MicroRNA expression is differentially altered by xenobiotic drugs in different human cell lines

Several noncoding microRNAs (miR or miRNA) have been shown to regulate the expression of drug-metabolizing enzymes and transporters. Xenobiotic drug-induced changes in enzyme and transporter expression may be associated with the alteration of miRNA expression. Therefore, this study investigated the impact of 19 xenobiotic drugs (e. g. dexamethasone, vinblastine, bilobalide and cocaine) on the expression of ten miRNAs (miR-18a, -27a, -27b, -124a, -148a, -324-3p, -328, -451, -519c and -1291) in MCF-7, Caco-2, SH-SY5Y and BE(2)-M17 cell systems. The data revealed that miRNAs were differentially expressed in human cell lines and the change in miRNA expression was dependent on the drug, as well as the type of cells investigated. Notably, treatment with bilobalide led to a 10-fold increase of miR-27a and a 2-fold decrease of miR-148a in Caco-2 cells, but no change of miR-27a and a 2-fold increase of miR-148a in MCF-7 cells. Neuronal miR-124a was generally down-regulated by psychoactive drugs (e. g. cocaine, methadone and fluoxetine) in BE(2)-M17 and SH-SY5Y cells. Dexamethasone and vinblastine, inducers of drug-metabolizing enzymes and transporters, suppressed the expression of miR-27b, -148a and -451 that down-regulate the enzymes and transporters. These findings should provide increased understanding of the altered gene expression underlying drug disposition, multidrug resistance, drug-drug interactions and neuroplasticity. Copyright (C) 2011 John Wiley & Sons, Ltd.

Termination of diamond surfaces with hydrogen, oxygen and fluorine using a small, simple plasma gun

We have formed and characterized polycrystalline diamond films with surfaces having hydrogen terminations, oxygen terminations, or fluorine terminations, using a small, simple and novel plasma gun to bombard the diamond surface, formed by plasma assisted CVD in a prior step, with ions of the wanted terminating species. The potential differences between surface regions with different terminations were measured by Kelvin Force Microscopy (KFM). The highest potential occurred for oxygen termination regions and the lowest for fluorine. The potential difference between regions with oxygen terminations and hydrogen terminations was about 80 mV, and between regions with hydrogen terminations and fluorine terminations about 150 mV. Regions with different terminations were identified and imaged using the secondary electron signal provided by scanning electron microscopy (SEM). since this signal presents contrast for surfaces with different electrical properties. The wettability of the surfaces with different terminations was evaluated, measuring contact angles. The sample with oxygen termination was the most hydrophilic, with a contact angle of 75 degrees. hydrogen-terminated regions with 83 degrees, and fluorine regions 93 degrees, the most hydrophobic sample. (C) 2010 Elsevier B.V. All rights reserved.

Observation of an Antimatter Hypernucleus

Nuclear collisions recreate conditions in the universe microseconds after the Big Bang. Only a very small fraction of the emitted fragments are light nuclei, but these states are of fundamental interest. We report the observation of antihypertritons-comprising an antiproton, an antineutron, and an antilambda hyperon-produced by colliding gold nuclei at high energy. Our analysis yields 70 +/- 17 antihypertritons (3/Lambda(H) over bar) and 157 +/- 30 hypertritons ((3)(Lambda)H). The measured yields of (3)(Lambda)H (3/Lambda(H) over bar) and (3)He ((3)(He) over bar) are similar, suggesting an equilibrium in coordinate and momentum space populations of up, down, and strange quarks and antiquarks, unlike the pattern observed at lower collision energies. The production and properties of antinuclei, and of nuclei containing strange quarks, have implications spanning nuclear and particle physics, astrophysics, and cosmology.

Sugarcane Phosphoribosyl Pyrophosphate Synthetase: Molecular Characterization of a Phosphate-independent PRS

Phosphoribosyl pyrophosphate synthetase (PRS-EC:2.7.6.1) is an important enzyme present in several metabolic pathways, thus forming a complex family of isoenzymes. However, plant PRS enzymes have not been extensively investigated. In this study, a sugarcane prs gene has been characterized from the Sugar Cane Expressed Sequence Tag Genome Project. This gene contains a 984-bp open reading frame encoding a 328-amino acid protein. The predicted amino acid sequence has 77% and 78% amino acid sequence identity to Arabidopsis thaliana and Spinacia oleracea PRS4, respectively. The assignment of sugarcane PRS as a phosphate-independent PRS isoenzyme (Class II PRS) is verified following enzyme assay and phylogenetic reconstruction of PRS homologues. To gain further insight into the structural framework of the phosphate independence of sugarcane PRS, a molecular model is described. This model reveals the formation of two conserved domains elucidating the structural features involved in sugarcane PRS phosphate independence. The recombinant PRS retains secondary structure elements and a quaternary arrangement consistent with known PRS homologues, based on circular dichroism measurements.

Two-dimensional QSAR studies on arylpiperazines as high-affinity 5-HT(1A) receptor ligands

5-HT(1A) receptor plays an important role in the delayed onset of antidepressant action of a class of selective serotonin reuptake inhibitors. Moreover, 5-HT(1A) receptor levels have been shown to be altered in patients suffering from major depression. In this work, hologram quantitative structure-activity relationship (HQSAR) studies were performed on a series of arylpiperazine compounds presenting affinity to the 5-HT(1A) receptor. The models were constructed with a training set of 70 compounds. The most significant HQSAR model (q(2) = 0.81, r(2) = 0.96) was generated using atoms, bonds, connections, chirality, and donor and acceptor as fragment distinction, with fragment size of 6-9. Predictions for an external test set containing 20 compounds are in good agreement with experimental results showing the robustness of the model. Additionally, useful information can be obtained from the 2D contribution maps.

Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations

Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.

Immigration, security and the public debate on US language policy : a critical discourse analysis of language attitudes in the United States of America

The narrative of the United States is of a "nation of immigrants" in which the language shift patterns of earlier ethnolinguistic groups have tended towards linguistic assimilation through English. In recent years, however, changes in the demographic landscape and language maintenance by non-English speaking immigrants, particularly Hispanics, have been perceived as threats and have led to calls for an official English language policy.This thesis aims to contribute to the study of language policy making from a societal security perspective as expressed in attitudes regarding language and identity originating in the daily interaction between language groups. The focus is on the role of language and American identity in relation to immigration. The study takes an interdisciplinary approach combining language policy studies, security theory, and critical discourse analysis. The material consists of articles collected from four newspapers, namely USA Today, The New York Times, Los Angeles Times, and San Francisco Chronicle between April 2006 and December 2007.Two discourse types are evident from the analysis namely Loyalty and Efficiency. The former is mainly marked by concerns of national identity and contains speech acts of security related to language shift, choice and English for unity. Immigrants are represented as dehumanised, and harmful. Immigration is given as sovereignty-related, racial, and as war. The discourse type of Efficiency is mainly instrumental and contains speech acts of security related to cost, provision of services, health and safety, and social mobility. Immigrants are further represented as a labour resource. These discourse types reflect how the construction of the linguistic 'we' is expected to be maintained. Loyalty is triggered by arguments that the collective identity is threatened and is itself used in reproducing the collective 'we' through hegemonic expressions of monolingualism in the public space and semi-public space. The denigration of immigrants is used as a tool for enhancing societal security through solidarity and as a possible justification for the denial of minority rights. Also, although language acquisition patterns still follow the historical trend of language shift, factors indicating cultural separateness such as the appearance of speech communities or the use of minority languages in the public space and semi-public space have led to manifestations of intolerance. Examples of discrimination and prejudice towards minority groups indicate that the perception of worth of a shared language differs from the actual worth of dominant language acquisition for integration purposes. The study further indicates that the efficient working of the free market by using minority languages to sell services or buy labour is perceived as conflicting with nation-building notions since it may create separately functioning sub-communities with a new cultural capital recognised as legitimate competence. The discourse types mainly represent securitising moves constructing existential threats. The perception of threat and ideas of national belonging are primarily based on a zero-sum notion favouring monolingualism. Further, the identity of the immigrant individual is seen as dynamic and adaptable to assimilationist measures whereas the identity of the state and its members are perceived as static. Also, the study shows that debates concerning language status are linked to extra-linguistic matters. To conclude, policy makers in the US need to consider the relationship between four factors, namely societal security based on collective identity, individual/human security, human rights, and a changing linguistic demography, for proposed language intervention measures to be successful.

Historielärares historier : Ämnesbiografi och ämnesförståelse hos gymnasielärare i historia

The overall aim of this study is to analyse history teachers’ understanding of the school subject history. The aim have also been to uncover what factors the history teachers say have affected their understanding of the school subject. Based on survey and interview methods, the question that this study deals with is: in the light of which general understanding of the school subject history, do the teachers make didactic choices on a daily basis? The first theme is biographical. The teachers’ life-history is taken into consideration and several factors in the teachers’ background and the school environment have been identified. It also seems as if the teachers’ understanding of the school subject goes from an elementary and searching approach to one that is more complex and convinced. The second theme is a more structural approach. The results shows three major orientations among the teachers’ general understanding namely, educational (bildung) orientation, critical orientation and identity orientation. Even though a main orientation can be seen among the teachers, an important result is also that the orientation is overall complex. At the most general level some patterns can be seen. First the connection between the teachers’ biography and their general understanding of the school subject. In the understanding of the school subject, it is also notable that teachers relate in different ways to history as science, history as identity and history from an ideological viewpoint. It is also possible to note some signs of change in the school subject history that follows a lager historiographical context.

Percepção de sucesso na carreira da mulher executiva brasileira

ROCHA, Jane Barbosa da. Percepção de sucesso na carreira da mulher executiva brasileira. 2013. 113f. Dissertação (Mestrado em Administração) - Universidade Municipal de São Caetano do Sul, São Caetano do Sul, 2013.

Modelo de precificação do seguro de crédito à exportação para o mercado brasileiro

O trabalho visa abordar os recentes conceitos da teoria econômica de seguro, aplicando-os especificamente ao seguro de crédito à exportação. O intuito é a construção de um modelo pioneiro de precificação do risco de crédito, ajustado ao contexto do mercado exportador brasileiro.

Alguns aspectos macro e microeconomicos da economia brasileira pos-Real

Analisam-se neste trabalho alguns aspectos macro e microeconômicos da economia brasileira Pós-Real. Do ponto de vista macroeconômico, aborda-se a troca de imposto inflacionário por poupança externa no fInanciamento do défIcit operacional do setor público, a evolução da denominação da dívida pública federal, bem como a pertinência de diferentes regimes cambiais em um ambiente de instabilidade de funções macroeconômicas. Inclui-se também nesta seção uma breve e simplifIcada simulação da evolução da renda per-capta em caso de elevação do nível de investimentos de 20% para 25% do PIB. Do ponto de vista microeconômico, apresentam-se algumas reflexões pertinentes às áreas de privatização, regulação e defesa da concorrência.