The isatin-Schiff base copper(II) complex Cu(isaepy)(2) acts as delocalized lipophilic cation, yields widespread mitochondrial oxidative damage and induces AMP-activated protein kinase-dependent apoptosis

We previously demonstrated that Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl) pyridine-N, N`] copper(II) [Cu(isaepy)(2)] was an efficient inducer of the apoptotic mitochondrial pathway. Here, we deeply dissect the mechanisms underlying the ability of Cu(isaepy)(2) to cause mitochondriotoxicity. In particular, we demonstrate that Cu(isaepy)(2) increases NADH-dependent oxygen consumption of isolated mitochondria and that this phenomenon is associated with oxy-radical production and insensitive to adenosine diphosphate. These data indicate that Cu(isaepy)(2) behaves as an uncoupler and this property is also confirmed in cell systems. Particularly, SH-SY5Y cells show: (i) an early loss of mitochondrial transmembrane potential; (ii) a decrease in the expression levels of respiratory complex components and (iii) a significant adenosine triphosphate (ATP) decrement. The causative energetic impairment mediated by Cu(isaepy)(2) in apoptosis is confirmed by experiments carried out with rho(0) cells, or by glucose supplementation, where cell death is significantly inhibited. Moreover, gastric and cervix carcinoma AGS and HeLa cells, which rely most of their ATP production on oxidative phosphorylation, show a marked sensitivity toward Cu(isaepy)(2). Adenosine monophosphate-activated protein kinase (AMPK), which is activated by events increasing the adenosine monophosphate: ATP ratio, is deeply involved in the apoptotic process because the overexpression of its dominant/negative form completely abolishes cell death. Upon glucose supplementation, AMPK is not activated, confirming its role as fuel-sensing enzyme that positively responds to Cu(isaepy)(2)-mediated energetic impairment by committing cells to apoptosis. Overall, data obtained indicate that Cu(isaepy)(2) behaves as delocalized lipophilic cation and induces mitochondrial-sited reactive oxygen species production. This event results in mitochondrial dysfunction and ATP decrease, which in turn triggers AMPK-dependent apoptosis.

A corpus approach to discursive constructions of a hip-hop identity

This chapter is an analysis of a 100,000-word corpus consisting of message-board postings on hip-hop websites. A discourse analysis of this corpus reveals three strategies employed by the posters to identify themselves as members of the hip-hop community in the otherwise anonymous setting of the internet: (1) defined openings and closings, (2) repeated use of slang and taboo terms, and (3) performance of verbal art. Each strategy is characterized by the codification of non-standard grammar and pronunciations characteristic of speech, as well as by the use of non-standard orthography. The purpose of the discourse is shown to be a performance of identity, whereby language is used and recognized as the discursive construction of one’s hip-hop identity.

The gay subject in business and its discursive formation: an exploration on power, knowledge and sexuality

Issues related to the reality of lesbian, gay, bisexual and transgender (LGBT) individuals are being incorporated into institutional and social discourses, and show the challenges that must be overcome towards citizenship. The inclusion of gay rights in the domain of institutions like the United Nations and the Brazilian Secretariat of Human Rights are a response to broader movements that places the gay subject as an important topic of debate in the social-political sphere. In this scenario, some institutions deserve close attention from researchers related to gay issues, the business environment being a good example. In this domain, diversity has become an important topic of debate between scholars, where the question of sexual identity in most cases does not appear. The literature that actually focuses on the theme is explored through approaches that are not able to break with universalisms and a normatized vocabulary. Therefore, this research explores discursive structures related to sexuality and examines the meanings construed throughout these structures as described by gay individuals working in business. Furthermore, it investigates patterns of discursive normative structures and consequential challenges faced by gay people in the working environment, and also complements the current debate both in the socio-political sphere and in academic reality on LGBT challenges. The Foucauldian notions of discourse, knowledge and power, and the main concepts of queer theory are incorporated to the analysis, as well as concepts related to the politics of post-colonial sexuality, subordination, and hegemonic forces, together with role of reflexivity in modernity and its impacts on secularized mental structures. The research design takes a phenomenological approach and bases its knowledge claim on a participatory perspective, where the sample chosen for data collection consisted of gay individuals working in the business environment, aiming at generate categories of meanings through the description of their experiences.

