Eph kinases and their ligands ephrins act in concert with sex hormones in regulating blood pressure

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN.

Defensive realism and the Concert of Europe

Why do great powers expand? Offensive realist John Mearsheimer claims that states wage an eternal struggle for power, and that those strong enough to seek regional hegemony nearly always do. Mearsheimer's evidence, however, displays a selection bias. Examining four crises between 1814 and 1840, I show that the balance of power restrained Russia, Prussia and France. Yet all three also exercised self-restraint; Russia, in particular, passed up chances to bid for hegemony in 1815 and to topple Ottoman Turkey in 1829. Defensive realism gives a better account of the Concert of Europe, because it combines structural realism with non-realist theories of state preferences.

Eph kinases and their ligands ephrins act in concert with sex hormones in regulating blood pressure

Les Erythropoietin-producing hepatocyte (EPH) sont la plus grande famille de récepteurs tyrosine kinase. Leurs ligands, les éphrines (EFNs), sont aussi des molécules exprimées à la surface cellulaire. Les EPH/EFNs sont impliqués dans de nombreux processus biologiques. L'hypertension artérielle (PA) est une maladie chronique qui, aujourd'hui, est devenue un problème médical critique dans le monde entier et un enjeu de santé publique. La découverte de nouvelles thérapeutiques de l'hypertension sont d'une grande importance pour la santé publique. Jusqu’à tout récemment, il existe seulement quelques études concernant le rôle de l’axe EPH/EFNs sur la fonction des cellules musculaires lisses vasculaires (CMLV). Dans nos études précédentes, nous avons montré qu'EPHB6 et EFNB1, de concert avec les hormones sexuelles, régulent la PA. Dans la présente étude, nous avons constaté que les différents membres de la famille EPH/EFN peuvent réguler soit positivement, soit négativement, la contractilité des CMLV et la PA: tandis que EPHB4 et EFNB2 appartiennent à la première catégorie, EFNB1, EFNB3 et EPHB6 appartiennent à la deuxième. In vivo, des souris males, mais non pas des femelles, porteuses d’une mutation EPHB4 (KO) spécifique du muscle lisse présentent une PA diminuée, comparée aux souris témoins (WT). Les CMLV de souris EPHB4 KO, en présence de testostérone, ont montré une contractilité réduite lors de la stimulation par la phényléphrine (PE). Au niveau moléculaire, la phosphorylation de la protéine kinase II dépendante de Ca2+/calmoduline et de la kinase de la chaine légère de la myosine (CLM) est augmentée, tandis que la phosphorylation de la kinase de la CLM est réduite dans les CMLV KO lors de la stimulation par PE, par rapport au WT CMLV. Cela fournit une base moléculaire à la réduction de la PA et de la contractilité des CMLV chez les souris EPHB4 KO. EFNB2 est le ligand majeur de l’EPHB4. Comme attendu, les souris EFNB2 KO spécifique du muscle lisse avaient un phénotype de PA semblable, quoique non identique, aux souris EPHB4 KO. Les souris mâles EFNB2 KO, mais pas femelles, sous régime régulier ou riche en sel, présentent une PA réduite, par rapport à leurs homologues WT. Au niveau cellulaire, les CMLV des souris KO ont montré une contractilité réduite lors de la stimulation par PE par rapport aux témoins WT. Une région de l’acide aminé (aa) 313 à l’aa 331 dans la partie intracellulaire d’EFNB2 est essentielle pour la signalisation inverse qui régule la contractilité des CMLV, selon des études de mutation-délétion. Dans une étude de génétique humaine, nous avons identifié, dans le gène EFNB2, six SNP qui étaient associées significativement au risque d'hypertension artérielle, de façon dépendante du sexe, ce qui corrobore nos résultats chez les souris. En revanche, la délétion du gène EFNB3 (KO) chez les souris femelles aboutit à une PA élevée et à une augmentation des résistances des petites artères in vivo, améliore la contractilité des petites artères ex-vivo et augmente la contractilité des CMLV in vitro. Les souris mâles KO ont une PA normale, mais la castration conduit à une augmentation significative de la PA dans les souris KO, mais pas dans les souris WT. Les CMLV des souris KO femelles ont montré une phosphorylation accrue de la CLM et une phosphorylation réduite de la kinase de la CLM, ce qui fournit à nouveau une base moléculaire aux phénotypes de PA et de contractilité des CMLV observés. Ce changement de signalisation est attribuable à une protéine adaptatrice Grip1. En effet, dans une étude d'association pan génomique par le Consortium International pour la Pression Sanguine, un SNP dans le gène GRIP1 a approché le seuil de significativité de la valeur p pour son association avec la pression diastolique. Nos recherches, pour la première fois, ont révélé que EPH/EFNs sont de nouveaux composants dans le système de régulation de la PA. Les membres de la famille EPH/EFN peuvent agir comme des forces Yin et Yang pour régler finement le tonus des vaisseaux pour assurer l'homéostasie de la PA et de sa régulation. Ces effets de EPH/EFNs dépendent du sexe et des niveaux d’hormones sexuelles. À partir de ces nouvelles connaissances, nous pourrions développer une nouvelle thérapie personnalisée pour l’hypertension artérielle, utilisant des antagonistes d'hormones sexuelles ou des thérapies de remplacement d'hormones sexuelles, selon les niveaux d'hormones sexuelles des patients et les mutations dans les gènes de l'EPH/EFN.

