Deep sequencing analysis reveals distinctive non-coding RNAs when comparing tumor multidrug-resistant cells and extracellular vesicles with drug-sensitive counterparts

This article is a result of the project NORTE-01-0145-FEDER-000029, supported by the Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This work was partially financed by the FEDER - Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020, and by Portuguese funds through FCT - Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). This work is also a result of the GenomePT project (POCI-01-0145-FEDER-022184), supported by the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT). The authors thank the Portuguese Foundation for Science and Technology (FCT) for the PhD grant of DS (SFRH/BD/98054/2013).Multidrug resistance (MDR) is one of the main limitations of cancer treatment. The overexpression of drug-eux pumps, such as P-glycoprotein (P-gp), is a major cause of MDR. Importantly, di erent studies have shown that extracellular vesicles (EVs) participate in the communication between MDR cells and drug-sensitive counterparts, promoting dissemination of the MDR phenotype. In the present work, we aimed to identify RNA species present in MDR cells and in EVs released by those cells, which may be associated with the MDR phenotype. The RNA content from two pairs (leukemia and lung cancer) of MDR (P-gp overexpressing) cells and their drug-sensitive counterparts, as well as from their EVs, was analyzed by deep sequencing. Our results showed distinctive transcripts for MDR cells and their EVs, when compared with their drug-sensitive counterparts. Remarkably, two pseudogenes (a novel pseudogene and RNA 5.8S ribosomal pseudogene 2) were found to be increased in EVs released by MDR cells in both leukemia and lung cancer models. Moreover, six miRs (miR-204-5p, miR-139-5p, miR-29c-5p, miR-551b-3p, miR-29b-2-5p, and miR-204-3p) exhibited altered levels in lung cancer MDR cells and their EVs. This study provides insights into the contribution of EVs to MDR.publishersversionpublishe

A Conceptual Model Combination for the Unification of Design and Tolerancing in Robust Design

In design engineering, the early consideration of tolerance chains contributes to robust design. For this, a link of design and tolerancing domains is essential. This paper presents a combination of the graph-based tolerancing approach and the Contact and Channel approach to link these domains. The combined approach is applied at a coinage machine. Here it provides detailed insights into state-dependent relations of embodiment and functions, which can improve robustness evaluation of the concept. This approach shows a possibility to bridge the gap between design and tolerancing domains

Current Challenges And Solution Approaches In Empirical Engineering Design Research – A Workshop For Empirical Research

The requirements on validity for studies in design research are very high. Therefore, this paper aims at identifying challenges that occur when setting up studies and suggests solution strategies to address them. Three different institutes combining their experience discussed several studies in a workshop. Resulting main challenges are to find a suitable task, to operationalise the variables and to deal with a high analysis effort per participant. Automation in data evaluation and a detailed practical guideline on studies in design research are considered necessary

Qualitative Modelling in Embodiment Design - Investigating the Contact and Channel Approach Through Analysis of Projects

Purposeful qualitative modelling of embodiment function relations is a challenge in embodiment design. This contribution investigates the applicability and usefulness of the Contact and Channel Approach as a qualitative modelling approach in a survey study. From 23 development and research projects, advantages and challenges regarding applicability and usefulness are identified. A further result is that many different models are used additionally to the Contact and Channel Approach. Based on the findings, research potential for optimization and development of links to other models emerges

A search for solar-like oscillations in K giants in the globular cluster M4

To expand the range in the colour-magnitude diagram where asteroseismology can be applied, we organized a photometry campaign to find evidence for solar-like oscillations in giant stars in the globular cluster M4. The aim was to detect the comb-like p-mode structure characteristic for solar-like oscillations in the amplitude spectra. The two dozen main target stars are in the region of the bump stars and have luminosities in the range 50-140 Lsun. We collected 6160 CCD frames and light curves for about 14000 stars were extracted. We obtain high quality light curves for the K giants, but no clear oscillation signal is detected. High precision differential photometry is possible even in very crowded regions like the core of M4. Solar-like oscillations are probably present in K giants, but the amplitudes are lower than classical scaling laws predict.Comment: 14 pages, 16 figures, accepted for publication in A&