A Transposição Didádica dos Gêneros do domínio do discursivo publicitários nos livros didáticos

Advertising text has been a subject of many investigations, because of its multimodal universe. Embodied by a linguistic and discursive materiality laying on scene persuasion, argumentation and power imagery of multissemiotics elements, the advertising text acts as an instrument of power, creating and destroying, promising and denying (CARVALHO, 2007). Advertising not only invites us to act for it, but directs us to look at it. It was under this moving look - of charm and interrogations - that discussions raised in this research were born. Investigations are directed to the school environment, in special, for the discursive advertising domain in Portuguese Language Textbook. It is from this environment that was born our research whose main objective is to analyze how does the didactic transposition of textual genres, described by Marcuschi (2008) as belonging to the "advertising" discourse domain (focusing on advertising genre) in didactic books teaching Portuguese Language before and after the advent of the PCN. Textbooks taken as reference for the study are historically situated in the 90s of the twentieth century and 10 century. Such books refer to elected 7th and 8th grades, currently corresponding to the 8th and 9th grades of elementary school. The choice is justified by the fact that in these Textbook teaching series the presence of advertising domain is recurrent and "didactized". In addition, we are also concerned in analyzing books that circulated around us and our regional reality. Hence, we elected books that were used by two public high schools: Municipal School Clementina Ana da Conceição in Jaçanã city in the Rio Grande do Norte state, State School for Elementary and High school Carlota Barreira in Areia city, Paraíba state. In our research the following categories of analysis were highlighted: (1) presence of advertising in DB, (2) fluctuation terminology: concepts and classifications; (3) The complexity of concepts facilitation, (4) what they propagate, and from which nature are the explored advertisements. From our analysis, we observe how the treatment of textual "advertising" genres have been inserted into Textbooks, and how occurs, in general, their didactic transposition. Focusing on the issue of fluctuating terminology, we noted the difficulty in drawing boundaries between the genres of advertising domain in the Textbooks. However, this also would result in the complexity - in the field of scientific knowledge - of delimiting genres of the same domain. To accomplish our studies, it was required a thorough and systematic dialogue with theories regarding the concept of "Didactic Transposition", due to the theoretical Chevallard Yves (1991), research on the textual genres - Bezerra (2005), Marcuschi (2008), Bazerman (2005), Swales (2004), among others - and studies involving the field of "Advertising" - Sandmann (2002), Carvalho (2007) and others

Em cantos de reis: a tradição discursiva em Autos de Natal

This study incorporates many areas of knowledge to the Linguistics field, as it centers the social historicity of Brazilian and autos potiguares on two analytical proposes: the presence of linguistic formulas - in its macrostructure - into the paradigm of discursive traditions, following Kabatek (2006), Koch and Oesterreicher (2007), besides the theory of Speech Acts, in its microstructure, proposed by Austin (1990) and Searle (1995). Under Zumthor (1993; 1997; 2000; 2005; 2010), the idea of textual variability (mouvance) was alluded, highlighting that the text is always modifying, according to the performance and reception of the language uses. Considering this theoretical framework, we focus on the trinomial linguistic formulas, orality and performance, in order to describe the dynamics of stability, variation and change, emphasizing yet how extra-linguistic social-historic cultural relations influence its composition. Such discuss is inherent more precisely to Textual Analysis in enhancing the orality tradition as a linguistic support. The text, in its turn, becomes effective as an evocation, motivated by the transmission, reception and variability from its conservation and reiteration. Naturally, a methodological support based on quali-quantitative research was chosen, based on Flick (2009), who justifies the corpus composed by Brazilian Folias de Reis chants and Bois de Reis potiguares . Thereby Language dynamics, subjacent to tradition which takes effect by the use of a common social memory, are observed from two dimensions: on the first, it evocates the sacralization (religious) in which they stand their devotion to biblical History; secondly, a dissacralization with identified and ideological values, inherent to a people culture. The chant shows, in this ludic impulse, a contextualized activity which results in the following conclusion: the changing and stability processes in textual macro and microstructures occur, at the same time, by the adjustment to the use of the text accomplishing a social-political function and an ethical-pedagogic one; supposedly, social relationships arise the tradition and it, on its turn, evocates the variability and the nomadism in the text

Esperando Ulisses: o mito de Penélope à luz da comparação diferencial e discursiva

From the many weavers known, the Queen of Ithaca is certainly among the most famous.Over the years,many writers have dedicated themselves to retell the myth of Penelope in their works by their own way. According to Ute Heidmann, the modern writers recurrence to the Greek myths in order to produce their texts is a renewing discursive practice, which gives new writing and relevance to the myth. (2003, p.47). This work deals with a differential and discursive comparative analysis on the myth of Penelope linking it with two short stories from Brazilian authors: Penélope by João do Rio (1919) and Penélope by Dalton Trevisan (1959). In order to do it, we are supported by: the works of Heidmann (2003, 2006, 2008) and Maingueneau (2006). We also concentrate ourselves on the temporal trace presented in both Penelope s myth and in its modern rewriting so that we can identify how each configuration of the classical myth develops into one of the most celebrated acts of this myth: the waiting. In order to so, we seek support on the studies by Paul Ricoeur (2006), Hans Meyerhoff (1976) and Benedito Nunes (1988)