Save the Date Classically Cuban Concert: Music for Martí

This is the save the date flyer for the event "Classically Cuban Concert: Music for Martí".

Littlefield Organ Series Halloween Organ Concert October 28, 2016

Concert Program

La marimba sí paga en Cali: Apropiaciones de las músicas de marimba como estrategia cultural en escenarios de industria cultural

El texto es el resultado del trabajo de investigación con dos agrupaciones musicales de la ciudad de Cali, durante el 2013 y el 2015. Hace una reflexión sociológica sobre la relación entre economía y cultura, a través de las apropiaciones que hacen estos músicos de las músicas de marimba del Pacífico del sur de Colombia, para posicionarse en escenarios de industria cultural. Con una metodología cualitativa basada en la interacción, estudia las trayectorias, prácticas y discursos de estos grupos que se consolidan en las estrategias que utilizan para ingresar en estos escenarios construidos como producto de fenómenos macrosociales globales y locales que permiten la transformación de la música como una herramienta mediadora para contar la cotidianidad que estas bandas viven en su ciudad.

Fundamental sounds

Fundamental Sounds was a live, intercultural and multidisciplinary concert that presented a new synthesis of music, performance & visual arts addressing the imperative of sustainability in a new and evocative form. The outcome was a ninety-minute concert, performed at a major concert hall venue, involving four live musicians, numerous performers & large-scale projections. The images and the concert were scripted in three key phases that spoke to three epochs of human evolution identified by ontological designer and futurist Tony Fry - ‘Pre-Settlement’, ‘Settlement’ and the era that he suggests that we have now entered – ‘Unsettlement’ (in mind body and spirit). The entire work was professionally recorded for presentation on DVD and audio CD.----- Fundamental Sounds achieved a new synthesis between quality performance forms and cogent critical ideas, engendering an increasingly reflective position for audiences around today’s “era of unsettlement” – an epoch Fry has recognized that we must now move to quickly displace through adopting fundamentally sustainable modes of being and becoming.----- The concert was well attended and evoked a range of strong, reflective reactions from its audiences who were also invited to join and participate within a subsequent ‘community of change’ initiated at that time.

Knowmore (House of Commons)

Knowmore (House of Commons) is a large scale generative interactive installation that incorporates embodied interaction, dynamic image creation, new furniture forms, touch sensitivity, innovative collaborative processes and multichannel generative sound creation. A large circular table spun by hand and a computer-controlled video projection falls on its top, creating an uncanny blend of physical object and virtual media. Participants’ presence around the table and how they touch it is registered, allowing up to five people to collaboratively ‘play’ this deeply immersive audiovisual work. Set within an ecological context, the work subtly asks what kind of resources and knowledges might be necessary to move us past simply knowing what needs to be changed to instead actually embodying that change, whilst hinting at other deeply relational ways of understanding and knowing the world. The work has successfully operated in two high traffic public environments, generating a subtle form of interactivity that allows different people to interact at different paces and speeds and with differing intentions, each contributing towards dramatic public outcomes. The research field involved developing new interaction and engagement strategies for eco-political media arts practice. The context was the creation of improved embodied, performative and improvisational experiences for participants; further informed by ‘Sustainment’ theory. The central question was, what ontological shifts may be necessary to better envision and align our everyday life choices in ways that respect that which is shared by all - 'The Commons'. The methodology was primarily practice-led and in concert with underlying theories. The work’s knowledge contribution was to question how new media interactive experience and embodied interaction might prompt participants to reflect upon the kind of resources and knowledges required to move past simply knowing what needs to be changed to instead actually embodying that change. This was achieved through focusing on the power of embodied learning implied by the works' strongly physical interface (i.e. the spinning of a full size table) in concert with the complex field of layered imagery and sound. The work was commissioned by the State Library of Queensland and Queensland Artworkers Alliance and significantly funded by The Australia Council for the Arts, Arts Queensland, QUT, RMIT Centre for Animation and Interactive Media and industry partners E2E Visuals. After premiering for 3 months at the State Library of Queensland it was curated into the significant ‘Mediations Biennial of Modern Art’ in Poznan, Poland. The work formed the basis of two papers, was reviewed in Realtime (90), was overviewed at Subtle Technologies (2010) in Toronto and shortlisted for ISEA 2011 Istanbul and included in the edited book/catalogue ‘Art in Spite of Economics’, a collaboration between Leonardo/ISAST (MIT Press); Goldsmiths, University of London; ISEA International; and Sabanci University, Istanbul.

