556 research outputs found

    DMPK prevents ROS-induced cell death by assembling a HK II-Src complex on mitochondrial surface

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    DMPK is a serine/threonine protein kinase that was initially proposed to be the cause of the most frequent adult muscular dystrophy, myotonic dystrophy 1 (DM1). Recently, it has been shown that DMPK is not the primary determinant of the DM1, but its deletion causes late onset myopathy and cardiac abnormalities in knock-out mice. Evidence present in the literature suggests a mitochondrial localization of high MW DMPK isoforms in muscle and cardiac tissue. However, to date, there is not a single association of mitochondria-anchored isoforms with the respective function of the organelle in the affected tissues. Therefore, we have examined the role of mitochondria-anchored isoform A, either by stably expressing it in cells lacking endogenous protein, or by stably silencing the endogenous one. DMPK significantly decreased levels of mitochondrial superoxide and consequently increased cell survival in prolonged serum and glucose depletion, both in SAOS-2 and rhabdomyosarcoma cells. At the molecular level we have found DMPK to interact with HK II and Src, increasing the HK II association to mitochondria. Detachment of HK II from mitochondria abolished differences in superoxide levels, while a HK II inhibitor 5-TG protected cells from death by stabilizing HK II on the OMM and by decreasing mitochondrial ROS in the absence of DMPK. Src activity was also important for HK II maintenance on OMM since its inhibition sensitized only DMPK-expressing cells to detachment of HK II. These data attribute an antiapoptotic role to DMPK due to an unprecedented link to HK II and its protective effect against mitochondrial ROS.DMPK è la serina/treonina protein kinasi, la quale è stata inizialmente proposta come la causa della più frequente distrofia muscolare negli adulti, la distrofia miotonica del tipo 1 (DM1). Recentemente si è visto che la DMPK non è la causa principale della DM1, ma la sua delezione causa miopatia ad insorgenza tardiva e anomalie cardiache nei topi knock-out. I dati presenti in letteratura attribuiscono la localizzazione mitocondriale alle isoforme ad alto peso molecolare nel muscolo e nel tessuto cardiaco. Comunque, finora non vi sono stati studi volti ad associare il ruolo delle isoforme mitocondriali della DMPK alla funzione dell’organulo nei tessuti in questione. Perciò, abbiamo deciso di esaminare il ruolo dall’isoforma A associata ai mitocondri, sia esprimendola stabilmente nelle cellule prive della DMPK endogena, sia silenziando stabilmente quella endogena. DMPK ha significativamente diminuito i livelli del superossido mitocondriale e, di conseguenza, ha aumentato la sopravvivenza delle cellule SAOS-2 e rabdomiosarcoma in deplezione di siero e glucosio. A livello molecolare, abbiamo trovato che la DMPK interagisce con HK II e Src aumentando l’associazione dell’HK II ai mitocondri. Il distacco dell’HK II dai mitocondri ha cancellato le differenze nei livelli di superossido, mentre l’inibitore dell’HK II 5-TG ha protetto le cellule dalla morte stabilizzando l’HK II sulla membrana mitocondriale esterna e diminuendo i livelli di ROS mitocondriali in assenza della DMPK. Src aveva la funzione di mantenere HK II sulla membrana mitocondriale esterna, in quanto la sua inibizione ha sensibilizzato le cellule al distacco dell’HK II solo se esprimevano la DMPK. Questo studio attribuisce un ruolo anti-apoptotico alla DMPK grazie all’interazione con HK II e la sua funzione protettiva contro i ROS di origine mitocondriale

    Civil-Military Cooperation (CIMIC) Pre-deployment and Orientation Courses in Europe, part 1.

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    In this article I would like to give a short summary about CIMIC pre-deployment and orientation courses available in Europe, and in the European Union at different institutions and training centers. The descriptions are based on some personal experience, also some are collected across interviews from other participants, and of course via open sources, like course catalogues. The aim of the article is to collect the special kind of courses and demonstrate the wide range of similarities as fact of integration and harmonization, but also try to highlight some small differencies. I would like to make a short list of institutions, course thematic, lecturers and duration of these courses. There are no scientific result in this article as standing alone, but my wider research area a comparative essey on the European Union member states and compare their relation to Common Security and Defence Policy, their participation in EUFOR (ongoing, military) missions, CIMIC activity and institutions and try to find the similarities and differences

