (5.68%), while the lowest frequency was found in San Andres Island (0.66%). Anti-HDV was found in 9 (5.20%) out of 173 anti-HBc and/or HBsAg positive samples, 8 of them from the Amazonas region and 1 from them Magdalena department. Conclusions/Significance: In conclusion, HBV, HCV and HDV infections are detected throughout Colombia in frequency levels that would place some areas as hyperendemic for HBV, especially those found in Amazonas and Magdalena departments. Novel strategies to increase HBV immunization in the rural population and to strengthen HCV surveillance are reinforced by these results.

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.

Recovery of the star formation history of the LMC from the VISTA survey of the Magellanic system

The VISTA near infrared survey of the Magellanic System (VMC) will provide deep YJK(s) photometry reaching stars in the oldest turn-off point throughout the Magellanic Clouds (MCs). As part of the preparation for the survey, we aim to access the accuracy in the star formation history (SFH) that can be expected from VMC data, in particular for the Large Magellanic Cloud (LMC). To this aim, we first simulate VMC images containing not only the LMC stellar populations but also the foreground Milky Way (MW) stars and background galaxies. The simulations cover the whole range of density of LMC field stars. We then perform aperture photometry over these simulated images, access the expected levels of photometric errors and incompleteness, and apply the classical technique of SFH-recovery based on the reconstruction of colour-magnitude diagrams (CMD) via the minimisation of a chi-squared-like statistics. We verify that the foreground MW stars are accurately recovered by the minimisation algorithms, whereas the background galaxies can be largely eliminated from the CMD analysis due to their particular colours and morphologies. We then evaluate the expected errors in the recovered star formation rate as a function of stellar age, SFR(t), starting from models with a known age-metallicity relation (AMR). It turns out that, for a given sky area, the random errors for ages older than similar to 0.4 Gyr seem to be independent of the crowding. This can be explained by a counterbalancing effect between the loss of stars from a decrease in the completeness and the gain of stars from an increase in the stellar density. For a spatial resolution of similar to 0.1 deg(2), the random errors in SFR(t) will be below 20% for this wide range of ages. On the other hand, due to the lower stellar statistics for stars younger than similar to 0.4 Gyr, the outer LMC regions will require larger areas to achieve the same level of accuracy in the SFR( t). If we consider the AMR as unknown, the SFH-recovery algorithm is able to accurately recover the input AMR, at the price of an increase of random errors in the SFR(t) by a factor of about 2.5. Experiments of SFH-recovery performed for varying distance modulus and reddening indicate that these parameters can be determined with (relative) accuracies of Delta(m-M)(0) similar to 0.02 mag and Delta E(B-V) similar to 0.01 mag, for each individual field over the LMC. The propagation of these errors in the SFR(t) implies systematic errors below 30%. This level of accuracy in the SFR(t) can reveal significant imprints in the dynamical evolution of this unique and nearby stellar system, as well as possible signatures of the past interaction between the MCs and the MW.

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.