Three-dimensional modeling of tongue during speech using MRI data

The tongue is the most important and dynamic articulator for speech formation, because of its anatomic aspects (particularly, the large volume of this muscular organ comparatively to the surrounding organs of the vocal tract) and also due to the wide range of movements and flexibility that are involved. In speech communication research, a variety of techniques have been used for measuring the three-dimensional vocal tract shapes. More recently, magnetic resonance imaging (MRI) becomes common; mainly, because this technique allows the collection of a set of static and dynamic images that can represent the entire vocal tract along any orientation. Over the years, different anatomical organs of the vocal tract have been modelled; namely, 2D and 3D tongue models, using parametric or statistical modelling procedures. Our aims are to present and describe some 3D reconstructed models from MRI data, for one subject uttering sustained articulations of some typical Portuguese sounds. Thus, we present a 3D database of the tongue obtained by stack combinations with the subject articulating Portuguese vowels. This 3D knowledge of the speech organs could be very important; especially, for clinical purposes (for example, for the assessment of articulatory impairments followed by tongue surgery in speech rehabilitation), and also for a better understanding of acoustic theory in speech formation.

Analysis of tongue shape and motion in speech production using statistical modeling

The mechanisms of speech production are complex and have been raising attention from researchers of both medical and computer vision fields. In the speech production mechanism, the articulator’s study is a complex issue, since they have a high level of freedom along this process, namely the tongue, which instigates a problem in its control and observation. In this work it is automatically characterized the tongues shape during the articulation of the oral vowels of Portuguese European by using statistical modeling on MR-images. A point distribution model is built from a set of images collected during artificially sustained articulations of Portuguese European sounds, which can extract the main characteristics of the motion of the tongue. The model built in this work allows under standing more clearly the dynamic speech events involved during sustained articulations. The tongue shape model built can also be useful for speech rehabilitation purposes, specifically to recognize the compensatory movements of the articulators during speech production.

MicroRNA-375 plays a dual role in prostate carcinogenesis

Background: Prostate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis. Results: MicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay. Conclusions: A dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.

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.

The invisible factors that can make the difference. Language management and knowledge transfer in multinational sites

The knowledge-based society we live in has stressed the importance of human capital and brought talent to the top of most wanted skills, especially to companies who want to succeed in turbulent environments worldwide. In fact, streams, sequences of decisions and resource commitments characterize the day-to-day of multinational companies (MNCs). Such decision-making activities encompass major strategic moves like internationalization and new market entries or diversification and acquisitions. In most companies, these strategic decisions are extensively discussed and debated and are generally framed, formulated, and articulated in specialized language often developed by the best minds in the company. Yet the language used in such deliberations, in detailing and enacting the implementation strategy is usually taken for granted and receives little if any explicit attention (Brannen & Doz, 2012) an can still be a “forgotten factor” (Marschan et al. 1997). Literature on language management and international business refers to lack of awareness of business managers of the impact that language can have not only in communication effectiveness but especially in knowledge transfer and knowledge management in business environments. In the context of MNCs, management is, for many different reasons, more complex and demanding than that of a national company, mainly because of diversity factors inherent to internationalization, namely geographical and cultural spaces, i.e, varied mindsets. Moreover, the way of functioning, and managing language, of the MNC depends on its vision, its values and its internationalization model, i.e on in the way the MNE adapts to and controls the new markets, which can vary essentially from a more ethnocentric to a more pluricentric focus. Regardless of the internationalization model followed by the MNC, communication between different business units is essential to achieve unity in diversity and business sustainability. For the business flow and prosperity, inter-subsidiary, intra-company and company-client (customers, suppliers, governments, municipalities, etc..) communication must work in various directions and levels of the organization. If not well managed, this diversity can be a barrier to global coordination and create turbulent environments, even if a good technological support is available (Feely et al., 2002: 4). According to Marchan-Piekkari (1999) the tongue can be both (i) a barrier, (ii) a facilitator and (iii) a source of power. Moreover, the lack of preparation for the barriers of linguistic diversity can lead to various costs, including negotiations’ failure and failure on internationalization.. On the other hand, communication and language fluency is not just a message transfer procedure, but above all a knowledge transfer process, which requires extra-linguistic skills (persuasion, assertiveness …) in order to promote credibility of both parties. For this reason, MNCs need a common code to communicate and trade information inside and outside the company, which will require one or more strategies, in order to overcome possible barriers and organization distortions.

