E2F modulates keratinocyte squamous differentiation. Implications for E2F inhibition in squamous cell carcinoma

E2F regulation is essential for normal cell cycle progression. Therefore, it is not surprising that squamous cell carcinoma cell lines (SCC) overexpress E2F1 and exhibit deregulated E2F activity when compared with normal keratinocytes. Indeed, deliberate E2F1 deregulation has been shown to induce hyperplasia and skin tumor formation. In this study, we report on a dual role for E2F as a mediator of keratinocyte proliferation and modulator of squamous differentiation. Overexpression of E2F isoforms in confluent primary keratinocyte cultures resulted in suppression of differentiation-associated markers. Moreover, we found that the DNA binding domain and the trans-activation domain of E2F1 are important in mediating suppression of differentiation. Use of a dominant/negative form of E2F1 ( E2F d/n) found that E2F inhibition alone is sufficient to suppress the activity of proliferation-associated markers but is not capable of inducing differentiation markers. However, if the E2F d/n is expressed in differentiated keratinocytes, differentiation marker activity is further induced, suggesting that E2F may act as a modulator of squamous differentiation. We therefore examined the effects of E2F d/n in a differentiation- insensitive SCC cell line. We found that treatment with the differentiating agent, 12-O-tetradecanoyl- phorbol-13-acetate (TPA), or expression of E2F d/n alone had no effect on differentiation markers. However, a combination of E2F d/n + TPA induced the expression of differentiation markers. Combined, these data indicate that E2F may play a key role in keratinocyte differentiation. These data also illustrate the unique potential of anti-E2F therapies in arresting proliferation and inducing differentiation of SCCs.

Endogenous angiotensin II modulates nNOS expression in renovascular hypertension

Nitric oxide (NO) influences renal blood flow mainly as a result of neuronal nitric oxide synthase (nNOS). Nevertheless, it is unclear how nNOS expression is modulated by endogenous angiotensin II, an inhibitor of NO function. We tested the hypothesis that the angiotensin II AT1 receptor and oxidative stress mediated by NADPH oxidase contribute to the modulation of renal nNOS expression in two-kidney, one-clip (2K1C) hypertensive rats. Experiments were performed on male Wistar rats (150 to 170 g body weight) divided into 2K1C (N = 19) and sham-operated (N = 19) groups. nNOS expression in kidneys of 2K1C hypertensive rats (N = 9) was compared by Western blotting to that of 2K1C rats treated with low doses of the AT1 antagonist losartan (10 mg·kg-1·day-1; N = 5) or the superoxide scavenger tempol (0.2 mmol·kg-1·day-1; N = 5), which still remain hypertensive. After 28 days, nNOS expression was significantly increased by 1.7-fold in the clipped kidneys of 2K1C rats and by 3-fold in the non-clipped kidneys of 2K1C rats compared with sham rats, but was normalized by losartan. With tempol treatment, nNOS expression increased 2-fold in the clipped kidneys and 1.4-fold in the non-clipped kidneys compared with sham rats. The changes in nNOS expression were not followed by changes in the enzyme activity, as measured indirectly by the cGMP method. In conclusion, AT1 receptors and oxidative stress seem to be primary stimuli for increased nNOS expression, but this up-regulation does not result in higher enzyme activity.

Enhancing reflexivity and technology in translation learning: case study on the use of ePortfolio as a training environment

In this paper we describe a casestudy of an experiment on how reflexivity and technology can enhance learning, by using ePorfolios as a training environment to develop translation skills. Translation is today a multiskilled job and translators need to assure their clients a good performance and quality, both in language and in technology domains. In order to accomplish it, for the translator all the tasks and processes he develops appear as crucial, being pretranslation and posttranslation processes equally important as the translation itself, namely as far as autonomy, reflexive and critical skills are concerned. Finally, the need and relevance for collaborative tasks and networks amongst virtual translation communities, led us to the decision of implementing ePortfolios as a tool to develop the requested skills and extend the use of Internet in translation, namely in terminology management phases, for the completion of each task, by helping students in the management of the projects deadlines, improving their knowledge on the construction and management of translation resources and deepening their awareness about the concepts related to the development and usability of ePorfolios.