    Creating emotional communication with interactive artwork

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    This pilot study contributes to the building of an art installation that aims to build an emotional communication loop with the audience. It will do so by reacting to or mimicking the audience's changes in emotional expressions according to emotional contagion dynamics. The study aims to inform the project by gaining a better understanding of emotional contagion patterns and the factors that may affect how people emotionally engage in this art context. The analysis of our early experiments shows reflex mechanisms of facial expression mimicry and counter-mimicry that follow patterns similar to those reported in the psychology literature. In fact, automatic mimicry and counter-mimicry correlated to some extent to whether or not the audience felt to be interacting with a real person. Furthermore, the results indicate that individual differences play a role in the way people can emotionally engage with this type of artwork. However, irrespective of these differences, the interaction led the audience to introspect and reflect about emotions

    Facial expression analysis by computational intelligence techniques

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    Electrical Engineering, Mathematics and Computer Scienc

    The rationale for a wider concept of Inclusive Education for teacher education: A case-study of Serbia

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    Teacher education for inclusive education (IE) is recognized as vital for improving quality and equity in education globally. In the Western Balkan countries it is also part of the transition process towards joining the European Union and has attracted international funding for IE-related projects. A key finding from research funded by the European Training Foundation, carried out by the authors as members of a seven-country research team in 2009-2010, was that the prevailing local understanding of IE was very narrow. In this article we hypothesize the reasons for this finding. We use a case study of school and teacher education systems in Serbia to explore how this understanding has constrained the development of IE and associated teacher education and limited the efficacy of some recent internationally supported developments. We identify both challenges and possible ways forward for teacher education for IE based on promoting a concept of IE that is both collaboratively agreed and comprehensive. © 2012 UNESCO IBE

    The interaction between facial recognition and the right to privacy in the era of big data.

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    reservedLa tesi esplora il rapporto fra l’utilizzo delle tecnologie di riconoscimento facciale e il diritto alla privacy nell’era dei big data, con particolare attenzione a come il riconoscimento facciale viene utilizzato e regolato nell’unioneeuropea

    If looks could talk: A system for automatic analysis of facial expressions

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    Researchers at Delft University of Technology have developed a computer system capable of recognising human facial expressions from images. The system can distinguish between 30 different units such as a smile, or raised eyebrows. It is intended for use by behavioural researchers and the medical profession. A psychologist might use it to automatically receive and analyse a series of photographs of people he wishes to observe. Psychologists archives are often crammed with photographs, and processing them is just the first step.In addition, over the last decade, researchers all over the world have been looking for ways to improve the way we communicate with computers, other than through a mouse and keyboard. The interface of new multimedia products must become more intelligent and user-friendly. This requires insight into a number of aspects of non-verbal communication

    Myotonic dystrophy protein kinase (DMPK) prevents ROS-induced cell death by assembling a hexokinase II-Src complex on the mitochondrial surface

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    The biological functions of myotonic dystrophy protein kinase (DMPK), a serine/threonine kinase whose gene mutations cause myotonic dystrophy type 1 (DM1), remain poorly understood. Several DMPK isoforms exist, and the long ones (DMPK-A/B/C/D) are associated with the mitochondria, where they exert unknown activities. We have studied the isoform A of DMPK, which we have found to be prevalently associated to the outer mitochondrial membrane. The kinase activity of mitochondrial DMPK protects cells from oxidative stress and from the ensuing opening of the mitochondrial permeability transition pore (PTP), which would otherwise irreversibly commit cells to death. We observe that DMPK (i) increases the mitochondrial localization of hexokinase II (HK II), (ii) forms a multimeric complex with HK II and with the active form of the tyrosine kinase Src, binding its SH3 domain and (iii) it is tyrosine-phosphorylated by Src. Both interaction among these proteins and tyrosine phosphorylation of DMPK are increased under oxidative stress, and Src inhibition selectively enhances death in DMPK-expressing cells after HK II detachment from the mitochondria. Down-modulation of DMPK abolishes the appearance of muscle markers in in vitro myogenesis, which is rescued by oxidant scavenging. Our data indicate that, together with HK II and Src, mitochondrial DMPK is part of a multimolecular complex endowed with antioxidant and pro-survival properties that could be relevant during the function and differentiation of muscle fibers
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