Talking about watching : using the video card game and wiki-web technology to engage IT students in developing observational skills.

Designers need to develop good observational skills in order to conduct user studies that reveal the subtleties of human interactions and adequately inform design activity. In this paper we describe a game format that we have used in concert with wiki-web technology, to engage our IT and Information Environments students in developing much sharper observational skills. The Video Card Game is a method of video analysis that is suited to design practitioners as well as to researchers. It uses the familiar format of a card game similar to "Happy Families,, to help students develop themes of interactions from watching video clips. Students then post their interaction themes on wiki-web pages, which allows the teaching team and other students to edit and comment on them. We found that the tangible (cards), game, role playing and sharing aspects of this method led to a much larger amount of interaction and discussion between student groups and between students and the teaching team, than we have achieved using our traditional teaching methods, while taking no more time on the part of the teaching staff. The quality of the resulting interaction themes indicates that this method fosters development of observational skills.In the paper we describe the motivations, method and results in full. We also describe the research context in which we collected the videotape data, and how this method relates to state of the art research methods in interaction design for ubiquitous computing technology.

Nodule

Nodule is 19'54" musical work for two electronic music performers, two laptop computers and a custom built, sensor-based microphone controller - the e-Mic (Extended Mic-stand Interface Controller). This interface was developed by one of the co-authors, Donna Hewitt. The e-Mic allows a vocal performer to manipulate their voice in real time by capturing physical gestures via an array of sensors - pressure, distance, tilt – in addition to ribbon controllers and an X-Y joystick microphone mount. Performance data are then sent to a computer, running audio-processing software, which is used to transform the audio signal from the microphone in real time. The work seeks to explore the liminal space between the electro-acoustic music tradition and more recent developments in the electronic dance music tradition. It does so on both a performative (gestural) and compositional (sonic) level. Visually, the performance consists of a singer and a laptop performer, hybridising the gestural context of these traditions. On a sonic level, the work explores hybridity at deeper levels of the musical structure than simple bricolage or collage approaches. Hybridity is explored at the level of the sonic gesture (source material), in production (audio processing gestures), in performance gesture, and in approaches to the use of the frequency spectrum, pulse and meter. The work was designed to be performed in a range of contexts from concert halls, to clubs, to rock festivals, across a range of staging and production platforms. As a consequence, the work has been tested in a range of audience contexts, and has allowed the transportation of compositional and performance practices across traditional audience demographic boundaries.

Re-imagining school through young people’s drawings

Children’s drawings provide rich qualitative data (Walker, 2008) and “valuable information for the assessment of children's environmental perceptions” (Barraza, 1999, p. 49). They are the primary data source being used to re-imagine school from a student perspective (Schratz & Steiner-Löffler, 1998) in a research project being carried out with primary school students in Queensland, Australia. This paper will report on the progress of this project which addresses a mostly unmet need for students’ perspectives to be included in school design (Rudduck & Flutter, 2004). Grade 5/6 students in a number of primary schools have been invited to submit annotated drawings with up to 200 words of text illustrating their ideal educational spaces. Using purpose-designed analytical tools, the submissions will be compared across student backgrounds and school types to obtain a better understanding of the needs and educational desires of young people in relation to changing learning environments. The findings will inform consideration of the design and use of educational spaces with all work exhibited through a dedicated website. The term ‘educational spaces’ avoids restrictive notions of what the concept of ‘school’ means, referring to any real or virtual space in which teaching and learning may occur or, as Ferguson and Seddon (2007) have referred to it, “the shifting imagery of education” that includes red brick schools and dispersed learning networks. The theoretical framework for this study is grounded in the work of Greene (1995) and Wright-Mills (2001) who cited the deployment of critical and empathic imagination in addressing education reform.