Some translation difficulties in the use of false friends in english

This paper will focus on some aspects of translation based on blending distinct linguistic domains such as English Language and Portuguese in using false friends in the English class in tertiary level students, reflecting namely on: 1. the choice of a word suitable to the context in L2 ; 2. the difficulties encountered by choice of that word that could be misleading, by relying in a false L1 reality that is going to adulterate reality in the L2 domain; 3. the difficulty in making such type of distinctions due to the lack of linguistic and lexical knowledge. 4. the need to study the cause of these difficulties by working, not only with their peers, but also with their language teacher to develop strategies to diminish and if possible to eradicate this type of linguistic and, above all, translation problem by making an inventory of those types of mistakes. In relation to the first point it is necessary to know that translation tasks involve much more than literal concepts ( Ladmiral, 1975) : furthermore it is necessary and suitable to realise that lexicon relies in significant contexts (Coseriu 1966), which connects both domains, that, at first sight do not seem to be compatible. In other words, although students have the impression they dominate lexicon due to the fact that they possess at least seven years of foreign language exposure that doesn’t mean they master the particularities engaged in such a delicate task as translation is concerned. There are some chromaticisms in the words (false friends), that need to be researched and analysed later on by both students and language teachers. The reason for such state of affairs lies in their academic formation, of a mainly general stream, which has enabled them only for knowledge of the foreign language, but not for the translation as a tool as it is required only when they reach the tertiary level. Besides, for their translations they rely, most of the times, on glossaries, whose dominant language is portuguese of Brazil, which is, obviously, much different from the portuguese mother tongue reality and even more of English. So it seems necessary to use with caution the working tools (glossaries) that work as surpluses, but could bring translation problems as we will see.

Intersubjectivity and poetic translation

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Pronoun-dropping or zero anaphora in translation from german into portuguese

In this article I will analyse anaphoric references in German texts and their transaltion into Portuguese. I will take as main corpus Heinrich Böll's novel Haus ohne Hüter and its translation into Portuguese by Jorge Rosa with the title Casa Indefesa. I will concentrate on the use of personal pronouns and possessives in references to both people and objects in source text and target text and I will present patterns of symmetries and asymmetries. I will claim that asymmetries in the translation of such anaphoric references can be accounted for mainly by differences in the pronominal systems and verbal systems of both languages and by differences in the way each language marks theme/topic continuity/discontinuity in discourse. Issues related to style and the translation of anaphors will also be addressed. I will finally raise some questions related to ambiguous references which can not be solved within the scope of syntax or semantics, thus requiring pragmatic interpretation based on cultural knowledge/world knowledge.

Intersubjectivity and a practical intersubjective ethics of translation

This essay suggests that the intersubjectivity in translation should be given priority because different stages of the translation activity have different subjects, and presents a practical intersubjective ethics of translation based on an interpretation of the intersubjective relations connected with translation activities in a perspective of game theory in the hope that it can equip us with better explanations of the translator’s calculations or considerations in the professional practice.

Literary translation and quality assessment analysis – its significance in translation training

This paper aims to highlight the role of translation quality assessment in translation training so as to develop students’ translation competence and skills to face translation problems. An analysis to assess literary translation quality is proposed before proceeding to discuss its pedagogical implementation.

Translation termination and protein folding pathway genes are not correlated in gastric cancer

Background: The eukaryotic release factor 3 (eRF3) has been shown to affect both tubulin and actin cytoskeleton, suggesting a role in cytoskeleton assembly, mitotic spindle formation and chromosome segregation. Also, direct interactions between eRF3 and subunits of the cytosolic chaperonin CCT have been described. Moreover, both eRF3a and CCT subunits have been described to be up-regulated in cancer tissues. Our aim was to evaluate the hypothesis that eRF3 expression levels are correlated with the expression of genes encoding proteins involved in the tubulin folding pathways. Methods: Relative expression levels of eRF1, eRF3a/GSPT1, PFDN4, CCT2, CCT4, and TBCA genes in tumour samples relative to their adjacent normal tissues were investigated using real time-polymerase chain reaction in 20 gastric cancer patients. Results: The expression levels of eRF3a/GSPT1 were not correlated with the expression levels of the other genes studied. However, significant correlations were detected between the other genes, both within intestinal and diffuse type tumours. Conclusions: eRF3a/GSPT1 expression at the mRNA level is independent from both cell translation rates and from the expression of the genes involved in tubulin-folding pathways. The differences in the patterns of expression of the genes studied support the hypothesis of genetically independent pathways in the origin of intestinal and diffuse type gastric tumours.