Expanding our therapeutic options: β-blockers for colon cancer?

Supported by U. Porto/Santander Totta (IJUP) (PP-IJUP2011-320)

Deregulated expression of selected histone methylases and demethylases in prostate carcinoma

Prostate cancer (PCa), a leading cause of cancer-related morbidity and mortality, arises through the acquisition of genetic and epigenetic alterations. Deregulation of histone methyltransferases (HMTs) or demethylases (HDMs) has been associated with PCa development and progression. However, the precise influence of altered HMTs or HDMs expression and respective histone marks in PCa onset and progression remains largely unknown. To clarify the role of HMTs and HDMs in prostate carcinogenesis, expression levels of 37 HMTs and 20 HDMs were assessed in normal prostate and PCa tissue samples by RT-qPCR. SMYD3, SUV39H2, PRMT6, KDM5A, and KDM6A were upregulated, whereas KMT2A-E (MLL1-5) and KDM4B were downregulated in PCa, compared with normal prostate tissues. Remarkably, PRMT6 was the histone modifier that best discriminated normal from tumorous tissue samples. Interestingly, EZH2 and SMYD3 expression levels significantly correlated with less differentiated and more aggressive tumors. Remarkably, SMYD3 expression levels were of independent prognostic value for the prediction of disease-specific survival of PCa patients with clinically localized disease submitted to radical prostatectomy. We concluded that expression profiling of HMTs and HDMs, especially SMYD3, might be of clinical usefulness for the assessment of PCa patients and assist in pre-therapeutic decision-making.

Regulation of histone H2A.Z expression is mediated by sirtuin 1 in prostate cancer

Histone variants seem to play a major role in gene expression regulation. In prostate cancer, H2A.Z and its acetylated form are implicated in oncogenes’ upregulation. SIRT1, which may act either as tumor suppressor or oncogene, reduces H2A.Z levels in cardiomyocytes, via proteasome-mediated degradation, and this mechanism might be impaired in prostate cancer cells due to sirtuin 1 downregulation. Thus, we aimed to characterize the mechanisms underlying H2A.Z and SIRT1 deregulation in prostate carcinogenesis and how they interact. We found that H2AFZ and SIRT1 were up- and downregulated, respectively, at transcript level in primary prostate cancer and high-grade prostatic intraepithelial neoplasia compared to normal prostatic tissues. Induced SIRT1 overexpression in prostate cancer cell lines resulted in almost complete absence of H2A.Z. Inhibition of mTOR had a modest effect on H2A.Z levels, but proteasome inhibition prevented the marked reduction of H2A.Z due to sirtuin 1 overexpression. Prostate cancer cells exposed to epigenetic modifying drugs trichostatin A, alone or combined with 5-aza-2’-deoxycytidine, increased H2AFZ transcript, although with a concomitant decrease in protein levels. Conversely, SIRT1 transcript and protein levels increased after exposure. ChIP revealed an increase of activation marks within the TSS region for both genes. Remarkably, inhibition of sirtuin 1 with nicotinamide, increased H2A.Z levels, whereas activation of sirtuin 1 by resveratrol led to an abrupt decrease in H2A.Z. Finally, protein-ligation assay showed that exposure to epigenetic modifying drugs fostered the interaction between sirtuin 1 and H2A.Z. We concluded that sirtuin 1 and H2A.Z deregulation in prostate cancer are reciprocally related. Epigenetic mechanisms, mostly histone post-translational modifications, are likely involved and impair sirtuin 1-mediated downregulation of H2A.Z via proteasome-mediated degradation. Epigenetic modifying drugs in conjunction with enzymatic modulators are able to restore the normal functions of sirtuin 1 and might constitute relevant tools for targeted therapy of prostate cancer patients

Phenotypic impact of deregulated expression of class I histone deacetylases in urothelial cell carcinoma of the bladder