Pkc1 acts through Zds1 and Gic1 to suppress growth and cell polarity defects of a yeast eIF5A mutant

eIF5A is a highly conserved putative eukaryotic translation initiation factor that has been implicated in translation initiation, nucleocytoplasmic transport, mRNA decay, and cell proliferation, but with no precise function assigned so far. We have previously shown that high-copy PKCI suppresses the phenotype of tif51A-1, a temperature-sensitive mutant of eIF5A in S. cerevisiae. Here, in an attempt to further understand how Pkc1 functionally interacts with eIF-5A, it was determined that PKCI suppression of tif51A-1 is independent of the cell integrity MAP kinase cascade. Furthermore, two new suppressor genes, ZDS1 and GIC1, were identified. We demonstrated that ZDS1 and ZDS2 are necessary for PKC1, but not for GIC1 suppression. Moreover, high-copy GIC1 also suppresses the growth defect of a PKCI mutant (stt1), suggesting the existence of a Pkc1-Zds1-Gic1 pathway. Consistent with the function of Gic1 in actin organization, the tif51A-1 strain shows an actin polarity defect that is partially recovered by overexpression of Pkc1 and Zds1 as well as Gic1. Additionally, PCL1 and BNI1, important regulators of yeast cell polarity, also suppress tif51A-1 temperature sensitiviiy Taken together, these data strongly Support the correlated involvement of Pkc1 and eIF5A in establishing actin polarity, which is essential for bud formation and G1/S transition in S. cerevisiae.

MicroRNA-100 Acts as a Tumor Suppressor in Human Bladder Carcinoma 5637 Cells

Bladder carcinoma is one of the most common tumors in the world and, despite the therapy currently available, most of the patients relapse. Better understanding of the factors involved in disease pathogenesis would provide insights for the development of more effective strategies in treatment. Recently, differential miRNA expression profiles in bladder urothelial carcinomas identified miR-100 down-regulation and miR-708 up-regulation among the most common alterations, although the possible influence of these miRNAs in the control of basic mechanisms in bladder tumors has not been addressed. In this context, the present study aimed to evaluate the in vitro effects of miR-100 forced expression and miR-708 inhibition in the bladder carcinoma cell line 5637. Our results showed that overexpression of miR-100 significantly inhibited growth when compared to controls at both times tested (72 and 96 hours, p<0.01) with a maximum effect at 72 hours reducing proliferation in 29.6 %. Conversely, no effects on cell growth were observed after inhibition of miR-708. MiR-100 also reduced colony formation capacity of 5637 cells by 24.4%. No alterations in cell cycle progression or apoptosis induction were observed. The effects of miR-100 on growth and clonogenicity capacity in 5637 cells evince a possible role of this miRNA in bladder carcinoma pathogenesis. Further studies are necessary to corroborate our findings and examine the potential use of this microRNA in future therapeutic interventions.

Brazilian Medicinal Plant Acts on Prostaglandin Level and Helicobacter pylori

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

TNF-alpha acts in the hypothalamus inhibiting food intake and increasing the respiratory quotient - Effects on leptin and insulin signaling pathways

Acting in the hypothalamus, tumor necrosis factor-alpha (TNF-alpha) produces a potent anorexigenic effect. However, the molecular mechanisms involved in this phenomenon are poorly characterized. In this study, we investigate the capacity of TNF-alpha to activate signal transduction in the hypothalamus through elements of the pathways employed by the anorexigenic hormones insulin and leptin. High dose TNF-a promotes a reduction of 25% in 12 h food intake, which is an inhibitory effect that is marginally inferior to that produced by insulin and leptin. In addition, high dose TNF-a increases body temperature and respiratory quotient, effects not reproduced by insulin or leptin. TNF-alpha, predominantly at the high dose, is also capable of activating canonical pro-inflammatory signal transduction in the hypothalamus, inducing JNK, p38, and NF kappa B, which results in the transcription of early responsive genes and expression of proteins of the SOCS family. Also, TNF-a activates signal transduction through JAK-2 and STAT-3, but does not activate signal transduction. through early and intermediary elements of the insulin/leptin signaling pathways such as IRS-2, Akt, ERK and FOXO1. When co-injected with insulin or leptin, TNF-a, at both high and low doses, partially impairs signal transduction through IRS-2, Akt, ERK and FOXO1 but not through JAK-2 and STAT-3. This effect is accompanied by the partial inhibition of the anorexigenic effects of insulin and leptin, when the low, but not the high dose of TNF-alpha is employed. In conclusion, TNF-alpha, on a dose-dependent way, modulates insulin and leptin signaling and action in the hypothalamus. (c) Published by Elsevier B.V.

Low intensity laser therapy (LILT) in vivo acts on the neutrophils recruitment and chemokines/cytokines levels in a model of acute pulmonary inflammation induced by aerosol of lipopolysaccharide from Escherichia coli in rat

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)