Modulation of translation factor's gene expression by histone deacetylase inhibitors in breast cancer cells

The histone deacetylase inhibitors sodium butyrate (NaBu) and trichostatin A (TSA) exhibit anti-proliferative activity by causing cell cycle arrest and apoptosis. The mechanisms by which NaBu and TSA cause apoptosis and cell cycle arrest are not yet completely clarified, although these agents are known to modulate the expression of several genes including cell-cycle- and apoptosis-related genes. The enzymes involved in the process of translation have important roles in controlling cell growth and apoptosis, and several of these translation factors have been described as having a causal role in the development of cancer. The expression patterns of the translation mechanism, namely of the elongation factors eEF1A1 and eEF1A2, and of the termination factors eRF1 and eRF3, were studied in the breast cancer cell line MCF-7 by real-time quantitative reverse transcription-polymerase chain reaction after a 24-h treatment with NaBu and TSA. NaBu induced inhibition of translation factors' transcription, whereas TSA caused an increase in mRNA levels. Thus, these two agents may modulate the expression of translation factors through different pathways. We propose that the inhibition caused by NaBu may, in part, be responsible for the cell cycle arrest and apoptosis induced by this agent in MCF-7 cells.

Contrastive terminology: semitic, anglo-germanic and latin concept building through complex terms. (avoiding one-way method procedures in translation

This paper aims to present a contrastive approach between three different ways of building concepts after proving the similar syntactic possibilities that coexist in terms. However, from the semantic point of view we can see that each language family has a different distribution in meaning. But the most important point we try to show is that the differences found in the psychological process when communicating concepts should guide the translator and the terminologist in the target text production and the terminology planning process. Differences between languages in the information transmission process are due to the different roles the different types of knowledge play. We distinguish here the analytic-descriptive knowledge and the analogical knowledge among others. We also state that none of them is the best when determining the correctness of a term, but there has to be adequacy criteria in the selection process. This concept building or term building success is important when looking at the linguistic map of the information society.

The Moving Text. Localization, translation and distribution

For some years now, translation theorist and educator Anthony Pym has been trying to establish a dialogue between the academic tradition he comes from and the world of the language industries into which he is meant to introduce his students: in other words, between the Translation Studies discipline and the localisation sector. This rapprochement is also the stated aim of his new book The Moving Text (p. 159). Rather than collect and synthesise what was previously dispersed over several articles, Pym has rewritten his material completely, both literally and conceptually, all in the light of the more than three decades of research he has conducted into the field of cross--cultural communication. The theoretical arguments are ably supported by a few short but telling and well-exploited examples.

Hydrogen peroxide sensing, signaling and regulation of transcription factors

The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm-nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and, (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes. We also discuss how H2O2 biological specificity results from diverse thiol protein sensors, with different reactivity of their sulfhydryl groups towards H2O2, being activated by different concentrations and times of exposure to H2O2. The specific regulation of local H2O2 concentrations is also crucial and results from H2O2 localized production and removal controlled by signals. Finally, we formulate equations to extract from typical experiments quantitative data concerning H2O2 reactivity with sensor molecules. Rate constants of 140 M-1s−1 and ≥ 1.3 × 103 M-1s−1 were estimated, respectively, for the reaction of H2O2 with KEAP1 and with an unknown target that mediates NRF2 protein synthesis. In conclusion, the multitude of H2O2 targets and mechanisms provides an opportunity for highly specific effects on gene regulation that depend on the cell type and on signals received from the cellular microenvironment.

Literature, translation and national identity: Christina Rossetti and Rosalía de Castro in the work of Plácido Castro

Plácido Castro‘s work has aroused our interest, because it evolves around the question of Galician personality and identity. While working as a journalist and a translator or while writing essays on different literary issues, Plácido Castro has never forgotten his roots or his nation. One could even say that his whole life turns around Galicia. Our purpose is to make a critical analysis of his work, especially as a translator, and try to show how he used translation in order to develop national conscience and identity and to see how far his ideology interfered in the interpretation and translation of Rossetti‘s poetry, in which he found a great similarity with Rosalìa de Castro‘s work.