Deregulated expression of histone deacetylases (HDACs) has been implicated in tumorigenesis. Herein, we investigated class I HDACs expression in bladder urothelial cell carcinoma (BUCC), its prognostic value and biological significance. Significantly increased transcript levels of all HDACs were found in BUCC compared to 20 normal mucosas, and these were higher in lower grade and stage tumors. Increased HDAC3 levels were associated with improved patient survival. SiRNA experiments showed decrease cell viability and motility, and increased apoptosis. We concluded that class I HDACs play an important role in bladder carcinogenesis through deregulation of proliferation, migration and apoptosis, constituting putative therapeutic targets

Aprendendo naturalmente: a importância da oralidade na aquisição da língua inglesa

Mestrado em Ensino Precoce do Inglês

P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection

BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLea and sLex antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests.

SMYD3 contributes to a more aggressive phenotype of prostate cancer and targets Cyclin D2 through H4K20me3

Prostate cancer (PCa) is one of the most incident cancers worldwide but clinical and pathological parameters have limited ability to discriminate between clinically significant and indolent PCa. Altered expression of histone methyltransferases and histone methylation patterns are involved in prostate carcinogenesis. SMYD3 transcript levels have prognostic value and discriminate among PCa with different clinical aggressiveness, so we decided to investigate its putative oncogenic role on PCa.We silenced SMYD3 and assess its impact through in vitro (cell viability, cell cycle, apoptosis, migration, invasion assays) and in vivo (tumor formation, angiogenesis). We evaluated SET domain's impact in PCa cells' phenotype. Histone marks deposition on SMYD3 putative target genes was assessed by ChIP analysis.Knockdown of SMYD3 attenuated malignant phenotype of LNCaP and PC3 cell lines. Deletions affecting the SET domain showed phenotypic impact similar to SMYD3 silencing, suggesting that tumorigenic effect is mediated through its histone methyltransferase activity. Moreover, CCND2 was identified as a putative target gene for SMYD3 transcriptional regulation, through trimethylation of H4K20.Our results support a proto-oncogenic role for SMYD3 in prostate carcinogenesis, mainly due to its methyltransferase enzymatic activity. Thus, SMYD3 overexpression is a potential biomarker for clinically aggressive disease and an attractive therapeutic target in PCa.

Cultural Intelligence (CQ) in Erasmus Mundus Students and Alumni: an exploratory study on the levels and antecedents of CQ

Erasmus Mundus Masters (EMM) are programs with a strong component of interculturality. Our study aimed at understanding the level of cultural intelligence (CQ) of EMM students and alumni, as well as some of the characteristics associated with higher levels of CQ. The study included 626 EMM students and alumni from 109 different countries that encompasses 6 continents. Ang and Van Dyne’s (2006) cultural intelligence scale was used; closed and open ended questions were used to describe the sample’s sociodemographic characteristics and experiences regarding interculturality. After validating and assessing the scale’s psychometric properties, relations between different variables were explored using Pearson’s correlation, ANOVA, t Tests, and GLM procedures. We then analysed the open ended responses to gain further insight on our results. Differences among respondents are mainly equated with international experience rather than nationality or training. Respondents’ open ended replies provided us with a deeper insight on why training seems to be so ineffective in developing CQ. This is a transversal study that uses self-reporting measures; also, questionnaires were conducted in English, which was not the mother tongue of most of the respondents. This work is consistent with the CQ literature, however we argue that training mentioned by respondents systematically fails to meet some of literature’s foremost conditions for effective CQ trainings and provide clues for the implementation of more successful initiatives. With an exceptionally diverse sample, this study contributes towards the understanding of mechanisms of developing CQ among EMM and international Students. Results can be useful for selection processes, training/development of CQ and reducing dropout/turnover.

Effects of Environmental Organochlorine Pesticides on Human Breast Cancer: Putative Involvement on Invasive Cell Ability

Human exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p′-dichlorodiphenyltrichloroethane (o,p′-DDT), and its metabolites p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and p,p′-dichlorodiphenyldichloroethane (p,p′-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p′-DDT, p,p′-DDE, and p,p′-DDD (50–1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.