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.

New modified electrochemical conductive paper support for BSA detection

Chemical sensors and biosensors are widely used to detect various kinds of protein target biomolecules. Molecularly Imprinted Polymers (MIPs) have raised great interest in this area, because these act as antibody-like recognition materials, with high affinity to the template molecule. Compared to natural antibodies, these are also of lower cost and higher stability. There are different types of supports used to carry MIP materials, mostly of these made of gold, favourably assembled on a Screen Printed Electrode (SPE) strategy. For this work a new kind of support for the sensing layer was developed: conductive paper. This support was made by modifying first cellulose paper with paraffin wax (to make it waterproof), and casting a carbon-ink on it afterwards, to turn it conductive. The SPAM approach previously reported in1 was employed herein to assemble to MIP sensing material on the conductive paper. The selected charged monomers were (vinylbenzyl) trimethlammonium chloride (positive charge) or vinylbenzoic acid (negative charge), used to generate binding positions with single-type charge (positive or negative). The non-specific binding area of the MIP layer was assembled by chronoamperometry-assisted polymerization (at 1 V, for 60, 120 or 180 seconds) of vinylbenzoate, cross-linked with ethylene glycol vinyl ether. The BSA biomolecules lying within the polymeric matrix were removed by Proteinase K action. All preparation stages of the MIP assembly were followed by FTIR, Raman spectroscopy and, electrochemical analysis. In general, the best results were obtained for longer polymerization times and positively charged binding sites (which was consistent with a negatively-charged protein under physiological pH, as BSA). Linear responses against BSA concentration ranged from 0.005 to 100 mg/mL, in PBS buffer standard solutions. The sensor was further calibrated in standard solutions that were prepared in synthetic or real urine, and the analytical response became more sensitive and stable. Compared to the literature, the detection capability of the developed device is better than most of the reported electrodes. Overall, the simplicity, low cost and good analytical performance of the BSA SPE device, prepared with positively charged binding positions, seems a suitable approach for practical application in clinical context. Further studies with real samples are required, as well as gathering with electronic-supporting devices to allow on-site readings.

POSTDATA – Towards publishing European poetry as linked open data

POSTDATA is a 5 year's European Research Council (ERC) Starting Grant Project that started in May 2016 and is hosted by the Universidad Nacional de Educación a Distancia (UNED), Madrid, Spain. The context of the project is the corpora of European Poetry (EP), with a special focus on poetic materials from different languages and literary traditions. POSTDATA aims to offer a standardized model in the philological field and a metadata application profile (MAP) for EP in order to build a common classification of all these poetic materials. The information of Spanish, Italian and French repertoires will be published in the Linked Open Data (LOD) ecosystem. Later we expect to extend the model to include additional corpora. There are a number of Web Based Information Systems in Europe with repertoires of poems available to human consumption but not in an appropriate condition to be accessible and reusable by the Semantic Web. These systems are not interoperable; they are in fact locked in their databases and proprietary software, not suitable to be linked in the Semantic Web. A way to make this data interoperable is to develop a MAP in order to be able to publish this data available in the LOD ecosystem, and also to publish new data that will be created and modeled based on this MAP. To create a common data model for EP is not simple since the existent data models are based on conceptualizations and terminology belonging to their own poetical traditions and each tradition has developed an idiosyncratic analytical terminology in a different and independent way for years. The result of this uncoordinated evolution is a set of varied terminologies to explain analogous metrical phenomena through the different poetic systems whose correspondences have been hardly studied – see examples in González-Blanco & Rodríguez (2014a and b). This work has to be done by domain experts before the modeling actually starts. On the other hand, the development of a MAP is a complex task though it is imperative to follow a method for this development. The last years Curado Malta & Baptista (2012, 2013a, 2013b) have been studying the development of MAP's in a Design Science Research (DSR) methodological process in order to define a method for the development of MAPs (see Curado Malta (2014)). The output of this DSR process was a first version of a method for the development of Metadata Application Profiles (Me4MAP) (paper to be published). The DSR process is now in the validation phase of the Relevance Cycle to validate Me4MAP. The development of this MAP for poetry will follow the guidelines of Me4MAP and this development will be used to do the validation of Me4MAP. The final goal of the POSTDATA project is: i) to be able to publish all the data locked in the WIS, in LOD, where any agent interested will be able to build applications over the data in order to serve final users; ii) to build a Web platform where: a) researchers, students and other final users interested in EP will be able to access poems (and their analyses) of all databases; b) researchers, students and other final users will be able to upload poems, the digitalized images of manuscripts, and fill in the information concerning the analysis of the poem, collaboratively contributing to a LOD dataset of poetry.