Visuacy, imagination, and engagement

Australia’s National Review of Visual Education (DEEWR, 2009) asserts the primacy of visual language ability, or ‘visuacy” in problem-solving. This paper reports on a recent university/schools research project with ‘at risk’ middle school students in which visuacy was promoted as a primary medium for obtaining data relating to issues of immediate concern to the students. Using a students-as-researchers approach, the project investigated middle school students’ perspectives on school engagement and disengagement. In this project, novice researchers used a variety of data gathering methods including photography, video interviews and drawn images as well as more traditional verbal methods, such as interviews, and quantitative methods, such as questionnaires. Engaging student imagination was a key focus of the approach taken by the project, acknowledging that student participants may be reluctant to enter dialogue with teachers and researchers on matters to which they have previously had little input. Students who have previously been marginalized and prevented from contributing their voices to educational forums often have difficulty in adjusting to the novelty of collaborative research with adults (Rudduck, 2003) and may be uncertain of their own place in the relationship that defines teacher/student interactions. It is argued that the project’s promotion of visuacy, alongside more traditional literacies and numeracy in education research, helped to overcome these concerns, engaged the imaginations of the student researchers, and provided a medium for the expression of the voices of marginalised young people.

The Remnant

An Interactive Installation with holographic 3D projections, satellite imagery, surround sound and intuitive body driven interactivity. Remnant (v.1) was commissioned by the 2010 TreeLine ecoArt event - an initiative of the Sunshine Coast Council and presented at a remnant block of subtropical rainforest called ‘Mary Cairncross Scenic Reserve’ - located 100kms north of Brisbane near the township of Maleny. V2 was later commissioned for KickArts Gallery, Cairns, re-presenting the work in a new open format which allowed audiences to both experience the original power of the work and to also understand the construction of the work's powerful illusory, visual spaces. This art-science project focused upon the idea of remnant landscapes - isolated blocks of forest (or other vegetation types) typically set within a patchwork quilt of surrounding farmed land. Participants peer into a mysterious, long tunnel of imagery whilst navigating entirely through gentle head movements - allowing them to both 'steer' in three dimensions and also 'alight', as a butterfly might, upon a sector of landscape - which in turn reveals an underlying 'landscape of mind'. The work challenges audiences to re-imagine our conceptions of country in ways that will lead us to better reconnect and sustain today’s heavily divided landscapes. The research field involved developing new digital image projection methods, alternate embodied interaction and engagement strategies for eco-political media arts practice. The context was the creation of improved embodied and improvisational experiences for participants, further informed by ‘eco-philosophical’ and sustainment theories. By engaging with deep conceptions of connectivity between apparently disparate elements, the work considered novel strategies for fostering new desires, for understanding and re-thinking the requisite physical and ecological links between ‘things’ that have been historically shattered. The methodology was primarily practice-led and in concert with underlying theories. The work’s knowledge contribution was to question how new media interactive experience and embodied interaction might prompt participants to reflect upon appropriate resources and knowledges required to generate this substantive desire for new approaches to sustainment. This accentuated through the power of learning implied by the works' strongly visual and kinaesthetic interface (i.e. the tunnel of imagery and the head and torso operated navigation). The work was commissioned by the 2010 TreeLine ecoArt event - an initiative of the Sunshine Coast Council and the second version was commissioned by Kickarts Gallery, Cairns, specifically funded by a national optometrist chain. It was also funded in development by Arts Queensland and reviewed in Realtime.

Resembling Florida : transpacific transfer of ideas from one Gold Coast to another

Despite different political structures and planning systems, striking physical similarities exist between the tourist destinations of the Gold Coasts of Queensland and Florida. Both have been fast developing sub-tropical coastal areas, subject to massive land booms, speculation, and entrepreneurs’ grand visions throughout their history. As a result, both have become tourist destinations of international renown. Drawing on historical sources, the present research seeks to investigate the extent to which these similarities result from taking American cities as a model for newer development in Australia; in this case from transferring planning and marketing ideas from one Gold Coast to another, with the development of the Florida Gold Coast setting precedent for the development of the Queensland Gold Coast.